Holmes Tremor due to Artery of Percheron Infarct: Clinical Case and Treatment Using Deep Brain Stimulation of the Vim and ZI Targets

Background: Holmes tremor (HT) arises from disruption of the cerebellothalamocortical pathways. A lesion can interrupt the projection at any point, resulting in this tremor. We describe a case of HT due to the rare artery of Percheron infarct and its successful treatment using deep brain stimulation. Case report: A 62-year-old woman with a right medial cerebral peduncle and bilateral thalamic stroke developed HT. Ventral intermediate nucleus (Vim) zona incerta (ZI) deep brain stimulation (DBS) surgery was performed, with improvement in her tremor. Discussion: Our case supports the theory that the more caudal ZI target in combination with Vim is beneficial in treating poorly DBS-responsive tremors such as HT

Collisional Stripping and Disruption of Super-Earths

The final stage of planet formation is dominated by collisions between planetary embryos. The dynamics of this stage determine the orbital configuration and the mass and composition of planets in the system. In the solar system, late giant impacts have been proposed for Mercury, Earth, Mars, and Pluto. In the case of Mercury, this giant impact may have significantly altered the bulk composition of the planet. Here we present the results of smoothed particle hydrodynamics simulations of high-velocity (up to ~5 v_esc) collisions between 1 and 10 M_Earth planets of initially terrestrial composition to investigate the end stages of formation of extrasolar super-Earths. As found in previous simulations of collisions between smaller bodies, when collision energies exceed simple merging, giant impacts are divided into two regimes: (1) disruption and (2) hit-and-run (a grazing inelastic collision and projectile escape). Disruption occurs when the impact parameter is near zero, when the projectile mass is small compared to the target, or at extremely high velocities. In the disruption regime, we derive the criteria for catastrophic disruption (when half the total colliding mass is lost), the transition energy between accretion and erosion, and a scaling law for the change in bulk composition (iron-to-silicate ratio) resulting from collisional stripping of a mantle.Comment: 10 pages, 1 table, 4 figures. Accepted for publication in ApJ Letter

Are affective factors related to individual differences in facial expression recognition?: Affective factors and facial expressions

Evidence that affective factors (e.g. anxiety, depression, affect) are significantly related to individual differences in emotion recognition is mixed. Palermo et al. (Palermo et al. 2018 J. Exp. Psychol. Hum. Percept. Perform.44, 503–517) reported that individuals who scored lower in anxiety performed significantly better on two measures of facial-expression recognition (emotion-matching and emotion-labelling tasks), but not a third measure (the multimodal emotion recognition test). By contrast, facial-expression recognition was not significantly correlated with measures of depression, positive or negative affect, empathy, or autistic-like traits. Because the range of affective factors considered in this study and its use of multiple expression-recognition tasks mean that it is a relatively comprehensive investigation of the role of affective factors in facial expression recognition, we carried out a direct replication. In common with Palermo et al. (Palermo et al. 2018 J. Exp. Psychol. Hum. Percept. Perform.44, 503–517), scores on the DASS anxiety subscale negatively predicted performance on the emotion recognition tasks across multiple analyses, although these correlations were only consistently significant for performance on the emotion-labelling task. However, and by contrast with Palermo et al. (Palermo et al. 2018 J. Exp. Psychol. Hum. Percept. Perform.44, 503–517), other affective factors (e.g. those related to empathy) often also significantly predicted emotion-recognition performance. Collectively, these results support the proposal that affective factors predict individual differences in emotion recognition, but that these correlations are not necessarily specific to measures of general anxiety, such as the DASS anxiety subscale

