Located on the Hellenic Arc, the Christiana‐Santorini‐Kolumbo (CSK) rift zone represents one of the most active and hazardous volcano‐tectonic systems in the Mediterranean. Although this rift zone ...has been intensively studied, its tectonic evolution and the interplay of volcanism and tectonism are still poorly understood. In this study, we use high‐resolution reflection seismic imagery to reconstruct the opening of the rift basins. For the first time, we relate the activity of individual faults with the activity of specific volcanic centers in space and time. Our analysis shows a pre‐volcanic NNE‐SSW‐oriented paleo basin underneath the CSK volcanoes, representing a transfer zone between Pliocene ESE‐WNW‐oriented basins, which was overprinted by a NE‐SW‐oriented tectonic regime hosting Late Pliocene volcanism that initiated at the Christiana Volcano. All subsequent volcanoes evolved parallel to this trend. Two major Pleistocene tectonic pulses preceded fundamental changes in the volcanism of the CSK rift including the occurrence of widespread small‐scale volcanic centers followed by focusing of activity at Santorini with increasing explosivity. The observed correlation between changes in the tectonic system and the magmatism of the CSK volcanoes suggests a deep‐seated tectonic control of the volcanic plumbing system. In turn, our analysis reveals the absence of large‐scale faults in basin segments affected by volcanism indicating a secondary feedback mechanism on the tectonic system. A comparison with the evolution of the neighboring Kos‐Nisyros‐Yali volcanic field zone and Rhodos highlights concurrent regional volcano‐tectonic changes, suggesting a potential arc‐wide scale of the observed volcano‐tectonic interplay.
Plain Language Summary
How do regional tectonic movements and large volcanoes interact? Seismological studies indicate complex volcano‐tectonic feedback links, but, so far, information on the long‐term interactions between tectonics and volcanism is rarely available. The Christiana‐Santorini‐Kolumbo (CSK) rift zone lies in the Aegean Sea and is notorious for its devastating volcanic eruptions, earthquakes, and tsunamis. This region offers the opportunity to study volcano‐tectonic interactions over several million years. In this study, we use high‐resolution seismic imagery to reconstruct the evolution of the rift basins and the CSK volcanoes. We find that all volcanoes lie in a Pliocene transfer zone connecting extensional basins. Volcanism initiated as this older tectonic regime was intersected by a NE‐SW‐directed fault system. Subsequently, all volcanoes evolved parallel to this trend. Several distinct tectonic reorganizations occurred in the Pleistocene, which had a pronounced influence on the CSK volcanoes. In turn, our analysis indicates that the emergence of volcanism also impacted the tectonic evolution of the rift system hindering the evolution of large‐scale normal faults in the volcanic basins. The observed tectonic reorganizations seem to reflect major changes in the stress regime of the Hellenic Arc, potentially also affecting adjacent volcanic centers whose volcano‐tectonic evolution is only poorly constrained so far.
Key Points
We reconstruct the volcano‐tectonic evolution of the Christiana‐Santorini‐Kolumbo rift zone using multichannel seismic data
The overprint of a Pleistocene NE‐SW striking fault system on a Pliocene E‐W oriented system initiated the emergence of volcanism
Regional tectonics had a primary control on the volcanic plumbing system, while magmatism had a secondary influence on the tectonic system
Afamelanotide for Erythropoietic Protoporphyria Langendonk, Janneke G; Balwani, Manisha; Anderson, Karl E ...
New England journal of medicine/The New England journal of medicine,
07/2015, Volume:
373, Issue:
1
Journal Article
Peer reviewed
Open access
In patients with erythropoietic protoporphyria, sensitivity to the sun leads to pain and compromised quality of life. In two clinical trials, one in Europe and one in the United States, a peptide ...analogue of an α-melanocyte–stimulating hormone alleviated symptoms.
