Trends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands

Hypopharynx cancer has the worst prognosis of all head and neck squamous cell cancers. Since the 1990s, a treatment shift has appeared from a total laryngectomy towards organ preservation therapies. Large randomized trials evaluating treatment strategies for hypopharynx cancer, however, remain scarce, and frequently this malignancy is evaluated together with larynx cancer. Therefore, our aim was to determine trends in incidence, treatment and survival of hypopharynx cancer. We performed a population-based cohort study including all patients diagnosed with T1-T4 hypopharynx cancer between 1991 and 2010 in the Netherlands. Patients were recorded by the national cancer registry database and verified by a national pathology database. 2999 patients were identified. The incidence increased significantly with 4.1% per year until 1997 and decreased non-significantly afterwards. For women, the incidence increased with 1.7% per year during the entire study period. Total laryngectomy as primary treatment significantly decreased, whereas radiotherapy and chemoradiation increased. The 5-year overall survival significantly increased from 28% in 1991-2000 to 34% in 2001-2010. Overall survival for T3 was equal for total laryngectomy and (chemo)radiotherapy, but for T4-patients the survival was significantly better after primary total laryngectomy (+/- adjuvant radiotherapy). This large population-based study demonstrates a shift in treatment preference towards organ preservation therapies. The 5-year overall survival increased significantly in the second decade. The assumed equivalence of organ preservation and laryngectomy may require reconsideration for T4 diseas

Variability and decadal trends in the Isfjorden (Svalbard) ocean climate and circulation – An indicator for climate change in the European Arctic

Isfjorden, a broad Arctic fjord in western Spitsbergen, has shown significant changes in hydrography and inflow of Atlantic Water (AW) the last decades that only recently have been observed in the Arctic Ocean north of Svalbard. Variability and trends in this fjord’s climate and circulation are therefore analysed from observational and reanalysis data during 1987 to 2017. Isfjorden experienced a shift in summer ocean structure in 2006, from AW generally in the bottom layer to AW (with increasing thickness) higher up in the water column. This shift, and a concomitant shift to less fast ice in Isfjorden are linked to positive trends in the mean sea surface temperature (SST) and volume weighted mean temperature (VT) in winter (SSTw/VTw: 0.7 ± 0.1/0.9 ± 0.3 °C 10 yr−1) and summer (SSTS/VTS: 0.7 ± 0.1/0.6 ± 0.1 °C 10 yr−1). Hence, the local mean air temperature shows similar trends in winter (1.9 ± 0.4 °C 10 yr−1) and summer (0.7 ± 0.1 °C 10 yr−1). Positive trends in volume weighted mean salinity in winter (0.21 ± 0.06 10 yr−1) and summer (0.07 ± 0.05 10 yr−1) suggest increased AW advection as a main reason for Isfjorden’s climate change. Local mean air temperature correlates significantly with sea ice cover, SST, and VT, revealing the fjord’s impact on the local terrestrial climate. In line with the shift in summer ocean structure, Isfjorden has changed from an Arctic type fjord dominated by Winter Deep and Winter Intermediate thermal and haline convection, to a fjord dominated by deep thermal convection of Atlantic type water (Winter Open). AW indexes for the mouth and Isfjorden proper show that AW influence has been common in winter over the last decade. Alternating occurrence of Arctic and Atlantic type water at the mouth mirrors the geostrophic control imposed by the Spitsbergen Polar Current (carrying Arctic Water) relative to the strength of the Spitsbergen Trough Current (carrying AW). During high AW impact events, Atlantic type water propagates into the fjord according to the cyclonic circulation along isobaths corresponding to the winter convection. Tides play a minor role in the variance in the currents, but are important in the side fjords where exchange with the warmer Isfjorden proper occurs in winter. This study demonstrates that Isfjorden and its ocean climate can be used as an indicator for climate change in the Arctic Ocean. The used methods may constitute a set of helpful tools for future studies also outside the Svalbard Archipelago.publishedVersio

Cardiovascular safety of celecoxib in acute myocardial infarction patients: a nested case-control study

The objective was to measure the impact of exposure to coxibs and non-steroidal antiinflammatory drugs (NSAID) on morbidity and mortality in older patients with acute myocardial infarction (AMI). A nested case-control study was carried out using an exhaustive population-based cohort of patients aged 66 years and older living in Quebec (Canada) who survived a hospitalization for AMI (ICD-9 410) between 1999 and 2002. The main variables were all-cause and cardiovascular (CV) death, subsequent hospital admission for AMI, and a composite end-point including recurrent AMI or CV death. Conditional logistic regressions were used to estimate the risk of mortality and morbidity. A total of 19,823 patients aged 66 years and older survived hospitalization for AMI in the province of Quebec between 1999 and 2002. After controlling for covariables, the risk of subsequent AMI and the risk of composite end-point were increased by the use of rofecoxib. The risk of subsequent AMI was particularly high for new rofecoxib users (HR 2.47, 95% CI 1.57–3.89). No increased risk was observed for celecoxib users. No increased risk of CV death was observed for patients exposed to coxibs or NSAIDs. Patients newly exposed to NSAIDs were at an increased risk of death (HR 2.22, 95% CI 1.30–3.77) and of composite end-point (HR 2.28, 95% CI 1.35–3.84). Users of rofecoxib and NSAIDs, but not celecoxib, were at an increased risk of recurrent AMI and of composite end-point. Surprisingly, no increased risk of CV death was observed. Further studies are needed to better understand these apparently contradictory results

Applicability and Cost Implications for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Based on the ODYSSEY Outcomes Trial: Insights From the Department of Veterans Affairs

In the recently presented ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab trial, alirocumab use in patients with acute coronary syndrome (ACS) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (or non–high-density lipoprotein cholesterol ≥100 mg/dL or apolipoprotein B ≥80 mg/dL) resulted in a 15% relative (1.6% absolute) reduction in the risk of major adverse cardiovascular events. We evaluated what proportion of patients in the VA Health Care System would qualify for alirocumab on the basis of ODYSSEY Outcomes criteria, how they are currently treated with LDL-C–lowering medications, and the cost implications if other evidence-based medications were used first before a proprotein convertase subtilisin/kexin type 9 inhibitor was considered

Very High-Risk ASCVD and Eligibility for Nonstatin Therapies Based on the 2018 AHA/ACC Cholesterol Guidelines

The 2018 American Heart Association/American College of Cardiology Multisociety Cholesterol Guidelines recommend risk stratification among patients with atherosclerotic cardiovascular disease (ASCVD) to identify “very high-risk ASCVD patients.” These patients have characteristics associated with a higher risk of recurrent ASCVD events; consequently, they derive a higher net absolute benefit from addition of ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to statin therapy. From a clinical and payer’s perspective, we assessed the proportion of patients with ASCVD who will qualify as very high-risk based on the guideline criteria, their current lipid management, and how this will change with maximizing statin therapy and stepwise use of ezetimibe before consideration for a PCSK9i, as recommended by the 2018 cholesterol guideline

Semiparametric theory and empirical processes in causal inference

In this paper we review important aspects of semiparametric theory and empirical processes that arise in causal inference problems. We begin with a brief introduction to the general problem of causal inference, and go on to discuss estimation and inference for causal effects under semiparametric models, which allow parts of the data-generating process to be unrestricted if they are not of particular interest (i.e., nuisance functions). These models are very useful in causal problems because the outcome process is often complex and difficult to model, and there may only be information available about the treatment process (at best). Semiparametric theory gives a framework for benchmarking efficiency and constructing estimators in such settings. In the second part of the paper we discuss empirical process theory, which provides powerful tools for understanding the asymptotic behavior of semiparametric estimators that depend on flexible nonparametric estimators of nuisance functions. These tools are crucial for incorporating machine learning and other modern methods into causal inference analyses. We conclude by examining related extensions and future directions for work in semiparametric causal inference

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results