Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating individual treatment effect: generalization bounds and algorithms

There is intense interest in applying machine learning to problems of causal inference in fields such as healthcare, economics and education. In particular, individual-level causal inference has important applications such as precision medicine. We give a new theoretical analysis and family of algorithms for predicting individual treatment effect (ITE) from observational data, under the assumption known as strong ignorability. The algorithms learn a "balanced" representation such that the induced treated and control distributions look similar. We give a novel, simple and intuitive generalization-error bound showing that the expected ITE estimation error of a representation is bounded by a sum of the standard generalization-error of that representation and the distance between the treated and control distributions induced by the representation. We use Integral Probability Metrics to measure distances between distributions, deriving explicit bounds for the Wasserstein and Maximum Mean Discrepancy (MMD) distances. Experiments on real and simulated data show the new algorithms match or outperform the state-of-the-art.
Locating input and output points in facilities design - a comparison of constructive, evolutionary, and exact methods

This paper formulates and compares four new approaches to optimally locate the input and output station for each department within a facility design such that material handling costs are minimized. This problem is an NP-hard combinatorial problem with many real-life applications of considerable economic consequence. A genetic algorithm (GA) is shown to be an effective and efficient optimization method when compared to integer programming, simulated annealing, and three versions of a greedy constructive heuristic on a suite of test problems of varying size. Seeding versus random initialization of GA populations are compared.
Diagnostic accuracy of two multiplex real-time polymerase chain reaction assays for the diagnosis of meningitis in children in a resource-limited setting

Introduction Accurate etiological diagnosis of meningitis is important, but difficult in resource-limited settings due to prior administration of antibiotics and lack of viral diagnostics. We aimed to develop and validate 2 real-time multiplex PCR (RT-PCR) assays for the detection of common causes of community-acquired bacterial and viral meningitis in South African children. Methods We developed 2 multiplex RT- PCRs for detection of S. pneumoniae, N. meningitidis, H. influenzae, enteroviruses, mumps virus and herpes simplex virus. We tested residual CSF samples from children presenting to a local paediatric hospital over a one-year period, whose CSF showed an abnormal cell count. Results were compared with routine diagnostic tests and the final discharge diagnosis. We calculated accuracy of the bacterial RT-PCR assay compared to CSF culture and using World Health Organisation definitions of laboratory-confirmed bacterial meningitis. Results From 292 samples, bacterial DNA was detected in 12 (4.1%) and viral nucleic acids in 94 (32%). Compared to CSF culture, the sensitivity and specificity of the bacterial RT-PCR was 100% and 97.2% with complete agreement in organism identification. None of the cases positive by viral RT-PCR had a bacterial cause confirmed on CSF culture. Only 9/90 (10%) of patients diagnosed clinically as bacterial meningitis or partially treated bacterial meningitis tested positive with the bacterial RT-PCR. Discussion In this population the use of 2 multiplex RT-PCRs targeting 6 common pathogens gave promising results. If introduced into routine diagnostic testing, these multiplex RT-PCR assays would supplement other diagnostic tests, and have the potential to limit unnecessary antibiotic therapy and hospitalisation.
The importance of mergers for the origin of intracluster stars in cosmological simulations of galaxy clusters

We study the origin of the diffuse stellar component (DSC) in 117 galaxy clusters extracted from a cosmological hydrodynamical simulation. We identify all galaxies present in the simulated clusters at 17 output redshifts, starting with z= 3.5, and then build the family trees for all the z= 0 cluster galaxies. The most massive cluster galaxies show complex family trees, resembling the merger trees of dark matter haloes, while the majority of other cluster galaxies experience only one or two major mergers during their entire life history. Then, for each diffuse star particle identified at z= 0, we look for the galaxy to which it once belonged at an earlier redshift, thus linking the presence of the DSC to the galaxy formation history. The main results of our analysis are as follows. (i) On average, half of the DSC star particles come from galaxies associated with the family tree of the most massive galaxy (bright cluster galaxy – hereafter BCG), one quarter comes from the family trees of other massive galaxies and the remaining quarter from dissolved galaxies. That is, the formation of the DSC is parallel to the build-up of the BCG and other massive galaxies. (ii) Most DSC star particles become unbound during mergers in the formation history of the BCGs and of other massive galaxies, independent of cluster mass. Our results suggest that the tidal stripping mechanism is responsible only for a minor fraction of the DSC. (iii) At cluster radii larger than 250 h−1 kpc, the DSC fraction from the BCG is reduced and the largest contribution comes from the other massive galaxies; in the cluster outskirts, galaxies of all masses contribute to the DSC. (iv) The DSC does not have a preferred redshift of formation: however, most DSC stars are unbound at z < 1. (v) The amount of DSC stars at z= 0 does not correlate strongly with the global dynamical history of clusters, and increases weakly with cluster mass.
Altered T-cell and regulatory cell repertoire in patients with diffuse cutaneous systemic sclerosis

Objectives: The aim of this study was to evaluate a wide spectrum of peripheral immune-competent cell types, reflecting overall disturbances in immune homeostasis, characteristic of systemic sclerosis (SSc). We also assessed visceral organ involvement and evaluated the relationship between cell proportions and clinical symptoms of the disease. Methods: Twenty-one patients with diffuse cutaneous SSc (dcSSc) and 15 healthy individuals participated in the study. Peripheral blood lymphocyte subgroups were quantified by flow cytometry, soluble cytokines were assessed by enzyme-linked immunosorbent assay (ELISA), serum complement levels were measured by nephelometry, and autoantibodies were determined by indirect immunofluorescence staining and ELISA technique. Functional tests of regulatory T (Treg) cells were also carried out. Results: Patients with SSc had higher percentages of activated CD3+/HLA-DR+ T cells. Comparing naive vs. memory subsets of CD4+ and CD8+ T cells, a shift towards central memory phenotype was observed in SSc. Natural killer (NK) and T-helper (Th)17 cell percentages were increased, while NKT, Th1, Treg type 1 (Tr1), and CD4+CD25+ Treg cell percentages were decreased in patients. Moreover, the suppressor activity of CD4+CD25+ Treg cells was lower in SSc. Negative correlations occurred between modified Rodnan skin score (MRSS) and Tr1 cell percentages and between complement levels and CD4+CD25+ Treg cells. We also found decreased interleukin (IL)-10 levels in SSc. Conclusions: Our data suggest that the increased Th17/CD4+CD25+ Treg ratio and the altered regulatory function of CD4+CD25+ Treg cells play an important role in the development of SSc. Moreover, our study reveals the potential role of the decreased profile of IL-10-producing Tr1 cells in the progression of disproportionate immune responses in SSc.
Ultrasound in regional anaesthesia

Ultrasound guidance is rapidly becoming the gold standard for regional anaesthesia. There is an ever growing weight of evidence, matched with improving technology, to show that the use of ultrasound has significant benefits over conventional techniques, such as nerve stimulation and loss of resistance. The improved safety and efficacy that ultrasound brings to regional anaesthesia will help promote its use and realise the benefits that regional anaesthesia has over general anaesthesia, such as decreased morbidity and mortality, superior postoperative analgesia, cost‐effectiveness, decreased postoperative complications and an improved postoperative course. In this review we consider the evidence behind the improved safety and efficacy of ultrasound‐guided regional anaesthesia, before discussing its use in pain medicine, paediatrics and in the facilitation of neuraxial blockade. The Achilles’ heel of ultrasound‐guided regional anaesthesia is that anaesthetists are far more familiar with providing general anaesthesia, which in most cases requires skills that are achieved faster and more reliably. To this ends we go on to provide practical advice on ultrasound‐guided techniques and the introduction of ultrasound into a department.
Active Learning for Smooth Problems

Recently it was shown that the true sample complexity of active learning is asymptotically better than that for passive learning. In many interesting cases, the improvement has been shown to be exponential [BHW08]; however, there are artificial examples in which the improvement is small. In this paper we provide a basis for a exponential improvements in active learning. We show that exponential improvements arise when the underlying learning problem is “smooth,” i.e., the hypothesis class, the instance space and the distribution can all be described by smooth functions. This provides a unified and simplified analysis for most known examples and significantly extends the class learning problems that are “actively learnable at an exponential rate. ”
Driver Gaze Behavior Is Different in Normal Curve Driving and when Looking at the Tangent Point

