Jamie D. Roitman
Nov 1, 2002; 22:9475-9489
Behavioral

Some of the troubling reports of corporate responses to COVID-19 include forced work in unsafe areas, not enough -- or any -- protection gear, massive layoffs and furloughs, and the sense that a critical mass of well-paid CEOs and politicians don't get that many people live paycheck to paycheck. There are exceptions though, and HP stands out, thanks to HR VP Tracy Keogh and CEO Enrique Lores.

Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.

SIGNIFICANCE STATEMENT Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.

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.

FSI Briefs No 1, April 2020. Regulatory policy responses should seek to support economic activity while preserving the financial system's soundness and ensuring transparency. The recommendation for banks to make full use of capital and liquidity buffers should go hand in hand with restrictions on dividends and bonuses and clarity concerning the process for rebuilding them. Flexibility in loan classification criteria for prudential and accounting purposes should be complemented with sufficient disclosure on the criteria banks use to assess creditworthiness. The publication of detailed guidance on the application of expected loss provisioning rules, combined with sensible transitional arrangements, may constitute a balanced approach to mitigating the unintended effects of the new accounting standards.

FSI Briefs No 4, April 2020. Currently, insurers are more likely to experience losses from financial market volatility than from higher insurance claims arising from Covid-19. Few insurance supervisors have seen a need to strengthen or adjust prudential requirements to insulate insurers from current financial market uncertainties. So far, authorities have responded mainly by taking measures to provide operational relief to insurers from regulatory and supervisory requirements so that they can continue providing insurance services. These measures will also help insurers to enhance risk monitoring of their Covid-19 financial exposures. Some authorities have set out expectations for insurers to conserve capital through prudent exercise of dividend and variable remuneration policies. The aim is to enhance their resilience against huge uncertainties from potential Covid-19 fallout. Other capital-related measures should relieve supervisory pressures and reduce the tendency of insurers to manage their investments in a procyclical manner. These measures include: extending the supervisory intervention ladder, triggering the countercyclical lever and recalibrating capital requirements. The far-reaching impact of Covid-19 calls for sustained vigilance by both supervisors and insurers. In the post-pandemic phase, the extraordinary measures currently warranted will need to be unwound through a carefully crafted exit strategy that preserves sound risk management practices and protects policyholders' interests.

Press release "Basel Committee coordinates policy and supervisory response to Covid-19", 20 March 2020

A look at support and regenerative policy initiatives by the Federal Reserve and the Government as more than 20 million jobs were lost in April 2020.

Hearing of Mr François Villeroy de Galhau, Governor of the Bank of France, before the Section for the Economy and Finance of the French Economic, Social and Environmental Council, Paris, 8 April 2020.

Remarks by Ms Isabel Schnabel, Member of the Executive Board of the European Central Bank, at a 24-Hour Global Webinar co-organised by the SAFE Policy Center on "The COVID-19 Crisis and Its Aftermath: Corporate Governance Implications and Policy Challenges", Frankfurt am Main, 16 April 2020.

Remarks by Mr Olli Rehn, Governor of the Bank of Finland, at the Reinventing Bretton Woods Committee Panel Discussion on "The world economy transformed: Reflections on policy responses and the future post pandemic monetary architecture", in the context of the virtual IMF Spring Meetings, Washington DC, 17 April 2020.

Contribution by Mr Fabio Panetta, Member of the Executive Board of the European Central Bank, published by Politico on 21 April 2020.

Speech by Mr Benjamin E Diokno, Governor of Bangko Sentral ng Pilipinas (BSP, the central bank of the Philippines), at an investor call with Standard Chartered Bank, Manila, 22 April 2020.

The federal government is looking to hire paramedics who can fly up to remote First Nations in case there’s a surge of COVID-19 cases, and officials say it’s evidence of a different approach to Indigenous health care than during the H1N1 outbreak.

FSI Briefs No 5, April 2020. In response to the Covid-19 pandemic, governments have launched guarantee programmes to support bank lending to companies, especially small and medium-sized enterprises. This is essential to avoid a sharp contraction in bank credit that would exacerbate the pandemic's adverse impact. The design of such programmes needs to strike a difficult balance between responding promptly to the pandemic and maintaining a sufficient level of prudence. Key features of a sample of programmes (eg target beneficiaries, coverage of the guarantee, loan terms, length of the programme) reflect this tension. Incentives were created for the banks to join these programmes by exploiting flexibility in existing prudential requirements, while central banks have often provided liquidity support. Programmes are, however, subject to operational challenges and, ultimately, fiscal capacity limits.

A look at support and regenerative policy initiatives by the Federal Reserve and the Government as more than 20 million jobs were lost in April 2020.

Central Bank of Chile Working Papers by Benjamín García and Juan Guerra-Salas

Martha Caldwell, Oman Frame, Terry Roller, Dr. Kris Felicello, John Seborowski, Jessica Hannigan, John Hannigan and Kelly Wickham Hurst share their suggestions for combating bullying.

