Occupational orthopedic problems and its relation to personal radiation protection in interventional radiology.

PURPOSE: Several studies report occupational orthopedic problems among interventional cardiologists. These health problems are usually multifactorial. However, the personal protective equipment used should play a major role. An online survey was conducted to determine the frequency of such health problems among interventional radiologists and to correlate them with the use of personal radiation protective clothing. MATERIAL AND METHODS: An anonymous online survey that comprised of 17 questions was sent via e-mail to 1427 members of the German Society for Interventional Radiology (DeGIR) in Germany, Austria and Switzerland. The questions were focused on interventional workload, the use of personal radiation protection apparel and orthopedic problems. Given the different scale levels, the associations between the variables were analyzed using different statistical methods. A significance level of p < 0.05 was chosen. RESULTS: There were 221 survey responders (15.5% response rate). About half of responders (47.7%) suffered from more than five episodes of orthopedic problems during their interventional career. Lumbar spine was involved in 81.7% of these cases, cervical spine in 32.8%, shoulder in 28.5% and knee in 24.7%. Because of orthopedic problems, 16.1% of the responders had to reduce and 2.7% had to stop their interventional practice. The number of affected body regions correlates with the fit of the radiation protection means (p < 0.05, r = 0.135) and the reduction of activity as an interventional radiologist (p < 0.05, r = -0.148). CONCLUSION: Overall, the survey reveals widespread orthopedic problems at several body regions among interventional radiologists, associated with the fit of radiation protection systems, among other factors. A connection between the orthopaedic complaints and the radiation protection system used could not be established.

Joint replacement increases radiation exposure to the staff in angiography: A phantom study.

INTRODUCTION: The present study investigates the influence of joint prostheses on the amount of scattered radiation in a simulated angiography set-up. MATERIALS AND METHODS: A clinical angiography system (Artis Zee, Siemens Healthineers, Germany) with a water phantom as a scattering object was used. The scattered radiation of the water phantom was repeatedly measured without prosthesis, with a knee prosthesis and a hip prosthesis made from titanium, aluminum, vanadium, ceramics and polyethylene. For radiation measurement an ionization chamber (ambient dose equivalent rate from 0.1 µSv/h - 100 Sv/h, UMo, Berthold Technologies, Germany) was used. It was positioned on the right side of the phantom simulating an interventional procedure via the right femoral artery. The ionization chamber was positioned at 5 different heights (30, 100, 130, 150 and 165 cm), simulating different body parts of the interventionist. In addition, the amount of scattered radiation in relation to the tube angulation was investigated. RESULTS: Averaged over all angulations at a height of 165 cm, the radiation dose was 2.7 times higher (1935 µSv/h, p < 0.01) when a hip prosthesis was present in comparison to no prosthesis (713 µSv/h). The radiation dose was 3.9 times higher with the integration of a knee prosthesis (2778 µSv/h, p < 0.01) compared to that without prosthesis. The average radiation dose over all angulations and all heights was 1491 µSv/h without prosthesis, 4538 µSv/h with a hip prothesis and 5023 µSv/h with a knee prosthesis respectively. CONCLUSION: This experimental study shows a significant increase in the radiation dose when a joint prosthesis is present in the examination field. Special attention and sufficient radiation protection is therefore necessary for investigations with implanted prostheses.

Scatter radiation reduction with a radiation-absorbing pad in interventional radiology examinations.

PURPOSE: Radiation-absorbing pads are an additional possibility to reduce scattered radiation at its source. The goal of this study is to investigate the efficacy of a new reusable radiation-absorbing pad at its origin in an experimental setup. MATERIAL AND METHODS: All measurements were carried out using a clinical angiography system with a standardized fluoroscopy protocol, different C-arm angulations and an anthropomorphic torso phantom as a scattering body. An ionization chamber was used to measure the radiation exposure at five different heights of a simulated operator during a simulated transfemoral angiography intervention. Measurements were carried out with and without radiation-absorbing pads with lead equivalents of 0.25 and 0.5 mm placed onto the scattering body. For all measurements a mobile acrylic shield and an under-table lead curtain was used. RESULTS: At all operator heights from 100 to 165 cm a significant radiation dose reduction of up to 80.6 % (p < 0.01) using the radiation-absorbing pad was measured, when compared to no radiation-absorbing pad. At the height of 165 cm the radiation-absorbing pad with a lead equivalence of 0.5 mm showed a significant radiation dose reduction (51.4 %, p < 0.01) in comparison to a lead equivalence of 0.25 mm. CONCLUSION: The addition of a radiation-absorbing pad to the standard protection means results in a significant dose reduction for the operator, particularly for upper body parts.