Several steering models in the visual science literature attempt to capture the visual strategies in curve driving. Some of them are based on steering points on the future path (FP), others on tangent points (TP). It is, however, challenging to differentiate between the models’ predictions in real–world contexts. Analysis of optokinetic nystagmus (OKN) parameters is one useful measure, as the different strategies predict measurably different OKN patterns. Here, we directly test this prediction by asking drivers to either a) “drive as they normally would” or b) to “look at the TP”. The design of the experiment is similar to a previous study by Kandil et al., but uses more sophisticated methods of eye–movement analysis. We find that the eye-movement patterns in the “normal” condition are indeed markedly different from the “tp” condition, and consistent with drivers looking at waypoints on the future path. This is the case for both overall fixation distribution, as well as the more informative fixation–by–fixation analysis of OKN. We find that the horizontal gaze speed during OKN corresponds well to the quantitative prediction of the future path models. The results also definitively rule out the alternative explanation that the OKN is produced by an involuntary reflex even while the driver is “trying” to look at the TP. The results are discussed in terms of the sequential organization of curve driving.
The Structure of Plasmodium falciparum Blood-Stage 6-Cys Protein Pf41 Reveals an Unexpected Intra-Domain Insertion Required for Pf12 Coordination

Plasmodium falciparum is an apicomplexan parasite and the etiological agent of severe human malaria. The complex P. falciparum life cycle is supported by a diverse repertoire of surface proteins including the family of 6-Cys s48/45 antigens. Of these, Pf41 is localized to the surface of the blood-stage merozoite through its interaction with the glycophosphatidylinositol-anchored Pf12. Our recent structural characterization of Pf12 revealed two juxtaposed 6-Cys domains (D1 and D2). Pf41, however, contains an additional segment of 120 residues predicted to form a large spacer separating its two 6-Cys domains. To gain insight into the assembly mechanism and overall architecture of the Pf12-Pf41 complex, we first determined the 2.45 Å resolution crystal structure of Pf41 using zinc single-wavelength anomalous dispersion. Structural analysis revealed an unexpected domain organization where the Pf41 6-Cys domains are, in fact, intimately associated and the additional residues instead map predominately to an inserted domain-like region (ID) located between two β-strands in D1. Notably, the ID is largely proteolyzed in the final structure suggesting inherent flexibility. To assess the contribution of the ID to complex formation, we engineered a form of Pf41 where the ID was replaced by a short glycine-serine linker and showed by isothermal titration calorimetry that binding to Pf12 was abrogated. Finally, protease protection assays showed that the proteolytic susceptibility of the ID was significantly reduced in the complex, consistent with the Pf41 ID directly engaging Pf12. Collectively, these data establish the architectural organization of Pf41 and define an essential role for the Pf41 ID in promoting assembly of the Pf12-Pf41 heterodimeric complex.
Structural basis for Rab11-dependent membrane recruitment of a family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1

Family of Rab11-interacting protein (FIP)3/Arfophlin-1 and FIP4/Arfophilin-2 are dual effectors for Rab11 and ADP ribosylation factor (ARF)5/ARF6, which are involved in membrane delivery from recycling endosomes to the plasma membrane during cytokinesis. Here, we define the distinct C-terminal binding regions of FIP3 and FIP4 for Rab11 and ARF5/ARF6. Furthermore, we determined the crystal structure of Rab11 in complex with the Rab11-binding domain (RBD) of FIP3. The long amphiphilic α-helix of FIP3-RBD forms a parallel coiled-coil homodimer, with two symmetric interfaces with two Rab11 molecules. The hydrophobic side of the RBD helix is involved in homodimerization and mediates the interaction with the Rab11 switch 1 region, whereas the opposite hydrophilic side interacts with the Rab11 switch 2 and is the major factor contributing to the binding specificity. The bivalent interaction of FIP3 with Rab11 at the C terminus allows FIP3 to coordinately function with other binding partners, including ARFs.
Interpreting the functional role of a novel interaction motif in prokaryotic sodium channels

