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

Moduli Redefinitions and Moduli Stabilisation

Field redefinitions occur in string compactifications at the one loop level. We review arguments for why such redefinitions occur and study their effect on moduli stabilisation and supersymmetry breaking in the LARGE volume scenario. For small moduli, although the effect of such redefinitions can be larger than that of the $\alpha'$ corrections in both the K\"ahler and scalar potentials, they do not alter the structure of the scalar potential. For the less well motivated case of large moduli, the redefinitions can dominate all other terms in the scalar potential. We also study the effect of redefinitions on the structure of supersymmetry breaking and soft terms.Comment: 21 pages, 3 figures; v2. references adde

Giant hydronephrosis mimicking progressive malignancy

BACKGROUND: Cases of giant hydronephroses are rare and usually contain no more than 1–2 litres of fluid in the collecting system. We report a remarkable case of giant hydronephrosis mimicking a progressive malignant abdominal tumour. CASE PRESENTATION: A 78-year-old cachectic woman presented with an enormous abdominal tumour, which, according to the patient, had slowly increased in diameter. Medical history was unremarkable except for a hysterectomy >30 years before. A CT scan revealed a giant cystic tumour filling almost the entire abdominal cavity. It was analysed by two independent radiologists who suspected a tumour originating from the right kidney and additionally a cystic ovarian neoplasm. Subsequently, a diagnostic and therapeutic laparotomy was performed: the tumour presented as a cystic, 35 × 30 × 25 cm expansive structure adhesive to adjacent organs without definite signs of invasive growth. The right renal hilar vessels could finally be identified at its basis. After extirpation another tumourous structure emerged in the pelvis originating from the genital organs and was also resected. The histopathological examination revealed a >15 kg hydronephrotic right kidney, lacking hardly any residual renal cortex parenchyma. The second specimen was identified as an ovary with regressive changes and a large partially calcified cyst. There was no evidence of malignant growth. CONCLUSION: Although both clinical symptoms and the enormous size of the tumour indicated malignant growth, it turned out to be a giant hydronephrosis. Presumably, a chronic obstruction of the distal ureter had caused this extraordinary hydronephrosis. As demonstrated in our case, an accurate diagnosis of giant hydronephrosis remains challenging due to the atrophy of the renal parenchyma associated with chronic obstruction. Therefore, any abdominal cystic mass even in the absence of other evident pathologies should include the differential diagnosis of a possible hydronephrosis. Diagnostic accuracy might be increased by a combination of endourological techniques such as retrograde pyelography and modern imaging modalities

A systematic review investigating fatigue, psychological and cognitive impairment following TIA and minor stroke:protocol paper

Approximately 20,000 people have a transient ischemic attack (TIA) and 23,375 have a minor stroke in England each year. Fatigue, psychological and cognitive impairments are well documented post-stroke. Evidence suggests that TIA and minor stroke patients also experience these impairments; however, they are not routinely offered relevant treatment. This systematic review aims to: (1) establish the prevalence of fatigue, anxiety, depression, post-traumatic stress disorder (PTSD) and cognitive impairment following TIA and minor stroke and to investigate the temporal course of these impairments; (2) explore impact on quality of life (QoL), change in emotions and return to work; (3) identify where further research is required and to potentially inform an intervention study

The effect of major depression on participation in preventive health care activities

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to determine whether major depressive episodes (MDE) contribute to a lower rate of participation in three prevention activities: blood pressure checks, mammograms and Pap tests.</p> <p>Methods</p> <p>The data source for this study was the Canadian National Population Health Survey (NPHS), a longitudinal study that started in 1994 and has subsequently re-interviewed its participants every two years. The NPHS included a short form version of the Composite International Diagnostic Interview (CIDI-SF) to assess past year MDE and also collected data on participation in preventive activities. Initially, we examined whether respondents with MDE in a particular year were less likely to participate in screening during that same year. In order to assess whether MDE negatively altered the pattern of participation, those successfully screened at the baseline interview in 1994 were identified and divided into cohorts depending on their MDE status. Proportional hazard models were used to quantify the effect of MDE on subsequent participation in screening.</p> <p>Results</p> <p>No effect of MDE on participation in the three preventive activities was identified either in the cross-sectional or longitudinal analysis. Adjustment for a set of relevant covariates did not alter this result.</p> <p>Conclusion</p> <p>Whereas MDE might be expected to reduce the frequency of participation in screening activities, no evidence for this was found in the current analysis. Since people with MDE may contact the health system more frequently, this may offset any tendency of the illness itself to reduce participation in screening.</p

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Molecular ecology meets systematic conservation planning

Integrative and proactive conservation approaches are critical to the long-term persistence of biodiversity. Molecular data can provide important information on evolutionary processes necessary for conserving multiple levels of biodiversity (genes, populations, species, and ecosystems). However, molecular data are rarely used to guide spatial conservation decision-making. Here, we bridge the fields of molecular ecology (ME) and systematic conservation planning (SCP) (the ‘why’) to build a foundation for the inclusion of molecular data into spatial conservation planning tools (the ‘how’), and provide a practical guide for implementing this integrative approach for both conservation planners and molecular ecologists. The proposed framework enhances interdisciplinary capacity, which is crucial to achieving the ambitious global conservation goals envisioned for the next decade

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease