The concurrent occurrence of drought and heat was more severe for maize growth than the single stress. However, both stresses induced the metabolites accumulation and enzymatic and non-enzymatic antioxidants to prevent the oxidative damage. The performance of Xida 899 was more prominent than the Xida 319. The greater tolerance of Xida 889 to heat and drought stresses was attributed to strong antioxidant defense system, higher osmolyte accumulation, and maintenance of photosynthetic pigments and nutrient balance compared with Xida 319.Maize is a sensitive crop to drought and heat stresses, particularly at the reproductive stages of development. The present study investigated the individual and interactive effects of drought (50% field capacity) and heat (38 °C/30 °C) stresses on morpho-physiological growth, yield, nutrient uptake and oxidative metabolism in two maize hybrids i.e., ‘Xida 889’ and ‘Xida 319’. The stress treatments were applied at tasseling stage for 15 days. Drought, heat and drought + heat stress caused oxidative stress by the over-production of ROS (O Among abiotic stresses, extreme temperature and water deficit conditions are two of the most frequent environmental threats to crop growth and productivity, and ultimately the food security under changing climate8. These stresses negatively affect the yield of major staple food crops9, that account for 60% of global food energy supply10. Previous studies showed that the combined drought and heat stresses caused a disproportionate damage on plant growth and productivity compared with each of individual stress15. Temperature above 35 °C affects the vegetative and reproductive growth of maize, from germination to grain filling16. However, the reproductive stages of the crop plants are more sensitive to combined drought and heat stresses than the vegetative stages, although each stress affected reproductive traits differently15. These stresses noticeably reduced the photosynthetic activity, altered oxidative metabolism, caused membrane instability17, affected stomatal conductance, and decreased the leaf area and water-use efficiency in maize and other cereal crops18. Nonetheless, the effects of these stress factors might be different depending on the plant species2.Under natural environments, crops are often subjected to different abiotic stresses simultaneously during their life cycle which adversely affect the growth and productivity of field crops19. Wahid et al.20 stated that the heat stress can be accompanied by drought because of rapid water loss from plant and soil surface under high temperature. While, Pie et al.21 reported that heat stress may occur in plants due to insufficient water supply to meet the evaporative demand. Both drought and heat stresses are well known to decrease the the nutrient uptake and photosynthetic efficiency of plants22. In wheat crop, heat stress during early as well as late season disturbed the growth period for various development stages  and reduced the organ size 23. Recently, Zandalinas et al.2 and Lamaoui et al.22 concluded that drought and heat stresses generally trigger similar physiological responses in plants, however, plants were severely damaged by the combined action of both stresses than by the individual stress factor, indicating that conserved defense mechanisms exist among different plant species to deal with a combination of heat and drought stresses. In order to adapt stress conditions, plants possess several mechanisms including accumulation of compatible solutes  and protective proteins (e.g. heat shock proteins), and activation of enzymatic  and non-enzymatic (e.g. reduced glutathione GSH) antioxidant systems25. However, it is worthy mentioned that the stress sequence imposition of heat and drought do not alter the global response to combined stresses2.Decreased and uneven precipitation can lead to more severe drought events, and high air temperature coupled with drought results in higher plant tissue temperatureZea mays L.) is one of the most important and widely grown crops in the world26. However, in many parts of the world, it is mainly cultivated in semi-arid environments and thus often faces high temperature, water scarcity, and a combination of these factors in field conditions28. Maize is originated from the tropics but is still sensitive to heat and drought stresses, particularly after 8th leaf stage29. In China, 60% of crops in maize growing regions are often subjected to heat and drought spells, which may result in 30% yield losses per year28. Owing to changing climatic patterns worldwide, it is projected that these stresses will become major threats to maize yields and will decrease the world maize production by 15–20% each year31.Maize  to investigate the individual and concurrent effects of heat and drought stresses on morpho-physiological growth, grain yield, osmolyte accumulation, nutrient uptake and oxidative status in maize, (2) to examine the basis of maize tolerance against drought and heat stresses, and (3) to assess the performance of two different maize hybrids under drought and/or heat stresses.Despite the frequent existence of combined heat and drought stress episodes under field conditions, most of the previous studies have focused on independent drought or heat stress responses in plantsDrought and heat stress conditions alone or in combination hampered the morphological growth, grain yield and yield related attributes of both maize cultivars. Compared with control, combined drought + heat stress significantly reduced the plant height, shoot fresh weight, shoot dry weight, stem diameter, leaf area, kernels/ear, 100-kernel weight, grain yield/plant and harvest index (HI) of two maize hybrids Tables . HoweverThe leaf chlorophyll concentration of maize hybrids decreased under stress conditions as compared with control. However, the negative effects of heat were more severe for chlorophyll contents than the individual effects of drought stress Fig. . CompareHeat stress resulted in a slight decrease of relative water contents (RWC) in both maize hybrids, and these values were statistically similar with control. However, drought stress significantly reduced the RWC in Xida 319, which were further decreased under drought + heat stress. The reduction of RWC in Xida 319 was greater under drought + heat stress than that in Xida 889 Fig. .2 concentration (Ci) was increased under drought and significantly enhanced by drought + heat stresses, while it was decreased slightly under heat stress , transpiration rate (Tr), and stomatal conductance (Gs) in both Xida 319 and Xida 889 hybrids were reduced by drought and drought + heat stresses. However, the reductions in these traits were more severe under combined drought + heat stresses than drought stress individually Fig. . As compess Fig. . The dro−) in both hybrids under stress conditions were statistically similar with control. At individual stress level, the superoxide anion radical (O2−) contents were higher under heat stress, while hydrogen peroxide (H2O2) contents were higher under drought stress  in both hybrids. Nevertheless, higher oxidative damage in Xida 319 indicated that this cultivar is less tolerant to heat and drought stresses than Xida 889  accumulation and the levels of membrane damage in two maize hybrids were increased under all stress conditions. However, the negative influence of drought + heat stress was more pronounced than those of individual stresses. The concentrations of hydroxyl free radical  were significantly increased under stress conditions as compared with control Fig. . The enhDrought and heat stresses regulated the accumulation of soluble sugars, free proline, and heat shock protein in hybrid maize hybrids Fig. . ExposurCompared with control treatment, heat stress did not significantly affect nitrogen (N) concentrations in root, leaf, and stem of both maize hybrids, while drought stress alone was found to significantly decrease the leaf N concentrations in both hybrids Table . The N c33. In the present experiment, drought and heat stress conditions reduced the plant height, leaf area and biomass accumulation that ultimately reduced the yield and related attributes of two maize hybrids, nevertheless, the negative effects of drought + heat stresses were more severe for both maize hybrids then their individual effects , however, the concentrations of N in roots and woody tissues were decreased with respect to control. Drought stress alone was found to significantly decrease the leaf N concentrations in both hybrids and stem P and stem K concentrations in Xida 889, compared with control , was applied 5 g per pot prior to sowing.The experiment was carried out in controlled green house at the College of Agronomy and Biotechnology, Southwest University, Chongqing, China  during spring 2017. The seeds of two maize hybrids i.e., Xida 889 and Xida 319 were obtained from Maize Research Institute, College of Agronomy and Biotechnology, Southwest University, Chongqing, China. Seeds were planted in plastic pots  filled with sandy-loam soil and farmyard manure in a proportion of 7:3. The total weight of each filled pot was 11 kg. In each pot, five seeds were initially sown and after emergence, two plants were maintained in each pot. Fertilizer containing urea, KCl and PThe maize plants were maintained up to tasseling stage under normal conditions. At the tasseling stage, plants were subjected to heat, drought, and combined stress treatments for a period of 15 days. For well-watered/control (Ck), and drought (D) stress conditions, the temperature was 28 °C/20 °C (day/night); while for heat (H) and drought + heat stress (D + H) treatments, temperature was set at 38 °C/30 °C (day/night). The relative humidity was in the range of 55–70%. The drought stress was imposed at 50% field capacity (FC). The drought stress treatments were regularly checked and maintained using a moisture meter TRIME-EZ/-IT . The experimental treatments were arranged in completely randomized design (CRD) under factorial arrangement. Each treatment was replicated three times, and there were five pots in each replicate.2 and stored at −80 °C for measuring different biochemical analysis.Fully expanded, healthy, and undamaged plant leaves (fourth from the top) from each replicate were sampled at 15 days after imposition of stress treatments. After washing with pure distilled water, plant leaves were frozen in the liquid Net al. (1911): LA = L × W × 0.75, where L indicates leaf length, W represents the maximum leaf width, and 0.75 is the factor used for determination of leaf area in maize. Plant height was measured using a meter scale, while electronic weighing balance was used to assess the shoot fresh and dry weights. Digimatic caliper  was used to measure stem diameter. For the analysis of yield parameters, six plants from each replication were randomly sampled and harvested at maturity. After sun-drying, the ears were manually shelled and yield constituents such as number of ears per plant, number of kernels rows per ear and grain yield per plant were recorded. The HI was calculated as the percent ratio of grain yield and biological yield.Leaf area (LA) of maize plants was assessed following the method of Montgomery 75. Extraction of 250 mg leaf without vein (leaf blade) was done with 10 ml ethanol-acetone (vol. 1:2), and the extract was transferred to 15 ml tube. The tubes were placed in dark to avoid light for 24 hours. The absorbance was measured at 645 nm, 663 nm, and 652 nm. The chlorophyll content was computed by the following formulae:Photosynthetic components were recorded on intact leaves from the forth branch from the top, at 15 days after imposition of stress treatments. The Chlorophyll concentrations  were determined according to Peng and Liu76. The fresh leaves from the uppermost branch were sampled from plants and were cut into small segments (1.5 cm length), weighed (FW: fresh weight), floated on distilled water for 3 h under low light, and weighed again for turgid weight (TW), after surface moisture was removed. Afterward, the leaf samples were oven dried at 80 °C for 24 h and dry weight (DW) was recorded. The RWC was calculated as follows:Relative water content of maize leaves was measured following the method of Barrs and Weatherley2 concentration (Ci) were recorded using a portable infrared gas exchange analyzer .The photosynthetic gas exchange attributes including net photosynthesis rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), and intercellular COLipid peroxidation in maize leaves was determined as MDA content; measured by thiobarbituric (TBA) method using ‘MDA Kit (A003-3)’ obtained from Suzhou Comin Biotechnology Co., Ltd., China. Lipid hydroperoxide decomposition products can condense with thibabituric acid (TBA) to produce red compounds. The absorbance for MDA was measured at 532 nm and represented as nmol/g fresh weight.2O2 and OH− in the leaves of maize were measured using the commercial ‘H2O2 Kit (H2O2-Y)’ and ‘OH− Kit (QZQ-G)’, respectively, obtained from Suzhou Comin Biotechnology Co., Ltd., China. H2O2 content was measured at 415 nm and expressed as μmol/g fresh weight. The ability to remove hydroxyl radicals measured at 536 nm and expressed as percent content. The contents of O2− in the leaves of maize were noted using the commercial ‘O2− kit (A052)’, obtained from Nanjing Jiancheng Bioengineering Institute, China. The O2− content was demonstrated as unit’s g−1 fresh weight and one unit was equivalent to superoxide anion radical inhibition by 1 mg of Vc for 40 minutes at 37 °C reaction24.The contents of H2O2 at 405 nm sec−1 in 1 mg tissue proteins. One unit of APX was defined as the amount of enzyme required for catalyzing 1μmol ASA at 290 nm min−1 of 1 mg tissue proteins in 1 ml of a reaction mixture.The activities of antioxidant enzymes were recorded using commercial kits in accordance with the instructions of manufacturer. The kits for total superoxide dismutase , catalase  and ascorbate peroxidase  were procured from Nanjing Jiancheng Bioengineering Institute, China. The absorbance readings of T-SOD, CAT and APX were detected at 550 nm, 405 nm and 290 nm, respectively. The T-SOD and CAT activities in maize leaves were articulated as U/mg protein, while APX activity was demonstrated as U/g protein. One unit (U) of T-SOD was the amount of enzyme required for 1 mg tissue proteins in 1 ml of a reaction mixture to raise SOD inhibition rates to 50% at 550 nm. One unit of CAT activity was estimated as the amount of enzyme that decomposes 1μmol H−1 for 1 mg tissue proteins in 1 ml of a reaction mixture. The absorbance for GSH was measured at 412 nm and expressed as μmol/g fresh weight. The absorbance for T-AOC was measured at 593 nm and expressed as U/mg protein. One unit of T-AOC was expressed as the amount that enhanced the absorbance by 0.01 at the 37 °C.The POD activity, GSH content and T-AOC in the leaves of maize were determined using the commercial kit ‘POD (POD-Y)’, ‘GSH (GSH-W)’ and ‘T-AOC (TAOC-G)’, respectively, obtained from Suzhou Comin Biotechnology Co., Ltd., China. One unit of POD activity was defined as the absorbance change of 0.005 at 470 nm min77. Fresh leaf material (0.5 g) was extracted using 5 ml of 3% sulphosalicylic acid for 10 min with shaking at 100 °C. The 2 ml of filtered aqueous extract was mixed with glacial acetic acid (2 ml) and acid ninhydrin reagent (2 ml), and heated (100 °C) for 30 min. The reaction mixture after cooling was segregated against toluene (4 ml) and the absorbance of the organic phase was recorded at 520 nm. The resulting values were related with a standard curve plotted using known amounts of proline . Total soluble sugar was estimated by anthracene ketone method as described by Zong and Wang78. The fresh leaf sample (0.2 g) was homogenized with 25 ml distilled water and centrifuged (4000 rpm) for 20 minutes. Anthracene (0.1 g) was dissolved in 100 ml diluted sulfuric acid to prepare anthracene sulfuric acid reagent. One ml extract and 5 ml anthracene sulfuric acid reagent were taken in a tube, shaken and put in boiling bath for 10 minutes. After 2 h stability, the sample was transferred in cuvette and the absorbance was read at 620 nm. The total protein content in the leaves of maize seedling was determined by Coomassie brilliant blue method using ‘Protein Quantification Kit (A045-2)’ obtained from Suzhou Comin Biotechnology Co., Ltd., China. The absorbance for protein was measured at 595 nm and unit of protein was quantified as mg/ml sample solution. The level of heat shock protein (HSP) in the leaves of maize was determined using the kit ‘HSP (YX-081916P)’ obtained from Sino Best Bio, Shanghai. The absorbance for HSP was measured at OD 450 nm and expressed as pg/ml sample solution.Free proline contents were assessed by following the acid ninhydrin method2SO4) in a sealed chamber79. Total N was determined using the Kjeldahl method80. The K level was analyzed using an Elemental Analyzer, while P concentration was determined by vanadate molybdate method using a UV/visible spectrophotometer as suggested by Chapman and Pratt81.Roots, stems and leaves were thoroughly washed with distilled water and were oven-dried at 105 °C for 1 hour and later at 80 °C until constant weight. Dry samples of 300 mg were digested with 8 ml sulfuric acid  technique using SPSS 22.0 software  whereas the differences between control and stress treatments were separated according to Duncan’s multiple range test at a 1% and 5% level of significance. SigmaPlot 13.0 software  was used for the graphical presentation of data.In summary, exposure of drought, heat and drought + heat stress at tasseling stage brought severe negative effects on growth and the yield attributes of the maize hybrids. Concurrent effects of drought + heat stress on photosynthetic components, osmolyte accumulation, enzymatic and non-enzymatic antioxidants and nutrients uptake of both maize hybrids were more severe than their individual effects. Under drought and heat stress conditions, higher ROS accumulation and rate of lipid peroxidation inhibited the photosynthetic efficiency and restricted the growth of maize. The levels of ROS scavengers were variable in both maize hybrids. Overall, the morpho-physiological growth, and yield performance of Xida 889 cultivar was better than the Xida 319 cultivar. The greater tolerance of Xida 889 to heat and drought stresses was attributed to strong antioxidant defense system, higher osmolyte accumulation, and maintenance of photosynthetic pigments and nutrient balance compared with Xida 319.


P < 0.05) higher incidence (12.5/100 000) and mortality (10.97/100 000) compared to NHW  and H/L , especially in rural counties. To investigate radiologic and blood‐based correlates of cachexia, we leveraged data from a subset of patients evaluated at two geographically distinct Florida Cancer Centers. In Blacks compared to NHW matched on stage, markers of PC‐induced cachexia were more frequent and included greater decreases in core musculature compared to corresponding healthy control patients (25.0% vs 10.1% lower), greater decreases in psoas musculature over time (10.5% vs 4.8% loss), lower baseline serum albumin levels (3.8 vs 4.0 gm/dL), and higher platelet counts (332.8 vs 268.7 k/UL). Together, these findings suggest for the first time that PC and cachexia may affect Blacks disproportionately. Given its nearly universal contribution to illness and PC‐related deaths, the early diagnosis and treatment of cachexia may represent an avenue to improve health equity, quality of life, and survival.Pancreatic cancer (PC) is characterized by racial/ethnic disparities and the debilitating muscle‐wasting condition, cancer cachexia. Florida ranks second in the number of PC deaths and has a large and understudied minority population. We examined the primary hypothesis that PC incidence and mortality rates may be highest among Black Floridians and the secondary hypothesis that biological correlates of cancer cachexia may underlie disparities. PC incidence and mortality rates were estimated by race/ethnicity, gender, and county using publicly available state‐wide cancer registry data that included approximately 2700 Black, 25 200 Non‐Hispanic White (NHW), and 3300 Hispanic/Latino (H/L) Floridians diagnosed between 2004 and 2014. Blacks within Florida experienced a significantly ( An understudied biological attribute of PC is cancer cachexia, an often progressive condition characterized by pathological loss of striated muscle  and fat stores, manifesting in the cardinal features of emaciation, weakness affecting functional status, impaired immune function, metabolic dysfunction, and poor quality of life (QoL).Several blood‐based biomarkers of cancer cachexia exist, including serum albumin  and platelets (a surrogate marker of inflammatory and immunologic responses to tumors); decreased serum albumin levels and high platelet counts have been shown to help identify cachexia and predict poor outcomes.In this study, we used publicly available data to examine PC incidence, mortality rates, and characteristics of patients diagnosed and treated for PC. As medical images and laboratory values for a diverse cohort of PC cases are not available in publicly available datasets, we leveraged data from two large and geographically separate Florida Cancer Centers to evaluate correlates of cachexia and focused on Blacks and NHW, the two racial groups with the highest PC burden.22.1P < 0.05.We conducted a retrospective, case‐only descriptive analysis of data from cancer registries and hospitals in Florida. Florida's Statewide Cancer Registry, the Florida Cancer Data System (FCDS), has received the NAACCR Gold Standard Award, highlighting the quality, completeness (95% or higher in terms of case ascertainment), and timeliness of data submissions.Since the on‐line incidence/mortality tool available through FCDS does not provide data on the volume and racial/ethnic distribution of PC cases diagnosed and treated at individual Florida hospitals, we complemented the publically available aggregate FCDS data with 2012‐2014 inpatient hospital discharge data from the Florida Agency for Health Care Administration (AHCA).2.2Prospectively maintained clinical databases were retrospectively reviewed to identify males and females aged 18 and above who self‐reported as Black or NHW and presented to the Gastrointestinal Clinic at the University of Florida Health Sciences Center  or Moffitt Cancer Center  with a strong clinical suspicion or diagnosis of PC between the years 2004 and 2014. These individuals provided written informed consent for biospecimens and data to be donated for research through Institutional Review Board‐approved protocols. Diagnostic confirmation was made using histology from tissue biopsies or surgical resection. Demographic, clinical, epidemiologic, and follow‐up data were collected from the medical record and cancer registry. Additionally, for purposes of comparison, we assessed measures of cachexia among a cohort of Black and NHW “healthy controls” who underwent non‐oncologic surgery at UF.2/m2). At UF, the percent difference between the PMI of healthy controls and the PMI of PC cases was also determined as follows: (preoperative PMI in cases—preoperative PMI in controls)/preoperative PMI in controls.Myopenia was assessed in a blinded fashion for each cohort using axial CT image analysis.2/m2). AW Server version 2.0  was used for postprocessing. To classify individuals as myopenic or not myopenic, we used validated gender specific cutoffs of PMI 2/m2 for women and <5.64 cm2/m2 for men) and gender‐ and BMI‐specific cut‐points of SMI2/m2 for men . Percent change in musculature over time was calculated for cases as follows: (baseline minus follow‐up muscle index)/baseline muscle index. Descriptive statistics were calculated using frequencies and percents for categorical variables and means and standard deviations for continuous variables.Total skeletal muscle was also measured at the caudal L3 level and included areas of all visible skeletal muscles such as the rectus abdominis; internal, external, and lateral obliques; psoas; quadratus lumborum; and erector spinae muscles. The threshold for this area included hounsfield unit values of −29‐150 which correspond to skeletal muscle. Total skeletal muscle area at L3 was divided by height squared to yield another measure of myopenia, skeletal muscle index (SMI) (cm33.1P < 0.001) PC burden than female Floridians of all races, with mean incidence rates of 13.20 versus 9.85 per 100 000 and mortality rates of 11.68 versus 8.47 per 100 000, respectively. Among males, mean PC incidence and mortality rates were not significantly different among Blacks compared to NHW. Black female Floridians, however, had significantly higher incidence  and mortality rates  than NHW women. H/L men and women in Florida have significantly lower incidence and mortality rates than NHW (P < 0.001). Race/ethnicity and gender‐specific trends in PC incidence and mortality over time suggest these rates are not improving . AHCA dataFCDS data3.3P < 0.05) PC incidence rates than NHW and H/L in the Central East Coast (St. Lucie county), Central West Coast (Sarasota and Pinellas counties), Central (Sumter and Desoto counties), and Panhandle regions (Leon county)  whose borders were previously defined based on the cost of living index  and the urban‐to‐rural population ratio.) Figure . The hig) Figure . RegionsHospital‐level inpatient dataAt the patient level, 14.9% of Blacks underwent pancreatic surgery compared to 17.8% of NHW and 19.0% of H/L.3.4Next, we evaluated biological correlates of cancer cachexia for Blacks and NHW treated at two Florida cancer centers. Preoperative CT images and serum albumin values were available for a retrospective cohort of 17 Black and 76 NHW PC cases matched on gender, age‐group, and clinical stage surgically treated at the UF Health Sciences Center . Figure 2/m2 vs 5.20 cm2/m2, P = 0.008). There was no correlation between BMI and PMI . Serum albumin levels in control patients were similar , and there was no correlation between albumin and PMI . Black patients with PC had a significantly lower PMI than Black controls  while the PMI of NHW patients with PC was similar to the index in NHW healthy controls . The calculated per cent differences in PMI between PC cases and controls revealed lower PMI between both Black and NHW at 25.0% and 10.1%, respectively. Figure For a cohort of 20 Black and 34 NHW “control” patients with benign non‐oncologic disease matched to PC cases on gender, age group, BMI, and Charlson Co‐morbidity Score, Black control patients were found to have a significantly greater preoperative PMI than NHW patients  who had a longitudinal series of CT scans (baseline/pretreatment and follow‐up) available. Compared to NHW cases, Black PC cases of both genders were diagnosed younger and had poorer mean survival Table , in line4A large, high‐quality cancer registry was used to assess PC burden in Florida, a state with racial/ethnic, geographical, and economic diversity.Surgery offers the best chance for survival, especially if performed at a high‐volume hospital but only 15%‐20% of PC cases are candidates for surgery.To study and target modifiable biological factors that may contribute to disparities, we generated the first preliminary data we are aware of to suggest Blacks may be at higher risk for developing advanced stages of cancer cachexia and early demise. Using objective measures of inferior nutritional and functional status, we show that decreases in psoas musculature over time were more pronounced among Blacks compared to NHW and that lower levels of albumin and higher levels of platelets were more commonly observed among Black males. Notably, we also show that Black patients suffer substantially more muscle wasting than NHW patients at diagnosis, even after matching for clinical stage. Platelets are markers of inflammatory and immunologic responses associated with pancreatic carcinogenesis, cachexia, and poor prognosis.Although promising, the cachexia‐related analyses have several limitations. First, these analyses were conducted using data from a retrospective series of PC cases from only two high‐volume cancer centers and may have been influenced by selection bias. Additionally, the small number of cases in each strata precluded multivariate modeling to assess associations with survival while adjusting for comorbidities, smoking history, and socioeconomic variables. Furthermore, this exploratory analysis did not include H/L patients. Despite these limitations, this is first analysis to explore biological correlates of PC cachexia in Blacks and NHW. This analysis would not have been feasible using data from statewide datasets through FCDS and AHCA or regional or national datasets such as SEER, the Cancer Genome Atlas Project, or the Cancer Imaging Atlas Project. Large prospective studies with longitudinal collection of data, images, and biospecimens from racially/ethnically diverse cohorts are needed to confirm and extend upon these speculative findings related to cancer cachexia and other biologically driven hypotheses.4.1Factors underlying PC disparities reflect the interplay of lifestyle, environmental, socioeconomic, policy, and biological determinants that influence cancer etiology and outcomes Table . ParamouThe authors declare no conflicts of interest.Study conceptualization/design: JBP, ACD, DKJ, JWC, JGT; Data curation: JBP, ACD, DKJ, JWC, MEC, JGT; Formal analysis/investigation: JBP, ACD, DKJ, JWC, MEC, JGT; Manuscript writing: JBP, ACD, DKJ, MEC, JGT; Manuscript review/approval: JBP, ACD, DKJ, JWC, MEC, D‐TC, JKT, TEB, JL, BDP, NBK, TJG, KNA, TH, SV, CKG, VNS, PJH, EMC, ARJ, JF, NM, JGT. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file.


We used these findings as foundations for our use of a novel approach—multi-trait analysis of genome-wide association studies —to combine two large genome-wide association studies (GWASs) of education and intelligence, increasing statistical power and resulting in the largest GWAS of intelligence yet reported. Our study had four goals: first, to facilitate the discovery of new genetic loci associated with intelligence; second, to add to our understanding of the biology of intelligence differences; third, to examine whether combining genetically correlated traits in this way produces results consistent with the primary phenotype of intelligence; and, finally, to test how well this new meta-analytic data sample on intelligence predicts phenotypic intelligence in an independent sample. By combining datasets using MTAG, our functional sample size increased from 199,242 participants to 248,482. We found 187 independent loci associated with intelligence, implicating 538 genes, using both SNP-based and gene-based GWAS. We found evidence that neurogenesis and myelination—as well as genes expressed in the synapse, and those involved in the regulation of the nervous system—may explain some of the biological differences in intelligence. The results of our combined analysis demonstrated the same pattern of genetic correlations as those from previous GWASs of intelligence, providing support for the meta-analysis of these genetically-related phenotypes.Intelligence, or general cognitive function, is phenotypically and genetically correlated with many traits, including a wide range of physical, and mental health variables. Education is strongly genetically correlated with intelligence ( In a po ability . Intelli ability , 4 a low ability . Intelli ability . These g ability . Heritab ability , 9 metho ability . Some of ability , 12. Mor ability , and GRE ability  using im ability  have beeRelatively few genetic variants have reliably been associated with intelligence differences . The spaTwo strategies have emerged in order to maximise power by increasing the sample size for loci discovery in intelligence research. The first involves the meta-analysis of many GWASs conducted on intelligence –21. HoweThe second method is to use a “proxy” phenotype  that shon = 78,308) [n = 329,417, which include individuals from UK Biobank).In the present study, we combined these two approaches by using MTAG , a newly 78,308) . We perf 78,308)   [n = 329,417) [N = 76,051, time 2, N = 9266, time 3, N = 2552, online, N = 33,065). UK Biobank participants who were included in the GWAS from Sniekers et al. [Summary statistics were obtained from GWAS meta-analyses of intelligence  , and edu329,417) . To maxis et al. . were omIn order to derive genetic correlations between intelligence  and health-related and other traits, we used summary statistics from 29 GWAS datasets. Supplementary Table Full details of the UK Biobank genotyping procedure are available elsewhere . BrieflyAdditional quality control steps were implemented in the present study and included the removal of participants with non-British ancestry  was included. MTAG was run using the default settings.MTAG  allows tP-value being genome wide significant (P < 5 × 10−8) and being independent from each other (r2 < 0.6) within a 1 mb window. Secondly, SNPs that were in LD of the independent lead SNPs (r2 ≥ 0.6) within a 1 mb window, and within 1000 genomes reference panel with a MAF of greater than 0.01 were included for further annotation. Thirdly, lead SNPs were identified as a subset of the independent significant SNPs (defined as above). Lead SNPs were defined as independent significant SNPs that were in LD with each other at r2 < 0.1, again with a 1 mb window. Fourthly, genomic risk loci were identified by merging lead SNPs if they were closer than 250 kb apart, meaning that a genomic risk locus could contain multiple independent significant SNPs and multiple lead SNPs. Finally, all SNPs in LD of r2 ≥ 0.6 with one of the independent significant SNPs formed the border or edge of the genomic risk loci. To map LD, the 1000 genomes phase 3 was used [Using the meta-analytic dataset produced by MTAG, genetic loci related to intelligence were identified using FUMA . First, was used .r2 ≥ 0.6, were nominally significant, and had a MAF of 0.01. To gauge the functional consequences of genetic variation at these SNPs they were first matched based on chromosome, base pair position, reference, and non-reference alleles to a database containing functional annotations including the ANNOVAR categories [Functional annotation was carried out in FUMA  using altegories , combinetegories , Regulomtegories , and chrtegories –42.The ANNOVAR  categoriChromatin states indicate the level of accessibility of genomic regions. This level of accessibility was described using a 15 point scale predicated for each variant using a hidden Markov model based on five chromatin marks for 127 epigenomes in the Roadmap Epigenomics Project . The lowP-value describing the association found with intelligence. Gene locations and boundaries were used from the NCBI build 37 and LD was controlled for using the 1000 genomes phase 3 release [Gene-based analysis was conducted using multi-marker analysis of genomic annotation (MAGMA) . SNPs th release . A BonfeIn order to identify the importance of particular tissue types relevant to individual differences in intelligence, a gene property analysis was conducted using MAGMA. The goal of this analysis was to determine if, in 30 broad tissue types, and 53 specific tissues, tissue-specific differential expression levels were predictive of the association of a gene with intelligence. Tissue types were taken from the GTEx v6 RNA-seq database  with expGene-set analysis was conducted using MAGMA  using coZ-score [χ2 statistic of >1.02 [χ2 > 80 were removed. LD scores and weights for use with European populations were downloaded from (http://www.broadinstitute.org/~bulik/eur_ldscores/). False discovery rate (FDR) was controlled for using Benjamini-Hochberg [APOE was removed and the analysis re-run in order to ensure that the large effects in this region did not bias the regression.In order to address whether the genetic architecture of the meta-analysis of correlated traits conducted here produced a phenotype with the same genetic architecture as intelligence, we derived genetic correlations across 29 cognitive, socio-economic status (SES), mental health, metabolic, anthropometric, reproductive, and health and wellbeing phenotypes. We used linkage disequilibrium score regression  to test Z-score  of >4 anof >1.02 . A minorof >1.02 , and so Hochberg  procedurHochberg . datasetHochberg . In the 2)/Pr(SNPs)). This ratio describes whether a functional annotation contains a greater or lesser proportion of the heritability than would be predicted by the proportion of SNPs it contains, Pr(h2)/Pr(SNPs) = 1. The proportion of the heritability of each category is used as the numerator, rather than the heritability of each category. Stratified LD Scores were calculated from the European-ancestry samples in the 1000 Genomes project (1000G) and only included the HapMap 3 SNPs with a minor allele frequency (MAF) of >0.05. A model was derived using 52 overlapping, functional categories. Correction for multiple testing was performed using a Bonferroni test on the 52 functional categories (α = 0.00096).Partitioned heritability was carried out using stratified linkage disequilibrium score regression . The goar2 < 0.25, 250 kb window). Polygenic scores were then derived for each participant as the sum of alleles associated with intelligence, weighted by the effect size from our meta-analytic intelligence dataset. A total of five polygenic risk scores were derived using the following P-value cut offs: 0.01, 0.05, 0.1, 0.5, and 1.The three smaller samples of individuals who performed the VNR test and had their genetic data released in the second release of the UK Biobank genetic data were used. The METAL meta-analysis and MTAG meta-analysis with education were re-run leaving out one of the groups who performed the VNR test. The group that was left out were then used as the target sample for polygenic prediction. Using our meta-analytic dataset on intelligence, polygenic risk scores were derived for intelligence in each of the VNR groups using PRSice . SNPs thχ2 of the Sniekers dataset from to 1.30 to 1.59, making it similar in statistical power to the Okbay education dataset [χ2 = 1.65).Genetic correlations performed for each of the four VNR groups whose genetic data were released in the second release of the UK Biobank genetic data against the Sniekers dataset  indicate dataset  , as well as SNPs found in intergenic regions 28%)  is combined . A totalP = 3.39 × 10−15), and the pituitary (P = 1.23 × 10−7) , the cerebellum (P = 1.00 × 10−15), the frontal cortex (P = 5.47 × 10−14), the anterior cingulate cortex (P = 4.61 × 10−12), the nucleus accumbens of the basal ganglia (P = 1.50 × 10−9), hippocampus (P = 2.77 × 10−9), amygdala (P = 9.80 × 10−9), hypothalamus (P = 2.51 × 10−8), caudate nucleus (P = 4.35 × 10−8), putamen (P = 1.69 × 10−7), and the substantia nigra (P = 6.46 × 10−4)  Fig. . An exam Fig. . AP-value = 5.59 × 10−10), the process by which neurons are generated from neural stem cells. Secondly, a role was also found for genes expressed in the synapse , consistent with previous studies showing a role for synaptic plasticity [P-value = 4.02 × 10−8). Fourthly, we find evidence for enrichment for neuron projection , neuron differentiation , and central nervous system neuron differentiation . Finally, we identify a role for oligodendrocyte differentiation . In addition to these novel results, the finding that regulation of cell development  is enriched for intelligence was replicated [In order to obtain information on the biological systems involved in intelligence differences that are influenced by genetic variation, we conducted gene-set analysis using all genes available irrespective of their level of association. Using a competitive test of enrichment implemented in MAGMA, we identified seven novel biological systems associated with intelligence differences Table . Firstlyasticity . ThirdlyP = 1.59 × 10−5), as were transcriptional start sites (P = 9.19 × 10−4). We also find enrichment of heritability for the histone marks of H3K9ac (P = 7.81 × 10−6), H3K4me1 (P = 1.43 × 10−5), H3K27ac PGC2 (P = 9.16 × 10−4), and H3K27ac Hnisz (P = 3.09 × 10−5). We also replicate the finding that regions of the genome that have undergone purifying selection are enriched for intelligence [P = 7.77 × 10−16)  could be predicted  and our meta-analytic sample . This indicates that the polygenic load for greater intelligence is associated with greater longevity, using parental longevity as a proxy phenotype.We next derived genetic correlations with 29 phenotypes both to obtain evidence suggesting that the results of our meta-analysis produced a phenotype with the same genetic architecture as intelligence, and to examine additional phenotypes that might be genetically correlated with intelligence Fig. . Many ofgression . We findgression  GWAS ; and years of education . The genetic correlation of 1 between our intelligence dataset and that of Sniekers further indicates that the underlying polygenic signal in our meta-analytic dataset is highly similar to that of intelligence, rather than being an average between education and intelligence . For bipolar disorder, previous results have indicated a negative genetic correlation using established measures of intelligence, although after correcting for multiple tests this estimate was not statistically significant [rg = 0.10, SE = 0.02), and a negative genetic correlation was found with both intelligence datasets .For the mental health variables, our meta-analytic intelligence dataset showed a pattern of genetic correlations more similar to Sniekers  GWAS on nificant . SimilarDifferences between the previous GWAS on intelligence  and our People with a higher level of cognitive function have been observed to have better physical and mental health, and to have longer lives , 7. ThisFirst, we found 187 independent associations for intelligence in our GWAS, and highlighted the role of 538 genes being involved in intelligence, a substantial advance on the 18 loci previously reported . Within Second, using two strategies, we uncovered additional functional elements of the genome associated with intelligence differences. Both of these methods used the whole polygenic signal in our final dataset rather than only the most significant regions as used in FUMA. Using MAGMA, we found that transcription differences in the brain and pituitary gland were associated with intelligence. This relationship with cortical tissues was found across the cortex and in multiple cortical tissues Fig. . Using sThird, we used our meta-analytic GWAS data to predict almost 7% of the variation in intelligence in one of three independent samples. The range of similar estimates across the three independent samples was 3.6 to 6.8%. Previous estimates of prediction have been ∼5% at most;  our resuFourth, we report the novel finding that the polygenic signal across our GWAS dataset clusters in genes involved in the process of neurogenesis, genes expressed in the synapse, and genes involved in the development of the nervous system, as well as those involved in myelination within the central nervous system due to their role in oligodendrocyte differentiation. This provides a rationale for a theory of how genetic differences, via their influence on physiological differences, contribute to variation in intelligence.The finding of neurogenesis gene-set enrichment for intelligence is persuasive, because neurogenesis has been linked to cognitive processes—particularly pattern separation and cognitive flexibility—in rodent models. New neurons are continually made in humans in the subgranular zone of the hippocampus and in the striatum;  in rodenOligodendrocyte differentiation was also identified by gene-set analysis as being involved in intelligence differences. The central nervous system of humans contains a very high percentage (~50%) of white matter, which is maintained by the action of oligodendrocytes . AbnormaFinally, we showed, using genetic correlations with 29 other traits, that our meta-analytic intelligence GWAS had a highly similar genetic architecture to that of intelligence alone. The genetic correlations that were produced using the meta-analytic intelligence GWAS did differ for some traits; this was most evident for schizophrenia, for which positive genetic correlations have been observed with education , but negrg = 0.70 to rg = 0.80, the genetic correlation with intelligence from the Sniekers dataset remained at rg = 1.00, showing that the MTAG procedure produces a phenotype with a highly similar genetic architecture to the trait of interest.This limitation—a greater proportion of variance that is common across education and intelligence in our results—has implications for the results of our GWAS, since those variants that gain the most signal from meta-analysis across genetically correlated traits will, by definition, show association with each trait in our meta-analysis. Whereas the final results of our GWAS did indicate the loci that are likely to be involved in intelligence differences, our GWAS may be overrepresented by effects that are also associated with education. Nevertheless, we did find associations on each chromosome that were not found in the most recent GWAS of education , and peaFuture work using large GWAS that are exclusively based on established tests of intelligence  will proSupplementary Table 1Supplementary Tables 2-7


One of the deficits observed in autism spectrum disorder (ASD) is impaired imaginative play. One form of imaginative play common in many typically developing (TD) children is having an imaginary companion (IC). The occurrence of ICs has not been investigated extensively in children with ASD. We examined differences in parent report of IC between TD and ASD populations in 215 (111 with ASD) gender-matched children aged between 2 and 8 years. Findings indicate that significantly fewer children with ASD created ICs, although there were many between-group similarities in IC forms and functions. Results are discussed in terms of qualitative differences in play, social attributions, and how children with ASD conceptualize their ICs’ minds.The online version of this article (10.1007/s10803-018-3540-y) contains supplementary material, which is available to authorized users. Imaginary or pretend play is an activity that typically developing (TD) children engage in frequently and spontaneously. However, children diagnosed with an autism spectrum disorder (ASD) show deficits in this behavior. Early in the ASD literature, Wing and Gould  proposedPast research on imaginative behavior in children diagnosed with ASD shows that this population is profoundly delayed in imaginative play  . Some studies report that having an IC is related to superior ToM and emotion understanding abilities  differed between ASD and TD children. We were also interested in investigating whether the ASD and TD groups differed with respect to the reported function of the IC or the age at which ICs were created. In addition, we explored factors relating to IC creation within the ASD group, investigating whether age at which children were diagnosed with ASD or children’s reported cognitive functioning related to the tendency to create an IC. Finally, the present study asked whether certain functions of ICs may be congruent with the needs  of children with ASD.M = 59.10 months, SD = 27.25); 79% (n = 88) were boys. The sample consisted of 85.6% Caucasians, 4.5% African Americans, 2.7% Asian, 3.6% Biracial, and 3.6% preferred not to answer. Information on economic status was not collected on this group. Parents reported that their children were diagnosed with ASD between 10 and 96 months of age . All diagnostic variables can be found in Table Participants were 111 parents of children with ASD . Only 81 boys participated, so seven boys were not matched. University ethics committees approved both protocols and all parents gave full informed consent.A second, previously existing data set of economically diverse parents of typically developing children reporting on their child’s IC status in a lab setting was used to compare the two groups. Participants were randomly matched with the ASD group based upon gender resulting in a TD group of 104 parents of children (81 boys) aged between 59- and 64- months  emails to listservs for families of children with ASD, (2) emails to agencies that had local, state, and national outreach, (3) flyers posed on social media, and (4) flyers handed out at different regional events. Parents then completed an online questionnaire through Qualtrics. Parents were provided with a link that