François Bachoc, José Betancourt, Reinhard Furrer, Thierry Klein.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1962--2008.

Abstract:
The asymptotic analysis of covariance parameter estimation of Gaussian processes has been subject to intensive investigation. However, this asymptotic analysis is very scarce for non-Gaussian processes. In this paper, we study a class of non-Gaussian processes obtained by regular non-linear transformations of Gaussian processes. We provide the increasing-domain asymptotic properties of the (Gaussian) maximum likelihood and cross validation estimators of the covariance parameters of a non-Gaussian process of this class. We show that these estimators are consistent and asymptotically normal, although they are defined as if the process was Gaussian. They do not need to model or estimate the non-linear transformation. Our results can thus be interpreted as a robustness of (Gaussian) maximum likelihood and cross validation towards non-Gaussianity. Our proofs rely on two technical results that are of independent interest for the increasing-domain asymptotic literature of spatial processes. First, we show that, under mild assumptions, coefficients of inverses of large covariance matrices decay at an inverse polynomial rate as a function of the corresponding observation location distances. Second, we provide a general central limit theorem for quadratic forms obtained from transformed Gaussian processes. Finally, our asymptotic results are illustrated by numerical simulations.

Karl Ewald, Ulrike Schneider.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 944--969.

Abstract:
We derive expressions for the finite-sample distribution of the Lasso estimator in the context of a linear regression model in low as well as in high dimensions by exploiting the structure of the optimization problem defining the estimator. In low dimensions, we assume full rank of the regressor matrix and present expressions for the cumulative distribution function as well as the densities of the absolutely continuous parts of the estimator. Our results are presented for the case of normally distributed errors, but do not hinge on this assumption and can easily be generalized. Additionally, we establish an explicit formula for the correspondence between the Lasso and the least-squares estimator. We derive analogous results for the distribution in less explicit form in high dimensions where we make no assumptions on the regressor matrix at all. In this setting, we also investigate the model selection properties of the Lasso and show that possibly only a subset of models might be selected by the estimator, completely independently of the observed response vector. Finally, we present a condition for uniqueness of the estimator that is necessary as well as sufficient.

In this paper we propose a bimodal gamma distribution using a quadratic transformation based on the alpha-skew-normal model. We discuss several properties of this distribution such as mean, variance, moments, hazard rate and entropy measures. Further, we propose a new regression model with censored data based on the bimodal gamma distribution. This regression model can be very useful to the analysis of real data and could give more realistic fits than other special regression models. Monte Carlo simulations were performed to check the bias in the maximum likelihood estimation. The proposed models are applied to two real data sets found in literature.

Effective property prediction methods can help accelerate the search for COVID-19 antivirals either through accurate in-silico screens or by effectively guiding on-going at-scale experimental efforts. However, existing prediction tools have limited ability to accommodate scarce or fragmented training data currently available. In this paper, we introduce a novel approach to learn predictors that can generalize or extrapolate beyond the heterogeneous data. Our method builds on and extends recently proposed invariant risk minimization, adaptively forcing the predictor to avoid nuisance variation. We achieve this by continually exercising and manipulating latent representations of molecules to highlight undesirable variation to the predictor. To test the method we use a combination of three data sources: SARS-CoV-2 antiviral screening data, molecular fragments that bind to SARS-CoV-2 main protease and large screening data for SARS-CoV-1. Our predictor outperforms state-of-the-art transfer learning methods by significant margin. We also report the top 20 predictions of our model on Broad drug repurposing hub.

The next seminar in the 2017–18 History of Pre-Modern Medicine seminar series takes place on Tuesday 30 January. Speaker: Professor Guido Alfani (Bocconi University, Milan) Plague in Italy and Europe during the 17th century: epidemiology and impact Abstract: After many years of relative… Continue reading

Matey Neykov, Han Liu.

Source: The Annals of Statistics, Volume 47, Number 5, 2472--2503.

Abstract:
This paper explores the information-theoretic limitations of graph property testing in zero-field Ising models. Instead of learning the entire graph structure, sometimes testing a basic graph property such as connectivity, cycle presence or maximum clique size is a more relevant and attainable objective. Since property testing is more fundamental than graph recovery, any necessary conditions for property testing imply corresponding conditions for graph recovery, while custom property tests can be statistically and/or computationally more efficient than graph recovery based algorithms. Understanding the statistical complexity of property testing requires the distinction of ferromagnetic (i.e., positive interactions only) and general Ising models. Using combinatorial constructs such as graph packing and strong monotonicity, we characterize how target properties affect the corresponding minimax upper and lower bounds within the realm of ferromagnets. On the other hand, by studying the detection of an antiferromagnetic (i.e., negative interactions only) Curie–Weiss model buried in Rademacher noise, we show that property testing is strictly more challenging over general Ising models. In terms of methodological development, we propose two types of correlation based tests: computationally efficient screening for ferromagnets, and score type tests for general models, including a fast cycle presence test. Our correlation screening tests match the information-theoretic bounds for property testing in ferromagnets in certain regimes.

Ability to work with each other. In the loosely coupled environment of a service-oriented architecture, separate resources don't need to know the details of how they each work, but they need to have enough common ground to reliably exchange messages without error or misunderstanding. Standardized specifications go a long way towards creating this common ground, but differences in implementation may still lead to breakdowns in communication. Interoperability is when services can interact with each other without encountering such problems.

Fan Li, Fan Li.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2389--2415.

Abstract:
Causal or unconfounded descriptive comparisons between multiple groups are common in observational studies. Motivated from a racial disparity study in health services research, we propose a unified propensity score weighting framework, the balancing weights, for estimating causal effects with multiple treatments. These weights incorporate the generalized propensity scores to balance the weighted covariate distribution of each treatment group, all weighted toward a common prespecified target population. The class of balancing weights include several existing approaches such as the inverse probability weights and trimming weights as special cases. Within this framework, we propose a set of target estimands based on linear contrasts. We further develop the generalized overlap weights, constructed as the product of the inverse probability weights and the harmonic mean of the generalized propensity scores. The generalized overlap weighting scheme corresponds to the target population with the most overlap in covariates across the multiple treatments. These weights are bounded and thus bypass the problem of extreme propensities. We show that the generalized overlap weights minimize the total asymptotic variance of the moment weighting estimators for the pairwise contrasts within the class of balancing weights. We consider two balance check criteria and propose a new sandwich variance estimator for estimating the causal effects with generalized overlap weights. We apply these methods to study the racial disparities in medical expenditure between several racial groups using the 2009 Medical Expenditure Panel Survey (MEPS) data. Simulations were carried out to compare with existing methods.

P Seguela
Feb 1, 1993; 13:596-604
Articles

02020-02-10: Europe

Speech by Mr Agustín Carstens, General Manager of the BIS, at the Eurofi Financial Forum, Helsinki, 12 September 2019.

Navigation often requires movement in three-dimensional (3D) space. Recent studies have postulated two different models for how head direction (HD) cells encode 3D space: the rotational plane hypothesis and the dual-axis model. To distinguish these models, we recorded HD cells in female rats while they traveled different routes along both horizontal and vertical surfaces from an elevated platform to the top of a cuboidal apparatus. We compared HD cell preferred firing directions (PFDs) in different planes and addressed the issue of whether HD cell firing is commutative—does the order of the animal's route affect the final outcome of the cell's PFD? Rats locomoted a direct or indirect route from the floor to the cube top via one, two, or three vertical walls. Whereas the rotational plane hypothesis accounted for PFD shifts when the animal traversed horizontal corners, the cell's PFD was better explained by the dual-axis model when the animal traversed vertical corners. Responses also followed the dual-axis model (1) under dark conditions, (2) for passive movement of the rat, (3) following apparatus rotation, (4) for movement around inside vertical corners, and (5) across a 45° outside vertical corner. The order in which the animal traversed the different planes did not affect the outcome of the cell's PFD, indicating that responses were commutative. HD cell peak firing rates were generally equivalent along each surface. These findings indicate that the animal's orientation with respect to gravity plays an important role in determining a cell's PFD, and that vestibular and proprioceptive cues drive these computations.

SIGNIFICANCE STATEMENT Navigating in a three-dimensional (3D) world is a complex task that requires one to maintain a proper sense of orientation relative to both local and global cues. Rodent head direction (HD) cells have been suggested to subserve this sense of orientation, but most HD cell studies have focused on navigation in 2D environments. We investigated the responses of HD cells as rats moved between multiple vertically and horizontally oriented planar surfaces, demonstrating that HD cells align their directional representations to both local (current plane of locomotion) and global (gravity) cues across several experimental conditions, including darkness and passive movement. These findings offer critical insights into the processing of 3D space in the mammalian brain.