Ivory vs. osseous ivory substitutes-Non-invasive diffractometric discrimination.

A new discrimination method for the bioapatite materials bone, antler and ivory was developed using X-ray diffractometry and comprises non-invasive measurements in order to take valuable objects into account. Our approach deals with the analysis of peak intensity ratios resulting from several measurements on each object. For instance, the intensity ratio of the apatite reflections 002 and 310 has been described in the literature as representing the degree of apatite crystal orientation and varies depending on the sample orientation. The decisive factor for the material identification is the value dispersion of intensity ratios resulting from the total of all measurements on one object. This pattern of data points, visualised via kernel density estimation (KDE), is characteristic for ivory, bone and antler, respectively, and enables the discrimination of these materials. The observation is justifiable since apatite crystal orientation adapts to the collagen fibre arrangement which shows major differences between different sorts of bioapatite materials. The patterns of data points were received via analysis of 88 objects made of bone (n = 30), antler (n = 27) and ivory (n = 31). In order to verify several identifications X-ray computer tomography was supplemented. The presented method usefully supplements already existing approaches concerning microscopic, elementary and biochemical analyses.

Protective Efficacy of Different Ocular Radiation Protection Devices: A Phantom Study.

PURPOSE: The aim of this study was to investigate the efficacy of different designs and types of ocular radiation protection devices depending on simulated varied body heights in a phantom-simulated thoracic intervention. MATERIALS AND METHODS: A clinical angiography system with a standardized fluoroscopy protocol with an anthropomorphic chest phantom as a scattering object and optically stimulated luminescence dosimeters for measuring radiation dose were used. The dosimeters were placed at the position of eyes of an anthropomorphic head phantom simulating the examiner. The head phantom was placed on a height-adjustable stand simulating the height of the examiner from 160 to 200 cm with 10 cm increments. The dose values were then measured with no radiation protection, a weightless-like radiation protection garment, radiation protection glasses and visors. RESULTS: The average dose reduction using radiation protection devices varied between 57.7 and 83.4% (p < 0.05) in comparison with no radiation protection. Some radiation protection glasses and visors showed a significant dose reduction for the eye lenses when the height of the examiner increased. The right eye was partially less protected, especially if the distances between the simulated examiner's head and the scatter object were small. CONCLUSION: All the investigated protection devices showed a significant reduction in radiation exposure to the simulated examiner. For some devices, the radiation dose increased with decreasing distance to the scattering object, especially for the right eye lens.

Logarithmic Upturn in Low-Temperature Electronic Transport as a Signature of d-Wave Order in Cuprate Superconductors.

In cuprate superconductors, high magnetic fields have been used extensively to suppress superconductivity and expose the underlying normal state. Early measurements revealed insulatinglike behavior in underdoped material versus temperature T, in which resistivity increases on cooling with a puzzling log(1/T) form. We instead use microwave measurements of flux-flow resistivity in YBa_{2}Cu_{3}O_{6+y} and Tl_{2}Ba_{2}CuO_{6+δ} to study charge transport deep inside the superconducting phase, in the low-temperature and low-field regime. Here, the transition from metallic low-temperature resistivity (dρ/dT>0) to a log(1/T) upturn persists throughout the superconducting doping range, including a regime at high carrier dopings in which the field-revealed normal-state resistivity is Fermi-liquid-like. The log(1/T) form is thus likely a signature of d-wave superconducting order, and the field-revealed normal state's log(1/T) resistivity may indicate the free-flux-flow regime of a phase-disordered d-wave superconductor.

An independent assessment of reliability of the Melbourne Cerebral Palsy Hip Classification System.

