Gravitational lensing of the cosmic microwave background generates a curl pattern in the observed polarization. This "B-mode" signal provides a measure of the projected mass distribution over the ...entire observable Universe and also acts as a contaminant for the measurement of primordial gravity-wave signals. In this Letter we present the first detection of gravitational lensing B modes, using first-season data from the polarization-sensitive receiver on the South Pole Telescope (SPTpol). We construct a template for the lensing B-mode signal by combining E-mode polarization measured by SPTpol with estimates of the lensing potential from a Herschel-SPIRE map of the cosmic infrared background. We compare this template to the B modes measured directly by SPTpol, finding a nonzero correlation at 7.7σ significance. The correlation has an amplitude and scale dependence consistent with theoretical expectations, is robust with respect to analysis choices, and constitutes the first measurement of a powerful cosmological observable.
The Planck cosmic microwave background temperature data are best fit with a ΛCDM model that mildly contradicts constraints from other cosmological probes. The South Pole Telescope (SPT) 2540 SPT-SZ ...survey offers measurements on sub-degree angular scales (multipoles ) with sufficient precision to use as an independent check of the Planck data. Here we build on the recent joint analysis of the SPT-SZ and Planck data in Hou et al. by comparing ΛCDM parameter estimates using the temperature power spectrum from both data sets in the SPT-SZ survey region. We also restrict the multipole range used in parameter fitting to focus on modes measured well by both SPT and Planck, thereby greatly reducing sample variance as a driver of parameter differences and creating a stringent test for systematic errors. We find no evidence of systematic errors from these tests. When we expand the maximum multipole of SPT data used, we see low-significance shifts in the angular scale of the sound horizon and the physical baryon and cold dark matter densities, with a resulting trend to higher Hubble constant. When we compare SPT and Planck data on the SPT-SZ sky patch to Planck full-sky data but keep the multipole range restricted, we find differences in the parameters ns and . We perform further checks, investigating instrumental effects and modeling assumptions, and we find no evidence that the effects investigated are responsible for any of the parameter shifts. Taken together, these tests reveal no evidence for systematic errors in SPT or Planck data in the overlapping sky coverage and multipole range and at most weak evidence for a breakdown of ΛCDM or systematic errors influencing either the Planck data outside the SPT-SZ survey area or the SPT data at .
Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection are limited. Studies comparing daptomycin or linezolid in treating VRE bloodstream infection have conflicting ...results and suggest daptomycin underdosing. The responses to different daptomycin doses have not been studied. We conducted a multicentre prospective cohort study to compare linezolid and daptomycin (≥6 mg/kg) for the treatment of VRE bloodstream infection. The primary outcome was 14-day mortality. We used multivariate logistic regression analysis for outcome analysis and a generalized additive model for dose-dependent response estimation. Two hundred twelve patients were included (daptomycin, n = 141; linezolid, n = 71). All-cause 14-day mortality was higher in the daptomycin group (36.9% vs. 21.1%; p 0.03). After adjusting for confounders in logistic regression, mortality was lower in the linezolid group (adjusted odds ratio (aOR), 0.45; 95% confidence interval (CI), 0.21–0.96; p 0.04). The generalized additive model showed that higher-dose daptomycin (≥9 mg/kg) was associated with better survival than lower-dose daptomycin (6–9 mg/kg). Logistic regression showed that linezolid (aOR, 0.36; 95% CI, 0.17–0.79; p 0.01) and higher-dose daptomycin (aOR, 0.26; 95% CI, 0.09–0.74; p 0.01) independently predicted lower mortality compared to lower-dose daptomycin. Linezolid was not superior to higher-dose daptomycin in terms of mortality (aOR, 1.40; 95% CI, 0.45–4.37; p 0.57). Higher-dose daptomycin had lower mortality than lower-dose daptomycin. Despite higher mortality for lower-dose daptomycin than linezolid, linezolid conferred no survival benefit compared to higher-dose daptomycin. Our findings suggest that the recommended daptomycin dose is suboptimal for treating VRE bacteraemia.
Background
Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), two difficult‐to‐treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway ...inhibitor (HPI), was approved in laBCC based on results from the BOLT trial.
Objective
To evaluate long‐term efficacy and safety of sonidegib in laBCC and mBCC in the BOLT 18‐ and 30‐month analyses.
Methods
BOLT (NCT01327053, ClinicalTrials.gov), a double‐blind phase 2 study, enrolled patients from July 2011 until January 2013. Eligible HPI‐treatment–naïve patients with laBCC not amenable to curative surgery/radiotherapy or mBCC were randomized 1 : 2 to sonidegib 200 mg (laBCC, n = 66; mBCC, n = 13) or 800 mg (laBCC, n = 128; mBCC, n = 23). Tumour response was assessed per central and investigator review.
