Body mass index (BMI), resting energy expenditure (REE) and fasting blood glucose (FBG) are major preoperative assessments of patients’ nutrition and metabolic state. The relations and effects of these indices on esophageal cancer patients’ postoperative short-term and long-term outcomes remain controversial and unclear. We aimed to study the impact of BMI, REE and FBG in esophageal cancer patients undergoing esophagectomy.Three hundred and six esophageal cancer patients who underwent esophagectomy were observed retrospectively. Clinical characteristics, postoperative complications and survival analysis were compared among different BMI, REE and FBG groups.p < 0.001) and low FBG (p = 0.003). No significant difference was found in case of mortality and postoperative complications among different groups. Low BMI , REE  and FBG  were related to poor survival. FBG ≤90 mg/dL was independently associated with poor survival . BMI and REE came to be stronger prognostic factors on lymph node-negative patients and proved to be independent prognostic indicators .There were significant linear relationships between REE, BMI and FBG indices, patients with low BMI tended to have low REE (BMI, REE and FBG are important prognostic factors in patients with esophageal cancer undergoing esophagectomy and preoperative evaluation of these indices help to determine the prognosis in these patients. Esophageal cancer (EC) is the eighth most common cancer and the sixth leading cause of cancer mortality worldwide . EsophagPrevious studies reported that high BMI was associated with increased risk of EAC while low BMI with ESCC . High BMDisorder of energy metabolism is a common phenomenon in cancer patients. The energy metabolic status among different cancers may not be the same. Many researchers assessed the resting energy expenditure on cancer patients and no unanimous conclusions have been drawn. In this study, patients’ preoperative REE was an estimated variable, and calculated by the Mifflin-St. Jeor equation . REE is Epidemiologic evidence suggests that elevated blood glucose is associated with many forms of cancer . HoweverSo the purpose of the study is to investigate the prognostic value using combined assessment of BMI, REE and FBG in esophageal cancer patients.Patients who underwent esophagectomy and lymph node dissections during Sep 1, 2003 to Dec 31, 2008 were observed. Twenty-three patients who had palliative or R1/R2 resections were excluded. Patients who had histology other than SCC or AC  were excluded. Patients who received neoadjuvant therapy were also excluded. Three hundred and six patients with histologic documentation of AC or SCC were included. All patients provided written consent and this retrospective study was approved by the Institutional Review Board of Huashan Hospital, Fudan University.Preoperative staging was performed in all patients by means of barium meal test, fibro-gastroscopy, computed tomography of the chest and abdomen and ultrasound of the neck and retroperitoneal lymph nodes. Some patients also received whole body positron emission tomography (PET)-CT scanning. All patients were assessed for physiological ability to undergo esophagectomy. These evaluations included pulmonary function test, cardiac function test and nutritional assessment.One hundred and eighty-six patients with tumors in middle or lower thoracic esophagus and no evidence of lymph node involvement in the superior mediastinum or neck region received transthoracic esophagectomy via left thoracotomy which also included a two-field lymphadenectomy; 53 patients with tumors in the middle or upper thoracic esophagus and possible lymph node metastasis in the superior mediastinum or neck region received McKeown 3-hole esophagectomy with three-field lymphadenectomy; 67 patients with tumors in the esophagogastric junction received esophagogastrectomy through median laparotomy.TNM staging was performed according to the AJCC 7th edition guidelines. Patients were followed up every 6 months for the first 3 years and then annually. Survival time was measured as the time from the date of surgery to the date of death or the latest follow-up time. Endoscopy, CT, PET-CT and Radionuclide bone scan were performed if recurrent or metastatic disease was suspected.Patients’ weight and height were measured at their first hospitalization. BMI was calculated as weight in kilograms divided by height in meters squared.REE was calculated by Mifflin-St. Jeor equation. The applied technique to calculate BMI is as follows: for males = 10 * weight (kg) + 6.25 * height (cm) - 5 * age (y) + 5; for females = 10 * weight (kg) + 6.25 * height (cm) - 5 * age (y) - 161. Both REE and REE/kg were calculated.The serum FBG concentration of patients was measured in the morning during the first hospitalization by hexokinase method after fasting for 10 h. Serum albumin was measured by means of the bromocresol purple method using automated equipments, and all patients were screened and excluded from acute and chronic liver disease. The complete blood count test  was carried out by an automated haematology analyser within one week prior to surgery. NLR was calculated as the ratio of neutrophils to lymphocytes in peripheral blood. These reagents and equipments were convenience-validated and standardized in our central clinical laboratory.The 6-month preoperative weight loss was also measured and patients were divided into three categories: No/Little (loss of 0 to 5 % body weight), Middle (loss of 5 to 10 % body weight) and Large (loss more than 10 % body weight).−1.kg−1 of enteral nutrition was supplied via a duodenum or jejunum feeding tube from the 2nd or 3rd postoperative day and gradually increased to the full dose of 25–30 kcal.day−1.kg−1. Some patients with low BMI or low serum albumin levels were treated with full dose of enteral nutrition from one week before surgery to the tenth day after surgery.During the first few days after surgery, patients were treated with total parenteral nutrition. An initial dose of 5–10 kcal.dayp < 0.05.All statistical analysis was performed with SPSS 16.0. Spearman rank order correlation coefficient (Spearman’s rho) for nonparametric data was used. Univariate analysis of survival was performed using Kaplan-Meier method and log-rank test to estimate the prognostic value. Multivariate analysis of survival was performed using Cox-regression model to estimate hazard ratios (HRs) with 95 % confidence intervals (CI) and identify independent prognostic factors. The level of significance was set to The clinical characteristics and 5-years survival rate are summarized in Table 2), n = 81 (26.5 %); normal (20–25 kg/m2), n = 186 (60.8 %) and high (>25 kg/m2), n = 39 (12.7 %). The median REE was 1387.5 kcal day−1 for male and 1064.0 kcal day−1 for female where we defined the median REE as the cutoff point and stratified patients into low REE group , n = 154 (50.3 %) and high REE group , n = 152 (49.7 %). The median REE/kg was 21.49 kcal.day−1.kg−1. Compared with 245 (80.1 %) patients with REE/kg < 23.2, 61 (19.9 %) patients with REE/kg ≥23.2 had significant worse survival, so 23.2 kcal.day−1.kg−1 was set as the cutoff point. We divided the patients into two groups according to serum FBG concentration where 108 patients (35.3 %) with low FBG (≤90 mg/dL) and 198 patients (64.7 %) with high FBG (>90 mg/dL).The BMI distribution was as follows: low (<20 kg/mp < 0.001) and advanced T-stage (p = 0.040) were more likely to fall in the low REE class. Smoking patients were more likely to be associated with low BMI class (p = 0.013), low FBG class (p = 0.039) but high REE/kg class (p = 0.001).As shown in Table p < 0.001).It was interesting to explore the relationship between REE and REE/kg. Both high REE and low REE/kg patients were found to have better survival, which was consistent with the spearman correlation analysis that found patients with high REE tended to have lower REE/kg (p < 0.001) and low FBG (p = 0.003). The trend of a linear association between REE and FBG could also be seen (p = 0.011).There were significant linear relations between BMI, REE, and FBG, patients with low BMI tended to have low REE (p = 0.006) and have lower BMI (p < 0.001).There were close relations between REE/kg and weight lost or BMI, patients with high REE/kg have been found to lose more weight (p = 0.025) and low albumin (p < 0.001).Low FBG was more likely to be seen in patients with high REE/kg (p = 0.022), and diabetes was more common in high BMI patients (p = 0.006). All the seven patients with cardiovascular disease belonged to low FBG class (p < 0.001). Observing the short-term outcomes, no significant difference was found in postoperative mortality and major postoperative complications among different BMI, REE, REE/kg and FBG groups.Preoperative comorbidities, mortality and postoperative complications among different groups of BMI, REE, REE/kg and FBG were presented in Table p < 0.001), but not Total lymphocyte counts (p = 0.780) or NLR (p = 0.787), which was positively related to survival. The spearman correlation analysis found higher serum albumin levels were observed in high BMI, REE and FBG but in low REE/kg groups.Univariate analysis of nutrition or inflammation-based prognostic factors found to be serum albumin , REE/kg , REE  or REE/kg  and OS. Age, differentiation, T-stage, N-stage, albumin  and FBG  were independent prognostic factors.Variables significant  in Univariate analysis were included in a multivariate analysis Table , which dX2 = 15.507 p < 0.001 and X2 = 14.717, p < 0.001, respectively), but no statistical significance in subgroup of N1-4 . Multivariate analysis of subgroups revealed BMI  and REE  were independent prognostic factors for N0 patients but not for N1-4 patients.In order to assess the impact of BMI and REE on different tumor stages, we divided patients into subgroups on the basis of N-stage (N0 vs. N1-4). Patients with higher BMI and REE had significantly better OS in subgroup of N0  and N1-4 group . But the multivariate prognostic analysis for subgroups of N0 and N1-4 exhibited that serum albumin as a weaker prognostic value than other potential prognostic factors. It may be explained by the different clinical characteristics of each subgroup which may impact on the prognostic value.Total lymphocyte counts, NLR and serum albumin were recognized as nutrition based or inflammation-based prognostic factors. Among the cancer patients, those with digestive tract malignancies were more likely to suffer from hypoalbuminaemia, which has been attributed to increased catabolism, obstruction of the digestive tract and the systemic inflammatory response . The comAs a particular nonspecific marker of systemic inflammation, an elevated NLR is hypothesized to be associated with poor survival in various solid tumors . But forA few studies focused on the influence of BMI on postoperative outcomes in patients with EC and had shown contradictory results, varying from no differences in postoperative complications and mortality to a higher incidence of individual complications (such as respiratory complications and anastomotic leak) in high BMI patients –7. In ouPrevious studies had revealed contradictory results regarding the association between BMI and long-term outcome in esophageal cancer patients –7, 23–25High blood glucose level makes patients more susceptible to certain postoperative complications such as surgical site infections, sepsis, myocardial ischemia and so on . But no p = 0.010). In addition, there was no significant association of REE with postoperative complications and mortality. To our knowledge, it is the first demonstration of the prognostic value of estimated REE in postoperative patients with EC. Our study also observed a significant linear correlation between BMI and REE (p < 0.001), showing that patients with low BMI tended to have low REE. As the estimated REE largely depends on patients’ weight and height, the worse prognosis for low REE patients may reflect that these patients are under-nourished and are likely to have poor prognosis as a result. In addition, patients with low REE tended to be associated with advanced T-stages, so we concluded that the advanced tumor stages may be another reason to explain the low REE patients’ worse survival.REE is believed to be elevated in several types of tumors, It has been hypothesized that increased energy expenditure may contribute to the development of malnutrition and weight loss . Our stuWe also explore the relationship between REE and REE/kg. We found the effect of REE on patient survival was opposite to that of REE/kg. Low REE as well as high REE/kg was found to be a potential worse prognostic indicator. The existing hypothesis of REE is, the sum of the metabolic activities of internal organs, muscle, bone, and adipose tissue and can reflect patient’s physiques and muscle volumes, but REE/kg may reflect the diffusion, consumption and metabolic rate of muscle. So patients with high REE/kg have been found to lose more weight, have lower BMI and have a worse survival, this finding is consistent with the hypothesis.In this research, low FBG was significantly associated with low BMI, albumin and REE, a potential explanation might be proposed. Individuals with esophageal cancer commonly experience metabolic abnormalities. The abnormal state of insulin (hyperinsulinemia or insulin resistance) is one cause, and it promotes cancer growth and progression through its effects on the insulin and insulin-like growth factor pathways . MeanwhiFollowing are the main limitations in our study. First, this is a retrospective study and the sample size is not large. Second, all-cause mortality is used instead of disease-specific deaths, the latter is difficult to confirm. Third, we only chose R0 patients, so our results may not be suitable for all patients.In conclusion, it is the first article to explore the prognostic significance of BMI, REE and FBG among patients with EC. FBG level ≤90 mg/dL was independently associated with poor survival for all patients. BMI and REE were important prognostic factors and the value was significant on lymph node negative patients. Therefore it is advisable that the combined assessment of BMI, REE and FBG can be used for a better preoperative assessment and prognostic evaluation in esophageal cancer patients.


