'I just need to know what they are and if you can help me': Medicalization and the search for legitimacy in people diagnosed with non-epileptic attack disorder

This paper focuses on the struggles for legitimacy expressed by people with non-epileptic attack disorder (NEAD), one of the most common manifestations of functional neurological disorder presenting to emergency and secondary care services. Nonepileptic attacks are episodes of altered experience, awareness, and reduced self-control that superficially resemble epileptic seizures or other paroxysmal disorders but are not associated with physiological abnormalities sufficient to explain the semiological features. "Organic" or medicalized explanations are frequently sought by patients as the only legitimate explanation for symptoms, and consequently, a diagnosis of NEAD is often contested. Drawing on narrative interviews with patients from a small exploratory study and using a sociological perspective, we propose that a psychological account of NEAD does not provide a sufficiently legitimate path into a socially sanctioned sick role. This is a reflection of the dominance of biomedicine and the associated processes of medicalization. These processes are, we argue, the sole route to achieving legitimacy. The stress-based or psychologically oriented explanations offered to patients in contemporary medical models of the etiology of NEAD engender an uncertain identity and social position and fail to provide many patients with an account of the nature or origin of their symptoms that they find satisfactory or convincing. These struggles for legitimacy (shared by others with functional or somatoform conditions) are sharpened by key features of the contemporary healthcare landscape, such as the increasing framing of health through a lens of 'responsibilization'. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Emerging zoonoses in marine mammals and seabirds of the Northeast U.S.

Author Posting. © IEEE, 2006. Author Posting. © IEEE, 2006. This article is posted here by permission of IEEE for personal use, not for redistribution. The definitive version was published in Proceedings Oceans 2006, Boston, MA, USA, 5 pp, doi:10.1109/OCEANS.2006.306826.In the Northeast United States, marine vertebrates come into contact with each other and with humans through a variety of mechanisms which allow for the transfer of pathogens from one taxa to another. Though there are many ways in which humans come into contact with infectious agents, there is an inadequate understanding of the prevalence of clinical and sub-clinical zoonotic agents in the marine vertebrates of the Northeast United States. We are strengthening our understanding of the issue by targeting marine mammals and seabirds of New England and screening normal and diseased individuals of this ecosystem to establish a baseline prevalence of zoonotic agents in this ecosystem. Samples from stranded, bycaught and wild marine mammals and seabirds have been found to be positive for our screened pathogens. Most notable are the diseases found in bycaught marine mammals as well as wild caught individuals. Our current focus is specifically on influenza A and B, brucellosis, leptospirosis, Giardia and Cryptosporidium. Samples for virology, bacterial screening and molecular screening are being archived and analyzed as practical. Our goal is to create an optimized PCR-based molecular detection protocol for the above agents.This research is supported by NOAA Ocean and Human Health Initiative Grant Number NA05NOS4781247 and NOAA Prescott Grant NA05NMF4391165

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BackgroundThe ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and resultsIn 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.

PurposeThis study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD.ResultsAdverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses).ConclusionsContinuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested

Deconvolving the contributions of cell-type heterogeneity on cortical gene expression

Complexity of cell-type composition has created much skepticism surrounding the interpretation of bulk tissue transcriptomic studies. Recent studies have shown that deconvolution algorithms can be applied to computationally estimate cell-type proportions from gene expression data of bulk blood samples, but their performance when applied to brain tissue is unclear. Here, we have generated an immunohistochemistry (IHC) dataset for five major cell-types from brain tissue of 70 individuals, who also have bulk cortical gene expression data. With the IHC data as the benchmark, this resource enables quantitative assessment of deconvolution algorithms for brain tissue. We apply existing deconvolution algorithms to brain tissue by using marker sets derived from human brain single cell and cell-sorted RNA-seq data. We show that these algorithms can indeed produce informative estimates of constituent cell-type proportions. In fact, neuronal subpopulations can also be estimated from bulk brain tissue samples. Further, we show that including the cell-type proportion estimates as confounding factors is important for reducing false associations between Alzheimer\u27s disease phenotypes and gene expression. Lastly, we demonstrate that using more accurate marker sets can substantially improve statistical power in detecting cell-type specific expression quantitative trait loci (eQTLs)

Application of behavior change techniques in a personalized nutrition Electronic Health intervention study: protocol for the web-based Food4Me randomized controlled trial

Background: In order to determine the efficacy of behavior change techniques (BCT) applied in dietary and physical activity intervention studies, it is first necessary to record and describe techniques which have been used during such interventions. Published frameworks used in dietary and smoking cessation interventions undergo continuous development and most are not adapted for online delivery. The Food4Me study (N=1607) provided the opportunity to use existing frameworks to describe standardized online techniques employed in a large-scale internet-based intervention to change dietary behaviour and physical activity. Objectives: To describe techniques embedded in the Food4Me study design and explain the selection rationale. To demonstrate the use of behaviour change technique taxonomies, develop standard operating procedures for training, and identify strengths and limitations of the Food4Me framework that will inform its use in future studies. Methods: The 6-month randomized controlled trial took place simultaneously in 7 European countries, with participants receiving one of 4 levels of personalized advice (generalized, intake-based, intake+phenotype-based and intake+phenotype+gene-based). A 3-phase approach was taken: (I), existing taxonomies were reviewed and techniques were identified a priori for possible inclusion in the Food4Me study; (II) a standard operating procedure was developed to maintain consistency in the use of methods and techniques across research centers; (III) the Food4Me BCT framework was reviewed and updated post intervention. An analysis of excluded techniques was also conducted. Results: Of 46 techniques identified a priori as being applicable to Food4Me, 17 were embedded in the intervention design. Eleven were from a dietary taxonomy and 6 from a smoking cessation taxonomy. In addition, the 4-category smoking cessation framework structure was adopted for clarity of communication. Smoking cessation texts were adapted for dietary use where necessary. A posteriori, a further 9 techniques were included. Examination of excluded items highlighted the distinction between techniques considered appropriate for face-to-face vs internet-based delivery. Conclusions: The use of existing taxonomies facilitated the description and standardization of techniques used in Food4Me. We recommend that for complex studies of this nature, technique analysis should be conducted a priori to develop standardized procedures and training, and reviewed a posteriori to audit the techniques actually adopted. The present framework description makes a valuable contribution to future systematic reviews and meta-analyses which explore technique efficacy and underlying psychological constructs. This was a novel application of the behavior change taxonomies, and was the first internet-based personalized nutrition intervention to use such a framework remotely

Meat consumption and risk of primary hip and knee joint replacement due to osteoarthritis: a prospective cohort study

Extent: 10p.Background: There is emerging evidence for a beneficial effect of meat consumption on the musculoskeletal system. However, whether it affects the risk of knee and hip osteoarthritis is unknown. We performed a prospective cohort study to examine the relationship between meat consumption and risk of primary hip and knee replacement for osteoarthritis. Methods: Eligible 35,331 participants were selected from the Melbourne Collaborative Cohort Study recruited during 1990-1994. Consumption of fresh red meat, processed meat, chicken, and fish was assessed using a food frequency questionnaire. Primary hip and knee replacement for osteoarthritis during 2001-2005 was determined by linking the cohort records to the Australian National Joint Replacement Registry. Results: There was a negative dose-response relationship between fresh red meat consumption and the risk of hip replacement (hazard ratio (HR) 0.94 per increase in intake of one time/week, 95% confidence interval (CI) 0.89-0.98). In contrast, there was no association with knee replacement risk (HR 0.98, 95% CI 0.94-1.02). Consumption of processed meat, chicken and fish were not associated with risk of hip or knee replacement. Conclusion: A high level consumption of fresh red meat was associated with a decreased risk of hip, but not knee, joint replacement for osteoarthritis. One possible mechanism to explain these differential associations may be via an effect of meat intake on bone strength and hip shape. Further confirmatory studies are warranted.Yuanyuan Wang, Julie Anne Simpson, Anita E Wluka, Dallas R English, Graham G Giles, Stephen Graves, Flavia M Cicuttin

Deficiency in the Multicopy Sycp3-Like X-Linked Genes Slx and Slxl1 Causes Major Defects in Spermatid Differentiation

Slx and Slxl1 are genes present in multiple copies on the mouse X chromosome. Using transgenically-delivered small interfering RNAs to disrupt their function, we show that Slx and Slxl1 are important for normal sperm differentiation and male fertility