Softmax-based Classification is k-means Clustering:Formal Proof, Consequences for Adversarial Attacks, and Improvement through Centroid Based Tailoring

We formally prove the connection between k-means clustering and the predictions of neural networks based on the softmax activation layer. In existing work, this connection has been analyzed empirically, but it has never before been mathematically derived. The softmax function partitions the transformed input space into cones, each of which encompasses a class. This is equivalent to putting a number of centroids in this transformed space at equal distance from the origin, and k-means clustering the data points by proximity to these centroids. Softmax only cares in which cone a data point falls, and not how far from the centroid it is within that cone. We formally prove that networks with a small Lipschitz modulus (which corresponds to a low susceptibility to adversarial attacks) map data points closer to the cluster centroids, which results in a mapping to a k-means-friendly space. To leverage this knowledge, we propose Centroid Based Tailoring as an alternative to the softmax function in the last layer of a neural network. The resulting Gauss network has similar predictive accuracy as traditional networks, but is less susceptible to one-pixel attacks; while the main contribution of this paper is theoretical in nature, the Gauss network contributes empirical auxiliary benefits

How to cheat the page limit

Every conference imposing a limit on the length of submissions must deal with the problem of page limit cheating: authors tweaking the parameters of the game such that they can squeeze more content into their paper. We claim that this problem is endemic, although we lack the data to formally prove this. Instead, this paper provides a far from exhaustive summary of ways to cheat the page limit, a case study involving the papers accepted for the Research and Applied Data Science tracks at the European Conference on Machine Learning and Principles and Practice of Knowledge Discovery in Databases (ECMLPKDD) 2019, and a discussion of ways for program chairs to tackle this problem. Of the 130 accepted papers in these two ECMLPKDD 2019 tracks, 68 satisfied the page limit; 62 (47.7%) turned out to spill over the page limit, by up to as much as 50%. To misappropriate a phrase from Darrell Huff's “How to Lie with Statistics,” we intend for this paper not to be a manual for swindlers; instead, nefarious paper authors already know these tricks, and honest program chairs must learn them in self-defense. This article is categorized under: Commercial, Legal, and Ethical Issues > Fairness in Data Mining

Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review

ABSTRACT: INTRODUCTION: Haemostatic therapy in surgical and/or massive trauma patients typically involves transfusion of fresh frozen plasma (FFP). Purified human fibrinogen concentrate may offer an alternative to FFP in some instances. In this systematic review, we investigated the current evidence for the use of FFP and fibrinogen concentrate in the perioperative or massive trauma setting. METHODS: Studies reporting the outcome (blood loss, transfusion requirement, length of stay, survival and plasma fibrinogen level) of FFP or fibrinogen concentrate administration to patients in a perioperative or massive trauma setting were identified in electronic databases (1995 to 2010). Studies were included regardless of type, patient age, sample size or duration of patient follow-up. Studies of patients with congenital clotting factor deficiencies or other haematological disorders were excluded. Studies were assessed for eligibility, and data were extracted and tabulated. RESULTS: Ninety-one eligible studies (70 FFP and 21 fibrinogen concentrate) reported outcomes of interest. Few were high-quality prospective studies. Evidence for the efficacy of FFP was inconsistent across all assessed outcomes. Overall, FFP showed a positive effect for 28% of outcomes and a negative effect for 22% of outcomes. There was limited evidence that FFP reduced mortality: 50% of outcomes associated FFP with reduced mortality (typically trauma and/or massive bleeding), and 20% were associated with increased mortality (typically surgical and/or nonmassive bleeding). Five studies reported the outcome of fibrinogen concentrate versus a comparator. The evidence was consistently positive (70% of all outcomes), with no negative effects reported (0% of all outcomes). Fibrinogen concentrate was compared directly with FFP in three high-quality studies and was found to be superior for > 50% of outcomes in terms of reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital stay and increasing plasma fibrinogen levels. We found no fibrinogen concentrate comparator studies in patients with haemorrhage due to massive trauma, although efficacy across all assessed outcomes was reported in a number of noncomparator trauma studies. CONCLUSIONS: The weight of evidence does not appear to support the clinical effectiveness of FFP for surgical and/or massive trauma patients and suggests it can be detrimental. Perioperatively, fibrinogen concentrate was generally associated with improved outcome measures, although more high-quality, prospective studies are required before any definitive conclusions can be drawn

