Introducing Veena Das and her interlocutors on 'Affliction: Health, Disease, Poverty'

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Using Language to Extend to Unseen Domains

It is expensive to collect training data for every possible domain that a vision model may encounter when deployed. We instead consider how simply verbalizing the training domain (e.g. "photos of birds") as well as domains we want to extend to but do not have data for (e.g. "paintings of birds") can improve robustness. Using a multimodal model with a joint image and language embedding space, our method LADS learns a transformation of the image embeddings from the training domain to each unseen test domain, while preserving task relevant information. Without using any images from the unseen test domain, we show that over the extended domain containing both training and unseen test domains, LADS outperforms standard fine-tuning and ensemble approaches over a suite of four benchmarks targeting domain adaptation and dataset bias

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen’s d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions

The effect of three hemostatic agents on early bone healing in an animal model

<p>Abstract</p> <p>Background</p> <p>Resorbable bone hemostasis materials, oxidized regenerated cellulose (ORC) and microfibrillar collagen (MFC), remain at the site of application for up to 8 weeks and may impair osteogenesis. Our experimental study compared the effect of a water-soluble alkylene oxide copolymer (AOC) to ORC and MFC versus no hemostatic material on early bone healing.</p> <p>Methods</p> <p>Two circular 2.7 mm non-critical defects were made in each tibia of 12 rabbits. Sufficient AOC, ORC or MFC was applied to achieve hemostasis, and effectiveness recorded. An autologous blood clot was applied to control defects. Rabbits were sacrificed at 17 days, tibiae excised and fixed. Bone healing was quantitatively measured by micro-computed tomography (micro-CT) expressed as fractional bone volume, and qualitatively assessed by histological examination of decalcified sections.</p> <p>Results</p> <p>Hemostasis was immediate after application of MFC and AOC, after 1-2 minutes with ORC, and >5 minutes for control. At 17 days post-surgery, micro-CT analysis showed near-complete healing in control and AOC groups, partial healing in the ORC group and minimal healing in the MFC group. Fractional bone volume was 8 fold greater in the control and AOC groups than in the MFC group (0.42 ± 0.06, 0.40 ± 0.03 vs 0.05 ± 0.01, <it>P </it>< 0.001) and over 1.5-fold greater than in the ORC group (0.25 ± 0.03, <it>P </it>< 0.05). By histology, MFC remained at the application site with minimal healing at the defect margins and early fibrotic tissue within the defect. ORC-treated defects showed partial healing but with early fibrotic tissue in the marrow space. Conversely, control and AOC-treated defects demonstrated newly formed woven bone rich in cellular activity with no evidence of AOC remaining at the application site.</p> <p>Conclusions</p> <p>Early healing appeared to be impaired by the presence of MFC and impeded by the presence of ORC. In contrast, AOC did not inhibit bone healing and suggest that AOC may be a better bone hemostatic material for procedures where bony fusion is critical and immediate hemostasis required.</p

Correlation-induced insulating topological phases at charge neutrality in twisted bilayer graphene

Twisted bilayer graphene (TBG) provides a unique framework to elucidate the interplay between strong correlations and topological phenomena in two-dimensional systems. The existence of multiple electronic degrees of freedom -- charge, spin, and valley -- gives rise to a plethora of possible ordered states and instabilities. Identifying which of them are realized in the regime of strong correlations is fundamental to shed light on the nature of the superconducting and correlated insulating states observed in the TBG experiments. Here, we use unbiased, sign-problem-free quantum Monte Carlo simulations to solve an effective interacting lattice model for TBG at charge neutrality. Besides the usual cluster Hubbard-like repulsion, this model also contains an assisted hopping interaction that emerges due to the non-trivial topological properties of TBG. Such a non-local interaction fundamentally alters the phase diagram at charge neutrality, gapping the Dirac cones even for infinitesimally small interaction. As the interaction strength increases, a sequence of different correlated insulating phases emerge, including a quantum valley Hall state with topological edge states, an intervalley-coherent insulator, and a valence bond solid. The charge-neutrality correlated insulating phases discovered here provide the sought-after reference states needed for a comprehensive understanding of the insulating states at integer fillings and the proximate superconducting states of TBG.Comment: 15 pages, 9 figures, 2 table

The striatum, the hippocampus, and short-term memory binding : volumetric analysis of the subcortical grey matter's role in mild cognitive impairment

Background: Deficits in short-term memory (STM) binding are a distinguishing feature of preclinical stages leading to Alzheimer’s disease (AD). However, the neuroanatomical correlates of conjunctive STM binding are largely unexplored. Here we examine the possible association between the volumes of hippocampi, parahippocampal gyri, and grey matter within the subcortical structures – all found to have foci that seemingly correlate with basic daily living activities in AD patients - with cognitive tests related to conjunctive STM binding. Materials and methods: Hippocampal, thalamic, parahippocampal and corpus striatum volumes were semi-automatically quantified in brain magnetic resonance images from 25 cognitively normal people and 21 patients with Mild Cognitive Impairment (MCI) at high risk of AD progression, who undertook a battery of cognitive tests and the short-term memory binding test. Associations were assessed using linear regression models and group differences were assessed using the Mann-Whitney U test. Results: Hippocampal and parahippocampal gyrus volumes differed between MCI and control groups. Although the grey matter volume in the globus pallidus (r=-0.71, p<0.001) and parahippocampal gyry (r=-0.63, p<0.05) correlated with a STM binding task in the MCI group, only the former remained associated with STM binding deficits in MCI patients, after correcting for age, gender and years of education (β=-0.56,P=0.042) although with borderline significance. Conclusions: Loss of hippocampal volume plays no role in the processing of STM binding. Structures within the basal ganglia, namely the globus pallidus, could be part of the extrahippocampal network supporting binding. Replication of this study in large samples is now needed

Insights into olive fruit surface functions: a comparison of cuticular composition, water permeability, and surface topography in nine cultivars during maturation

Olive (Olea europaea L.) growing has outstanding economic relevance in Spain, the main olive oil producer and exporter in the world. Fruit skin properties are very relevant for fruit and oil quality, water loss, and susceptibility to mechanical damage, rots, and infestations, but limited research focus has been placed on the cuticle of intact olive fruit. In this work, fruit samples from nine olive cultivars ('Arbequina,' 'Argudell,' 'Empeltre,' 'Farga,' 'Manzanilla,' 'Marfil,' 'Morrut,' 'Picual,' and 'Sevillenca') were harvested from an experimental orchard at three different ripening stages (green, turning, and ripe), and cuticular membranes were enzymatically isolated from fruit skin. The total contents of cuticular wax and cutin significantly differed among cultivars both in absolute and in relative terms. The wax to cutin ratio generally decreased along fruit maturation, with the exception of 'Marfil' and 'Picual.' In contrast, increased water permeance values in ripe fruit were observed uniquely for 'Argudell,' 'Morrut,' and 'Marfil' fruit. The toluidine blue test revealed surface discontinuities on green samples of 'Argudell,' 'Empeltre,' 'Manzanilla,' 'Marfil,' and 'Sevillenca' fruit, but not on 'Arbequina,' 'Farga,' 'Morrut,' or 'Picual.' No apparent relationship was found between water permeability and total wax coverage or the results of the toluidine blue test. The composition of cuticular waxes and cutin monomers was analyzed in detail, and sections of fruit pericarp were stained in Sudan IV for microscopy observations. Skin surface topography was also studied by means of fringe projection, showing large differences in surface roughness among the cultivars, 'Farga' and 'Morrut' fruits displaying the most irregular surfaces. Cultivarrelated differences in cuticle and surface features of fruit are presented and discussed.This work was funded by grant AGL2015-64235-R from the Plan Nacional de I+D, Ministry of Education and Science, Spain. CD is the recipient of a predoctoral scholarship granted by the Universitat de Lleida. PH-L was recipient of a PhD scholarship from Zespri™ International. HH was supported by an Oversea Study Program, Guangzhou Elite Project, China

CD44v6 high membranous expression is a predictive marker of therapy response in gastric cancer patients

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002-2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p < 0.05), particularly those with heterogeneous CD44v6-positive and -negative populations (CD44v6_3+) (p < 0.007 and p < 0.009). Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.This work was funded by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020–Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work was also financed by the projects NORTE-01-0145-FEDER-000003 and NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); project POCI-01-0145-FEDER-016390 and SAICTPAC/0022/2015, funded by ERDF, POCI, and FCT; project PTDC/CTM-NAN/120958/2010, from FCT; and by project PTDC/BTM-TEC/30164/2017 funded by ERDF funds through the COMPETE 2020–POCI, Portugal 2020, and by FCT. Salary support to G.M.A. by PTDC/BTM-TEC/30164/2017 project; C.P. was supported by the grant SFRH/BD/113031/2015 from FCT.info:eu-repo/semantics/publishedVersio

Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer

The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case-control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations