Amir Bashir, Carlos M. Carvalho, P. Richard Hahn, M. Beatrix Jones.

Source: Bayesian Analysis, Volume 14, Number 4, 1075--1090.

Abstract:
A variety of computationally efficient Bayesian models for the covariance matrix of a multivariate Gaussian distribution are available. However, all produce a relatively dense estimate of the precision matrix, and are therefore unsatisfactory when one wishes to use the precision matrix to consider the conditional independence structure of the data. This paper considers the posterior predictive distribution of model fit for these covariance models. We then undertake post-processing of the Bayes point estimate for the precision matrix to produce a sparse model whose expected fit lies within the upper 95% of the posterior predictive distribution of fit. The impact of the method for selecting the zero elements of the precision matrix is evaluated. Good results were obtained using models that encouraged a sparse posterior (G-Wishart, Bayesian adaptive graphical lasso) and selection using credible intervals. We also find that this approach is easily extended to the problem of finding a sparse set of elements that differ across a set of precision matrices, a natural summary when a common set of variables is observed under multiple conditions. We illustrate our findings with moderate dimensional data examples from finance and metabolomics.

Georg Lindgren.

Source: Statistical Science, Volume 34, Number 1, 100--128.

Abstract:
We describe and compare how methods based on the classical Rice’s formula for the expected number, and higher moments, of level crossings by a Gaussian process stand up to contemporary numerical methods to accurately deal with crossing related characteristics of the sample paths. We illustrate the relative merits in accuracy and computing time of the Rice moment methods and the exact numerical method, developed since the late 1990s, on three groups of distribution problems, the maximum over a finite interval and the waiting time to first crossing, the length of excursions over a level, and the joint period/amplitude of oscillations. We also treat the notoriously difficult problem of dependence between successive zero crossing distances. The exact solution has been known since at least 2000, but it has remained largely unnoticed outside the ocean science community. Extensive simulation studies illustrate the accuracy of the numerical methods. As a historical introduction an attempt is made to illustrate the relation between Rice’s original formulation and arguments and the exact numerical methods.

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

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

Stefan Klöppel
Mar 3, 2010; 30:3271-3275
BRIEF COMMUNICATION

Masaki Yamamoto
May 22, 2019; 39:4179-4192
Neurobiology of Disease

Peter Klivenyi
Jan 1, 2000; 20:1-7
Cellular

Lennart Mucke
Jun 1, 2000; 20:4050-4058
Cellular

Italian translation of the BIS Quarterly Review, December 2017

Italian translation of the BIS press release about the BIS Quarterly Review, December 2017

Italian translation of the BIS Quarterly Review, December 2018

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

Customer service doesn't have to suffer while your company goes through a difficult transition. In fact, 78 percent of consumers said they stopped doing business with a company because of poor customer service. Now is the time to show your most valuable buyers how you'll keep them informed, updated and respected throughout this crisis by adapting your practices to the moment.

02020-02-02: Sea Ice in the Sea of Okhotsk

Exiting low inflation traps by "consensus": nominal wages and price stability - Speech by Luiz A Pereira da Silva and Benoît Mojon, based on the keynote speech at the Eighth High-level Policy Dialogue between the Eurosystem and Latin American Central Banks, Cartagena de Indias, Colombia, 28-29 November 2019.

Giving birth triggers a wide repertoire of physiological and behavioral changes in the mother to enable her to feed and care for her offspring. These changes require coordination and are often orchestrated from the CNS, through as of yet poorly understood mechanisms. A neuronal population with a central role in puerperal changes is the tuberoinfundibular dopamine (TIDA) neurons that control release of the pituitary hormone, prolactin, which triggers key maternal adaptations, including lactation and maternal care. Here, we used Ca²⁺ imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons in vitro to examine whether they adapt their cellular and network activity according to reproductive state. In the high-prolactin state of lactation, TIDA neurons shift to faster membrane potential oscillations, a reconfiguration that reverses upon weaning. During the estrous cycle, however, which includes a brief, but pronounced, prolactin peak, oscillation frequency remains stable. An increase in the hyperpolarization-activated mixed cation current, I_h, possibly through unmasking as dopamine release drops during nursing, may partially explain the reconfiguration of TIDA rhythms. These findings identify a reversible plasticity in hypothalamic network activity that can serve to adapt the dam for motherhood.