TDPB) and characterised it in detail by MALDI‐TOF MS, UV/Vis/NIR spectroscopy, time‐dependent DFT, cyclic voltammetry and EPR spectroscopy. TDPB is part of an underdeveloped class of π‐conjugated molecules with great potential for organic electronics, display and sensor applications. It is redox active and reacts with acids to form radical cations. Acid‐doped TDPB shows behaviour similar to discotic liquid crystals, with X‐ray scattering investigations revealing columnar self‐assembled arrays. The combination of unpaired electrons and supramolecular stacking suggests that star‐shaped oligo(aniline)s like TDPB have the potential to form conducting nanowires and organic magnetic materials.We have prepared a simple star‐shaped oligo(aniline) ( We based our initial structures on the isomers and conformations of other oligo(aniline)s determined by X‐ray diffraction,TDPB. In the second step, we used the CAM‐B3LYP functionalWe used a two‐step process to model TDPB, that is, with one, two or three arms oxidised. These results imply that any mixture of these states should have practically indistinguishable UV/Vis/NIR spectra. The spectral similarity of the oxidised forms of TDPB shows the arms have little electronic influence on one another, and act as isolated dianiline species. These observations are consistent with absorption spectra of other π‐conjugated molecules with meta substitution at a benzene ring.DPPD, which shows very similar experimental and simulated UV/Vis/NIR spectra of the reduced and oxidised states .TD‐DFT simulations yielded similar UV/Vis/NIR absorption maxima (in the range 445–450 nm) for all the possible oxidised states of TDPB in THF or ethanol solutions caused a comparable colour change from red to green. When a strong aqueous mineral acid such as HCl, HBr or H2SO4 was used, a precipitate formed within a few seconds, leaving a colourless supernatant after a few minutes . In contrast, protonic doping with organic Brønsted acids (Scheme CSA), bis(2‐ethylhexyl)sulfosuccinic acid (AOT) and bis(2‐ethylhexyl) hydrogenphosphate (BEHP). All three reacted with TDPB in THF to form solutions showing a UV/Vis/NIR absorption band with a maximum at approximately 775 nm. See Figure CSA‐doped species .Oxidised solid samples of PANI and oligo(aniline)s typically form a conducting state  upon addition of Brønsted or Lewis acids. The semiconducting to conducting transition is marked by a colour change from blue to green and accompanied, in PANI, by an increase in DC conductivity values of approximately 10 to 13 orders of magnitude.TDPB is a good match for the observed spectra, with a calculated UV/Vis/NIR maximum of 772 nm, compared to the experimental maxima of approximately 775 nm. Phenyl‐capped dianiline (DPPD) forms a similar species with a similar absorption spectrum in acidic conditions.TDPB, as its simulated UV/Vis/NIR maximum of 923 nm is 150 nm higher than the experimental value. Other possibilities that cannot be ruled out include a triplet dicationic diradical, and doublet and quartet tricationic triradical speciesλmax values of 755, 750 and 751 nm, respectively; see Supporting Information for further details). These results clearly show that TDPB forms species containing unpaired electrons when oxidised samples are exposed to acids.TD‐DFT simulations assisted in identifying the species responsible for the experimentally observed UV/Vis/NIR absorption Figure . The radTDPB was confirmed: after CSA was added, a signal appeared at 3370 G, indicating the formation of an open‐shell, paramagnetic doped species  spectroscopy showed no response for acid‐free oxidised solutions, as expected for a closed‐shell, diamagnetic species s doped with acid surfactants can form supramolecular thermotropic liquid‐crystalline phases,CSA in a m‐cresol solution.CSA or AOT were drop‐cast onto hydrophobized glass slides and investigated by polarized light microscopy (PLM) to reveal any birefringent textures and thus anisotropic organization. When low‐boiling solvents such as THF, ethanol and propan‐1‐ol were used, the solvents evaporated quickly to leave very viscous films that could not be sheared by hand. When using octan‐1‐ol (a higher boiling point solvent used in previous tetra(aniline)‐based studiesTDPB materials. In short, solutions of TDPB in THF were doped with CSA or AOT and the solvent allowed to evaporate. Samples were then prepared according to a previously published method,To determine the exact nature of supramolecular ordering leading to the observed birefringence, we performed two‐dimensional wide‐angle X‐ray scattering (2D WAXS) on extruded filaments of the doped TDPB molecules; 3) two prominent but isotropic reflections are obvious in the patterns for TDPB doped with CSA and AOT. The features in the small‐angle region (A) are attributed to stacks that are formed by the TDPB molecules, while the wide‐angle reflection (B) is attributed to the typical intermolecular π‐stacking distance of 0.36 nm. The scattering patterns are clearly influenced by the nature and steric bulk of the dopant, as reflected by the inter‐stack distance , separated by regions of disordered acid dopants.A number of important features are notable in the 2D patterns: 1) there is very little orientational dependence in the scattering patterns; 2) a relatively intense amorphous halo is observed in both cases, consistent with disordered acid dopant molecules surrounding more ordered aggregates of Further experiments with tailor‐made pro‐mesogenic protonating agents and varying doping ratios are envisaged to gain further insight into this new class of conducting star‐shaped oligo(aniline)s and any liquid‐crystalline phases formed. In addition, a more rigid core is likely to induce stronger interstack ordering, which may lead to the formation of nanowires. Such nanostructures have been extensively developed for triarylaminesTDPB has been determined. TD‐DFT simulation of the UV/Vis/NIR spectra of all the oxidation states and doped forms of TDPB shows that computational chemistry can be used to characterise and distinguish π‐conjugated materials with complex behaviour. The length of the arms and the π‐conjugation pattern at the core of TDPB causes it to form radical cationic species in acidic conditions. The ability to create molecular systems with unpaired electrons is important for applications that rely on electrical conductivity or magnetism. When doped, TDPB shows a tendency to self‐assemble into weakly ordered supramolecular columnar aggregates. In future, through further design and structural modifications of this motif (such as planarization of the core of the star‐shaped oligo(aniline) or by using pro‐mesogenic protonating agents), novel radical‐containing supramolecular nanostructures can be created. This work thus provides opportunities for focused future investigations aimed at further developing the full potential of semiconducting and conducting star‐shaped π‐conjugated molecules, and exploring applications, for example, in sensing and generation of reactive oxygen species.In conclusion, the effect of chemical structure on spectra, spin and supramolecular ordering of the star‐shaped oligo(aniline) derivative N‐Phenyl‐1,4‐phenylenediamine , 1,3,5‐tris(4‐bromophenyl)benzene , bis(dibenzylideneacetone)palladium(0) , XPhos , and sodium tert‐butoxide  were added to a round‐bottom flask under nitrogen. Anhydrous toluene (40 mL) was added and the reaction mixture was heated to 110 °C for 2 days. The reaction mixture was then allowed to cool to room temperature, and the solvent was removed under reduced pressure. The residue was dissolved in a minimal volume of THF (ca. 5 mL), phenylhydrazine  was added and the mixture was stirred under nitrogen at room temperature for 30 min. Hexane was added (ca. 50 mL) until a pale‐brown‐coloured opaque suspension formed. The suspension was allowed to settle for 1 h, and was then filtered. The precipitate was washed by stirring in water for 1 h, then filtered and freeze dried to afford the product  as a light brown powder. 1H NMR : δ=8.08 , 7.91 , 7.66 , 7.64 , 7.18 , 7.08 , 6.98 , 6.73 ppm ; 13C NMR : δ=144.77, 144.58, 141.35, 136.74, 136.05, 130.34, 129.09, 127.69, 121.24, 120.04, 119.58, 118.41, 116.63, 115.17 ppm; IR (neat) 3385, 3025, 1597, 1508, 1494, 1296, 1183, 818, 746, 693, 614 cm−1; HRMS‐MALDI m/z calcd for C60H48N6: 852.3940; found: 852.3942.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


