On March 20, the ADA will release an on-demand webinar offering answers to frequently asked questions about infection control protocol and procedures related to COVID-19.

The ADA posted an on-demand webinar March 20 offering answers to frequently asked questions about infection control in the midst of the COVID-19 pandemic.

A microbe found in mosquitoes that appears to block malaria could be used to control spread of the disease in humans, according to researchers in Kenya and Britain.

OBJECTIVE

To investigate the association of the cardiovascular risk factor lipoprotein (Lp)(a) and vascular complications in patients with type 1 diabetes.

OBJECTIVE

To study whether the effects of intensive glycemic control on major vascular outcomes (a composite of major macrovascular and major microvascular events), all-cause mortality, and severe hypoglycemia events differ among participants with different levels of 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and hemoglobin A_1c (HbA_1c) at baseline.

OBJECTIVE

To assess the efficacy and safety of a 1:1 fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) versus lixisenatide (Lixi) in insulin-naive Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs).

OBJECTIVE

The role of U300 glargine insulin for the inpatient management of type 2 diabetes (T2D) has not been determined. We compared the safety and efficacy of glargine U300 versus glargine U100 in noncritically ill patients with T2D.

Growing numbers of African and Asian migrants are moving through Latin America, many hoping to reach the United States or Canada after expensive, arduous, and often dangerous journeys that can take months or even years. As more extracontinental migrants transit through South and Central America, Colombia, Panama, and Costa Rica have developed the most comprehensive policies to manage these flows, sometimes working in coordination with the U.S. government.

OBJECTIVE

Bariatric surgery is an effective treatment for obesity, but it is unknown if outcomes differ between adults with early- versus adult-onset obesity. We investigated how obesity status at 20 years of age affects outcomes after bariatric surgery later in life.

OBJECTIVE

To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes.

Joseph A. Granata
Jan 1, 2015; 33:14-19
Feature Articles

Huy A. Tran
Jul 1, 2004; 22:141-143
Case Studies

Jay S. Skyler
Oct 1, 2004; 22:162-166
Feature Articles

Edward C. Chao
Jan 1, 2014; 32:4-11
Feature Articles

As the threat of COVID-19 continues, infectious disease expert and TED Fellow Adam Kucharski answers five key questions about the novel coronavirus, providing necessary perspective on its transmission, how governments have responded and what might need to change about our social behavior to end the pandemic. (This video is excerpted from a 70-minute interview between Kucharski and head of TED Chris Anderson. Listen to the full interview at http://go.ted.com/adamkucharski. Recorded March 11, 2020)

"It is timely that the higher education sector examines paths forward to address and indeed engage in the new environment in which it will work in the future. This fellowship explored two approaches to engage students more deeply in their education. The first approach is generally termed 'interdisciplinary studies' where students define their own program of study; the second approach focuses on topic structure where students are given a wide range of choice and in effect can build a topic that suits their interests."--Page iv.

This researchprojectimplemented a randomizedcontrolledtrial ofthe SEAM program in Terms 3 and 4 ofthe 2016 school year. The purpose of the study was to determine the effects of the SEAM program. The study enrolled 448 treatment group students who were referred to SATOs for potential SEAM intervention, and 448 matched control group students who were not referred to SATOs. Approximately one-third of treatment group students received a compulsory conference notice, approximately one-third of treatment students' families signed an attendance plan, about 20% had a compulsory conference take place, and payment was suspended for approximately 5% of treatment students. No significant differences following any of these interventions were observed between treatment and control students.

Hypertension -- Diet therapy -- Recipes.

Gun control -- Australia.

Goal (Psychology)

England : Society of Medical Officers of Health in England, [192-?]

Rockville, Maryland : National Institute on Drug Abuse, 1986.

Sihai Dave Zhao, Yet Tien Nguyen.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 110--142.

Abstract:
It is frequently of interest to identify simultaneous signals, defined as features that exhibit statistical significance across each of several independent experiments. For example, genes that are consistently differentially expressed across experiments in different animal species can reveal evolutionarily conserved biological mechanisms. However, in some problems the test statistics corresponding to these features can have complicated or unknown null distributions. This paper proposes a novel nonparametric false discovery rate control procedure that can identify simultaneous signals even without knowing these null distributions. The method is shown, theoretically and in simulations, to asymptotically control the false discovery rate. It was also used to identify genes that were both differentially expressed and proximal to differentially accessible chromatin in the brains of mice exposed to a conspecific intruder. The proposed method is available in the R package github.com/sdzhao/ssa.

Victor Coscrato, Rafael Izbicki, Rafael B. Stern.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 2, 230--250.

Abstract:
Despite its common practice, statistical hypothesis testing presents challenges in interpretation. For instance, in the standard frequentist framework there is no control of the type II error. As a result, the non-rejection of the null hypothesis $(H_{0})$ cannot reasonably be interpreted as its acceptance. We propose that this dilemma can be overcome by using agnostic hypothesis tests, since they can control the type I and II errors simultaneously. In order to make this idea operational, we show how to obtain agnostic hypothesis in typical models. For instance, we show how to build (unbiased) uniformly most powerful agnostic tests and how to obtain agnostic tests from standard p-values. Also, we present conditions such that the above tests can be made logically coherent. Finally, we present examples of consistent agnostic hypothesis tests.