PURPOSE: Neuromuscular (NM) hip dysplasia is common in patients with cerebral palsy (CP). Traditionally, migration percentage (MP) has been used to measure the severity of NM hip dysplasia; however, the MP has some limitations. The purpose of this study is to determine the intra- and inter-reliability of the Melbourne Cerebral Palsy Hip Classification System in the typical paediatric population of patients with CP. METHODS: A total of 65 anteroposterior pelvis radiographs in patients (age range 12 years to 21 years) with CP spanning all grades (I to VI) of the classification system were identified and collected for analysis in this institutional review board approved study. Four paediatric orthopaedic surgeons and one orthopaedic surgical resident classified each radiograph according to the Melbourne system. Then, at least four weeks later, the raters repeated the process with a re-randomised order of radiographs. Statistical analysis was performed using the intraclass correlation coefficient (ICC) where < 0 denotes poor agreement and > 0.8 indicates almost perfect agreement. RESULTS: The interobserver reliability was found to be excellent with the ICC of 0.853 (0.813 to 0.887) and 0.839 (0.795 to 0.877). The intraobserver reliability was also found to be excellent with the ICC in the range of 0.838 to 0.933 among the raters. Subgroup analysis indicated no differences in the reliability of observers based on clinical experience. CONCLUSION: This study independently demonstrates that the Melbourne Cerebral Palsy Hip Classification System for NM hip dysplasia in patients with CP can be reliably used for communication among various healthcare providers and research and epidemiological purposes.

Alterations of hair cortisol and dehydroepiandrosterone in mother-infant-dyads with maternal childhood maltreatment.

BACKGROUND: Child maltreatment (CM) has severe effects on psychological and physical health. The hypothalamic-pituitary-adrenal (HPA) axis, the major stress system of the body, is dysregulated after CM. The analysis of cortisol and dehydroepiandrosterone (DHEA) in scalp hair presents a new and promising methodological approach to assess chronic HPA axis activity. This study investigated the effects of CM on HPA axis activity in the last trimester of pregnancy by measuring the two important signaling molecules, cortisol and DHEA in hair, shortly after parturition. In addition, we explored potential effects of maternal CM on her offspring's endocrine milieu during pregnancy by measuring cortisol and DHEA in newborns' hair. METHODS: CM was assessed with the Childhood Trauma Questionnaire (CTQ). Cortisol and DHEA were measured in hair samples of 94 mothers and 30 newborns, collected within six days after delivery. Associations of maternal CM on her own and her newborn's cortisol as well as DHEA concentrations in hair were analyzed with heteroscedastic regression models. RESULTS: Higher CM was associated with significantly higher DHEA levels, but not cortisol concentrations in maternal hair. Moreover, maternal CM was positively, but only as a non-significant trend, associated with higher DHEA levels in the newborns' hair. CONCLUSIONS: Results suggest that the steroid milieu of the mother, at least on the level of DHEA, is altered after CM, possibly leading to non-genomic transgenerational effects on the developing fetus in utero. Indeed, we observed on an explorative level first hints that the endocrine milieu for the developing child might be altered in CM mothers. These results need extension and replication in future studies. The measurement of hair steroids in mothers and their newborns is promising, but more research is needed to better understand the effects of a maternal history of CM on the developing fetus.

Thermomechanical method for cement extraction in revision arthroplasty.

BACKGROUND: In joint revision surgery, bone cement extraction remains a major challenge which even today has not seen a satisfactory solution yet. We studied in an experimental setting the impact of heat sources on the mechanical properties and microstructure of bone cement and determined the glass transition temperature (T G) of bone cement. As a result, it would be possible to establish a thermomechanical method which makes use of the structural and material-specific property changes inherent in bone cement at elevated temperatures. METHODS: Prepared samples of polymerized bone cement were thermoanalyzed with a Netzsch STA 409 C thermal analyzer. Samples weighing approx. 55 mg were heated to 390 °C at a rate of 5 K/min. Both simultaneous differential thermal analysis and thermogravimetry were employed. The thermomechanically induced changes in the microstructure of the material were analyzed with a computed tomography scanner specifically developed for materials testing (3D-µXCT). RESULTS: The bone cement changed from a firm elastic state over entropy-plastic (air atmosphere 60-155 °C) to a plastic viscosity state (air atmosphere >155 °C). Between 290 and 390 °C, the molten mass disintegrated (decomposition temperature). CONCLUSION: Our study was able to determine the glass transition temperature (T G) of bone cement which was about 60 and 65 °C under air and nitrogen, respectively. Heating the dry bone cement up to at least 65 °C would be more than halve the strength needed to detach it. Bone cement extraction would then be easy and swift.

