Alberto Cassese, Weixuan Zhu, Michele Guindani, Marina Vannucci.

Source: Bayesian Analysis, Volume 14, Number 2, 553--572.

Abstract:
In many applications, investigators monitor processes that vary in space and time, with the goal of identifying temporally persistent and spatially localized departures from a baseline or “normal” behavior. In this manuscript, we consider the monitoring of pneumonia and influenza (P&I) mortality, to detect influenza outbreaks in the continental United States, and propose a Bayesian nonparametric model selection approach to take into account the spatio-temporal dependence of outbreaks. More specifically, we introduce a zero-inflated conditionally identically distributed species sampling prior which allows borrowing information across time and to assign data to clusters associated to either a null or an alternate process. Spatial dependences are accounted for by means of a Markov random field prior, which allows to inform the selection based on inferences conducted at nearby locations. We show how the proposed modeling framework performs in an application to the P&I mortality data and in a simulation study, and compare with common threshold methods for detecting outbreaks over time, with more recent Markov switching based models, and with spike-and-slab Bayesian nonparametric priors that do not take into account spatio-temporal dependence.

Suprateek Kundu, Bani K. Mallick, Veera Baladandayuthapani.

Source: Bayesian Analysis, Volume 14, Number 2, 449--476.

Abstract:
There has been an intense development in the Bayesian graphical model literature over the past decade; however, most of the existing methods are restricted to moderate dimensions. We propose a novel graphical model selection approach for large dimensional settings where the dimension increases with the sample size, by decoupling model fitting and covariance selection. First, a full model based on a complete graph is fit under a novel class of mixtures of inverse–Wishart priors, which induce shrinkage on the precision matrix under an equivalence with Cholesky-based regularization, while enabling conjugate updates. Subsequently, a post-fitting model selection step uses penalized joint credible regions to perform model selection. This allows our methods to be computationally feasible for large dimensional settings using a combination of straightforward Gibbs samplers and efficient post-fitting inferences. Theoretical guarantees in terms of selection consistency are also established. Simulations show that the proposed approach compares favorably with competing methods, both in terms of accuracy metrics and computation times. We apply this approach to a cancer genomics data example.

Susan Gruber, Mark J. van der Laan.

Source: Statistical Science, Volume 34, Number 1, 82--85.

Abstract:
Dorie and co-authors (DHSSC) are to be congratulated for initiating the ACIC Data Challenge. Their project engaged the community and accelerated research by providing a level playing field for comparing the performance of a priori specified algorithms. DHSSC identified themes concerning characteristics of the DGP, properties of the estimators, and inference. We discuss these themes in the context of targeted learning.

London : Cleanair, Smoke-free Environment (33 Stillness Rd, London, SE23 1NG), [198-?]

London : Cleanair, Smoke-free Environment (33 Stillness Rd, London, SE23 1NG), [198-?]

WT Newsome
Jun 1, 1988; 8:2201-2211
Articles

EL Bienenstock
Jan 1, 1982; 2:32-48
Articles

Cristopher M. Niell
Jul 23, 2008; 28:7520-7536
BehavioralSystemsCognitive

French translation of the Press Release on the pre-release of two special chapters of the Annual Economic Report of the BIS, 17 June 2018. Trust is the missing link in today's cryptocurrencies - Cryptocurrencies' model of generating trust limits their potential to replace conventional money, the Bank for International Settlements (BIS) writes in its Annual Economic Report (AER), a new title launched this year.

French translation of BIS press release on the presentation of the Annual Economic Report 2018, 24 June 2018. Les responsables des politiques publiques peuvent prolonger la phase de croissance actuelle en engageant des réformes structurelles, en restaurant les marges de manoeuvre monétaires et budgétaires pour faire face aux menaces futures et en encourageant une mise en oeuvre rapide des réformes réglementaires, indique la Banque des Règlements Internationaux (BRI) dans son Rapport économique annuel. ...

To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452.

Speech by Mr Agustín Carstens, General Manager of the BIS, at the Fourteenth ASBA-BCBS-FSI High-level Meeting on Global and Regional Supervisory Priorities, Lima, 1 October 2019.

Knowledge about objects encompasses not only their prototypical features but also complex, atypical, semantic knowledge (e.g., "Pizza was invented in Naples"). This fMRI study of male and female human participants combines univariate and multivariate analyses to consider the cortical representation of this more complex semantic knowledge. Using the categories of food, people, and places, this study investigates whether access to spatially related geographic semantic knowledge (1) involves the same domain-selective neural representations involved in access to prototypical taste knowledge about food; and (2) elicits activation of neural representations classically linked to places when this geographic knowledge is accessed about food and people. In three experiments using word stimuli, domain-relevant and atypical conceptual access for the categories food, people, and places were assessed. Results uncover two principles of semantic representation: food-selective representations in the left insula continue to be recruited when prototypical taste knowledge is task-irrelevant and under conditions of high cognitive demand; access to geographic knowledge for food and people categories involves the additional recruitment of classically place-selective parahippocampal gyrus, retrosplenial complex, and transverse occipital sulcus. These findings underscore the importance of object category in the representation of a broad range of knowledge, while showing how the cross recruitment of specialized representations may endow the considerable flexibility of our complex semantic knowledge.

SIGNIFICANCE STATEMENT We know not only stereotypical things about objects (an apple is round, graspable, edible) but can also flexibly combine typical and atypical features to form complex concepts (the metaphorical role an apple plays in Judeo-Christian belief). In this fMRI study, we observe that, when atypical geographic knowledge is accessed about food dishes, domain-selective sensorimotor-related cortical representations continue to be recruited, but that regions classically associated with place perception are additionally engaged. This interplay between categorically driven representations, linked to the object being accessed, and the flexible recruitment of semantic stores linked to the content being accessed, provides a potential mechanism for the broad representational repertoire of our semantic system.

Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and related neurodegenerative tauopathies. Here, we conducted PET along with postmortem assays to investigate time course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female mice were analyzed in this study. We observed that radiosignals derived from [¹¹C]flumazenil, a tracer for benzodiazepine receptor, in rTg4510 mice were significantly lower than the levels in nontransgenic littermates at 2-3 months of age. In contrast, retentions of (E)-[¹¹C]ABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory, but not excitatory, synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 mice at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits. Our findings indicate that tau-induced disruption of the inhibitory synapse may be a critical trigger of progressive neurodegeneration, resulting in massive neuronal loss, and PET assessments of inhibitory versus excitatory synapses potentially offer in vivo indices for hyperexcitability and excitotoxicity early in the etiologic pathway of neurodegenerative tauopathies.

SIGNIFICANCE STATEMENT In this study, we examined the in vivo status of excitatory and inhibitory synapses in the brain of the rTg4510 tauopathy mouse model by PET imaging with (E)-[¹¹C]ABP688 and [¹¹C]flumazenil, respectively. We identified inhibitory synapse as being significantly dysregulated before brain atrophy at 2 months of age, while excitatory synapse stayed relatively intact at this stage. In line with this observation, postmortem assessment of brain tissues demonstrated selective attenuation of inhibitory synaptic constituents accompanied by the upregulation of cFos before the formation of tau pathology in the forebrain at young ages. Our findings indicate that selective degeneration of inhibitory synapse with hyperexcitability in the cortical circuit constitutes the critical early pathophysiology of tauopathy.

Nicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster, coding for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChR) subunits, to nicotine addiction. β4*nAChRs have been implicated in nicotine withdrawal, aversion, and reinforcement. Here we show that β4*nAChRs also are involved in non-nicotine-mediated responses that may predispose to addiction-related behaviors. β4 knock-out (KO) male mice show increased novelty-induced locomotor activity, lower baseline anxiety, and motivational deficits in operant conditioning for palatable food rewards and in reward-based Go/No-go tasks. To further explore reward deficits we used intracranial self-administration (ICSA) by directly injecting nicotine into the ventral tegmental area (VTA) in mice. We found that, at low nicotine doses, β4KO self-administer less than wild-type (WT) mice. Conversely, at high nicotine doses, this was reversed and β4KO self-administered more than WT mice, whereas β4-overexpressing mice avoided nicotine injections. Viral expression of β4 subunits in medial habenula (MHb), interpeduncular nucleus (IPN), and VTA of β4KO mice revealed dose- and region-dependent differences: β4*nAChRs in the VTA potentiated nicotine-mediated rewarding effects at all doses, whereas β4*nAChRs in the MHb-IPN pathway, limited VTA-ICSA at high nicotine doses. Together, our findings indicate that the lack of functional β4*nAChRs result in deficits in reward sensitivity including increased ICSA at high doses of nicotine that is restored by re-expression of β4*nAChRs in the MHb-IPN. These data indicate that β4 is a critical modulator of reward-related behaviors.

SIGNIFICANCE STATEMENT Human genetic studies have provided strong evidence for a relationship between variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and nicotine addiction. Yet, little is known about the role of β4 nicotinic acetylcholine receptor (nAChR) subunit encoded by this cluster. We investigated the implication of β4*nAChRs in anxiety-, food reward- and nicotine reward-related behaviors. Deletion of the β4 subunit gene resulted in an addiction-related phenotype characterized by low anxiety, high novelty-induced response, lack of sensitivity to palatable food rewards and increased intracranial nicotine self-administration at high doses. Lentiviral vector-induced re-expression of the β4 subunit into either the MHb or IPN restored a "stop" signal on nicotine self-administration. These results suggest that β4*nAChRs provide a promising novel drug target for smoking cessation.

For visually guided navigation, the use of environmental cues is essential. Particularly, detecting local boundaries that impose limits to locomotion and estimating their location is crucial. In a series of three fMRI experiments, we investigated whether there is a neural coding of navigational distance in the human visual cortex (both female and male). We used virtual reality software to systematically manipulate the distance from a viewer perspective to different types of a boundary. Using a multivoxel pattern classification employing a linear support vector machine, we found that the occipital place area (OPA) is sensitive to the navigational distance restricted by the transparent glass wall. Further, the OPA was sensitive to a non-crossable boundary only, suggesting an importance of the functional constraint of a boundary. Together, we propose the OPA as a perceptual source of external environmental features relevant for navigation.

SIGNIFICANCE STATEMENT One of major goals in cognitive neuroscience has been to understand the nature of visual scene representation in human ventral visual cortex. An aspect of scene perception that has been overlooked despite its ecological importance is the analysis of space for navigation. One of critical computation necessary for navigation is coding of distance to environmental boundaries that impose limit on navigator's movements. This paper reports the first empirical evidence for coding of navigational distance in the human visual cortex and its striking sensitivity to functional constraint of environmental boundaries. Such finding links the paper to previous neurological and behavioral works that emphasized the distance to boundaries as a crucial geometric property for reorientation behavior of children and other animal species.

Nestin, an intermediate filament protein widely used as a marker of neural progenitors, was recently found to be expressed transiently in developing cortical neurons in culture and in developing mouse cortex. In young cortical cultures, nestin regulates axonal growth cone morphology. In addition, nestin, which is known to bind the neuronal cdk5/p35 kinase, affects responses to axon guidance cues upstream of cdk5, specifically, to Sema3a. Changes in growth cone morphology require rearrangements of cytoskeletal networks, and changes in microtubules and actin filaments are well studied. In contrast, the roles of intermediate filament proteins in this process are poorly understood, even in cultured neurons. Here, we investigate the molecular mechanism by which nestin affects growth cone morphology and Sema3a sensitivity. We find that nestin selectively facilitates the phosphorylation of the lissencephaly-linked protein doublecortin (DCX) by cdk5/p35, but the phosphorylation of other cdk5 substrates is not affected by nestin. We uncover that this substrate selectivity is based on the ability of nestin to interact with DCX, but not with other cdk5 substrates. Nestin thus creates a selective scaffold for DCX with activated cdk5/p35. Last, we use cortical cultures derived from Dcx KO mice to show that the effects of nestin on growth cone morphology and on Sema3a sensitivity are DCX-dependent, thus suggesting a functional role for the DCX-nestin complex in neurons. We propose that nestin changes growth cone behavior by regulating the intracellular kinase signaling environment in developing neurons. The sex of animal subjects is unknown.

SIGNIFICANCE STATEMENT Nestin, an intermediate filament protein highly expressed in neural progenitors, was recently identified in developing neurons where it regulates growth cone morphology and responsiveness to the guidance cue Sema3a. Changes in growth cone morphology require rearrangements of cytoskeletal networks, but the roles of intermediate filaments in this process are poorly understood. We now report that nestin selectively facilitates phosphorylation of the lissencephaly-linked doublecortin (DCX) by cdk5/p35, but the phosphorylation of other cdk5 substrates is not affected. This substrate selectivity is based on preferential scaffolding of DCX, cdk5, and p35 by nestin. Additionally, we demonstrate a functional role for the DCX-nestin complex in neurons. We propose that nestin changes growth cone behavior by regulating intracellular kinase signaling in developing neurons.

Storms reveal, then hide, the ship's sand-covered remains every decade or so

Darin Isaac was elected on Wednesday as the new chief of the Selkirk First Nation in Yukon. Isaac also held the position for two terms from 2005 to 2011. He has also served as a councillor for three terms.

Days before Saint John council passed a motion to ensure Saint John Energy could not be sold, the Ontario cities of Peterborough and Orillia both got approval to sell their municipally owned power distribution companies.

A St. John's cardiologist says public health restrictions put in place under the COVID-19 pandemic, while justified, may be harming cardiac patients whose procedures have been postponed indefinitely as well as heart patients who are avoiding hospitals.

COVID-19 is not an equal opportunity pandemic. As Memorial president Vianne Timmons writes in this guest column, women are often in harm's way because of their work.

Successful modification of the bacterial artificial chromosome (BAC) after two-step BAC engineering is confirmed in two separate polymerase chain reactions (PCRs). The first reaction (5' co-integrate PCR) uses a forward 5' co-integrate primer (a sequence located upstream of the 5' end of the A-box) and a reverse 3' primer on the vector (175PA+50AT) or within the reporter sequence or mutated region as appropriate. The second reaction (3' co-integrate PCR) uses a forward 5' primer on the recA gene (RecA1300S) and a reverse 3' co-integrate primer (a sequence located downstream from the 3' end of the B-box). Those colonies shown to be positive in PCR analysis are further tested for sensitivity to UV light. After the resolution, colonies that have lost the excised recombination vector including sacB and recA genes become UV light sensitive.

Press release about the Basel Committee publishing consultation paper on revisions to the credit valuation adjustment risk framework, 28 November 2019.

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

Press release about the Basel Committee launching the consolidated Basel Framework, 16 December 2019.

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

BIS statement, 16 March 2020.

Press release about Basel Committee assesses members' implementation of the Net Stable Funding Ratio and large exposures framework, 19 March 2020

Press release "Basel Committee coordinates policy and supervisory response to Covid-19", 20 March 2020

Press release "Governors and Heads of Supervision announce deferral of Basel III implementation to increase operational capacity of banks and supervisors to respond to Covid-19", 27 March 2020

BCBS Press release "Basel Committee sets out additional measures to alleviate the impact of Covid-19", 3 April 2020

BCBS Press release "Basel Committee and IOSCO announce deferral of final implementation phases of the margin requirements for non-centrally cleared derivatives", 3 April 2020

BCBS Press release "Basel III monitoring results based on end-June 2019 data published by the Basel Committee", 8 April 2020

BCBS Press release "Basel Committee issues progress report on banks' implementation of the 'Principles for effective risk data aggregation and reporting'", 29 April 2020

Acute myeloid leukemia is an aggressive cancer of the blood-forming system. It affects the hematopoietic stem cells, or blood stem cells, of various white blood cells and of the red blood cells and platelets.

Kristy-Lyn Kemp can't believe how close she came to potentially starting a COVID-19 outbreak at her new job.

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%).

Information technology, health care, and consumer discretionary stocks that outperformed in the last decade have done well in the first four months of 2020.

The Vancouver Whitecaps said it has ordered two player to self-quarantine for 14 days after they violated club and league orders to abide by physical distancing guidelines in B.C.

The chief of Millbrook First Nation says the Nova Scotia RCMP's competition for its new communication centre was "distorted and biased," arbitrarily inflating the price of his community's proposal to reach a "predetermined outcome."

Darin Isaac has been elected chief of the Selkirk First Nation while Jeremy Harper, Morris Morrison, Carmen Lee Baker and Ashley Edzerza were voted in as councillors. Cody Sims has been elected youth councillor.

The B.C. Lions opened the draft with a bang, securing the No. 1 pick from the Calgary Stampeders then taking Williams first overall.

Even though this year's food truck season is looking dicey, Tyler Schmidt says he's doing his best to find business where he can.

The Pittsburgh Steelers selected Canadian receiver Chase Claypool in the second round of the NFL draft Friday night. Claypool was the 17th player taken in the round, 49th overall.

The notion that he is bound for four more years is pure superstition.

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