SIGNIFICANCE STATEMENT Motherhood requires profound behavioral and physiological adaptations to enable caring for offspring, but the underlying CNS changes are poorly understood. Here, we show that, during lactation, neuroendocrine dopamine neurons, the "TIDA" cells that control prolactin secretion, reorganize their trademark oscillations to discharge in faster frequencies. Unlike previous studies, which typically have focused on structural and transcriptional changes during pregnancy and lactation, we demonstrate a functional switch in activity and one that, distinct from previously described puerperal modifications, reverses fully on weaning. We further provide evidence that a specific conductance (I_h) contributes to the altered network rhythm. These findings identify a new facet of maternal brain plasticity at the level of membrane properties and consequent ensemble activity.

Gamma-band oscillations (GBOs) elicited by transient nociceptive stimuli are one of the most promising biomarkers of pain across species. Still, whether these GBOs reflect stimulus encoding in the primary somatosensory cortex (S1) or nocifensive behavior in the primary motor cortex (M1) is debated. Here we recorded neural activity simultaneously from the brain surface as well as at different depths of the bilateral S1/M1 in freely-moving male rats receiving nociceptive stimulation. GBOs measured from superficial layers of S1 contralateral to the stimulated paw not only had the largest magnitude, but also showed the strongest temporal and phase coupling with epidural GBOs. Also, spiking of superficial S1 interneurons had the strongest phase coherence with epidural GBOs. These results provide the first direct demonstration that scalp GBOs, one of the most promising pain biomarkers, reflect neural activity strongly coupled with the fast spiking of interneurons in the superficial layers of the S1 contralateral to the stimulated side.

SIGNIFICANCE STATEMENT Nociceptive-induced gamma-band oscillations (GBOs) measured at population level are one of the most promising biomarkers of pain perception. Our results provide the direct demonstration that these GBOs reflect neural activity coupled with the spike firing of interneurons in the superficial layers of the primary somatosensory cortex (S1) contralateral to the side of nociceptive stimulation. These results address the ongoing debate about whether nociceptive-induced GBOs recorded with scalp EEG or epidurally reflect stimulus encoding in the S1 or nocifensive behavior in the primary motor cortex (M1), and will therefore influence how experiments in pain neuroscience will be designed and interpreted.

To determine whether Cav1.2 voltage-gated Ca²⁺ channels contribute to astrocyte activation, we generated an inducible conditional knock-out mouse in which the Cav1.2 α subunit was deleted in GFAP-positive astrocytes. This astrocytic Cav1.2 knock-out mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response. Deletion of Cav1.2 channels in GFAP-positive astrocytes during cuprizone-induced demyelination leads to a significant reduction in the degree of astrocyte and microglia activation and proliferation in mice of either sex. Concomitantly, the production of proinflammatory factors such as TNFα, IL1β and TGFβ1 was significantly decreased in the corpus callosum and cortex of Cav1.2 knock-out mice through demyelination. Furthermore, this mild inflammatory environment promotes oligodendrocyte progenitor cells maturation and myelin regeneration across the remyelination phase of the cuprizone model. Similar results were found in animals treated with nimodipine, a Cav1.2 Ca²⁺ channel inhibitor with high affinity to the CNS. Mice of either sex injected with nimodipine during the demyelination stage of the cuprizone treatment displayed a reduced number of reactive astrocytes and showed a faster and more efficient brain remyelination. Together, these results indicate that Cav1.2 Ca²⁺ channels play a crucial role in the induction and proliferation of reactive astrocytes during demyelination; and that attenuation of astrocytic voltage-gated Ca²⁺ influx may be an effective therapy to reduce brain inflammation and promote myelin recovery in demyelinating diseases.

SIGNIFICANCE STATEMENT Reducing voltage-gated Ca²⁺ influx in astrocytes during brain demyelination significantly attenuates brain inflammation and astrocyte reactivity. Furthermore, these changes promote myelin restoration and oligodendrocyte maturation throughout remyelination.

One of the first signs of viral infection is body-wide aches and pain. Although this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization is well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-β) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I IFNs stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double-stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.

