Background Although ecologic association and animal studies support a direct effect of dietary fat on the development of breast cancer, results of epidemiologic studies have been inconclusive. ...Methods We prospectively analyzed the association between fat consumption and the incidence of postmenopausal invasive breast cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort comprising 188 736 postmenopausal women who completed a 124-item food-frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models with adjustment for energy and potential confounding factors. All statistical tests were two-sided. Results Over an average follow-up of 4.4 years, the cohort yielded 3501 cases of invasive breast cancer. The hazard ratio of breast cancer for the highest (median intake, 40.1% energy from total fat; 434 cases per 100 000 person-years) versus the lowest (median intake, 20.3% energy from total fat; 392 cases per 100 000 person-years) quintile of total fat intake was 1.11 (95% CI = 1.00 to 1.24; Ptrend = .017). The corresponding hazard ratio for a twofold increase in percent energy from total fat on the continuous scale was 1.15 (95% CI = 1.05 to 1.26). Positive associations were also found for subtypes of fat (hazard ratio for a twofold increase in percent energy from saturated fat = 1.13; 95% CI = 1.05 to 1.22; from monounsaturated fat, HR = 1.12; 95% CI = 1.03 to 1.21; from polyunsaturated fat, HR = 1.10, 95% CI = 1.01 to 1.20). Correction for measurement error in nutrient intakes, on the basis of a calibration substudy that used two 24-hour dietary recalls, strengthened the associations, yielding an estimated hazard ratio for total fat of 1.32 (95% CI = 1.11 to 1.58). Secondary analyses showed that associations between total, saturated, and monounsaturated fat intakes were confined to women who were not using menopausal hormone therapy at baseline. Conclusion In this large prospective cohort with a wide range of fat intake, dietary fat intake was directly associated with the risk of postmenopausal invasive breast cancer.
Kabuki or Niikawa–Kuroki syndrome (KS) is a rare disorder with multiple malformations and recurrent infections, especially otitis media. This study aimed to investigate the genetic defects in Kabuki ...syndrome and determine if immune status is related to recurrent otitis media. Fourteen patients from 12 unrelated families were enrolled in the 9‐year study period (2005–2013). All had Kabuki faces, cleft palate, developmental delay, mental retardation, and the short fifth finger. Recurrent otitis media (12/14) and hearing impairment (8/14) were also more common features. Immunologic analysis revealed lower memory CD19+ cells (11/13), lower memory CD4+ cells (8/13), undetectable anti‐HBs antibodies (7/13), and antibody deficiency (7/13), including lower IgA (4), IgG (2), and IgG2 (1). Naïve emigrant lymphocytes, lymphocyte proliferation function, complement activity, and superoxide production in polymorphonuclear cells were all normal. All the patients had KMT2D mutations and 10 novel mutations of R1252X, R1757X,Y1998C, P2550R fs2604X, Q4013X, G5379X, E5425K, R5432X, R5432W, and R5500W. Resembling the phenotype of common variable immunodeficiency, KS patients with antibody deficiency, decreased memory cells, and poor vaccine response increased susceptibility to recurrent otitis media. Large‐scale prospective studies are warranted to determine if regular immunoglobulin supplementation decreases the frequency of otitis media and severity of hearing impairment.
To evaluate accuracy and interobserver variability with the use of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 for detection of prostate cancer at multiparametric magnetic ...resonance (MR) imaging in a biopsy-naïve patient population.
This retrospective HIPAA-compliant study was approved by the local ethics committee, and written informed consent was obtained from all patients for use of their imaging and histopathologic data in future research studies. In 101 biopsy-naïve patients with elevated prostate-specific antigen levels who underwent multiparametric MR imaging of the prostate and subsequent transrectal ultrasonography (US)-MR imaging fusion-guided biopsy, suspicious lesions detected at multiparametric MR imaging were scored by five readers who were blinded to pathologic results by using to the newly revised PI-RADS and the scoring system developed in-house. Interobserver agreement was evaluated by using κ statistics, and the correlation of pathologic results with each of the two scoring systems was evaluated by using the Kendall τ correlation coefficient.
Specimens of 162 lesions in 94 patients were sampled by means of transrectal US-MR imaging fusion biopsy. Results for 87 (54%) lesions were positive for prostate cancer. Kendall τ values with the PI-RADS and the in-house-developed scoring system, respectively, at T2-weighted MR imaging in the peripheral zone were 0.51 and 0.17 and in the transitional zone, 0.45 and -0.11; at diffusion-weighted MR imaging, 0.42 and 0.28; at dynamic contrast material-enhanced MR imaging, 0.23 and 0.24, and overall suspicion scores were 0.42 and 0.49. Median κ scores among all possible pairs of readers for PI-RADS and the in-house-developed scoring system, respectively, for T2-weighted MR images in the peripheral zone were 0.47 and 0.15; transitional zone, 0.37 and 0.07; diffusion-weighted MR imaging, 0.41 and 0.57; dynamic contrast-enhanced MR imaging, 0.48 and 0.41; and overall suspicion scores, 0.46 and 0.55.
Use of the revised PI-RADS provides moderately reproducible MR imaging scores for detection of clinically relevant disease.
Abstract
We present the four-year survey results of monthly submillimeter monitoring of eight nearby (<500 pc) star-forming regions by the JCMT Transient Survey. We apply the Lomb–Scargle Periodogram ...technique to search for and characterize variability on 295 submillimeter peaks brighter than 0.14 Jy beam
−1
, including 22 disk sources (Class II), 83 protostars (Class 0/I), and 190 starless sources. We uncover 18 secular variables, all of them protostars. No single-epoch burst or drop events and no inherently stochastic sources are observed. We classify the secular variables by their timescales into three groups: Periodic, Curved, and Linear. For the Curved and Periodic cases, the detectable fractional amplitude, with respect to mean peak brightness, is ∼4% for sources brighter than ∼0.5 Jy beam
−1
. Limiting our sample to only these bright sources, the observed variable fraction is 37% (16 out of 43). Considering source evolution, we find a similar fraction of bright variables for both Class 0 and Class I. Using an empirically motivated conversion from submillimeter variability to variation in mass accretion rate, six sources (7% of our full sample) are predicted to have years-long accretion events during which the excess mass accreted reaches more than 40% above the total quiescently accreted mass: two previously known eruptive Class I sources, V1647 Ori and EC 53 (V371 Ser), and four Class 0 sources, HOPS 356, HOPS 373, HOPS 383, and West 40. Considering the full protostellar ensemble, the importance of episodic accretion on few years timescale is negligible—only a few percent of the assembled mass. However, given that this accretion is dominated by events on the order of the observing time window, it remains uncertain as to whether the importance of episodic events will continue to rise with decades-long monitoring.
Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), ...leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.
Antimonene is a promising two-dimensional (2D) material that is calculated to have a significant fundamental bandgap usable for advanced applications such as field-effect transistors, photoelectric ...devices, and the quantum-spin Hall (QSH) state. Herein, we demonstrate a phenomenon termed topological proximity effect, which occurs between a 2D material and a three-dimensional (3D) topological insulator (TI). We provide strong evidence derived from hydrogen etching on Sb2Te3 that large-area and well-ordered antimonene presents a 2D topological state. Delicate analysis with a scanning tunneling microscope of the evolutionary intermediates reveals that hydrogen etching on Sb2Te3 resulted in the formation of a large area of antimonene with a buckled structure. A topological state formed in the antimonene/Sb2Te3 heterostructure was confirmed with angle-resolved photoemission spectra and density-functional theory calculations; in particular, the Dirac point was located almost at the Fermi level. The results reveal that Dirac fermions are indeed realized at the interface of a 2D normal insulator (NI) and a 3D TI as a result of strong hybridization between antimonene and Sb2Te3. Our work demonstrates that the position of the Dirac point and the shape of the Dirac surface state can be tuned by varying the energy position of the NI valence band, which modifies the direction of the spin texture of Sb-BL/Sb2Te3 via varying the Fermi level. This topological phase in 2D-material engineering has generated a paradigm in that the topological proximity effect at the NI/TI interface has been realized, which demonstrates a way to create QSH systems in 2D-material TI heterostructures.