Voltage-gated sodium channels enable the translocation of sodium ions across cell membranes and play crucial roles in electrical signaling by initiating the action potential. In humans, mutations in sodium channels give rise to several neurological and cardiovascular diseases, and hence they are targets for pharmaceutical drug developments. Prokaryotic sodium channel crystal structures have provided detailed views of sodium channels, which by homology have suggested potentially important functionally related structural features in human sodium channels. A new crystal structure of a full-length prokaryotic channel, NavMs, in a conformation we proposed to represent the open, activated state, has revealed a novel interaction motif associated with channel opening. This motif is associated with disease when mutated in human sodium channels and plays an important and dynamic role in our new model for channel activation.
The BTB-zinc Finger Transcription Factor Abrupt Acts as an Epithelial Oncogene in Drosophila melanogaster through Maintaining a Progenitor-like Cell State

The capacity of tumour cells to maintain continual overgrowth potential has been linked to the commandeering of normal self-renewal pathways. Using an epithelial cancer model in Drosophila melanogaster, we carried out an overexpression screen for oncogenes capable of cooperating with the loss of the epithelial apico-basal cell polarity regulator, scribbled (scrib), and identified the cell fate regulator, Abrupt, a BTB-zinc finger protein. Abrupt overexpression alone is insufficient to transform cells, but in cooperation with scrib loss of function, Abrupt promotes the formation of massive tumours in the eye/antennal disc. The steroid hormone receptor coactivator, Taiman (a homologue of SRC3/AIB1), is known to associate with Abrupt, and Taiman overexpression also drives tumour formation in cooperation with the loss of Scrib. Expression arrays and ChIP-Seq indicates that Abrupt overexpression represses a large number of genes, including steroid hormone-response genes and multiple cell fate regulators, thereby maintaining cells within an epithelial progenitor-like state. The progenitor-like state is characterised by the failure to express the conserved Eyes absent/Dachshund regulatory complex in the eye disc, and in the antennal disc by the failure to express cell fate regulators that define the temporal elaboration of the appendage along the proximo-distal axis downstream of Distalless. Loss of scrib promotes cooperation with Abrupt through impaired Hippo signalling, which is required and sufficient for cooperative overgrowth with Abrupt, and JNK (Jun kinase) signalling, which is required for tumour cell migration/invasion but not overgrowth. These results thus identify a novel cooperating oncogene, identify mammalian family members of which are also known oncogenes, and demonstrate that epithelial tumours in Drosophila can be characterised by the maintenance of a progenitor-like state.
Diagnosed hypertension in Canada: incidence, prevalence and associated mortality

Background: Hypertension is a leading risk factor for cardiovascular diseases. Our objectives were to examine the prevalence and incidence of diagnosed hypertension in Canada and compare mortality among people with and without diagnosed hypertension. Methods: We obtained data from linked health administrative databases from each province and territory for adults aged 20 years and older. We used a validated case definition to identify people with hypertension diagnosed between 1998/99 and 2007/08. We excluded pregnant women from the analysis. Results: This retrospective population-based study included more than 26 million people. In 2007/08, about 6 million adults (23.0%) were living with diagnosed hypertension and about 418 000 had a new diagnosis. The age-standardized prevalence increased significantly from 12.5% in 1998/99 to 19.6% in 2007/08, and the incidence decreased from 2.7 to 2.4 per 100. Among people aged 60 years and older, the prevalence was higher among women than among men, as was the incidence among people aged 75 years and older. The prevalence and incidence were highest in the Atlantic region. For all age groups, all-cause mortality was higher among adults with diagnosed hypertension than among those without diagnosed hypertension. Interpretation: The overall prevalence of diagnosed hypertension in Canada from 1998 to 2008 was high and increasing, whereas the incidence declined during the same period. These findings highlight the need to continue monitoring the effectiveness of efforts for managing hypertension and to enhance public health programs aimed at preventing hypertension.
Expression of HER2 and C-KIT in Nasopharyngeal Carcinoma: Implications for a New Therapeutic Approach

