Peggy Cénac, Basile de Loynes, Yoann Offret, Arnaud Rousselle.

Source: Bernoulli, Volume 26, Number 2, 858--892.

Abstract:
The recurrence and transience of persistent random walks built from variable length Markov chains are investigated. It turns out that these stochastic processes can be seen as Lévy walks for which the persistence times depend on some internal Markov chain: they admit Markov random walk skeletons. A recurrence versus transience dichotomy is highlighted. Assuming the positive recurrence of the driving chain, a sufficient Fourier criterion for the recurrence, close to the usual Chung–Fuchs one, is given and a series criterion is derived. The key tool is the Nagaev–Guivarc’h method. Finally, we focus on particular two-dimensional persistent random walks, including directionally reinforced random walks, for which necessary and sufficient Fourier and series criteria are obtained. Inspired by ( Adv. Math. 208 (2007) 680–698), we produce a genuine counterexample to the conjecture of ( Adv. Math. 117 (1996) 239–252). As for the one-dimensional case studied in ( J. Theoret. Probab. 31 (2018) 232–243), it is easier for a persistent random walk than its skeleton to be recurrent. However, such examples are much more difficult to exhibit in the higher dimensional context. These results are based on a surprisingly novel – to our knowledge – upper bound for the Lévy concentration function associated with symmetric distributions.

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.

Benjamin Meyer
Jul 3, 2019; 39:5326-5335
Systems/Circuits

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

The transcription factor Nurr1 has been identified to be ectopically induced in the striatum of rodents expressing l-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression. We used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) male rats. In a second cohort, rats received the Nurr1 agonist amodiaquine (AQ) together with l-DOPA or ropinirole. All rats received a chronic DA agonist and were evaluated for LID severity. Finally, we performed single-unit recordings and dendritic spine analyses on striatal medium spiny neurons (MSNs) in drug-naïve rAAV-injected male parkinsonian rats. rAAV-GFP injected LID-resistant hemi-parkinsonian Lewis rats displayed mild LID and no induction of striatal Nurr1 despite receiving a high dose of l-DOPA. However, Lewis rats overexpressing Nurr1 developed severe LID. Nurr1 agonism with AQ exacerbated LID in F344 rats. We additionally determined that in l-DOPA-naïve rats striatal rAAV-Nurr1 overexpression (1) increased cortically-evoked firing in a subpopulation of identified striatonigral MSNs, and (2) altered spine density and thin-spine morphology on striatal MSNs; both phenomena mimicking changes seen in dyskinetic rats. Finally, we provide postmortem evidence of Nurr1 expression in striatal neurons of l-DOPA-treated PD patients. Our data demonstrate that ectopic induction of striatal Nurr1 is capable of inducing LID behavior and associated neuropathology, even in resistant subjects. These data support a direct role of Nurr1 in aberrant neuronal plasticity and LID induction, providing a potential novel target for therapeutic development.

SIGNIFICANCE STATEMENT The transcription factor Nurr1 is ectopically induced in striatal neurons of rats exhibiting levodopa-induced dyskinesia [LID; a side-effect to dopamine replacement strategies in Parkinson's disease (PD)]. Here we asked whether Nurr1 is causing LID. Indeed, rAAV-mediated expression of Nurr1 in striatal neurons was sufficient to overcome LID-resistance, and Nurr1 agonism exacerbated LID severity in dyskinetic rats. Moreover, we found that expression of Nurr1 in l-DOPA naïve hemi-parkinsonian rats resulted in the formation of morphologic and electrophysiological signatures of maladaptive neuronal plasticity; a phenomenon associated with LID. Finally, we determined that ectopic Nurr1 expression can be found in the putamen of l-DOPA-treated PD patients. These data suggest that striatal Nurr1 is an important mediator of the formation of LID.