Results
With 30 months of follow‐up, among patients treated with sonidegib 200 mg (approved dose), objective response rates were 56.1% (central) and 71.2% (investigator) in laBCC and 7.7% (central) and 23.1% (investigator) in mBCC. Tumour responses were durable as follows: median duration of response was 26.1 months (central) and 15.7 months (investigator) in laBCC and 24.0 months (central) and 18.1 months (investigator) in mBCC. Five patients with laBCC and three with mBCC in the 200‐mg arm died. Median overall survival was not reached in either population; 2‐year overall survival rates were 93.2% (laBCC) and 69.3% (mBCC). In laBCC, efficacy was similar regardless of aggressive or non‐aggressive histology. Sonidegib 200 mg continued to have a better safety profile than 800 mg, with lower rates of grade 3/4 adverse events (43.0% vs. 64.0%) and adverse events leading to discontinuation (30.4% vs. 40.0%).
Conclusion
Sonidegib continued to demonstrate long‐term efficacy and safety in these populations. These data support the use of sonidegib 200 mg per local treatment guidelines.
Background and purpose
Recent large series studies have demonstrated that dehydration is common amongst stroke subjects and is associated with poor outcome. However, the effects of hydration status ...on the development of collaterals have never been discussed. In this study, the hypothesis that hydration status is an important factor for developing collaterals after acute middle cerebral artery (MCA) infarction was tested.
Methods
Eighty‐seven patients with acute infarction due to occlusion of the MCA were enrolled. Two collateral markers, posterior cerebral artery (PCA) laterality and fluid‐attenuated inversion recovery hyperintense vessels (HVs) were assessed from magnetic resonance imaging. Dehydration status was defined by a nitrogen to creatinine ratio ≧ of 15. The associations between dehydration status and the development of collaterals were estimated.
Results
Sixty‐one of 87 patients (70.1%) were identified as dehydrated. The development of PCA laterality and HVs shows a significant difference between dehydrated and euhydrated patients. A serum nitrogen to creatinine ratio <15, diastolic blood pressure and the presence of a dense MCA on computed tomography were significantly associated with the development of PCA laterality. A serum nitrogen to creatinine ratio <15, the initial National Institutes of Health Stroke Scale score, the presence of a dense MCA and calcifications of the internal carotid artery on computed tomography were significantly associated with the development of HVs. Dehydration remained an independent negative predictor for the development of PCA laterality and HVs in the multivariate analysis.
Conclusions
Hydration status is associated with the development of collateral flow after acute MCA occlusion. This preliminary study provides an imaging clue that hydration status and early hydration therapy could be important for acute stroke management.
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Summary
North American horses are commonly exposed to Leptospira organisms. Leptospira Bratislava is the most common infecting serovar but this serovar has not been confirmed to cause clinical ...disease in North American horses. Leptospira Pomona type kennewicki is responsible for most of the clinical diseases (leptospirosis) in North American horses. Leptospirosis is most commonly associated with diseases of the placenta and fetus, the kidneys and the eyes in horses. In‐utero infections in pregnant mares may result in abortion, neonatal illness or birth of an antibody positive healthy foal. Acute renal failure in younger horses and recurrent uveitis in adult horses are other well documented clinical syndromes of leptospirosis. Abortions, neonatal disease and acute renal failure are caused by a subacute infection, while horses with Leptospira associated recurrent uveitis develop ocular disease months or years after the initial Leptospira infection. Diagnosis of Leptospirosis is made by a combination of antigen or antibody testing methods. Mares that abort following Leptospira infection have no additional clinical signs at the time of abortion but may shed the offending Leptospira spp. in the urine for several weeks. Antibiotic treatments are sometimes used in hopes of decreasing Leptospira shedding in infected horses or prophylactically in exposed pregnant mares but documentation of efficacy is lacking. Horses with Leptospira ‐ associated acute renal failure can be successfully treated with antibiotics and supportive care. Recurrent uveitis is commonly associated with leptospirosis in North American horses and although horses may have chronic intraocular infection triggering an immune disease, systemic antimicrobial therapy has not been effective in eliminating the organism from the eye. An equine approved Leptospira Pomona type kennewicki vaccine is now available in North America.
