In late 2003, Norway passed a law mandating 40% representation of each gender on the board of public limited liability companies. The primary objective of this reform was to increase the ...representation of women in top positions in the corporate sector and decrease the gender disparity in earnings within that sector. We document that the women appointed to these boards post-reform were observably more qualified than their female predecessors along many dimensions, and that the gender gap in earnings within boards fell substantially. However, we see no robust evidence that the reform benefited the larger set of women employed in the companies subject to the quota. Moreover, the reform had no clear impact on highly qualified women whose qualifications mirror those of board members but who were not appointed to boards. Finally, we find mixed support for the view that the reform affected the decisions of young women. While the reform was not accompanied by any change in female enrollment in business education programmes, we do see some improvements in labour market outcomes for young women with graduate business degrees in their early career stages; however, we observe similar improvements for young women with graduate science degrees, suggesting this may not be due to the reform. Overall, seven years after the board quota policy fully came into effect, we conclude that it had very little discernible impact on women in business beyond its direct effect on the women who made it into boardrooms.
Magnetic resonance-guided focused ultrasound in combination with intravenously injected microbubbles has been shown to transiently open the blood-brain barrier, and reduce beta-amyloid and tau ...pathology in animal models of Alzheimer's disease. Here, we used focused ultrasound to open the blood-brain barrier in five patients with early to moderate Alzheimer's disease in a phase I safety trial. In all patients, the blood-brain barrier within the target volume was safely, reversibly, and repeatedly opened. Opening the blood-brain barrier did not result in serious clinical or radiographic adverse events, as well as no clinically significant worsening on cognitive scores at three months compared to baseline. Beta-amyloid levels were measured before treatment using
F-florbetaben PET to confirm amyloid deposition at the target site. Exploratory analysis suggested no group-wise changes in amyloid post-sonication. The results of this safety and feasibility study support the continued investigation of focused ultrasound as a potential novel treatment and delivery strategy for patients with Alzheimer's disease.
MR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous ...system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BBB opening in eloquent primary motor cortex in four volunteers with amyotrophic lateral sclerosis (ALS). Here, we show successful BBB opening using MRgFUS as demonstrated by gadolinium leakage at the target site immediately after sonication in all subjects, which normalized 24 hours later. The procedure was well-tolerated with no serious clinical, radiologic or electroencephalographic adverse events. This study demonstrates that non-invasive BBB permeabilization over the motor cortex using MRgFUS is safe, feasible, and reversible in ALS subjects. In future, MRgFUS can be coupled with promising therapeutics providing a targeted delivery platform in ALS.
Abstract
Small vessel diseases (SVDs) are a group of disorders that result from pathological alteration of the small blood vessels in the brain, including the small arteries, capillaries and veins. ...Of the 35-36 million people that are estimated to suffer from dementia worldwide, up to 65% have an SVD component. Furthermore, SVD causes 20-25% of strokes, worsens outcome after stroke and is a leading cause of disability, cognitive impairment and poor mobility. Yet the underlying cause(s) of SVD are not fully understood. Magnetic resonance imaging has confirmed enlarged perivascular spaces (PVS) as a hallmark feature of SVD. In healthy tissue, these spaces are proposed to form part of a complex brain fluid drainage system which supports interstitial fluid exchange and may also facilitate clearance of waste products from the brain. The pathophysiological signature of PVS and what this infers about their function and interaction with cerebral microcirculation, plus subsequent downstream effects on lesion development in the brain has not been established. Here we discuss the potential of enlarged PVS to be a unique biomarker for SVD and related brain disorders with a vascular component. We propose that widening of PVS suggests presence of peri-vascular cell debris and other waste products that form part of a vicious cycle involving impaired cerebrovascular reactivity, blood-brain barrier dysfunction, perivascular inflammation and ultimately impaired clearance of waste proteins from the interstitial fluid space, leading to accumulation of toxins, hypoxia, and tissue damage. Here, we outline current knowledge, questions and hypotheses regarding understanding the brain fluid dynamics underpinning dementia and stroke through the common denominator of SVD.
Our day-to-day experiences are often similar to one another, occurring in the same place at the same time of day, with common people and objects, and with a shared purpose. Humans have an episodic ...memory to represent unique, personal events that are rich in detail 1. For this to occur, at least two basic neural mechanisms are required: one to orthogonalize or “separate” overlapping input patterns at encoding and another to reinstate or “complete” memories from partial cues at retrieval 2–6. To what extent do these purported “pattern separation” and “pattern completion” mechanisms rely on distinct subfields of the hippocampus 6? Computational models 4–6 and lesion and genetic studies in rodents 7–12 largely point to the dentate gyrus as responsible for pattern separation and the CA3 and CA1 subfields for pattern completion (but see 13–16). In high-resolution fMRI studies of humans, behavioral discrimination and completion tasks designed to approximate pattern separation and pattern completion, respectively, elicit the predicted pattern of activity in the dentate gyrus and CA3/CA1 17–21. Likewise, impaired behavioral discrimination has been demonstrated in individuals with hippocampal lesions 22, 23, but the lesions most likely encompass other subfields. Examination of these processes in individuals with selective lesions to hippocampal subfields is needed to infer causation 19. Here, we report the rare case of BL, a 54-year-old man with bilateral ischemic lesions to the hippocampus 24 primarily affecting the dentate gyrus. Studying BL provides the unique opportunity to directly evaluate theories of hippocampal function that assign the dentate gyrus a specific role in discriminating old from new memories.
•We report the rare case of BL, a memory-impaired man with damage to his hippocampus•BL’s hippocampal lesions primarily affected his dentate gyrus•BL was found to be selectively impaired at discriminating similar items in memory•Findings point to how similar memories are differentiated in the human brain
Baker et al. report the rare case of BL, a man with selective lesions to the dentate gyrus of the hippocampus. Their findings provide the first direct human evidence that the dentate gyrus is needed for discriminating similar memories and that this ability is dissociable from, but most likely interacts with, the ability to complete partial memories.
Aetiological and clinical heterogeneity is increasingly recognized as a common characteristic of Alzheimer's disease and related dementias. This heterogeneity complicates diagnosis, treatment, and ...the design and testing of new drugs. An important line of research is discovery of multimodal biomarkers that will facilitate the targeting of subpopulations with homogeneous pathophysiological signatures. High-throughput 'omics' are unbiased data-driven techniques that probe the complex aetiology of Alzheimer's disease from multiple levels (e.g. network, cellular, and molecular) and thereby account for pathophysiological heterogeneity in clinical populations. This review focuses on data reduction analyses that identify complementary disease-relevant perturbations for three omics techniques: neuroimaging-based subtypes, metabolomics-derived metabolite panels, and genomics-related polygenic risk scores. Neuroimaging can track accrued neurodegeneration and other sources of network impairments, metabolomics provides a global small-molecule snapshot that is sensitive to ongoing pathological processes, and genomics characterizes relatively invariant genetic risk factors representing key pathways associated with Alzheimer's disease. Following this focused review, we present a roadmap for assembling these multiomics measurements into a diagnostic tool highly predictive of individual clinical trajectories, to further the goal of personalized medicine in Alzheimer's disease.
Too young to leave the nest? Black, Sandra E; Devereux, Paul J; Salvanes, Kjell G
The review of economics and statistics,
05/2011, Letnik:
93, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Using Norwegian data, we examine effects of school starting age (SSA). Unlike much recent literature, we can separate SSA from test age effects using scores from IQ tests taken outside school at ...about age 18. We find a small, negative effect of starting school older but much larger positive effects of age at test. Also, starting older leads to lower earnings until about age 30. We find little impact of SSA on educational attainment, but boys who start older are less likely to have poor mental health at age 18. Additionally, starting school older has a negative effect on the probability of teenage pregnancy.
Perivascular spaces include a variety of passageways around arterioles, capillaries and venules in the brain, along which a range of substances can move. Although perivascular spaces were first ...identified over 150 years ago, they have come to prominence recently owing to advances in knowledge of their roles in clearance of interstitial fluid and waste from the brain, particularly during sleep, and in the pathogenesis of small vessel disease, Alzheimer disease and other neurodegenerative and inflammatory disorders. Experimental advances have facilitated in vivo studies of perivascular space function in intact rodent models during wakefulness and sleep, and MRI in humans has enabled perivascular space morphology to be related to cognitive function, vascular risk factors, vascular and neurodegenerative brain lesions, sleep patterns and cerebral haemodynamics. Many questions about perivascular spaces remain, but what is now clear is that normal perivascular space function is important for maintaining brain health. Here, we review perivascular space anatomy, physiology and pathology, particularly as seen with MRI in humans, and consider translation from models to humans to highlight knowns, unknowns, controversies and clinical relevance.
In this study, we explore a new approach for analyzing changes in the gender pay gap that uses direct measures of job tasks and gives a comprehensive characterization of how work for men and women ...has changed in recent decades. Using data from West Germany, we find that women have witnessed relative increases in nonroutine analytic and interactive tasks. The most notable difference between the genders is, however, the pronounced relative decline in routine task inputs among women, driven, at least in part, by technological change. These changes explain a substantial fraction of the closing of the gender wage gap.
Abstract Symmetry is a gait characteristic that is increasingly measured and reported, particularly in the stroke patient population. However, there is no accepted standard for assessing symmetry ...making it difficult to compare across studies and establish criteria to guide clinical decision making. This study compares the most common expressions of spatiotemporal gait symmetry to describe post-stroke gait and makes recommendations regarding the most suitable measure for standardization. The following symmetry equations were compared: symmetry ratio, symmetry index, gait asymmetry and symmetry angle using step length, swing time, stance time, double support time and an intra-limb ratio of swing: stance time. Comparisons were made within a group of 161 community-dwelling, ambulatory individuals with stroke and 81 healthy adults as a reference group. Our analysis supports the recommendations of the symmetry ratio as the equation for standardization and step length, swing time and stance time as the gait parameters to be used in the equation. Future work should focus on establishing the intra-individual variability of these measures and linking them to mechanisms of gait dysfunction.
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