Sensory systems integrate multiple stimulus features to generate coherent percepts. Spectral surround suppression, the phenomenon by which sound-evoked responses of auditory neurons are suppressed by stimuli outside their receptive field, is an example of this integration taking place in the auditory system. While this form of global integration is commonly observed in auditory cortical neurons, and potentially used by the nervous system to separate signals from noise, the mechanisms that underlie this suppression of activity are not well understood. We evaluated the contributions to spectral surround suppression of the two most common inhibitory cell types in the cortex, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM⁺) interneurons, in mice of both sexes. We found that inactivating SOM⁺ cells, but not PV+ cells, significantly reduces sustained spectral surround suppression in excitatory cells, indicating a dominant causal role for SOM⁺ cells in the integration of information across multiple frequencies. The similarity of these results to those from other sensory cortices provides evidence of common mechanisms across the cerebral cortex for generating global percepts from separate features.

SIGNIFICANCE STATEMENT To generate coherent percepts, sensory systems integrate simultaneously occurring features of a stimulus, yet the mechanisms by which this integration occurs are not fully understood. Our results show that neurochemically distinct neuronal subtypes in the primary auditory cortex have different contributions to the integration of different frequency components of an acoustic stimulus. Together with findings from other sensory cortices, our results provide evidence of a common mechanism for cortical computations used for global integration of stimulus features.

Persistent alterations in neuronal activity elicit homeostatic plastic changes in synaptic transmission and/or intrinsic excitability. However, it is unknown whether these homeostatic processes operate in concert or at different temporal scales to maintain network activity around a set-point value. Here we show that chronic neuronal hyperactivity, induced by M-channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in cultured hippocampal pyramidal neurons from mice of either sex. Homeostatic changes of intrinsic excitability occurred at a fast timescale (1–4 h) and depended on ongoing spiking activity. This fast intrinsic adaptation included plastic changes in the threshold current and a distal relocation of FGF14, a protein physically bridging Na_v1.6 and K_v7.2 channels along the axon initial segment. In contrast, synaptic adaptations occurred at a slower timescale (~2 d) and involved decreases in miniature EPSC amplitude. To examine how these temporally distinct homeostatic responses influenced hippocampal network activity, we quantified the rate of spontaneous spiking measured by multielectrode arrays at extended timescales. M-Channel blockade triggered slow homeostatic renormalization of the mean firing rate (MFR), concomitantly accompanied by a slow synaptic adaptation. Thus, the fast intrinsic adaptation of excitatory neurons is not sufficient to account for the homeostatic normalization of the MFR. In striking contrast, homeostatic adaptations of intrinsic excitability and spontaneous MFR failed in hippocampal GABAergic inhibitory neurons, which remained hyperexcitable following chronic M-channel blockage. Our results indicate that a single perturbation such as M-channel inhibition triggers multiple homeostatic mechanisms that operate at different timescales to maintain network mean firing rate.

SIGNIFICANCE STATEMENT Persistent alterations in synaptic input elicit homeostatic plastic changes in neuronal activity. Here we show that chronic neuronal hyperexcitability, induced by M-type potassium channel inhibition, triggered intrinsic and synaptic homeostatic plasticity at different timescales in hippocampal excitatory neurons. The data indicate that the fast adaptation of intrinsic excitability depends on ongoing spiking activity but is not sufficient to provide homeostasis of the mean firing rate. Our results show that a single perturbation such as M-channel inhibition can trigger multiple homeostatic processes that operate at different timescales to maintain network mean firing rate.

New study extends previous results limited to just two islands to 188 species of lizard across Caribbean as well as Central and South America

People and businesses are rallying to support the Muslim community in Fort McMurray recover after widespread flooding that damaged many neighbourhoods.

The Bank of Canada, the Bank of England, the Bank of Japan, the European Central Bank, the Sveriges Riksbank and the Swiss National Bank, together with the Bank for International Settlements (BIS), have created a group to share experiences as they assess the potential case for central bank digital currency (CBDC) in their home jurisdictions. (Press release, 21 January 2020)

In this most unique of drafts, filled with technological concerns and even uncertainty when real football might return, there was one constant Thursday night: Joe Burrow.

While players are stuck in self isolation, they don’t need to worry about trying to stop Alexander Ovechkin’s “knuckleball” type shot.

Flurries or rain showers are in the forecast for Hamilton on Friday, Environment Canada says.

The post Apps for Kids at Home: Teach Remotely with Free Classroom Curriculum appeared first on SOLIDWORKS Education Blog.

This report summarises the main results of a stocktake conducted by the Basel Committee of its members' initiatives on climate-related financial risks.

Bank of Finland Research Discussion Papers by Eleonora Granziera and Markus Sihvonen

Netherlands Bank DNB Occasional Studies by Peter Wierts and Harro Boven

Acne vulgaris is an extraordinarily common skin condition in adolescents. The mainstays of acne treatment have remained largely unchanged over recent years. In the context of increasing antibiotic resistance worldwide, there is a global movement away from antibiotic monotherapy toward their more restrictive use. Classically reserved for nodulocystic acne, isotretinoin has become the drug of choice by dermatologists for moderate to severe acne. Given the virtually ubiquitous nature of acne in teenagers, there remains an appreciable need for novel therapies. In this article, we will cover the currently used acne treatments, evaluate the issues and data supporting their use, explore the issues of compliance and the mental health implications of acne care, and recommend directions for the field of acne management in adolescents in the years ahead.

WHEN you are a 6ft 3in tall, world-class tennis player with long arms, broad shoulders and a slim torso, buying off the peg is far from easy.

THE Murray window is closing but Tennis Scotland appear to be diving through it just in time. Failing to adequately capitalise on the ongoing successes of Andy and Jamie has been a long-time frustration of the family, with mum Judy vehement in her criticism of the governing bodies for their inertia.

ANDY MURRAY may need to have another operation as he continues his bid to return to top-level tennis.

FOUR-TIME grand slam champion, Jamie Murray, will headline the Brodies Invitational tennis tournament, which has relocated to Edinburgh for this summer’s edition.

ANDY MURRAY has had a bumpy ride over the past couple of years, undergoing hip surgery, staging a comeback which saw him win his first title in two years before another injury setback has seen him sidelined since the tail-end of last year.

SIR Andy Murray has sent a heartfelt message to NHS staff for their heroic work during the coronavirus crisis.

ANDY MURRAY will swap a tennis racket for a games controller when he takes part in a virtual Madrid Open later this month.

Andy Murray does not think getting the professional tennis circuit back up and running should be a priority any time soon.

Former Vice President Joe Biden’s recent remarks on his willingness to work with segregationists resurrected his long-ago efforts to oppose school busing. Will it hurt his campaign?

BEING a full-time, voluntary, unpaid carer, since November 2018, for my wife, who has dementia, I would like to ask a question of the Scottish Government, especially Jeane Freeman, the health secretary.

More than a third of the 30 biggest school districts in the United States are not using any math or English/language arts curricula that are rated highly for alignment to state standards, a new study from the Center for American Progress finds.

There are times when I wish my family’s life revolved a little less around Andy Murray. Two words, "Andy’s playing", are sufficient reason for outings to be delayed or abandoned; invitations turned down; even holiday dates tweaked.

Source: The Weather Channel - A majority of Americans say they believe climate change contributed to the severity of the hurricanes that devastated Florida, Texas and parts of the Caribbean over the past six weeks, according to a new Washington Post-ABC News poll.

Former Vice President Joe Biden’s recent remarks on his willingness to work with segregationists resurrected his long-ago efforts to oppose school busing. Will it hurt his campaign?

Primary care providers (PCPs) identify patients with undescended testis (UDT) and refer them to surgical specialists. Referral beyond the recommended times for orchiopexy has been reported, and PCPs' accuracy in identifying and distinguishing UDTs from retractile testes has been questioned.

We describe 3 observations that are strongly correlated with UDT, that is, birth history of UDT, prematurity, and visible scrotal asymmetry. UDT diagnoses are best made by 8 months of age, to reduce confusion with testicular retraction and to facilitate timely orchiopexy. (Read the full article)

Mixed prevalence rates of co-occurring psychiatric and neurodevelopmental conditions have been reported in children diagnosed with an autism spectrum disorder (ASD). ASD diagnoses remain fairly stable within a continuum, but some do not meet criteria for an ASD diagnosis years after initial diagnosis.

Co-occurring neurodevelopmental and psychiatric conditions may explain, in part, why the diagnosis of an ASD may change with age. (Read the full article)

Preterm children born between 29 and 36 gestational weeks are at higher risk of developmental delay. The Ages and Stages Questionnaires (ASQ) have been recommended as a developmental screening tool.

