Search

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the United Kingdom). Data on invasive EOC diagnosed in women aged 15-99 years during 1995-2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group, and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995-2014 among women aged 65-99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma 'not otherwise specified' with estimates ranging between 4.4% and 7.4% in women aged 15-64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival. This article is protected by copyright. All rights reserved.

BACKGROUND: The global burden of pancreatic cancer has steadily increased, while the prognosis after pancreatic cancer diagnosis remains poor. This study aims to compare the stage- and age-specific pancreatic cancer net survival (NS) for seven high-income countries: Australia, Canada, Denmark, Ireland, New Zealand, Norway, and United Kingdom. METHODS: The study included over 35,000 pancreatic cancer cases diagnosed during 2012–2014, followed through 31 December 2015. The stage- and age-specific NS were calculated using the Pohar-Perme estimator. RESULTS: Pancreatic cancer survival estimates were low across all 7 countries, with 1-year NS ranging from 21.1% in New Zealand to 30.9% in Australia, and 3-year NS from 6.6% in the UK to 10.9% in Australia. Most pancreatic cancers were diagnosed with distant stage, ranging from 53.9% in Ireland to 83.3% in New Zealand. While survival differences were evident between countries across all stage categories at one year after diagnosis, this survival advantage diminished, particularly in cases with distant stage. CONCLUSION: This study demonstrated the importance of stage and age at diagnosis in pancreatic cancer survival. Although progress has been made in improving pancreatic cancer prognosis, the disease is highly fatal and will remain so without major breakthroughs in the early diagnosis and management.

Background Immortal time bias is common in observational studies but is typically described for pharmacoepidemiology studies where there is a delay between cohort entry and treatment initiation. Methods This study used the Clinical Practice Research Datalink (CPRD) and linked national mortality data in England from 2000 to 2019 to investigate immortal time bias for a specific life-long condition, intellectual disability. Life expectancy (Chiang’s abridged life table approach) was compared for 33,867 exposed and 980,586 unexposed individuals aged 10+ years using five methods: (1) treating immortal time as observation time; (2) excluding time before date of first exposure diagnosis; (3) matching cohort entry to first exposure diagnosis; (4) excluding time before proxy date of inputting first exposure diagnosis (by the physician); and (5) treating exposure as a time-dependent measure. Results When not considered in the design or analysis (Method 1), immortal time bias led to disproportionately high life expectancy for the exposed population during the first calendar period (additional years expected to live: 2000–2004: 65.6 [95% CI: 63.6,67.6]) compared to the later calendar periods (2005–2009: 59.9 [58.8,60.9]; 2010–2014: 58.0 [57.1,58.9]; 2015–2019: 58.2 [56.8,59.7]). Date of entry of diagnosis (Method 4) was unreliable in this CPRD cohort. The final methods (Method 2, 3 and 5) appeared to solve the main theoretical problem but residual bias may have remained. Conclusions We conclude that immortal time bias is a significant issue for studies of life-long conditions that use electronic health record data and requires careful consideration of how clinical diagnoses are entered onto electronic health record systems.

The Department of Homeland Security (DHS) formally incorporated Human Systems Integration (HSI) in systems and policy development in 2012. Since then, DHS components have been establishing HSI capabilities to meet their unique human needs. This discussion panel will focus on the operational transformation and governance strategy for implementing a successful human systems integration (HSI) program across components within the Department of Homeland Security (DHS). Members of the Transportation Security Administration (TSA), United States Coast Guard (USCG), and Department of Homeland Security Science and Technology Directorate (DHS S&T) will discuss the challenges faced when advocating for HSI, and the best practices developed to better integrate research activities with systems engineering.

Background Royston-Parmar flexible parametric survival models (FPMs) can be fitted on either the cause-specific hazards or cumulative incidence scale in the presence of competing risks. An advantage of modelling within this framework for competing risks data is the ease at which alternative predictions to the (cause-specific or subdistribution) hazard ratio can be obtained. Restricted mean survival time (RMST) is one such measure. This has an attractive interpretation, especially when the proportionality assumption is violated. Compared to similar measures, fewer assumptions are required and it does not require extrapolation. Furthermore, one can easily obtain the expected number of life-years lost, or gained, due to a particular cause of death, which is a further useful prognostic measure as introduced by Andersen. Methods We present various measures, including the expected life-years lost due to a cause of death, which can be predicted for a specific covariate pattern to facilitate interpretation in observational studies. Summaries are also provided at the population-level using standardisation to obtain marginal measures. RMST is obtained in the presence of competing risks using Royston-Parmar FPMs. Predictions are illustrated using English colorectal data and are obtained using the Stata post-estimation command, standsurv. Results Reporting such measures facilitate interpretation of a competing risks analysis, particularly when the proportional hazards assumption is not appropriate. Standardisation provides a useful way to obtain marginal estimates to make absolute comparisons between two covariate groups. Predictions can be made at various time-points and presented visually for each cause of death to better understand the overall impact of different covariate groups. Conclusions We describe estimation of RMST and expected life-years lost, both partitioned by each competing cause of death after fitting a single FPM on either the log-cumulative subdistribution, or cause-specific hazards scale. These can be used to facilitate interpretation of a competing risks analysis when the proportionality assumption is in doubt.

Background When quantifying the probability of survival in cancer patients using cancer registration data, it is common to estimate marginal relative survival, which under assumptions can be interpreted as marginal net survival. Net survival is a hypothetical construct giving the probability of being alive if it was only possible to die of the cancer under study, enabling comparisons between populations with differential mortality rates due to causes other the cancer under study. Marginal relative survival can be estimated non-parametrically (Pohar Perme estimator) or in a modeling framework. In a modeling framework, even when just interested in marginal relative survival it is necessary to model covariates that affect the expected mortality rates (e.g. age, sex and calendar year). The marginal relative survival function is then obtained through regression standardization. Given that these covariates will generally have non-proportional effects, the model can become complex before other exposure variables are even considered. Methods We propose a flexible parametric model incorporating restricted cubic splines that directly estimates marginal relative survival and thus removes the need to model covariates that affect the expected mortality rates. In order to do this the likelihood needs to incorporate the marginal expected mortality rates at each event time taking account of informative censoring. In addition time-dependent weights are incorporated into the likelihood. An approximation is proposed through splitting the time scale into intervals, which enables the marginal relative survival model to be fitted using standard software. Additional weights can be incorporated when standardizing to an external reference population. Results The methods are illustrated using national cancer registry data. In addition, a simulation study is performed to compare different estimators; a non-parametric approach, regression-standardization and the new marginal relative model. The simulations study shows the new approach is unbiased and has good relative precision compared to the non-parametric estimator. Conclusion The approach enables estimation of standardized marginal relative survival without the need to model covariates that affect expected mortality rates and thus reduces the chance of model misspecification.

n/a

In a competing risks analysis, interest lies in the cause-specific cumulative incidence function (CIF) which can be calculated by either (1) transforming on the cause-specific hazard (CSH) or (2) through its direct relationship with the subdistribution hazard (SDH). We expand on current competing risks methodology from within the flexible parametric survival modelling framework (FPM) and focus on approach (2). This models all cause-specific CIFs simultaneously and is more useful when we look to questions on prognosis. We also extend cure models using a similar approach described by Andersson et. al. for flexible parametric relative survival models. Using SEER public use colorectal data, we compare and contrast our approach with standard methods such as the Fine & Gray model, and show that many useful out-of-sample predictions can be made after modelling the cause-specific CIFs using a FPM approach. Alternative link functions may also be incorporated such as the logit link. Models can also be easily extended for time-dependent effects.

In an effort to identify genes that have a major effect on macrophage function during viral infection, we employed differential display reverse transcription (DDRT)-PCR to capture expressed sequence tags (ESTs) of swine alveolar macrophages infected by the porcine reproductive and respiratory syndrome virus (PRRSV). Sequence analyses showed that approximately 60% of these ESTs had significant similarity (> or =93%) to known pig ESTs or genes or matched sequences from other species with homology > or =80%. To determine chromosomal localization, PCR-based mapping was performed across either swine somatic cell hybrid or radiation hybrid panels. A total of 48 porcine viral response ESTs were mapped via the swine somatic cell panel or the INRA-Minnesota porcine Radiation Hybrid (IMpRH) panel (LOD > 6.0). Northern blot analyses confirmed PRRSV-induced altered transcript expression for several ESTs, including a 2'-5' oligoadenylate synthetase and a putative dual-specificity phosphatase. These virus-response ESTs represent good candidate genes for understanding PRRSV pathogenesis and for dissecting host genes which may have major effect on disease resistance.

