Abstract Lack of sexual interest is the most common sexual complaint among women. However, factors affecting sexual desire in women have rarely been studied. While the role of the brain in ...integrating the sensory, attentional, motivational, and motor aspects of sexual response is commonly acknowledged as important, little is known about specific patterns of brain activation and sexual interest or response, particularly among women. We compared 20 females with no history of sexual dysfunction (NHSD) to 16 women with hypoactive sexual desire disorder (HSDD) in a functional magnetic resonance imaging (fMRI) study that included assessment of subjective sexual arousal, peripheral sexual response using a vaginal photoplethysmograph (VPP), as well as brain activation across three time points. Video stimuli included erotic, sports, and relaxing segments. Subjective arousal to erotic stimuli was significantly greater in NHSD participants compared with HSDD. In the erotic–sports contrast, NHSD women showed significantly greater activation in the bilateral entorhinal cortex than HSDD women. In the same contrast, HSDD females demonstrated higher activation than NHSD females in the medial frontal gyrus (Brodmann area (BA) 10), right inferior frontal gyrus (BA 47) and bilateral putamen. There were no between group differences in VPP-correlated brain activation and peripheral sexual response was not significantly associated with either subjective sexual response or brain activation patterns. Findings were consistent across the three experimental sessions. The results suggest differences between women with NHSD and HSDD in encoding arousing stimuli, retrieval of past erotic experiences, or both. The findings of greater activation in BA 10 and BA 47 among women with HSDD suggest that this group allocated significantly more attention to monitoring and/or evaluating their responses than NHSD participants, which may interfere with normal sexual response.
In this study the use of functional MRI (fMRI) for measuring language lateralization non-invasively was examined. The subjects were seven patients with histories of temporal lobe epilepsy who had ...undergone Wada testing for pre-surgical evaluation. Four patients were left-hemisphere-dominant and three were right-hemisphere-dominant for language. They received fMRI scans while they made semantic or perceptual judgments about visually presented words. Regions of the inferior frontal gyrus (pars triangularis and pars orbitalis) and neighbouring orbital cortex, corresponding to portions of Brodmann areas 45, 46 and 47, exhibited significant increases in activation during semantic relative to perceptual judgments. Lateralization of the increases in activation were consistent with the Wada test assessments of hemispheric language dominance in each of the seven patients. These results suggest that, in addition to providing a tool for investigating human cognitive processes, fMRI has significant clinical potential as a non-invasive measure of language lateralization.
Consistent evidence-practice gaps in osteoarthritis (OA) care are observed in primary care settings globally. Building workforce capacity to deliver high-value care requires a contemporary ...understanding of barriers to care delivery. We aimed to explore barriers to OA care delivery among clinicians and students.
A cross-sectional, multinational study sampling clinicians (physiotherapists, primary care nurses, general practitioners (GPs), GP registrars; total possible denominator: n = 119,735) and final-year physiotherapy and medical students (denominator: n = 2,215) across Australia, New Zealand and Canada. Respondents answered a survey, aligned to contemporary implementation science domains, which measured barriers to OA care using categorical and free-text responses.
1886 clinicians and 1611 students responded. Items within the domains ‘health system’ and ‘patient-related factors’ represented the most applicable barriers experienced by clinicians (25–42% and 20–36%, respectively), whereas for students, ‘knowledge and skills’ and ‘patient-related factors’ (16–24% and 19–28%, respectively) were the most applicable domains. Meta-synthesis of qualitative data highlighted skills gaps in specific components of OA care (tailoring exercise, nutritional/overweight management and supporting positive behaviour change); assessment, measurement and monitoring; tailoring care; managing case complexity; and translating knowledge to practice (especially among students). Other barriers included general infrastructure limitations (particularly related to community facilities); patient-related factors (e.g., beliefs and compliance); workforce-related factors such as inconsistent care and a general knowledge gap in high-value care; and system and service-level factors relating to financing and time pressures, respectively.
Clinicians and students encounter barriers to delivery of high-value OA care in clinical practice/training (micro-level); within service environments (meso-level); and within the health system (macro-level).
Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific ...brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.
To describe the occurrence of fatigue in a large sample of breast cancer survivors relative to general population norms and to identify demographic, medical, and psychosocial characteristics of ...fatigued survivors.
Breast cancer survivors in two large metropolitan areas completed standardized questionnaires as part of a survey study, including the RAND 36-item Health Survey, Center for Epidemiological Studies-Depression Scale, Breast Cancer Prevention Trial Symptom Checklist, Medical Outcomes Study Sleep Scale, and demographic and treatment-related measures.
On average, the level of fatigue reported by the breast cancer survivors surveyed (N = 1,957) was comparable to that of age-matched women in the general population, although the breast cancer survivors were somewhat more fatigued than a more demographically similar reference group. Approximately one third of the breast cancer survivors assessed reported more severe fatigue, which was associated with significantly higher levels of depression, pain, and sleep disturbance. In addition, fatigued women were more bothered by menopausal symptoms and were somewhat more likely to have received chemotherapy (with or without radiation therapy) than nonfatigued women. In multivariate analyses, depression and pain emerged as the strongest predictors of fatigue.
Although the majority of breast cancer survivors in this large and diverse sample did not experience heightened levels of fatigue relative to women in the general population, there was a subgroup of survivors who did report more severe and persistent fatigue. We identified characteristics of these women that may be helpful in elucidating the mechanisms underlying fatigue in this population, as well as directing intervention efforts.
Congenital heart disease (CHD) is present in 1% of live births, yet identification of causal mutations remains challenging. We hypothesized that genetic determinants for CHDs may lie in the protein ...interactomes of transcription factors whose mutations cause CHDs. Defining the interactomes of two transcription factors haplo-insufficient in CHD, GATA4 and TBX5, within human cardiac progenitors, and integrating the results with nearly 9,000 exomes from proband-parent trios revealed an enrichment of de novo missense variants associated with CHD within the interactomes. Scoring variants of interactome members based on residue, gene, and proband features identified likely CHD-causing genes, including the epigenetic reader GLYR1. GLYR1 and GATA4 widely co-occupied and co-activated cardiac developmental genes, and the identified GLYR1 missense variant disrupted interaction with GATA4, impairing in vitro and in vivo function in mice. This integrative proteomic and genetic approach provides a framework for prioritizing and interrogating genetic variants in heart disease.
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•GATA4:TBX5 interactome in CPs is enriched in de novo variants associated with CHD•A method for scoring interactome variants identified GLYR1 as a candidate CHD gene•GLYR1 and GATA4 widely co-occupied and co-activated cardiac developmental genes•The GLYR1 CHD variant disrupted interaction with GATA4 and impaired cardiogenesis
The integration of human protein-protein interactome networks of endogenous transcription factors known to be involved in cardiac malformations with the largest whole-exome-sequencing dataset of trios with congenital heart disease identified an enrichment of rare de novo variants among interactome proteins, pointing to candidate disease genes.
Abstract
A robust pipeline of floating wind energy has emerged with a general trend of projects becoming larger, further from shore, and placed in increasingly energetic seas. The installation ...process for these farms involves the pre-assembly of components onshore or in sheltered waters before towing the platform to the operational location using tugs. It can be expected that such marine operations will be repeated in reverse at the time of decommissioning. The cost and safety of these operations will be influenced by the tugs used, towing speed, the local metocean conditions, the platform/turbine characteristics and other factors. This paper investigates the hydrodynamic characteristics of a large semi-submersible floating offshore wind turbine (FOWT) under tow. The motions of the FOWT are analysed using a numerical tool and validated using a towing test. A framework is proposed for the assessment of FOWT towing operations. Various limiting factors have been identified and the hydrodynamic performance of the system has been evaluated using the framework.
The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and ...cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal.
There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients.
This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (< or = 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients.
The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.
The identification of specialized, functional regions of the human cortex is a vital precondition for neuroscience and clinical neurosurgery. Functional imaging modalities are used for their ...delineation in living subjects, but these methods rely on subject cooperation, and many regions of the human brain cannot be activated specifically.
Diffusion tractography is a novel tool to identify such areas in the human brain, utilizing underlying white matter pathways to separate regions of differing specialization. We explore the reproducibility, generalizability and validity of diffusion tractography-based localization in four functional areas across subjects, timepoints and scanners, and validate findings against fMRI and post-mortem cytoarchitectonic data. With reproducibility across modalities, clustering methods, scanners, timepoints, and subjects in the order of 80–90%, we conclude that diffusion tractography represents a useful and objective tool for parcellation of the human cortex into functional regions, enabling studies into individual functional anatomy even when there are no specific activation paradigms available.
Recently, multiparticle-correlation measurements of relativistic p/d/^{3}He+Au, p+Pb, and even p+p collisions show surprising collective signatures. Here, we present beam-energy-scan measurements of ...two-, four-, and six-particle angular correlations in d+Au collisions at sqrts_{NN}=200, 62.4, 39, and 19.6 GeV. We also present measurements of two- and four-particle angular correlations in p+Au collisions at sqrts_{NN}=200 GeV. We find the four-particle cumulant to be real valued for d+Au collisions at all four energies. We also find that the four-particle cumulant in p+Au has the opposite sign as that in d+Au. Further, we find that the six-particle cumulant agrees with the four-particle cumulant in d+Au collisions at 200 GeV, indicating that nonflow effects are subdominant. These observations provide strong evidence that the correlations originate from the initial geometric configuration, which is then translated into the momentum distribution for all particles, commonly referred to as collectivity.
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