Seismotectonic setting at the North Anatolian Fault Zone after the 1999 Mw=7.4 Izmit earthquake based on high-resolution aftershock locations

International audienceThe most recent devastating earthquakes that occurred along the North Anatolian Fault Zone (NAFZ) in northwestern Turkey were the 1999 Izmit (Mw=7.4) and Düzce (Mw=7.1) events. In this study we present a catalog of Izmit aftershock hypocenters that was deduced from a network covering the entire 140 km long rupture of the mainshock. 7348 events with a location accuracy better than 5 km are analysed. Aftershocks were observed along the entire ruptured segment along a 20 km wide band of activity. Events are clustered in distinct regions and dominantly occur at 5 to 15 km depth. The eastern termination of the Izmit rupture is characterized by a sharp and steeply dipping boundary exactly where the Düzce mainshock initiated 87 days after the Izmit event. Relocation of the events using double-difference technology results in 4696 high-resolution hypocenters that allow resolving the internal structure of the seismically active areas with a resolution of 300 m (horizontal) and 400m (vertical). Below the Akyazi Plain, representing a small pull-apart structure at a triple junction of the NAFZ, we identify planes of activity that can be correlated with nodal planes of EW extensional normal faulting aftershocks. Along the easternmost Karadere-Düzce segment we identify the down-dip extension of the Karadere fault that hosted about 1 m of right-lateral coseismic slip. At the easternmost rupture we correlate a cloud-type distribution of seismic activity with the largest aftershocks in this area, a subevent of the Izmit mainshock and the Düzce mainshock that all have an almost identical focal mechanism. This part of the NAFZ is interpreted as a classical example of a seismic barrier along the fault

A high-dose pulse steroid regimen for controlling active chronic graft-versus-host disease

AbstractCorticosteroids remain essential for controlling active chronic graft-versus-host disease (cGVHD). However, the optimum dose and administration schedule is unknown. We have reviewed our results in 61 patients with severe refractory cGVHD who were treated with a high-dose pulse steroid regimen (PS) consisting of methylprednisolone at 10 mg/kg per day for 4 consecutive days, with subsequent tapering doses. After 4 days, all patients received a course of additional immunosuppressive therapy. The median age of the 56 patients who were evaluable for response was 32 years (range, 0.2-57 years). Patients had failed a median of 2 (range, 1-5) treatments prior to the PS. The median follow-up for 45 surviving patients after PS was 1.5 years. The probability of survival at 1 year and 2 years after PS was 88% (95% confidence interval [CI], 76%-95%) and 81% (95% CI, 65%-91%), respectively. Twenty-seven patients (48%) showed a major response to PS with substantial improvement of cGVHD manifestations, including softening of the skin, increased range of motion, and improved performance status; 15 patients (27%) showed a minor response, defined as improvement in some but not all symptoms of cGVHD. Of the 42 responders, 21 (50%) had progression of their cGVHD afterwards. The median time to progression was 1.9 years. The probability of progression at 1 and 2 years after PS was 36% (95% CI, 23%-53%) and 54% (95% CI, 38%-71%), respectively. The probability of progression at 1 year was 25% (95% CI, 12%-47%) and 55% (95% CI, 32%-81%) for patients who had major and minor response, respectively (hazard ratio, 2.13). Ten of the 42 responders (24%) were able to discontinue all systemic immunosuppressive treatments. The probability of discontinuation at 1 and 2 years after PS was 9% (95% CI, 3%-25%) and 27% (95% CI, 15%-48%), respectively. The treatment was well tolerated with no serious adverse events. Our results suggest that PS is a well-tolerated regimen for achieving rapid clinical response in the majority of patients with cGVHD who failed on multiple previous therapies. Further studies are warranted to maintain the efficacy of this regimen by combining with new active agents in cGVHD.Biol Blood Marrow Transplant 2001;7(9):495-502

KNOWLEDGE LEVELS AND ATTITUDES OF INTERNISTS ABOUT THE RELATIONSHIP BETWEEN PERIODONTAL DISEASE AND DIABETES

AIMS: Periodontitis is a multifactorial, chronic inflammatory disease that can cause irreversible damage to the supporting tissues surrounding the teeth and consequently tooth loss if left untreated, and has been listed as the sixth major complication of diabetic patients. The aim of our study was to evaluate the knowledge levels and attitudes of internists about the relationship between periodontal disease and diabetes. METHODS: In our study, our questionnaire with 22 questions was applied to internists via whatsapp®, e-mail and directly. Participants were asked about specific periodontal complications that they believed patients diagnosed with diabetes were more susceptible to, and their awareness of the bidirectional relationship between diabetes and periodontal diseases was evaluated. 112 internists answered (45% male, 55% female) our questionnaire. RESULTS: 70% of the internists participating in our survey are between the ages of 25-35. 92.7% of internists know that the department that diagnoses and treats gingival diseases is the periodontology clinic. Despite this, only 72.7% refer their patients with gingival bleeding to the periodontology clinic. 58.4% of internists reported that they did not learn about the relationship between periodontal disease and systemic health during medical school education, and 89% stated that the effect of periodontal disease on systemic health should be explained in medical school education. CONCLUSIONS: Periodontal disease and diabetes are thought to share a common pathogenesis that includes increased inflammatory response at local and systemic levels, and it is known that there is a bidirectional relationship. Therefore, successful treatment of both will affect each other positively. It has been observed that internists have knowledge about diabetes and periodontal disease in Turkey, but it is thought that it would be beneficial to consider the relationship between diabetes and periodontal disease in more detail within the education program of the medical faculty