they could access at their own computer or on their phone. The questionnaire took anywhere from 3 to 20 min to fill out depending on whether the parent reported that their child had created an IC.Parents of typically developing children were participating in a larger ongoing longitudinal study of which the IC questionnaire was a part. They completed a variation of this questionnaire in person on paper at a lab. They did not complete the section on demographics, diagnostics, and education at the time they were given the questionnaire. The last seven free-response questions about ICs were also not given to these parents.Parents of children with ASD first completed four forced-choice questions about demographics: age, sex, race, and ethnicity. These questions were followed by three forced-choice questions about the child’s educational environment: whether they were publicly or privately educated, if they had individualized education plans, the type of school programs they attended, and a free response item to clarify school situation. Finally, they answered three forced-choice questions about the child’s diagnoses, checking all labels that applied, including a high or low functioning option, and “other” which allowed them to type in additional diagnoses, the type of professional who provided the diagnoses, and the age at time of an ASD diagnosis.does your child have an imaginary friend or have they had one in the past? . If parents of children with ASD did not report their child having an IC, they were thanked for participating and the questionnaire closed. If the parent responded affirmatively, they were taken to an adaptation of Taylor and Carlson’s  = 1.21, p = .272, V = .10. There was also no association between gender and IC status in the TD population χ2(1) = 1.53, p = .216, V = .12. Age was not related to whether or not children created ICs in the ASD F = 0.53, p = .585, η2 = .012, or TD, F = 0.06, p = .814, η2 = .001, populations.Based on parent report, 16.2% of children diagnosed with ASD were reported as having created ICs. Of the children creating ICs, 38.8% were iICs and 61.1% were POs, such as a stuffed toy or doll. Examples of these can be seen in Table 2(1) = 21.37, p < .001, V = .32. When only looking at the differences between iIC and PO creation, children in the ASD sample were less likely than the TD children to create iICs η2(1) = 5.40, p = .020, V = .29.Chi square analyses were used to investigate whether children diagnosed with ASD were as likely as their TD counterparts to create ICs. IC creation was significantly less common in the ASD sample, χF = 5.09, p = .031, η2 = .130. Age of first parent reported IC interaction examining group differences between iIC and PO creation was investigated in children with ASD and then in TD children in an ANOVA. No effect was found for the type of IC in ASD, F = 0.19, p = .672, η2 = .012; or TD populations, F = 0.07, p = .800, η2 = .004. Means and standard deviations for age related variables can be found in Table Group differences in the age parents reported their child beginning to play with their IC were investigated using a one way ANOVA. Children with ASD began playing with ICs significantly later than TD children according to their parents, F1,5 = 5.09,t(37) = 1.36, p = .251, d = .38. There were also no differences in social attributions attributed in children with iICs versus POs in either the ASD, t(16) = 1.72, p = .105, d = .84 or TD groups, t(19) = − 0.55, p = .586, d = .24. Means and standard deviations for social attribution variables can be found in Table Parental reports on IC descriptions and interactions were coded to reflect social attributions ascribed to the IC by their children. The data for the ASD and TD groups are presented in Table t7 = 1.36,2(2) = 1.34, p = .512, V = .18. Parents were also asked if their child dislikes anything about their IC. Significantly more parents in the TD group reported their children disliking things about their IC than in the ASD population t(34) = 3.69, p = .002 .Parent description of their child’s ICs were then analyzed to look further into the forms and functions that these entities represented in the population of children with ASD. The two main themes of social support or comfort were found running through the questionnaires related to the function of the child’s IC. Table 2(1) = 6.74, p = .009. The model explained 11.2% (Nagelkerke R2) of the variance. Children’s age of diagnosis was further investigated by looking at differences in age of diagnosis between iIC, NIC, and PO children in an ANOVA finding a main effect of group F = 3.47, p = .035, η2 = .067. Post-hoc analyses indicated that children creating POs were diagnosed at a significantly younger age than NIC children (p = .037), however there were no differences in age of diagnosis between iIC and PO children (p = .822), or iIC and NIC children (p = 1.000). All age-related variables can be found in Table p = .603).A binomial logistic regression was used to investigate whether the age of first diagnosis related to the likelihood of a child creating an IC. The regression model was statistically significant χParents of children diagnosed with ASD were also asked whether their child uses the IC to communicate needs. Of the 17 parents reporting a child with an IC, three  of the parents responded that their child did speak through the IC to communicate their needs, whereas 13  responded that their child did not use the IC in this way, and one  was unsure.This exploratory study’s main aim was to discover what proportion of children diagnosed with ASD created ICs, investigating potential differences in ICs both within the ASD group and in comparison with TD children. Our findings indicate that a substantial minority of children diagnosed with ASD (16.2%) do spontaneously create ICs, with similar features to TD children’s ICs in some respects . Furthermore, ICs’ gender and their reported social attributions did not differ between groups. However, parents of children with ASD were less likely than those of TD children to indicate that their children had created an IC to their knowledge, and when parents did notice IC play, it was at a later age than TD parents. Furthermore, the type of IC (iIC or PO) differed in that, compared with their TD peers, the ASD sample created fewer iICs, and were less likely to talk to their parent about disliking parts of their IC’s personalities. Within group differences in children diagnosed with ASD revealed earlier diagnoses for children creating ICs and IC type.Finding a subset of children with ASD who spontaneously create ICs is contrary to much of the research on imagination in children with ASD, and in some instances, even the diagnosis itself APA . HoweverThe finding that children diagnosed with ASD were not reported to dislike things about their ICs as frequently as TD children suggests that the ICs that are created by children with ASD might have less well developed personalities and minds, due to documented problems in ASD children in conceptualizing other minds  of the children with ASD with ICs reportedly used their IC for communicative purposes. ICs have been shown to have many communicative functions in TD children Hoff , but comThe results reported here should be interpreted in light of some limitations of the present study. All measures were assessed by parental report. Although parents of TD children have been shown to be the best at reporting the imaginative lives of their children Gleason , future A second limitation is that the group of ASD children reported to have ICs was small, meaning that the within-group analyses were lacking in power. The third issue is one of generalizability. The parents of children with ASD were recruited mainly from Facebook support groups and local ASD events, and is therefore not a representative sample. Finally, matching participants on age, and including a comparison group of children with developmental delay to allow for matching ASD children for cognitive functioning, would provide more information on which aspects of IC creation and play may be the unique to children diagnosed with ASD.Broadly, our results confirm much of the research on deficits in ASD children’s spontaneous imagination behavior. However, the similarities identified between the ICs of TD children and those with ASD who had created ICs suggest that differences between TD and ASD children on this specific high-level imaginative behavior may be quantitative rather than qualitative.Below is the link to the electronic supplementary material.Supplementary material 1 (SAV 1371 KB)


The improved current densities and PCEs are attributed to the reduced work function, enhanced absorption, and improved interfacial contact by using CMC and ZnO as co‐interface. This approach of fabricating interface materials from biorenewable sources for OSCs is simple, scalable, and cost‐effective, representing a promising direction for the development of smart interface and green electronics.Advanced interface materials made from petrochemical resources have been extensively investigated for organic solar cells (OSCs) over the past decades. These interface materials have demonstrated excellent performances in OSC devices. However, the limited resources, high‐cost, and non‐ecofriendly nature of petrochemical‐based interface materials restrict their commercial applications. Here, a facile and effective approach to prepare cellulose and its derivatives as a cathode interface layer for OSCs with enhanced performance from rice straw of agroforestry residues is demonstrated. By employing this carboxymethyl cellulose sodium (CMC) into OSCs, a highly efficient inverted OSC is constructed, and a power conversion efficiency (PCE) of 12.01% is realized using poly dithiophene))‐ An effective approach to prepare cellulose as interface of organic solar cells (OSCs) with enhanced performance from rice straw of agroforestry residues is demonstrated. A highly efficient inverted OSC is constructed and a power conversion efficiency (PCE) of 12.01% is realized using PBDB‐T:IT‐M as the active layer, which shows over 9.4% improvement in the PCE compared to that of a counterpart device (PCE = 10.98%). The research on organic solar cells (OSCs) has made an immense progress over the last one decade because OSCs possess multiple advantages, such as light‐weight, efficient, economical and large‐area fabrication.2CO3,N,N‐dimethylamino)propyl)‐2,7‐fluorene)‐alt‐2,7‐], polyethylenimine, and polyethylenimine ethoxylated (PEIE)) were found to be effective interface modifiers with matched performance of these devices, compared to the devices using conventional interlayer materials (Ca/Mg).To develop effective cathode interfacial materials, interface barrier should be minimized with improved electron mobility. Generally, interface barrier originates directly from the mismatch of the energy levels between the active layer and electrodes. Therefore, the key is to design suitable interfacial materials which can significantly reduce the interface barrier between the electrodes and active layer. In the past decades, numerous attempts have been made and significant progresses have been achieved for the cathode interface modification of OSCs. For example, few metallic salts, including LiF, CsF, and CsCellulose and its derivatives are one of the promising natural materials due to their abundant, biorenewable, biodegradable and environmentally friendly characteristics.alt‐benzodithiophene‐4,8‐dione)] (PBDB‐T) and 3,9‐bis‐6/7‐methyl)‐indanone))‐5,5,11,11‐tetrakis(4‐hexylphenyl)‐dithieno‐s‐indacenodithiophene (IT‐M) is employed as the photoactive layer  for the transfer and collection of electrons. A blend of poly dithiophene))‐−8 Pa. Ultraviolet photoelectron spectroscopy (UPS) was employed with He I (hv = 21. 22 eV), sample was added with −5 V bias. Before the measurement, the sample was cleaned by Ar ion sputter. As shown in FigureJSC).In order to tune the energy barrier between indium‐tin oxide (ITO) and active layer materials, double layer structure of ZnO and CMC was introduced. The experimental measurement of WF was carried out in an electron spectroscopy for chemical analysis (ESCA) system of an X‐ray photoelectron spectrometer with the vacuum value of 5 × 10 I hv = . 22 eV, FigureJSC as well as the device efficiency.The morphologies of ITO/ZnO and ITO/ZnO/CMC films were investigated by atomic force microscopy (AFM), as shown in x/Ag by using ZnO and CMC as interface layers. In contrast approaches, devices with pristine ZnO were also prepared. The current density–voltage (J–V) and external quantum efficiency (EQE) curves are shown in FigureTableJSC of 16.57 mA cm−2, an open‐circuit voltage (VOC) of 0.935 V, fill factor (FF) of 70.83%, and a PCE of 10.97%, which is in agreement with the reported results.VOC of 0.935 V, JSC of 17.87 mA cm−2, and FF of 71.87%, respectively. Similarly, when the ITO/ZnO/CMC layer was annealed at 150 °C, a high PCE of 11.63% was obtained with the VOC, JSC, and FF of 0.932 eV, 17.48 mA cm−2, and 71.41%, subsequently. Although the ITO/ZnO/CMC device annealed at 150 °C exhibited less PCE (11.63%) compared to the ITO/ZnO/CMC device annealed at 120 °C (12.01%), but still the PCE was significantly higher (5.7%) than that of the control device (10.97%). Among all the devices, the devices with ITO/ZnO/CMC  demonstrated the best performance. For these devices with CMC layer, the JSC was increased significantly, especially for the device with CMC . An enhanced JSC of 17.87 mA cm−2 was observed, which was ≈7.8% higher than that of pristine ZnO‐based devices, resulting an improvement in PCE by 9.4% (12.01% versus 10.98%). The increase in JSC was ascribed to the enhanced light absorption by the active layer. All of the devices by employing CMC as interlayer showed better performance than that of pristine ZnO‐based ones, indicating a strong potential of CMC layer for the interfacial modification of OSCs.The inverted OSCs were fabricated with the configuration of ITO/ZnO/CMC/PBDB‐T:IT‐M/MoOJSC from the integration of the EQE curves is 17.4 mA cm−2 , 16.71 mA cm−2 , and 16.3 mA cm−2 (pristine ZnO), which is a less than ≈5% mismatch than that of the JSC value from the J–V curves. The present mismatch is from the difference of spectrum, measured environment, the size of light spot, and flatness of the sample. Generally, the J–V curves are tested under a simulated sunlight with full solar spectrum, while their EQEs are measured from a single wavelength light from 300 to 900 nm with an interval of 10 nm. On the other hand, the measured environment was different for EQE and J–V characteristics. The EQEs were measured in air without encapsulation, while J–V curves were obtained in the inner box. The water and oxygen in air would lead to the decreased EQE. The high EQE in the devices with CMC layer  was from the increased absorption provided by the promoted transmission haze of the CMC layer. Dark J–V characteristic was also tested which provided some important information for the changes of these interface layers. As it can be seen in Figure FigureJSC, whereas VOC and FF remain almost the same.The EQE curves of these OSCs with/without CMC layer are presented in Figure RCT) is related to the active layer/electrode interfaces and the active layers, the corresponding series resistance (RS) contains the sheet resistance (Rsheet) of the electrodes.RCT values of these devices with the active layer of PBDB‐T:IT‐M with or without CMC layer at different annealing temperature are 37.79 , 41.88 , and 52.44 (ITO/ZnO) Ω cm2, respectively. Among all devices, RCT value of CMC‐based device annealing at 120 °C is lowest, indicating the improved the electron transfer and collection in these OSCs. In comparison, the device with pristine ZnO layer exhibited a slight larger RCT value than that of the others. This reveals that CMC layer has played a decisive role to improve the charge transfer and collection, which is in line with the reduced properties of the dark J–V characteristics.The effects of ITO/ZnO, ITO/ZnO/CMC annealing at 120 °C, and ITO/ZnO/CMC annealing at 150 °C were investigated to elucidate the charge transfer and collection mechanism. As shown in the inserted image of Figure J–V curves , which is inconsistent with the results from the electron‐only devices of ZnO/CMC/PBDB‐T:IT‐M and ZnO/PBDB‐T:IT‐M . The current densities and PCEs were enhanced in these devices with CMC modified layer. The improved current densities and PCEs are attributed to the decreased work function, increased absorption, and interfacial contact by using CMC and ZnO as co‐interface. Our findings will provide a new way to develop new interlayer materials from agroforestry residues with improved efficiency for green organic electronic devices.In conclusion, a facile and effective approach was developed to prepare cellulose and its derivatives as interfacial materials for efficient OSCs from rice straw agroforestry residues. By using these CMCs as interfacial modifiers at different annealing temperature, the enhanced PCEs and current densities in inverted OSCs were observed. The highest PCE of 12.01% for inverted OSC based on PBDB‐T:IT‐M as the active layer was obtained with a The authors declare no conflict of interest.Supporting InformationClick here for additional data file.


Atrial fibrillation (AF) is the most common arrhythmia in patients undergoing percutaneous coronary intervention (PCI).Large administrative data may provide further insight into temporal trends in the prevalence and burden of AF in patients who underwent PCI.Using the National Inpatient Sample database in the U.S., AF patients ≥18 years who underwent PCI between 2005 and 2014 and were identified by the International Classification of Diseases, ninth revision, Clinical Modification, were examined. In‐hospital mortality, morbidity, resource use, and medical costs were evaluated in crude and propensity‐matched analyses.P < .001); there was also a greater proportion of comorbidities. There was a marked increase in AF prevalence among those aged ≥65 years and those undergoing elective PCIs. AF was independently associated with higher in‐hospital mortality and higher rates of transient ischaemic attack/stroke, bleeding complications, and non‐home discharge. Excessive in‐hospital mortality, stroke rate, gastrointestinal bleeding, blood transfusion, length of stay, and costs among AF hospitalizations were consistently observed throughout the study period.Among an estimated 6 272 232 hospitalizations, of patients undergoing PCI, AF prevalence was 9.9% and steadily increased from 8.6% to 12.0% between 2005 and 2014 (AF becomes more prevalent in patients undergoing PCI, possibly due to a higher comorbidity, particularly in elderly patients with non‐acute indications. Less favorable trends in mortality, bleeding, and stroke among AF patients who underwent PCI were consistent over time. Continuous efforts are needed to improve outcomes and manage strategies for AF patients undergoing PCI. AFatrial fibrillationICD‐9‐CMinternational classification of diseases, ninth edition, clinical modificationSTEMIST‐segment elevation myocardial infarctionNSTEMInon‐ST‐segment elevation myocardial infarctionNISnational inpatient SamplePCIpercutaneous coronary interventionTIAtransient ischemic attack1Atrial fibrillation (AF) is the most common type of arrhythmia. The prevalence of AF in the general population of the US is 1% among all adults and 9% for those older than 80 years.Until recently, considerable efforts have been made to determine the optimal antithrombotic therapeutic approach for simultaneously preventing thromboembolic events and bleeding complications.The aims of this study were to describe (a) changing trends in the prevalence of AF among patients who underwent PCI, (b) patient/hospital characteristics and clinical risk profiles of these patients, and (c) temporal trends and outcomes of in‐hospital mortality, in‐hospital morbidity, medical costs, and resource use among propensity‐matched cohorts of AF and non‐AF patients who underwent PCI.22.1We used the National Inpatient Sample (NIS) database derived from administrative data between 2005 and 2014 for this retrospective, observational study. The NIS is the largest publicly available, all‐payer administrative database in the US and contains information regarding patient discharge from around 4500 hospitals in ~45 states.2.2We used international classification of diseases, ninth edition, clinical modification (ICD‐9‐CM) procedure codes  to identify all hospitalizations of ages ≥18 years who underwent PCI . The validation and use of the ICD‐9‐CM codes for identifying PCI numbers in the US has been described in previous studies.2.3To reduce any bias associated with patient/hospital characteristics among AF and non‐AF hospitalizations, we performed 1:1 the nearest‐neighbor matching with a caliper of 0.15 using the MatchIt R package (v3.0.2).2.4The primary outcomes analyzed were (a) in‐hospital mortality; (b) in‐hospital morbidity ; (c) length‐of‐stay; (d) non‐home discharge; and (e) in‐hospital cost. These outcomes were compared between crude and propensity‐matched cohorts, both with and without AF.2.5In‐hospital outcome and trend analyses were performed in unweighted and weighted data, respectively, which are a standard methodology used in other studies using NIS data.t test, Mann‐Whitney U‐test, and chi‐square test for normally distributed continuous variables, non‐normally distributed continuous variables, and categorical variables, respectively. In‐hospital outcomes for propensity‐matched cohorts were assessed by multivariate logistic regression analysis using variables included for propensity matching. To detect the significant timing of the changing slope in AF prevalence during the study period, we used Davies test (k = 10) by segmented R package (v0.5.3.0).P values <.05 were considered statistically significant, and all statistical analyses were two‐sided and performed using R software . The R package survey (version 3.33) was used to analyze the weighted database.For trend analysis, the Mann‐Kendall test was performed for proportions and continuous data during the study period. Categorical variables are presented as percentages. Continuous variables are presented as mean ± SD or median (interquartile range) according to the normality of distribution. The Shapiro‐Wilk test was used to examine the normality of distribution. Patient/hospital characteristics and in‐hospital outcomes were compared using the Student's 3P < .001). Moreover, AF prevalence of all groups stratified by age, sex, and indication for PCI increased over time , except for those with ST‐segment elevation myocardial infarction (STEMI) (P = .28). By stratifying for age, AF prevalence among hospitalizations ≥65 years old markedly increased from 13.2% to 18.4% (39% increase), whereas this prevalence increased from 3.7% to 5.6% (51% increase) among those <65 years old during the study period. AF prevalence stratified by indications among STEMI hospitalizations remained very consistent, having only rose from 9.1% to 9.8% (7.7% increase), whereas the prevalence in NSTEMI hospitalizations increased from 8.6% to 11.7% (36.0% increase). A prominent increase in AF prevalence was observed in hospitalizations who underwent elective PCI . Figure P < .001, P < .001, and P = .004, respectively).Hospitalizations data from 6 272 232 weighted in‐patient PCI cases were included. Of these hospitalizations, 619 956 (9.9%) had AF and 5 652 276 (90.1%) did not have AF. A total of 33.7% of hospitalizations were women, and the median age of all hospitalizations was 65 years (56‐74 years). The prevalence of AF among hospitalizations who underwent PCI significantly increased from 8.6% in 2005 to 12.0% in 2014 (40.0% increase) . The rate of drug‐eluting stent use in AF hospitalizations who underwent PCI did not change during the study duration . During the study period, there was a significant downward trend in vascular complications and an upward trend in non‐home discharge rates in AF hospitalizations . However, there were no significant changes in the trends of length of stay, medical costs, TIA/stroke, gastrointestinal bleeding, and blood transfusion in AF hospitalizations during the study period. Increased rates of in‐hospital mortality, in‐hospital morbidity, costs, and prolonged