42 research outputs found
Implications of extinction due to meteoritic smoke in the upper stratosphere
Recent optical observations of aerosols in the upper stratosphere and mesosphere show significant amounts of extinction at altitudes above about 40 km where the stratospheric sulfate aerosol layer ends. Recent modeling of this region reveals that meteoritic smoke settling from the mesosphere and its interaction with the upper part of the sulfate aerosol layer is the origin of the observed extinction. Extinction in this region has major implications for the interpretation and analysis of several kinds of aerosol data (satellite and lidar). We compare observations from the SAGE II satellite and from NOAA's lidar located at Mauna Loa, Hawaii to extinction profiles derived from the Whole Atmosphere Community Climate Model (WACCM) coupled with the Community Aerosol and Radiation Model for Atmospheres (CARMA). Our results show that a major source of extinction exists in the region above about 30 km that must be addressed by all remote sensing instruments that have traditionally used the stratosphere above about 30 km as an aerosol free region to estimate the molecular component of their total extinction. It is also shown that meteoritic smoke not only contributes to but also becomes the dominant source of aerosol extinction above 35 km and poleward of 30 degrees in latitude, as well as above 40 km in the tropics. After addressing the concerns described here, current and past observations of this region could be reanalyzed to further our understanding of meteoritic dust in the upper stratosphere
ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.
Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild-moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8-14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different
LUMiC(A (R)) Endoprosthetic Reconstruction After Periacetabular Tumor Resection:Short-term Results
Reconstruction of periacetabular defects after pelvic tumor resection ranks among the most challenging procedures in orthopaedic oncology, and reconstructive techniques are generally associated with dissatisfying mechanical and nonmechanical complication rates. In an attempt to reduce the risk of dislocation, aseptic loosening, and infection, we introduced the LUMiC(A (R)) prosthesis (implantcast, Buxtehude, Germany) in 2008. The LUMiC(A (R)) prosthesis is a modular device, built of a separate stem (hydroxyapatite-coated uncemented or cemented) and acetabular cup. The stem and cup are available in different sizes (the latter of which is also available with silver coating for infection prevention) and are equipped with sawteeth at the junction to allow for rotational adjustment of cup position after implantation of the stem. Whether this implant indeed is durable at short-term followup has not been evaluated. (1) What proportion of patients experience mechanical complications and what are the associated risk factors of periacetabular reconstruction with the LUMiC(A (R)) after pelvic tumor resection? (2) What proportion of patients experience nonmechanical complications and what are the associated risk factors of periacetabular reconstruction with the LUMiC(A (R)) after pelvic tumor resection? (3) What is the cumulative incidence of implant failure at 2 and 5 years and what are the mechanisms of reconstruction failure? (4) What is the functional outcome as assessed by Musculoskeletal Tumor Society (MSTS) score at final followup? We performed a retrospective chart review of every patient in whom a LUMiC(A (R)) prosthesis was used to reconstruct a periacetabular defect after internal hemipelvectomy for a pelvic tumor from July 2008 to June 2014 in eight centers of orthopaedic oncology with a minimum followup of 24 months. Forty-seven patients (26 men [55%]) with a mean age of 50 years (range, 12-78 years) were included. At review, 32 patients (68%) were alive. The reverse Kaplan-Meier method was used to calculate median followup, which was equal to 3.9 years (95% confidence interval [CI], 3.4-4.3). During the period under study, our general indications for using this implant were reconstruction of periacetabular defects after pelvic tumor resections in which the medial ilium adjacent to the sacroiliac joint was preserved; alternative treatments included hip transposition and saddle or custom-made prostheses in some of the contributing centers; these were generally used when the medial ilium was involved in the tumorous process or if the LUMiC(A (R)) was not yet available in the specific country at that time. Conventional chondrosarcoma was the predominant diagnosis (n = 22 [47%]); five patients (11%) had osseous metastases of a distant carcinoma and three (6%) had multiple myeloma. Uncemented fixation (n = 43 [91%]) was preferred. Dual-mobility cups (n = 24 [51%]) were mainly used in case of a higher presumed risk of dislocation in the early period of our study; later, dual-mobility cups became the standard for the majority of the