The rodent borne Puumala hantavirus (PUUV) causes haemorrhagic fever with renal syndrome in central and northern Europe. The number of cases has increased and northern Sweden has experienced large outbreaks in 1998 and 2006–2007 which raised questions regarding the level of immunity in the human population.A randomly selected population aged between 25 and 74 years from northern Sweden were invited during 2009 to participate in a WHO project for monitoring of trends and determinants in cardiovascular disease. Health and risk factors were evaluated and sera from 1,600 participants were available for analysis for specific PUUV IgG antibodies using a recombinant PUUV nucleocapsid protein ELISA.p < 0.05). The identified risk factors were smoking (OR = 1.67), living in rural areas (OR = 1.92), and owning farmland or forest (OR = 2.44). No associations were found between previous PUUV exposure and chronic lung disease, diabetes, hypertension, renal dysfunction, stroke or myocardial infarction.The overall seroprevalence in the investigated population was 13.4 %, which is a 50 % increase compared to a similar study only two decades previously. The prevalence of PUUV IgG increased with age, and among 65–75 years it was 22 %. More men (15.3 %) than women (11.4 %) were seropositive  contains supplementary material, which is available to authorized users. Bunyaviridae family are globally spread and each human pathogenic hantavirus is carried by different rodents [nephropathia epidemica characterized by abrupt onset of fever, resembling influenza with myalgia, headache, fatigue and varying degrees of renal impairment [Myodes glareolus, and the incidence of PUUV infection is correlated to the size of the bank vole populations [Hantaviruses of the  rodents . The vir rodents . In the  rodents . In Scanpairment . In addipairment . The serpairment . In Swedpairment , 6. Hantpairment . The priulations . Person-ulations . In Euroulations . Known rulations , 10–13. ulations , 11 and ulations –16.Furthermore, several studies indicate possible association to hypertension and renal impairment , 18 althDuring the winter 2006–2007 a very large outbreak of PUUV infection occurred in northern Sweden [The aims of the present study were; to define the current seroprevalence of PUUV infection in northern Sweden; to define risk factors for infection, and link these findings to demographic and health data in a large, randomly selected and stratified population sample. In addition, we investigated potential associations between previous PUUV infection and cardiovascular risk factors and/or chronic diseases.The MONICA project, “Multinational Monitoring of Trends and Determinants in Cardiovascular Disease” was initiated by the World Health Organisation (WHO) in 1982. The purpose was to study levels, trends and risk factors of stroke and coronary disease globally . In nortDuring spring 2009, 2,500 individuals from the counties of Norrbotten and Västerbotten were randomly selected. 250 males and 250 females from each age group 25–34, 25–44, 45–54, 55–64 and 65–74 were invited to participate. After signing a written consent, they received a free health check including measuring of arterial blood pressure, waist − hip ratio and Body Mass Index (BMI). Levels of S − Creatinine were measured.A questionnaire regarding quality of life, previous and present illness, social support, health, work, physical activity, diet and use of tobacco was answered.n = 771), were contacted and asked to complete a basic questionnaire of which 485 answered. They were on average younger , less likely to being married/cohabitant , and less likely to have a university education  than the participants. They more often reported themselves as diabetics , and as smokers . BMI, based on self − reported height and weight, was equivalent to the BMI measured in participants (data not shown). Treatment with hypertensive medication  and lipid − lowering drugs  did not differ significantly between participants and non − participants.Subjects not responding to the study invitation , secondary school (ten to twelve years of school) or university studies (higher education). The participants were asked to describe their main occupation, descriptions later classified according to the “Nordic standard of occupational classification” of 1985 . In ordeSmoking habits were classified as regular smoker, smoking a least one cigarette a day, or non-smokers . Individα × max–1.209 × 0.993Age × 1.018  × 1.159 (if black) (Scr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is −0.329 for females and −0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1.Blood pressure was measured in a standardized manner, mean value of two measurements, taken with Hawksley’s random − zero sphygmomanometer. Hypertension was defined as a mean systolic blood pressure ≥ 140 mmHg or a mean diastolic blood pressure ≥ 90 mmHg or use of hypertensive medication. Questions about asthma, chronic obstructive pulmonary disease, diabetes, stroke and hospitalisation for acute myocardial infarction were answered with yes or no. Renal affection was measured according to the CKD − EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, glomerular filtration rate (GFR) = 141 × minEscherichia coli as previously described [To perform the indirect enzyme − linked immunosorbent assay (ELISA), 96 − well microtiter plates (NUNC Immuno plates) were coated with PUUV nucleocapsid protein (diluted 1/600 in PBS) produced in escribed . The plaFor cut − off calculations, 106 sera from children under the age of 5 years old were analysed as above. From these results the cut off was calculated as mean + 3 standard deviations (SD), corresponding to an OD value of 0.240.Binary logistic regression was used for simple group comparisons. To simultaneously analyse several possible risk factors associated with hantavirus infection , multiple logistic regression was used. Outcome was presented by odds ratios (OR) with corresponding 95 % confidence intervals (CI). The level of statistical significance was set to 0.05. Statistical analyses were carried out using SPSS 18.1.X2-test for categorical variables.Non-responders and responders were compared using t-test for continuous variables and n = 214), and significantly higher in men than in women . There was an increasing seropositivity associated to older age for both sexes. In the age group 65–75 years, the prevalence was 22 %  participated. Of these, blood samples were available for testing in 1600 individuals. The overall prevalence of PUUV IgG antibodies in serum was 13.4 % (p < 0.001). However, this difference was not significant in the multiple regression analyses when adjusted for sex, age, education, smoking, and living area   when compared with non-farm- or forest owners.No relation was found between the presence of PUUV antibodies and hypertension, renal impairment, or self-reported asthma, chronic obstructive pulmonary disease, diabetes, previous acute myocardial infarction or cerebral insult , even after adjusting for age, sex, level of education, and living area. This finding is in accordance with previous case-control studies from Finland and Sweden , 13. It Furthermore, in accordance with previous findings, there was a strong relation between living in rural, forested areas or close to farms and being at risk of hantavirus infection , 13. RisThere was a non-significant higher seroprevalence of those in agricultural work and industrial occupations potentially due to more rodent contact. PUUV infection is more often diagnosed in males and is suggested to reflect increased exposure in male’s recreational and occupational activities . Men areAlthough PUUV has been detected in human saliva, implicating a possible risk for person-to-person transmission , no incrPUUV infection is correlated to an increased risk for cardiovascular complications i.e., stroke and myocardial infarction . MoreoveA study from Finland, showed higher glomerular filtration rate (GFR) and higher systolic blood pressure in patients who had been diagnosed with PUUV infection 3–7 years earlier, compared to a healthy, seronegative control group . HoweverFor detection of PUUV IgG by ELISA we used the full-length nucleocapsid protein, while a previous study used a truncated nucleocapsid protein . An ELISWe have investigated the seroprevalence of Puumala hantavirus that causes haemorrhagic fever with renal syndrome in northern Sweden using a large, randomized and population based cohort.PUUV antibody presence in serum samples from 1,600 participants was analysed and 13 % were found to be positive. This is substantially higher than previous studies in the same area and might be explained by several PUUV outbreaks in the region, including the large outbreak in 2007. In the older population (65–75 years) as many as one in five individuals have had a PUUV infection and was more common in men than in women.Smoking, living in rural areas, and owning farmland or forest was identified as risk factors for contracting a PUUV infection. Increased awareness in risk areas, appropriate protection from rodent secreta, and possibly a future vaccine would be of value for the identified high-risk groups.


