Meta-Amortized Variational Inference and Learning

Despite the recent success in probabilistic modeling and their applications, generative models trained using traditional inference techniques struggle to adapt to new distributions, even when the target distribution may be closely related to the ones seen during training. In this work, we present a doubly-amortized variational inference procedure as a way to address this challenge. By sharing computation across not only a set of query inputs, but also a set of different, related probabilistic models, we learn transferable latent representations that generalize across several related distributions. In particular, given a set of distributions over images, we find the learned representations to transfer to different data transformations. We empirically demonstrate the effectiveness of our method by introducing the MetaVAE, and show that it significantly outperforms baselines on downstream image classification tasks on MNIST (10-50%) and NORB (10-35%).Comment: First 2 authors contributed equall

A naturalistic study of treatment outcomes with aripiprazole in young people with first episode psychosis

Objective: Adequate treatment of a first psychotic episode in young people is a difficult challenge but may be of critical importance for changing the course of psychotic illness. Pharmacotherapy is the standard treatment of psychosis, however there is a paucity of data specific to first-episode psychosis.Methods: In this study 12 young people who presented with a psychotic episode at a specialised early intervention service were commenced on treatment with aripiprazole. They were assessed at baseline and weeks 4, 6, 24 and 48 using a broad battery of outcome measures. Case notes were also examined.Results: Data was available for 6 participants at week 48, and of those, one remained on treatment with Aripiprazole at endpoint. Case histories were typified by presentations that included illicit substance use and treatments characterised by several changes in medications. No single treatment choice predominated. Most participants tolerated treatment and showed symptomatic improvement with individualised therapy.Conclusion: Most participants showed improvement during the treatment period. Aripiprazole was one of many medications used in this study and may have been useful for the treatment of some individuals with first episode psychosis.<br /

An Image-Free Opto-Mechanical System for Creating Virtual Environments and Imaging Neuronal Activity in Freely Moving Caenorhabditis elegans

Non-invasive recording in untethered animals is arguably the ultimate step in the analysis of neuronal function, but such recordings remain elusive. To address this problem, we devised a system that tracks neuron-sized fluorescent targets in real time. The system can be used to create virtual environments by optogenetic activation of sensory neurons, or to image activity in identified neurons at high magnification. By recording activity in neurons of freely moving C. elegans, we tested the long-standing hypothesis that forward and reverse locomotion are generated by distinct neuronal circuits. Surprisingly, we found motor neurons that are active during both types of locomotion, suggesting a new model of locomotion control in C. elegans. These results emphasize the importance of recording neuronal activity in freely moving animals and significantly expand the potential of imaging techniques by providing a mean to stabilize fluorescent targets

Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?

Tyrosine kinases are important cellular signaling proteins that have a variety of biological activities including cell proliferation and migration. Multiple kinases are involved in angiogenesis, including receptor tyrosine kinases such as the vascular endothelial growth factor receptor. Inhibition of angiogenic tyrosine kinases has been developed as a systemic treatment strategy for cancer. Three anti-angiogenic tyrosine kinase inhibitors (TKIs), sunitinib, sorafenib and pazopanib, with differential binding capacities to angiogenic kinases were recently approved for treatment of patients with advanced cancer (renal cell cancer, gastro-intestinal stromal tumors, and hepatocellular cancer). Many other anti-angiogenic TKIs are being studied in phase I-III clinical trials. In addition to their beneficial anti-tumor activity, clinical resistance and toxicities have also been observed with these agents. In this manuscript, we will give an overview of the design and development of anti-angiogenic TKIs. We describe their molecular structure and classification, their mechanism of action, and their inhibitory activity against specific kinase signaling pathways. In addition, we provide insight into what extent selective targeting of angiogenic kinases by TKIs may contribute to the clinically observed anti-tumor activity, resistance, and toxicity. We feel that it is of crucial importance to increase our understanding of the clinical mechanism of action of anti-angiogenic TKIs in order to further optimize their clinical efficacy

187 Prospective Study of Futile Care in the Neuroscience Intensive Care Unit

Abstract INTRODUCTION: Our health care system spends a significant amount of resources on futile care, ie, continued medical therapy when there is no reasonable hope of cure or benefit. Nowhere is this more evident than in the neuroscience intensive care unit (NSICU), because intensive care medicine has become exceedingly proficient at maintaining cardiopulmonary function even in the face of catastrophic brain injury. METHODS: We identified patients who were admitted to the NSICU with partial loss of brainstem reflexes even after initial stabilization. Sixty-six patients were included and were followed prospectively. RESULTS: At the end of our follow-up period, 47 patients had died. Five patients intermittently followed simple commands but were bedridden, incontinent, and dependent on a tracheostomy. Fourteen were comatose, vegetative, or locked in. In 46 of 66 patients a do not resuscitate (DNR) conversation was documented after an average stay of 5.6 days. In 35 of those cases (76%) proxies agreed to DNR. Average ICU stay was 10.3 days for these patients, compared with 16.7 days for cases in which a DNR discussion was never documented. There was a trend toward higher likelihood of agreeing to DNR with Hispanic proxies compared with white and African American proxies (P = .058), and for patients with some form of insurance compared with patients with no insurance (P = .08). CONCLUSION: In our sample of 66 patients with severe brain injury, no patient recovered independence and over two-thirds died. Whenever a DNR discussion was held, there was a high likelihood that the proxies would agree to DNR. These patients spent a significantly shorter time in the ICU, reducing strain on both their families and the health care system. This study demonstrates the importance of having timely, frank DNR discussions with families of patients with devastating brain injuries, and provides evidence that the likelihood of a good outcome in these cases is exceedingly low

Discernment of Children's True and False Memory Reports: Police Officers and Laypersons.

Adults' ability to accurately evaluate children's statements can have far-reaching consequences within the legal system. This study examined the evaluations of police officers ("experts") and laypersons ("nonexperts") when presented with videotaped interviews of children aged 3 and 5 years who provided either true or false reports or denials. Participants were drawn from several counties in the eastern United States. Children's interview statements fell within four statement types: accurate reports, false reports, accurate denials, and false denials. Both groups of participants displayed overbelief in false denials. Several control variables predicted accuracy, including children's age and children's race. A significant interaction emerged: Experts (vs. nonexperts) had greater odds of being accurate when judging false reports (vs. false denials). These findings highlight the challenges adults face when distinguishing between various types of children's statements. The results have important implications for legal contexts, emphasizing that fact finders need to be mindful of the risks associated with both overaccepting false denials and accepting false reports

Vitamin D-3 Supplementation and Upper Respiratory Tract Infections in a Randomized, Controlled Trial

Background. Randomized controlled trials testing the association between vitamin D status and upper respiratory tract infection (URTI) have given mixed results. During a multicenter, randomized controlled trial of colorectal adenoma chemoprevention, we tested whether 1000 IU/day vitamin D3 supplementation reduced winter episodes and duration of URTI and its composite syndromes, influenza-like illness (ILI; fever and ≥2 of sore throat, cough, muscle ache, or headache) and colds (no fever, and ≥2 of runny nose, nasal congestion, sneezing, sore throat, cough, swollen or tender neck glands)

Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection

Periodic outbreaks of highly pathogenic avian H5N1 influenza viruses and the current H1N1 pandemic highlight the need for a more detailed understanding of influenza virus pathogenesis. To investigate the host transcriptional response induced by pathogenic influenza viruses, we used a functional-genomics approach to compare gene expression profiles in lungs from 129S6/SvEv mice infected with either the fully reconstructed H1N1 1918 pandemic virus (1918) or the highly pathogenic avian H5N1 virus Vietnam/1203/04 (VN/1203). Although the viruses reached similar titers in the lung and caused lethal infections, the mean time of death was 6 days for VN/1203-infected animals and 9 days for mice infected with the 1918 virus. VN/1203-infected animals also exhibited an earlier and more potent inflammatory response. This response included induction of genes encoding components of the inflammasome. VN/1203 was also able to disseminate to multiple organs, including the brain, which correlated with changes in the expression of genes associated with hematological functions and lipoxin biogenesis and signaling. Both viruses elicited expression of type I interferon (IFN)-regulated genes in wild-type mice and to a lesser extent in mice lacking the type I IFN receptor, suggesting alternative or redundant pathways for IFN signaling. Our findings suggest that VN/1203 is more pathogenic in mice as a consequence of several factors, including the early and sustained induction of the inflammatory response, the additive or synergistic effects of upregulated components of the immune response, and inhibition of lipoxin-mediated anti-inflammatory responses, which correlated with the ability of VN/1203 to disseminate to extrapulmonary organs