KM Harris
Aug 1, 1989; 9:2982-2997
Articles

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.

Mary Pearson, who was briefly engaged to the writer's brother, may be the real-life counterpart of Lydia Bennet from "Pride and Prejudice"

Hamish Wilson, radio producer and actor

Lord Armstrong of Ilminster

Educators, public health authorities, and law enforcement are confronting an increasing number of cases in which youth made sexual images of themselves and other minors and transmitted them via cell phones and the Internet.

This study provides the first detailed and comprehensive national estimate of the percentage of youth who create and distribute various kinds of sexual images. (Read the full article)

Gallbladder disease in children is an evolving entity and studies suggest an increasing frequency of symptomatic pediatric gallbladder disease and resultant cholecystectomies.

Hispanic ethnicity and obesity are epidemiologically significant risk factors for symptomatic gallbladder disease in the pediatric population. (Read the full article)

Autism is widely considered a heterogeneous disorder in terms of etiology and phenotype. Although autism is usually a lifelong disorder, little is known about the rate or timing of how children develop regarding their communication and social functioning.

Utilizing annual evaluations for a large population of children with autism, we describe the 6 most common trajectories from diagnosis through age 14 years. Trajectories revealed considerable variation, and high socioeconomic status children were more likely to experience rapid improvement. (Read the full article)

More than one-tenth pediatric patients use complementary and alternative medicines (CAM) for their medial conditions in the United States. Traditional Chinese medicine (TCM) is the most commonly used CAM in East Asia but large-scale epidemiologic studies are lacking.

In comparing TCM and non-TCM users among children in Taiwan, children’s age and parental TCM use were strongly associated with TCM use. Additionally, dyspepsia and allergic rhinitis were positively related to increasing TCM use. (Read the full article)

Recent investigations of pubertal onset in US girls suggest earlier maturation. The situation for US boys is unknown, and existing investigations are outdated and lack information on a key physical marker of male puberty: testicular enlargement.

US boys appear to be developing secondary sexual characteristics and achieving testicular enlargement 6 months to 2 years earlier than commonly used norms, with African American boys entering Tanner stages 2 to 4 earlier than white or Hispanic boys. (Read the full article)

Osteopathy of prematurity continues to occur in preterm infants. Osteopathy of prematurity can cause rib fractures in ex-preterm infants.

Rib fractures in ex-preterm infants are often posterior and multiple. Posterior rib fractures may not be diagnostic of nonaccidental injury in ex-preterm infants. (Read the full article)

National asthma treatment guidelines include the recommendation that all asthma patients receive a written asthma action plan. No previous study has sought to examine the readability, suitability, and content of asthma action plans within a nationally representative sample.

Although variability was found across written asthma action plans, and improvements in readability, suitability, and content are needed, there were also many common elements that would support a move to a single universal standard action plan. (Read the full article)

Validated questionnaires can improve the identification of psychosocial problems among children. The Strengths and Difficulties Questionnaire (SDQ) 3-4 is a promising option. However, no studies are available that examine the psychometric properties of the SDQ parent form 3-4.

The results of this study show that the SDQ 3-4 is a valid tool for the identification of psychosocial problems in preschool-aged children. (Read the full article)

Although the metabolic syndrome is associated with obesity, not all obese children have insulin resistance and metabolic syndrome, and nonobese children may develop these abnormalities. Associated factors have not been well described.

There was a 6.6% prevalence of nonobese children who were insulin-resistant, associated with a family history of hypertension. There was a 21.3% prevalence of obese who were not insulin-resistant, associated with a low waist circumference. (Read the full article)

Rates of screen media use have risen in parallel with rates of obesity among young people. Identifying the specific characteristics of media use that are associated with obesity can help elucidate the explanatory processes and inform effective interventions.

This study examines the associations between BMI and characteristics of media use including the type of device, duration of use, and attention to the medium. The more that participants paid primary attention to television, the higher their BMI. (Read the full article)

Pediatric palliative care (PC) can be beneficial to children with life-threatening conditions and their families by providing symptom management and control, sibling support, bereavement services, spiritual guidance, support in decision-making about limiting burdensome medical interventions, and advance directives.

Little is known about actual receipt of PC by dying children. This study compares characteristics of dying children by receipt of PC and highlights underserved patient groups who could be targeted to improve access. (Read the full article)

Children with chronic pain complaints seem to represent an increasing portion of general pediatric inpatient services. Few data exist, however, on the characteristics of this population, their length of stay, or the best approach to their evaluation and management.