length of stay in AF hospitalizations were consistently observed throughout the study period  AF prevalence in patients who underwent PCI steadily increased from 8.6% in 2005 to 12.0% in 2014, with a marked increase among elderly patients and those who underwent elective PCI; (b) in‐hospital mortality and morbidity, such as TIA/stroke, vascular complications, and cardiogenic shock, were independently associated with AF even after adjustment for patient/hospital covariates; (c) the in‐hospital mortality, non‐home discharge, length of stay, and in‐hospital costs were higher in AF patients than in non‐AF patients; (d) the vascular complications in AF patients had decreased during the study period. However, in‐hospital mortality, stroke rate, length of stay, and medical costs in AF patients remained consistent over time, and the rate of non‐home discharge significantly increased. To the best of our knowledge, this study is the largest and the most recent evaluation of trends and outcomes among AF patients who have undergone PCI.In this nationwide study, almost 1 in 10 patients had AF during their hospitalization, and AF prevalence steadily increased by 14.0% over the study period. The reason for the increase in AF among patients who underwent PCI might be that these individuals were more likely to have clinically predisposed AF comorbiditiesWhen stratifying by PCI indications, AF prevalence in STEMI patients remained nearly the same (only increasing from 9.1% to 9.8% between 2005 and 2014). This finding is consistent with a previous multinational study of acute coronary syndrome, which reported a slightly decreased prevalence from 12.9% in 2000 to 11.1% in 2007,Our data identified racial disparities in the prevalence of AF in patients undergoing PCI; a higher prevalence of AF was observed in white than in black and Hispanic patients. Previous studies also reported that AF is less prevalent and left atrial appendage occlusions are performed less frequently in black and Hispanic than in white patients.Our study reported a 1.5% in‐hospital mortality among non‐AF patients, compared to a 3.2% risk among AF patients in the crude cohort. These rates were comparable with a previous study that analyzed a prospective multicenter registry in Michigan, which assessed AF history among patients who underwent PCI and reported in‐hospital mortality of 1.3% and 3.2% (non‐AF vs AF patients).Prior studies have reported that both pre‐existing AF and new‐onset AF are associated with an increased risk of significant in‐hospital mortality as well as cardiovascular/bleeding complications in the setting of PCI and acute coronary syndrome.P = .345), bleeding event , blood transfusion , and vascular complications  in AF patients using propensity‐matched cohorts.In this study, we showed that AF patients were at a higher risk for thrombotic and bleeding complications, such as TIA/stroke, gastrointestinal bleeding, blood transfusion, and vascular complications in the crude cohort, which is consistent with results of prior studies.Higher rates of thrombotic and bleeding complications might be related to the fact that AF itself is associated with an increased risk of thromboembolisms, and AF patients are more likely to take oral anticoagulants plus dual antiplatelet drugs. Previous guidelines during the study period recommended “triple therapy” for AF patients who underwent PCI and those who had a high CHADS2 score.Consistent with the rapid evolution of the antithrombotic strategy for AF and PCI, guidelines and consensus documents incorporating new evidences are frequently updated.4.1Our study has a number of limitations, which are similar to those of other studies using large administrative databases. First, this study has the potential for any bias inherent to retrospective observational studies. Second, there may be substantial coding errors and coding bias derived from the ICD‐9‐CM codes. However, similar approaches for capturing data on the prevalence AF and PCI were used in previous studies.5Using the largest nationally representative cohort of trends in demographics and outcomes for AF patients who underwent PCI, we demonstrated that the overall AF prevalence among patients who underwent PCI continuously increased, particularly in elderly patients and those who underwent elective PCIs. AF patients continued to show high in‐hospital mortality, morbidity, and medical costs over the recent decade. This study highlights the continued need to identify preventive and management strategies to reduce risks and costs associated with AF patients undergoing PCI.The authors declare no potential conflict of interests.Appendix S1. Supporting InformationClick here for additional data file.


Humans can exploit recognition memory as a simple cue for judgment. The utility of recognition depends on the interplay with the environment, particularly on its predictive power  in a domain. It is, therefore, an important question whether people are sensitive to differences in recognition validity between domains. Strategic, intra-individual changes in the reliance on recognition have not been investigated so far. The present study fills this gap by scrutinizing within-person changes in using a frugal strategy, the recognition heuristic (RH), across two task domains that differed in recognition validity. The results showed adaptive changes in the reliance on recognition between domains. However, these changes were neither associated with the individual recognition validities nor with corresponding changes in these validities. These findings support a domain-adaptivity explanation, suggesting that people have broader intuitions about the usefulness of recognition across different domains that are nonetheless sufficiently robust for adaptive decision making. The analysis of metacognitive confidence reports mirrored and extended these results. Like RH use, confidence ratings covaried with task domain, but not with individual recognition validities. The changes in confidence suggest that people may have metacognitive access to information about global differences between task domains, but not to individual cue validities.The online version of this article (10.1007/s00426-017-0962-7) contains supplementary material, which is available to authorized users. Organisms have to make predictions and inferences in an inherently uncertain world. An influential perspective on judgment and decision making suggests that humans achieve this by relying on available cues (pieces of information) that are only probabilistically related to some criterion in the environment —that explains people’s strategic inferences when two items must be ordered along a quantitative criterion . According to the RH, if one item is recognized  and the other is not , then the recognized item is inferred to have the higher value on the criterion dimension . The RH has been extensively investigated  provides a particularly simple cue for inference that is retrieved rapidly and with little effort , which measures the strength of covariation between recognition memory and the criterion dimension.As any other rule of thumb, the RH is not a bad or good strategy per se: its success depends on the interplay with the environment, that is, the fit to the problem at hand , but not their distance to a geographical reference point, the city Interlaken (α = 0.51). Correspondingly, participants relied more on recognitionα = 0.87) than of their height above sea level (α = 0.53). Data from Pachur, Mata, and Schooler (2009) also indicated that people’s reliance on recognition was substantially higher (0.80 vs. 0.30) in a domain with high-recognition validity  than in a domain with low-recognition validity . These findings suggest that the group averages of RH use closely match the mean recognition validity in a given domain and that recognition validity is a central factor explaining how frequently the RH is applied. However, it is still an open question whether and how single individuals adaptively adjust their reliance on recognition. In the literature, two different interpretations have been discussed how adaptive RH use may come about.In a review on the RH, Gigerenzer and Goldstein  exploredon: Pohl  found thmatching hypothesis; see also Pachur & Hertwig, environment adaptivity hypothesis); in this case, adaptive changes in strategy use may result from having fuzzier intuitions about the usefulness of a cue in a given domain rather than considering (or even computing) individual cue validities. Even though these intuitions may not be perfect, they could nonetheless foster adaptive decision-making and robustly capture rank differences in cue validities across tasks , experiments in various fields of psychology have shown that effects of independent variables are often different in within- and between-subjects designs  implies dynamic within-person changes in behavior. Crucially however, the aforementioned hypotheses about adaptive RH use have never been tested In this study, we addressed these issues and set out to investigate adaptive use of the RH within the same decision-makers across two task domains that strongly differed in their recognition validity, using a modeling approach that provides estimates of individual parameters as well as their correlations. In addition, we aimed to gain further insight into people’s adaptive RH use by considering their metacognitive reports.relative change in confidence as a function of task environment and the relation with strategy use. We expected that people’s confidence should be influenced by the ecological validity of the most relevant cue in probabilistic inference problems  could, place higher confidence in judgments following recognition . Therefore, if people are sensitive to the individual validity of recognition, as the matching hypothesis suggests, their confidence in decisions that follow the RH should correlate with their individual cue validities. In the absence of such a correlation, however, one could conclude that people have little metacognitive access or intuition about their recognition validities, which would provide further evidence against the matching hypothesis. In contrast, the environment adaptivity hypothesis implies that if people had metacognitive access to the validity of recognition across different domains, then their mean confidence ratings should also differ between these task domains. In the following, we tested these predictions about RH use and associated confidence reports using a within-subjects design.M = 36.6 years; SD = 11.2; range 20–69), recruited through Amazon’s Mechanical Turk service ; in the distance domain, participants indicated which of two cities was located closer to the city of Dubai . We chose these two domains because they are expected to differ strongly in recognition validity  and whether and when they left the browser window or tab during the study .We used the most common stimulus material for investigating the RH, the names of real-word cities. Sixteen city names were selected from a larger pool. As mentioned above, one name (Dubai) served as geographical reference point for the distance domain; the remaining 15 names were used for the comparative judgment task. For each participant, 70 pairs of city names  were randomly selected for the comparative judgment task; for a given participant, this same set of 70 pairs was then used in all experimental domains. Halfway through data collection, we mirrored the screen position of the city names in the pairs .r-model because it effectively disentangles reliance on recognition (as assumed by the RH) from the use of further knowledge (or any other strategy). Specifically, the r-model provides probability estimates for the reliance on recognition (parameter r), for the cue validity of further knowledge, and of recognition. Further details are in “To measure participants’ heuristic reliance on recognition, we used a multinomial processing tree (MPT) modeling approach that makes it possible to evaluate goodness-of-fit and to conduct model comparisons  and the correlations (ρ) among the model parameters. The standard deviations represent the variability between participants and are close to zero when