BACKGROUND—Reproductive factors provide an early window into a woman’s coronary heart disease (CHD) risk; however, their contribution to CHD risk stratification is uncertain.
METHODS AND RESULTS—In ...the Women’s Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C statistic, net reclassification index (or net reclassification index with risk categories of <5%, 5 to <10%, and ≥10% 10-year risk of CHD), and integrated discriminatory index were assessed. Among 72 982 women (CHD events, n=4607; median follow-up,12.0 interquartile range, 8.3–13.7 years; mean standard deviation age, 63.2 7.2 years), an age-adjusted reproductive risk factor model had a C statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages, and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C statistic increased from 0.726 to 0.730; integrated discriminatory index, 0.0013; P<0.0001). Net reclassification for women with events was not improved (net reclassification index events, 0.007; P=0.18); and, for women without events, net reclassification was marginally improved (net reclassification index nonevents, 0.002; P=0.04)
CONCLUSIONS—Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination, and do not materially improve net reclassification.
CONTEXT Some observational data suggest that hormone replacement therapy (HRT)
may reduce the risk of cognitive decline and dementia but results have been
conflicting. OBJECTIVE To review and ...evaluate studies of HRT for preventing cognitive decline
and dementia in healthy postmenopausal women. DATA SOURCES Studies with English-language abstracts identified in MEDLINE (1966-August
2000), HealthSTAR (1975-August 2000, PsychINFO (1984-August 2000); Cochrane
Library databases; and articles listed in reference lists of key articles. STUDY SELECTION Randomized controlled trials and cohort studies were reviewed for the
effects of HRT on cognitive decline; cohort and case-control studies were
reviewed for dementia risk. No randomized controlled trials regarding dementia
risk were identified. DATA EXTRACTION Twenty-nine studies met inclusion criteria and were rated. Two reviewers
rated study quality independently and 100% agreement was reached on Jadad
scores and 80% agreement was reached on US Preventive Services Task Force
quality scores. A final score was reached through consensus if reviewers disagreed. DATA SYNTHESIS Studies of cognition were not combined quantitatively because of heterogeneous
study design. Women symptomatic from menopause had improvements in verbal
memory, vigilance, reasoning, and motor speed, but no enhancement of other
cognitive functions. Generally, no benefits were observed in asymptomatic
women. A meta-analysis of observational studies suggested that HRT was associated
with a decreased risk of dementia (summary odds ratio, 0.66; 95% confidence
interval, 0.53-0.82). However, possible biases and lack of control for potential
confounders limit interpretation of these studies. Studies did not contain
enough information to assess adequately the effects of progestin use, various
estrogen preparations or doses, or duration of therapy. CONCLUSIONS In women with menopausal symptoms, HRT may have specific cognitive effects,
and future studies should target these effects. The meta-analysis found a
decreased risk of dementia in HRT users but most studies had important methodological
limitations.
Summary
The paper focuses on the identification of atypical fractures (AFFs). This paper examines the concordance between objective classification and expert subjective review. We believe the paper ...adds critical information about how to apply the American Society of Bone and Mineral Research (ASBMR) criteria to diagnose AFFs and is of high interest to the field.
Introduction
Assess American Society of Bone and Mineral Research (ASBMR) criteria for identifying atypical femoral fractures (AFFs).
Methods
Two orthopedic surgeons independently evaluated radiographs of 372 fractures, applying ASBMR criteria. We assessed ease of applying ASBMR criteria and whether criteria-based assessment matched qualitative expert assessment.
Results
There was up to 27% uncertainty about how to classify specific features. 84% of films were classified similarly for the presence of AFF according to ASBMR criteria; agreement increased to 94% after consensus meeting. Of 37 fractures categorized as AFFs based on ASBMR criteria, 23 (62.2%) were considered AFFs according to expert assessment (not relying on criteria). Only one (0.5%) femoral shaft fracture that did not meet ASBMR criteria was considered an AFF per expert assessment. The number of major ASBMR features present (four vs five) and whether there was periosteal or endosteal thickening (“beaking” or “flaring”) played major roles in the discrepancies between ASBMR criteria-based and expert-based determinations.
Conclusions
ASBMR AFF criteria were useful for reviewers but several features were difficult to interpret. Expert assessments did not agree with the ASBMR classification in almost one-third of cases, but rarely identified an AFF when a femoral shaft fracture did not meet ASBMR AFF criteria. Experts identified lateral cortical transverse fracture line and associated new-bone formation along with no or minimal comminution as crucial features necessary for the definition of atypical femoral fractures.
To reveal sleep health phenotypes in older adults and examine their associations with time to 5-year all-cause and cardiovascular mortality.
Prospective longitudinal cohorts.
The Study of ...Osteoporotic Fractures and Outcomes of Sleep Disorders in Older Men Study.