Durba Bhattacharya, Sourabh Bhattacharya.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 1, 71--89.

Abstract:
Present day bio-medical research is pointing towards the fact that cognizance of gene–environment interactions along with genetic interactions may help prevent or detain the onset of many complex diseases like cardiovascular disease, cancer, type2 diabetes, autism or asthma by adjustments to lifestyle. In this regard, we propose a Bayesian semiparametric model to detect not only the roles of genes and their interactions, but also the possible influence of environmental variables on the genes in case-control studies. Our model also accounts for the unknown number of genetic sub-populations via finite mixtures composed of Dirichlet processes. An effective parallel computing methodology, developed by us harnesses the power of parallel processing technology to increase the efficiencies of our conditionally independent Gibbs sampling and Transformation based MCMC (TMCMC) methods. Applications of our model and methods to simulation studies with biologically realistic genotype datasets and a real, case-control based genotype dataset on early onset of myocardial infarction (MI) have yielded quite interesting results beside providing some insights into the differential effect of gender on MI.

Motion synthesis in a dynamic environment has been a long-standing problem for character animation. Methods using motion capture data tend to scale poorly in complex environments because of their larger capturing and labeling requirement. Physics-based controllers are effective in this regard, albeit less controllable. In this paper, we present CARL, a quadruped agent that can be controlled with high-level directives and react naturally to dynamic environments. Starting with an agent that can imitate individual animation clips, we use Generative Adversarial Networks to adapt high-level controls, such as speed and heading, to action distributions that correspond to the original animations. Further fine-tuning through the deep reinforcement learning enables the agent to recover from unseen external perturbations while producing smooth transitions. It then becomes straightforward to create autonomous agents in dynamic environments by adding navigation modules over the entire process. We evaluate our approach by measuring the agent's ability to follow user control and provide a visual analysis of the generated motion to show its effectiveness.

Chanmin Kim, Michael J. Daniels, Joseph W. Hogan, Christine Choirat, Corwin M. Zigler.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1927--1956.

Abstract:
Emission control technologies installed on power plants are a key feature of many air pollution regulations in the US. While such regulations are predicated on the presumed relationships between emissions, ambient air pollution and human health, many of these relationships have never been empirically verified. The goal of this paper is to develop new statistical methods to quantify these relationships. We frame this problem as one of mediation analysis to evaluate the extent to which the effect of a particular control technology on ambient pollution is mediated through causal effects on power plant emissions. Since power plants emit various compounds that contribute to ambient pollution, we develop new methods for multiple intermediate variables that are measured contemporaneously, may interact with one another, and may exhibit joint mediating effects. Specifically, we propose new methods leveraging two related frameworks for causal inference in the presence of mediating variables: principal stratification and causal mediation analysis. We define principal effects based on multiple mediators, and also introduce a new decomposition of the total effect of an intervention on ambient pollution into the natural direct effect and natural indirect effects for all combinations of mediators. Both approaches are anchored to the same observed-data models, which we specify with Bayesian nonparametric techniques. We provide assumptions for estimating principal causal effects, then augment these with an additional assumption required for causal mediation analysis. The two analyses, interpreted in tandem, provide the first empirical investigation of the presumed causal pathways that motivate important air quality regulatory policies.

Luis Gutiérrez, Andrés F. Barrientos, Jorge González, Daniel Taylor-Rodríguez.

Source: Bayesian Analysis, Volume 14, Number 2, 649--675.

Abstract:
We propose a Bayesian nonparametric strategy to test for differences between a control group and several treatment regimes. Most of the existing tests for this type of comparison are based on the differences between location parameters. In contrast, our approach identifies differences across the entire distribution, avoids strong modeling assumptions over the distributions for each treatment, and accounts for multiple testing through the prior distribution on the space of hypotheses. The proposal is compared to other commonly used hypothesis testing procedures under simulated scenarios. Two real applications are also analyzed with the proposed methodology.

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.

Peter J. Diggle, Emanuele Giorgi, Julienne Atsame, Sylvie Ntsame Ella, Kisito Ogoussan, Katherine Gass.

Source: Statistical Science, Volume 35, Number 1, 42--50.

Abstract:
Vector-borne diseases have long presented major challenges to the health of rural communities in the wet tropical regions of the world, but especially in sub-Saharan Africa. In this paper, we describe the contribution that statistical modelling has made to the global elimination programme for one vector-borne disease, onchocerciasis. We explain why information on the spatial distribution of a second vector-borne disease, Loa loa, is needed before communities at high risk of onchocerciasis can be treated safely with mass distribution of ivermectin, an antifiarial medication. We show how a model-based geostatistical analysis of Loa loa prevalence survey data can be used to map the predictive probability that each location in the region of interest meets a WHO policy guideline for safe mass distribution of ivermectin and describe two applications: one is to data from Cameroon that assesses prevalence using traditional blood-smear microscopy; the other is to Africa-wide data that uses a low-cost questionnaire-based method. We describe how a recent technological development in image-based microscopy has resulted in a change of emphasis from prevalence alone to the bivariate spatial distribution of prevalence and the intensity of infection among infected individuals. We discuss how statistical modelling of the kind described here can contribute to health policy guidelines and decision-making in two ways. One is to ensure that, in a resource-limited setting, prevalence surveys are designed, and the resulting data analysed, as efficiently as possible. The other is to provide an honest quantification of the uncertainty attached to any binary decision by reporting predictive probabilities that a policy-defined condition for action is or is not met.

William W. Seeley
Feb 28, 2007; 27:2349-2356
BehavioralSystemsCognitive

Georg S. Kranz
Nov 12, 2014; 34:15466-15475
Systems/Circuits

William W. Seeley
Feb 28, 2007; 27:2349-2356
BehavioralSystemsCognitive

Microglial cells are considered as sensors of brain pathology by detecting any sign of brain lesions, infections, or dysfunction and can influence the onset and progression of neurological diseases. They are capable of sensing their neuronal environment via many different signaling molecules, such as neurotransmitters, neurohormones and neuropeptides. The neuropeptide VGF has been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide and has been shown to signal via C3aR1 and C1qBP receptors. The effect of TLQP21 on microglial functions in health or disease is not known. Studying microglial cells in acute brain slices, we found that TLQP21 impaired metabotropic purinergic signaling. Specifically, it attenuated the ATP-induced activation of a K⁺ conductance, the UDP-stimulated phagocytic activity, and the ATP-dependent laser lesion-induced process outgrowth. These impairments were reversed by blocking C1qBP, but not C3aR1 receptors. While microglia in brain slices from male mice lack C3aR1 receptors, both receptors are expressed in primary cultured microglia. In addition to the negative impact on purinergic signaling, we found stimulating effects of TLQP21 in cultured microglia, which were mediated by C3aR1 receptors: it directly evoked membrane currents, stimulated basal phagocytic activity, evoked intracellular Ca²⁺ transient elevations, and served as a chemotactic signal. We conclude that TLQP21 has differential effects on microglia depending on C3aR1 activation or C1qBP-dependent attenuation of purinergic signaling. Thus, TLQP21 can modulate the functional phenotype of microglia, which may have an impact on their function in health and disease.

SIGNIFICANCE STATEMENT The neuropeptide VGF and its peptides have been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide that activates C1qBP receptors, which are expressed by microglia. We show here, for the first time, that TLQP21 impairs P2Y-mediated purinergic signaling and related functions. These include modulation of phagocytic activity and responses to injury. As purinergic signaling is central for microglial actions in the brain, this TLQP21-mediated mechanism might regulate microglial activity in health and disease. We furthermore show that, in addition to C1qBP, functional C3aR1 responses contribute to TLQP21 action on microglia. However, C3aR1 responses were only present in primary cultures but not in situ, suggesting that the expression of these receptors might vary between different microglial activation states.

Reward has a remarkable ability to invigorate motor behavior, enabling individuals to select and execute actions with greater precision and speed. However, if reward is to be exploited in applied settings, such as rehabilitation, a thorough understanding of its underlying mechanisms is required. In a series of experiments, we first demonstrate that reward simultaneously improves the selection and execution components of a reaching movement. Specifically, reward promoted the selection of the correct action in the presence of distractors, while also improving execution through increased speed and maintenance of accuracy. These results led to a shift in the speed-accuracy functions for both selection and execution. In addition, punishment had a similar impact on action selection and execution, although it enhanced execution performance across all trials within a block, that is, its impact was noncontingent to trial value. Although the reward-driven enhancement of movement execution has been proposed to occur through enhanced feedback control, an untested possibility is that it is also driven by increased arm stiffness, an energy-consuming process that enhances limb stability. Computational analysis revealed that reward led to both an increase in feedback correction in the middle of the movement and a reduction in motor noise near the target. In line with our hypothesis, we provide novel evidence that this noise reduction is driven by a reward-dependent increase in arm stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate motor performance without compromising accuracy.

SIGNIFICANCE STATEMENT While reward is well-known for enhancing motor performance, how the nervous system generates these improvements is unclear. Despite recent work indicating that reward leads to enhanced feedback control, an untested possibility is that it also increases arm stiffness. We demonstrate that reward simultaneously improves the selection and execution components of a reaching movement. Furthermore, we show that punishment has a similar positive impact on performance. Importantly, by combining computational and biomechanical approaches, we show that reward leads to both improved feedback correction and an increase in stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate performance without compromising accuracy. This work suggests that stiffness control plays a vital, and underappreciated, role in the reward-based imporvemenets in motor control.

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.

This photo was taken from the Tunnel View at Yosemite National Park. The photo is of Bridalveil Fall consumed by smoke due to controlled burning on the Yosemite Valley floor.

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

It works like a very fine "molecular knob" able to modulate the electrical activity of the neurons of our cerebral cortex, crucial to the functioning of our brain.