This study defines the demographic, diagnostic, procedural, and episode of care characteristics for children admitted to the acute care setting with chronic pain syndromes. Admission rates are rising, lengths of stay are substantial, and comorbid diagnoses are common. (Read the full article)

Pain in children with cerebral palsy is underrecognized and undertreated and negatively affects quality of life. Communication challenges and multiple pain etiologies complicate management. There is a wide range of pain prevalence reported in the literature (14% to 73%).

The impact of pain on activities in children with cerebral palsy across a wide age range and motor abilities is investigated. Physician-identified causes of pain are systematically assessed and reported. Concordance of physician and caregiver identification of pain is evaluated. (Read the full article)

Pediatric myasthenia encompasses a group of rare and underdiagnosed conditions affecting the neuromuscular junction. Symptoms include fluctuating skeletal muscle weakness, which can progress to respiratory failure if left untreated. The autoimmune form of this condition, in particular, is treatable.

This study describes the incidence, clinical features, diagnostic testing, and treatment trends of pediatric myasthenia in Canada, which have not been previously reported in the literature. (Read the full article)

Youth are frequent consumers of movies that contain high levels of violence, and violent content in films, especially those rated PG-13, has been increasing over time.

Content analyses seldom examine how violence is portrayed with other health risk behaviors, such smoking, drinking, and sex. This study presents an innovative way to characterize on-screen violent content and demonstrates the extent to which risk behaviors co-occur within films. (Read the full article)

The emergency department (ED) is a critical contact location for youth violence interventions. Information on the characteristics of youth, motivations for fights leading to the injury, as well as previous health service utilization of assault-injured youth seeking care is lacking.

Assault-injured youth are characterized in a systematic sample demonstrating frequent ED use and the need to address substance use and lethal means of force in interventions; context and motivations for the fight are novel and will inform intervention efforts. (Read the full article)

Palliative care is an increasingly important element of pediatric care for children with noncurable, terminal conditions. Freestanding hospices represent one model of care provision; however, little research on this approach has been conducted.

This report documents the experience of North America’s first freestanding hospice over 15 years to better understand the characteristics of children and families enrolled and to establish baseline information for future studies and program planning. (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)

Most studies of fetal alcohol syndrome and fetal alcohol spectrum disorders (FASD) prevalence in the general population of the United States have been carried out using passive methods (surveillance or clinic-based studies), which underestimate rates of FASD.

Using active case ascertainment methods among children in a representative middle class community, rates of fetal alcohol syndrome and total FASD are found to be substantially higher than most often cited estimates for the general US population. (Read the full article)

Pediatric autoimmune hepatitis is an uncommon condition; children and youth can present with a diverse and insidious clinical course and biochemical features. Response to treatment is generally good, and transplantation is rarely needed.

This population-based study adds knowledge regarding the incidence of pediatric autoimmune hepatitis in Canada, as well as a description of diagnostic and therapeutic approaches among centers. Long-term outcomes are also described. (Read the full article)

The American Academy of Pediatrics discourages providers from dismissing families who refuse vaccines for their children, yet some providers continue to do so.

We show that ~1 in 5 pediatricians dismiss families who refuse vaccines, and there is significant regional variation in the practice. Dismissing families for refusing vaccines was also associated with stricter state nonmedical exemption policies. (Read the full article)

Valor Collegiate Academies has been in the top 5 percent of Tennessee schools on growth and achievement every year since it started in 2014. But Tom visited Valor because of the well-regarded Valor Compass, a holistic human-development program.

QPX7728 is a new ultra-broad-spectrum inhibitor of serine and metallo beta-lactamases from a class of cyclic boronates that gave rise to vaborbactam. The spectrum and mechanism of beta-lactamase inhibition by QPX7728 were assessed using purified enzymes from all molecular classes. QPX7728 inhibits class A ESBLs (IC₅₀ range 1-3 nM) and carbapenemases such as KPC (IC₅₀ 2.9±0.4 nM) as well as class C P99 (IC₅₀ of 22±8 nM) with a potency that is comparable or higher than recently FDA approved BLIs avibactam, relebactam and vaborbactam. Unlike those other BLIs, QPX7728 is also a potent inhibitor of class D carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from A. baumannii (OXA-23/24/58, IC₅₀ range 1-2 nM) as well as MBLs such as NDM-1 (IC₅₀ 55±25 nM), VIM-1 (IC₅₀ 14±4 nM) and IMP-1 (IC₅₀ 610±70 nM). Inhibition of serine enzymes by QPX7728 is associated with progressive inactivation with a high efficiency k₂/K ranging from of 6.3 x 10⁴ (for P99) to 9.9 x 10⁵ M^-1 s^-1 (for OXA-23). This inhibition is reversible with variable stability of the QPX7728-beta-lactamase complexes with target residence time ranging from minutes to several hours: 5-20 minutes for OXA carbapenemases from A. baumanii, ~50 minutes for OXA-48 and 2-3 hours for KPC and CTX-M-15. QPX7728 inhibited all tested serine enzymes at 1:1 molar ratio. Metallo-beta-lactamases NDM, VIM, and IMP were inhibited by a competitive mechanism with fast-on-fast-off kinetics, with K_is of 7.5±2.1 nM, 32±14 nM and 240±30 nM for VIM-1, NDM-1 and IMP-1, respectively. QPX7728 ultra-broad-spectrum of BLI inhibition combined with its high potency enables combinations with multiple different beta-lactam antibiotics.

Leishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL and current drug regimens present several drawbacks such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase-1 (MetAP1), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activity of eight novel MetAP1 inhibitors (OJT001-OJT008) were investigated. Three compounds OJT006, OJT007, and OJT008 demonstrated potent anti-proliferative effect in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect was diminished by almost 10-fold in transgenic L. major promastigotes overexpressing MetAP1_LM in comparison to wild-type promastigotes. Furthermore, the in vivo activity of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the control group, OJT008 significantly decreased footpad parasite load by 86%, and exhibited no toxicity against in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection.

Omadacycline is a novel aminomethylcycline with activity against Gram-positive and -negative organisms, including Haemophilus influenzae, which is one of the leading causes of community-acquired bacterial pneumonia (CABP). The evaluation of antimicrobial agents against H. influenzae using standard murine infection models is challenging due to the low pathogenicity of this species in mice. Therefore, 24-hour dose-ranging studies using a one-compartment in vitro infection model were undertaken with the goal of characterizing the magnitude of the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) associated with efficacy for a panel of five clinical H. influenzae isolates. These five isolates, which had MIC values of 1 or 2 mg/L, were exposed to omadacycline total-drug epithelial lining fluid (ELF) concentration-time profiles based on those observed in healthy volunteers following intravenous omadacycline administration. Relationships between change in log₁₀ colony forming units (CFU) from baseline at 24 hours and total-drug ELF AUC/MIC ratio for each isolate and the isolates pooled together were evaluated using Hill-type models and non-linear least squares regression. As evidenced by the high coefficient of determination (r²) of 0.88 to 0.98, total-drug ELF AUC/MIC ratio described the data well for each isolate and the isolates pooled together. The median total-drug ELF AUC/MIC ratio associated with net bacterial stasis and 1- and 2-log₁₀ CFU/mL reductions from baseline at 24 hours was 6.91, 8.91, and 11.1, respectively. These data were useful to support the omadacycline dosing regimens selected for the treatment of patients with CABP, as well as susceptibility breakpoints for H. influenzae.

Jessica L. Barrington-Trimis
May 1, 2020; 145:e20191652-e20191652
ARTICLES

Andrea T. Cruz
Apr 8, 2020; 0:peds.2020-0834v2-e20200834
COMMENTARY

Marcia E. Herman-Giddens
Apr 1, 1997; 99:505-512
ARTICLES

Qing Xu, Sylvie Huet, Eric Perret and Guillaume Deffuant: The drivers of conversion to organic farming, which is still a residual choice in agriculture, are poorly understood. Many scholars argue that farm characteristics can determine this choice but do not exclude the role of social dynamics. To study this issue, we developed an agent-based model in which agents' decisions to shift to organic farming are based on a comparison between satisfaction with the current situation and potential satisfaction with an alternative farming strategy. A farmer agent’s satisfaction is modelled using the Theory of Reasoned Action. This makes it necessary to compare an agent's productions over time with those of other agents to whom the former attributes considerable credibility (“important others”). Moreover, farmers make technical changes that affect their productions by imitating other credible farmers. While we first used this model to examine simple and abstract farm populations, here we also adapted it for use with data from an Agricultural Census concerning the farm characteristics of dairy farming in 27 French “cantons”. Based on domain expertise, data and previous research, we propose certain laws for modelling the impact of conversion on the farm production of milk and the environment. The simulations with “real” populations of farms confirm the important impact of farm characteristics. However, our results also suggest a complex impact of social dynamics that can favour or impede the diffusion of organic farming through dynamic implicit networks of similarity and credibility. We confirm the great importance of demographic changes in farm characteristics.

  Introduction Character modeling is the process of creating a character within the 3D space of computer programs. The techniques for character modeling are essential for third - and first - person e...

Bengali actor-politician Tapas Pal, who died of a cardiac arrest at 61, will be remembered as Kedar Chatterjee. That is the name of the character the actor and former Trinamool Congress lawmaker...

Recently, I read an article about how failure is the stepping stone to success in life. It instantly struck a chord and a thought came zinging from nowhere about what happens to the failed arcs of a...

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Hi,

I am trying to characterize a D flip-flop for low voltage operation (0.6V) using Cadence Liberate (V16). This is a positive edge triggered D flip flop based on true-single-phase clocking scheme. After the characterization, the measurements reported for hold constraint arcs seem to deviate significantly from its (spectre) spice simulation.

The constraint and the power settings to the liberate are as follows : 

# -------------------------------------------- Timing Constraints --------------------------------------------------------------------------------
### Input waveform ###
set_var predriver_waveform 2;# 2=use pre-driver waveform
### Capacitance ###
set_var min_capacitance_for_outputs 1;# write min_capacitance attribute for output pins
### Timing ###
set_var force_condition 4
### Constraint ###
set_var constraint_info 2
#set_var constraint_search_time_abstol 1e-12 ;# 1ps resolution for bisection search
set_var nochange_mode 1 ;# enable nochange_* constraint characterization
### min_pulse_width ###
set_var conditional_mpw 0
set_var constraint_combinational 2

#---------------------------------------------- CCS Settings ----------------------------------------------------------------------------------------
set_var ccsn_include_passgate_attr 1
set_var ccsn_model_related_node_attr 1
set_var write_library_is_unbuffered 1

set_var ccsp_min_pts 15 ;# CCSP accuracy
set_var ccsp_rel_tol 0.01 ;# CCSP accuracy
set_var ccsp_table_reduction 0 ;# CCSP accuracy
set_var ccsp_tail_tol 0.02 ;# CCSP accuracy
set_var ccsp_related_pin_mode 2 ;# use 3 for multiple input switching scnarios and Voltus only libraries

#----------------------------------------------- Power ---------------------------------------------------------------------------------------------------
### Leakage ###
set_var max_leakage_vector [expr 2**10]
set_var leakage_float_internal_supply 0 ;# get worst case leakage for power switch cells when off
set_var reset_negative_leakage_power 1 ;# convert negative leakage current to 0

### Power ###
set_var voltage_map 1 ;# create pg_pin groups, related_power_pin / related_ground_pin
set_var pin_based_power 0 ;# 0=based on VDD only; 1=power based on VDD and VSS (default);
set_var power_combinational_include_output 0 ;# do not include output pins in when conditions for combinational cells

set_var force_default_group 1
set_default_group -criteria {power avg} ;# use average for default power group

#set_var power_subtract_leakage 4 ;# use 4 for cells with exhaustive leakage states.
set_var subtract_hidden_power 2 ;# 1=subtract hidden power for all cells
set_var subtract_hidden_power_use_default 3 ;# 3=subtract hidden power from matched when condition then default group
set_var power_multi_output_binning_mode 1 ;# binning for multi-output cell considered for both timing and power arcs
set_var power_minimize_switching 1
set_var max_hidden_vector [expr 2**10]
#--------------------------------------------------------------------------------------------------------------------------------------------------------------

I specifically used set_var constraint_combinational 2 in the settings, in case the Bisection pass/fail mode fails to capture the constraints. In my spice simulation, the hold_rise (D=1, CLK=R, Q=R) arc at-least requires ~250 ps for minimum CLK/D slew combination (for the  by default smallest capacitive load as per Liberate)  while Liberate reports only ~30 ps. The define_cell template to this flip flop is pretty generic, which does not have any user specified arcs. So which settings most likely affecting the constraint measurements in Liberate and how can I debug this issue ?

Thanks

Anuradha

Cadence Liberate Trio Characterization Suite, ARM-based Graviton Processors, and Amazon Web Services (AWS) Cloud have joined forces to cater to the High-Performance Computing, Machine Learning/Artificial Intelligence, and Big Data Analytics sectors. (read more)

Let’s review a key characteristic feature of Cadence Liberate AMS Mixed-Signal Characterization that offers to you ease of use along with many other benefits like automation of standard Liberty model creation and improvement of up to 20X throughput.(read more)

In this blog, I will brief you about two very useful Rapid Adoption Kits (RAKs) for Liberate LV Library Validation.(read more)

A recap of the blogs published in the Library Characterization Tidbits blog series.(read more)

Read how the Cadence Liberate Characterization solution effectively enables you to characterize only the failed or new arcs of a standard cell.(read more)

In recognition of the widely acknowledged studies that show that organizations with gender equality perform better financially, this year POWERGEN International, along with partner UL, is launching a new awards program that seeks out women of good character.

In recognition of the widely acknowledged studies that show that organizations with gender equality perform better financially, this year POWERGEN International, along with partner UL, is launching a new awards program that seeks out women of good character.

In recognition of the widely acknowledged studies that show that organizations with gender equality perform better financially, this year POWERGEN International, along with partner UL, is launching a new awards program that seeks out women of good character.