Director Lenny Abrahamson and stars Daisy Edgar-Jones and Paul Mescal discuss making the sex scenes in Hulu's "Normal People," based on Sally Rooney's book.

SONOMA, Calif. – For a weekend with an IndyCar Series championship on the line and a season climaxing at Sonoma Raceway, there might not be two more relaxed drivers than Simon Pagenaud and Will Power.

At Indiana University, the invincibility of youth and the freedom of college life are shattered by a school year cut short.

After coronavirus restrictions are lifted, Indianapolis bars and breweries will face challenges in terms of short-term staffing and long-term survival

When the government eases restrictions, how will social and work life be different?

Ghana is well known for its elaborate funerals and rowdy election campaigns so coronavirus is changing everything.

The Ontario government has given hardware stores leave to reopen, as of Saturday, but the experience for shoppers will not be what it used to be.

Young medical students and health-care workers simply want to keep contributing in the only home they know.

Mathias Uhlén
Dec 1, 2005; 4:1920-1932
Research

Jürgen Cox
Sep 1, 2014; 13:2513-2526
Technological Innovation and Resources

Mohamad Navab
Sep 1, 2000; 41:1495-1508
Articles

Mohamad Navab
Sep 1, 2000; 41:1481-1494
Articles

Ronald M. Krauss
Jan 1, 1982; 23:97-104
Articles

The PET radiotracer ⁶⁸Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA-11) shows potential as an imaging biomarker for recurrent and metastatic prostate cancer. The purpose of this study was to determine repeatability of ⁶⁸Ga-PSMA-HBED-CC in a test-retest trial in subjects with metastatic prostate adenocarcinoma. Methods: Subjects with metastatic prostate cancer underwent two PET/CT scans with ⁶⁸Ga-PSMA-HBED-CC within 14 days (mean 6 ± 4 d). Lesions in bone, nodes, prostate/bed, and visceral organs as well as representative normal tissues (salivary glands and spleen) were segmented separately by two readers. Absolute and percent differences in SUV_max and SUVmean were calculated for all test-retest regions. Repeatability was assessed using percentage difference, within-subject coefficient of variation (wCV), repeatability coefficient (RC), and Bland-Altman analysis. Results: 18 subjects were evaluated, 16 of which demonstrated local or metastatic disease on ⁶⁸Ga-PSMA-HBED-CC PET/CT. A total of 136 lesions were segmented in bone (n = 99), nodes (n = 27), prostate/bed (n = 7), and viscera (n = 3). The wCV for SUV_max was 11.7% for bone lesions and 13.7% for nodes. The RC was ±32.5% SUV_max for bone lesions and ±37.9% SUV_max for nodal lesions, meaning 95% of the normal variability between two measurements will be within these numbers, so larger differences are likely attributable to true biological changes in tumor rather than normal physiologic or measurement variability. wCV in the salivary glands and spleen was 8.9% and 10.7% SUVmean, respectively. Conclusion: Repeatability measurements for PET/CT test-retest with ⁶⁸Ga-PSMA-HBED-CC show a wCV 12-14% SUV_max and RC ±33-38% SUV_max in bone and nodal lesions. These estimates are an important aspect of ⁶⁸Ga-PSMA-HBED-CC as a quantitative imaging biomarker. These estimates are similar to those reported for ¹⁸F-FDG, suggesting that ⁶⁸Ga-PSMA-HBED-CC PET/CT may be useful in monitoring response to therapy.

Jeroen van Smeden
Apr 7, 2020; 0:jlr.RA120000639v1-jlr.RA120000639
Research Articles

Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) stratum corneum ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active, epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in stratum corneum ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered stratum corneum ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS. 

Objective:

GPR40 is a G protein-coupled receptor regulating free fatty acid-induced insulin secretion. We have generated transgenic mice overexpressing the human GPR40 gene (hGPR40-Tg) under control of the mouse insulin II promoter and have used them to examine the role of GPR40 in the regulation of insulin secretion and glucose homeostasis.

Lena Eliasson
May 1, 2020; 69:804-812
Small Noncoding RNAs in Diabetes

Industries across the world face uncertainty, as no one entity can absolutely declare when or if economies will revert to normal in the wake of COVID-19. The local entertainment industry suffers the same uncertainty – and to address it, the Jamaica...

Joseph G. Yu
Oct 1, 2002; 51:2968-2974
Obesity Studies

BRIDGETOWN, Barbados, CMC – A few weeks before the official start of the 2020 Atlantic Hurricane Season, forecasters at the US-based Colorado State University are warning that the six-month period will be more active than normal. The CSU...

Insulin-induced hypoglycemia leads to far-ranging negative consequences in patients with diabetes. Components of the counterregulatory response (CRR) system that help minimize and reverse hypoglycemia and coordination between those components are well studied but not yet fully characterized. Here, we tested the hypothesis that acyl-ghrelin, a hormone that defends against hypoglycemia in a preclinical starvation model, is permissive for the normal CRR to insulin-induced hypoglycemia. Ghrelin knockout (KO) mice and wild-type (WT) littermates underwent an insulin bolus-induced hypoglycemia test and a low-dose hyperinsulinemic-hypoglycemic clamp procedure. Clamps also were performed in ghrelin-KO mice and C57BL/6N mice administered the growth hormone secretagogue receptor agonist HM01 or vehicle. Results show that hypoglycemia, as induced by an insulin bolus, was more pronounced and prolonged in ghrelin-KO mice, supporting previous studies suggesting increased insulin sensitivity upon ghrelin deletion. Furthermore, during hyperinsulinemic-hypoglycemic clamps, ghrelin-KO mice required a 10-fold higher glucose infusion rate (GIR) and exhibited less robust corticosterone and growth hormone responses. Conversely, HM01 administration, which reduced the GIR required by ghrelin-KO mice during the clamps, increased plasma corticosterone and growth hormone. Thus, our data suggest that endogenously produced acyl-ghrelin not only influences insulin sensitivity but also is permissive for the normal CRR to insulin-induced hypoglycemia.

28 January 2016

How China responds to the challenges of resource security and sustainability, working with others, will help define its reputation as a responsible actor on the world stage in the next decade, according to a new paper.

• It is time to upgrade global resource governance
• Meaningful progress cannot be achieved without China
• China will need to be both innovative and pragmatic in its approach
• New modes of cooperation are needed
• Changes in China’s economy present opportunities and risks

OBJECTIVE

To assess functional β-cell capacity in type 2 diabetes during 2 years of remission induced by dietary weight loss.

I’ve been talking to a man, we have mutual interest in each other. We talked on the phone for over an hour the night before last and it was an amazing conversation. The next day he had no contact with me, which in my mind it didn’t bother me and still kind of isn’t I think he just is doing his own thing and likes his personal space. I’m not too bothered or worried but still questioning why? Is it normal for a man to kinda disappear and have no contact for a day?

Paris : G. Steinheil, 1892.

A private pre-K-12 school in Idaho welcomes students back after its coronavirus shutdown, but with shortened days, a closed cafeteria, no bus service, and other signs that things aren't back to normal.

Spanking new stadiums in Los Angeles and Las Vegas unveiled in prime time. Business as usual, and you really can't blame the NFL for that. “The release of the NFL schedule is something our fans eagerly anticipate every year, as they look forward with hope and optimism to the season ahead,” Commissioner Roger Goodell said.

Vincent Brault, Christine Keribin, Mahendra Mariadassou.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1234--1268.

Abstract:
The Latent Block Model (LBM) is a model-based method to cluster simultaneously the $d$ columns and $n$ rows of a data matrix. Parameter estimation in LBM is a difficult and multifaceted problem. Although various estimation strategies have been proposed and are now well understood empirically, theoretical guarantees about their asymptotic behavior is rather sparse and most results are limited to the binary setting. We prove here theoretical guarantees in the valued settings. We show that under some mild conditions on the parameter space, and in an asymptotic regime where $log (d)/n$ and $log (n)/d$ tend to $0$ when $n$ and $d$ tend to infinity, (1) the maximum-likelihood estimate of the complete model (with known labels) is consistent and (2) the log-likelihood ratios are equivalent under the complete and observed (with unknown labels) models. This equivalence allows us to transfer the asymptotic consistency, and under mild conditions, asymptotic normality, to the maximum likelihood estimate under the observed model. Moreover, the variational estimator is also consistent and, under the same conditions, asymptotically normal.

Uttam Bandyopadhyay, Shirsendu Mukherjee, Atanu Biswas.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 2, 291--303.

Abstract:
In adaptive crossover design, our goal is to allocate more patients to a promising treatment sequence. The present work contains a very simple three period crossover design for two competing treatments where the allocation in period 3 is done on the basis of the data obtained from the first two periods. Assuming normality of response variables we use a reliability functional for the choice between two treatments. We calculate the allocation proportions and their standard errors corresponding to the possible treatment combinations. We also derive some asymptotic results and provide solutions on related inferential problems. Moreover, the proposed procedure is compared with a possible competitor. Finally, we use a data set to illustrate the applicability of the proposed design.

Andreas Anastasiou, Robert E. Gaunt.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 1, 136--149.

Abstract:
We use the delta method and Stein’s method to derive, under regularity conditions, explicit upper bounds for the distributional distance between the distribution of the maximum likelihood estimator (MLE) of a $d$-dimensional parameter and its asymptotic multivariate normal distribution. Our bounds apply in situations in which the MLE can be written as a function of a sum of i.i.d. $t$-dimensional random vectors. We apply our general bound to establish a bound for the multivariate normal approximation of the MLE of the normal distribution with unknown mean and variance.

Khamis K. Said, Wei Ning, Yubin Tian.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 2, 280--300.

Abstract:
In this paper, we study the change point problem for the skew normal distribution model from the view of model selection problem. The detection procedure based on the modified information criterion (MIC) for change problem is proposed. Such a procedure has advantage in detecting the changes in early and late stage of a data comparing to the one based on the traditional Schwarz information criterion which is well known as Bayesian information criterion (BIC) by considering the complexity of the models. Due to the difficulty in deriving the analytic asymptotic distribution of the test statistic based on the MIC procedure, the bootstrap simulation is provided to obtain the critical values at the different significance levels. Simulations are conducted to illustrate the comparisons of performance between MIC, BIC and likelihood ratio test (LRT). Such an approach is applied on two stock market data sets to indicate the detection procedure.

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.

O. Collier, L. Comminges, A.B. Tsybakov.

Source: Bernoulli, Volume 26, Number 3, 1989--2020.

Abstract:
We study the problem of estimation of $N_{gamma }( heta )=sum_{i=1}^{d}| heta _{i}|^{gamma }$ for $gamma >0$ and of the $ell _{gamma }$-norm of $ heta $ for $gamma ge 1$ based on the observations $y_{i}= heta _{i}+varepsilon xi _{i}$, $i=1,ldots,d$, where $ heta =( heta _{1},dots , heta _{d})$ are unknown parameters, $varepsilon >0$ is known, and $xi _{i}$ are i.i.d. standard normal random variables. We find the non-asymptotic minimax rate for estimation of these functionals on the class of $s$-sparse vectors $ heta $ and we propose estimators achieving this rate.

Nicolas Privault, Grzegorz Serafin.

Source: Bernoulli, Volume 26, Number 1, 587--615.

Abstract:
We derive normal approximation bounds in the Kolmogorov distance for sums of discrete multiple integrals and weighted $U$-statistics made of independent Bernoulli random variables. Such bounds are applied to normal approximation for the renormalized subgraph counts in the Erdős–Rényi random graph. This approach completely solves a long-standing conjecture in the general setting of arbitrary graph counting, while recovering recent results obtained for triangles and improving other bounds in the Wasserstein distance.

Vice President Pence’s trip to Iowa shows how the Trump administration’s aims to move past coronavirus are sometimes complicated by the virus itself.

Jami J. Mulgrave, Subhashis Ghosal.

