Can Pediatric Primary Care Practices Afford Integrated Behavioral Health? A Comparison of 5 Pediatric Practices.

Licensed behavioral health providers (LBHPs) were integrated into 5 pediatric primary care practices in southeast and east Texas from October 2018 through March 2020. LBHPs Licensed behavioral health providers across the sites were 3 licensed clinical social workers (LCSW), 1 psychologist, and 1 nurse practitioner (NP). Practices provided data for 6 to 15 months. Overall, 2769 units of behavioral health services were provided to 746 children over 2243 hours. Across 4 sites, 44.3% of behavioral health patients were diagnosed with trauma disorders, 22.1% with anxiety, 19.3% with attention-deficit hyperactivity disorder, 15.1% with depression, and 10.9% with disruptive behavior disorders. Overall, the model was financially successful at 2 sites (LCSWs) and unsuccessful at 1 site (NP). The other 2 sites demonstrated potential for financial sustainability with increased behavioral health patient volume. Overall, this model is a financially viable option for pediatric primary care practices with adequate patient volumes to provide integrated behavioral health services.

Probing the energetic particle environment near the Sun.

NASA's Parker Solar Probe mission1 recently plunged through the inner heliosphere of the Sun to its perihelia, about 24 million kilometres from the Sun. Previous studies farther from the Sun (performed mostly at a distance of 1 astronomical unit) indicate that solar energetic particles are accelerated from a few kiloelectronvolts up to near-relativistic energies via at least two processes: 'impulsive' events, which are usually associated with magnetic reconnection in solar flares and are typically enriched in electrons, helium-3 and heavier ions2, and 'gradual' events3,4, which are typically associated with large coronal-mass-ejection-driven shocks and compressions moving through the corona and inner solar wind and are the dominant source of protons with energies between 1 and 10 megaelectronvolts. However, some events show aspects of both processes and the electron-proton ratio is not bimodally distributed, as would be expected if there were only two possible processes5. These processes have been very difficult to resolve from prior observations, owing to the various transport effects that affect the energetic particle population en route to more distant spacecraft6. Here we report observations of the near-Sun energetic particle radiation environment over the first two orbits of the probe. We find a variety of energetic particle events accelerated both locally and remotely including by corotating interaction regions, impulsive events driven by acceleration near the Sun, and an event related to a coronal mass ejection. We provide direct observations of the energetic particle radiation environment in the region just above the corona of the Sun and directly explore the physics of particle acceleration and transport.

A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC.

BACKGROUND: Despite the significant antitumor activity of pembrolizumab in NSCLC, clinical benefit has been less frequently observed in patients whose tumors harbor EGFR mutations compared to EGFR wild-type patients. Our single-center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with programmed death ligand 1 (PD-L1) expression ≥50%. METHODS: We conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation-positive, advanced NSCLC and PD-L1-positive (≥1%, 22C3 antibody) tumors. Pembrolizumab was administered 200 mg every 3 weeks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab. RESULTS: Enrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. Eighty-two percent of trial patients were treatment naïve, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression ≥50%. Only 1 patient had an objective response (9%), but repeat analysis of this patient's tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment-related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern. CONCLUSIONS: Pembrolizumab's lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting.

Observation of the 6°Fe nucleosynthesis-clock isotope in galactic cosmic rays.

Iron-60 ((60)Fe) is a radioactive isotope in cosmic rays that serves as a clock to infer an upper limit on the time between nucleosynthesis and acceleration. We have used the ACE-CRIS instrument to collect 3.55 × 10(5) iron nuclei, with energies ~195 to ~500 mega-electron volts per nucleon, of which we identify 15 (60)Fe nuclei. The (60)Fe/(56)Fe source ratio is (7.5 ± 2.9) × 10(-5) The detection of supernova-produced (60)Fe in cosmic rays implies that the time required for acceleration and transport to Earth does not greatly exceed the (60)Fe half-life of 2.6 million years and that the (60)Fe source distance does not greatly exceed the distance cosmic rays can diffuse over this time, ⪍1 kiloparsec. A natural place for (60)Fe origin is in nearby clusters of massive stars.

GALACTIC COSMIC RAYS IN THE LOCAL INTERSTELLAR MEDIUM: VOYAGER 1 OBSERVATIONS AND MODEL RESULTS.

Since 2012 August Voyager 1 has been observing the local interstellar energy spectra of Galactic cosmic-ray nuclei down to 3 MeV nuc-1 and electrons down to 2.7 MeV. The H and He spectra have the same energy dependence between 3 and 346 MeV nuc-1, with a broad maximum in the 10-50 MeV nuc-1 range and a H/He ratio of 12.2 ± 0.9. The peak H intensity is ~15 times that observed at 1 AU, and the observed local interstellar gradient of 3-346 MeV H is -0.009 ± 0.055% AU-1, consistent with models having no local interstellar gradient. The energy spectrum of electrons (e - + e +) with 2.7-74 MeV is consistent with E -1.30±0.05 and exceeds the H intensity at energies below ~50 MeV. Propagation model fits to the observed spectra indicate that the energy density of cosmic-ray nuclei with >3 MeV nuc-1 and electrons with >3 MeV is 0.83-1.02 eV cm-3 and the ionization rate of atomic H is in the range of 1.51-1.64 × 10-17 s-1. This rate is a factor >10 lower than the ionization rate in diffuse interstellar clouds, suggesting significant spatial inhomogeneity in low-energy cosmic rays or the presence of a suprathermal tail on the energy spectrum at much lower energies. The propagation model fits also provide improved estimates of the elemental abundances in the source of Galactic cosmic rays.

The economic impact of implementing a multiple inflammatory biomarker-based approach to identify, treat, and reduce cardiovascular risk.

OBJECTIVES: To develop an economic model to estimate the change in the number of events and costs of non-fatal myocardial infarction (MI) and non-fatal ischemic stroke (IS) as a result of implementing routine risk-stratification with a multiple inflammatory biomarker approach. METHODS: Reductions in the numbers of non-fatal MI and non-fatal IS events and in related per-member-per-month (PMPM) and 5-year costs (excluding test costs) due to biomarker testing were modeled for a US health plan with one million beneficiaries. Inputs for the model included literature-based MI and IS incidence rates, healthcare costs associated with MI and IS, laboratory results of biomarker testing, MI and IS hazard ratios related to biomarker levels, patient monitoring and intervention costs and use/costs of preventative pharmacotherapy. Preventative pharmacotherapy inputs were based on an analysis of pharmacy claims data. Costs savings (2013 USD) were assessed for patients undergoing biomarker testing compared to the standard of care. Data from MDVIP and Cleveland Heart Lab supported two critical inputs: (1) treatment success rates and (2) the population distribution of biomarker testing. Incidence rates, hazard ratios, and other healthcare costs were obtained from the literature. RESULTS: For a health plan with one million members, an estimated 21,104 MI and 22,589 IS events occurred in a 5-year period. Routine biomarker testing among a sub-group of beneficiaries ≥35 years old reduced non-fatal MI and IS events by 2039 and 1869, respectively, yielding cost savings of over $187 million over 5 years ($3.13 PMPM), excluding test costs. Results were sensitive to changes in treatment response rates. Nonetheless, cost savings were observed for all input values. CONCLUSIONS: This study suggests that health plans can realize substantial cost savings by preventing non-fatal MI and IS events after implementation of routine biomarker testing. Five-year cost savings before test costs could exceed $3.13 PMPM.

Negotiating the radiologically isolated syndrome.

Multiple sclerosis, always challenging, hands down a particular gauntlet with the concept of the radiologically isolated syndrome. This article discusses what it is, recent developments in the field and how these patients should be managed.

Voyager 1 observes low-energy galactic cosmic rays in a region depleted of heliospheric ions.

On 25 August 2012, Voyager 1 was at 122 astronomical units when the steady intensity of low-energy ions it had observed for the previous 6 years suddenly dropped for a third time and soon completely disappeared as the ions streamed away into interstellar space. Although the magnetic field observations indicate that Voyager 1 remained inside the heliosphere, the intensity of cosmic ray nuclei from outside the heliosphere abruptly increased. We report the spectra of galactic cosmic rays down to ~3 × 10(6) electron volts per nucleon, revealing H and He energy spectra with broad peaks from 10 × 10(6) to 40 × 10(6) electron volts per nucleon and an increasing galactic cosmic-ray electron intensity down to ~10 × 10(6) electron volts.

Needs and preferences for the prevention of intimate partner violence among Hispanics: a community's perspective.

Research suggest that Hispanics in the U.S. are disproportionately affected by the consequences of intimate partner violence. Nevertheless, few intimate partner violence prevention interventions have been developed to address the unique needs and preferences of this population. The Partnership for Domestic Violence Prevention is a community-based participatory research project that assessed the needs and preferences for prevention programs for Hispanics in Miami-Dade County. Nine focus groups with domestic violence service providers, victims and general community members were conducted (N = 76). Four major themes emerged from the focus groups. These included immigrants and teens as the highest priority groups to target in prevention efforts, culture as a double-edged sword, the system that helps and hurts the victim, and the need for wide-scale prevention programs that would reach Hispanics systematically. The results from this study have important implications for the development of intimate violence prevention interventions targeting Hispanics in the U.S.

Parkinson disease loci in the mid-western Amish.

