Miracle-dz/UniFAR-FTUs huggingface dataset:
Composite Partial Likelihood Estimation Under Length-Biased Sampling, With Application to a Prevalent Cohort Study of Dementia

The Canadian Study of Health and Aging (CSHA) employed a prevalent cohort design to study survival after onset of dementia, where patients with dementia were sampled and the onset time of dementia was determined retrospectively. The prevalent cohort sampling scheme favors individuals who survive longer. Thus, the observed survival times are subject to length bias. In recent years, there has been a rising interest in developing estimation procedures for prevalent cohort survival data that not only account for length bias but also actually exploit the incidence distribution of the disease to improve efficiency. This article considers semiparametric estimation of the Cox model for the time from dementia onset to death under a stationarity assumption with respect to the disease incidence. Under the stationarity condition, the semiparametric maximum likelihood estimation is expected to be fully efficient yet difficult to perform for statistical practitioners, as the likelihood depends on the baseline hazard function in a complicated way. Moreover, the asymptotic properties of the semiparametric maximum likelihood estimator are not well-studied. Motivated by the composite likelihood method (Besag 1974), we develop a composite partial likelihood method that retains the simplicity of the popular partial likelihood estimator and can be easily performed using standard statistical software. When applied to the CSHA data, the proposed method estimates a significant difference in survival between the vascular dementia group and the possible Alzheimer's disease group, while the partial likelihood method for left-truncated and right-censored data yields a greater standard error and a 95% confidence interval covering 0, thus highlighting the practical value of employing a more efficient methodology. To check the assumption of stable disease for the CSHA data, we also present new graphical and numerical tests in the article. The R code used to obtain the maximum composite partial likelihood estimator for the CSHA data is available in the online Supplementary Material, posted on the journal web site.
Defining MCI in the Framingham Heart Study Offspring: Education Versus WRAT-based Norms

Introduction:Psychometric definitions of mild cognitive impairment (MCI) typically use cut-off levels set at 1.5 SDs below age-adjusted and education-adjusted norms, assuming that the education adjustment accounts for premorbid abilities. However, noncognitive factors impact educational attainment, potentially leading to incorrect categorization as MCI. We examined whether using an adjustment based on reading performance [Wide Range Achievement Test (WRAT) Reading] improved MCI diagnostic accuracy. Methods:A total of 935 Framingham Offspring (mean age, 72±5 y) underwent tests of memory, executive function, abstraction, language, and visuospatial function as part of a neuropsychological test battery. Domain-specific test scores were regressed onto age and WRAT score, or education, to define MCI. Survival analyses were used to relate baseline MCI to incident dementia. Results:The 2 MCI definitions differed most for the lowest and highest education groups. The WRAT definition was more strongly associated with incident dementia for all 5 tests. MCI level abstraction performance was associated with incident dementia using the WRAT definition (HR=3.20, P=0.033), but not the education definition (HR=1.19, P=0.814). Discussion:The WRAT should be considered along with the standard measure of years of education, as it may be a better surrogate marker of premorbid abilities.
Cortical development in typically developing children with symptoms of hyperactivity and impulsivity: support for a dimensional view of attention deficit hyperactivity disorder.

OBJECTIVE There is considerable epidemiological and neuropsychological evidence that attention deficit hyperactivity disorder (ADHD) is best considered dimensionally, lying at the extreme end of a continuous distribution of symptoms and underlying cognitive impairments. The authors investigated whether cortical brain development in typically developing children with symptoms of hyperactivity and impulsivity resembles that found in the syndrome of ADHD. Specifically, they examined whether a slower rate of cortical thinning during late childhood and adolescence, which they previously found in ADHD, is also linked to the severity of symptoms of hyperactivity and impulsivity in typically developing children. METHOD In a longitudinal analysis, a total of 193 typically developing children with 389 neuroanatomic magnetic resonance images and varying levels of symptoms of hyperactivity and impulsivity (measured with the Conners' Parent Rating Scale) were contrasted with 197 children with ADHD with 337 imaging scans. The relationship between the rates of regional cortical thinning and severity of symptoms of hyperactivity/impulsivity was determined. RESULTS Youth with higher levels of hyperactivity/impulsivity had a slower rate of cortical thinning, predominantly in prefrontal cortical regions, bilaterally in the middle frontal/premotor gyri, extending down the medial prefrontal wall to the anterior cingulate; the orbitofrontal cortex; and the right inferior frontal gyrus. For each increase of one point in the hyperactivity/impulsivity score, there was a decrease in the rate of regional cortical thinning of 0.0054 mm/year (SE=0.0019 mm/year). Children with ADHD had the slowest rate of cortical thinning. CONCLUSIONS Slower cortical thinning during adolescence characterizes the presence of both the symptoms and syndrome of ADHD, providing neurobiological evidence for dimensionality of the disorder.
Sleep-Related Problems and the Effects of Anxiety Treatment in Children and Adolescents