ML scale in Northwestern Turkey from 1999 Izmit aftershocks: updates

We present an update of the local magnitude scale previously calibrated for Northwestern Turkey by Baumbach et al. (2003). The path coverage in the westernmost part of the analysed area has been increased, as well as the number of amplitudes for distance greater than 110 km. Furthermore, a set of recordings from accelerometric stations operated by the Kandilli Observatory and Earthquake Research Institute (KOERI) has been merged with the recordings by the Sapanca-Bolu and GermanTaskForce seismological networks. In all, 4047 recordings from 528 earthquakes recorded by 31 seismometers and 23 accelerometers are considered to calibrate the local magnitude scale over a hypocentral distance range from 10 to 190 km. By analyzing the unit covariance matrix and the resolution matrix, we show how the source-to-station geometries of the seismic and strong motion networks affect the uncertainties of the computed station corrections, attenuation coefficients, and magnitudes. The assumptions made concerning the reference station correction, and the change in the amplification for the Wood-Anderson torsion seismograph from 2800 to 2080 (Uhrhammer and Collins, 1990) introduced an offset of about 0.34 in the magnitudes with respect to Baumbach et al. (2003), with the updated local magnitude scale ranges from 0.50 to 5.91. The distribution of the residuals with distance confirms that the extension of both the magnitude and distance ranges and the improved path coverage have preserved the high quality that characterized the data set analyzed by Baumbach et al. (2003)

ML scale in Northwestern Turkey from 1999 Izmit aftershock: updates

Abstract We present an update of the local magnitude scale previously calibrated for northwestern Turkey by Baumbach et al. (2003). The path coverage in the westernmost part of the analyzed area has been increased, as well as the number of amplitudes for distance greater than 110 km. Furthermore, a set of recordings from accelerometric stations operated by the Kandilli Observatory and Earthquake Research Institute (KOERI) has been merged with the recordings by the Sapanca-Bolu and German Task Force seismological networks. In all, 4047 recordings from 528 earthquakes recorded by 31 seismometers and 23 accelerometers are considered to calibrate the local magnitude scale over a hypocentral distance range from 10 to 190 km. By analyzing the unit covariance matrix and the resolution matrix, we show how the source-to-station geometries of the seismic and strong-motion networks affect the uncertainties of the computed station corrections, attenuation coefficients, and magnitudes. The assumptions made concerning the reference station correction, and the change in the amplification for the Wood–Anderson torsion seismograph from 2800 to 2080 (Uhrhammer and Collins, 1990) introduced an offset of about 0.34 in the magnitudes with respect to Baumbach et al. (2003), with the updated local magnitude scale ranges from 0.50 to 5.91. The distribution of the residuals with distance confirms that the extension of both the magnitude and distance ranges and the improved path coverage have preserved the high quality that characterized the data set analyzed by Baumbach et al. (2003)

A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice

Our goal is to develop a rapid and scalable system for functionally evaluating deregulated genes in multiple myeloma (MM). Here, we forcibly expressed human cMYC and KRAS12V in mouse T2 B cells (IgM+B220+CD38+IgD+) using retroviral transduction and transplanted these cells into lethally irradiated recipient mice. Recipients developed plasmacytomas with short onset (70 days) and high penetrance, whereas neither cMYC nor KRAS12V alone induced disease in recipient mice. Tumor cell morphology and cell surface biomarkers (CD138+B220−IgM−GFP+) indicate a plasma cell neoplasm. Gene set enrichment analysis further confirms that the tumor cells have a plasma cell gene expression signature. Plasmacytoma cells infiltrated multiple loci in the bone marrow, spleen and liver; secreted immunoglobulins; and caused glomerular damage. Our findings therefore demonstrate that deregulated expression of cMYC with KRAS12V in T2 B cells rapidly generates a plasma cell disease in mice, suggesting utility of this model both to elucidate molecular pathogenesis and to validate novel targeted therapies

Eltrombopag for the treatment of immune thrombocytopenia: The aegean region of Turkey experience

Objective: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. Materials and Methods: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. Results: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. Conclusion: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events. © 2015 Turkish Society of Hematology. All rights reserved

Lenalidomide for the Treatment of Relapsed and Refractory Multiple Myeloma

Lenalidomide is an amino-substituted derivative of thalidomide with direct antiproliferative and cytotoxic effects on the myeloma tumor cell, as well as antiangiogenic activity and immunomodulatory effects. Together with the introduction of bortezomib and thalidomide, lenalidomide has significantly improved the survival of patients with relapsed and refractory myeloma. The most common adverse events associated with lenalidomide include fatigue, skin rash, thrombocytopenia, and neutropenia. In addition, when lenalidomide is combined with dexamethasone or other conventional cytotoxic agents, there is an increase in the incidence of venous thromboembolic events. There is now evidence that continued treatment with lenalidomide has a significant impact on survival by improving the depth and duration of response. This highlights the value of adverse event management and appropriate dose adjustments to prevent toxicity, and of allowing continued treatment until disease progression. In this review, we will discuss the different lenalidomide-based treatment regimens for patients with relapsed/refractory myeloma. This is accompanied by recommendations of how to manage and prevent adverse events associated with lenalidomide-based therapy

Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task

Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia

AbstractCombinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality. TAC+MTX was used more frequently in older patients and, in recent years, in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier absolute neutrophil count recovery in SIB recipients. Other outcomes did not differ statistically between the 2 regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after hematopoietic cell transplantation for acquired aplastic anemia. Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia