Confound-leakage: confound removal in machine learning leads to leakage

BACKGROUND: Machine learning (ML) approaches are a crucial component of modern data analysis in many fields, including epidemiology and medicine. Nonlinear ML methods often achieve accurate predictions, for instance, in personalized medicine, as they are capable of modeling complex relationships between features and the target. Problematically, ML models and their predictions can be biased by confounding information present in the features. To remove this spurious signal, researchers often employ featurewise linear confound regression (CR). While this is considered a standard approach for dealing with confounding, possible pitfalls of using CR in ML pipelines are not fully understood. RESULTS: We provide new evidence that, contrary to general expectations, linear confound regression can increase the risk of confounding when combined with nonlinear ML approaches. Using a simple framework that uses the target as a confound, we show that information leaked via CR can increase null or moderate effects to near-perfect prediction. By shuffling the features, we provide evidence that this increase is indeed due to confound-leakage and not due to revealing of information. We then demonstrate the danger of confound-leakage in a real-world clinical application where the accuracy of predicting attention-deficit/hyperactivity disorder is overestimated using speech-derived features when using depression as a confound. CONCLUSIONS: Mishandling or even amplifying confounding effects when building ML models due to confound-leakage, as shown, can lead to untrustworthy, biased, and unfair predictions. Our expose of the confound-leakage pitfall and provided guidelines for dealing with it can help create more robust and trustworthy ML models

The Usefulness of the APACHE II Score in Obstetric Critical Care: A Structured Review.

OBJECTIVE: To assess the performance of the Acute Physiology and Chronic Health Evaluation II (APACHE II) mortality prediction model in pregnant and recently pregnant women receiving critical care in low-, middle-, and high-income countries during the study period (1985-2015), using a structured literature review. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Evidence-Based Medicine Reviews, searched for articles published between 1985 and 2015. STUDY SELECTION: Twenty-five studies (24 publications), of which two were prospective, were included in the analyses. Ten studies were from high-income countries (HICs), and 15 were from low- and middle-income countries (LMICs). Median study duration and size were six years and 124 women, respectively. DATA SYNTHESIS: ICU admission complicates 0.48% of deliveries, and pregnant and recently pregnant women account for 1.49% of ICU admissions. One quarter were admitted while pregnant, three quarters of these for an obstetric indication and for a median of three days. The median APACHE II score was 10.9, with a median APACHE II-predicted mortality of 16.6%. Observed mortality was 4.6%, and the median standardized mortality ratio was 0.36 (interquartile range 0.23 to 0.73). The standardized mortality ratio was < 0.9 in 24 of 25 studies. Women in HICs were more frequently admitted with a medical comorbidity but were less likely to die than were women in LMICs. CONCLUSION: The APACHE II score consistently overestimates mortality risks for pregnant and recently pregnant women receiving critical care, whether they reside in HICs or LMICs. There is a need for a pregnancy-specific outcome prediction model for these women

Operator theory and function theory in Drury-Arveson space and its quotients

The Drury-Arveson space $H^2_d$, also known as symmetric Fock space or the $d$-shift space, is a Hilbert function space that has a natural $d$-tuple of operators acting on it, which gives it the structure of a Hilbert module. This survey aims to introduce the Drury-Arveson space, to give a panoramic view of the main operator theoretic and function theoretic aspects of this space, and to describe the universal role that it plays in multivariable operator theory and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page

Reasons and Means to Model Preferences as Incomplete

Literature involving preferences of artificial agents or human beings often assume their preferences can be represented using a complete transitive binary relation. Much has been written however on different models of preferences. We review some of the reasons that have been put forward to justify more complex modeling, and review some of the techniques that have been proposed to obtain models of such preferences

Sequencing the genome of the Atlantic salmon (Salmo salar)

The International Collaboration to Sequence the Atlantic Salmon Genome (ICSASG) will produce a genome sequence that identifies and physically maps all genes in the Atlantic salmon genome and acts as a reference sequence for other salmonids

Comparison of two doses and two routes of administration of misoprostol after pre-treatment with mifepristone for early pregnancy termination

<p>Abstract</p> <p>Background</p> <p>It is not known whether a 400 μg dose of misoprostol has a similar efficacy as an 800 μg dose when administered sublingually or vaginally 24 hours after 200 mg mifepristone.</p> <p>Methods</p> <p>It is proposed to undertake a placebo-controlled, randomized, non-inferiority trial (3% margin of equivalence) of the two misoprostol doses when administered sublingually or vaginally using factorial design. A total of 3008 pregnant women (< 63 days of gestational age) who request legal termination of pregnancy will be recruited for the trial at 16 clinics in ten countries providing abortion services. Eligible women willing to join the study will be allocated randomly to one of the four treatment groups within each centre. Women in all treatment groups will first receive 200 mg mifepristone, followed 24 hours later by either 400 μg or 800 μg misoprostol, administered either sublingually or vaginally. The dose and route of administration of misoprostol will be blinded to women, each woman receiving four tablets vaginally and four tablets sublingually, two or four of which are 200 μg tablets of misoprostol and the rest are placebo tablets.</p> <p>The four treatment regimens will be compared in terms of: (i) their efficacy to induce complete abortion; (ii) induction-to-abortion interval when possible; (iii) the frequency of side effects; and (iv) women's perceptions. The initial judgment of the outcome of treatment is made at the follow-up visit on day 15 of the study and the final assessment four weeks later. It is estimated that the clinical phase will require 12–14 months for data collection.</p> <p>To compare the two routes and two doses, relative risks (RR) of failure to achieve a complete abortion and failure to terminate pregnancy and the two-sided 95% CIs will be calculated by standard methods, as well as risk differences and two-sided 95% CIs. The latter will be used to test the non-inferiority hypotheses (at 2.5% level of significance) for achieving complete abortion. The factorial structure will be taken into account in the analysis after testing the interaction.</p> <p>Trial registration</p> <p>ISRCTN87811512</p

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Composite Dirac Neutrinos

We present a mechanism that naturally produces light Dirac neutrinos. The basic idea is that the right-handed neutrinos are composite. Any realistic composite model must involve `hidden flavor' chiral symmetries. In general some of these symmetries may survive confinement, and in particular, one of them manifests itself at low energy as an exact $B-L$ symmetry. Dirac neutrinos are therefore produced. The neutrinos are naturally light due to compositeness. In general, sterile states are present in the model, some of them can naturally be warm dark matter candidates.Comment: 12 pages; Sec. IIC updated; minor corrections; published versio

Lead exposure in adult males in urban Transvaal Province, South Africa during the apartheid era

Human exposure to lead is a substantial public health hazard worldwide and is particularly problematic in the Republic of South Africa given the country’s late cessation of leaded petrol. Lead exposure is associated with a number of serious health issues and diseases including developmental and cognitive deficiency, hypertension and heart disease. Understanding the distribution of lifetime lead burden within a given population is critical for reducing exposure rates. Femoral bone from 101 deceased adult males living in urban Transvaal Province (now Gauteng Province), South Africa between 1960 and 1998 were analyzed for lead concentration by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Of the 72 black and 29 white individuals sampled, chronic lead exposure was apparent in nearly all individuals. White males showed significantly higher median bone lead concentration (ME = 10.04 µg·g−1), than black males (ME = 3.80 µg·g−1) despite higher socioeconomic status. Bone lead concentration covaries significantly, though weakly, with individual age. There was no significant temporal trend in bone lead concentration. These results indicate that long-term low to moderate lead exposure is the historical norm among South African males. Unexpectedly, this research indicates that white males in the sample population were more highly exposed to lead

How acceptable are antiretrovirals for the prevention of sexually transmitted HIV? A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention

Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence