12 research outputs found
Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment.
Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities
The ethics of entrepreneurial philanthropy
A salient if under researched feature of the new age of global inequalities is the rise to prominence of entrepreneurial philanthropy, the pursuit of transformational social goals through philanthropic investment in projects animated by entrepreneurial principles. Super-wealthy entrepreneurs in this way extend their suzerainty from the domain of the economic to the domains of the social and political. We explore the ethics and ethical implications of entrepreneurialphilanthropy through systematic comparison with what we call customaryphilanthropy, which preferences support for established institutions and social practices. We analyse the ethical statements made at interview by 24 elite UK philanthropists, 12 customary and 12 entrepreneurial, to reveal the co-existence of two ethically charged narratives of elite philanthropic motivations, each instrumental in maintaining the established socio-economic order. We conclude that entrepreneurial philanthropy, as an ostensibly efficacious instrument of social justice, is ethically flawed by its unremitting impulse toward ideological purity
Age and date for early arrival of the Acheulian in Europe (Barranc de la Boella, la Canonja, Spain)
The first arrivals of hominin populations into Eurasia during the Early Pleistocene are currently considered to have occurred
as short and poorly dated biological dispersions. Questions as to the tempo and mode of these early prehistoric settlements
have given rise to debates concerning the taxonomic significance of the lithic assemblages, as trace fossils, and the
geographical distribution of the technological traditions found in the Lower Palaeolithic record. Here, we report on the
Barranc de la Boella site which has yielded a lithic assemblage dating to ,1 million years ago that includes large cutting
tools (LCT). We argue that distinct technological traditions coexisted in the Iberian archaeological repertoires of the late
Early Pleistocene age in a similar way to the earliest sub-Saharan African artefact assemblages. These differences between
stone tool assemblages may be attributed to the different chronologies of hominin dispersal events. The archaeological
record of Barranc de la Boella completes the geographical distribution of LCT assemblages across southern Eurasia during
the EMPT (Early-Middle Pleistocene Transition, circa 942 to 641 kyr). Up to now, chronology of the earliest European LCT
assemblages is based on the abundant Palaeolithic record found in terrace river sequences which have been dated to the
end of the EMPT and later. However, the findings at Barranc de la Boella suggest that early LCT lithic assemblages appeared
in the SW of Europe during earlier hominin dispersal episodes before the definitive colonization of temperate Eurasia took
place.The research at Barranc de la Boella has been carried out with the financial support of the Spanish Ministerio de Economı´a y Competitividad (CGL2012-
36682; CGL2012-38358, CGL2012-38434-C03-03 and CGL2010-15326; MICINN project HAR2009-7223/HIST), Generalitat de Catalunya, AGAUR agence (projects
2014SGR-901; 2014SGR-899; 2009SGR-324, 2009PBR-0033 and 2009SGR-188) and Junta de Castilla y Leo´n BU1004A09. Financial support for Barranc de la Boella
field work and archaeological excavations is provided by the Ajuntament de la Canonja and Departament de Cultura (Servei d’Arqueologia i Paleontologia) de la
Generalitat de Catalunya. A. Carrancho’s research was funded by the International Excellence Programme, Reinforcement subprogramme of the Spanish Ministry
of Education. I. Lozano-Ferna´ndez acknowledges the pre-doctoral grant from the Fundacio´n Atapuerca. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript