14 research outputs found
Questioning Market Aversion in Gender Equality Strategies: Designing Legal Mechanisms for the Promotion of Gender Equality in the Family and the Market
This Article suggests that tax and welfare policies that promote gender equality require creative thinking about the design of social mechanisms for the promotion of women. It offers a framework for expanding the institutional imagination in order to recalibrate welfare state reforms to promote women. In particular, we advocate the creative use of legal tools and doctrine to dismantle existing dichotomies between private and public, understand the various goals different mechanisms can serve and reassemble them to promote different mixes of normative goals. We propose doing so by looking simultaneously at two fields of redistribution: welfare state benefits and services on the one hand and income taxation on the other. These two fields serve similar goals and accordingly, we argue, should be analyzed in light of the same policy considerations and normative underpinnings. Since the goals of these two fields are comparable, the mechanisms that both fields use should also be compatible
Questioning Market Aversion in Gender Equality Strategies: Designing Legal Mechanisms for the Promotion of Gender Equality in the Family and the Market
This Article suggests that tax and welfare policies that promote gender equality require creative thinking about the design of social mechanisms for the promotion of women. It offers a framework for expanding the institutional imagination in order to recalibrate welfare state reforms to promote women. In particular, we advocate the creative use of legal tools and doctrine to dismantle existing dichotomies between private and public, understand the various goals different mechanisms can serve and reassemble them to promote different mixes of normative goals. We propose doing so by looking simultaneously at two fields of redistribution: welfare state benefits and services on the one hand and income taxation on the other. These two fields serve similar goals and accordingly, we argue, should be analyzed in light of the same policy considerations and normative underpinnings. Since the goals of these two fields are comparable, the mechanisms that both fields use should also be compatible
EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy
Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0–49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease
Questioning Market Aversion in Gender Equality Strategies: Designing Legal Mechanisms for the Promotion of Gender Equality in the Family and the Market
This Article suggests that tax and welfare policies that promote gender equality require creative thinking about the design of social mechanisms for the promotion of women. It offers a framework for expanding the institutional imagination in order to recalibrate welfare state reforms to promote women. In particular, we advocate the creative use of legal tools and doctrine to dismantle existing dichotomies between private and public, understand the various goals different mechanisms can serve and reassemble them to promote different mixes of normative goals. We propose doing so by looking simultaneously at two fields of redistribution: welfare state benefits and services on the one hand and income taxation on the other. These two fields serve similar goals and accordingly, we argue, should be analyzed in light of the same policy considerations and normative underpinnings. Since the goals of these two fields are comparable, the mechanisms that both fields use should also be compatible
Hidden Conversations, Missed Opportunities: Can Artificial Intelligence Capture Social Determinants of Health Discussions in Behavioral Health Sessions?
Objective: This study examined how often social determinants of health (SDoH) are discussed in therapy and documented in progress notes.
Materials and Methods: We randomly sampled 100 treatment sessions, provided by 38 mental health experts in 5 U.S. behavioral health programs. Sessions were captured via a specialized artificial intelligence (AI) platform for behavioral health and segmented into 1,762 therapist-client micro-dialogues. Psychologists then labeled the micro-dialogues and reviewed progress notes to identify SDoH-related topics.
Results: SDoH were discussed in 86% of sessions, with the primary topics being economic stability (34.0%) and social and community context (29.1%). However, only 52.3% of progress notes included any mention of SDoH.
Conclusions: Most behavioral therapy sessions involve discussions on SDoH, yet only half are adequately documented in the progress notes. Ambient AI shows promise in enhancing SDoH data capture, potentially advancing mental healthcare and informing health policy decisions
Exploring Alzheimer’s Disease Molecular Variability via Calculation of Personalized Transcriptional Signatures
Despite huge investments and major efforts to develop remedies for Alzheimer’s disease (AD) in the past decades, AD remains incurable. While evidence for molecular and phenotypic variability in AD have been accumulating, AD research still heavily relies on the search for AD-specific genetic/protein biomarkers that are expected to exhibit repetitive patterns throughout all patients. Thus, the classification of AD patients to different categories is expected to set the basis for the development of therapies that will be beneficial for subpopulations of patients. Here we explore the molecular heterogeneity among a large cohort of AD and non-demented brain samples, aiming to address the question whether AD-specific molecular biomarkers can progress our understanding of the disease and advance the development of anti-AD therapeutics. We studied 951 brain samples, obtained from up to 17 brain regions of 85 AD patients and 22 non-demented subjects. Utilizing an information-theoretic approach, we deciphered the brain sample-specific structures of altered transcriptional networks. Our in-depth analysis revealed that 7 subnetworks were repetitive in the 737 diseased and 214 non-demented brain samples. Each sample was characterized by a subset consisting of ~1–3 subnetworks out of 7, generating 52 distinct altered transcriptional signatures that characterized the 951 samples. We show that 30 different altered transcriptional signatures characterized solely AD samples and were not found in any of the non-demented samples. In contrast, the rest of the signatures characterized different subsets of sample types, demonstrating the high molecular variability and complexity of gene expression in AD. Importantly, different AD patients exhibiting similar expression levels of AD biomarkers harbored distinct altered transcriptional networks. Our results emphasize the need to expand the biomarker-based stratification to patient-specific transcriptional signature identification for improved AD diagnosis and for the development of subclass-specific future treatment
Novel Biologically Active Silver-Avidin Hybrids
Coupling of biologically active proteins, for example, enzymes and binding proteins, with metals carries huge potential inherent in the integration of these hybrids with miniaturized electronics, medical devices, and in vivo imaging. Here we propose and demonstrate feasibility of the preparation of novel, biologically active silver-avidin hybrids by electroless silver deposition directed to the surface of single, soluble avidin molecules, with retention of their solubility and highly specific biotin binding capacity. The process is based on conjugation of silver ions reducing polymers to avidin surface, followed by the addition of silver ions under mild physiological conditions. The partially overlapping silver patches thus obtained on the protein’s surface provided soluble, biologically active hybrids, retaining their specific biotin binding capability of both low-molecular-weight and high-molecular-weight biotinylated molecules and exhibiting enhanced thermal stability. The hybrids thus obtained were successfully used for molecular imaging of cancer cells prelabeled with biotinylated monoclonal antibody