Focusing on hunger strikers, Garasic enumerates a number of compelling arguments to force-feed: possible mental illness and diminished capacity, depression, lack of suicidal intent and an underlying ...desire to live rather than die as well as Kant's dicta to shun suicide and avoid using others as means. Many prison systems permit force-feeding because hunger strikes incite unrest and threaten to break down a carefully crafted institution specifically designed to ensure social order.
The present study evaluates the cost-effectiveness of two follow-up routines: a strict follow-up with frequent visits, imaging, and laboratory examinations was compared to a follow-up with infrequent ...visits that were scheduled mainly on the basis of the patient's symptoms.
A retrospective evaluation was undertaken of 130 patients who underwent a complete resection of non-small cell lung cancer (NSCLC). All patients had complete follow-up for at least 2 years after their operation. The patients were separated into two groups: strict (n = 67), with a routine follow-up policy; and symptom (n = 63), seen on a symptom-oriented basis. The costs of the follow-up routines and the yield of each schedule were compared between the two groups.
There were no significant differences in the disease-free interval until the first detection of recurrence. In most patients, metastatic diseases were diagnosed on the basis of symptoms, rather than by routine tests. The patients who had recurrent cancer diagnosed after surgery had a dismal survival rate irrespective of the follow-up schedule. The majority of patients with recurrence died of malignancy within a 2-year period. The costs of strict vs symptom follow-up were significantly different, because of the greater number of routine imaging procedures performed in patients having strict follow-up. On the other hand, when we analyzed only the frequency of hospitalization and the cost per day of hospital treatment for medical problems other than cancer recurrence, the patients in the strict group had a less expensive follow-up than the patients in the symptom group.
The present study showed that a more cost-effective routine follow-up scheme should be advised for patients with completely resected NSCLC, without affecting overall outcome. Routine imaging follow-up is of questionable value, and it may be indicated only in academic settings.
Objectives: Few studies have examined differences in age of onset of first self-reported instrumental activities of daily living difficulty, much less differences by race. Our objective was to ...determine whether there are differences in the first reported difficulty with IADLs between Black and white older adults. Methods: We analyzed data from N = 1168 participants in the Advanced Cognitive Training in Independent and Vital Elderly (ACTIVE) study. A multiple group discrete-time multiple-event process survival mixture (MEPSUM) model was used to estimate the hazard of incident IADL difficulty in seven IADL task groups. Results: No statistically significant differences were identified in the first reported IADL task group difficulty between Black and white older adults. Discussion: Our findings indicate similar patterns of early IADL difficulty in Black and white older adults, suggesting that previously reported racial disparities in ability to perform IADLs may be attributable to differences in absolute risk, not timing.
The small GTPase KRAS is localized at the plasma membrane where it functions as a molecular switch, coupling extracellular growth factor stimulation to intracellular signaling networks. In this ...process, KRAS recruits effectors, such as RAF kinase, to the plasma membrane where they are activated by a series of complex molecular steps. Defining the membrane-bound state of KRAS is fundamental to understanding the activation of RAF kinase and in evaluating novel therapeutic opportunities for the inhibition of oncogenic KRAS-mediated signaling. We combined multiple biophysical measurements and computational methodologies to generate a consensus model for authentically processed, membrane-anchored KRAS. In contrast to the two membrane-proximal conformations previously reported, we identify a third significantly populated state using a combination of neutron reflectivity, fast photochemical oxidation of proteins (FPOP), and NMR. In this highly populated state, which we refer to as “membrane-distal” and estimate to comprise ∼90% of the ensemble, the G-domain does not directly contact the membrane but is tethered via its C-terminal hypervariable region and carboxymethylated farnesyl moiety, as shown by FPOP. Subsequent interaction of the RAF1 RAS binding domain with KRAS does not significantly change G-domain configurations on the membrane but affects their relative populations. Overall, our results are consistent with a directional flycasting mechanism for KRAS, in which the membrane-distal state of the G-domain can effectively recruit RAF kinase from the cytoplasm for activation at the membrane.
BACKGROUND
We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of ...Dementia for the Longitudinal Aging Study of India (LASI‐DAD).
METHODS
Linear regression was used to assess the association between APOE ε4 and global‐ and domain‐specific cognitive function in 2563 participants (mean age 69.6 ± 7.3 years; 53% female). Effect modification by age, sex, and education were explored using interaction terms and subgroup analyses.
RESULTS
APOE ε4 was inversely associated with most cognitive measures (p < 0.05). This association was stronger with advancing age for the Hindi Mental State Examination (HMSE) score (βε4×age = −0.44, p = 0.03), orientation (βε4×age = −0.07, p = 0.01), and language/fluency (βε4×age = −0.07, p = 0.01), as well as in females for memory (βε4×male = 0.17, p = 0.02) and language/fluency (βε4×male = 0.12, p = 0.03).