We sought to determine the expression and prognostic significance of HER2 and c-KIT proteins in nasopharyngeal carcinoma (NPC). In this retrospective study, immunohistochemical stains for HER2 and c-KIT were performed on formalin-fixed paraffin-embedded sections from 49 patients with NPC who were treated at our hospital from 1971 to 2000. The clinical and immunohistochemical data were correlated, including gender, ethnic origin, age, histological type, EBV status (EBER in situ hybridization), stage, and overall survival. HER2 expression was not found in the tested samples. C-KIT overexpression was found in 33% (16/49) of the patients. Nine of the 16 samples (56%) were strongly positive for c-KIT protein (staining of >50% of the tumor cells). C-KIT expression was associated with younger age. C-KIT was not found in patients with squamous carcinoma or in those with negative EBV status, although these two groups consisted of only five patients each. Although c-KIT–positive cases tended to be associated with slightly better survival, this was not statistically significant. C-KIT protein was expressed in one third of the NPC patients in this study, only in EBV-positive, undifferentiated, or nonkeratinizing carcinoma patients. Further study is needed to check whether c-KIT expression is correlated with c-KIT DNA mutations and to test the possibility of treatment with imatinib mesylate (Gleevec). HER2 protein was negative in the same tested specimens.
Promoter-Specific Expression and Genomic Structure of IgLON Family Genes in Mouse

IgLON family is composed of five genes: Lsamp, Ntm, Opcml, Negr1, and Iglon5; encoding for five highly homologous neural adhesion proteins that regulate neurite outgrowth and synapse formation. In the current study we performed in silico analysis revealing that Ntm and Opcml display similar genomic structure as previously reported for Lsamp, characterized by two alternative promotors 1a and 1b. Negr1 and Iglon5 transcripts have uniform 5′ region, suggesting single promoter. Iglon5, the recently characterized family member, shares high level of conservation and structural qualities characteristic to IgLON family such as N-terminal signal peptide, three Ig domains, and GPI anchor binding site. By using custom 5′-isoform-specific TaqMan gene-expression assay, we demonstrated heterogeneous expression of IgLON transcripts in different areas of mouse brain and several-fold lower expression in selected tissues outside central nervous system. As an example, the expression of IgLON transcripts in urogenital and reproductive system is in line with repeated reports of urogenital tumors accompanied by mutations in IgLON genes. Considering the high levels of intra-family homology shared by IgLONs, we investigated potential compensatory effects at the level of IgLON isoforms in the brains of mice deficient of one or two family members. We found that the lack of IgLONs is not compensated by a systematic quantitative increase of the other family members. On the contrary, the expression of Ntm 1a transcript and NEGR1 protein was significantly reduced in the frontal cortex of Lsamp-deficient mice suggesting that the expression patterns within IgLON family are balanced coherently. The actions of individual IgLONs, however, can be antagonistic as demonstrated by differential expression of Syp in deletion mutants of IgLONs. In conclusion, we show that the genomic twin-promoter structure has impact on both anatomical distribution and intra-family interactions of IgLON family members. Remarkable variety in the activity levels of 1a and 1b promoters both in the brain and in other tissues, suggests complex functional regulation of IgLONs by alternative signal peptides driven by 1a and 1b promoters.
Metrics for performance benchmarking of multi-robot exploration

Performance benchmarking has become an important topic within robotics. It is indeed, a critical way to compare different solutions under different conditions. In this paper, we focus on performance benchmarking of multi-robot systems which explore and map unknown terrains. We present a collection of metrics to objectively compare different algorithms that can be applied to collaborative multi-robot exploration. We also identify parameters that impact robotic fleet performances. By varying the parameters, we can identify strengths and limits of an algorithm. This work is also a first concrete step to address the general problem of objectively comparing different multi-robot coordination algorithms. We illustrate these contributions with realistic simulations of the frontier-based exploration strategy. The simulations were implemented in ROS, which enables to uncouple the control software from the drivers of the robot body. We can therefore use the same code on both simulation and real robots.