Marked improvement in the success rate of medical management of early pregnancy failure following the implementation of a novel institutional protocol and treatment guidelines: a follow-up study.

PURPOSE: To analyze the success rate, time to passage of tissue and subjective patient experience of a newly implemented protocol for medical management of early pregnancy failure (EPF) over a 2-year period. METHODS: A retrospective chart review of all patients with early pregnancy failure primarily opting for medical management was performed. 200 mg mifepristone were administered orally, followed by a single vaginal dose of 800 mcg misoprostol after 36-48 h. We followed-up with our patients using a written questionnaire. RESULTS: 167 women were included in the present study. We observed an overall success rate of 92 %, defined as no need for surgical management after medication administration. We could not identify predictive values for success in a multivariate regression analysis. Most patients (84 %) passed tissue within 6 h after misoprostol administration. The protocol was well tolerated with a low incidence of side effects. Pain was managed well with sufficient analgesics. Responders to the questionnaire felt adequately informed prior to treatment and rated their overall experience as positive. CONCLUSION: The adaption of the institutional medical protocol resulted in a marked improvement of success rate when compared to the previously used protocol (92 vs. 61 %). We credit this increase to the adjusted medication schema as well as to targeted physician education on the expected course and interpretation of outcome measures. Our results underscore that the medical management of EPF is a safe and effective alternative to surgical evacuation in the clinical setting.

Long-term outcomes of lung transplant recipients with hepatitis C infection: a retrospective study of the U.S. transplant registry.

BACKGROUND: Chronic hepatitis C patients in need of a lung transplant are often considered ineligible due to their infection. AIM: To assess the association of hepatitis C virus (HCV) infection with long-term outcomes of lung transplants. METHODS: From the Scientific Registry of Transplant Recipients (1995-2011), we selected all adults with and without HCV infection who underwent lung transplantation. RESULTS: A total of 17 762 lung transplant recipients were included (55.5% bilateral). Of those, 319 (1.83%) had positive HCV serology. The HCV-positive recipients were 1.6 years younger, less Caucasian and more African-American, and had a significantly higher rate of co-infection with hepatitis B virus (all P < 0.001). Post-transplant patients were discharged alive at similar rates regardless of HCV status: 88.4% in HCV+ vs. 90.3% in HCV- (P = 0.25). The mortality rates were also similar at 1 and 2 years after transplantation (20.7% in HCV+ vs. 19.2% in HCV- and 31.6% in HCV+ vs. 28.9% in HCV-, respectively; both P > 0.05), but at post-transplant year 3 year, mortality rate in HCV+ became significantly higher (42.5% vs. 36.4%, P = 0.04) and remained higher for the duration of the follow-up (mean 9.1 years, max 18.4 years). In multivariate survival analysis, after adjustment for confounders, being HCV+ was associated with higher mortality: adjusted hazard ratio 1.24 (1.04-1.46), P = 0.01. No association of HCV infection with time to graft loss was found (P = 0.92). CONCLUSIONS: Chronic HCV infection is associated with a moderate increase in post-lung transplant mortality. Treatment of HCV in lung transplant recipients may, therefore, result in improvement of post-transplant outcomes.

Psychosocial Risk Factors for Child Welfare among Postpartum Mothers with a History of Childhood Maltreatment and Neglect.

Background: Childhood maltreatment (CM) can increase the risk of psychosocial risk factors in adulthood (e. g. intimate partner violence, financial problems, substance abuse or medical problems). The transition to parenthood presents those affected by CM with particular challenges, in addition to usual birth-related stressors. Methods: In this cross-sectional study a total of 240 women were interviewed in the puerperium with respect to CM experiences, using the German version of the Childhood Trauma Questionnaire (CTQ). Current psychosocial risk factors (e. g. financial concerns, maternal mental illness, single parent) were assessed using the Constance Index (KINDEX) for early childhood risk factors. Associations between CM experience and psychosocial risk factors were calculated using simple correlation. Results: The average age of participants was 33 years. On the CTQ 13.8 % of participants reported emotional abuse, 6.7 % physical abuse and 12.5 % sexual abuse, while 32.1 % reported emotional neglect and 7.5 % physical neglect during childhood. With rising severity of CM, more psychosocial risk factors (KINDEX) were present. Conclusions: This study shows a clear association between experiences of maltreatment during childhood and the presence of psychosocial stressors among women in the puerperium. Regular screening for a history of CM and parental psychosocial stressors should be conducted early, i.e. during pregnancy, to avoid negative consequences for the child.