POTs: Protective Optimization Technologies

Algorithmic fairness aims to address the economic, moral, social, and political impact that digital systems have on populations through solutions that can be applied by service providers. Fairness frameworks do so, in part, by mapping these problems to a narrow definition and assuming the service providers can be trusted to deploy countermeasures. Not surprisingly, these decisions limit fairness frameworks' ability to capture a variety of harms caused by systems. We characterize fairness limitations using concepts from requirements engineering and from social sciences. We show that the focus on algorithms' inputs and outputs misses harms that arise from systems interacting with the world; that the focus on bias and discrimination omits broader harms on populations and their environments; and that relying on service providers excludes scenarios where they are not cooperative or intentionally adversarial. We propose Protective Optimization Technologies (POTs). POTs provide means for affected parties to address the negative impacts of systems in the environment, expanding avenues for political contestation. POTs intervene from outside the system, do not require service providers to cooperate, and can serve to correct, shift, or expose harms that systems impose on populations and their environments. We illustrate the potential and limitations of POTs in two case studies: countering road congestion caused by traffic-beating applications, and recalibrating credit scoring for loan applicants.Comment: Appears in Conference on Fairness, Accountability, and Transparency (FAT* 2020). Bogdan Kulynych and Rebekah Overdorf contributed equally to this work. Version v1/v2 by Seda G\"urses, Rebekah Overdorf, and Ero Balsa was presented at HotPETS 2018 and at PiMLAI 201

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Methotrexate Is a JAK/STAT Pathway Inhibitor

Background: The JAK/STAT pathway transduces signals from multiple cytokines and controls haematopoiesis, immunity and inflammation. In addition, pathological activation is seen in multiple malignancies including the myeloproliferative neoplasms (MPNs). Given this, drug development efforts have targeted the pathway with JAK inhibitors such as ruxolitinib. Although effective, high costs and side effects have limited its adoption. Thus, a need for effective low cost treatments remains. Methods & Findings: We used the low-complexity Drosophila melanogaster pathway to screen for small molecules that modulate JAK/STAT signalling. This screen identified methotrexate and the closely related aminopterin as potent suppressors of STAT activation. We show that methotrexate suppresses human JAK/STAT signalling without affecting other phosphorylation-dependent pathways. Furthermore, methotrexate significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F, a mutation associated with most human MPNs. Methotrexate acts independently of dihydrofolate reductase (DHFR) and is comparable to the JAK1/2 inhibitor ruxolitinib. However, cells treated with methotrexate still retain their ability to respond to physiological levels of the ligand erythropoietin. Conclusions: Aminopterin and methotrexate represent the first chemotherapy agents developed and act as competitive inhibitors of DHFR. Methotrexate is also widely used at low doses to treat inflammatory and immune-mediated conditions including rheumatoid arthritis. In this low-dose regime, folate supplements are given to mitigate side effects by bypassing the biochemical requirement for DHFR. Although independent of DHFR, the mechanism-of-action underlying the low-dose effects of methotrexate is unknown. Given that multiple pro-inflammatory cytokines signal through the pathway, we suggest that suppression of the JAK/STAT pathway is likely to be the principal anti-inflammatory and immunosuppressive mechanism-of-action of low-dose methotrexate. In addition, we suggest that patients with JAK/STAT-associated haematological malignancies may benefit from low-dose methotrexate treatments. While the JAK1/2 inhibitor ruxolitinib is effective, a £43,200 annual cost precludes widespread adoption. With an annual methotrexate cost of around £32, our findings represent an important development with significant future potential

Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response

<p>Abstract</p> <p>Background</p> <p>Despite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes.</p> <p>Results</p> <p>Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals.</p> <p>Conclusion</p> <p>These changes in permeability, apoptosis, and gene expression provide further evidence of progressive retinal malfunction with increasing duration of diabetes. The specific gene expression changes confirmed in multiple sets of animals indicate that pro-inflammatory, anti-vascular barrier, and neurodegenerative changes occur in tandem with functional increases in apoptosis and vascular permeability. These responses are shared with the clinically documented inflammatory response in diabetic retinopathy suggesting that this model may be used to test anti-inflammatory therapeutics.</p

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

To compare the prevalence of cognitive, neurological, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm (EP)

Measurement of the inclusive isolated-photon cross section in pp collisions at √s = 13 TeV using 36 fb−1 of ATLAS data

The differential cross section for isolated-photon production in pp collisions is measured at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC using an integrated luminosity of 36.1 fb. The differential cross section is presented as a function of the photon transverse energy in different regions of photon pseudorapidity. The differential cross section as a function of the absolute value of the photon pseudorapidity is also presented in different regions of photon transverse energy. Next-to-leading-order QCD calculations from Jetphox and Sherpa as well as next-to-next-to-leading-order QCD calculations from Nnlojet are compared with the measurement, using several parameterisations of the proton parton distribution functions. The predictions provide a good description of the data within the experimental and theoretical uncertainties. [Figure not available: see fulltext.

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council