Jere Koskela, Paul A. Jenkins, Adam M. Johansen, Dario Spanò.

Source: The Annals of Statistics, Volume 48, Number 1, 560--583.

Abstract:
We study weighted particle systems in which new generations are resampled from current particles with probabilities proportional to their weights. This covers a broad class of sequential Monte Carlo (SMC) methods, widely-used in applied statistics and cognate disciplines. We consider the genealogical tree embedded into such particle systems, and identify conditions, as well as an appropriate time-scaling, under which they converge to the Kingman $n$-coalescent in the infinite system size limit in the sense of finite-dimensional distributions. Thus, the tractable $n$-coalescent can be used to predict the shape and size of SMC genealogies, as we illustrate by characterising the limiting mean and variance of the tree height. SMC genealogies are known to be connected to algorithm performance, so that our results are likely to have applications in the design of new methods as well. Our conditions for convergence are strong, but we show by simulation that they do not appear to be necessary.

Gaoxiang Jia, Xinlei Wang, Qiwei Li, Wei Lu, Ximing Tang, Ignacio Wistuba, Yang Xie.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1617--1647.

Abstract:
Formalin-fixed paraffin-embedded (FFPE) samples have great potential for biomarker discovery, retrospective studies and diagnosis or prognosis of diseases. Their application, however, is hindered by the unsatisfactory performance of traditional gene expression profiling techniques on damaged RNAs. NanoString nCounter platform is well suited for profiling of FFPE samples and measures gene expression with high sensitivity which may greatly facilitate realization of scientific and clinical values of FFPE samples. However, methodological development for normalization, a critical step when analyzing this type of data, is far behind. Existing methods designed for the platform use information from different types of internal controls separately and rely on an overly-simplified assumption that expression of housekeeping genes is constant across samples for global scaling. Thus, these methods are not optimized for the nCounter system, not mentioning that they were not developed for FFPE samples. We construct an integrated system of random-coefficient hierarchical regression models to capture main patterns and characteristics observed from NanoString data of FFPE samples and develop a Bayesian approach to estimate parameters and normalize gene expression across samples. Our method, labeled RCRnorm, incorporates information from all aspects of the experimental design and simultaneously removes biases from various sources. It eliminates the unrealistic assumption on housekeeping genes and offers great interpretability. Furthermore, it is applicable to freshly frozen or like samples that can be generally viewed as a reduced case of FFPE samples. Simulation and applications showed the superior performance of RCRnorm.

Holger Sambale, Arthur Sinulis.

Source: Bernoulli, Volume 26, Number 3, 1863--1890.

Abstract:
We derive sufficient conditions for a probability measure on a finite product space (a spin system ) to satisfy a (modified) logarithmic Sobolev inequality. We establish these conditions for various examples, such as the (vertex-weighted) exponential random graph model, the random coloring and the hard-core model with fugacity. This leads to two separate branches of applications. The first branch is given by mixing time estimates of the Glauber dynamics. The proofs do not rely on coupling arguments, but instead use functional inequalities. As a byproduct, this also yields exponential decay of the relative entropy along the Glauber semigroup. Secondly, we investigate the concentration of measure phenomenon (particularly of higher order) for these spin systems. We show the effect of better concentration properties by centering not around the mean, but around a stochastic term in the exponential random graph model. From there, one can deduce a central limit theorem for the number of triangles from the CLT of the edge count. In the Erdős–Rényi model the first-order approximation leads to a quantification and a proof of a central limit theorem for subgraph counts.

China says it will improve public health systems after criticism of its early response to the virus.

Larry R. Squire
Oct 14, 2009; 29:12711-12716
40th Anniversary Retrospective

Christelle Peyron
Dec 1, 1998; 18:9996-10015
Articles

PR Montague
Mar 1, 1996; 16:1936-1947
Articles

Geoffrey M. Boynton
Jul 1, 1996; 16:4207-4221
Articles

Speech by Mr Claudio Borio, Head of the Monetary and Economic Department of the BIS, at the OECD-G20 High Level Policy Seminar, Paris, 11 September 2019.

Op-ed by Mr Agustín Carstens, General Manager of the BIS, published in The Business Times Singapore, 13 November 2019.

Lecture by Mr Agustín Carstens, General Manager of the BIS, at the Princeton University, Princeton, New Jersey, 5 December 2019.

