Background. During the 2012-2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza lineage viruses in the United States. Methods. Patients with acute cough illness for ≤7 ...days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as 100% × (1 - adjusted odds ratio) for vaccination in cases versus test-negative controls. Results. Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval CI, 43%-55%) overall, 39% (95% CI, 29%-47%) against influenza A(H3N2), 66% (95% CI, 58%-73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%-63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50-64 years (52%; 95% CI, 33%-65%) and persons aged 6 months-8 years (51%; 95% CI, 32%-64%) and lowest among persons aged ≥65 years (11%; 95% CI, -41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011-2012 vaccine 1 year earlier. Conclusions. The 2012-2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation.
The loss of Arctic sea ice has emerged as a leading signal of global warming. This, together with acknowledged impacts on other components of the Earth system, has led to the term “the new Arctic.” ...Global coupled climate models predict that ice loss will continue through the twenty-first century, with implications for governance, economics, security, and global weather. A wide range in model projections reflects the complex, highly coupled interactions between the polar atmosphere, ocean, and cryosphere, including teleconnections to lower latitudes. This paper summarizes our present understanding of how heat reaches the ice base from the original sources—inflows of Atlantic and Pacific Water, river discharge, and summer sensible heat and shortwave radiative fluxes at the ocean/ice surface—and speculates on how such processes may change in the new Arctic. The complexity of the coupled Arctic system, and the logistic and technological challenges of working in the Arctic Ocean, require a coordinated interdisciplinary and international program that will not only improve understanding of this critical component of global climate but will also provide opportunities to develop human resources with the skills required to tackle related problems in complex climate systems. We propose a research strategy with components that include 1) improved mapping of the upper- and middepth Arctic Ocean, 2) enhanced quantification of important process, 3) expanded long-term monitoring at key heat-flux locations, and 4) development of numerical capabilities that focus on parameterization of heat-flux mechanisms and their interactions.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Seascape ecology, the marine-centric counterpart to landscape ecology, is rapidly emerging as an interdisciplinary and spatially explicit ecological science with relevance to marine management, ...biodiversity conservation, and restoration. While important progress in this field has been made in the past decade, there has been no coherent prioritisation of key research questions to help set the future research agenda for seascape ecology. We used a 2-stage modified Delphi method to solicit applied research questions from academic experts in seascape ecology and then asked respondents to identify priority questions across 9 interrelated research themes using 2 rounds of selection. We also invited senior management/conservation practitioners to prioritise the same research questions. Analyses highlighted congruence and discrepancies in perceived priorities for applied research. Themes related to both ecological concepts and management practice, and those identified as priorities include seascape change, seascape connectivity, spatial and temporal scale, ecosystem-based management, and emerging technologies and metrics. Highest-priority questions (upper tercile) received 50% agreement between respondent groups, and lowest priorities (lower tercile) received 58% agreement. Across all 3 priority tiers, 36 of the 55 questions were within a ±10% band of agreement. We present the most important applied research questions as determined by the proportion of votes received. For each theme, we provide a synthesis of the research challenges and the potential role of seascape ecology. These priority questions and themes serve as a roadmap for advancing applied seascape ecology during, and beyond, the UN Decade of Ocean Science for Sustainable Development (2021-2030).
ABSTRACT
The stratigraphic architecture of Early Jurassic strata exposed along a >10 km long transect in the Chachil Graben, an exhumed marine rift depocentre in the Neuquén Basin (Argentina), ...provides insights into the sedimentological and stratigraphic expression of the syn‐rift to post‐rift transition. A change from syn‐rift intrabasinal carbonate to post‐rift extrabasinal siliciclastic sedimentation is recorded, as well as variations in sediment supply and dispersal patterns across rift‐related topography. The late syn‐rift was marked by a transgression and development of a shallow‐marine carbonate system, including carbonate platform deposits perched on fault‐block highs and periplatform deposits accumulated in fault‐block lows, which overlies continental volcano‐sedimentary syn‐rift deposits. Differential subsidence and basin deepening induced retrogradation of the carbonate system, which was progressively drowned and overlain by organic‐rich calcareous mudstone that draped across rift structures at the onset of the early post‐rift. The first extrabasinal siliciclastic influx led to progradation of an early post‐rift intraslope lobe complex into the graben, which is associated with kilometre‐scale clastic injectites. The depositional architecture, facies distribution and pinch‐out style of intraslope lobes record the effects of an inherited compaction hinge, which acted as an oblique counterslope to sediment gravity flows. The occurrence of combined‐flow bedforms, widespread erosion, and limited facies segregation across lobes bearing different hybrid event bed types, is in sharp contrast to sedimentological characteristics of existing intraslope lobe models. Documentation of the syn‐rift to post‐rift transition stratigraphy permitted identification of changes in thickness and facies resulting from the passive infill of inherited topography with early post‐rift differential compaction. This architecture contrasts markedly with those developed during syn‐rift normal faulting. Furthermore, the influence of local inherited topography on the development of early post‐rift lobes is key to improve subsurface prediction of sandstone distribution and quality during assessment of hydrocarbon reservoirs and carbon storage sites.
SummaryBackgroundPopulation-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of ...the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends. MethodsIn this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control. FindingsIn 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995–2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010–14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer. InterpretationThe joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival. FundingCanadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.
Background: The British Columbia randomized radiation trial was designed to determine the survival impact of locoregional radiation therapy in premenopausal patients with lymph node–positive breast ...cancer treated by modified radical mastectomy and adjuvant chemotherapy. Three hundred eighteen patients were assigned to receive no further therapy or radiation therapy (37.5 Gy in 16 fractions). Previous analysis at the 15-year follow-up showed that radiation therapy was associated with a statistically significant improvement in breast cancer survival but that improvement in overall survival was of only borderline statistical significance. We report the analysis of data from the 20-year follow-up. Methods: Survival was analyzed by the Kaplan–Meier method. Relative risk estimates were calculated by the Wald test from the proportional hazards regression model. All statistical tests were two-sided. Results: At the 20 year follow up (median follow up for live patients: 249 months) chemotherapy and radiation therapy, compared with chemotherapy alone, were associated with a statistically significant improvement in all end points analyzed, including survival free of isolated locoregional recurrences (74% versus 90%, respectively; relative risk RR = 0.36, 95% confidence interval CI = 0.18 to 0.71; P = .002), systemic relapse–free survival (31% versus 48%; RR = 0.66, 95% CI = 0.49 to 0.88; P = .004), breast cancer-free survival (48% versus 30%; RR = 0.63, 95% CI = 0.47 to 0.83; P = .001), event-free survival (35% versus 25%; RR = 0.70, 95% CI = 0.54 to 0.92; P = .009), breast cancer-specific survival (53% versus 38%; RR = 0.67, 95% CI = 0.49 to 0.90; P = .008), and, in contrast to the 15-year follow-up results, overall survival (47% versus 37%; RR = 0.73, 95% CI = 0.55 to 0.98; P = .03). Long-term toxicities, including cardiac deaths (1.8% versus 0.6%), were minimal for both arms. Conclusion: For patients with high-risk breast cancer treated with modified radical mastectomy, treatment with radiation therapy (schedule of 16 fractions) and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone, and it is well tolerated, with acceptable long-term toxicity.
The contribution of genetics to stroke risk, and whether this differs for different stroke subtypes, remainsuncertain. Genomewide complex trait analysis allows heritability to be assessed from ...genomewide association study (GWAS) data. Previous candidate gene studies have identified many associations with stoke but whether these are important requires replication in large independent data sets. GWAS data sets provide a powerful resource to perform replication studies.
We applied genomewide complex trait analysis to a GWAS data set of 3752 ischemic strokes and 5972 controls and determined heritability for all ischemic stroke and the most common subtypes: large-vessel disease, small-vessel disease, and cardioembolic stroke. By systematic review we identified previous candidate gene and GWAS associations with stroke and previous GWAS associations with related cardiovascular phenotypes (myocardial infarction, atrial fibrillation, and carotid intima-media thickness). Fifty associations were identified.
For all ischemic stroke, heritability was 37.9%. Heritability varied markedly by stroke subtype being 40.3% for large-vessel disease and 32.6% for cardioembolic but lower for small-vessel disease (16.1%). No previously reported candidate gene was significant after rigorous correction for multiple testing. In contrast, 3 loci from related cardiovascular GWAS studies were significant: PHACTR1 in large-vessel disease (P=2.63e(-6)), PITX2 in cardioembolic stroke (P=4.78e(-8)), and ZFHX3 in cardioembolic stroke (P=5.50e(-7)).