reconstructions. Silver-coated acetabular cups were used in 29 reconstructions (62%); because only the largest cup size was available with silver coating, its use depended on the cup size that was chosen. We used a competing risk model to estimate the cumulative incidence of implant failure. Six patients (13%) had a single dislocation; four (9%) had recurrent dislocations. The risk of dislocation was lower in reconstructions with a dual-mobility cup (one of 24 [4%]) than in those without (nine of 23 [39%]) (hazard ratio, 0.11; 95% CI, 0.01-0.89; p = 0.038). Three patients (6%; one with a preceding structural allograft reconstruction, one with poor initial fixation as a result of an intraoperative fracture, and one with a cemented stem) had loosening and underwent revision. Infections occurred in 13 reconstructions (28%). Median duration of surgery was 6.5 hours (range, 4.0-13.6 hours) for patients with an infection and 5.3 hours (range, 2.8-9.9 hours) for those without (p = 0.060); blood loss was 2.3 L (range, 0.8-8.2 L) for patients with an infection and 1.5 L (range, 0.4-3.8 L) for those without (p = 0.039). The cumulative incidences of implant failure at 2 and 5 years were 2.1% (95% CI, 0-6.3) and 17.3% (95% CI, 0.7-33.9) for mechanical reasons and 6.4% (95% CI, 0-13.4) and 9.2% (95% CI, 0.5-17.9) for infection, respectively. Reasons for reconstruction failure were instability (n = 1 [2%]), loosening (n = 3 [6%]), and infection (n = 4 [9%]). Mean MSTS functional outcome score at followup was 70% (range, 33%-93%). At short-term followup, the LUMiC(A (R)) prosthesis demonstrated a low frequency of mechanical complications and failure when used to reconstruct the acetabulum in patients who underwent major pelvic tumor resections, and we believe this is a useful reconstruction for periacetabular resections for tumor or failed prior reconstructions. Still, infection and dislocation are relatively common after these complex reconstructions. Dual-mobility articulation in our experience is associated with a lower risk of dislocation. Future, larger studies will need to further control for factors such as dual-mobility articulation and silver coating. We will continue to follow our patients over the longer term to ascertain the role of this implant in this setting. Level IV, therapeutic study
Treatment-Related Survival Patterns in Diffuse Intrinsic Pontine Glioma (DIPG) Using a Historical Cohort: A Report from the European Society for Pediatric Oncology DIPG/DMG Registry
Background:Our aim is to investigate the association of treatment with survival in patients with diffuse intrinsic pontine glioma (DIPG), by examining six historical treatment paths.Methods:We retrospectively analyzed data from 409 patients with radiologically centrally reviewed DIPG, sourced from the GPOH HIT-HGG trial database and the SIOPE DIPG/DMG Registry. Survival outcomes were estimated using the Kaplan Meier method and univariable and multivariable Cox proportional hazard models were estimated to study treatment effect.Results:Median overall survival (OS) from diagnosis was 11.2 months (95% CI, 10.5-11.9). Patients who by choice received no frontline treatment had an OS of 3.0 months (95% CI, 2.0-4.0), while those treated with radiation therapy (RT) alone had a median OS of 10.4 months (95% CI, 9.1-11.8). Those receiving RT combined with chemotherapy had the longest median OS of 11.7 months (95% CI, 10.8-12.6). Median survival after first progression (PPS) was 4.1 months (95% CI, 3.5-4.7). Patients who relapsed and did not receive treatment had a PPS of 2.2 months (95% CI, 1.8-2.6), while those treated with chemotherapy alone had a PPS of 4.4 months (95% CI, 3.7-5.0), and those who underwent reirradiation, with or without chemotherapy, had the longest survival after relapse of 6.6 months (95% CI, 5.3-8.0). Treatment differences remained significant in multivariable analysis adjusted for age and symptom duration, in both the diagnosis and relapse setting.Conclusions:This study shows increased survival outcomes associated with radio- and chemotherapy treatment or a combination thereof, at diagnosis and relapse, in a historical DIPG cohort
Age-related differences of oncological outcomes in primary extremity soft tissue sarcoma: a multistate model including 6260 patients
Abstract Purpose: No studies extensively compared the young adults (YA, 18e39 years),
middle-aged (40e69 year
The Lactobacillus plantarum ftsH Gene Is a Novel Member of the CtsR Stress Response Regulon
FtsH proteins have dual chaperone-protease activities and are involved in protein quality control under
stress conditions. Although the functional role of FtsH proteins has been clearly established, the regulatory
mechanisms controlling ftsH expression in gram-positive bacteria remain largely unknown. Here we show that
ftsH of Lactobacillus plantarum WCFS1 is transiently induced at the transcriptional level upon a temperature
upshift. In addition, disruption of ftsH negatively affected the growth of L. plantarum at high temperatures.
