Ultra-Low-Power Superconductor Logic

We have developed a new superconducting digital technology, Reciprocal Quantum Logic, that uses AC power carried on a transmission line, which also serves as a clock. Using simple experiments we have demonstrated zero static power dissipation, thermally limited dynamic power dissipation, high clock stability, high operating margins and low BER. These features indicate that the technology is scalable to far more complex circuits at a significant level of integration. On the system level, Reciprocal Quantum Logic combines the high speed and low-power signal levels of Single-Flux- Quantum signals with the design methodology of CMOS, including low static power dissipation, low latency combinational logic, and efficient device count.Comment: 7 pages, 5 figure

Adversarial Learning for Feature Shift Detection and Correction

Data shift is a phenomenon present in many real-world applications, and while there are multiple methods attempting to detect shifts, the task of localizing and correcting the features originating such shifts has not been studied in depth. Feature shifts can occur in many datasets, including in multi-sensor data, where some sensors are malfunctioning, or in tabular and structured data, including biomedical, financial, and survey data, where faulty standardization and data processing pipelines can lead to erroneous features. In this work, we explore using the principles of adversarial learning, where the information from several discriminators trained to distinguish between two distributions is used to both detect the corrupted features and fix them in order to remove the distribution shift between datasets. We show that mainstream supervised classifiers, such as random forest or gradient boosting trees, combined with simple iterative heuristics, can localize and correct feature shifts, outperforming current statistical and neural network-based techniques. The code is available at https://github.com/AI-sandbox/DataFix

Deep history of cultural and linguistic evolution among Central African hunter-gatherers

Human evolutionary history in Central Africa reflects a deep history of population connectivity. However, Central African hunter-gatherers (CAHGs) currently speak languages acquired from their neighbouring farmers. Hence it remains unclear which aspects of CAHG cultural diversity results from long-term evolution preceding agriculture and which reflect borrowing from farmers. On the basis of musical instruments, foraging tools, specialized vocabulary and genome-wide data from ten CAHG populations, we reveal evidence of large-scale cultural interconnectivity among CAHGs before and after the Bantu expansion. We also show that the distribution of hunter-gatherer musical instruments correlates with the oldest genomic segments in our sample predating farming. Music-related words are widely shared between western and eastern groups and likely precede the borrowing of Bantu languages. In contrast, subsistence tools are less frequently exchanged and may result from adaptation to local ecologies. We conclude that CAHG material culture and specialized lexicon reflect a long evolutionary history in Central Africa

Analysis and Computational Dissection of Molecular Signature Multiplicity

Molecular signatures are computational or mathematical models created to diagnose disease and other phenotypes and to predict clinical outcomes and response to treatment. It is widely recognized that molecular signatures constitute one of the most important translational and basic science developments enabled by recent high-throughput molecular assays. A perplexing phenomenon that characterizes high-throughput data analysis is the ubiquitous multiplicity of molecular signatures. Multiplicity is a special form of data analysis instability in which different analysis methods used on the same data, or different samples from the same population lead to different but apparently maximally predictive signatures. This phenomenon has far-reaching implications for biological discovery and development of next generation patient diagnostics and personalized treatments. Currently the causes and interpretation of signature multiplicity are unknown, and several, often contradictory, conjectures have been made to explain it. We present a formal characterization of signature multiplicity and a new efficient algorithm that offers theoretical guarantees for extracting the set of maximally predictive and non-redundant signatures independent of distribution. The new algorithm identifies exactly the set of optimal signatures in controlled experiments and yields signatures with significantly better predictivity and reproducibility than previous algorithms in human microarray gene expression datasets. Our results shed light on the causes of signature multiplicity, provide computational tools for studying it empirically and introduce a framework for in silico bioequivalence of this important new class of diagnostic and personalized medicine modalities

Novel Textbook Outcomes following emergency laparotomy:Delphi exercise

Background: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy. Methods: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1–5) of individual outcome measures. There were separate questions for non-trauma and trauma. A patient engagement exercise was undertaken after round 2 to inform the final round. Results: A total of 337 participants from 53 countries participated in all three rounds of the exercise. The final Textbook Outcomes were divided into ‘early’ and ‘longer-term’. For non-trauma patients the proposed early Textbook Outcome was ‘Discharged from hospital without serious postoperative complications (Clavien–Dindo ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation or death). For trauma patients it was ‘Discharged from hospital without unexpected transfusion after haemostasis, and no serious postoperative complications (adapted Clavien–Dindo for trauma ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation on or death)’. The longer-term Textbook Outcome for both non-trauma and trauma was ‘Achieved the early Textbook Outcome, and restoration of baseline quality of life at 1 year’. Conclusion: Early and longer-term Textbook Outcomes have been agreed by an international consensus of experts for non-trauma and trauma emergency laparotomy. These now require clinical validation with patient data.</p

A questionnaire-wide association study of personality and mortality:The Vietnam Experience Study

OBJECTIVE: We examined the association between the Minnesota Multiphasic Personality Inventory (MMPI) and all-cause mortality in 4462 middle-aged Vietnam-era veterans.METHODS: We split the study population into half-samples. In each half, we used proportional hazards (Cox) regression to test the 550 MMPI items' associations with mortality over 15years. In all participants, we subjected significant (p&lt;.01) items in both halves to principal-components analysis (PCA). We used Cox regression to test whether these components predicted mortality when controlling for other predictors (demographics, cognitive ability, health behaviors, and mental/physical health).RESULTS: Eighty-nine items were associated with mortality in both half-samples. PCA revealed Neuroticism/Negative Affectivity, Somatic Complaints, Psychotic/Paranoia, and Antisocial components, and a higher-order component, Personal Disturbance. Individually, Neuroticism/Negative Affectivity (HR=1.55; 95% CI=1.39, 1.72), Somatic Complaints (HR=1.66; 95% CI=1.52, 1.80), Psychotic/Paranoid (HR=1.44; 95% CI=1.32, 1.57), Antisocial (HR=1.79; 95% CI=1.59, 2.01), and Personal Disturbance (HR=1.74; 95% CI=1.58, 1.91) were associated with risk. Including covariates attenuated these associations (28.4 to 54.5%), though they were still significant. After entering Personal Disturbance into models with each component, Neuroticism/Negative Affectivity and Somatic Complaints were significant, although Neuroticism/Negative Affectivity's were now protective (HR=0.73; 95% CI=0.58, 0.92). When the four components were entered together with or without covariates, Somatic Complaints and Antisocial were significant risk factors.CONCLUSIONS: Somatic Complaints and Personal Disturbance are associated with increased mortality risk. Other components' effects varied as a function of variables in the model

Evidence synthesis as the key to more coherent and efficient research

<p>Abstract</p> <p>Background</p> <p>Systematic review and meta-analysis currently underpin much of evidence-based medicine. Such methodologies bring order to <it>previous </it>research, but <it>future </it>research planning remains relatively incoherent and inefficient.</p> <p>Methods</p> <p>To outline a framework for evaluation of health interventions, aimed at increasing coherence and efficiency through i) making better use of information contained within the existing evidence-base when designing future studies; and ii) maximising the information available and thus potentially reducing the need for future studies.</p> <p>Results</p> <p>The framework presented insists that an up-to-date meta-analysis of existing randomised controlled trials (RCTs) should always be considered before future trials are conducted. Such a meta-analysis should inform critical design issues such as sample size determination. The contexts in which the use of individual patient data meta-analysis and mixed treatment comparisons modelling may be beneficial before further RCTs are conducted are considered. Consideration should also be given to how any newly planned RCTs would contribute to the totality of evidence through its incorporation into an updated meta-analysis. We illustrate how new RCTs can have very low power to change inferences of an existing meta-analysis, particularly when between study heterogeneity is taken into consideration.</p> <p>Conclusion</p> <p>While the collation of existing evidence as the basis for clinical practice is now routine, a more coherent and efficient approach to planning future RCTs to strengthen the evidence base needs to be developed. The framework presented is a proposal for how this situation can be improved.</p

Prospective, observational, multicenter study on minimally invasive gastrectomy for gastric cancer: robotic, laparoscopic and open surgery compared on operative and follow-up outcomes - IMIGASTRIC II study protocol: IMIGASTRIC II

Background:Several meta-analyses have tried to defi ne the role of minimally invasive approaches.&nbsp;However, further evidence to get a wider spread of these methods is necessary. Current&nbsp;studies describe minimally invasive surgery as a possible alternative to open surgery&nbsp;but deserving further clarifi cation. However, despite the increasing interest, the&nbsp;difficulty of planning prospective studies of adequate size accounts for the low level of&nbsp;evidence, which is mostly based on retrospective experiences.A multi-institutional prospective study allows the collection of an impressive amount&nbsp;of data to investigate various aspects of minimally invasive procedures with the&nbsp;opportunity of developing several subgroup analyses.A prospective data collection with high methodological quality on minimally invasive&nbsp;and open gastrectomies can clarify the role of diff erent procedures with the aim to&nbsp;develop specifi c guidelines.Methods and analysis:a multi-institutional prospective database will be established including information on&nbsp;surgical, clinical and oncological features of patients treated for gastric cancer with&nbsp;robotic, laparoscopic or open approaches and subsequent follow-up.The study has been shared by the members of the International study group on&nbsp;Minimally Invasive surgery for GASTRIc Cancer (IMIGASTRIC)The database is designed to be an international electronic submission system and a&nbsp;HIPPA protected real time data repository from high volume gastric cancer centers.Ethics:This study is conducted in compliance with ethical principles originating from the&nbsp;Helsinki Declaration, within the guidelines of Good Clinical Practice and relevantlaws/regulations.Trial registration number:NCT0275108

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