Battery chargers are a necessary part of any mobile electronic device. Because a mobile phone battery is a high-energy storage unit, care must be taken in the design of the entire charging system. This paper discusses the overall charging system for a mobile phone as well as some key factors that make battery chargers unique. The design of a switch-mode battery charger is presented, including subsystem circuit architecture, stability analysis, and sequencing logic, plus the key performance parameters of the design are summarized.

Hearing over a wide range of sound intensities is thought to require complementary coding by functionally diverse spiral ganglion neurons (SGNs), each changing activity only over a subrange. The foundations of SGN diversity are not well understood but likely include differences among their inputs: the presynaptic active zones (AZs) of inner hair cells (IHCs). Here we studied one candidate mechanism for causing SGN diversity—heterogeneity of Ca(2+) influx among the AZs of IHCs—during postnatal development of the mouse cochlea. Ca(2+) imaging revealed a change from regenerative to graded synaptic Ca(2+) signaling after the onset of hearing, when in vivo SGN spike timing changed from patterned to Poissonian. Furthermore, we detected the concurrent emergence of stronger synaptic Ca(2+) signals in IHCs and higher spontaneous spike rates in SGNs. The strengthening of Ca(2+) signaling at a subset of AZs primarily reflected a gain of Ca(2+) channels. We hypothesize that the number of Ca(2+) channels at each IHC AZ critically determines the firing properties of its corresponding SGN and propose that AZ heterogeneity enables IHCs to decompose auditory information into functionally diverse SGNs.

It is axiomatic that evaluation plays a major role in all phases of the systematic approach to improving human performance. Implementing performance interventions without following up through evaluation means that positive results, though hoped for, cannot be directly verified. In such a case, an organization may train, create job aids, buy new equipment or institute any number of other interventions without the means to determine whether these "investments" actually improved performance and provided a reasonable "return." Because training is unquestionably among its more resource-intensive and pervasive interventions, the Coast Guard recently analyzed the evaluation of training to establish policies and procedures to ensure that its training efforts are effective. This paper describes the Coast Guard's newly implemented training evaluation policy and associated responsibilities and infrastructure.

The geminal α-methytene protons in 3-ethylnaphthalene-l,2-oxide show chemical shift nonequivalence in 1 H NMR spectra recorded at ambient temperature consistent with a high barrier to enantiomerization via the orepine tautomer. The methylene protons in α-benzoyloxytoluene-2,3-oxide which are a singlet at ambient temperature split into an AB system at -135 °C and there is evidence of ca . 5% of the oxepine isomer. Lineshape analysis of the coalescing arene oxide AB Signals provides the activation parameters for the valence isomerization/degenerate racemization process: ΔGXXX = 7.6 kcal mol -1 , ΔHXXX = 8.6 kcal mol -l , ΔSXXX= 5.8 cal K -l mol -1 .

Low temperature 13 C n.m.r. investigations of the title compounds, (R 2 ,N) 2 ,PPh, indicate that contrary to previous suggestions they adopt a conformation where both nitrogen lone pairs are approximately orthogonal to the phosphorus lone pair; the PN rotational barriers were determined to be 7.2 and 8.4 kcal mol −1 for R = Et and CH 2 Ph respectively.

The preparation of a new class of oxaziridines containing an N-phosphinoyl group is described. The compounds were otained by peroxyacid oxidation of N-phosphinoyl imines under basic or neutral conditions, and characterised by n.m.r. spectroscopy. Relevant 2JPC, 3JPH, and 1JCH coupling constants are reported. An X-ray structure analysis of the title compound establishes that the 2-diphenylphosphinoyl group is trans to the 3-aryl ring. The P–N bond length (1.76A) is abnormally high for an aminophosphorus (V) compound and the nitrogen atom is pyramidal (Σ= 280°). This geometry is interpreted in terms of an unusually low degree of π-bonding between nitrogen and phosphorus due to the high s-character of the nitrogen lone pair.

Novel stable N-phosphinoyl oxaziridines have been prepared and characterized by n.m.r. and mass spectrometry; they function as oxidants towards phosphines, sulphides, and alknes.

Low temperature n.m.r. studies on 2-cyano- and 2-ethoxycarbonyl-7-ethyloxepine establish a non-planar ring geometry with a ring inversion barrier of 6.5 kcal mol–1(27.2 kJ mol–1), and provide evidence of a rotational isomerism involving the 2-ethoxycarbonyl substituent; an X-ray crystallographic analysis of 2-t-butoxycarbonyloxepine confirms the non-planar boat geometry.