Muteb Alharthi, Theodore Kypraios, Philip D. O’Neill.

Source: Bayesian Analysis, Volume 14, Number 3, 927--956.

Abstract:
We consider the problem of model choice for stochastic epidemic models given partial observation of a disease outbreak through time. Our main focus is on the use of Bayes factors. Although Bayes factors have appeared in the epidemic modelling literature before, they can be hard to compute and little attention has been given to fundamental questions concerning their utility. In this paper we derive analytic expressions for Bayes factors given complete observation through time, which suggest practical guidelines for model choice problems. We adapt the power posterior method for computing Bayes factors so as to account for missing data and apply this approach to partially observed epidemics. For comparison, we also explore the use of a deviance information criterion for missing data scenarios. The methods are illustrated via examples involving both simulated and real data.

L. F. South, A. N. Pettitt, C. C. Drovandi.

Source: Bayesian Analysis, Volume 14, Number 3, 773--796.

Abstract:
Sequential Monte Carlo (SMC) methods for sampling from the posterior of static Bayesian models are flexible, parallelisable and capable of handling complex targets. However, it is common practice to adopt a Markov chain Monte Carlo (MCMC) kernel with a multivariate normal random walk (RW) proposal in the move step, which can be both inefficient and detrimental for exploring challenging posterior distributions. We develop new SMC methods with independent proposals which allow recycling of all candidates generated in the SMC process and are embarrassingly parallelisable. A novel evidence estimator that is easily computed from the output of our independent SMC is proposed. Our independent proposals are constructed via flexible copula-type models calibrated with the population of SMC particles. We demonstrate through several examples that more precise estimates of posterior expectations and the marginal likelihood can be obtained using fewer likelihood evaluations than the more standard RW approach.

Marcos Oliveira Prates, Renato Martins Assunção, Erica Castilho Rodrigues.

Source: Bayesian Analysis, Volume 14, Number 2, 623--647.

Abstract:
Spatial confounding between the spatial random effects and fixed effects covariates has been recently discovered and showed that it may bring misleading interpretation to the model results. Techniques to alleviate this problem are based on decomposing the spatial random effect and fitting a restricted spatial regression. In this paper, we propose a different approach: a transformation of the geographic space to ensure that the unobserved spatial random effect added to the regression is orthogonal to the fixed effects covariates. Our approach, named SPOCK, has the additional benefit of providing a fast and simple computational method to estimate the parameters. Also, it does not constrain the distribution class assumed for the spatial error term. A simulation study and real data analyses are presented to better understand the advantages of the new method in comparison with the existing ones.

Haolun Shi, Guosheng Yin.

Source: Bayesian Analysis, Volume 14, Number 2, 399--425.

Abstract:
Bayesian approaches to phase II clinical trial designs are usually based on the posterior distribution of the parameter of interest and calibration of certain threshold for decision making. If the posterior probability is computed and assessed in a sequential manner, the design may involve the problem of multiplicity, which, however, is often a neglected aspect in Bayesian trial designs. To effectively maintain the overall type I error rate, we propose solutions to the problem of multiplicity for Bayesian sequential designs and, in particular, the determination of the cutoff boundaries for the posterior probabilities. We present both theoretical and numerical methods for finding the optimal posterior probability boundaries with $alpha$ -spending functions that mimic those of the frequentist group sequential designs. The theoretical approach is based on the asymptotic properties of the posterior probability, which establishes a connection between the Bayesian trial design and the frequentist group sequential method. The numerical approach uses a sandwich-type searching algorithm, which immensely reduces the computational burden. We apply least-square fitting to find the $alpha$ -spending function closest to the target. We discuss the application of our method to single-arm and double-arm cases with binary and normal endpoints, respectively, and provide a real trial example for each case.

Christophe Leterrier
Feb 28, 2018; 38:2135-2145
Viewpoints

Karim Fifel
Jan 24, 2018; 38:784-786
Journal Club

KM Harris
Jul 1, 1992; 12:2685-2705
Articles

Jeremy R. Manning
Oct 28, 2009; 29:13613-13620
BehavioralSystemsCognitive

RU Muller
Jul 1, 1987; 7:1951-1968
Articles

Gregor Thut
Sep 13, 2006; 26:9494-9502
BehavioralSystemsCognitive

Chris Englund
Jan 5, 2005; 25:247-251
BRIEF COMMUNICATION

The Linux Foundation will host ToIP, a cross-industry effort to ensure more secure data handling over the Internet. This new foundation is an independent project enabling trustworthy exchange and verification of data between any two parties on the Internet. The ToIP Foundation will provide a robust common standard to instill confidence that data is coming from a trusted source.

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans.

SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale.

Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf. Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness.

SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.

The detection and segmentation of meaningful figures from their background is one of the primary functions of vision. While work in nonhuman primates has implicated early visual mechanisms in this figure–ground modulation, neuroimaging in humans has instead largely ascribed the processing of figures and objects to higher stages of the visual hierarchy. Here, we used high-field fMRI at 7 Tesla to measure BOLD responses to task-irrelevant orientation-defined figures in human early visual cortex (N = 6, four females). We used a novel population receptive field mapping-based approach to resolve the spatial profiles of two constituent mechanisms of figure–ground modulation: a local boundary response, and a further enhancement spanning the full extent of the figure region that is driven by global differences in features. Reconstructing the distinct spatial profiles of these effects reveals that figure enhancement modulates responses in human early visual cortex in a manner consistent with a mechanism of automatic, contextually driven feedback from higher visual areas.

SIGNIFICANCE STATEMENT A core function of the visual system is to parse complex 2D input into meaningful figures. We do so constantly and seamlessly, both by processing information about visible edges and by analyzing large-scale differences between figure and background. While influential neurophysiology work has characterized an intriguing mechanism that enhances V1 responses to perceptual figures, we have a poor understanding of how the early visual system contributes to figure–ground processing in humans. Here, we use advanced computational analysis methods and high-field human fMRI data to resolve the distinct spatial profiles of local edge and global figure enhancement in the early visual system (V1 and LGN); the latter is distinct and consistent with a mechanism of automatic, stimulus-driven feedback from higher-level visual areas.

The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ.

SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies.

Hydrocephalus is a pathologic condition associated with various brain diseases, including Alzheimer's disease (AD). Dysfunctional ependymal cells (EpCs) are believed to contribute to the development of hydrocephalus. It is thus of interest to investigate EpCs' development and function. Here, we report that vacuolar protein sorting-associated protein 35 (VPS35) is critical for EpC differentiation, ciliogenesis, and survival, and thus preventing neonatal hydrocephalus. VPS35 is abundantly expressed in EpCs. Mice with conditional knock-out (cKO) of Vps35 in embryonic (Vps35^GFAP-Cre and Vps35^Emx1-Cre) or postnatal (Vps35^Foxj1-CreER) EpC progenitors exhibit enlarged lateral ventricles (LVs) and hydrocephalus-like pathology. Further studies reveal marked reductions in EpCs and their cilia in both Vps35^GFAP-Cre and Vps35^Foxj1-CreER mutant mice. The reduced EpCs appear to be due to impairments in EpC differentiation and survival. Additionally, both Vps35^GFAP-Cre and Vps35^Foxj1-CreER neonatal pups exhibit increased cell proliferation and death largely in a region close to LV-EpCs. Many microglia close to the mutant LV-EpC region become activated. Depletion of the microglia by PLX3397, an antagonist of colony-stimulating factor 1 receptor (CSF1R), restores LV-EpCs and diminishes the pathology of neonatal hydrocephalus in Vps35^Foxj1-CreER mice. Taken together, these observations suggest unrecognized functions of Vps35 in EpC differentiation, ciliogenesis, and survival in neonatal LV, and reveal pathologic roles of locally activated microglia in EpC homeostasis and hydrocephalus development.

SIGNIFICANCE STATEMENT This study reports critical functions of vacuolar protein sorting-associated protein 35 (VPS35) not only in promoting ependymal cell (EpC) differentiation, ciliogenesis, and survival, but also in preventing local microglial activation. The dysfunctional EpCs and activated microglia are likely to induce hydrocephalus.

Basic facts The world contains an estimated 1 400 million cubic km of water. Only 0.003% of this vast amount, about 45 000 cubic km, are what is called “fresh water resources” - water that theoretically can be used for drinking, hygiene, agriculture and industry. But not all of this water is accessible. For example, seasonal flooding makes water extremely difficult [...]

Today’s fisheries sector hosts a multibillion dollar industry that is a vital source of food and nutrition, employment, trade, economic wellbeing and recreation. What is blue growth? The concept of a "blue economy" came out of the 2012 Rio+20 Conference and emphasizes conservation and sustainable management, based on the premise that healthy ocean ecosystems are more productive and a must for sustainable [...]

The sites include the 5,000-year-old tomb of Meresankh III, the Red Monastery and the Mosque-Madrassa of Sultan Barquq

Funeral parlors' enterprising staff offered burial packages to suit every social strata and budget

Demand for service is not expected to recover in the coming weeks, says Marine Atlantic.