This study examined (a) demographic and clinical characteristics associated with sleep-related problems (SRPs) among youth with anxiety disorders, and (b) the impact of anxiety treatment: cognitive-behavioral therapy (CBT; Coping Cat), medication (sertraline), their combination, and pill placebo on SRPs. Youth (N = 488, ages 7–17, 50% female, 79% White) with a principal diagnosis of generalized anxiety disorder, separation anxiety disorder, or social phobia participated. SRPs were reported by parents and youth. Findings differed by informant and by type of SRP, with evidence that SRPs are associated with age, anxiety severity, externalizing problems, functional impairment, and family burden at pretreatment. Anxiety treatment reduced SRPs; effect sizes were small to medium. Reductions in parent-reported separation-related sleep difficulties were significantly greater in active treatment than in the placebo condition, with the greatest reductions reported by parents of youth whose active treatment was multimodal or included sertraline. Youth whose anxiety treatment involved CBT reported significantly greater decreases in dysregulated sleep (e.g., sleeplessness). Both CBT for anxiety and sertraline appear to be somewhat effective in reducing SRPs, and multimodal treatment may be preferable depending on the symptom presentation. To inform practice, future research should examine a broad range of SRPs, incorporate objective measures of sleep, and evaluate the impact of behavioral strategies that directly target SRPs in youth with anxiety disorders.
Heritability of mandibular cephalometric variables in twins with completed craniofacial growth.

OBJECTIVES To determine genetic and environmental impact on mandibular morphology using lateral cephalometric analysis of twins with completed mandibular growth and deoxyribonucleic acid (DNA) based zygosity determination. MATERIALS AND METHODS The 39 cephalometric variables of 141 same gender adult pair of twins were analysed. Zygosity was determined using 15 specific DNA markers and cervical vertebral maturation method was used to assess completion of the mandibular growth. A genetic analysis was performed using maximum likelihood genetic structural equation modelling (GSEM). RESULTS The genetic heritability estimates of angular variables describing horizontal mandibular position in relationship to cranial base and maxilla were considerably higher than in those describing vertical position. The mandibular skeletal cephalometric variables also showed high heritability estimates with angular measurements being considerably higher than linear ones. Results of this study indicate that the angular measurements representing mandibular skeletal morphology (mandibular form) have greater genetic determination than the linear measurements (mandibular size). CONCLUSIONS The shape and sagittal position of the mandible is under stronger genetic control, than is its size and vertical relationship to cranial base.
Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction

Abstract Background: Little information is available about the prevalence and impact on exercise capacity and outcome of iron deficiency in heart failure with mid-range (HFmrEF) and preserved (HFpEF) ejection fraction in comparison to heart failure with reduced ejection-fraction (HFrEF). Furthermore, no data is available about the progression of ID in patients without baseline anaemia. Methods: We evaluated baseline iron and haemoglobin-status in a single-centre, prospective heart failure database. Baseline functional status, VO2max, echocardiography and clinical-outcome (all-cause mortality and heart failure admissions) were evaluated. ID, anaemia, HFrEF, HFmrEF and HFpEF were defined according to established criteria. Results: A total of 1197 patients (71% male) were evaluated (HFrEF, n = 897; HFmrEF, n = 229; HFpEF, n = 72). The overall prevalence of ID was 53% (50% in HFrEF; 61% in HFmrEF; 64% in HFpEF) and 36% for anaemia. ID was associated with a lower VO2max in patients with HFrEF, HFmrEF and HFpEF (p < .001 in all). Iron status more closely related to a poor VO2max than anaemia status (p < .001). Furthermore, poor clinical-outcome was more strongly associated with iron status than anaemia status. Exposing eight patients without anaemia to iron deficiency for 39 months resulted in one patient developing new-onset anaemia (defined as progression of ID). Patients with progression of ID exhibited a significant higher risk of heart failure hospitalisation and all-cause mortality (HR = 1.4; CI = 1.01–1.94; p = .046) than patients without progression. Conclusions: Iron deficiency is common in patients with HFrEF, HFmrEF and HFpEF, and negatively affects VO2max and clinical-outcome. Progression of iron deficiency parallels an increased risk for worsening of heart failure.
Transient Prosopometamorphopsia Restricted to the Left Eye Caused by Ischemia at the Right Splenium of the Corpus Callosum

We herein report a patient who developed transient prosopometamorphopsia restricted to the left eye caused by ischemia of the right splenium of the corpus callosum. A 66-year-old right-handed woman suddenly noticed that the left eyes of people she encountered appeared markedly adducted to their noses. On emergent admission, neurological and ophthalmological examinations revealed no abnormalities. Diffusion-weighted magnetic resonance imaging showed a small, hyperintense lesion at the right splenium of the corpus callosum. In this case, information on the right visual field projected to the left occipital lobe might have been obstructed on transmission to the right hemisphere through the splenium of the corpus callosum.
Regulation of the basement membrane by epithelia generated forces

