Multi-input multi-output (MIMO) detection by a colony of ants

The traditional mobile radio channel has always suffered from the detrimental effects of multipath fading. The use of multiple antennae at both ends of the wireless channel has proven to be very effective in combatting fading and enhancing the channel's spectral efficiency. To exploit the benefits offered by Multi-Input Multi-Output (MIMO) systems, both the transmitter and the receiver have to be optimally designed. In this thesis, we are concerned with the problem of receiver design for MIMO systems in a spatial multiplexing scheme. The MIMO detection problem is an NP-hard combinatorial optimization problem. Solving this problem to optimality requires an exponential search over the space of all possible transmitted symbols in order to find the closest point in a Euclidean sense to the received symbols; a procedure that is infeasible for large systems. We introduce a new heuristic algorithm for the detection of a MIMO wireless system based on the Ant Colony Optimization (ACO) metaheuristic. The new algorithm, AntMIMO, has a simple architecture and achieves near maximum likelihood performance in polynomial time

Benzylic Dehydroxylation of Echinocandin antifungal drugs restores efficacy against resistance conferred by mutated Glucan Synthase

Each year, infections caused by fungal pathogens claim the lives of about 1.6 million people and affect the health of over a billion people worldwide. Among the most recently developed antifungal drugs are the echinocandins, which noncompetitively inhibit β-glucan synthase, a membrane-bound protein complex that catalyzes the formation of the main polysaccharide component of the fungal cell wall. Resistance to echinocandins is conferred by mutations in FKS genes, which encode the catalytic subunit of the β-glucan synthase complex. Here, we report that selective removal of the benzylic alcohol of the nonproteinogenic amino acid 3S,4S-dihydroxy-l-homotyrosine of the echinocandins anidulafungin and rezafungin, restored their efficacy against a large panel of echinocandin-resistant Candida strains. The dehydroxylated compounds did not significantly affect the viability of human-derived cell culture lines. An analysis of the efficacy of the dehydroxylated echinocandins against resistant Candida strains, which contain mutations in the FKS1 and/or FKS2 genes of the parental strains, identified amino acids of the Fks proteins that are likely to reside in proximity to the l-homotyrosine residue of the bound drug. This study describes the first example of a chemical modification strategy to restore the efficacy of echinocandin drugs, which have a critical place in the arsenal of antifungal drugs, against resistant fungal pathogens.The authors thank J. Berman and D. Perlin for providing Candida strains. This work was supported by the Israel Science Foundation Grant 179/19 (Micha Fridman). TG acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00 and from the “la Caixa” Foundation under the agreements LCF/PR/GN18/50310010 and LCF/PR/HR21/00737. They also thank E. Ainbinder. O. Singer, and Y. Fried from the Stem Cell Unit of Life Science Core Facilities, the Weizmann Institute of Science. They especially thank H. Barr, head of HTS and Medicinal Chemistry Units at the Maurice and Vivienne Wohl Institute for Drug Discovery, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science.Peer ReviewedPostprint (published version

The recovery ice stream: Synergy of satellite and airborne remote sensing for flow dynamics

The Recovery Ice Stream with its large catchment basin plays an important role in discharging ice from East Antarctica into the Weddell Sea through the Filchner Ice Shelf. Its scientific interest is also linked to the discovery that the ice flow is influenced by the discharge of several subglacial lakes, which could trigger a faster flow due to reduced friction on the glacier bed. We analyzed surface elevations of the Recovery Glacier system in Antarctica derived from time series of TanDEM-X data with focus on location of subglacial lakes. The absolute calibration of the TanDEM-X DEMs was performed using airborne laser altimetry datasets from NASA’s Operation Icebridge ATM and AWI’s Polar 6. In addition the grounding line position for the neighbouring Slessor, Bailey and Recovery glaciers was estimated through DInSAR with TerraSAR-X data acquired in 2014 and 2015

Pseudomonassin, a new bioactive ribosomally synthesised and post-translationally modified peptide from Pseudomonas sp. SST3