Distribution and characteristics of newly-defined subgroups of type 2 diabetes in randomised clinical trials : Post hoc cluster assignment analysis of over 12,000 study participants

Publisher Copyright: © 2022Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m2. “Severe insulin-resistant diabetes” was found least often (4.6 %) and prevalence of “mild age-related diabetes” (23.9 %) was mainly influenced by age at onset of diabetes and age cut-offs. Subgroup characteristics were widely comparable to those from real-world cohorts, but all subgroups showed higher frequencies of diabetes-related complications which were associated with longer diabetes duration. A high proportion of “severe insulin-deficient diabetes” (25.4 %) was identified with poor pre-study glycaemic control. Conclusions: Classification of RCT participants into newly-defined diabetes subgroups revealed the existence of a heterogeneous population of T2DM. For future RCTs, subgroup-based randomisation of T2DM will better define the target population and relevance of the outcomes by avoiding clinical heterogeneity.Peer reviewe

Characterization of a novel and specific inhibitor for the pro-apoptotic protease Omi/HtrA2

Omi/HtrA2 is a mammalian serine protease with high homology to bacterial HtrA chaperones. Omi/HtrA2 is localized in mitochondria and is released to the cytoplasm in response to apoptotic stimuli. Omi/HtrA2 induces cell death in a caspase-dependent manner by interacting with the inhibitor of apoptosis protein as well as in a caspase-independent manner that relies on its protease activity. We describe the identification and characterization of a novel compound as a specific inhibitor of the proteolytic activity of Omi/HtrA2. This compound (ucf-101) was isolated in a high throughput screening of a combinatorial library using bacterially made Omi-(134-458) protease and fluorescein-casein as a generic substrate. ucf-101 showed specific activity against Omi/HtrA2 and very little activity against various other serine proteases. This compound has a natural fluorescence that was used to monitor its ability to enter mammalian cells. ucf-101, when tested in caspase-9 (-/-) null fibroblasts, was found to inhibit Omi/HtrA2-induced cell death

Biomarkers of rapid chronic kidney disease progression in type 2 diabetes.

Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.We acknowledge all the SUMMIT partners (http://www.imi-summit.eu/) for their assistance with this project. This work was funded by the Innovative Medicine Initiative under grant agreement no. IMI/115006 (the SUMMIT consortium) and the Go-DARTS cohort was funded by the Chief Scientists Office Scotland.This is the accepted manuscript of a paper published in Kidney International (Looker et al., Kidney International, 2015 doi: 10.1038/ki.2015.199). The final version is available at http://dx.doi.org/10.1038/ki.2015.19

A conserved regulatory program drives emergence of the lateral plate mesoderm

Cardiovascular cell lineages emerge with kidney, smooth muscle, and limb skeleton progenitors from the lateral plate mesoderm (LPM). How the LPM emerges during development and how it has evolved to form key lineages of the vertebrate body plan remain unknown. Here, we captured LPM formation by transgenic in toto imaging and lineage tracing using the first pan-LPM enhancer element from the zebrafish gene draculin (drl). drl LPM enhancer-based reporters are specifically active in LPM-corresponding territories of several chordate species, uncovering a universal LPM-specific gene program. Distinct from other mesoderm, we identified EomesA, FoxH1, and MixL1 with BMP/Nodal-controlled Smad activity as minimally required factors to drive drl-marked LPM formation. Altogether, our work provides a developmental and mechanistic framework for LPM emergence and the in vitro differentiation of cardiovascular cell types. Our findings suggest that the LPM may represent an ancient cell fate domain that predates ancestral vertebrates