BEVContrast: Self-Supervision in BEV Space for Automotive Lidar Point Clouds

We present a surprisingly simple and efficient method for self-supervision of 3D backbone on automotive Lidar point clouds. We design a contrastive loss between features of Lidar scans captured in the same scene. Several such approaches have been proposed in the literature from PointConstrast, which uses a contrast at the level of points, to the state-of-the-art TARL, which uses a contrast at the level of segments, roughly corresponding to objects. While the former enjoys a great simplicity of implementation, it is surpassed by the latter, which however requires a costly pre-processing. In BEVContrast, we define our contrast at the level of 2D cells in the Bird's Eye View plane. Resulting cell-level representations offer a good trade-off between the point-level representations exploited in PointContrast and segment-level representations exploited in TARL: we retain the simplicity of PointContrast (cell representations are cheap to compute) while surpassing the performance of TARL in downstream semantic segmentation.Comment: Accepted to 3DV 202

The Boston criteria version 2.0 for cerebral amyloid angiopathy:a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study

BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. FUNDING: US National Institutes of Health (R01 AG26484)

The future of sensitivity analysis: an essential discipline for systems modeling and policy support

Sensitivity analysis (SA) is en route to becoming an integral part of mathematical modeling. The tremendous potential benefits of SA are, however, yet to be fully realized, both for advancing mechanistic and data-driven modeling of human and natural systems, and in support of decision making. In this perspective paper, a multidisciplinary group of researchers and practitioners revisit the current status of SA, and outline research challenges in regard to both theoretical frameworks and their applications to solve real-world problems. Six areas are discussed that warrant further attention, including (1) structuring and standardizing SA as a discipline, (2) realizing the untapped potential of SA for systems modeling, (3) addressing the computational burden of SA, (4) progressing SA in the context of machine learning, (5) clarifying the relationship and role of SA to uncertainty quantification, and (6) evolving the use of SA in support of decision making. An outlook for the future of SA is provided that underlines how SA must underpin a wide variety of activities to better serve science and society

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Génotoxicité des rayonnements ionisants au cours de l'ovogenèse chez les mammifères

Female fertility depends in part on the number and quality of oocytes. Ionising radiation (IR) has genotoxic effects that can induce cell death. DNA double strand breaks (DSBs) are the most deleterious lesions induced by IR and are dealt with by more or less faithful repair mechanisms such as homologous recombination (HR) or non-homologous end joining (NHEJ). We experimentally investigated radiosensitivity and DSB repair mechanisms in the mouse and human oocyte using in vivo and in vitro models in an integrated perspective. In mouse, oocytes in the ovarian reserve (LD50 8Gy). Radiation-resistant oocytes are able to survive in the long term, can be ovulated and fertilized. Irradiated mice had transient fertility indicating the functionality of the radioresistant oocytes. However, IR exposure alters oocyte quality by increasing the aneuploidy rate in a manner that correlates with increased embryonic lethality. After irradiation, reserve oocytes exclusively use HR with RAD51 loading. In contrast, growing oocytes engage less DNA resection. These use the canonical NHEJ, mandatory for their survival after irradiation. In growing oocytes the presence of 53BP1 is in favour of a non-resecting management of CBDs. The study of mice invalidated for Xlf allowed us to demonstrate the involvement of canonical NHEJ in the radioresistance of growing oocytes in mouse. In human ovaries, using of an organotypic culture system, we showed the higher radioresistance of reserve oocytes compared to mouse ones. The presence of 53BP1 suggests that NHEJ may be involved in this oocyte survival as for growing murine oocytes.Taken together, these data suggest that oocyte quality may be affected after irradiation and that natural conceptions after IR exposure may be at risk of hereditary effects.La fertilité féminine dépend en partie du nombre et de la qualité des ovocytes. Les cassures double brin de l’ADN (CDBs) sont les lésions les plus délétères induites par les rayonnements ionisants (RI). Elles peuvent conduire à la mort cellulaire ou être prises en charge par des mécanismes de réparation plus ou moins fidèles tels que la recombinaison homologue (RH) ou par jonctions des extrémités non homologues (NHEJ). Nous avons étudié expérimentalement la radiosensibilité ovocytaire et les mécanismes de réparation des CDBs chez la Souris et chez la Femme en utilisant des modèles in vivo et in vitro dans une perspective intégrée. Chez la souris, les ovocytes de la réserve ovarienne (DL50 8Gy). Les ovocytes radio-résistants sont capables de survivre à long terme, peuvent être ovulés et fécondés. Les souris irradiées conservent une fertilité transitoire témoignant de la fonctionnalité des ovocytes radio-résistants. Cependant, l’exposition aux RI altère la qualité ovocytaire en augmentant le taux d’aneuploïdie de manière corrélée à une augmentation de la mortalité embryonnaire. Après irradiation, les ovocytes de la réserve s’engagent exclusivement dans la RH avec le chargement de RAD51. Au contraire, les ovocytes entrés en croissance engagent moins la résection. Ces derniers utilisent le NHEJ canonique, nécessaire à leur survie après irradiation. Dans les ovocytes en croissance la présence de 53BP1 est en faveur d’une prise en charge non-résective des CDBs. L’étude de souris invalidées pour Xlf nous a permis de démontrer l’implication du NHEJ canonique dans la radiorésistance des ovocytes en croissance chez la souris. Chez la Femme, l’utilisation d’un système de culture organotypique de fragments ovariens nous a permis de démontrer la plus forte radiorésistance des ovocytes de la réserve comparativement à la souris. La présence de 53BP1 suggère que le NHEJ pourrait être impliqué dans cette survie ovocytaire comme pour les ovocytes murins en croissance. L’ensemble de ces données suggèrent que la qualité ovocytaire peut être affectée après irradiation et que les conceptions naturelles après exposition aux RI pourraient être à risque d’effets héréditaires

Genotoxicity of Ionizing Radiation During Oogenesis in Mammals

La fertilité féminine dépend en partie du nombre et de la qualité des ovocytes. Les cassures double brin de l’ADN (CDBs) sont les lésions les plus délétères induites par les rayonnements ionisants (RI). Elles peuvent conduire à la mort cellulaire ou être prises en charge par des mécanismes de réparation plus ou moins fidèles tels que la recombinaison homologue (RH) ou par jonctions des extrémités non homologues (NHEJ). Nous avons étudié expérimentalement la radiosensibilité ovocytaire et les mécanismes de réparation des CDBs chez la Souris et chez la Femme en utilisant des modèles in vivo et in vitro dans une perspective intégrée. Chez la souris, les ovocytes de la réserve ovarienne (DL50 8Gy). Les ovocytes radio-résistants sont capables de survivre à long terme, peuvent être ovulés et fécondés. Les souris irradiées conservent une fertilité transitoire témoignant de la fonctionnalité des ovocytes radio-résistants. Cependant, l’exposition aux RI altère la qualité ovocytaire en augmentant le taux d’aneuploïdie de manière corrélée à une augmentation de la mortalité embryonnaire. Après irradiation, les ovocytes de la réserve s’engagent exclusivement dans la RH avec le chargement de RAD51. Au contraire, les ovocytes entrés en croissance engagent moins la résection. Ces derniers utilisent le NHEJ canonique, nécessaire à leur survie après irradiation. Dans les ovocytes en croissance la présence de 53BP1 est en faveur d’une prise en charge non-résective des CDBs. L’étude de souris invalidées pour Xlf nous a permis de démontrer l’implication du NHEJ canonique dans la radiorésistance des ovocytes en croissance chez la souris. Chez la Femme, l’utilisation d’un système de culture organotypique de fragments ovariens nous a permis de démontrer la plus forte radiorésistance des ovocytes de la réserve comparativement à la souris. La présence de 53BP1 suggère que le NHEJ pourrait être impliqué dans cette survie ovocytaire comme pour les ovocytes murins en croissance. L’ensemble de ces données suggèrent que la qualité ovocytaire peut être affectée après irradiation et que les conceptions naturelles après exposition aux RI pourraient être à risque d’effets héréditaires.Female fertility depends in part on the number and quality of oocytes. Ionising radiation (IR) has genotoxic effects that can induce cell death. DNA double strand breaks (DSBs) are the most deleterious lesions induced by IR and are dealt with by more or less faithful repair mechanisms such as homologous recombination (HR) or non-homologous end joining (NHEJ). We experimentally investigated radiosensitivity and DSB repair mechanisms in the mouse and human oocyte using in vivo and in vitro models in an integrated perspective. In mouse, oocytes in the ovarian reserve (LD50 8Gy). Radiation-resistant oocytes are able to survive in the long term, can be ovulated and fertilized. Irradiated mice had transient fertility indicating the functionality of the radioresistant oocytes. However, IR exposure alters oocyte quality by increasing the aneuploidy rate in a manner that correlates with increased embryonic lethality. After irradiation, reserve oocytes exclusively use HR with RAD51 loading. In contrast, growing oocytes engage less DNA resection. These use the canonical NHEJ, mandatory for their survival after irradiation. In growing oocytes the presence of 53BP1 is in favour of a non-resecting management of CBDs. The study of mice invalidated for Xlf allowed us to demonstrate the involvement of canonical NHEJ in the radioresistance of growing oocytes in mouse. In human ovaries, using of an organotypic culture system, we showed the higher radioresistance of reserve oocytes compared to mouse ones. The presence of 53BP1 suggests that NHEJ may be involved in this oocyte survival as for growing murine oocytes.Taken together, these data suggest that oocyte quality may be affected after irradiation and that natural conceptions after IR exposure may be at risk of hereditary effects

