Towards zero-shot language modeling

Can we construct a neural language model which is inductively biased towards learning human language? Motivated by this question, we aim at constructing an informative prior for held-out languages on the task of character-level, open-vocabulary language modeling. We obtain this prior as the posterior over network weights conditioned on the data from a sample of training languages, which is approximated through Laplace’s method. Based on a large and diverse sample of languages, the use of our prior outperforms baseline models with an uninformative prior in both zero-shot and few-shot settings, showing that the prior is imbued with universal linguistic knowledge. Moreover, we harness broad language-specific information available for most languages of the world, i.e., features from typological databases, as distant supervision for held-out languages. We explore several language modeling conditioning techniques, including concatenation and meta-networks for parameter generation. They appear beneficial in the few-shot setting, but ineffective in the zero-shot setting. Since the paucity of even plain digital text affects the majority of the world’s languages, we hope that these insights will broaden the scope of applications for language technology

Barriers and supports to implementation of MDI/spacer use in nine Canadian pediatric emergency departments: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Despite recent research supporting the use of metered dose inhalers with spacer devices (MDI/spacers) in pediatric emergency departments (PEDs) for acute exacerbations of asthma, uptake of this practice has been slow. The objectives of this study were to determine the barriers and supports to implementing MDI/spacer research and to identify factors associated with early and late adoption of MDI/spacers in Canadian PEDs.</p> <p>Methods</p> <p>Using a comparative case study design, we classified nine tertiary care pediatric hospital PEDs based on their stage of implementation. Data were collected using focus group interviews with physicians, registered nurses (RNs), and respiratory therapists (RTs), and individual interviews with both patient care and medical directors at each site. Initial coding was based on the Ottawa Model of Research Use (OMRU) categories of elements known to influence the uptake of innovations.</p> <p>Results</p> <p>One hundred and fifty healthcare professionals from nine different healthcare institutions participated in this study. Lack of leadership in the form of a research champion, a lack of consensus about the benefits of MDI/spacers among staff, perceived resistance from patients/parents, and perceived increased cost and workload associated with MDI/spacer use were the most prevalent barriers to the adoption of the MDI/spacer. Common strategies used by early-adopting sites included the active participation of all professional groups in the adoption process in addition to a well-planned and executed educational component for staff, patients, and families. Early adopter sites were also more likely to have the MDI/spacer included in a clinical protocol/pathway.</p> <p>Conclusion</p> <p>Potential barriers and supports to implementation have been identified that will help EDs adopt MDI/spacer use. Future interventions intended to increase MDI/spacer use in PEDs will need to be sensitive to the barriers identified in this study.</p

Structural Discrimination of Robustness in Transcriptional Feedforward Loops for Pattern Formation

Signaling pathways are interconnected to regulatory circuits for sensing the environment and expressing the appropriate genetic profile. In particular, gradients of diffusing molecules (morphogens) determine cell fate at a given position, dictating development and spatial organization. The feedforward loop (FFL) circuit is among the simplest genetic architectures able to generate one-stripe patterns by operating as an amplitude detection device, where high output levels are achieved at intermediate input ones. Here, using a heuristic optimization-based approach, we dissected the design space containing all possible topologies and parameter values of the FFL circuits. We explored the ability of being sensitive or adaptive to variations in the critical morphogen level where cell fate is switched. We found four different solutions for precision, corresponding to the four incoherent architectures, but remarkably only one mode for adaptiveness, the incoherent type 4 (I4-FFL). We further carried out a theoretical study to unveil the design principle for such structural discrimination, finding that the synergistic action and cooperative binding on the downstream promoter are instrumental to achieve absolute adaptive responses. Subsequently, we analyzed the robustness of these optimal circuits against perturbations in the kinetic parameters and molecular noise, which has allowed us to depict a scenario where adaptiveness, parameter sensitivity and noise tolerance are different, correlated facets of the robustness of the I4-FFL circuit. Strikingly, we showed a strong correlation between the input (environment-related) and the intrinsic (mutation-related) susceptibilities. Finally, we discussed the evolution of incoherent regulations in terms of multifunctionality and robustness

Territoriality and the organization of technology during the Last Glacial Maximum in southwestern Europe

Climate changes that occurred during the Last Glacial Maximum (LGM) had significant consequences in human eco-dynamics across Europe. Among the most striking impacts are the demographic contraction of modern humans into southern refugia and the potential formation of a population bottleneck. In Iberia and southern France transformations also included the occurrence of significant technological changes, mostly marked by the emergence of a diverse set of bifacially-shaped stone projectiles. The rapid dissemination of bifacial technologies and the geographical circumscription of specific projectile morphologies within these regions have been regarded as evidence for: (1) the existence of a system of long-distance exchange and social alliance networks; (2) the organization of human groups into cultural facies with well-defined stylistic territorial boundaries. However, the degree and modes in which cultural transmission have occurred within these territories, and how it may have influenced other domains of the adaptive systems, remains largely unknown. Using southern Iberia as a case-study, this paper presents the first quantitative approach to the organization of lithic technology and its relationship to hunter-gatherers' territorial organization during the LGM. Similarities and dissimilarities in the presence of morphological and metric data describing lithic technologies are used as a proxy to explore modes and degrees of cultural transmission. Statistical results show that similarities in technological options are dependent on the chronology and geographical distance between sites and corroborate previous arguments for the organization of LGM settlement in Southern Iberia into discrete eco-cultural facies.STSM COST action (ref. COST-STSM-TD0902-10855); FCT, contract ref. DL 57/2016/CP1361/ CT0026. Work at Vale Boi is funded by the project ALG-01-0145-FEDER-27833 - PTDC/HAR-ARQ/27833/2017.info:eu-repo/semantics/publishedVersio

Regulation of immunity during visceral Leishmania infection

Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protective type I immune responses capable of activating infected phagocytes to kill intracellular amastigotes. However, despite the induction of protective responses, disease progresses due to a multitude of factors that impede an optimal response. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue architecture and a defective humoral response. We will review how these responses are orchestrated during the course of infection, including both early and chronic stages, focusing on the spleen and the liver, which are the main target organs of visceral Leishmania in the host. A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED). VR is supported by a post-doctoral fellowship granted by the KINDReD consortium. RS thanks the Foundation for Science and Technology (FCT) for an Investigator Grant (IF/00021/2014). This work was supported by grants to JE from ANR (LEISH-APO, France), Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE acknowledges the support of the Canada Research Chair Program

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Is cell polarity under mechanical control in plants?

Plant cells experience a tremendous amount of mechanical stress caused by turgor pressure. Because cells are glued to their neighbors by the middle lamella, supracellular patterns of physical forces are emerging during growth, usually leading to tension in the epidermis. Cortical microtubules have been shown to reorient in response to these mechanical stresses, and to resist them, indirectly via their impact on the anisotropic structure of the cell wall. In a recent study, we show that the polar localization of the auxin efflux carrier PIN1 can also be under the control of physical forces, thus linking cell growth rate and anisotropy by a common mechanical signal. Because of the known impact of auxin on the stiffness of the cell wall, this suggests that the mechanical properties of the extracellular matrix play a crucial signaling role in morphogenesis, notably controlling the polarity of the cell, as observed in animal systems

Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease

Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI) in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease.This work was funded by Projects AGL2008-00748 and AGL2010-16678-GAN from the Spanish Government, and Grant 2005 FI 01116 from Generalitat de Catalunya Spain.S