Real-world evaluation of TNF-inhibitor utilization in rheumatoid arthritis.

OBJECTIVES: To evaluate 12-month treatment patterns, healthcare resource use (HCRU), and costs for patients with rheumatoid arthritis (RA), following initiation of index TNF inhibitors (TNFi) and subsequent biologic DMARDs (bDMARDs). METHODS: This was a retrospective cohort analysis of adults with RA newly initiating TNFi in the Truven Marketscan Commercial Claims and Encounters and Medicare Supplemental Databases during 2010-2013. A sub-group of patients who switched to a bDMARD within 12 months post-index and within 180 days of last index TNFi were subsequently evaluated over 12 months. TNFi/bDMARD treatment patterns were characterized as: continuers, no gap >180 days in prescription/administration of index TNFi; discontinuers, gap >180 days; switchers, initiated new bDMARD. Concomitant conventional synthetic DMARD use, co-morbid chronic illnesses, and RA severity were assessed. All-cause/RA-related HCRU and costs were evaluated 12 months post-index. RESULTS: Of 9567 identified patients, 67.2%, 17.3%, and 15.4% were continuers, discontinuers, and switchers, respectively. Switchers had the highest 12-month unadjusted mean all-cause costs of $34,585 vs $33,051 for continuers (p = 0.1158) and $24,915 for discontinuers (p < 0.0001; discontinuers vs continuers, p < 0.0001). RA-related costs comprised 82.8%, 31.4%, and 85.7% of total costs for continuers, discontinuers, and switchers, respectively. Of 764 switchers, 68.2% switched to alternative TNFi (cyclers), the rest to non-TNFi bDMARDs; 36.7% of patients who switched to TNFi switched again (to third-line bDMARD) vs 27.6% (p = 0.0313) of those who switched to non-TNFi bDMARDs. Switchers to non-TNFi bDMARDs had higher mean 12-month all-cause costs of $76,580 compared with $50,689 for switchers to alternative TNFi (p < 0.0001); biologic-administration visits comprised 78.8% of the greater total RA-related costs of switchers to non-TNFi bDMARDs. CONCLUSIONS: Real-world TNFi discontinuation/switching rates correspond to randomized controlled trial non-response rates. TNFi cycling is common and associated with an increased likelihood of switching to third-line bDMARD. Switching to non-TNFi bDMARDs was associated with higher costs, mostly attributed to in-office administrations.

A wireless patch for sleep respiratory disorders applications.

This paper presents a conformable wireless patch and its mobile application for physical activity, spO2 and pCO2 recording associated to digital biomarkers that aim at providing the clinicians with a reliable computer-aided diagnosis tool for rapid and continuous monitoring of sleep respiratory disorders. Each part of the system is described and results are presented and discussed. The reflectance sp02 sensor has been tested in vivo on several body sites and several subjects then compared to a reference device. The electrochemical tcpO2 sensor has been validated in vitro. Based on these physiological parameters, the proposed algorithms to automatically identifying sleep respiratory events are compared to a reference index.

Well-differentiated neuroendocrine neoplasia: relapse-free survival and predictors of recurrence after curative intended resections.