The properties of acoustic speech have previously been investigated as possible cues for depression in adults. However, these studies were restricted to small populations of patients and the speech ...recordings were made during patients' clinical interviews or fixed-text reading sessions. Symptoms of depression often first appear during adolescence at a time when the voice is changing, in both males and females, suggesting that specific studies of these phenomena in adolescent populations are warranted. This study investigated acoustic correlates of depression in a large sample of 139 adolescents (68 clinically depressed and 71 controls). Speech recordings were made during naturalistic interactions between adolescents and their parents. Prosodic, cepstral, spectral, and glottal features, as well as features derived from the Teager energy operator (TEO), were tested within a binary classification framework. Strong gender differences in classification accuracy were observed. The TEO-based features clearly outperformed all other features and feature combinations, providing classification accuracy ranging between 81%-87% for males and 72%-79% for females. Close, but slightly less accurate, results were obtained by combining glottal features with prosodic and spectral features (67%-69% for males and 70%-75% for females). These findings indicate the importance of nonlinear mechanisms associated with the glottal flow formation as cues for clinical depression.
Empyema is a rare but important complication among patients with end-stage renal disease (ESRD). However, a nationwide, propensity-matched cohort study has never been performed.
We conducted a ...retrospective cohort study using data from the National Health Insurance Research Database of Taiwan. The ESRD group consisted of 82 765 patients diagnosed between 2000 and 2008. The comparison group consisted of individuals without kidney disease selected at a 1:1 ratio matched by propensity score estimated with age, gender, year of diagnosis and comorbidities. The occurrence of empyema was monitored until the end of 2011. The hazard ratios (HRs) of empyema were estimated using the Cox proportional hazards model.
The incidence of empyema was 2.76-fold higher in the ESRD group than in the comparison group (23.7 vs. 8.19/10 000 person-years, P <0.001), with an adjusted HR of 3.01 95% confidence interval (CI) = 2.67-3.39. There was no difference of the incidence of empyema between hemodialysis (HD) and peritoneal dialysis (PD) (adjusted HR = 0.96, 95% CI = 0.75-1.23). In addition, 30-day mortality rate since empyema diagnosis was significantly higher in ESRD group than the comparison group (15.9% vs. 10.9%), with an adjusted OR of 1.69 (95% CI = 1.17-2.44).
The risk of empyema was significantly higher in patients with ESRD than in those without kidney disease. The occurrence of empyema was without difference in patients undergoing HD compared to those undergoing PD. The 30-day mortality rate since empyema diagnosis was also significantly higher in patients with ESRD.
Pharmaceuticals and personal care products (PPCPs) are ubiquitous in sewage, adversely affecting ecosystems and human health. In this study, an S-scheme magnetic ZnFe2O4/ammoniated MoS2 ...(ZnFe2O4/A-MoS2) heterojunction as a visible-light-driven PMS activator for PPCP degradation was developed. ZnFe2O4/A-MoS2 achieves improved photocatalytic activity because the construction of S-scheme heterojunction promotes the separation of the highly reductive photogenerated electrons. The optimized photocatalyst (10%-ZnFe2O4/A-MoS2, 0.2 g/L) achieved 100% removal of 2 ppm carbamazepine (CBZ) within 2.5 min at a PMS dosage of 0.5 mM (initial pH 7.0). Mechanistic investigation revealed that the separated electrons to the ZnFe2O4 reactive center of the heterojunction facilitated PMS activation and generated SO4 ·– as the dominant reactive species for CBZ degradation. The system exhibited excellent practicability in various samples of actual sewage, where most sewage components negatively impacted CBZ degradation. Further, the chloride ions in high-salinity sewage could be activated to generate additional reactive chlorine species for PPCP degradation. The heterojunction possesses outstanding reusability and stability in treating various water conditions. This work provides mechanistic and practical perspectives in developing novel S-type heterojunctions for recalcitrant pollutant treatment.