Erythropoietic protoporphyria is a rare, autosomal recessive inborn error of metabolism that typically manifests in early childhood as severe painful photosensitivity. The photosensitivity results from accumulated protoporphyrin in erythroid cells and tissues because of the decreased activity of ferrochelatase, the heme biosynthetic enzyme that inserts iron into protoporphyrin to form heme.
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An X-linked form of erythropoietic protoporphyria
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that accounts for 2 to 10% of cases results from a gain of function of erythroid-specific aminolevulinic acid synthase 2.
Pathophysiologically, protoporphyrin is released from erythroid cells into the circulation, gains access to the vascular endothelium and liver, and is excreted . . .
Aim The standard treatment for patients with clinically resectable rectal cancer is surgery. Postoperative radiochemotherapy (RCT) is recommended for advanced disease (pT3/4 or pN+). In recent ...years, encouraging results of pre‐operative radiotherapy have been reported. This prospective randomized phase‐III‐trial (CAO/ARO/AIO‐94) compares the efficacy of neoadjuvant RCT to standard postoperative RCT. We report on the design of the study and first results with regard to toxicity of RCT and postoperative morbidity.
Patients and methods Patients with locally advanced operable rectal cancer (uT3/4 or uN+, Mason CS III/IV) were randomly assigned to pre or postoperative RCT: A total dose of 50.4 Gy (single dose 1.8 Gy) was applied to the tumour and the pelvic lymph nodes. 5‐FU (1000 mg/m2/d) was administered concomitantly in the 1th and 5th week of radiation as 120 h‐continuous infusion. Four additional cycles of 5‐FU‐chemotherapy (500 mg/m2/d, i.v.‐bolus) were applied. RCT was identical in both arms except for a small‐volume boost of 5.4 Gy postoperatively. The time interval between RCT and surgery was 4–6 weeks in both arms. Techniques of surgery were standardized and included total mesorectal excision. Primary endpoints of the study are 5‐year survival and local and distant control. Secondary endpoints include the rate of curative (R0) resection and sphincter saving procedures, toxicity of RCT, surgical complications and quality of life.
Results As of July 2002, 805 patients were randomized from 26 participating institutions. Acute toxicity (WHO) of RCT was low, with less than 15% of patients experiencing grade 3 or higher toxicity: The principal toxicity was diarrhea, with 12% in the postoperative RCT‐arm and 11% in the pre‐operative RCT‐arm having grade 3‐, and 1% in either arm having grade 4‐diarrhea. Erythema, nausea and leukopenia were the next common toxicities, with less than 3% of patients in either arm suffering grade 3 or greater leukopenia or nausea. Postoperative complication rates were similar in both arms, with 12% (postop. RCT) and 12% (pre‐op. RCT) of patients, respectively, suffering from anastomotic leakage, 3% (postop. RCT) and 3% (pre‐op. RCT) from postoperative bleeding, and 6% (postop. RCT) and 4% (pre‐op. RCT) from delayed wound healing.
Conclusion The patient accrual to the trial is satisfactory. Neoadjuvant RCT is well tolerated and bears no higher risk for postoperative morbidity.
Landslides associated with flank collapse are volumetrically the most significant sediment transport process around volcanic islands. Around Montserrat, in the Lesser Antilles, individual landslide ...deposits have volumes (1 to 20km3) that are up to two orders of magnitude larger than recent volcanic dome collapses (up to 0.2km3). The largest landslide deposits were emplaced in at least two stages, initiated by the emplacement of volcanic debris avalanches which then triggered larger-scale failure of seafloor sediment, with deformation propagating progressively downslope for up to 30km on gradients of <1°. An unusually detailed seismic, side-scan sonar and bathymetric dataset shows that the largest landslide off Montserrat (forming Deposit 8) incorporated ~70m of in-situ sediment stratigraphy, and comprises ~80% seafloor sediment by volume. Well-preserved internal bedding and a lack of shortening at the frontally-confined toe of the landslide, shows that sediment failure involved only limited downslope transport. We discuss a range of models for progressively-driven failure of in-situ bedded seafloor sediment. For Deposit 8 and for comparable deposits elsewhere in the Lesser Antilles, we suggest that failure was driven by an over-running surface load that generated excess pore pressures in a weak and deforming undrained package of underlying stratigraphy. A propagating basal shear rupture may have also enhanced the downslope extent of sediment failure. Extensive seafloor-sediment failure may commonly follow debris avalanche emplacement around volcanic islands if the avalanche is emplaced onto a fine-grained parallel-bedded substrate. The timing of landslides off Montserrat is clustered, and associated with the deposition of thick submarine pyroclastic fans. These episodes of enhanced marine volcaniclastic input are separated by relatively quiescent periods of several 100ka, and correspond to periods of volcanic edifice maturity when destructive processes dominate over constructive processes.