Tumor metastasis involves a progressive loss of tissue architecture and dissolution of structural boundaries between the epithelium and connective tissue. The basement membrane (BM), a specialized network of extracellular matrix proteins forms a barrier that physically restricts pre-invasive lesions such that they remain as local insults. The BM is not a static structure, but one that is constantly regenerated and remodeled in the adult organism. Matrix organization also regulates cell function. Thus alterations in the balance of synthesis, remodeling and proteolytic degradation of the extracellular matrix proteins may contribute to a loss of structural integrity. However, the de novo assembly and maintenance of the complex structural properties of in vivo basement membranes remain elusive. Here, this paper highlights the current understanding on the structural properties and the establishment of the BM, and discusses the potential role of self-generated forces in adult tissue remodeling and the maintenance of the BM as a malignancy suppressor.
Association of Inflammation-Related and microRNA Gene Expression with Cancer-Specific Mortality of Colon Adenocarcinoma

Purpose: Inflammatory genes and microRNAs have roles in colon carcinogenesis; therefore, they may provide useful biomarkers for colon cancer. This study examines the potential clinical utility of an inflammatory gene expression signature as a prognostic biomarker for colon cancer in addition to previously examined miR-21 expression. Experimental Design: Quantitative reverse transcriptase-PCR. was used to measure the expression of 23 inflammatory genes in colon adenocarcinomas and adjacent noncancerous tissues from 196 patients. These data were used to develop models for cancer-specific mortality on a training cohort (n = 57), and this model was tested in both a test (n = 56) and a validation (n = 83) cohort. Expression data for miR-21 were available for these patients and were compared and combined with inflammatory gene expression. Results: PRG1, IL-10, CD68, IL-23a, and IL-12a expression in noncancerous tissue, and PRG1, ANXA1, IL-23a, IL-17a, FOXP3, and HLA-DRA expression in tumor tissues were associated with poor prognosis based on Cox regression (|Z-score| >1.5) and were used to generate the inflammatory risk score (IRS). IRS was associated with cancer-specific mortality in the training, test (P = 0.01), and validation (P = 0.02) cohorts. This association was strong for stage II cases (P = 0.002). Expression of miR-21 was associated with IL-6, IL-8, IL-10, IL-12a, and NOS2a, providing evidence that the function of this microRNA and these inflammatory genes are linked. Both IRS and miR-21 expression were independently associated with cancer-specific mortality, including stage II patients alone. Conclusion: IRS and miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients. (Clin Cancer Res 2009;15(18):5878–87)
All PUFAs are not created equal: absence of CHD benefit specific to linoleic acid in randomized controlled trials and prospective observational cohorts.

Advice to maintain or increase consumption of the omega-6 polyunsaturated fatty acid (n–6 PUFA) linoleic acid (LA) should be derived from interventional and observational trials evaluating the specific effects of dietary LA, rather than effects of n–3 PUFAs or total PUFAs. Failure to make a clear distinction among PUFA species may result in inadvertently attributing health effects of n–3 PUFAs to linoleic acid. Pooled analyses of randomized controlled trials (RCTs) of clinical CHD events [1] and intermediate risk factors [2] and pooled analyses of nonrandomized prospective observational trials of clinical CHD events [3] are often cited as providing strong concordant evidence [1, 4] that LA is cardioprotective. These pooled analyses [1–3] form the primary basis for recent population-wide advice to maintain or increase n–6 PUFA [5–7]. However, total PUFA rather than n–6 LA, was defined as the independent variable for statistical calculations in all three pooled analyses [1–3] (table 1), then interpreted as attributable to LA [4–8]. In this paper we: (1) establish that a clear distinction was not made between n–3 and n–6 PUFAs in pooled analyses of randomized and nonrandomized trials (tables 2, ​,3),3), (2) report whether a clear distinction was made between n–3 and n–6 PUFAs in each individual trial before pooling, (3) assess strengths and limitations of randomized and nonrandomized study designs for disentangling respective intakes of n–6 and n–3 PUFA species, and (4) highlight the necessity of making a clear distinction between PUFA species for interpreting the results of clinical trials and formulating dietary guidelines. Table 1 Defining the independent variable in pooled analyses cited as concordant evidence for CHD benefits of n–6 PUFAs Table 2 General characteristics of 8 randomized controlled dietary intervention trials that substituted PUFAs for saturated and trans fatty acids Table 3 Characteristics of 11 nonrandomized observational trials that assessed PUFA intake
The evolution of the cancer formulary review in Canada: Can centralization improve the use of economic evaluation?