At 12 months’ corrected age (CA), the ASQ was insufficient in identifying delays on both mental and psychomotor scales of the Bayley Scales of Infant Development but was accurate in detecting mental delay at CA of 24 months. (Read the full article)

Anecdotal accounts that suggest elopement behavior occurs in children with autism spectrum disorders (ASDs), that injuries and fatalities can result, and that associated family burden and stress are substantial. However, there has been little research characterizing the phenomenon or its frequency.

Nearly half of children with an ASD elope, and more than half of these "go missing." Elopement is associated with autism severity, and is often goal-directed. Addressing elopement behavior is an important aspect of intervention for many individuals with ASDs. (Read the full article)

It has been widely thought for the past 20 years that recurrent low blood glucose levels ≤2.5 mmol/L (45 mg/dL), even in the absence of any suggestive clinical signs, can harm a preterm infant’s long-term development.

This prospective study showed the outcome at 2 and 15 years later for the preterm infants who had a blood glucose level this low in the first 10 days of life did not differ from that of matched controls. (Read the full article)

The importance of transition from pediatric to adult health care for youth with special health care needs has gained increasing attention over the past decade, but fewer than half of this population received needed transition preparation in 2005–2006.

This study reports on transition findings from the 2009–2010 National Survey of Children with Special Health Care Needs and finds no discernible improvements since 2005–2006. New clinical recommendations and care processes should help to accelerate transition improvements in the future. (Read the full article)

Although unnecessary for children with headache and normal history, computed tomography (CT) scans are widely used. Fewer than 1% of pediatric brain abnormalities present with headache as the only symptom. Furthermore, repeated CT scans may increase lifetime risk of cancer.

CT scans continue to be used to diagnose isolated pediatric headaches despite existing practice parameters. Although emergency department visits were correlated with greater likelihood of CT scan use, these scans were widely used across a variety of clinical settings. (Read the full article)

Palivizumab prophylaxis prevents respiratory syncytial virus lower respiratory tract infection. An association between respiratory syncytial virus infection and subsequent recurrent wheezing has been suggested by many studies. Only a few studies conducted from Europe and North America have addressed this causal association.

In a prospective, multicenter, case-control study of 440 children with high follow-up rate of 98.4%, palivizumab prophylaxis administered to preterm Japanese infants (33–35 weeks’ gestational age) in their first respiratory season reduced the incidence of subsequent recurrent wheezing up to 3 years. (Read the full article)

Use of complementary and alternative medicine (CAM) is increasingly common among American youth; however, information on use of CAM among youth with recurrent headache (HA) is limited.

Youth across a range of chronic conditions experience HA. These youth are more likely to use CAM. Use and expenditures for conventional medical care, and increased difficulties in activity and functioning are greater for youth with HA who use CAM. (Read the full article)

Although frequent utilizers of emergency departments (EDs) are targeted for quality improvement initiatives across the United States, little is known about the health services these patients receive in the ED.

Eight percent of children account for 24% of ED visits and 31% of all costs. Frequent utilizers of pediatric EDs, especially infants without a chronic condition, are least likely to need medications, testing, and hospital admission during their ED visits. (Read the full article)

Vesicoureteral reflux is recognized as an important risk factor for recurrent urinary tract infection and renal scarring. Less is known about the contribution of other risk factors to these outcomes.

This study found that information about vesicoureteral reflux and bladder and bowel dysfunction can be used to identify children at low, medium, and high risk of recurrent urinary tract infection, information that clinicians could use to select children for specific preventive therapies. (Read the full article)

Making a diagnosis of Kawasaki disease (KD) is often a diagnostic dilemma. This dilemma is confounded when children present with symptoms consistent with known, common respiratory viruses and/or with KD symptoms that could potentially be attributed to a respiratory virus.

Patients with KD commonly have a concurrent respiratory viral infection. Clinicians should not dismiss the diagnosis of KD based on the presence of respiratory symptoms. Furthermore, a positive respiratory virus test result should not be used to exclude the diagnosis of KD. (Read the full article)