At the beginning of the year we took a tour of 6 incredible plants you might not have heard of. Diets worldwide – from forest roots and leaves such as the moringa in Africa and parts of Asia to cardoon, the close relative of the artichoke in Europe – are varied, suited to local environment and can counter malnutrition and [...]

Sheltering in place doesn’t mean you can’t study up for your next European adventure

The smart tool gives users step-by-step instructions based on WHO’s handwashing protocol

Global real residential property prices rose 1.4% year/year in aggregate in Q3 2019, reflecting subdued developments both in advanced (+ 1.5%) and emerging market economies (+ 1.3%).

Remarks by Ms Isabel Schnabel, Member of the Executive Board of the European Central Bank, at a 24-Hour Global Webinar co-organised by the SAFE Policy Center on "The COVID-19 Crisis and Its Aftermath: Corporate Governance Implications and Policy Challenges", Frankfurt am Main, 16 April 2020.

Contribution by Mr Fabio Panetta, Member of the Executive Board of the European Central Bank, published by Politico on 21 April 2020.

The German soccer league reported 10 positive tests for the coronavirus among 36 clubs in the Bundesliga and second division on Monday.

The European repo market has held up well amid the initial volatility created by the economic slowdown caused by COVID-19,...

The post European Repo Demonstrates Its Resilience appeared first on OpenMarkets.

Throughout the year Bus4Life provides encouragement to local pastors and OM teams in Eastern Europe, partnering with them to share the Gospel.

The Toronto Maple Leafs have signed Finnish defenceman Mikko Lehtonen to a one-year, entry-level contract for the 2020-21 season, the club announced Monday.

Close to 300 series at various frequencies for 60 countries have been updated.

Monthly and annual data have been updated for 60 countries. The average length of the monthly series is more than to 55 years. Some annual series go back to the middle of the 19th century - or even earlier for several countries.

Introductory remarks (by videoconference) by Mr Luis de Guindos, Vice-President of the European Central Bank, to the Committee on Economic and Monetary Affairs of the European Parliament, Frankfurt am Main, 7 May 2020.

Several European countries, including Switzerland and Germany, are demanding all user data generated by coronavirus contact tracing apps be stored on-device, rather than aggregated on a centralized server.

A previously healthy 9-year-old immigrant girl from Mexico was evaluated in the emergency department (ED) with one week of fatigue, fevers, rhinorrhea, and cough. She initially presented to her primary pediatrician, where a complete blood count revealed neutropenia, prompting referral to the ED. In the ED, she was found to be influenza A–positive. Because of dehydration, she received intravenous fluids and was admitted to the pediatric hospital medicine service. After 2 days, influenza symptoms improved, and oral intake increased. However, she was noted to have decreased bilateral lower-extremity strength, absent Achilles reflexes, decreased lower-extremity sensation and proprioception, a positive result on the Romberg sign, and abnormal heel-to-shin testing results. These findings prompted an urgent neurology consultation. After extensive imaging, laboratory evaluation, and further consultations, a diagnosis was established.

Bus4Life is OM’s mobile missions centre to the unreached people of Central and Eastern Europe, bringing books and also participating in summer programmes, as it did in summer 2017.

Property index exchange-traded fund Proptrax is a cheap and easy way to gain exposure to the property market, says an analyst.

A Fin24 user looks to an expert for help in improving his credit score by paying off his debt.

Temaki

UEFA Grassroots Day has been marked in Munich and all over Europe with a series of especially arranged activities promoting the message that football is open to everyone.

Febrile neutropenia is a common complication in children with cancer. Traditionally, even low-risk episodes have been managed entirely in an inpatient setting, and discharge of the patients has been delayed until resolution of fever and sustainable hematopoietic recovery.

The results of this decision-analytic model evaluating low-risk febrile neutropenia episodes suggest that the substantially higher costs of inpatient management cannot be justified on the basis of safety and efficacy considerations or patient/parent preferences. Uncertainty remains whether intravenous or oral treatment might be the preferable route of drug administration in an ambulatory setting. (Read the full article)

Some studies reveal an association between exposure to alcohol consumption in movies and youth drinking, but the evidence is sparse.

Exposure to alcohol consumption in movies is associated with youth binge drinking, is little influenced by cultural differences between countries (Germany, Iceland, Italy, Netherlands, Poland, and Scotland), and is specific to movie alcohol, not movie smoking, depictions. (Read the full article)

Health care professionals face problems managing obesity and often fail to follow guidelines for its management in practice. Only a few single-country reports are available describing delivery of primary care to children with obesity.

Nearly all primary pediatric care providers from 4 European countries recognize the importance of obesity in pediatric practice, but only half use BMI clinically, and many lack the confidence and the infrastructure needed for providing care to patients with obesity. (Read the full article)

Small for gestational age neonates (weight <10th percentile) are at risk for neutropenia during the first days after birth. However, the duration, responsible mechanism, and outcomes of this variety of neonatal neutropenia are not precisely known.

Six percent of small for gestational age neonates had neutrophils <1000/μL, with an average neutropenia duration of 7 days. Neutropenia was more closely linked with small for gestational age status than maternal hypertension. This neutropenia is associated with elevated nucleated red blood cell count and increased odds of necrotizing enterocolitis. (Read the full article)

"We can do better," Germany coach Silvia Neid concluded after her side joined France and Sweden in making it to the quarter-finals of the Olympic tournament in unspectacular fashion.

A Fin24 reader who bought a property in December 2019 sent his registration papers off just before the lockdown was announced, which was unfortunately too late. A property law expert responds.

A group of Bulgarian teenagers and leaders took part in this year’s TeenStreet Europe for the first time and experienced God in new ways.

Lyon extended their record tally of final wins to six while their run of four victories in a row is twice the next best.

Objectives: Carbapenemase-producing Enterobacterales and specifically KPC-producing Klebsiella pneumoniae (KPC-Kp) are rapidly spreading worldwide. The prognosis of ventilator-associated pneumonia (VAP) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) is not well known. Our study tries to assess whether ventilator-associated pneumonia caused by a KPC-Kp strain is associated with higher all-cause mortality than if caused by carbapenem-susceptible isolates.

Study design and methods: This is a retrospective cohort study of patients with VAP due to K. pneumoniae from a 35-bed polyvalent Intensive Care Unit in a university hospital (> 40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression).

Results. We analyze 69 cases of K. pneumoniae VAP of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/mL). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [lsqb]HR[rsqb] 1.25; 95% CI: 0.46–3.41). Adequate targeted therapy (HR 0.03; 95% CI: <0.01–0.23) was associated with all-cause mortality.

Conclussion. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used.

Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum β-lactamases (ESBLs) as principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel ESBL inhibitor developed in combination with cefepime for empiric treatment of serious Gram-negative infections in settings where ESBLs are prevalent. Cefepime-enmetazobactam has been investigated in a phase 3 trial in patients with complicated urinary tract infections or acute pyelonephritis. This study examined pharmacokinetic-pharmacodynamic (PK-PD) relationships of enmetazobactam, in combination with cefepime, for ESBL-producing isolates of Klebsiella pneumoniae in 26-hour murine neutropenic thigh infection models. Enmetazobactam dose fractionation identified time above a free threshold concentration (fT > C_T) as the PK-PD index predictive of efficacy. Nine ESBL-producing isolates of K. pneumoniae, resistant to cefepime and piperacillin-tazobactam, were included in enmetazobactam dose-ranging studies. The isolates encoded CTX-M-type, SHV-12, DHA-1 and OXA-48 β-lactamases and covered a cefepime-enmetazobactam MIC range from 0.06 to 2 μg/ml. Enmetazobactam restored the efficacy of cefepime against all isolates tested. Sigmoid curve fitting across the combined set of isolates identified enmetazobactam PK-PD targets for stasis and for a 1-log₁₀ bioburden reduction of 8% and 44% fT > 2 μg/ml, respectively, with a concomitant cefepime PK-PD target of 40 – 60% fT > cefepime-enmetazobactam MIC. These findings support clinical dose selection and breakpoint setting for cefepime-enmetazobactam.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicentre trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90ms mean QTc-prolongation per 100ng/mL increase in piperaquine concentration. The effect of piperaquine on absolute QTc-interval estimated a mean maximum QTc-interval of 456ms (EC₅₀=209ng/mL). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98-2.46% risk of having QTc-prolongation > 60ms in all treatment settings. Although piperaquine administration resulted in QTc-prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern.

Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing K. pneumoniae isolate.

Many transferable quinolone-resistance mechanisms have been already identified in Gram-negative bacteria. The plasmid-encoded 65 amino-acid long ciprofloxacin-modifying enzyme, namely CrpP, was recently identified in Pseudomonas aeruginosa. We analyzed a collection of 100 clonally-unrelated and multidrug-resistant P. aeruginosa clinical isolates among which 46 (46%) were found positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. Those crpP-like genes were chromosomally located, as part of PAGI-like pathogenicity genomic islands.