N = 1722 men and women aged ≥65 years matched 1:1 on sociodemographic and clinical measures.
Self-reported habitual sleep health characteristics (satisfaction, daytime sleepiness, timing, efficiency, and duration) measured at an initial visit and longitudinal follow-up for mortality.
Latent class analysis revealed 3 sleep health phenotypes: (1) heightened sleep propensity (HSP; medium to long duration, high sleepiness, high efficiency/satisfaction; n = 322), (2) average sleep (AS; medium duration, average efficiency, high satisfaction, low sleepiness; n = 1,109), and (3) insomnia with short sleep (ISS; short to medium duration, low efficiency/satisfaction, moderate sleepiness; n = 291). Phenotype predicted time to all-cause mortality (χ2 = 9.4, P = .01), with HSP conferring greater risk than AS (hazard ratio 95% confidence interval = 1.48 1.15-1.92) or ISS (1.52 1.07-2.17), despite ISS reporting the poorest mental and physical health. Although sex did not formally moderate the relationship between phenotype and mortality, subgroup analyses indicated that these findings were driven primarily by women. Phenotype did not predict cardiovascular mortality.
These analyses support the utility of examining multidimensional sleep health profiles by suggesting that the combination of long sleep, high efficiency/satisfaction, and daytime sleepiness—previously identified as independent risk factors—may be components of a single high-risk sleep phenotype, HSP. Further investigation of sex differences and the mechanisms underlying mortality risk associated with HSP is warranted.
Previous studies have reported that breast cancer patients who used estrogen replacement therapy (ERT) have more favorable tumor characteristics and decreased mortality compared with nonusers. ...However, these findings may be due partly to increased medical surveillance in ERT users and detection of early stage tumors. Postmenopausal women with biopsy-proven breast cancer (n = 108) were identified based on their participation in screening mammography. Based on self-administered questionnaires completed at the time of mammography, 29 of these were users of ERT. Tumor characteristics (histology size, nodal status, and estrogen receptor content) of ERT users were compared with those of nonusers. After adjusting for potentially confounding variables, the odds ratios (OR) describing the relationship between ERT use and the risk of invasive histopathology (OR = 1.35, 95% CI = 0.48, 3.75), positive nodes (OR = 2.43, 95% CI = 0.59, 10.10), size > or = 2.0 cm (OR = 2.34, CI = 0.66, 8.27), or negative estrogen receptor status (OR = 1.08, 95% CI = 0.18, 9.38) were > 1, although none reached statistical significance. When the subjects were separated into two prognostic groups based on the presence or absence of adverse prognostic indices, ERT users had a statistically significantly increased risk of being in the poor prognostic group (tumor size > or = 2.0 cm or positive nodes or negative estrogen receptor content) (OR = 4.48, 95% CI = 1.10, 18.30). The risk was highest in current users (OR = 6.28, 95% CI = 1.16, 34.00), users for 5 or more years (OR = 7.77, 95% CI = 1.09, 55.60), and users of nonconjugated estrogen (OR = 9.63, 95% CI = 1.18, 78.60). Although our sample size is small and we do not currently have information on long-term outcomes, the findings from this screening population suggest that ERT may have an adverse effect on important breast cancer prognostic indices.
Drug delivery across the blood-brain barrier (BBB) is one of the biggest challenges in modern medicine due to the BBB's highly semipermeable property that limits most therapeutic agents of brain ...diseases to enter the central nervous system (CNS). In recent years, nanoparticles, especially carbon dots (CDs), exhibit many unprecedented applications for drug delivery. Several types of CDs and CD-ligand conjugates have been reported successfully penetrating the BBB, which shows a promising progress in the application of CD-based drug delivery system (DDS) for the treatment of CNS diseases. In this review, our discussion of CDs includes their classification, preparations, structures, properties, and applications for the treatment of neurodegenerative diseases, especially Alzheimer's disease (AD) and brain tumor. Moreover, abundant functional groups on the surface, especially amine and carboxyl groups, allow CDs to conjugate with diverse drugs as versatile drug nanocarriers. In addition, structure of the BBB is briefly described, and mechanisms for transporting various molecules across the BBB and other biological barriers are elucidated. Most importantly, recent developments in drug delivery with CDs as BBB-penetrating nanodrugs and drug nanocarriers to target CNS diseases especially Alzheimer's disease and brain tumor are summarized. Eventually, future prospects of the CD-based DDS are discussed in combination with the development of artificial intelligence and nanorobots.