Before COVID-19 hit, Hemliss Eloïse Konan had plans for how she'd spend her summer in Sudbury. After finishing her first year at Laurentian University, Konan planned to stay in residence, and get a job for the summer.

Differential detergent fractionation of cells is a rapid method for extraction of cytoplasmic and nuclear proteins in preparation of an immunoprecipitation. This method can be applied for use of adherent or suspension cells and can significantly reduce nonspecific background in an immunoprecipitation by separation of cellular compartments into individual fractions. The lysis of cells by differential detergents permits the rapid extraction of proteins from the cytoplasm (digitonin), the cytoplasmic membranes, and organelles (Triton X-100), and nucleoplasm (Tween/DOC), facilitated through the use of distinct extraction buffers. Cytoplasmic and nuclear matrix proteins as well as DNA are left behind during the detergent-based extraction.

BIS Bulletin No 9, April 2020. By allowing banks to run down some of their buffers, policymakers are sending a strong signal about their resolve to lessen the economic fallout from the pandemic. Such prudential measures complement the main policy levers: monetary and fiscal instruments. To avoid a reduction in credit to the real economy, authorities need to ensure that banks have the capacity and willingness to make use of the flexibility afforded by the buffer release. Payout restrictions on banks and risk-sharing between banks and the public sector will be key. For banks to continue playing a positive role in the supply of funding during the recovery, they should maintain usable buffers for a long period, as losses from a severe recession will take time to materialise.

Press release: Basel Committee invites comments on the design of a prudential treatment for crypto-assets, 12 December 2019.

The Bank of Canada, the Bank of England, the Bank of Japan, the European Central Bank, the Sveriges Riksbank and the Swiss National Bank, together with the Bank for International Settlements (BIS), have created a group to share experiences as they assess the potential case for central bank digital currency (CBDC) in their home jurisdictions. (Press release, 21 January 2020)

Basel Committee Press release "Basel Committee meets to review vulnerabilities and emerging risks, advance supervisory initiatives and promote Basel III implementationl", 27 February 2020.

Fifty thousand jobs were lost in Nova Scotia in April, reflecting the devastating economic impact of the first full month of public health orders to prevent the spread of COVID-19.

The only daily TV news package to focus on Nova Scotians and their stories

A Dalhousie University scientist and a NSCAD textile professor are teaming up to create a new fabric. It could be used to locally manufacture personal protective equipment like surgical masks. As the CBC's Colleen Jones reports, they have received a COVID-19 grant to study the idea.

As Nova Scotians gazed up at the Canadian Forces Snowbirds soaring through the clouds last weekend, Matt MacKenzie was looking down and feeling the weight of successive tragedies that had enveloped his home province. 

Over the 13 hours the mass shooting took place across Nova Scotia on April 18 and 19, the RCMP called in resources from New Brunswick to help. However, the two municipal police forces closest to Portapique were not asked to respond directly at any point, CBC News has learned.

The latest death was at the Northwood long-term care home in Halifax.

Global real residential property prices rose 1.4% year/year in aggregate in Q3 2019, reflecting subdued developments both in advanced (+ 1.5%) and emerging market economies (+ 1.3%).

Hearing of Mr François Villeroy de Galhau, Governor of the Bank of France, before the Section for the Economy and Finance of the French Economic, Social and Environmental Council, Paris, 8 April 2020.

From stage to sofa: NAC brings local arts to homes in new livestream initiative  Connected to India

The Carolina Panthers have agreed to a four-year, $64 million contract extension with All-Pro Christian McCaffrey, a person familiar with the contract negotiation told The Associated Press, making McCaffrey the highest-paid running back in the NFL.

An idea that began when a classicist went to a brewery to sip beers and ponder the history of hops has brought to life an ancient ale.

Toronto officials reported 180 new cases of COVID-19 on Thursday, a figure that represents a dip when compared to the more than 200 cases announced daily this week. 

Colleen Jones, Sidney Crosby among many preeminent local sports figures reacting in the aftermath of Sunday's killing rampage.

The post Aero Design Series – Stock Wheel – Part 1: Intro and Initial Mockup appeared first on SOLIDWORKS Education Blog.

Close to 300 series at various frequencies for 60 countries have been updated.

BCBS Press release "Basel Committee publishes stocktake report on climate-related financial risk initiatives'", 30 April 2020

This report summarises the main results of a stocktake conducted by the Basel Committee of its members' initiatives on climate-related financial risks.

Central Bank of Chile Working Papers by Tomás Gómez, Alejandro Jara and David Moreno

Apple is shifting a substantial portion of its current AirPods production from China to Vietnam, and appears to be considering a release schedule later than previously predicted for an AirPods refresh.