SIGNIFICANCE STATEMENT It is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. Although specific mechanisms have been discovered for diverse bacterial and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type I interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling), which is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity

We will only achieve zero hunger if we speak on behalf of those unable to represent themselves. That was a key message during an event titled “Zero Hunger: are we ready?” at FAO headquarters in Rome, Italy, on Friday, 11 October. “Hungry people have no voice, they are different from all others,” said FAO Director-General José Graziano da Silva (pictured, left). “We [...]

Ecosystem services make human life possible by, for example, providing nutritious food and clean water, regulating disease and climate, supporting the pollination of crops and soil formation, and providing recreational, cultural and spiritual benefits. In 2014, the value of ecosystem services was estimated at a staggering US$ 125 trillion.  Ecosystem services, provided by biodiversity, are fundamental to food production and [...]

The Farmers’ Market has been postponed for Friday 6 March and until further notice.

The COVID-19 pandemic is currently one of the world’s most pressing issues and one that is increasingly shaping government policies. To help provide policy support and information to member [...]

How the beloved figure has become a lightning rod in a heated environmental debate

The findings further refute the outdated notion that humans' capacity for complex artistic expression evolved exclusively in Europe

Traces of lead pollution frozen in a glacier confirm that British lead production waned just before the death of Thomas Becket

The icy breath of the north covered everything around with ice cover. But the Restless Barents Sea does not want to give up.

Rice terraces in Longji,China.

The government of the Northwest Territories has made an exemption on border restrictions for a veterinarian from Alberta to practice in the territory, after he received public and political support.

Police used their conductive energy weapons four times during the arrest of a 31-year-old man who they say was smashing windows with a piece of rebar.

The premier’s office confirmed the news in an email statement, blaming visibility issues under "very specific lighting conditions."

A physiotherapist in Thunder Bay, Ont., has had his licence suspended until September, as part of a disciplinary hearing.

Job of The Week: CEO – Nordoff Robbins Music Therapy http://bit.ly/aFIMNM

A man is in police custody following an incident that briefly put the Burin Peninsula community of Lawn on high alert on Friday morning. 

Philip Pynn is being released from federal prison for a second time, after breaching conditions landed him back behind bars last year — but it's not clear where he can live.

Mice, rats, or hamsters are immunized by giving biweekly injections of a purified antigen, cultured cells, or cDNA. For mice, if a pure, soluble protein antigen is being used and is abundant, a dose of 50–100 µg in adjuvant at each immunization is a sensible general recommendation; for rats and hamsters, a dose of 100–200 µg is sufficient. Lower doses can be used for antigens with higher immunogenicity. Adjuvants (Freund's, Ribi, Hunter's TiterMax, ImmunEasy, or Alum) should be mixed with the immunizing antigen for the first two immunizations only; Complete Freund's adjuvant is only used with the first immunization. Subsequent immunizations are performed in phosphate-buffered saline (PBS) or normal saline, with or without Incomplete Freund's adjuvant. The choice of adjuvant is dependent on the subclass of immunoglobulin required. Over the course of the 6-wk immunization schedule, each animal usually receives a total of six injections (three subcutaneous and three intraperitoneal). Once a good titer has developed against the antigen of interest, regular boosts and bleeds are performed to collect the maximum amount of serum. For rats and hamsters, boosts should be spaced every 2–3 wk, and serum samples of 400–500 µL should be collected 10–12 d after each boost. For mice, boosts should be spaced every 2–3 wk, and serum samples of 200–300 µL should be collected 10–12 d after each boost.

Our ongoing celebration of the Library of Congress National Book Festival continues with former Secretary of State Condoleezza Rice discussing "Democracy: Stories from the Long Road to Freedom" on the Main Stage at the 2017 Festival.

Application deadline: 17 May 2020 | Banking Settlements Centre | Location: Basel, Switzerland

No global real estate market despite higher price synchronisation and growing role of international investors, central banks find (Press release, 18 February 2020)

Graduation is on hold for Dalhousie University medical student Manveer Bal, so he's decided to spend his newfound free time volunteering at the epicentre of the COVID-19 outbreak in Nova Scotia.

Police say efforts to find the driver of an abandoned car in Kings County last week likely saved his life.