Percutaneous radiofrequency ablation combined with vertebral augmentation has emerged as a minimally invasive treatment for patients with vertebral metastases who do not respond to or have ...contraindications to radiation therapy. The prevalence of posterior vertebral body metastases presents access and treatment challenges in the unique anatomy of the spine. The purpose of this study was to evaluate the safety and efficacy of simultaneous bipedicular radiofrequency ablation using articulating bipolar electrodes combined with vertebral augmentation for local tumor control of spinal metastases.
Imaging-guided simultaneous bipedicular radiofrequency ablation combined with vertebral augmentation was performed in 27 patients (33 tumors) with vertebral metastases selected following multidisciplinary consultations, to achieve local tumor control in this retrospective study. Tumor characteristics, procedural details, and complications were documented. Pre- and postprocedural cross-sectional imaging was evaluated to assess local tumor control rates.
Thirty-three tumors were successfully ablated in 27 patients. Posterior vertebral body or pedicle involvement or both were present in 94% (31/33) of cases. Sixty-seven percent (22/33) of the tumors involved ≥75% of the vertebral body volume. Posttreatment imaging was available for 79% (26/33) of the treated tumors. Local tumor control was achieved in 96% (25/26) of tumors median imaging follow up of 16 weeks. No complications were reported, and no patients had clinical evidence of metastatic spinal cord compression at the treated levels.
Simultaneous bipedicular radiofrequency ablation combined with vertebral augmentation is safe and effective for local tumor control of vertebral metastases. Articulating bipolar electrodes enable the placement and proximity necessary for optimal confluence of the ablation zones. Local tumor control may lead to more durable pain palliation, prevent disease progression, and reduce skeletal-related events of the spine.
We report a B-mode power spectrum measurement from the cosmic microwave background (CMB) polarization anisotropy observations made using the SPTpol instrument on the South Pole Telescope. This work ...uses 500 deg2 of SPTpol data, a five-fold increase over the last SPTpol B-mode release. As a result, the bandpower uncertainties have been reduced by more than a factor of two, and the measurement extends to lower multipoles: 52 < ℓ < 2301 . Data from both 95 and 150 GHz are used, allowing for three cross-spectra: 95 GHz × 95 GHz , 95 GHz × 150 GHz , and 150 GHz × 150 GHz . B -mode power is detected at very high significance; we find P ( B B < 0 ) = 5.8 × 10−71, corresponding to a 18.1σ detection of power. With a prior on the galactic dust from Planck, WMAP and BICEP2/Keck observations, the SPTpol B-mode data can be used to set an upper limit on the tensor-to-scalar ratio, r < 0.44 at 95% confidence (the expected 1σ constraint on r given the measurement uncertainties is 0.22). We find the measured B-mode power is consistent with the Planck best-fit Λ CDM model predictions. Scaling the predicted lensing B-mode power in this model by a factor Alens, the data prefer Alens = 1.17 ± 0.13 . These data are currently the most precise measurements of B-mode power at ℓ > 320.
Summary
What is known and objective
Rhabdomyolysis is a severe potential adverse drug reaction of statin therapy. We report a case of rhabdomyolysis due to drug–drug interaction (DDI) between ...atorvastatin and fluconazole and review the literature.
Case summary
A 70‐year‐old woman received atorvastatin for hyperlipidaemia without any problem for 4 years. When intravenous fluconazole was added for treating a fungal infection, rhabdomyolysis developed 2 weeks later. Removal of atorvastatin led to the resolution of her rhabdomyolysis.
What is new and conclusion
Our case demonstrates that in some subjects even a moderate CYP3A4 inhibitor such as fluconazole may lead to rhabdomyolysis in subjects receiving a statin.
Characteristics of reported cases of rhabdomyolysis associated with drug interaction between statins and fluconazole.
Radiation therapy (RT) and concurrent chemotherapy RT (CCRT) generate radiation‐induced oral mucositis (OM) and lower quality of life (QOL). This study assessed the impact of a saline mouth rinse ...regimen and education programme on radiation‐induced OM symptoms, and QOL in oral cavity cancer (OCC) patients receiving RT or CCRT. Ninety‐one OCC patients were randomly divided into a group that received saline mouth rinses and an education programme and a control group that received standard care. OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS‐moo and UW‐QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT. Patients in both groups had significantly higher levels of physical and social‐emotional QOL at 8 weeks after beginning RT or CCRT compared to the first visit. Patients in the saline rinse group had significantly better physical and social‐emotional QOL as compared to the standard care group at 8 weeks. Radiation‐induced OM symptoms and overall QOL were not different between the groups. We thus conclude the saline rinse and education programme promote better physical and social‐emotional QOL in OCC patients receiving RT/CCRT.
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