Bath : And sold by Underwood, London, 1825.

London : [Published not identified], 1876.

Rockville, Maryland : National Institute on Drug Abuse, [1983]

[United States] : National Technical Information Service, United States Department of Commerce, 1984.

Bertrand Clarke, Jennifer Clarke

Source: Statist. Surv., Volume 6, 1--73.

Abstract:
We review predictive techniques from several traditional branches of statistics. Starting with prediction based on the normal model and on the empirical distribution function, we proceed to techniques for various forms of regression and classification. Then, we turn to time series, longitudinal data, and survival analysis. Our focus throughout is on the mechanics of prediction more than on the properties of predictors.

Wenjie Wang, Robert Aseltine, Kun Chen, Jun Yan.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 51--73.

Abstract:
The concept of integrating data from disparate sources to accelerate scientific discovery has generated tremendous excitement in many fields. The potential benefits from data integration, however, may be compromised by the uncertainty due to incomplete/imperfect record linkage. Motivated by a suicide risk study, we propose an approach for analyzing survival data with uncertain event times arising from data integration. Specifically, in our problem deaths identified from the hospital discharge records together with reported suicidal deaths determined by the Office of Medical Examiner may still not include all the death events of patients, and the missing deaths can be recovered from a complete database of death records. Since the hospital discharge data can only be linked to the death record data by matching basic patient characteristics, a patient with a censored death time from the first dataset could be linked to multiple potential event records in the second dataset. We develop an integrative Cox proportional hazards regression in which the uncertainty in the matched event times is modeled probabilistically. The estimation procedure combines the ideas of profile likelihood and the expectation conditional maximization algorithm (ECM). Simulation studies demonstrate that under realistic settings of imperfect data linkage the proposed method outperforms several competing approaches including multiple imputation. A marginal screening analysis using the proposed integrative Cox model is performed to identify risk factors associated with death following suicide-related hospitalization in Connecticut. The identified diagnostics codes are consistent with existing literature and provide several new insights on suicide risk, prediction and prevention.

Seth Flaxman, Michael Chirico, Pau Pereira, Charles Loeffler.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2564--2585.

Abstract:
We propose a generic spatiotemporal event forecasting method which we developed for the National Institute of Justice’s (NIJ) Real-Time Crime Forecasting Challenge (National Institute of Justice (2017)). Our method is a spatiotemporal forecasting model combining scalable randomized Reproducing Kernel Hilbert Space (RKHS) methods for approximating Gaussian processes with autoregressive smoothing kernels in a regularized supervised learning framework. While the smoothing kernels capture the two main approaches in current use in the field of crime forecasting, kernel density estimation (KDE) and self-exciting point process (SEPP) models, the RKHS component of the model can be understood as an approximation to the popular log-Gaussian Cox Process model. For inference, we discretize the spatiotemporal point pattern and learn a log-intensity function using the Poisson likelihood and highly efficient gradient-based optimization methods. Model hyperparameters including quality of RKHS approximation, spatial and temporal kernel lengthscales, number of autoregressive lags and bandwidths for smoothing kernels as well as cell shape, size and rotation, were learned using cross validation. Resulting predictions significantly exceeded baseline KDE estimates and SEPP models for sparse events.

Federico Castelletti, Guido Consonni.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2289--2311.

Abstract:
A signalling pathway is a sequence of chemical reactions initiated by a stimulus which in turn affects a receptor, and then through some intermediate steps cascades down to the final cell response. Based on the technique of flow cytometry, samples of cell-by-cell measurements are collected under each experimental condition, resulting in a collection of interventional data (assuming no latent variables are involved). Usually several external interventions are applied at different points of the pathway, the ultimate aim being the structural recovery of the underlying signalling network which we model as a causal Directed Acyclic Graph (DAG) using intervention calculus. The advantage of using interventional data, rather than purely observational one, is that identifiability of the true data generating DAG is enhanced. More technically a Markov equivalence class of DAGs, whose members are statistically indistinguishable based on observational data alone, can be further decomposed, using additional interventional data, into smaller distinct Interventional Markov equivalence classes. We present a Bayesian methodology for structural learning of Interventional Markov equivalence classes based on observational and interventional samples of multivariate Gaussian observations. Our approach is objective, meaning that it is based on default parameter priors requiring no personal elicitation; some flexibility is however allowed through a tuning parameter which regulates sparsity in the prior on model space. Based on an analytical expression for the marginal likelihood of a given Interventional Essential Graph, and a suitable MCMC scheme, our analysis produces an approximate posterior distribution on the space of Interventional Markov equivalence classes, which can be used to provide uncertainty quantification for features of substantive scientific interest, such as the posterior probability of inclusion of selected edges, or paths.