Génotoxicité des rayonnements ionisants au cours de l'ovogenèse chez les mammifères

Female fertility depends in part on the number and quality of oocytes. Ionising radiation (IR) has genotoxic effects that can induce cell death. DNA double strand breaks (DSBs) are the most deleterious lesions induced by IR and are dealt with by more or less faithful repair mechanisms such as homologous recombination (HR) or non-homologous end joining (NHEJ). We experimentally investigated radiosensitivity and DSB repair mechanisms in the mouse and human oocyte using in vivo and in vitro models in an integrated perspective. In mouse, oocytes in the ovarian reserve (LD50 8Gy). Radiation-resistant oocytes are able to survive in the long term, can be ovulated and fertilized. Irradiated mice had transient fertility indicating the functionality of the radioresistant oocytes. However, IR exposure alters oocyte quality by increasing the aneuploidy rate in a manner that correlates with increased embryonic lethality. After irradiation, reserve oocytes exclusively use HR with RAD51 loading. In contrast, growing oocytes engage less DNA resection. These use the canonical NHEJ, mandatory for their survival after irradiation. In growing oocytes the presence of 53BP1 is in favour of a non-resecting management of CBDs. The study of mice invalidated for Xlf allowed us to demonstrate the involvement of canonical NHEJ in the radioresistance of growing oocytes in mouse. In human ovaries, using of an organotypic culture system, we showed the higher radioresistance of reserve oocytes compared to mouse ones. The presence of 53BP1 suggests that NHEJ may be involved in this oocyte survival as for growing murine oocytes.Taken together, these data suggest that oocyte quality may be affected after irradiation and that natural conceptions after IR exposure may be at risk of hereditary effects.La fertilité féminine dépend en partie du nombre et de la qualité des ovocytes. Les cassures double brin de l’ADN (CDBs) sont les lésions les plus délétères induites par les rayonnements ionisants (RI). Elles peuvent conduire à la mort cellulaire ou être prises en charge par des mécanismes de réparation plus ou moins fidèles tels que la recombinaison homologue (RH) ou par jonctions des extrémités non homologues (NHEJ). Nous avons étudié expérimentalement la radiosensibilité ovocytaire et les mécanismes de réparation des CDBs chez la Souris et chez la Femme en utilisant des modèles in vivo et in vitro dans une perspective intégrée. Chez la souris, les ovocytes de la réserve ovarienne (DL50 8Gy). Les ovocytes radio-résistants sont capables de survivre à long terme, peuvent être ovulés et fécondés. Les souris irradiées conservent une fertilité transitoire témoignant de la fonctionnalité des ovocytes radio-résistants. Cependant, l’exposition aux RI altère la qualité ovocytaire en augmentant le taux d’aneuploïdie de manière corrélée à une augmentation de la mortalité embryonnaire. Après irradiation, les ovocytes de la réserve s’engagent exclusivement dans la RH avec le chargement de RAD51. Au contraire, les ovocytes entrés en croissance engagent moins la résection. Ces derniers utilisent le NHEJ canonique, nécessaire à leur survie après irradiation. Dans les ovocytes en croissance la présence de 53BP1 est en faveur d’une prise en charge non-résective des CDBs. L’étude de souris invalidées pour Xlf nous a permis de démontrer l’implication du NHEJ canonique dans la radiorésistance des ovocytes en croissance chez la souris. Chez la Femme, l’utilisation d’un système de culture organotypique de fragments ovariens nous a permis de démontrer la plus forte radiorésistance des ovocytes de la réserve comparativement à la souris. La présence de 53BP1 suggère que le NHEJ pourrait être impliqué dans cette survie ovocytaire comme pour les ovocytes murins en croissance. L’ensemble de ces données suggèrent que la qualité ovocytaire peut être affectée après irradiation et que les conceptions naturelles après exposition aux RI pourraient être à risque d’effets héréditaires