Peatlands cover very large extents in northern regions and play a significant role in the global carbon cycle by functioning as a carbon sink. Large-scale satellite based monitoring systems, such as ...the Sentinel-2 Multispectral Instrument (MSI), are necessary to improve our understanding of how these ecosystems respond to climate change by providing verifiable land products. For instance, satellite-based land product validation approaches can benefit from airborne hyperspectral imagery and in-situ data, which provide higher spatial and spectral resolution baselines, ideal for measuring vegetation changes (e.g. phenology, LAI) at local scales. Here, we assessed the short-term phenospectral dynamics (spectral changes indicated by specific spectral features as a function of phenology) of five ombrotrophic peatland vegetation physiognomies over four dates at the Mer Bleue bog in Canada. We took advantage of a unique remote sensing data acquisition campaign aiming to validate Sentinel-2A land products, and analyzed three spatially and spectrally distinctive datasets (i.e. field spectra, VISNIR airborne hyperspectral imagery (HSI) and Sentinel-2A imagery) over the first half of the 2016 growing season. By implementing a bottom-up approach, first we assessed the airborne HSI's capability to detect phenological changes as compared to in-situ acquired field spectroscopy measurements in a 10 ha area at Mer Bleue and evaluated the spectral features characteristic of these phenological changes. Second, over the entire Mer Bleue area (28,000 ha), we compared a series of four Sentinel-2A images to four airborne HSI mosaics (spatially and spectrally resampled to Sentinel-2A) to assess the utility of Sentinel-2A for detecting small spectral variations due to phenological changes (i.e. greening). In addition, for this second comparison, three spectral vegetation indices were derived from the Sentinel-2A images and the airborne HSI mosaics. The spectral comparisons between the airborne HSI and the field spectroscopy data revealed clear phenological changes from the airborne HSI. For instance, a closer agreement between reflectance measured by the field spectrometer and the airborne HSI spectral response was found in the visible region (450–680 nm). A greater difference however, was consistently seen in the near-infrared region (681–866 nm) across the four dates. Narrow spectral features in three regions of the visible range (global minima, red absorption, green peak), indicating changes in vegetation colour, were consistent for both datasets and with expected phenological patterns at Mer Bleue. At the landscape level, Sentinel-2A mirrored the spectral changes depicted by the resampled HSI data. However, band level, pair-wise comparisons showed significant differences (p < 0.001) in reflectance for each band, with Sentinel-2A exhibiting higher reflectance values than the HSI for the first three dates. Only for the last date (June 23rd) did the airborne HSI have higher reflectance values or no significant difference with the Sentinel-2A data. Overall, our three datasets captured the short-term phenological changes at Mer Bleue and have provided promising results in terms of using the Sentinel-2A MSI sensor to monitor these changes at the landscape level.
•A bottom-up approach was developed & implemented for Sentinel-2 product validation•Phenospectral changes were captured by all three levels of measurement at Mer Bleue.•Sentinel-2 has potential for assessing phenological changes in northern peatlands.
The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression “signatures” were ...identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA) which correlated with better survival. We further analyzed the effects of HLA-DRA on survival and correlated gene expression with protein status and tumor-infiltrating lymphocytes. The 5-year overall survival was 24% in the lowest 10% of HLA-DRA expression, 37% in the 10% to 25% group, 50% in the 25% to 50% group, and 55% for patients in the highest 50%. Further analysis demonstrated that the hazard ratio of death was a nonlinear function of HLA-DRA expression. Adjustment for the International Prognostic Index did not alter the impact of HLA-DRA on survival. Other MHC class II genes were found to predict survival similarly. Microarray HLA-DRA expression correlated with the presence or absence of human leukocyte antigen-DR (HLA-DR) protein in 20 of 22 cases assessed. Fewer tumor-infiltrating CD8+ T cells were detected in MHC class II-negative cases compared with positive cases (2.8% versus 11.0%; P = .001), supporting the hypothesis that loss of tumor immunosurveillance has a devastating effect on patient outcome in DLBCL. (Blood. 2004; 103:4251-4258)
Patients with follicular lymphoma may survive for periods ranging from less than a year to several decades. In this study, DNA-microarray analysis of gene expression in specimens of follicular ...lymphoma showed that two genetic signatures predicted the length of survival with a high degree of accuracy. Surprisingly, one signature consisted of genes that are typically expressed in normal T cells, and the other consisted of genes expressed in monocytes and dendritic cells.
DNA-microarray analysis of gene expression in specimens of follicular lymphoma showed that two genetic signatures predicted survival with a high degree of accuracy.
Follicular lymphoma is the second most common form of non-Hodgkin's lymphoma, accounting for about 22 percent of all cases.
1
The clinical course of follicular lymphoma is variable: in some patients the disease is indolent and slowly progressive over a period of many years, with waxing and waning lymphadenopathy, whereas in others the disease progresses rapidly, often with transformation to aggressive lymphoma and early death.
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3
Management includes observation, chemotherapy, hematopoietic stem-cell transplantation, and immunologic therapies based on antibodies to B cells
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or idiotype vaccines.
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There is no conclusive evidence that any of these approaches offers a clinically significant . . .
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