Eric Beutner, Laurent Bordes, Laurent Doyen.

Source: Bernoulli, Volume 26, Number 1, 557--586.

Abstract:
Virtual age models are very useful to analyse recurrent events. Among the strengths of these models is their ability to account for treatment (or intervention) effects after an event occurrence. Despite their flexibility for modeling recurrent events, the number of applications is limited. This seems to be a result of the fact that in the semiparametric setting all the existing results assume the virtual age function that describes the treatment (or intervention) effects to be known. This shortcoming can be overcome by considering semiparametric virtual age models with parametrically specified virtual age functions. Yet, fitting such a model is a difficult task. Indeed, it has recently been shown that for these models the standard profile likelihood method fails to lead to consistent estimators. Here we show that consistent estimators can be constructed by smoothing the profile log-likelihood function appropriately. We show that our general result can be applied to most of the relevant virtual age models of the literature. Our approach shows that empirical process techniques may be a worthwhile alternative to martingale methods for studying asymptotic properties of these inference methods. A simulation study is provided to illustrate our consistency results together with an application to real data.

Pantelis Samartsidis, Shaun R. Seaman, Anne M. Presanis, Matthew Hickman, Daniela De Angelis.

Source: Statistical Science, Volume 34, Number 3, 486--503.

Abstract:
Researchers are often challenged with assessing the impact of an intervention on an outcome of interest in situations where the intervention is nonrandomised, the intervention is only applied to one or few units, the intervention is binary, and outcome measurements are available at multiple time points. In this paper, we review existing methods for causal inference in these situations. We detail the assumptions underlying each method, emphasize connections between the different approaches and provide guidelines regarding their practical implementation. Several open problems are identified thus highlighting the need for future research.

Timothy J. Schoenfeld
May 1, 2013; 33:7770-7777
BehavioralSystemsCognitive

Fiona Doetsch
Jul 1, 1997; 17:5046-5061
Articles

French translation of Press Release about BIS General Manager Agustín Carstens giving a speech on "Money in the digital age: what role for central banks?" (6 February 2018)

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans.

SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale.

The PFC, through its high degree of interconnectivity with cortical and subcortical brain areas, mediates cognitive and emotional processes in support of adaptive behaviors. This includes the formation of fear memories when the anticipation of threat demands learning about temporal or contextual cues, as in trace fear conditioning. In this variant of fear learning, the association of a cue and shock across an empty trace interval of several seconds requires sustained cue-elicited firing in the prelimbic cortex (PL). However, it is unknown how and when distinct PL afferents contribute to different associative components of memory. Among the prominent inputs to PL, the hippocampus shares with PL a role in both working memory and contextual processing. Here we tested the necessity of direct hippocampal input to the PL for the acquisition of trace-cued fear memory and the simultaneously acquired contextual fear association. Optogenetic silencing of ventral hippocampal (VH) terminals in the PL of adult male Long-Evans rats selectively during paired trials revealed that direct communication between the VH and PL during training is necessary for contextual fear memory, but not for trace-cued fear acquisition. The pattern of the contextual memory deficit and the disruption of local PL firing during optogenetic silencing of VH-PL suggest that the VH continuously updates the PL with the current contextual state of the animal, which, when disrupted during memory acquisition, is detrimental to the subsequent rapid retrieval of aversive contextual associations.

SIGNIFICANCE STATEMENT Learning to anticipate threat from available contextual and discrete cues is crucial for survival. The prelimbic cortex is required for forming fear memories when temporal or contextual complexity is involved, as in trace fear conditioning. However, the respective contribution of distinct prelimbic afferents to the temporal and contextual components of memory is not known. We report that direct input from the ventral hippocampus enables the formation of the contextual, but not trace-cued, fear memory necessary for the subsequent rapid expression of a fear response. This finding dissociates the contextual and working-memory contributions of prelimbic cortex to the formation of a fear memory and demonstrates the crucial role for hippocampal input in contextual fear learning.

Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. We recently showed, in aged female rhesus monkeys, that systemic administration of MSC-EVs enhances recovery of function after injury of the primary motor cortex, likely through enhancing plasticity in perilesional motor and premotor cortices. Here, using in vitro whole-cell patch-clamp recording and intracellular filling in acute slices of ventral premotor cortex (vPMC) from rhesus monkeys (Macaca mulatta) of either sex, we demonstrate that MSC-EVs reduce injury-related physiological and morphologic changes in perilesional layer 3 pyramidal neurons. At 14-16 weeks after injury, vPMC neurons from both vehicle- and EV-treated lesioned monkeys exhibited significant hyperexcitability and predominance of inhibitory synaptic currents, compared with neurons from nonlesioned control brains. However, compared with vehicle-treated monkeys, neurons from EV-treated monkeys showed lower firing rates, greater spike frequency adaptation, and excitatory:inhibitory ratio. Further, EV treatment was associated with greater apical dendritic branching complexity, spine density, and inhibition, indicative of enhanced dendritic plasticity and filtering of signals integrated at the soma. Importantly, the degree of EV-mediated reduction of injury-related pathology in vPMC was significantly correlated with measures of behavioral recovery. These data show that EV treatment dampens injury-related hyperexcitability and restores excitatory:inhibitory balance in vPMC, thereby normalizing activity within cortical networks for motor function.

SIGNIFICANCE STATEMENT Neuronal plasticity can facilitate recovery of function after cortical injury, but the underlying mechanisms and efficacy of therapeutic interventions promoting this plasticity in primates are not well understood. Our recent work has shown that intravenous infusions of mesenchymal-derived extracellular vesicles (EVs) that are involved in cell-to-cell inflammatory and trophic signaling can enhance recovery of motor function after injury in monkey primary motor cortex. This study shows that this EV-mediated enhancement of recovery is associated with amelioration of injury-related hyperexcitability and restoration of excitatory-inhibitory balance in perilesional ventral premotor cortex. These findings demonstrate the efficacy of mesenchymal EVs as a therapeutic to reduce injury-related pathologic changes in the physiology and structure of premotor pyramidal neurons and support recovery of function.

The tuberal hypothalamus is comprised of the dorsomedial, ventromedial, and arcuate nuclei, as well as parts of the lateral hypothalamic area, and it governs a wide range of physiologies. During neurogenesis, tuberal hypothalamic neurons are thought to be born in a dorsal-to-ventral and outside-in pattern, although the accuracy of this description has been questioned over the years. Moreover, the intrinsic factors that control the timing of neurogenesis in this region are poorly characterized. Proneural genes, including Achate-scute-like 1 (Ascl1) and Neurogenin 3 (Neurog3) are widely expressed in hypothalamic progenitors and contribute to lineage commitment and subtype-specific neuronal identifies, but the potential role of Neurogenin 2 (Neurog2) remains unexplored. Birthdating in male and female mice showed that tuberal hypothalamic neurogenesis begins as early as E9.5 in the lateral hypothalamic and arcuate and rapidly expands to dorsomedial and ventromedial neurons by E10.5, peaking throughout the region by E11.5. We confirmed an outside-in trend, except for neurons born at E9.5, and uncovered a rostrocaudal progression but did not confirm a dorsal-ventral patterning to tuberal hypothalamic neuronal birth. In the absence of Neurog2, neurogenesis stalls, with a significant reduction in early-born BrdU⁺ cells but no change at later time points. Further, the loss of Ascl1 yielded a similar delay in neuronal birth, suggesting that Ascl1 cannot rescue the loss of Neurog2 and that these proneural genes act independently in the tuberal hypothalamus. Together, our findings show that Neurog2 functions as a classical proneural gene to regulate the temporal progression of tuberal hypothalamic neurogenesis.

SIGNIFICANCE STATEMENT Here, we investigated the general timing and pattern of neurogenesis within the tuberal hypothalamus. Our results confirmed an outside-in trend of neurogenesis and uncovered a rostrocaudal progression. We also showed that Neurog2 acts as a classical proneural gene and is responsible for regulating the birth of early-born neurons within the ventromedial hypothalamus, acting independently of Ascl1. In addition, we revealed a role for Neurog2 in cell fate specification and differentiation of ventromedial -specific neurons. Last, Neurog2 does not have cross-inhibitory effects on Neurog1, Neurog3, and Ascl1. These findings are the first to reveal a role for Neurog2 in hypothalamic development.

Hydrocephalus is a pathologic condition associated with various brain diseases, including Alzheimer's disease (AD). Dysfunctional ependymal cells (EpCs) are believed to contribute to the development of hydrocephalus. It is thus of interest to investigate EpCs' development and function. Here, we report that vacuolar protein sorting-associated protein 35 (VPS35) is critical for EpC differentiation, ciliogenesis, and survival, and thus preventing neonatal hydrocephalus. VPS35 is abundantly expressed in EpCs. Mice with conditional knock-out (cKO) of Vps35 in embryonic (Vps35^GFAP-Cre and Vps35^Emx1-Cre) or postnatal (Vps35^Foxj1-CreER) EpC progenitors exhibit enlarged lateral ventricles (LVs) and hydrocephalus-like pathology. Further studies reveal marked reductions in EpCs and their cilia in both Vps35^GFAP-Cre and Vps35^Foxj1-CreER mutant mice. The reduced EpCs appear to be due to impairments in EpC differentiation and survival. Additionally, both Vps35^GFAP-Cre and Vps35^Foxj1-CreER neonatal pups exhibit increased cell proliferation and death largely in a region close to LV-EpCs. Many microglia close to the mutant LV-EpC region become activated. Depletion of the microglia by PLX3397, an antagonist of colony-stimulating factor 1 receptor (CSF1R), restores LV-EpCs and diminishes the pathology of neonatal hydrocephalus in Vps35^Foxj1-CreER mice. Taken together, these observations suggest unrecognized functions of Vps35 in EpC differentiation, ciliogenesis, and survival in neonatal LV, and reveal pathologic roles of locally activated microglia in EpC homeostasis and hydrocephalus development.

SIGNIFICANCE STATEMENT This study reports critical functions of vacuolar protein sorting-associated protein 35 (VPS35) not only in promoting ependymal cell (EpC) differentiation, ciliogenesis, and survival, but also in preventing local microglial activation. The dysfunctional EpCs and activated microglia are likely to induce hydrocephalus.

The bright blue pigment that adorns the Bust of Nefertiti’s crown can now be used to study molecular biology

The severity of this year's bleaching is second only to 2016, during which a third of the reef’s corals died

Expelled by animals as a waste product, the gas appears to play a crucial role in keeping these bizarre, burrowing rodents safe

With Washington, D.C. COVID-19 state of emergency, Smithsonian officials say museums to close Saturday, March 14; events canceled through May 3

Tulips, cherry blossoms and orchids supply a ray of hope during self-isolation

A new book explores how George Washington shaped the group of advisors as an institution to meet his own needs

Follow the Frenchman who remade the woods surrounding a royal estate into the world’s first nature preserve

Architects and planners from the Netherlands are advising coastal cities worldwide on how to live with water

11 startups to pitch at NEXT Canada's virtual Venture Reveal  BetaKit

FIR against 15 members for song ’n dance event  Mumbai Mirror

Business inventories are the dollar amount of inventories held by manufacturers, wholesalers, and retailers. The level of inventories in relation to sales is an important indicator of the near-term direction of production activity.

The province's networks of labs processed 15,179 tests in the last 24 hours, more than any of the three days previous but still short of the 16,000 tests per day target set back in April.

Opening remarks by Ms Christine Lagarde, President of the European Central Bank, at the Online Edition of The State of the Union conference organised by the European University Institute, 8 May 2020.

Caitlin, an intern with OM, participates in African and communications orientation in South Africa before flying to Madagascar.

Nathan Schmutz of Switzerland has enjoyed the challenge of immersing himself in a whole new culture.

Two stories from the Africa Trek--an intense discipleship experience for people from different nations who travel and minister together throughout Southern Africa.

BACKGROUND AND OBJECTIVES:

Systems of care emphasize parent-delivered intervention for children with autism spectrum disorder (ASD). Meanwhile, multiple studies document psychological distress within these parents. This pilot longitudinal randomized controlled trial compared the parent-implemented Early Start Denver Model (P-ESDM) to P-ESDM plus mindfulness-based stress reduction (MBSR) for parents. We evaluated changes in parent functioning during active treatment and at follow-up.

Asthma is a significant public health issue, impacting quality of life, morbidity, and health care costs nationally. Stock asthma rescue medication policies authorize school districts to maintain unassigned albuterol and enable trained staff members to administer the medication in response to asthma symptoms, exercise premedication, and asthma emergencies. Stock asthma rescue (or reliever) medication laws serve as an important fail-safe measure. Such laws provide districts with the ability to respond if a student has an asthma emergency at school but either lacks a diagnosis or does not have access to their own medication. As of September 2019, 13 states have enacted either a law or regulation authorizing the stocking of asthma rescue medication in schools: Arizona, Colorado, Georgia, Illinois, Missouri, New Hampshire, New Jersey, New Mexico, Oklahoma, Ohio, Texas, Utah, and West Virginia. Three additional states provide stock albuterol asthma guidelines but do not have legislation: Indiana, New York, and Nebraska. Some states have found that these policies reduce the need for 911 calls and emergency medical services transports as a result of asthma exacerbations. Initial data also demonstrate that these policies reach populations in need and improve health outcomes. This case study will describe the current state of asthma in Illinois, an innovative policy solution to address asthma emergencies in schools, and the steps taken to advocate for stock asthma rescue medication in Illinois. Legislation for stock albuterol in Illinois was signed into law in August 2018.