participants are homogeneous and are large in the case of substantial diversity.Estimation of the model parameters relied on a Bayesian approach . We also found no conclusive evidence for an effect on accuracy in a comparison between participants who had left the browser tab at least once and participants who never did so  = − 1.46, p = 0.14, BF10 = 0.55). Finally, we conducted the analyses (that we report in the subsequent “n = 49 out of 99) who had left the browser tab at least once during the 140 trials of the comparative judgment task. Notably, we obtained largely the same results with this reduced dataset after following this strict exclusion criterion. Because exclusion of participants or individual trials did not affect our main conclusions, we included all participants and trials in the subsequent analyses. We nevertheless also report the results of the same analyses following the cautious strategy of excluding participants who left the browser . We then examined the frequencies of these “lost-focus events” for each participant and domain. Notably, participants rarely left the experiment tab. In the recognition task, only 6 out of 99 participants left the browser tab once in 16 trials, and no participant left the browser tab more than once. All six participants who left the browser tab once during the recognition task also did so at least once during the comparative judgment task. Therefore, we focused in our data checks on those participants who left the browser tab during the comparative judgment task. During the 140 trials of the comparative judgment task, 50.5% of participants never left the browser tab, 12% left the browser tab once, 24.2% left the browser tab between 2 and 5 times, 8.1% left the browser tab between 6 and 10 times, and 5.05% left the browser tab more than 10 times. The maximum number of times that a participant left the tab was 17. A single-trial analysis showed that all trials in which a participant left the browser tab resulted in correct comparative judgments. Therefore, we examined whether this had an effect on accuracy in the comparative judgment task. We found no correlation between the number of times a participant left the browser tab and the mean accuracy , in which only one city name was recognized , or in which both city names were unrecognized .M = 52.92% (SD= 10.6%) of the 15 cities used for the comparative judgment task. This resulted in a proportion of M = 51.14% cases (SD = 6.40%), where the RH was applicable . Note that, recognition rate and applicability of the RH was identical between domains because they included the same pairs of city names.On average, participants recognized t(98) = 6.09, p < 0.01, d = 0.61, BF10 = 5.2 × 105. Moreover, the mean recognition validity α was higher for judgments of city populations than of distances, t(98) = 21.80, p < 0.01, d = 2.19, BF10 = 1.1 × 1036; and the accordance rate to the RH was higher for judgments of city populations than of distances, t(98) = 9.85, p < 0.01, d = 0.99, BF10 = 2.45 × 1013. The knowledge validity β was slightly lower for judgments of populations than of distances, t(98) = − 2.40, p < 0.05, d = 0.24. Together, these results suggest that the judgment domains differed as expected with our manipulation. These findings are also largely in line with a previous study that used similar domains , Δr = 0.57, 95% credibility interval: , thereby following a corresponding change in the validity of recognition {Δa = 0.32, }. Importantly, neither the validity of participants’ further knowledge {Δb = − 0.03, } nor the probability of making valid inferences on guessing trials (UU pairs) {Δg = 0.02, } differed credibly between domains.Table r (reliance on the recognition cue). However, does the variability in using the RH reflect individual differences in recognition validity, as the matching hypothesis suggests? An examination of the latent-trait correlations within domains provided little support for this possibility: Neither within the population domain {ρrPOPaPOP = 0.38 } nor in the distance domain {ρrDIST aDIST = − 0.06 }, did we find credible correlations among model parameters r and a . Interestingly, however, RH use was correlated across domains {ρrDISTrPOP = 0.38 }, indicating some stability in people’s strategy preferences above and beyond the adaptive changes in RH use between environments.We also observed individual differences in all model parameters  adaptively changed their reliance on the RH, to varying degrees  with a mixed logistic regression that models the relation of choice confidence and judgment accuracy. In this analysis, the slope parameter provides a measure of metacognitive sensitivity. The difference in slope between conditions as a function of confidence , therefore, quantifies any potential differences in metacognitive sensitivity between domains. Notably, we found no significant interaction between confidence and domain, χ(1) = 0.16, p = 0.68, BF10 = 0.01, suggesting similar metacognitive sensitivity across domains. Based on this finding, we proceeded to compare the reported absolute confidence values between the two domains.We next examined the role of confidence and its relation to adaptive strategy use. To this end, we first investigated potential differences in r = − 0.04, t(97) = − 0.44, p = 0.66, BF10 = 0.21, or in the distance domain, r = − 0.08, t(97) = − 0.83, p = 0.40, BF10 = 0.23. People may have systematic over- or under-confidence tendencies  = − 1.18, p = 0.24, BF10 = 0.12.We compared individual confidence values across domains. To examine the implications of the matching hypothesis, we examined whether participants’ confidence tracked individual cue validities; that is, whether participants with higher α showed higher mean confidence on trials on which they followed the RH. To explore this possibility, we estimated the correlation between α and individual mean confidence on RU + trials Fig. a. There F = 8.521, p < 0.001, η2 = 0.106. That is, the effect of task domain on people’s confidence reports differed across the specific trial types in the comparative judgment task. Follow-up t tests revealed no differences in mean confidence on RR, UU, or RU − trial types between the population and the distance domains: all ts < 1.24, all BFs10 < 0.26. Notably, however, confidence ratings for RU + trials were significantly higher in the population than the distance domain , t(72) = 4.38, p < 0.001, d = 0.51, BF10 = 490. That is, confidence differences between domains emerged mainly on those judgment trials where the recognized object was chosen and the RH was applicable . Moreover, there was a significant main effect of trial type, F = 140.2, p < 0.001, η2 = 0.661. The main effect of domain F = 1.933, p = 0.169, η2 = 0.026 did not reach significance.Finally, we examined mean confidence ratings across domains and trial types to evaluate the impact of task environment. Figure In sum, while participants did not show differences in metacognitive sensitivity between domains, we found differences in their (absolute) confidence ratings between domains, specifically on RU + trials. This suggests that recognition-validity differences between domains were available to metacognitive monitoring, even though differences in valid further knowledge and in criterion knowledge were negligible across these domains.M = 0.38, SD = 0.35) and the distance  domains . The similar levels of criterion knowledge in participants’ rankings suggest that the task difficulty was comparable across domains. However, including the unrecognized cities in the analysis revealed a significant difference in criterion knowledge between the population  and distance  domains . These findings could suggest that for unrecognized city names , features such as their spelling or sound may nonetheless help people to make judgments of criterion values and that such features might be more helpful for judgments of the population than of the distance criterion.We used participants’ responses in the ranking task to estimate their criterion knowledge. For this purpose, we calculated the Spearman’s rank correlation for each domain between each participant’s ranking and the correct ranking of cities  = 16.28, p < 0.001, d = 2.30, BF10 = 2.09 × 1018, and in the reliance on recognition (r model parameter), t(49) = 5.70, p < 0.001, d = 0.81, BF10 = 2.3 × 105.We also repeated our analyses with a restricted sample of χ2(1) = 2.03, p = 0.15, BF10 = 0.05]. Moreover, we found no correlations between α and mean confidence for either the population domain , the distance domain  or the change scores between the two . The 4  × 2 (domain) ANOVA on mean confidence ratings showed no significant interaction F = 1.27, p = 0.29, η2 = 0.04. We nevertheless explored domain differences in follow-up t tests and again found that the confidence differences between domains on RU + trials remained  whereas there were again no significant confidence differences between domains on RR or RU − trial types . Unlike the results with the full dataset, however, the confidence difference between domains in UU trials reached significance .Concerning confidence reports, the linear model again revealed no interaction effect, suggesting that metacognitive sensitivity did not differ between domains [T = 231, p = 0.10, BF10 = 0.16) when we included only the recognized cities. And, again, the same analysis including all cities indicated higher criterion knowledge for the population domain than the distance domain . Taken together, the re-analyses with a restricted sample of participants largely confirmed the main conclusions reported for the whole sample.Finally, there were again no differences in criterion knowledge between domains (asymptotic one-sample permutation test r parameters across the two different domains); importantly, above and beyond this stability, people showed flexible and adaptive behavior and substantially reduced their use of recognition in a situation where this was less useful.In this study, participants made comparative judgments on a criterion dimension in two different task domains: In a population domain, where following recognition cues leads to relatively accurate judgments and in a distance domain, where this is unlikely. We observed that a clear majority of participants adaptively adjusted their reliance on recognition  and utilized recognition less frequently in a domain with lower recognition validity. We extended previous research by showing that this adaptive change occurs within individuals. This finding fills an important gap in the literature and could only be presumed so far on the basis of comparisons across group averages or across studies. Notably, one recent study found that individual differences in heuristic use of recognition are relatively stable across time, choice objects (different samples of city names), domains (success of celebrities vs. success of films), and presentation formats , suggesting that people could have trait-like strategy preferences  when recognition cues are more valid? Based on previous theorizing, we reconsidered two possibilities in our within-subjects design: the matching hypothesis, which suggests that people are sensitive to their individual recognition validities; and the environment adaptivity hypothesis, which instead suggests that participants are only sensitive to more global differences between domains  led to similarly high confidence as when both names were recognized. In other words, not recognizing a name contributed more to people’s confidence in the population than the distance domain. Moreover, in line with the notion that confidence is influenced by the most valid available cue  in the former was higher than the validity of further available knowledge (β = 0.68) in the latter. Overall, these findings are in line with the predictions of an extended environment adaptivity hypothesis and suggest that participants are also sensitive on a metacognitive level in which domain name recognition is more or less helpful.Notably, the mean confidence ratings for judgments on RU + pairs and on r in the present analyses could be alternatively interpreted as the degree of reliance on recognition, relative to other cues or information