BACKGROUND: Resection with curative intention is the cornerstone of treatment in patients with neuroendocrine tumors. A proportion of patients will relapse after R0 resection, but the factors predictive of recurrence are not well understood. METHODS: A database established 1998 at the University Hospital Marburg was queried for all patients with documented R0 resection. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Uni- and multivariate analyses were performed. RESULTS: 180 patients with a median age of 52 years entered the analysis. We observed 77 recurrences after a median time of 2.9 years. 24% of the recurrences occurred later than 5 years after operation. Median recurrence-free survival of the whole cohort was 101 months. In univariate analysis grade by Ki-67, stage, high lymph node ratio and microangioinvasion were significant predictors of recurrence. On multivariate analysis these parameters were confirmed as independent prognostic parameters with stage and microangioinvasion being the most important predictors. CONCLUSIONS: After R0 resection of neuroendocrine tumors, postoperative surveillance should be extended to at least 10 years. Patients with distant metastases and microangioinvasion are at high risk of recurrence. Clinical trials of adjuvant treatment protocols are indicated in these patients.

Expression of cancer testis antigens CT10 (MAGE-C2) and GAGE in gastrointestinal stromal tumors.

INTRODUCTION: Expression of cancer testis antigens (CTAs) has been associated with prognosis in gastrointestinal stromal tumors (GIST) and other malignancies. CTAs are currently being investigated for cancer immunotherapy. MATERIALS AND METHODS: We analyzed two CTAs, CT10/MAGE-C2 and GAGE, in 51 GIST by immunohistochemistry and correlated it with established histopathological criteria for malignancy. RESULTS: GAGE expression was found in 6/51 (12%) patients, whereas 5/51 (10%) patients expressed CT10/MAGE-C2. 7/51(14%) patients expressed at least one of both CTAs, in 4/51 (8%) patients both CTAs were positive. High-grade GIST are more likely to express GAGE (p = 0.002) and CT10/MAGE-C2 (p = 0.007) compared to less aggressive tumors. All patients with GAGE or CT10/MAGE-C2 expression had moderate- or high-risk of recurrence according to the established risk criteria. The presence of GAGE correlates with mitotic rate (p = 0.001) and tumor size (p = 0.02), but not with tumor location (p = 0.60). CT10/MAGE-C2 also significantly correlates with mitotic rate (p = 0.004) and tumor size (p = 0.002), whereas no correlation could be found with tumor location (p = 0.36). DISCUSSION: CT10/MAGE-C2 and GAGE should be explored together with other previously described CTAs as targets for immunotherapy of GIST in cases, which are refractory to conventional therapy.

Differential activity of GSK-3 isoforms regulates NF-κB and TRAIL- or TNFα induced apoptosis in pancreatic cancer cells.

While TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in neoplastic cells, many tumors, including pancreatic ductal adenocarcinoma (PDA), display intrinsic resistance, highlighting the need for TRAIL-sensitizing agents. Here we report that TRAIL-induced apoptosis in PDA cell lines is enhanced by pharmacological inhibition of glycogen synthase kinase-3 (GSK-3) or by shRNA-mediated depletion of either GSK-3α or GSK-3ß. In contrast, depletion of GSK-3ß, but not GSK-3α, sensitized PDA cell lines to TNFα-induced cell death. Further experiments demonstrated that TNFα-stimulated IκBα phosphorylation and degradation as well as p65 nuclear translocation were normal in GSK-3ß-deficient MEFs. Nonetheless, inhibition of GSK-3ß function in MEFs or PDA cell lines impaired the expression of the NF-κB target genes Bcl-xL and cIAP2, but not IκBα. Significantly, the expression of Bcl-xL and cIAP2 could be reestablished by expression of GSK-3ß targeted to the nucleus but not GSK-3ß targeted to the cytoplasm, suggesting that GSK-3ß regulates NF-κB function within the nucleus. Consistent with this notion, chromatin immunoprecipitation demonstrated that GSK-3 inhibition resulted in either decreased p65 binding to the promoter of BIR3, which encodes cIAP2, or increased p50 binding as well as recruitment of SIRT1 and HDAC3 to the promoter of BCL2L1, which encodes Bcl-xL. Importantly, depletion of Bcl-xL but not cIAP2, mimicked the sensitizing effect of GSK-3 inhibition on TRAIL-induced apoptosis, whereas Bcl-xL overexpression ameliorated the sensitization by GSK-3 inhibition. These results not only suggest that GSK-3ß overexpression and nuclear localization contribute to TNFα and TRAIL resistance via anti-apoptotic NF-κB genes such as Bcl-xL, but also provide a rationale for further exploration of GSK-3 inhibitors combined with TRAIL for the treatment of PDA.