The Drosophila nervous system is ensheathed by a layer of outer glial cells, the perineurial glia, and a specialized extracellular matrix, the neural lamella. The function of perineurial glial cells and how they interact with the extracellular matrix are just beginning to be elucidated. Integrin-based focal adhesion complexes link the glial membrane to the extracellular matrix, but little is known about integrin's regulators in the glia. The transmembrane Ig domain protein Basigin/CD147/EMMPRIN is highly expressed in the perineurial glia surrounding the Drosophila larval nervous system. Here we show that Basigin associates with integrin at the focal adhesions to uphold the structure of the glia-extracellular matrix sheath. Knockdown of Basigin in perineurial glia using RNAi results in significant shortening of the ventral nerve cord, compression of the glia and extracellular matrix in the peripheral nerves, and reduction in larval locomotion. We determined that Basigin is expressed in close proximity to integrin at the glial membrane, and that expression of the extracellular integrin-binding domain of Basigin is sufficient to rescue peripheral glial compression. We also found that a reduction in expression of integrin at the membrane rescues the ventral nerve cord shortening, peripheral glial compression, and locomotor phenotypes, and that reduction in the integrin-binding protein Talin can partially rescue glial compression. These results identify Basigin as a potential negative regulator of integrin in the glia, supporting proper glial and extracellular matrix ensheathment of the nervous system.

SIGNIFICANCE STATEMENT The glial cells and extracellular matrix play important roles in supporting and protecting the nervous system, but the interactions between these components have not been well characterized. Our study identified expression of a conserved Ig superfamily protein, Basigin, at the glial membrane of Drosophila where it associates with the integrin-based focal adhesion complexes to ensure proper ensheathment of the CNS and PNS. Loss of Basigin in the glia results in an overall compression of the nervous system due to integrin dysregulation, which causes locomotor defects in the animals. This underlies the importance of glia-matrix communication for structural and functional support of the nervous system.

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that play critical roles in neuronal development and nervous system function. Here, we developed a model to study NMDARs in early development in zebrafish, by generating CRISPR-mediated lesions in the NMDAR genes, grin1a and grin1b, which encode the obligatory GluN1 subunits. While receptors containing grin1a or grin1b show high Ca²⁺ permeability, like their mammalian counterpart, grin1a is expressed earlier and more broadly in development than grin1b. Both grin1a^–/– and grin1b^–/– zebrafish are viable. Unlike in rodents, where the grin1 knockout is embryonic lethal, grin1 double-mutant fish (grin1a^–/–; grin1b^–/–), which lack all NMDAR-mediated synaptic transmission, survive until ~10 d dpf (days post fertilization), providing a unique opportunity to explore NMDAR function during development and in generating behaviors. Many behavioral defects in the grin1 double-mutant larvae, including abnormal evoked responses to light and acoustic stimuli, prey-capture deficits, and a failure to habituate to acoustic stimuli, are replicated by short-term treatment with the NMDAR antagonist MK-801, suggesting that they arise from acute effects of compromised NMDAR-mediated transmission. Other defects, however, such as periods of hyperactivity and alterations in place preference, are not phenocopied by MK-801, suggesting a developmental origin. Together, we have developed a unique model to study NMDARs in the developing vertebrate nervous system.

SIGNIFICANCE STATEMENT Rapid communication between cells in the nervous system depends on ion channels that are directly activated by chemical neurotransmitters. One such ligand-gated ion channel, the NMDAR, impacts nearly all forms of nervous system function. It has been challenging, however, to study the prolonged absence of NMDARs in vertebrates, and hence their role in nervous system development, due to experimental limitations. Here, we demonstrate that zebrafish lacking all NMDAR transmission are viable through early development and are capable of a wide range of stereotypic behaviors. As such, this zebrafish model provides a unique opportunity to study the role of NMDAR in the development of the early vertebrate nervous system.

FAO will use World Food Day this year to promote one of the five pillars of Zero Hunger Challenge. The theme of the campaign will be “Sustainable Food Systems for Food Security and Nutrition.” Events in more than 120 countries – supported by videos, an issues paper, posters, media interviews and more – will communicate the message that our food systems [...]

Maize, rice and wheat are fundamental to world food security. We must safeguard production in the world’s grain belts and rice bowls, and increase yields in countries where production has to substantially improve as populations grow. Climate change adds new pressures on cereals, including rising temperatures and a higher incidence of pests, diseases, droughts and floods. FAO’s model of ecosystem-based agriculture, [...]

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 [...]

  We can’t really talk about the planet’s most pressing environmental problems without talking about food systems. And by food systems, we also mean the agriculture that it takes to support them: farming, fisheries, forestry and the value chains that provide food and fiber for our daily lives. 

Early conservation research and scientific expeditions laid the groundwork and helped to convince the public national parks were a good idea

Perhaps the cigar-shaped object is a shard from a shredded planetary body, a computer simulation suggests

64-year-old John Neville, in agony and needing his wisdom tooth extracted, has been navigating a complex tangle of COVID-19 restrictions in an unsuccessful attempt at getting emergency dental care.

Remarks by Benoît Cœuré, Head of the Bank for International Settlements Innovation Hub, at the Reinventing Bretton Woods Committee - Chamber of Digital Commerce webinar on "The world economy transformed", 17 April 2020.

European Systemic Risk Board Occasional Papers by Greg Ros

Central Bank of Chile Working Papers by Andrés Sagner

You probably remember last year’s video; The Benefits of the Structure System Tool in SOLIDWORKS 2019. By popular demand, Elite Applications Engineer Colin Murphy is back to highlight the benefits of the Structure System tool in SOLIDWORKS 2020!   What

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CONTEXT:

Recommendations conflict regarding universal application of formal screening instruments in primary care (PC) and PC-like settings for autism spectrum disorder (ASD).

CONTEXT:

Research reveals racial, ethnic, and socioeconomic disparities in autism diagnosis; there is limited information on potential disparities related to other dimensions of services.

Schools can't even afford to hire enough teachers, so why are we surprised that teachers are turning to a website for resources? asks Kat Tipton.

After investing eight years on a system that fell far short of expectations, the city is gearing up to replace or fix it.

Framed prints of Steven Camley's cartoons are available by calling 0141 302 6210

Middle and high schools principals shared stories about trying to replace As, Bs, and Cs with more meaningful measures of student learning, but ran into obstacles and pushback at every step.

The availability of rapid response systems to assist deteriorating patients is the standard of care in children’s hospitals. Metrics for evaluating their effectiveness include cardiac and respiratory arrest rates, rare events that require years of data to show significant improvements.

A proximate outcome for in-hospital mortality among patients receiving rapid response system assistance was developed. This "critical deterioration" metric was eightfold more common than arrests and demonstrated criterion and construct validity, facilitating meaningful evaluation over shorter periods of time. (Read the full article)

Percentile charts for birth weight are used to assess the somatic development of neonates (small, appropriate, or large for gestational age).

A systematic error was identified in the majority of birth weight percentile charts. As a consequence, small for gestational age rates are overestimated and large for gestational age rates are underestimated; ~5% of neonates are misclassified. (Read the full article)

Systematic screening for child abuse of all children presenting at emergency departments might increase the detection rate of child abuse but studies to support this proposal are scarce.

Systematic screening for child abuse in emergency departments is effective in increasing the detection of suspected child abuse. Training emergency department staff and requiring screening legally at emergency departments increase the extent of screening. (Read the full article)

Stressful events adversely affect the immune system, particularly the natural killer (NK) cells. Infants in the NICUs are exposed to stressful stimuli. The effect of massage therapy on the immune system of preterm infants has not been investigated.

This randomized placebo-controlled study found daily massage performed in stable preterm infants for a minimum of 5 days was associated with an increase in NK cell cytotoxicity despite lower absolute NK cell numbers compared with controls. (Read the full article)

Early readmission of apparently healthy newborns may result from inadequate assessment of a newborn’s readiness for discharge. Knowledge of the frequency, causes, and variation in the rate of newborn readmissions may assist in developing quality improvement interventions.

Feeding problems and jaundice, both potentially preventable, are the leading causes of readmission. Late preterm and early term newborns are more likely to be readmitted and should have close follow-up after discharge from a well baby nursery. (Read the full article)

Systematic health disparities in adults with systemic lupus erythematosus are well documented and are likely driven by biologic as well as modifiable factors. Sociodemographic factors and health care delivery characteristics have been associated with poor outcomes.

In hospitalized children with systemic lupus erythematosus, race and ethnicity were associated with increased risk for ICU admissions, end-stage renal disease, and death. Identification of sociodemographic factors associated with outcomes is important to address the needs of these vulnerable patients. (Read the full article)

Early establishment of a dental home is critical for addressing the "silent epidemic" of early childhood caries. Physicians and dentists have worked to improve children’s access to dental care, but little is known about caregivers’ role in this context.

Addressing factors that affect the establishment of a child’s dental home, such as caregivers’ dental neglect and problem-driven care-seeking behaviors, is essential. Caregiver engagement seems to be pivotal for increasing use of preventive services while decreasing episodic and problem-initiated care. (Read the full article)

Studies on adult patients who have Crohn disease have shown a comparative benefit of anti-TNFα versus placebo and thiopurines. These same studies have not been done in children, because of time, cost, and ethical (withholding an efficacious treatment) challenges.

Anti-TNFα therapy administered in routine practice to children with Crohn disease was more effective than usual care at achieving clinical and corticosteroid-free remission. Using data from the ImproveCareNow learning health system for observational research is feasible and produces valuable evidence. (Read the full article)

A substantial gap exists between what is recommended for effective primary care of children and what takes place. Patient-centered health information technologies have been used to gather information and counsel parents, however, have not been integrated directly with electronic health records nor been speech-based to improve decision-making at the point-of-care.

This study shows that a ubiquitous technology, the telephone, can be successfully used to automatically assess and counsel parents before pediatric primary care visits as well as inform their primary care clinicians in a way that is feasible and effective for multiple important issues. (Read the full article)

In 2009, only 58% of pediatricians were using electronic health records (EHRs), most of which were lacking pediatric functionality. The American Recovery and Reinvestment Act (ARRA) of 2009 accelerated the implementation of EHRs in pediatric offices.

The effects of ARRA have remained largely unmeasured in pediatrics. This study provides information on the prevalence and functionalities of EHRs, as well as physicians’ perceptions. (Read the full article)