Genome mining and metabolomics have become valuable tools in natural products research to evaluate and identify potential new chemistry from bacteria. In the search for new compounds from the deep-sea organism, Pseudomonas sp. SST3, from the South Shetland Trough, Antarctica, a co-cultivation with a second deep-sea Pseudomonas zhaodongensis SST2, was undertaken to isolate pseudomonassin, a ribosomally synthesised and post-translationally modified peptide (RiPP) that belongs to a class of RiPP called lasso peptides. Pseudomonassin was identified using a genome-mining approach and isolated by means of mass spectrometric guided isolation. Extensive metabolomics analysis of the co-cultivation of Pseudomonas sp. SST3 and P. zhaodongensis SST2, Pseudomonas sp. SST3 and Escherichia coli, and P. zhaodongensis SST2 and E. coli were performed using principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA), which revealed potential new metabolites in the outlier regions of the co-cultivation, with other metabolites identified previously from other species of Pseudomonas. The sequence of pseudomonassin was completely deduced using high collision dissociation tandem mass spectrometry (HCD-MS/MS). Preliminary studies on its activity against the pathogenic P. aeruginosa and its biofilm formation have been assessed and produced a minimum inhibitory concentration (MIC) of 63 μg/mL and 28 μg/mL, respectively

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

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Identification of a New Gene in Which Variants Are Responsible for Arthrogryposis Multiplex Congenita

L’arthrogrypose multiple congénitale (AMC) est une maladie rare caractérisée par des rétractions d’au moins deux articulations distinctes présentes à la naissance. L’AMC est génétiquement hétérogène et des variants dans de très nombreux gènes ont été identifiés. Notre projet a eu pour but d’identifier de nouvelles causes génétiques de l’AMC en utilisant le séquençage de l’exome entier (WES).Dans le gène SCN1A, nous avons identifié des variants pathogéniques dominants survenus de novo chez trois patients non apparentés. SCN1A code Nav1.1, un composant des canaux sodiques voltage-dépendants exprimés au niveau de l’AIS (Axon Initial Segment) et des nœuds de Ranvier et contribue à l’initiation et la propagation des potentiels d’action. Nous avons montré que SCN1A est exprimé dans le cerveau et la moelle épinière mais pas dans le muscle à des stades du développement similaires à l’âge de l’apparition de l’AMC et que l’AMC est due à un défaut de SCN1A dans le cortex moteur.Nous montrons pour la première fois que des variants de SCN1A sont responsables d’un déficit moteur sévère provoquant l’AMC, suggérant un rôle critique de SCN1A dans le développement moteur. Ces résultats élargissent le spectre phénotypique de SCN1A allant d’une encéphalopathie épileptique sévère isolée ou associée à un défaut moteur causant l’arthrogrypose (Jaber et al. sous presse). Nos données élargissent ainsi le groupe des AMC liées à une atteinte du système nerveux central et précisément celles causées par des anomalies des canaux ioniques tels que NALCN ou CACNA1E.Arthrogryposis multiplex congenita (AMC) is a rare disease characterized by the presence of multiple joint contractures at birth. AMC includes a large spectrum of diseases which result from variants in genes encoding components required for neuromuscular junctions, skeletal muscle, motor neurons, peripheral nerves or connective tissues. AMC may also result from central nervous involvement. Despite important progress in this field, many AMC patients remain genetically undiagnosed. Our project aimed at identifying novel genes in which variants can cause AMC. We identified pathogenic de novo dominant variants in SCN1A gene in three unrelated patients. SCN1A encodes Nav1.1 voltage-dependent sodium channel, a critical component of axon initial segment and nodes of Ranvier. We showed that SCN1A is expressed in both brain and spinal cord but not in skeletal muscle at a developmental stage similar to that of AMC observation and showed that AMC is caused by brain involvement.We showed that SCN1A variants are responsible for early onset motor defect leading to AMC indicating a critical role of SCN1A in prenatal motor development and broadening the phenotypic spectrum of variants in SCN1A (Jaber et al. in press). Altogether, our data enlarge the group of AMC linked to central nervous system involvement and caused by variants of genes encoding channels such as NALCN or CACNA1E

Geodetic mass balance of the Patagonian Icefields derived from SRTM and TanDEM-X data.

We compare ice elevation from TanDEM-X Raw DEMs of summer 2014 and from the SRTM C-band DEM of summer 2000 over the Northern Patagonian Icefield (NPI) in order to obtain a detailed map of ice elevation change rates over the last 14 years. The geodetic method is used to compute the mass balance for this region and for the nearby Southern Patagonian Icefield (SPI). The method is outlined along with the error budget estimation. The backscattering coefficient of the data is analyzed in order to exclude elevation biases due to signal penetration in snow and firn