Bemisia tabaci (Gennadius) is an important agricultural insect pest worldwide. The B and Q biotypes are the two most predominant and devastating biotypes prevalent across China. However, there are few studies regarding the occurrence of the Q biotype in Fujian Province, China, where high insecticide resistance has been reported in the B biotype. Differences in some biological characteristics between the B and Q biotypes, especially insecticide resistance, are considered to affect the outcome of their competition. Extensive surveys in Fujian revealed that the B biotype was predominant during 2005–2014, whereas the Q biotype was first detected in some locations in 2013 and widely detected throughout the province in 2014. Resistance to neonicotinoids (that have been used for more than 10 years) exhibited fluctuations in open fields, but showed a continual increasing trend in protected areas. Resistance to lambda-cyhalothrin, chlorpyrifos, and abamectin exhibited a declining trend. Resistance to novel insecticides, such as nitenpyram, pymetrozine, sulfoxaflor, and cyantraniliprole, in 2014 was generally below a moderate level. A decline in insecticide resistance in the B biotype and the rapid buildup of protected crops under global temperature increase may have promoted the establishment of the Q biotype in Fujian.The whitefly  Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) has been one of the most devastating and economically important agricultural insect pests worldwide in recent decadesThe whitefly Bemisia tabaci has long been considered a complex species and the term “biotype” has been used to designate whitefly populations134567891011121315B. tabaci was first recorded in 1949, but did not cause significant damage until the mid-1990sB. tabaci caused nationwide concern, when the notorious invasive biotype B largely supplanted the indigenous whitefly species and plagued many provinces where it caused serious yield losses in many crops20et al.In China, B. tabaci that are available.Whitefly control depends heavily on insecticides because of their easy application, quick action, and high efficacy. However, repeated spray applications result in the overuse of insecticides and induce various issues e.g. environmental pollution and impact on non-target organisms23252615172227B. tabaci in Fujian since 2005, and some findings of two experiments conducted in 2005 and 2009 were released by He et al.et al.We have monitored the biotype and insecticide resistance status of B. tabaci collected from various areas of Fujian from 2005 to 2014 are shown in Distribution and dynamics of B. tabaci were monitored in 2005, 2009, and 2014 , was found to displace the Q biotype in six generations when exposed to a low dose of neonicotinoid insecticideet al.30et al.515A stronger resistance to insecticide is often regarded as a major cause for the establishment and the dominance of the Q biotype38540B. tabaci in open fields sharply increased in early 2000s and maintained a high level until approximately 2010, and then gradually declined to a low level in Fujian. The population decline lowered the demand for insecticide application in recent years, which resulted in a drop in resistance in overall  and protected areas (103.77–118.41 mg A.I. L−1) relative to the recommended field concentration of 66.66 mg A.I. L−1 indicated a potentially high risk in using cyantraniliprole to control B. tabaci. Xie et al.B. tabaci, although it was highly effective against eggs and larvae.Cyantraniliprole and sulfoxaflor were temporally registered in China in 2012 and 2013, respectively, and their commercial products were available on the market in 2013. Although cyantraniliprole, being an anthranilic diamide insecticide, acts exclusively on the ryanodine receptor in insects, it was thought to be highly efficacious against B. tabaci and Trialeurodes vaporariorum55−1, a considerably low LC50 value (0.64–12.61 mg A.I. L−1) along with slope values less than 1.5 were found in the four populations, suggesting that sulfoxaflor may be an important new tool for whitefly control.Sulfoxaflor targets insect nicotinic acetylcholine receptors (nAChRs) and functions discriminately with other insecticides acting at nAChRs, like neonicotinoidsThe Q biotype was first detected in some areas in 2013, followed by frequent detection throughout Fujian Province in 2014. However, the whitefly population was predominated by the B biotype during 2005–2014, although the Q biotype appeared to be increased in proportion not only in open fields but also in protected areas. The abundant B biotype, with high levels of resistance, may prevent the colonization of the Q biotype even in cropping systems where insecticides were overused, although the Q biotype was thought to be more resistant. The establishment of the Q biotype, however, might have been facilitated by the decline in the abundance of the B biotype which resulted in a drop in insecticide resistance, as well as a warming environment, that is, the rapid buildup of protected agriculture in the context of global temperature rise.B. tabaci, regardless of biotype. Four novel insecticides, nitenpyram, pymetrozine, and sulfoxaflor, are suitable for controlling both biotypes of B. tabaci in open fields and protected agricultures, although cyantraniliprole should be used prudently. Judicious rotation of conventional and novel insecticides should be adopted in whitefly resistance management.Resistance to neonicotinoids used for more than 10 years exhibited fluctuations in open fields, but a continual increase in protected areas. Conversely, a continuous decline was observed for conventional insecticides, such as pyrethroids and organophosphates. Resistance variance reflects the change in intensity of insecticide utilization. Application reduction, therefore, contributes to some extent to the decline in resistance, which indicates the importance of rational rotation in insecticide resistance management. No resistance was found to abamectin during 2005–2014 demonstrating that it is a powerful insecticide against 2 and then transferred into plastic ventilated petri dishes (Φ = 3.5 cm) where cotton leaves, placed with their adaxial surface downwards onto the agar, were provided for whitefly population maintenance. For those used for biotype determination, samples were either anesthetized by CO2, stored in 95% ethanol, and taken back to the laboratory where they were frozen at −20 °C or host plant leaves, along with whiteflies, were placed in plastic bags, and then taken back to the laboratory and frozen at −20 °C.Samples in open field and protect area populations of whiteflies were collected from various crops, but primarily from vegetables in intensive agricultural regions throughout Fujian Province, China in 2005, 2009, 2011, 2013, and 2014 . Adult wet al.et al.et al.−1 BSA, 0.25 mM of dNTPs, 2.5 mM MgCl2, 75 ng C1-J-2195, 75 ng L2-N-3014, and 4 μL of DNA. Amplification was conducted in an Eppendorf thermocycler using the following parameters: 94 °C for 5 min, followed by 35 cycles at 94 °C for 1 min, 50 °C for 1 min, 72 °C for 1 min, and a final extension at 72 °C for 5 min. PCR products were electrophoresed in 1.2% agarose gel and purified by Promega DNA gel extraction kit and sequenced directly in two strands by Invitrogen . Biotype was determined for 24 individual adults for each population.For whitefly samples collected in 2005 and 2009, direct sequencing of the mitochondrial cytochrome oxidase I (mtCOI) gene was used to identify the biotype of whitefly individuals. The methodology followed He et al.Bemisia tabaci biotypes were easily identified based on the criterion of 478 bp for the B biotype and 303 bp for the Q biotypeThe biotype of whiteflies collected in 2011, 2013, and 2014 was determined individually through the amplification of the mtCOI gene by PCR with the specific primers described in Shatters The commercial formulated insecticides used for leaf-dip bioassays were: imidacloprid ; thiamethoxam ; nitenpyram ; chlorpyrifos ; lambda-cyhalothrin ; pymetrozine ; abamectin ; spirotetramat ; cyantraniliprole ; and sulfoxaflor .1 generation adults were used for bioassays. Leaf dip bioassays with B. tabaci adults followed the methodology of He et al.B. tabaci female adults were briefly anesthetized with CO2 and gently transferred onto the leaf discs. Each petri dish was then covered with a perforated lid and placed inverted in a growth chamber at 25 ± 1 °C, 65 ± 5% RH, and 14:10 h (L:D) photoperiod. Each insecticide treatment was repeated three times and mortality was recorded after 48 h, with the exception of pymetrozine, which was examined after 96 h.Samples collected from fields were reared on cotton plants in the laboratory at 25–28 °C, 65 ± 5% RH, and 14:10 h (L:D) photoperiod, and the F50 values were determined by the absence of the overlap of the 95% confidence limits. Resistance factors (RFs) were obtained by dividing LC50 values by the corresponding values of the susceptible population (Lab-S) reared in laboratory without exposure to any insecticides since 2008. Based on Ahmad and ArifData were corrected for control mortality using Abbott’s formulaMaps were created by using the R statistical program version 2.15.2How to cite this article: Yao, F.-L. et al. Dynamics of Bemisia tabaci biotypes and insecticide resistance in Fujian province in China during 2005–2014. Sci. Rep.7, 40803; doi: 10.1038/srep40803 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


DAPT, autophagy was greatly diminished, and differentiation was also impaired. Further, to better understand the relationship between Notch signalling and autophagy in podocyte differentiation, rapamycin was added to enhance autophagy levels in DAPT‐treated cells, and as a result, nephrin was recovered and DAPT‐induced injury was ameliorated. Therefore, we put forward that autophagy is involved in kidney development and podocyte differentiation regulated by Notch signalling.Podocyte dysfunction results in glomerular diseases accounted for 90% of end‐stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation. Intriguingly, when Notch signalling was down‐regulated by  The morphological development of kidney is from comma to S‐shaped bodies and finally to nephrons that consist of glomerulus, proximal tubule and distal tubule It is generally known that the function of Notch signalling pathway is to determine cellular differentiation and organ development. There are four Notch receptors in mammals Notch 1/2/3/4), and they interact with transmembrane ligands of the Delta  and Jagged  families. Each of them displays a specific cell and tissue type during development /3/4, andAutophagy pathway is the efficient intracellular protein degradation system, and it is essential for maintaining cellular homeostasis N‐[N‐]‐S‐phenylglycine t‐butyl ester (DAPT) was purchased from Sigma‐Aldrich  (D5942‐5MG). Foetal bovine serum (FBS) and 3‐‐2, 5‐diphenyltetrazolium bromide (MTT) were bought from Sigma Chemical Co., . As for antibodies, anti‐LC3 antibody (M186‐3) was obtained from MBL  and anti‐β‐actin antibody from Santa Cruz Biotechnology, Inc. . Anti‐Beclin‐1 antibody (D40C5) was purchased from Cell Signaling Technology . Anti‐Hes‐1 (ab71559), anti‐Notch1 (ab52627), anti‐NICD (ab52301) and anti‐nephrin (ab58968) antibody were bought from Abcam . What needs to be noted is that anti‐Notch1 (ab52627) recognizes both the Notch 1 receptor at the membrane and the proteolytic processing NICD, while the anti‐NICD (ab52301) only recognizes NICD according to Abcam Technology's instructions. The Alexa 594‐conjugated goat antimouse IgG secondary antibody (CA11008S) and 594‐conjugated goat anti‐rabbit IgG secondary antibody (CA11012S) were obtained from Invitrogen . The 647‐conjugated goat anti‐rabbit IgG secondary antibody (A21235) was purchased from Life Technologies . The DAPI (C0060) was brought from Solarbio Life Science . The chemiluminescent HRP substrate was purchased from Millipore Corporation . All the above antibodies were made in the USA.All animal procedures were accorded to protocols approved by the Animal Care Committee of the Animal Center at the Chinese Academy of Sciences in Shanghai. C57/BL6 mice  were provided by the Experimental Animal Center of the Chinese Academy Medical Sciences. Mice were maintained under standard laboratory conditions under artificial 12‐hrs light/12‐hrs dark cycle, and two female mice were paired with one male (2:1) for a period of 5–6 days until mating in vivoThe conditionally immortalized mouse podocyte clone 5 (MPC5) cells, established by Mundel When shifted to 37°C, podocytes were randomly divided into two groups during the differentiation: the control group and the DAPT‐treated group. These two groups were continued to be divided into three subgroups: undifferentiated podocytes (recorded as differentiating Day 1), differentiating cells (cultured in 37°C for 7 days and recorded as differentiating Day 7) and differentiated ones (cultured in 37°C for 14 days and recorded as differentiating Day 14). DAPT was used to down‐regulate all Notch signalling with the onset of podocyte differentiation (0.5 μM), and lasted for 1, 7 and 14 days, respectively. After differentiation, podocytes were confirmed by the identification of nephrin, a podocyte differentiation marker Western blot assay of renal cortex and podocytes was performed as previously described, and procedures were as follows. They were lysed in lysis buffer . Proteins were extracted for the analysis, and an equal amount of protein loading was separated by SDS‐PAGE on 10% gels, after that transferred to a nitrocellulose membrane. Non‐specific binding sites were blocked by 5% no‐fat milk powder in phosphate‐buffered saline (PBS) with 0.05% Tween‐20 for 2 hrs at room temperature. The membranes were incubated in anti‐LC3, anti‐Hes‐1, anti‐β‐actin, anti‐nephrin, anti‐Notch1, anti‐Beclin‐1 and anti‐NICD antibodies, respectively. After 12 hrs of incubation at 4°C, the membranes were washed in TBST for 10 min. ×4, followed by incubation with anti‐rabbit IgG (H+L), HRP conjugate  or antimouse IgG (H+L) HRP conjugate  for 1 hrs at room temperature. All experiments were performed at least three times. For analysis, quantitative analyses were achieved by scanning and determining the intensity of the hybridization signals. IMAGEJ software was used to evaluate the differences between the sample of interest and the β‐actin antibodies, respectively.Immunofluorescence analyses were performed as previously described Dilution of primary antibodies:Notch1 : 1:500;LC3 : 1:500P62 (ab56416): 1:500The secondary antibodies:The Alexa 488‐conjugated goat antimouse IgG secondary antibody  and 647‐conjugated goat anti‐rabbit IgG secondary antibody  as well as the Alexa 594‐conjugated goat antimouse IgG secondary antibody (CA11008S) were used at 1:1000.Imaging was conducted with a confocal microscope , and the fluorescent intensity was quantified using IMAGEJ software .The three various differentiating stages of MPC5 cells were treated with DAPT (0.5 μM) along with the differentiation for 1 day, 7 days and 14 days, respectively, which were named as differentiating Day 1, Day 7 and Day 14. After fixation in 4% paraformaldehyde for half an hour, cells were washed with PBS 5 min. ×3 and permeabilized with 0.5% Triton X‐100 and then they were blocked with 10% NGS for 2 hrs at room temperature. Following that, podocytes were incubated with anti‐LC3, anti‐NICD and anti‐nephrin antibodies and thereafter, washed with PBS, and MPC5 cells were incubated with the Alexa 594‐conjugated goat antimouse IgG secondary antibody (1:1000) and 647‐conjugated goat anti‐rabbit IgG secondary antibody (1:1000). Subsequently, the podocyte nuclei were stained by DAPI. Samples were examined under a fluorescence microscope , and the fluorescent intensity was quantified as previously reported anova followed by the LSD post hoc test, and statistical significance was defined as P < 0.05. All experiments were performed at least in triplicate.Sample size was in accordance with previous studies for animal experiments In our experiment, nephrin expression was detected in different developmental stages to identify the degree of renal development as well as podocyte maturation. The birth date of mice was recorded as post‐natal Day 0 (P0), and kidneys of P1, P5, P7, P14, P28 and P49 (mature mice) were collected and renal cortex was separated, where the podocytes were localized. It was observed that nephrin increased all the way through the renal development, from P1 to adulthood  in kidneys of P1, P5, P7, P14, P28 and P49. The Notch1 bands are shown in Figure in vitro experiments were as follows.Double immunofluorescence staining analysis was conducted with LC3 and Notch1 Fig. , which pTo identify how Notch pathway directly affects podocyte maturation, the MPC5 cells were cultured and three differentiated stages were studied: podocytes of undifferentiated, differentiating and differentiated were recorded as differentiating days 1, 7 and 14, respectively. As γ‐secretase cleavage of Notch generates NICD, which was the NICD, NICD represented for Notch activation. Therefore, NICD and Hes‐1, the typical downstream protein of Notch1 signalling, were detected within podocyte differentiation.It was showed that both NICD and Hes‐1 accumulated mostly in differentiating podocytes Fig. C and D, To figure out the underlying mechanism by which Notch pathway influenced podocytes, Notch pathway was down‐regulated using DAPT during the entire differentiation process (0.5 μM). DAPT was a γ‐secretase inhibitor, which could block all Notch signalling In the control group, little Beclin‐1 expression can be recognized in undifferentiated MPC5 cells  during the maturation of podocytes.In support of this notion, double staining with anti‐NICD and anti‐LC3 antibodies was performed Fig. . It was To further study the outcome of DAPT‐induced autophagic reduction, the podocyte‐specific protein nephrin was detected. As seen in control cells, nephrin expression was enhanced as podocytes differentiated, and reached a plateau on Day 14, marking the maturation Fig. B. NevertImmunocytofluorescence assay was also performed and nephrin was stained Fig. C and D. In the section above, we speculated that Notch inhibition in podocytes decreased autophagy levels and diminished differentiation marker nephrin. Further, we enhanced the autophagy level by rapamycin, which is a mTORC1 inhibitor and inducer of autophagy The MPC5 cells were incubated in the medium without DAPT, containing DAPT (0.5 μM), DAPT (0.5 μM) + rapamycin (10 ng/ml) and rapamycin (10 ng/ml) and differentiated for 7 days (as differentiating cells). In DAPT‐treated cells, autophagy status that reflected by Beclin‐1, LC3II/I ratio and P62 was augmented by rapamycin Fig. D and F.Molecules of Notch signalling were decreased by DAPT Fig. B and C; As to podocyte differentiation marker nephrin, it was diminished when Notch signalling was down‐regulated by DAPT Fig. G, but thNotch signalling is an evolutionarily conserved cell–cell communication When we study the underlying mechanism by which Notch pathway modulates podocyte differentiation during renal development, we found reports illustrating that autophagy was related with Notch signalling pathway To better demonstrate their correlation, MPC5 cells were cultured, and all Notch pathways were down‐regulated by DAPT, the inhibitor of all Notch signalling Autophagy is increasingly recognized for the important role in specific cytosolic rearrangements needed for proliferation and differentiation during embryogenesis and post‐natal development In conclusion, autophagy is not only involved in widely reported disease models ZY conceived and designed the experiments. CYZ, WL and JKW performed the experiments. CYZ and WL analysed the data. CYZ, WL and JKW contributed to reagents/materials/analysis tools. CYZ, WL and ZY wrote and edited the manuscript.The authors have declared that no competing interest exists.


Q, uniform coverage of optical absorption, in addition to uniform photocarrier generation and transport. As the first demonstration of ultra‐broadband absorption with the introduction of spatial corrugation to the ultrathin metal film electrode–cathode Fabry–Perot cavity, future applications of the same concept in other light‐harvesting devices utilizing different materials and structures are expected.The application of nanophotonic structures for organic solar cells (OSCs) is quite popular and successful, and has led to increased optical absorption, better spectral overlap with solar irradiances, and improved charge collection. Significant improvements in the power conversion efficiency (PCE) have also been reported, exceeding 11%. Nonetheless, with the given material properties of OSCs with low optical absorption, narrow spectrum, short transport length of carriers, and nonuniform photocarrier generations resulting from the nanophotonic structure, the PCE of single‐junction OSCs has been stagnant over the past few years, at a barrier of 12%. Here, an ultrathin inverted OSC structure with the highest efficiency of ≈13.0%, while being made from widely used organic materials, is demonstrated. By introducing a smooth spatial corrugation to the vertical plasmonic cavity enclosing the active layer, in‐plane propagation modes and hybridized Fabry–Perot cavity modes inside the corrugated cavity are derived to achieve an ultralow  At the current stage, no report has been presented for single‐junction OSCs providing broadband and uniform optical absorption yet within an ultrathin active layer (≈100 nm), while employing widely used organic materials. In addition, current reports repeatedly show a significant reduction in the fill factors (FF) of nanophotonic structure‐based OSCs thiophen‐2‐yl)benzodithiophene)‐71‐butyric acid methyl ester (PBDTT‐F‐TT:PC71BM). First, working on a simple structure of ultrathin metal film (UTMF)‐electrode OSC by employing the optical–electrical multiphysics analysis, we reveal that it is the spectral engineering, perfecting the absorption band of the active layer, not the  mobility, which defines the present device performances bottleneck of OSC. Then, by introducing a smooth spatial corrugation to the active layer cavity of the UTMF‐electrode OSC, without any penalty to electrical transports, we derive a strong multipeak in‐plane plasmonic propagation modes in addition to the broadening of the Fabry–Perot cavity modes in the UTMF‐electrode OSC: in order to achieve highly uniform (>85%) and ultralow Q (330–775 nm) absorption, which provide near‐perfect spectral overlap to the ultrathin (120 nm) PBDTT‐F‐TT:PC71BM active layer. Equally importantly, based on the drift current distributions from the optical–electrical multiphysics modeling, we also show that the proposed corrugated cavity structure provides excellent electrical scale length, with negligible scattering. Detailed analysis is carried out on the influence of the corrugated cavity to the optical field hybridization, exciton generation rate, charge carrier collection efficiency, and electrical conversion efficiency, in order to provide deeper insight into the origin of full‐visible optical absorption, and thus to enlighten a systematic pathway in the tuning of electrical performance of OSCs.In this paper, we show the feasibility of an organic solar cell of near ≈13% PCE, in inverted configurations of widely used organic materials of polyoxy]benzodithiophene‐2,6‐diyl)(3‐fluoro‐2‐[(2‐ethylhexyl)‐carbonyl]‐thienothiophenediyl)):‐phenyl‐C22.1Figure71BM, while neglecting material absorption, κ = 0) and Figure 71BM‐filled cavity, strong absorption at the large material absorption wavelength (550–700 nm) is obtained at the active layer thickness of 100 nm, concurring with previous experimental reports,First, as a control reference Figure1a, we µe,h, and also at a much larger value of 10 µe,h  and mobility values . First, for an inverted OSC of 100 nm active layer with µe,h (green lines), a PCE of 10.9%, an open‐circuit voltage of 0.815 V, a short‐circuit current of 18.57 mA cm−2, and a fill factor  of 71.7% were obtained, in good agreement with previous experimental reports.Clarified the importance of optical absorption, in terms of material‐absorption‐weighted device resonance engineering, we now investigate the electrical effect of carrier mobility on the power conversion efficiency of OSC. For this purpose, we perform coupled optical–electrical analysis,µe,h to 10 µe,h, improved FF values were obtained at each fixed active layer thickness (71.7–76.2% for 100 nm and 59.3–69.2% for 270 nm), as expected. Nonetheless, since the 100 nm active layer device with µe,h provides better FF  is set to be much larger than that of conventional sub‐wavelength gratingsA/P), in order to retain a small modulation‐induced wave‐vector perturbation, zk. This ensures the local Fabry–Perot resonance condition remains intact, while promoting the hybridization with the multipeak in‐plane propagation modes residing inside the active layer.To derive a uniform coverage of optical absorption overcoming the narrowband cavity mode, we first investigate the spectral response of the reference UTMF‐cavity under different angle of incidence (AOI). 71BM, κ = 0) and Figure P/4 < 2500 nm and 1000 nm < A < 2500 nm (see the Supporting Information).Figure Q (330–775 nm) and highly uniform (>85%) strong optical absorption, stretching from the near UV to the near IR range. Compared to the UTMF‐electrode reference cell, the AM1.5 weight‐averaged figure of merit (see the Supporting Information) in the optical absorption was calculated to have increased by ≈21.5%. It is emphasized that this large enhancement of optical absorption signifying the contribution from the corrugated cavity, directly translates to the huge increase of short‐circuit current  in the ranges of 1000 nm ≤ P/4 ≤ 2500 nm and 1000 nm ≤ A ≤ 2500 nm, and showed a maximum of ≈13.0% at P/4 = 2100 nm and A = 1200 nm. It is worth mentioning that the optimal structure in terms of optical absorption  resulted in slightly lower PCE .To find the optimal  structure of the CC‐UTMF OSC, different sets of FigureJ–V curve . When compared to Figure µe,h), slightly increased currents have been observed. However, since the carrier collection is already very efficient in thin active layers  when compared to the increased optical absorption with the corrugated cavity. The details of the overall performance of the OSCs are summarized in Tablee Figure b and PCE371BM active layer. Ultralow Q (330–775 nm), highly uniform (>85%) coverage of optical absorption is derived from the hybridized Fabry–Perot cavity mode and multipeak in‐plane propagation modes, without any penalty in the electrical carrier transport dynamics. Compared to the flat UTMF OSC, large improvements of ≈21.5% in optical absorption, ≈21.0% in the short‐circuit current, and ≈19.7% in the PCE enhancements are confirmed from optical–electrical multidisciplinary numerical analysis, thereby realizing 13% of PCE for the first time for the OSC, notably with widely used organic materials. Clearly revealing the significance of spectral engineering, driven by the corrugated cavity, we anticipate the application of the same concept to ultrathin OSCs based on other materials, such as PBDB‐T:IT‐M for the realization of even higher PCE. Moreover, it is emphasized that the use of optical–electrical multiphysics analysis should be considered in the proper identification and overcoming strategy of the performance limiting factor , for any type of solar cells.In conclusion, the highest performance of an organic solar cell of ≈13.0% PCE was numerically demonstrated by identifying the limitation of conventional UTMF OSC through optical–electrical multiphysics analysis and then introducing a corrugated cavity structure which perfects the spectral engineering over the optical absorption of the ultrathin PBDTT‐F‐TT:PC4Structure of the Reference UTMF OSC and Corrugated Cavity UTMF OSCs: The reference OSC and suggested CC‐UTMF OSC assumed the same material compositions, except for the corrugation. The reference flat UTMF OSC was constructed with a structure of TeO2/UTMF‐Ag/FPI‐PEIE/PBDTT‐F‐TT:PC71BM/MoO3/Ag  and A is the amplitude of the minor axis . For the efficient electrical charge transport and optical transparency, TeO2 was selected as a capping layer.3, UTMF‐Ag, and TeO2 were set as 10, 6, 12, and 50 nm, respectively.x‐axis. Putting the PDMS film in an oven at 40 °C under vacuum, sinusoidal corrugation structure could be obtained, from mechanical strain tuning. It was noted that the period and geometry of the corrugation could be controlled with the process parameters used in the fabrication of the release rate and compressive stress.The corrugation structure in Figure Coupled Optical–Electrical Device Simulations: All simulations were performed using the finite element method, implemented in COMSOL Multiphysics. The optical and electrical properties of BHJ OSCs were modeled by solving organic semiconductor equations consisting of two parts: the optical and electrical domains. First, the optical part solved Maxwell's equations for specified illumination conditions and then calculated the electric field intensity |E|2 for the later determination of exciton generation rates. The optical absorption in the active layer was obtained as a fraction of the absorbed incident power  under AM1.5G illumination conditions. Optical parameters used in the calculation included complex refractive indices of PBDTT‐F‐TT:PC71BM, MoO3, FPI‐PEIE and TeO2, taken from ref. µN, pµ) from ref. q is the elementary charge, kB is the Boltzmann constant, φ is the electrostatic potential, D is the Onsager–Braun dissociation  dissociation),Q is the local dissociation probability, R is the local recombination rate,µN and pµ are the electron and hole motilities, p and n are the charge carrier densities, peq and neq are the equilibrium densities, and nτ and pτ are the lifetimes of the electrons and holes, respectively. The exciton generation rate (in the active layer) was obtained from Gopt(λ) = ε″|E|2/2h–, where ε″ is the imaginary part of the dielectric permittivity, and h– is the reduced Planck constant. Further details of the optical and electrical simulation can be found in the previous papers,J–V characteristics, corresponding discussions, and list of fundamental parameters.Verification of the used model in comparison to experimental results of ref. The authors declare no conflict of interest.SupplementaryClick here for additional data file.