Source: Bayesian Analysis, Volume 15, Number 2, 449--475.

Abstract:
Gaussian graphical models have been used to study intrinsic dependence among several variables, but the Gaussianity assumption may be restrictive in many applications. A nonparanormal graphical model is a semiparametric generalization for continuous variables where it is assumed that the variables follow a Gaussian graphical model only after some unknown smooth monotone transformations on each of them. We consider a Bayesian approach in the nonparanormal graphical model by putting priors on the unknown transformations through a random series based on B-splines where the coefficients are ordered to induce monotonicity. A truncated normal prior leads to partial conjugacy in the model and is useful for posterior simulation using Gibbs sampling. On the underlying precision matrix of the transformed variables, we consider a spike-and-slab prior and use an efficient posterior Gibbs sampling scheme. We use the Bayesian Information Criterion to choose the hyperparameters for the spike-and-slab prior. We present a posterior consistency result on the underlying transformation and the precision matrix. We study the numerical performance of the proposed method through an extensive simulation study and finally apply the proposed method on a real data set.

Andrea Cremaschi, Raffaele Argiento, Katherine Shoemaker, Christine Peterson, Marina Vannucci.

Source: Bayesian Analysis, Volume 14, Number 4, 1271--1301.

Abstract:
Gaussian graphical models are useful tools for exploring network structures in multivariate normal data. In this paper we are interested in situations where data show departures from Gaussianity, therefore requiring alternative modeling distributions. The multivariate $t$ -distribution, obtained by dividing each component of the data vector by a gamma random variable, is a straightforward generalization to accommodate deviations from normality such as heavy tails. Since different groups of variables may be contaminated to a different extent, Finegold and Drton (2014) introduced the Dirichlet $t$ -distribution, where the divisors are clustered using a Dirichlet process. In this work, we consider a more general class of nonparametric distributions as the prior on the divisor terms, namely the class of normalized completely random measures (NormCRMs). To improve the effectiveness of the clustering, we propose modeling the dependence among the divisors through a nonparametric hierarchical structure, which allows for the sharing of parameters across the samples in the data set. This desirable feature enables us to cluster together different components of multivariate data in a parsimonious way. We demonstrate through simulations that this approach provides accurate graphical model inference, and apply it to a case study examining the dependence structure in radiomics data derived from The Cancer Imaging Atlas.

Luis Gutiérrez, Eduardo Gutiérrez-Peña, Ramsés H. Mena.

Source: Bayesian Analysis, Volume 14, Number 2, 427--447.

Abstract:
This work presents a Bayesian predictive approach to statistical shape analysis. A modeling strategy that starts with a Gaussian distribution on the configuration space, and then removes the effects of location, rotation and scale, is studied. This boils down to an application of the projected normal distribution to model the configurations in the shape space, which together with certain identifiability constraints, facilitates parameter interpretation. Having better control over the parameters allows us to generalize the model to a regression setting where the effect of predictors on shapes can be considered. The methodology is illustrated and tested using both simulated scenarios and a real data set concerning eight anatomical landmarks on a sagittal plane of the corpus callosum in patients with autism and in a group of controls.

Matteo Carandini
Nov 1, 1997; 17:8621-8644
Articles

Italian translation of the BIS press release about the BIS Quarterly Review, December 2018

French translation of the BIS press release about the BIS Quarterly Review, December 2018

Spanish translation of the BIS press release about the BIS Quarterly Review, December 2018

Fire scientist say that Saskatchewan say Canadian Forest Service is updating their interactive maps every month from May to September this year so people can check the fire map in their region. Saskatchewan is one of the highest chances of fire this year.

Imagining America between the crisis and the cure.

Manitoba municipalities will be receiving most of their operating funding from the province sooner than usual because of the COVID-19 pandemic, the province announced Friday.

Retailers around the world are adjusting their business models in the face of COVID-19 social distancing requirements. Two consumer reports on shopping pattern changes during the pandemic offer two main findings: a) It is crucial for merchants to create ways to connect with new and long-term customers; and b) Consumers can not fully solve the empty shelf problem through buying online.