Today's commentaries on bullying in schools come from Ann Mausbach, Kim Morrison, Signe Whitson, Sandy Harris, Julie Combs, and Stacey Edmonson, Dr. Elizabeth Englander, Tamara Fyke, Stuart Ablon and Alisha Pollastri.

A five-part series on mistakes made by school administrators is wrapped-up today with commentaries from Dr. Lynell Powell, Stuart Ablon, Alisha Pollastri, Diane Mora and many comments from readers

Marc Tucker responds to Checker Finn's recent critique of the new international teacher quality study from NCEE and Linda Darling-Hammond, Empowered Educators.

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)

The US Surgeon General has determined that the relationship between movie smoking exposure (MSE) and youth smoking is causal; however, it is not known whether movie rating influences how adolescents respond.

The response to PG-13–rated MSE was indistinguishable from R-rated MSE. An R rating for smoking could reduce smoking onset in the United States by 18% (by eliminating PG-13 MSE), an effect similar to making all parents maximally authoritative in their parenting. (Read the full article)

A dose-response relationship exists between light irradiance and decrease of total serum bilirubin concentration (TsB) at relatively low irradiances. It has been questioned whether by increasing irradiance a "saturation point" exists, above which no further decrease of TsB is seen.

We found a linear relation between light irradiance in the range of 20 to 55 μW/cm²/nm and decrease in TsB after 24 hours of therapy, with no evidence of a saturation point. (Read the full article)

Caffeine has predictable effects on cardiovascular function in both adults and children. Our previous work has shown that there are gender differences in this cardiovascular response, with boys having a greater change in heart rate and blood pressure than girls.

This study shows that the gender differences in cardiovascular response to caffeine emerge after puberty and there are some differences in postpubertal girls across the menstrual cycle. (Read the full article)

Oral vaccine responses are low in children from less-developed countries perhaps as a result of intestinal dysbiosis. New high-throughput DNA-based methods allow characterization of intestinal microbiota as a predictor of vaccine responses.

High abundance of stool Actinobacteria, including Bifidobacterium, was associated with higher responses to oral and parenteral vaccines and a larger thymus in Bangladeshi infants. Conversely, high abundance of Clostridiales, Enterobacteriales, and Pseudomonadales was associated with neutrophilia and lower vaccine responses. (Read the full article)

Some parents choose to "spread out" the recommended vaccine schedule for their child by decreasing the number of simultaneous vaccines or delaying certain vaccines until an older age. Epidemiologic studies demonstrate increasing numbers of parents are choosing to delay vaccines.

We demonstrate that almost all providers encounter requests to spread out vaccines in a typical month and, despite concerns, increasing numbers are agreeing to do so. Providers report many strategies in response to requests but think few are effective. (Read the full article)

Outbreaks of serogroup B meningococcal disease occur at universities and other organizations. Until October 2014, options for control of serogroup B outbreaks were limited by the absence of a licensed vaccine for serogroup B meningococcal disease in the United States.

We describe a serogroup B outbreak at a university in 2013 and the campaign with investigational serogroup B vaccine held in response. This was the first use of a serogroup B vaccine as an outbreak response in the United States. (Read the full article)

Adding second-stage automated auditory brainstem response (ABR) testing for infants who failed the initial OAE test in a two-stage neonatal hearing screening has been shown to reduce false referrals to the hearing clinic.

Infants with hearing loss may be missed by a 2-stage hearing screening because they pass the automated ABR test. In our study, a significant number of infants with hearing loss >45 decibel hearing level passed screening with automated ABR. (Read the full article)

Makeda Brome, Pia Hansen, Linda Gojak, Marian Small, Kenneth Baum and David Krulwich share their thoughts on the biggest challenges facing math teachers.

The United Nations Security Council decided on 10 April to deploy a peacekeeping mission in the Central African Republic (CAR) which will take over the mission of the African Union (MISCA), which itself succeeded the mission of the Economic Community of Central African States (MICOPAX).

Periodontitis as a biofilm-associated inflammatory disease is highly prevalent worldwide. It severely affects oral health and yet closely links to systemic diseases like diabetes and cardiovascular disease. Porphyromonas gingivalis as a ‘keystone' periodontopathogen drives the shift of microbe-host symbiosis to dysbiosis, and critically contributes to the pathogenesis of periodontitis. Persisters are a tiny subset of biofilm-associated microbes highly tolerant to lethal treatment of antimicrobials, and notably metronidazole-tolerant P. gingivalis persisters have recently been identified by our group. This study further explored the interactive profiles of metronidazole-treated P. gingivalis persisters (M-PgPs) with human gingival epithelial cells (HGECs). P. gingivalis cells (ATCC 33277) at stationary phase were treated with lethal dosage of metronidazole (100 μg/ml, 6 hours) for generating M-PgPs. The interaction of M-PgPs with HGECs was assessed by microscopy, flow cytometry, cytokine profiling and qPCR. We demonstrated that the overall morphology and ultra-cellular structure of M-PgPs remained unchanged. Importantly, M-PgPs maintained the capabilities to adhere to and invade into HGECs. Moreover, M-PgPs significantly suppressed pro-inflammatory cytokine expression in HGECs at a comparable level with the untreated P. gingivalis cells, through the thermo-sensitive components. The present study reveals that P. gingivalis persisters induced by lethal treatment of antibiotics could maintain their capabilities to adhere to and invade into human gingival epithelial cells, and perturb the innate host responses. Novel strategies and approaches need to be developed for tackling P. gingivalis and favourably modulating the dysregulated immuno-inflammatory responses for oral/periodontal health and general wellbeing.

The Cpx stress response is widespread among Enterobacteriaceae. We have previously reported a mutation in cpxA in a multidrug resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields to a single amino acid substitution (Y144N) located in the periplasmic sensor domain of CpxA. In this work, we sought to characterize this mutation in Escherichia coli by using genetic and biochemical approaches. Here, we show that cpxA^Y144N is an activated allele that confers resistance to β-lactams and aminoglycosides in a CpxR-dependent manner, by regulating the expression of the OmpF porin and the AcrD efflux pump, respectively. We also demonstrate the intimate interconnection between Cpx system and peptidoglycan integrity on the expression of an exogenous AmpC β-lactamase by using imipenem as a cell wall active antibiotic or inactivation of penicillin-binding proteins. Moreover, our data indicate that the Y144N substitution abrogates the interaction between CpxA and CpxP and increase phosphotransfer activity on CpxR. Because the addition of a strong AmpC inducer such as imipenem is known to causes abnormal accumulation of muropeptides (disaccharide-pentapeptide, N-acetylglucosamyl-1,6-anhydro-N-acetylmuramyl-l-alanyl-d-glutamy-meso-diaminopimelic-acid-d-alanyl-d-alanine) in the periplasmic space, we propose these molecules activate the Cpx system by displacing CpxP from the sensor domain of CpxA. Altogether, these data could explain why large perturbations to peptidoglycan caused by imipenem lead to mutational activation of the Cpx system and bacterial adaptation through multidrug resistance. These results also validate the Cpx system, in particular the interaction between CpxA and CpxP, as a promising therapeutic target.

Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.

Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.

Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.

The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens.

Funders have been both fast and thoughtful about how to work with national and local partners to listen to needs from the field, identify best practices, and deploy resources quickly, says Celine Coggins.

"This pandemic has given us an opportunity to think boldly about students' educational needs and how to creatively respond to them," says Katherine Haley.

Elizabeth Stringer Keefe, Becky Shiring, Katie Robinson, Dr. Sonny Magana and Dr. Monica Burns contribute their suggestions on using tech to differentiate instruction.

MASC has successfully designed and delivered critical equipment and supplies needed to protect health care workers and patients during the COVID-19 pandemic.

Effective immediately and for the foreseeable future, the Entrepreneurship and Assistance Clinic is expanding its scope and service offerings to small Pennsylvania businesses, in response to the COVID-19 pandemic.

Young adults born prematurely with very low birth weight (≤1500 g) have higher blood pressure than do their counterparts born at term. We tested whether they also have higher blood pressure reactivity to psychosocial stress, which may be a more-specific predictor of long-term cardiovascular morbidity. Systolic and diastolic blood pressure levels for 44 very low birth weight adults (mean age: 23.1 years; SD: 2.3 years) and 37 control subjects (mean age: 23.6 years; SD: 2.0 years) were measured through noninvasive finger photoplethysmography during a standardized psychosocial stress challenge (Trier Social Stress Test). Baseline and task values and their difference (ie, reactivity) served as outcome variables. In comparison with the control group, the very low birth weight group had 7.9 mm Hg higher diastolic blood pressure during the task and 4.8 mm Hg higher diastolic reactivity, with adjustment for gender and age, height, and BMI at testing. A similar trend was seen for systolic blood pressure during the baseline period and the task, but the group differences were not statistically significant. Our results indicate that very low birth weight is associated with elevated blood pressure reactivity to psychosocial stress and, therefore, may increase the risk of cardiovascular morbidity.

Angel Cintron Jr., Connie Parham, Catlin Tucker, Sheri Edwards, Cheryl Costello, William J. Tolley and George Station explore what blended learning is and how it can be made most effective.

As the world continues to face the ongoing impacts of the global coronavirus pandemic, Penn State President Eric Barron outlined Friday the University’s actions over the past five months to address the challenges, protect the health and safety of the University community, and prepare for the future.

Education Week asked three 8th grade teachers to evaluate real student responses to an open-ended question on the National Assessment of Educational Progress in social studies. Here's what they said.

The Scottish Parliament has announced it will suspend public engagement activities as it prioritises supporting parliamentary business and responding to the Coronavirus.

Lewis Macdonald MSP has been elected as a temporary Deputy Presiding Officer (DPO) of the Scottish Parliament. The election was held as part of the Parliament's response to the coronavirus pandemic.

The Presiding Officer has today written to all Members to set out new business plans this week. The first ever Members’ Virtual Question Time will be held this Friday, 17 April at 2:30pm.