Considering that skin is the largest organ, we hypothesized that human bone morphogenetic protein receptor type IB (BmprIB)+ dermal cells could have enhanced osteogenic capacity in the healing of critical‐sized calvarial defects in an immunodeficient mouse model. In this study, immunohistochemical staining revealed that BmprIB was expressed throughout reticular dermal cells; the positive expression rate of BmprIB was 3.5% ± 0.4% in freshly separated dermal cells, by flow cytometry. Furthermore, in vitro osteogenic capacity of BmprIB+ cells was confirmed by osteogenic‐related staining and marker gene expression compared with unsorted dermal cells. In vivo osteogenic capacity was demonstrated by implantation of human BmprIB+ cell/coral constructs in the treatment of 4‐mm diameter calvarial defects in an immunodeficient mouse model compared with implantation of unsorted cell/coral constructs and coral scaffold alone. These results indicate that the selective cell population BmprIB from human dermis is a promising osteogenic progenitor cell that can be a large‐quantity and high‐quality cell source for bone tissue engineering and regeneration. S Dermal cells are a promising cell population for bone regeneration; unfortunately, the osteogenic potential of unsorted cells was quite low. This study demonstrated that a specific cell population in human dermis—bone morphogenetic protein receptor IB (BmprIB)+ cells—exhibited significantly higher osteogenic potential than unsorted dermal cells by repairing critical‐sized calvarial defects in an immunodeficient mouse model. This animal study is an extension of a previous in vitro finding in which BmprIB was proven as a marker for enrichment of osteogenic precursor‐like cells in human dermis, indicating that the selective cell population BmprIB from human dermis is a promising osteogenic progenitor cell that can provide a large‐quantity and high‐quality cell source for bone tissue engineering.Large bone defects are clinically challenging. Bone tissue engineering is a promising approach for bone regeneration Skin, the largest organ of the human body, consists of the epidermis, dermis, and appendages, such as hair follicles. Adult multipotent stem cells have been identified from all skin locations, such as stem cells from epidermis n = 8) following approval of the Ethics Committee of Shanghai Jiaotong University School of Medicine; informed written consent was provided by the parents. The foreskin specimen was depleted of subcutaneous tissue and cut into approximately 5 mm × 2 mm pieces. Next, the specimen was incubated in 8 U/ml Dispase  at 4°C overnight. The dermis was separated from the epidermis, cut into small pieces, and further digested in 2 mg/ml collagenase , which was diluted in Dulbecco's modified Eagle's medium–low glucose (DMEM‐lg)  at 37°C for 3 hours in a shaking water bath. The cell suspensions were filtered through a 40‐μm cell strainer  and either processed for magnetic‐activated cell sorting (BmprIB+ cells) or directly placed in 10‐cm culture plates  with complete medium containing DMEM‐lg supplemented with 10% fetal bovine serum (FBS) (Thermo Fisher), 100 U/ml penicillin, and 100 μg/ml streptomycin  at a density of 1 × 105/cm2.Foreskin samples were obtained from routine circumcision of children aged 6 months to 12 years of age (https://www.rndsystems.com), and further incubated with anti‐PE microbeads . The BmprIB+ cells were obtained as the incubated cell suspensions passed through the Miltenyi Biotec AutoMACS device, according to the manufacturer's instructions. Briefly, freshly isolated dermal cells were incubated in an incubation buffer (PBS containing 0.5% BSA) containing PE‐conjugated anti‐human BmprIB antibody (R&D Systems) for 60 minutes, followed by incubation with anti‐PE microbeads (Miltenyi Biotec) for 15 minutes. The incubation process was conducted on ice. Cells were passed through a 40‐μm cell strainer before running the AutoMACS device. The obtained cells were plated in complete medium at 37°C, 5% CO2, with medium changed after 24 hours to remove nonadherent cells. Cells were grown in medium that was changed every 3 days until they reached 80% confluence. They were then trypsinized and passaged.For magnetic‐activated cell sorting, the cell suspensions were centrifuged and resuspended in phosphate‐buffered saline  containing 0.5% bovine serum albumin , labeled with phycoerythrin (PE)‐conjugated anti‐human BmprIB antibody  and processed by following the manufacturer's protocols to localize BmprIB+ cells. Briefly, the sections were incubated with an anti‐human BmprIB antibody (Abcam) at 4°C overnight, followed by incubation with horseradish peroxidase‐conjugated goat anti‐mouse IgG antibody (Sigma‐Aldrich) at 4°C for 30 minutes.For localization of BmprIB+ cells in the dermis, freshly obtained human foreskin samples were fixed in 4% paraformaldehyde (Sigma‐Aldrich), dehydrated in graded ethanol solutions, and paraffin embedded. Immunohistochemical staining was performed by using a primary antibody against human BmprIB .To determine the percentage of BmprIB+ cells in the dermis, flow cytometric analysis of cell suspensions was performed using PE anti‐human BmprIB antibody according to the manufacturer's instructions. Briefly, the cells were incubated with PE anti‐human BmprIB antibody in a cytometry buffer  for 60 minutes, then washed, centrifuged, and resuspended. Finally, analysis was performed on a flow cytometer instrument  at wavelengths of 570 and 600 nm.The Alamar Blue assay (Thermo Fisher) was performed in triplicate to measure the proliferation and viability of the BmprIB+ cells (BmprIB) according to the manufacturer's protocol. In brief, the BmprIB+ cells and usDCs were placed into 96‐well plates (BD Biosciences) at 2 × 10−8 M), β‐phosphoglycerol (10 mM), and ascorbic acid (50 mg/L)  after reaching 80% confluence at passage 2. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) staining at day 7 and alizarin red S (ARS) staining for calcium nodules at day 28, as well as quantitative real‐time polymerase chain reaction (PCR) for osteogenic marker gene expression of ALP, osteocalcin (OCN), osteopontin (OPN), and bone sialoprotein (BSP) in triplicate experiments. Briefly, RNA from cell samples was prepared with Trizol (Thermo Fisher ) and cDNA was synthesized from RNA using reverse transcriptase . Real‐time PCR was performed in an ABI 7300 real‐time PCR system (Thermo Fisher) using the SYBR Premix Ex Tag kit (TaKaRa Biotechnology). The following primers were used: β‐actin: forward, 5′‐CATCTCTTGCTCGAAGTCCA‐3′ and reverse, 5′‐ATCA TGTTTGAGACCTTCAA‐3′; human ALP: forward, 5′‐TACAAGCACTCCCACTTCATC‐3′ and reverse, 5′‐AGACCCAATAGGTAGTCCACAT‐3′; human OCN: forward, 5′‐CTCACACTCCTCGCCCTATT‐3′ and reverse, 5′‐ CCCAGCCATTGATACAGGTAG‐3′; human OPN: forward, 5′–CATGAGAATTGCAGTGATTTGCT‐3′ and reverse 5′‐CTTGGAAGGGTCTGTGGGG‐3′; and human BSP: forward, 5′‐ TGCAATCCAGCTTCCCAAGA‐3′ and reverse 5′‐ TTGACGCCCGTGTATTCGTAC‐3′.Sorted and unsorted cells were induced in osteogenic medium containing complete medium supplemented with dexamethasone (10http://www.scanco.ch) was performed to characterize the coral structure.The coral used in this study was obtained from Hainan, China. The coral had porosity of 59.5% ± 7.0%, a mean pore diameter of 180 ± 55 μm, and wall thickness of 88 ± 26 μm. Natural corals were manufactured into wafers 4 mm in diameter by 1‐mm thick; they were washed ultrasonically and autoclaved before they were used as scaffolds in the following experiments. Microcomputed tomography  at passage 2 were seeded on coral wafers at a density of 2 × 105 cells per scaffold (approximately 1.5 × 107 cells per cm3). The suspensions of 5 μl of cells per scaffold were carefully pipetted onto the scaffolds in 6‐well plates and incubated for 1 hour to allow for cell attachment before the remainder of the culture medium was added to cover the cell/scaffold complexes. The scaffolds were incubated in complete medium for 3 days before they were transferred into osteogenic medium in 6‐well plates for 21‐day static culture, with medium change every 3 days.For the preparation of premature tissue constructs, both sorted and unsorted cell suspensions  at wavelengths of 570 and 600 nm. Nonseeded coral scaffolds incubated in complete medium were used as blank controls.For cell proliferation assays on the coral scaffolds, sorted and unsorted cells were seeded onto scaffolds in 24‐well plates at a density of 5 × 10http://www.philips.com) was used to determine the adhesion and growth of BmprIB+ cells on the scaffolds at days 1, 3, and 7. After cell seeding at a density of 2 × 105 cells per scaffold in regular culture medium, the constructs were fixed at days 1, 3, and 7 in 2.5% glutaraldehyde, postfixed with 0.1% osmium tetroxide, dehydrated through an ethanol series, dried in a CO2 dryer, coated with gold, and examined with SEM. The coral scaffold alone was also observed using SEM.Scanning electronic microscopy  phosphate substrate solution and alkaline buffer solution in a 37°C water bath for 15 minutes. The absorbance at 405 nm was measured with a spectrophotometer after 0.05 M NaOH was added to stop the reaction; a standard PNP curve with known concentration was used to determine the unknown samples. The osteocalcin content was also evaluated using a human osteocalcin RIA Kit  according to the manufacturer's instructions. Briefly, the samples were incubated with 100 μl of antiosteocalcin serum and 100 μl of 125I‐labeled osteocalcin antigen for competitive binding reaction at 4°C for 24 hours. After the reaction, 500 μl of separating agent was added to each tube and incubated for 20 minutes at room temperature. The radioactivity (in counts per minute) of the precipitate was measured by a radiation monitoring instrument . The binding rate of each sample was calculated and, based on the standard curve, the osteocalcin content of each sample was subsequently determined.The ALP activity and osteocalcin content were evaluated in the constructs at days 1, 3, 7, 14, 21, and 28 after osteogenic induction. For the ALP activity assay, the cell/coral constructs were washed with PBS, homogenized with Tris buffer , and ultrasonically disintegrated. The cell lysates were incubated with The animal experimental protocol was approved by the Animal Care and Experiment Committee of Shanghai Jiaotong University School of Medicine. After anesthesia, an incision of approximately 2 cm was made sagittally to expose the parietal calvarium; the periosteum was carefully removed with swabs on the right side of the parietal bones. A hollow drill was applied to create 4‐mm diameter defects, which were demonstrated in previous studies as unlikely to spontaneously heal http://www.emdmillipore.com), and anti‐CD31 .For in vivo osteogenic analysis, histological examinations were performed 6 weeks after surgery. Six mice in each group were euthanized. Harvested parietal bone samples were washed in PBS, fixed in 4% paraformaldehyde for 1 day, decalcified for 2 weeks in 10% ethylenediamine tetraacetic acid disodium salt (Sigma‐Aldrich) solutions, dehydrated in graded ethanol solutions, paraffin embedded, sectioned to 10 μm, and mounted on glass slides. Hematoxylin and eosin (H&E) staining, Masson trichrome staining, and immunohistochemical staining were carried out to evaluate bone formation, structure remodeling, and angiogenesis. The primary antibodies used in immunohistochemical staining were as follows: antiosteopontin , antiosteocalcin , anti‐bone sialoprotein . Goldner trichrome staining was carried out to evaluate bone formation and remodeling: mineralized bone stained green, osteoid stained red, and cartilage stained purple.For hard‐tissue histology, the remaining 