► Marine volcanic debris avalanche emplacement can lead to much larger sediment failure. ► Failure is progressive, through in situ-strata, and frontally non-emergent. ► Sediment failure propagates on very low gradients, dominating final deposit volume. ► Process involves undrained loading and/or shear rupture, and may be repeated widely. ► Landslide timing reflects timescales of volcanic edifice growth and destruction.
SUMMARY Standard seismic acquisition and processing require appropriate source–receiver offsets. P-cable technology represents the opposite, namely, very short source–receiver offsets at the price of ...increased spatial and lateral resolution with a high-frequency source. To use this advantage, a processing flow excluding offset information is required. This aim can be achieved with a processing tuned to diffractions because point diffractions scatter the same information in the offset and midpoint direction. Usually, diffractions are small amplitude events and a careful diffraction separation is required as a first step. We suggest the strategy to use a multiparameter stacking operator, for example, common-reflection surface, and stack along the midpoint direction. The obtained kinematic wave-front attributes are used to calculate time-migration velocities. A diffractivity map serves as a filter to refine the velocities. This strategy is applied to a 3-D P-cable data set to obtain a time-migrated image.
Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, ...and also identified potential prognostic factors.
Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3-6 months and analyzed using repeated-measures ANOVA.
Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (-1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness.Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC.
We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.
Accumulating evidence suggests that higher Mediterranean diet (MedDiet) adherence is associated with higher global cognitive performance and brain structural integrity as well as decreased risk of ...Alzheimer disease (AD) and vascular dementia (VaD).
We directly examined cross-sectional associations between the MedDiet and cognitive and neuroimaging phenotypes associated with AD and VaD (separately) in a cohort of nondemented, nondepressed older adults.
Community-dwelling older adults (n = 82; aged ∼68.8 y; 50% female, 50% minority) underwent dietary (Block Food Frequency Questionnaire 2005) and neuropsychological assessments and neuroimaging. MedDiet scores were quantified with the use of published criteria, and participants were divided into High and Low (median split) adherence groups. We focused our neuropsychological investigation on cognitive phenotypes primarily associated with AD i.e., learning and memory (L&M) and VaD (i.e., information processing and executive functioning). AD neuroimaging phenotypes consisted of hippocampal and dentate gyrus volumes quantified using T1-weighted images and the FreeSurfer 6.0 segmentation pipeline (http://surfer.nmr.mgh.harvard.edu). The VaD neuroimaging phenotype consisted of total white matter hyperintensity (WMH) volumes quantified using combined T1-weighted and T2-fluid-attenuated inversion recovery images. Neuroimaging metrics were adjusted for total intracranial volume. Separate multivariable linear regression models controlling for age, sex, education, body mass index, and caloric intake examined the associations between MedDiet groups (High compared with Low) and cognitive and neuroimaging outcomes.
When compared with the Low MedDiet group, the High MedDiet group was associated with better L&M performance and larger dentate gyri. MedDiet adherence was not associated with information processing, executive functioning, or WMH.
Results highlight the association between increasing MedDiet adherence and specific cognitive and neuroimaging phenotypes that, when altered, are associated with AD.
Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Hillemanns P, Dörk T. High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from ...Belarus.
Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital‐based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first‐degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first‐degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non‐carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.
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