DISCUSSION
APOE ε4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals.
Highlights
APOE ε4 carriers had lower global and domain‐specific cognitive performance.
Females and older individuals may be more susceptible to ε4 effects.
For most cognitive measures, there was no interaction between ε4 and education.
This study investigated the acceptability of daily use of free oral pre-exposure prophylaxis (PrEP) and associated factors among transgender women sex workers in Shenyang, China, following a briefing ...on PrEP. A total of 183 HIV negative or sero-status unknown participants completed the cross-sectional survey. The prevalence of acceptability of daily use of free oral PrEP was 61.2%. Adjusting for education level and monthly income, variables on negative attitudes toward PrEP (i.e., having concerns about the side-effects of PrEP) Adjusted odds ratios (AOR): 0.26, perceived subjective norms (i.e., perceiving support from male partners to take PrEP) (AOR: 2.08), and perceived behavioral control (e.g., perceiving complete control over using PrEP) (AOR: 2.10–16.72) were significantly associated with acceptability of daily use of free oral PrEP. In addition, experiencing violence during sex work, perceived risk of contracting HIV from clients and probable anxiety were also significant. Future PrEP promotion campaigns should consider these factors.
•Algorithms had lower sensitivity for classification of incident versus prevalent dementia.•97.5% or lower specificity led to bias towards the null in time-to-event analyses.•Differential performance ...by exposure status can lead to bias in any direction.•Researchers should consider study goals in algorithm development.
Dementia algorithms are often developed in cross-sectional samples but implemented in longitudinal studies to ascertain incident dementia. However, algorithm performance may be higher in cross-sectional settings, and this may impact estimates of risk factor associations.
We used data from the Religious Orders Study and the Memory and Aging Project (N = 3460) to assess the performance of example algorithms in classifying prevalent dementia in cross-sectional samples versus incident dementia in longitudinal samples. We used an applied example and simulation study to characterize the impact of varying sensitivity, specificity, and unequal sensitivity or specificity between exposure groups (differential performance) on estimated hazard ratios from Cox models.
Using all items, algorithm sensitivity was higher for prevalent (0.796) versus incident dementia (0.719); hazard ratios had slight bias. Sensitivity differences were larger using a subset of items (0.732 vs. 0.600) and hazard ratios were 13%–19% higher across adjustment sets compared to estimates using gold-standard dementia status. Simulations indicated specificity and differential algorithmic performance between exposure groups may have large effects on hazard ratios.
Algorithms developed using cross-sectional data may be adequate for longitudinal settings when performance is high and non-differential. Poor specificity or differential performance between exposure groups may lead to biases.
frail older adults may be more vulnerable to stressors, resulting in steeper declines in cognitive function. Whether the frailty-cognition link differs by cognitive domain remains unclear; however, ...it could lend insight into underlying mechanisms.
we tested whether domain-specific cognitive trajectories (clock-drawing test, (CDT), immediate and delayed recall, orientation to date, time, president and vice-president naming) measured annually (2011-2016) differ by baseline frailty (physical frailty phenotype) in the National Health and Aging Trends Study (n = 7,439), a nationally representative sample of older adult U.S. Medicare beneficiaries, using mixed effects models to describe repeated measures of each cognitive outcome. To determine if the association between frailty and subsequent cognitive change differed by education, we tested for interaction using the Wald test.
we observed steeper declines for frail compared to non-frail participants in each domain-specific outcome, except for immediate recall. Largest differences in slope were observed for CDT (difference = -0.12 (standard deviations) SD/year, 95%CI: -0.15, -0.08). By 2016, mean CDT scores for frail participants were 1.8 SD below the mean (95%CI: -1.99, -1.67); for non-frail participants, scores were 0.8 SD below the mean (95%CI: -0.89, -0.69). Associations differed by education for global cognitive function (Pinteraction < 0.001) and for each domain-specific outcome: CDT (Pinteraction < 0.001), orientation (Pinteraction < 0.001), immediate (Pinteraction < 0.001) and delayed (Pinteraction < 0.001) word recalls.
frailty is associated with lower levels and steeper declines in cognitive function, with strongest associations for executive function. These findings suggest that aetiologies are multifactorial, though primarily vascular related; further research into its association with dementia sub-types and related pathologies is critical.
Abstract
Measurement error, although ubiquitous, is uncommonly acknowledged and rarely assessed or corrected in epidemiologic studies. This review offers a straightforward guide to common problems ...caused by measurement error in research studies and a review of several accessible bias-correction methods for epidemiologists and data analysts. Although most correction methods require criterion validation including a gold standard, there are also ways to evaluate the impact of measurement error and potentially correct for it without such data. Technical difficulty ranges from simple algebra to more complex algorithms that require expertise, fine tuning, and computational power. However, at all skill levels, software packages and methods are available and can be used to understand the threat to inferences that arises from imperfect measurements.
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