Rates of serious infections, opportunistic infections, inflammatory bowel disease, and malignancies in subjects receiving etanercept vs. controls from clinical trials in ankylosing spondylitis: a pooled analysis.

OBJECTIVES: Therapies involving anti-tumour necrosis factor are associated with increased risk of serious infections, opportunistic infections, and some types of malignancies in subjects with rheumatic diseases. However, limited data have been collected for subjects with ankylosing spondylitis (AS). The aim of this retrospective analysis of all sponsor-conducted trials was to examine the rates of serious infections, inflammatory bowel disease (IBD), malignancies, and non-malignant skin cancers during treatment in subjects with AS. METHOD: Data from five randomized controlled trials (one sulfasalazine-controlled, four placebo-controlled) and four open-label studies evaluating etanercept were pooled for analyses. All randomized subjects who received at least one dose of treatment were included in the study. RESULTS: Analyses included 1323 subjects (> 1500 subject-years of treatment). Rate ratios of serious infections and IBD events for etanercept vs. placebo/sulfasalazine during the double-blind studies were 2.19 [95% confidence interval (CI) 0.22-107.79] and 1.09 (95% CI 0.06-64.56), respectively. There were no reports of opportunistic infections. Using the Surveillance, Epidemiology and End Results database, the standardized incidence ratio for malignancies was 1.47 (95% CI 0.54-3.21). CONCLUSIONS: These data suggest that etanercept is well tolerated in subjects with AS. Despite the large number of patients, the 95% CI data all cross 1.0, limiting possible conclusions. No new safety signals were observed.

Nodal quasiparticle dynamics in the heavy fermion superconductor CeCoIn5 revealed by precision microwave spectroscopy.

CeCoIn5 is a heavy fermion superconductor with strong similarities to the high-Tc cuprates, including quasi-two-dimensionality, proximity to antiferromagnetism and probable d-wave pairing arising from a non-Fermi-liquid normal state. Experiments allowing detailed comparisons of their electronic properties are of particular interest, but in most cases are difficult to realize, due to their very different transition temperatures. Here we use low-temperature microwave spectroscopy to study the charge dynamics of the CeCoIn5 superconducting state. The similarities to cuprates, in particular to ultra-clean YBa2Cu3O(y), are striking: the frequency and temperature dependence of the quasiparticle conductivity are instantly recognizable, a consequence of rapid suppression of quasiparticle scattering below T(c); and penetration-depth data, when properly treated, reveal a clean, linear temperature dependence of the quasiparticle contribution to superfluid density. The measurements also expose key differences, including prominent multiband effects and a temperature-dependent renormalization of the quasiparticle mass.

SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells.

SOX2 (Sex-determining region Y (SRY)-Box2) has important functions during embryonic development and is involved in cancer stem cell (CSC) maintenance, in which it impairs cell growth and tumorigenicity. However, the function of SOX2 in pancreatic cancer cells is unclear. The objective of this study was to analyze SOX2 expression in human pancreatic tumors and determine the role of SOX2 in pancreatic cancer cells regulating CSC properties. In this report, we show that SOX2 is not expressed in normal pancreatic acinar or ductal cells. However, ectopic expression of SOX2 is observed in 19.3% of human pancreatic tumors. SOX2 knockdown in pancreatic cancer cells results in cell growth inhibition via cell cycle arrest associated with p21(Cip1) and p27(Kip1) induction, whereas SOX2 overexpression promotes S-phase entry and cell proliferation associated with cyclin D3 induction. SOX2 expression is associated with increased levels of the pancreatic CSC markers ALDH1, ESA and CD44. Importantly, we show that SOX2 is enriched in the ESA(+)/CD44(+) CSC population from two different patient samples. Moreover, we show that SOX2 directly binds to the Snail, Slug and Twist promoters, leading to a loss of E-Cadherin and ZO-1 expression. Taken together, our findings show that SOX2 is aberrantly expressed in pancreatic cancer and contributes to cell proliferation and stemness/dedifferentiation through the regulation of a set of genes controlling G1/S transition and epithelial-to-mesenchymal transition (EMT) phenotype, suggesting that targeting SOX2-positive cancer cells could be a promising therapeutic strategy.