There is substantial heritability for ischemic stroke, but this varies for different stroke subtypes. Previous candidate gene associations contribute little to this heritability, but GWAS studies in related cardiovascular phenotypes are identifying robust associations. The heritability data, and data from GWAS, suggest detecting additional associations will depend on careful stroke subtyping.
The Early Jurassic Los Molles Formation in the Neuquén Basin of western Argentina is a rare example of well‐exposed syn‐rift to post‐rift stratigraphy. In the Chachil Graben, the onset of the early ...post‐rift stage is marked by drowning of a carbonate system and the development of two deep‐marine intraslope lobe complexes. This field‐based study in the Chachil Graben involved field mapping and correlating eleven stratigraphic logs, and petrographic analysis to document how grain size and texture within intraslope lobe sandstones change from the lobe centre to their frontal pinch‐out. Eight different bed‐scale facies are identified and inferred to be formed by turbulent (turbidites; Type A and B beds), transient turbulent–laminar (transitional flow deposits; Type C, D, E and F beds), laminar gravity flows (debrites; Type G) and post‐depositional clastic injections (injectites; Type H beds). Fifteen lobes form two stacked lobe complexes that show stratigraphic evolution from a lower argillaceous sandstone‐dominated lobe complex, built by transitional flow deposits, to an upper coarser‐grained, sandier lobe complex largely constructed by turbidites. Petrographic analysis quantified sandstone mineralogy, matrix content, grain size and sorting, revealing that both lobe complexes are volcanic arc‐sourced. This study proposes that the differences in the character of the two lobe complexes are due to maturation of sediment transport routes through progressive healing of the intraslope relief, with a concomitant decrease in substrate erosion and flow bulking. Also proposed here is a model for intraslope lobe complex development that accounts for the impact of flow‐confinement on flow behaviour and transformation induced by the inherited topography. Bed type distribution suggests that high‐density flows terminate more abruptly against confining slopes and produce greater depositional variability than lower‐density flows. This integrated petrographic, architectural and sedimentary process model provides new insights into how post‐rift intraslope lobe systems may act as hydrocarbon reservoirs, aquifers and carbon storage sites.
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the ...context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials. Radiotherapy dose painting strategies based on hypoxia imaging require careful refinement prior to clinical investigation. This review will summarize the role of hypoxia, highlight the potential of hypoxia as a therapeutic target, and outline past and ongoing hypoxia-targeted therapy trials in NSCLC. Evidence supporting radiotherapy dose painting based on hypoxia imaging will be critically appraised. Carefully selected hypoxia biomarkers suitable for integration within future NSCLC hypoxia-targeted therapy trials will be examined. Research gaps will be identified to guide future investigation. Although this review will focus on NSCLC hypoxia, more general discussions (eg, obstacles of hypoxia biomarker research and developing a framework for future hypoxia trials) are applicable to other tumor sites.
► We examined separate cognitive processes that underlie the task of driving. ► Simulated driving and cognitive tasks were assessed after sleep deprivation. ► Psychomotor vigilance was a key ...component of the variation in driving impairment.
Driving is a complex task, which can be broken down into specific cognitive processes. In order to determine which components contribute to drowsy driving impairments, the current study examined simulated driving and neurocognitive performance after one night of sleep deprivation. Nineteen professional drivers (age 45.3±9.1) underwent two experimental sessions in randomised order: one after normal sleep and one after 27h total sleep deprivation. A simulated driving task (AusEd), the psychomotor vigilance test (PVT), and neurocognitive tasks selected from the Cognitive Drug Research computerised neurocognitive assessment battery (simple and choice RT, Stroop Task, Digit Symbol Substitution Task, and Digit Vigilance Task) were administered at 10:00h in both sessions. Mixed-effects ANOVAs were performed to examine the effect of sleep deprivation versus normal sleep on performance measures. To determine if any neurocognitive tests predicted driving performance (lane position variability, speed variability, braking RT), neurocognitive measures that were significantly affected by sleep deprivation were then added as a covariate to the ANOVAs for driving performance. Simulated driving performance and neurocognitive measures of vigilance and reaction time were impaired after sleep deprivation (p<0.05), whereas tasks examining processing speed and executive functioning were not significantly affected by sleep loss. PVT performance significantly predicted specific aspects of simulated driving performance. Thus, psychomotor vigilance impairment may be a key cognitive component of driving impairment when sleep deprived. The generalisability of this finding to real-world driving remains to be investigated.
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