6 mice in each group were euthanized 24 weeks postoperatively. Parietal bones were fixed in 4% paraformaldehyde for 1 day, dehydrated in an ethanol series and toluene, and embedded in methyl methacrylate. The blocks were sectioned into 10‐μm slices using a hard‐tissue microtome . Detailed evaluation of bone structural parameters determined by µCT analysis was also carried out, including bone volume (BV), bone volume fraction , trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), and connect density (Conn.D).Long‐term bone formation was evaluated 24 weeks postoperatively, taking into consideration coral degradation and bone remodeling. Three‐dimensional (3D) reconstruction of the µCT images was performed and the repair percentage of the defects, which was defined as the opaque area over total defect area, was processed using associated software GE AW4.1 . Statistically significant differences of three groups were determined using one‐way analysis of variance and Tukey test. Other data between the two groups in the current study were assessed using Student's t test. A p value less than .05 was considered statistically significant.Numerical data are presented as the mean and the standard deviation of the mean. All statistical analyses were performed with SPSS 13.0    Fig. . In cont05) Fig. .The surgical procedures and animal model Fig.  appearedTo investigate premature tissue constructs implanted in vivo, histological analyses were used to evaluate viability, osteogenesis, and angiogenesis 6 weeks postsurgery. Both H&E staining and Masson trichrome staining Fig.  revealedThe mice were euthanized 24 weeks after surgery. The tissue samples Fig.  were evan = 6; p < .05) ,BV/TV ratio (%), the Tb.N (1/mm), and the Tb.Th (mm), showed a similar trend as opacity volume (%)  Fig. . Other i05) Fig. , such as(%) Fig. . The Tb.(%) Fig. , indicatHard‐tissue sections stained by Goldner trichrome were used to evaluate bone formation and remodeling at 24 weeks. The defects were completely repaired by mature bone in the BmprIB group and partially repaired by osteoid in the usDCs group, whereas osteoid tissue was unremarkable in the coral‐alone group Fig. . BesidesDermal cells are a promising cell population for bone regeneration; unfortunately, the osteogenic potential of unsorted cells is quite low It is well‐known that the Bmp/Bmpr pathway plays an important role in osteogenesis The anatomical niche of BmprIB+ cells in the dermis has not been completely defined. The heterogeneous fibroblast lineages of the dermis, as described by Driskell et al. Coral is frequently used as a substitute for treating bone defects. As a natural material, the porous structure and inorganic calcium compounds make it a potential candidate for bone tissue engineering because these properties benefit cell adhesion and proliferation as well as complete degradation in vivo In this study, we observed that the coral scaffolds, which were all cut from the same coral block, were mostly absorbed at 24 weeks in vivo; however, a small fraction of intact coral could still be observed, especially in the control group with coral alone. This difference may be due to the minor differences in the cutting direction and, more importantly, the local osteoclast recruitment and activity. Whether BmprIB+ cells and usDCs played a role in osteoclast recruitment and activation was unclear; however, we did notice that the degradation velocities of coral scaffolds in the coral‐alone group were much slower than in the cell‐seeded groups in vivo. As the survival of seed cells in engineered bone greatly relies on vasculature to deliver nutrients, new bone formation is closely associated with adequate neovascularization. In the current study, our data demonstrated that coral scaffolds were suitable for vessel ingrowth when implanted for treatment of calvarial defects.Our study demonstrated that BmprIB+ cells isolated from human dermis possess enhanced osteogenic potential in both in vitro and in vivo studies, suggesting that BmprIB+ dermal cells are a promising cell source for bone tissue engineering. Despite the success of BmprIB+ dermal cells in the repair of calvarial defects, several mysteries need to be uncovered in further investigations. First, as the osteogenic potential is not necessary for skin injury repair, the physiological role of BmprIB+ cells in the dermis remains to be defined. Second, precise comparison of BmprIB+ cells with other MSCs, such as BMSCs or ASCs, is essential. Third, an immunodeficient animal model was used in this study to avoid immune issues associated with donor cells, while immunology research on the use of allogeneic BmprIB+ cells as seed cells is of great importance. Fourth, juvenile foreskins were used as a cell source in this study. Considering that the primary candidate patients for most tissue engineering applications are older, a future study will investigate the population of BmprIB+ cells in adult skin biopsies and its potential application for bone defect repair.The low expression or yield of BmprIB+ cells also exists in human ASCs. McArdle et al. found that freshly isolated ASCs stained for BMPrIB‐PE‐Cy7 demonstrated that 7.9% of the population was BMPrIB+ cells T.W.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; J.H. and Y.Z.: collection and assembly of data, data analysis and interpretation; W.S.: collection and assembly of data; J.D.: provision of study material; M.P.: manuscript writing, final approval of manuscript; L.Z.: conception and design, manuscript writing, final approval of manuscript.The authors indicated no potential conflicts of interest.


Statin therapy is a cornerstone of cardiovascular disease risk reduction for people with diabetes mellitus. Past reports have shown race‐sex differences in statin use in general populations, but statin patterns by race and sex in those with diabetes mellitus have not been thoroughly studied.LDL‐C) >100 mg/dL or were taking statins recruited for the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2007. Exposures included race‐sex groups  and factors that may influence healthcare utilization. Proportions and prevalence ratios were calculated for statin use and LDL‐C control. Statin use for WM, BM, WW, and BW was 66.0%, 57.8%, 55.0%, and 53.6%, respectively (P<0.001). After adjustment for healthcare utilization factors, statin use was lower for BM, WW, and BW compared with WM . LDL‐C control among those taking statins for WM, BM, WW, and BW was 75.3%, 62.7%, 69.0%, and 56.0%, respectively (P<0.001). After adjustment, LDL‐C control was lower for BM, WW, and BW compared with WM .Our sample of 4288 adults ≥45 years of age with diagnosed diabetes mellitus who had low‐density lipoprotein cholesterol (LDL‐C control were only partly explained by factors influencing health services utilization. Healthcare provider awareness of these disparities may help to close the observed race‐sex gaps in statin use and LDL‐C control among people with diabetes mellitus.Race‐sex disparities in statin use and  Individuals with diabetes mellitus are at high risk of coronary heart disease (CHD), and when they experience a clinical CHD event they have a worse prognosis than individuals without diabetes mellitus.Although statin use has increased in the United States since 2003,The REGARDS study has been described previously.The current cross‐sectional analysis used baseline REGARDS data. Of 7629 participants with diabetes mellitus, we selected participants who reported having been told by a healthcare professional that they had diabetes mellitus or who reported taking diabetes mellitus medications  . The outcomes were (1) statin use among the study sample, and (2) LDL‐C control, defined as LDL‐C<100 mg/dL among those taking statins. Statin use was determined through the medication inventory conducted during the in‐home visit, which included all medications taken in the last 2 weeks. LDL‐C was estimated using the Friedewald equation for participants with serum triglycerides <400 mg/dL.We examined associations between race‐sex groups and statin use guided by the Andersen and Aday model of influences on healthcare utilization Figure .23 FactoPredisposing factors included age, annual household income, highest education level attained (<high school graduation versus ≥graduation), and region of residence (stroke belt or buckle or neither).Enabling factors included health insurance (insured versus not), having a usual source of medical care (clinic or doctor versus not), and area‐level poverty .2 based on in‐home measures of height and weight); depressive symptoms Need factors were divided into perceived need and evaluated need. Perceived need was reflected in report of having been told by a doctor they had high cholesterol and medication adherence assessed via the 4‐item Morisky Medication Adherence Scale.P‐values reported using analysis of variance for continuous variables and chi‐squared tests for categorical variables. Prevalence of statin use and LDL‐C control among statin users were calculated by race‐sex group, and P‐values from chi‐squared tests were reported. Proportions of participants with statin use and controlled LDL‐C, statin use and uncontrolled LDL‐C, and no statin use and uncontrolled LDL‐C were also calculated by race‐sex group.Characteristics of participants were compared across race‐sex groups. The distributions of continuous variables were checked for normality, and means and standard deviations were reported. Unadjusted tests of association between race‐sex groups and other characteristics were performed and P‐values were reported. The level of statistical significance for all tests of association was ∝=0.05.Prevalence ratios of statin use among BM, WW, and BW compared to WM were then calculated using Poisson regression with a robust variance estimator. Four incrementally adjusted models were constructed with race‐sex group as the main exposure and statin use as the dependent variable. Model 1 minimally adjusted for age, model 2 added the remaining predisposing factors, model 3 added enabling factors, and model 4 added perceived and evaluated need factors. LDL‐C was not adjusted for in models of statin use because we did not have pretreatment LDL‐C values for those taking statins. Models were repeated using LDL‐C control as the dependent variable among participants treated with statins. The Wald chi‐squared test was used to jointly test for equality of parameter estimates for BM, WW, and BW, and Poisson regression models were fitted using multiply imputed data. Missing information was imputed by chained equations with m=30 imputations and 10 iterations.Baseline characteristics across race‐sex groups of the 4288 participants in the analytic sample are shown in Table In this sample, 57.9% of participants were taking statins. Compared with WM, the prevalence of statin use was 8.3, 11.0, and 12.4 percentage points lower for BM, WW, and BW, respectively . Additional sources of support include grants R01 HL080477  and K24 HL111154 (Safford and Gamboa), both from the National Heart, Lung, and Blood Institute , and grant K01 DK095928 (Carson) from the Agency for Healthcare Research and Quality . Representatives of the funding agencies have not been involved in the review of the manuscript and were not directly involved in the collection, management, analysis, or interpretation of the data.Dr Safford receives salary support for investigator‐initiated research from Amgen, Inc. Dr Brown participates on observational research with Amgen, Inc, and is the site Principal Investigator for a clinical trial with Omthera Pharmaceuticals. Dr Carson has received salary support for investigator‐initiated research from Amgen, Inc. No other authors reported any disclosures.