Summary Public reimbursement of drugs is a costly proposition for health care systems. Decisions to add drugs to the public formulary are often guided by review processes and committees. The evolution of the formulary review process in Canada's publicly funded health system is characterized by increased centralization and systematization. In the past, the review of evidence and recommendation was conducted at the regional level, but was replaced with the pan‐Canadian Oncology Drug Review in 2011. We assess the extent to which centralization and systematization of the review process have responded to past challenges, focusing on the use of economic evaluation in the process. Past challenges with economic evaluation experienced by regionalized review committees were identified from literature and qualitative data collected in the province of Nova Scotia. We categorize these using a typology with a macro‐, meso, and micro‐level hierarchy, which provides a useful framework for understanding at which level change is required, and who has the authority to influence change. Using grounded theory methods, we identify approaches used by Nova Scotia past committee members to compensate for perceived shortcomings of the process. These include an undue reliance on other committee members, on the multidisciplinarity of the committee, and on past decisions. Using a policy analysis approach, we argue that centralization and systematization of the review process only partially address the shortcomings of the previous regionalized process. Lessons from Canada can inform policy discussions across all health systems, where similar challenges with the formulary review process have been identified. © 2016 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.
Transparency for the Public Good: When Feeling Powerful Does and Does Not Affect Willingness to Sacrifice for the Environment

ABSTRACT In two studies, we tested the hypothesis that the effect of feeling powerful on willingness to sacrifice for the preservation of shared resources depends on whether such willingness is expressed publically or privately. Participants were randomly assigned to either a power priming condition or a control condition and then completed measures assessing their attitudes, future intentions, and willingness to sacrifice for environmental conservation. Consistent with our hypothesis, the psychological experience of power decreased people's environmental attitudes and willingness to sacrifice for the environment, but only when these responses were made privately. These findings suggest that a sense of power, when experienced in private, influences the way individuals feel about and intend to engage in pro-environmental sacrifice. The findings also suggest that this effect may be eliminated when judgments are made transparently, in public view.
Summary measure of discrimination in survival models based on cumulative/dynamic time-dependent ROC curves

Assessments of the discriminative performance of prognostic models have led to the development of several measures that extend the concept of discrimination as evaluated by the receiver operating characteristics curve and the area under the receiver operating characteristic curve (AUC) of diagnostic settings. Thus, several time-dependent-receiver operating characteristic curve and AUC(t) have been proposed. One of the most used, the cumulative/dynamic AUCC,D(t) is the probability that, given two randomly chosen patients, one having failed before t and the other having failed after t, the prognostic marker will be correctly ranked. In this paper, we propose a weighted AUCC,D(t) with time- and data-dependent weights as a summary measure of the mean AUCC,D(t), restricted to a finite time range to ensure its clinical relevance. A simulation study shows that estimated restricted mean AUC increased with the strength of association of the covariate with the outcome, with low impact of censoring, and adequate coverage of bootstrap confidence intervals. We illustrate this methodology to two real datasets from two randomized clinical trials to assess the prognostic factors of the overall mortality in patients who have compensated cirrhosis and to assess the prognostic factors of event-free survival in patients who have acute myeloid leukemia.
Oestrogen Receptor α Localisation in the Prefrontal Cortex of Three Mammalian Species

Oestrogen modulates cognitive function and affective behaviours subserved by the prefrontal cortex (PFC). Identifying and localising oestrogen receptor (ER)α, in human PFC will contribute to our understanding of the molecular mechanism of oestrogen action in this region. Inferences about the site of action of oestrogen in human brain are derived largely from studies performed in nonhuman mammalian species; however, the congruence of findings across species has not been demonstrated. Furthermore, the laminar, cellular, and subcellular localisation of ERα in the cortex is debated. Therefore, we compared the distribution of ERα in human dorsolateral prefrontal cortex (DLPFC) with that of monkey DLPFC and rat medial PFC. Immunohistochemistry performed on frontal cortex from the three species demonstrated ERα positive cells throughout all layers of the PFC, in pyramidal and nonpyramidal neurones, with both nuclear and cytoplasmic immunoreactivity. Western blot analyses and preabsorption studies confirmed that the antibody used recognised ERα and not ERβ. A strong ERα immunoreactive band corresponding to the full‐length ERα protein (65–67 kDa) in the frontal cortex of all three species matched the size of the predominant immunoreactive band detected in breast cancer cell lines known to express ERα. Additionally, other ERα immunoreactive proteins of varying molecular weight in breast cancer cells, rat ovary and mammalian brain were detected, suggesting that ERα may exist in more than one form in the mammalian frontal cortex. The present study provides evidence that ERα protein exists in neurones in mammalian PFC and that ERα is anatomically well‐positioned to directly mediate oestrogen action in these neurones.