Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Publisher Copyright: © 2023, The Author(s).Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.Peer reviewe

Quality criteria for qualitative inquiries in logistics

This paper confronts the traditional way of judging logistics research that is based on concepts such as validity and reliability. It does so by drawing attention to parallel criteria from interpretivist research approaches, including credibility, transferability, dependability and confirmability. The aim is not to replace traditional criteria, but to present these alternative views relating to research quality and to reflect on the resulting criteria’s possible role in logistics. A basic assumption of this paper is the recognition of several trends in the logistics discipline that indicate a departure from the traditional positivistic paradigm towards multi-paradigmatic research efforts. These include the use of a variety of qualitative and quantitative research methods. It is suggested that researchers in logistics, when dealing with certain ‘soft’ issues of logistics, should consider and benefit from these alternative criteria

Leiðir til „hámörkunar“: Daóísku wuwei og sálrænu flæði teflt saman

Á okkar tímum höfum við náð þvílíkum framförum á sviðum tækni og vísinda og við höfum aukið lífsgæði okkar til muna, sérstaklega á ákveðnum svæðum veraldar. Með aukinni hnattvæðingu höfum við tengst hvort öðru á hátt sem okkur gat einungis dreymt um áður. Samskipti heimshorna á milli eru eins einföld og að opna símann okkar og höfum við getað lært af menningu annarra í heiminum. En á kostnað hvers? Með tækninni höfum við brúað bilið til staða sem áður voru fjarlægir en um leið fjarlægst náttúruna sem umlykur okkur hér og nú. Þrátt fyrir allar þessar tækniframfarir stöndum við frammi fyrir vandamálum sem aldrei hafa verið alvarlegri og má hugsanlega einmitt rekja til þessara framfara. Misskipting auðæfa hefur aldrei verið meiri og loftslagsbreytingar af mannavöldum ógna tilveru okkur á þessari plánetu. Hefur markmiðsrökvísi og einstaklingshyggja blindað sýn okkar? Erum við of upptekin af sjálfum okkur að við sjáum ekki stóru myndina? Hvernig færum við athygli okkar að því sem skiptir raunverulega máli? Hvernig ,,hámörkum“ við færni okkar og okkur sem manneskjur? Í þessari ritgerð ætla ég að líta á tvö hugtök sem reyna að svara því og bera þau saman. Ég mun skoða hvort það sé grundvallarmunur á vestrænni og austrænni hugsun þegar kemur að ,,hámörkun“ í sögulegu samhengi og hvað við vestrænir íbúar getum lært af daóisma

Organising Sustainability Competencies through Quality Management: Integration or Specialisation

A significant step in integrating environmental sustainability into daily operations is through product development. One way to achieve such integration of environmental considerations into product development is by relating sustainability competencies to practices of Quality Management. However, practices seem to vary for how competencies within environmental sustainability are organised in order to make sustainability more actionable. This study explores two ways of organising sustainability competencies in product development: integration and specialisation. The organisation of sustainability competency is illustrated through two cases; one case in which sustainability is integrated with the quality management competency, and the other in which a new competency focusing on sustainability has been added as a separate function in product development. It is suggested that the organisation of sustainability competency influences the extent of environmental impact. Further, trade-offs, such as material source versus weight may not be exploited when sustainability is integrated as one area of responsibility for another specialty competency, suggesting a lack of sufficient competency within environmental sustainability to recognise potential trade-offs between—for example—quality and environmental impact

Incorporating impoverished communities in sustainable supply chains

Purpose The purpose of this paper is to explore recent calls to include social and environmental considerations in supply chains by analyzing the sourcing of raw materials from impoverished communities to reduce environmental impacts and social exclusion in biofuels production. Design/methodology/approach A case study methodology based on interviews and focus groups with supply chain members and other stakeholders is conducted in Brazil, a major biofuels producer and user. Two supply chain cases, fuel ethanol and biodiesel, illustrate the challenges of recent government policies and industry attempts to improve sustainability within the supply chain. Findings Although government and industry recognize the importance of providing opportunities for impoverished communities in biofuels supply chains, there remain considerable pressures to economize at the expense of sustainable supply chain policies. Sourcing from impoverished farmers who lack basic business knowledge, and distrust industry and government policy, compound these challenges. Research limitations/implications While sustainability research now emphasizes the importance of considering interactions among economic, environmental, and social parameters, little is known about integrating poorly educated, impoverished farmers within supply chains. Basic business education is needed, and further research should explore entrepreneurial dynamics within impoverished communities. Practical implications Supply chain managers should acquire skills for engaging with impoverished farmers lacking formal education. Cooperatives can bridge knowledge asymmetries between buyers and suppliers, but will require support from industry if sustainable supply chain policies are to succeed. Originality/value Most sustainable supply chain scholars acknowledge the importance providing opportunities for impoverished communities, but few have explored how potential entrepreneurs from impoverished communities can participate as productive supply chain members