Previous evidence has shown that Parkinson disease (PD) has a heritable component, but only a small proportion of the total genetic contribution to PD has been identified. Genetic heterogeneity complicates the verification of proposed PD genes and the identification of new PD susceptibility genes. Our approach to overcome the problem of heterogeneity is to study a population isolate, the mid-western Amish communities of Indiana and Ohio. We performed genome-wide association and linkage analyses on 798 individuals (31 with PD), who are part of a 4,998 member pedigree. Through these analyses, we identified a region on chromosome 5q31.3 that shows evidence of association (p value < 1 × 10(-4)) and linkage (multipoint HLOD = 3.77). We also found further evidence of linkage on chromosomes 6 and 10 (multipoint HLOD 4.02 and 4.35 respectively). These data suggest that locus heterogeneity, even within the Amish, may be more extensive than previously appreciated.

The psychological impact of diagnostic food challenges to confirm the resolution of peanut or tree nut allergy.

BACKGROUND: Twenty percent of children outgrow peanut allergy and 10% outgrow tree nut allergy. Resolution can be confirmed by a food challenge. Little is known about the psychosocial impact of the challenge. We aimed to investigate effects of a food challenge on anxiety, stress and quality of life (QoL) in children and their mothers on the day of a food challenge to peanuts or nuts, and in the months following the challenge. METHODS: One hundred and three families participated. Forty children undergoing food challenges to access resolution of allergy, and their mothers, completed validated questionnaires to measure generic and food specific quality of life, stress and anxiety prior to challenge, on the day of investigation and 3-6 months later. Sixty-three children with no clinical indication to challenge (i.e. in the opinion of the allergist had persistent allergy) acted as comparison group completing questionnaires 3-6 months apart. RESULTS: Mothers reported raised anxiety on the day of challenge (P = 0.007), but children were less anxious. The children (P = 0.01) and mothers (P = 0.01) had improved food-related, but not general, QoL 3-6 months following challenge. Children reported lower anxiety levels following the challenge (P = 0.02), but anxiety remained unchanged in mothers. The improvements in maternal and children's QoL and anxiety levels were irrespective of the challenge outcome and despite co-existing food allergies in 50% of children. CONCLUSIONS: Mothers experienced increased anxiety on the day of food challenge, unlike the children, perhaps reflecting the differences in their perceived risks. Food challenges are associated with improved food-related QoL in the following months even in those with a positive challenge.

Anisotropic intrinsic spin Hall effect in quantum wires.

We use numerical simulations to investigate the spin Hall effect in quantum wires in the presence of both Rashba and Dresselhaus spin-orbit coupling. We find that the intrinsic spin Hall effect is highly anisotropic with respect to the orientation of the wire, and that the nature of this anisotropy depends strongly on the electron density and the relative strengths of the Rashba and Dresselhaus spin-orbit couplings. In particular, at low densities, when only one subband of the quantum wire is occupied, the spin Hall effect is strongest for electron momentum along the [N110] axis, which is the opposite of what is expected for the purely 2D case. In addition, when more than one subband is occupied, the strength and anisotropy of the spin Hall effect can vary greatly over relatively small changes in electron density, which makes it difficult to predict which wire orientation will maximize the strength of the spin Hall effect. These results help to illuminate the role of quantum confinement in spin-orbit-coupled systems, and can serve as a guide for future experimental work on the use of quantum wires for spin-Hall-based spintronic applications.

The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: a review.

Food allergy affects 6% of children but there is no cure, and strict avoidance of index allergens along with immediate access to rescue medication is the current best management. With specialist care, morbidity from food allergy in children is generally low, and mortality is very rare. However, there is strong evidence that food allergy and food hypersensitivity has an impact on psychological distress and on the quality of life (QoL) of children and adolescents, as well as their families. Until recently, the measurement of QoL in allergic children has proved difficult because of the lack of investigative tools available. New instruments for assessing QoL in food allergic children have recently been developed and validated, which should provide further insights into the problems these children encounter and will enable us to measure the effects of interventions in patients. This review examines the published impact of food allergy on affected children, adolescents and their families. It considers influences such as gender, age, disease severity, co-existing allergies and external influences, and examines how these may impact on allergy-related QoL and psychological distress including anxiety and depression. Implications of the impact are considered alongside avenues for future research.

Spectral vs. temporal auditory processing in specific language impairment: a developmental ERP study.

Pre-linguistic sensory deficits, especially in "temporal" processing, have been implicated in developmental language impairment (LI). However, recent evidence has been equivocal with data suggesting problems in the spectral domain. The present study examined event-related potential (ERP) measures of auditory sensory temporal and spectral processing, and their interaction, in typical children and those with LI (7-17 years; n=25 per group). The stimuli were three CV syllables and three consonant-to-vowel transitions (spectral sweeps) isolated from the syllables. Each of these six stimuli appeared in three durations (transitions: 20, 50, and 80 ms; syllables: 120, 150, and 180 ms). Behaviorally, the group with LIs showed inferior syllable discrimination both with long and short stimuli. In ERPs, trends were observed in the group with LI for diminished long-latency negativities (the N2-N4 peaks) and a developmentally transient enhancement of the P2 peak. Some, but not all, ERP indices of spectral processing also showed trends to be diminished in the group with LI specifically in responses to syllables. Importantly, measures of the transition N2-N4 peaks correlated with expressive language abilities in the LI children. None of the group differences depended on stimulus duration. Therefore, sound brevity did not account for the diminished spectral resolution in these LI children. Rather, the results suggest a deficit in acoustic feature integration at higher levels of auditory sensory processing. The observed maturational trajectory suggests a non-linear developmental deviance rather than simple delay.

Subband anticrossing and the spin Hall effect in quantum wires.

We report on numerical simulations of the intrinsic spin Hall effect in semiconductor quantum wires as a function of the Rashba spin-orbit coupling strength, the electron density, and the width of the wire. We find that the strength of the spin Hall effect does not depend monotonically on these parameters, but instead exhibits a local maximum. This behavior is explained by considering the dispersion relation of the electrons in the wire, which is characterized by the anticrossing of adjacent subbands. These results lead to a simple estimate of the optimal wire width for spin Hall transport experiments, and simulations indicate that this optimal width is independent of disorder. The anticrossing of adjacent subbands is related to a quantum phase transition in momentum space, and is accompanied by an enhancement of the Berry curvature and subsequently in the magnitude of the spin Hall effect.

Evaluation of a novel animal model for teaching intubation.

BACKGROUND: Medical colleges, which face dwindling financial resources, are often forced to rely on inexpensive means of providing students with relevant learning opportunities. PURPOSES: In this article, we present an evaluation of a novel animal model to be used to teach medical students, resident physicians, and allied health personnel advanced airway management skills, namely, endotracheal intubation. METHODS: Over 3 years of regularly scheduled teaching laboratories, 140 students had exposure to both a traditional teaching manikin and a whitetail deer head on which to learn rescue airway techniques. We measured participants on successfully completing an intubation, and we timed them to determine length of time to complete it. Participants also rated the experience across a variety of dimensions. RESULTS: Students reported being very satisfied with the learning experience and were able to perform the techniques more quickly and accurately using the animal model. CONCLUSIONS: The deer airway model is superior to the manikin airway model in teaching endotracheal intubation to students. It should be considered as a viable alternative in medical education settings.

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines.

Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53-442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC50 > 8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.

Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia.

The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate whether ALL cells have an altered metabolism, we initially compared the transcriptional profiles of 22 specimens from paediatric patients diagnosed with ALL to five CD34+ specimens isolated from bone marrow, which was verified in an independent cohort of 101 specimens. Profiling revealed the upregulation of genes facilitating glycolysis in the ALL specimens compared to the CD34+ specimens, while those involved in the tricarboxylic acid cycle were downregulated. Functional studies supported the microarray findings threefold: (1) higher expression of the glucose transport protein glucose transporter 1 in ALL compared to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose. While metabolic alterations have been well documented in solid tumours, this is the first study to provide direct evidence for the existence of metabolic changes in the leukaemic cells of ALL patients. The finding offers new options for targeted therapy for ALL patients.

Auditory semantic networks for words and natural sounds.

Does lexical processing rely on a specialized semantic network in the brain, or does it draw on more general semantic resources? The primary goal of this study was to compare behavioral and electrophysiological responses evoked during the processing of words, environmental sounds, and non-meaningful sounds in semantically matching or mismatching visual contexts. A secondary goal was to characterize the dynamic relationship between the behavioral and neural activities related to semantic integration using a novel analysis technique, ERP imaging. In matching trials, meaningful-sound ERPs were characterized by an extended positivity (200-600 ms) that in mismatching trials partly overlapped with centro-parietal N400 and frontal N600 negativities. The mismatch word-N400 peaked later than the environmental sound-N400 and was only slightly more posterior in scalp distribution. Single-trial ERP imaging revealed that for meaningful stimuli, the match-positivity consisted of a sensory P2 (200 ms), a semantic positivity (PS, 300 ms), and a parietal response-related positivity (PR, 500-800 ms). The magnitudes (but not the timing) of the N400 and PS activities correlated with subjects' reaction times, whereas both the latency and magnitude of the PR was correlated with subjects' reaction times. These results suggest that largely overlapping neural networks process verbal and non-verbal semantic information. In addition, it appears that semantic integration operates across different time scales: earlier processes (indexed by the PS and N400) utilize the established meaningful, but not necessarily lexical, semantic representations, whereas later processes (indexed by the PR and N600) are involved in the explicit interpretation of stimulus semantics and possibly of the required response.