Sequence analysis and mapping of the ftsH transcriptional start site revealed a potential operator sequence for
the CtsR repressor, partially overlapping the 35 sequence of the ftsH promoter. In order to verify whether
CtsR is able to recognize and bind the ftsH promoter, CtsR proteins of Bacillus subtilis and L. plantarum were
overproduced, purified, and used in DNA binding assays. CtsR from both species bound specifically to the ftsH
promoter, generating a single protein-DNA complex, suggesting that CtsR may control the expression of L.
plantarum ftsH. In order to confirm this hypothesis, a ctsR mutant strain of L. plantarum was generated.
Expression of ftsH in the ctsR mutant strain was strongly upregulated, indicating that ftsH of L. plantarum is
negatively controlled by CtsR. This is the first example of an ftsH gene controlled by the CtsR repressor, and
the first of the low-GC gram-positive bacteria where the regulatory mechanism has been identified
The Lactobacillus plantarum ftsH Gene Is a Novel Member of the CtsR Stress Response Regulon â–¿
FtsH proteins have dual chaperone-protease activities and are involved in protein quality control under stress conditions. Although the functional role of FtsH proteins has been clearly established, the regulatory mechanisms controlling ftsH expression in gram-positive bacteria remain largely unknown. Here we show that ftsH of Lactobacillus plantarum WCFS1 is transiently induced at the transcriptional level upon a temperature upshift. In addition, disruption of ftsH negatively affected the growth of L. plantarum at high temperatures. Sequence analysis and mapping of the ftsH transcriptional start site revealed a potential operator sequence for the CtsR repressor, partially overlapping the −35 sequence of the ftsH promoter. In order to verify whether CtsR is able to recognize and bind the ftsH promoter, CtsR proteins of Bacillus subtilis and L. plantarum were overproduced, purified, and used in DNA binding assays. CtsR from both species bound specifically to the ftsH promoter, generating a single protein-DNA complex, suggesting that CtsR may control the expression of L. plantarum ftsH. In order to confirm this hypothesis, a ΔctsR mutant strain of L. plantarum was generated. Expression of ftsH in the ΔctsR mutant strain was strongly upregulated, indicating that ftsH of L. plantarum is negatively controlled by CtsR. This is the first example of an ftsH gene controlled by the CtsR repressor, and the first of the low-G+C gram-positive bacteria where the regulatory mechanism has been identified
Characterization of the CtsR Stress Response Regulon in Lactobacillus plantarum â–¿ â€
Lactobacillus plantarum ctsR was characterized. ctsR was found to be cotranscribed with clpC and induced in response to various abiotic stresses. ctsR deletion conferred a heat-sensitive phenotype with peculiar cell morphological features. The transcriptional pattern of putative CtsR regulon genes was examined in the ΔctsR mutant. Direct CtsR-dependent regulation was demonstrated by DNA-binding assays using recombinant CtsR and the promoters of the ctsR-clpC operon and hsp1