Waiting for child developmental and rehabilitation services: an overview of issues and needs

Concern about the length of time that children, young people, and families may have to wait to access assessment, diagnostic, interventional, therapeutic, and supportive child developmental and rehabilitation (CDR) services is widespread, but adequate data collection and research on this issue remain limited. We review key concepts and issues relevant to waiting for CDR services from the published literature, a national workshop devoted to this topic, and international experience. We conclude that gaps in data, evidence, and consensus challenge our ability to address the issue of waiting for CDR services in a systematic way. A program of research coupled with actions based on consensus-building is required. Research priorities include acquiring evidence of the appropriateness and effectiveness of different models of intervention and rehabilitation services, and documenting the experience and expectations of waiting families. Consensus-building processes are critical to identify, categorize, and prioritize \u27sentinel\u27 components of CDR service pathways: (1) to reduce the inherent complexity of the field; (2) to create benchmarks for waiting for these respective services; and (3) to develop definitions for wait-time subcomponents in CDR services. Collection of accurate and replicable data on wait times for CDR services can be used to document baseline realities, to monitor and improve system performance, and to conduct comparative and analytic research in the field of CDR services

Fast-evolving noncoding sequences in the human genome

BACKGROUND: Gene regulation is considered one of the driving forces of evolution. Although protein-coding DNA sequences and RNA genes have been subject to recent evolutionary events in the human lineage, it has been hypothesized that the large phenotypic divergence between humans and chimpanzees has been driven mainly by changes in gene regulation rather than altered protein-coding gene sequences. Comparative analysis of vertebrate genomes has revealed an abundance of evolutionarily conserved but noncoding sequences. These conserved noncoding (CNC) sequences may well harbor critical regulatory variants that have driven recent human evolution. RESULTS: Here we identify 1,356 CNC sequences that appear to have undergone dramatic human-specific changes in selective pressures, at least 15% of which have substitution rates significantly above that expected under neutrality. The 1,356 'accelerated CNC' (ANC) sequences are enriched in recent segmental duplications, suggesting a recent change in selective constraint following duplication. In addition, single nucleotide polymorphisms within ANC sequences have a significant excess of high frequency derived alleles and high F(ST)values relative to controls, indicating that acceleration and positive selection are recent in human populations. Finally, a significant number of single nucleotide polymorphisms within ANC sequences are associated with changes in gene expression. The probability of variation in an ANC sequence being associated with a gene expression phenotype is fivefold higher than variation in a control CNC sequence. CONCLUSION: Our analysis suggests that ANC sequences have until very recently played a role in human evolution, potentially through lineage-specific changes in gene regulation

Implementation and Quality Improvement of a Screening and Counseling Program for Unhealthy Alcohol Use in an Academic General Internal Medicine Practice

Unhealthy alcohol use is the third leading cause of preventable death in the United States (U.S.). The U.S. Preventive Services Task Force recommends screening for unhealthy alcohol use but little is known about how best to do so. We used quality improvement techniques to implement a systematic approach to screening and counseling primary care patients for unhealthy alcohol use. Components included use of validated screening and assessment instruments; an evidence-based 2-visit counseling intervention using motivational interviewing techniques for those with risky drinking behaviors who did not have an alcohol use disorder (AUD); shared decision making about treatment options for those with an AUD; support materials for providers and patients; and training in motivational interviewing for faculty and residents. Over the course of one year, we screened 52% (N=5,352) of our clinic’s patients and identified 294 with positive screens. Of those 294, appropriate screening-related assessments and interventions were documented for 168 and 72 patients, respectively. Although we successfully implemented a systematic screening program and structured processes of care, ongoing quality improvement efforts are needed to screen the rest of our patients and to improve the consistency with which we provide and document appropriate interventions

Evaluating models for lithospheric loss and intraplate volcanism beneath the Central Appalachian Mountains

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Long, M. D., Wagner, L. S., King, S. D., Evans, R. L., Mazza, S. E., Byrnes, J. S., Johnson, E. A., Kirby, E., Bezada, M. J., Gazel, E., Miller, S. R., Aragon, J. C., & Liu, S. Evaluating models for lithospheric loss and intraplate volcanism beneath the Central Appalachian Mountains. Journal of Geophysical Research: Solid Earth, 126(10), (2021): e2021JB022571, https://doi.org/10.1029/2021JB022571.The eastern margin of North America has been shaped by a series of tectonic events including the Paleozoic Appalachian Orogeny and the breakup of Pangea during the Mesozoic. For the past ∼200 Ma, eastern North America has been a passive continental margin; however, there is evidence in the Central Appalachian Mountains for post-rifting modification of lithospheric structure. This evidence includes two co-located pulses of magmatism that post-date the rifting event (at 152 and 47 Ma) along with low seismic velocities, high seismic attenuation, and high electrical conductivity in the upper mantle. Here, we synthesize and evaluate constraints on the lithospheric evolution of the Central Appalachian Mountains. These include tomographic imaging of seismic velocities, seismic and electrical conductivity imaging along the Mid-Atlantic Geophysical Integrative Collaboration array, gravity and heat flow measurements, geochemical and petrological examination of Jurassic and Eocene magmatic rocks, and estimates of erosion rates from geomorphological data. We discuss and evaluate a set of possible mechanisms for lithospheric loss and intraplate volcanism beneath the region. Taken together, recent observations provide compelling evidence for lithospheric loss beneath the Central Appalachians; while they cannot uniquely identify the processes associated with this loss, they narrow the range of plausible models, with important implications for our understanding of intraplate volcanism and the evolution of continental lithosphere. Our preferred models invoke a combination of (perhaps episodic) lithospheric loss via Rayleigh-Taylor instabilities and subsequent small-scale mantle flow in combination with shear-driven upwelling that maintains the region of thin lithosphere and causes partial melting in the asthenosphere.The authors acknowledge support from the U.S. National Science Foundation EarthScope and GeoPRISMS programs via grants EAR-1460257 (R. L. Evans), EAR-1249412 (E. Gazel), EAR-1249438 (E. A. Johnson), EAR-1250988 (S. D. King), EAR-1251538 (E. Kirby), and EAR-1251515 (M. D. Long). The collection and dissemination of most of the geophysical data and models discussed in this study were facilitated by the Incorporated Research Institutions for Seismology (IRIS). The facilities of the IRIS Consortium are supported by the United States National Science Foundation under Cooperative Agreement EAR-1261681

KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib

BACKGROUND: Somatic mutations in the gene for the epidermal growth factor receptor (EGFR) are found in adenocarcinomas of the lung and are associated with sensitivity to the kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Lung adenocarcinomas also harbor activating mutations in the downstream GTPase, KRAS, and mutations in EGFR and KRAS appear to be mutually exclusive. METHODS AND FINDINGS: We sought to determine whether mutations in KRAS could be used to further enhance prediction of response to gefitinib or erlotinib. We screened 60 lung adenocarcinomas defined as sensitive or refractory to gefitinib or erlotinib for mutations in EGFR and KRAS. We show that mutations in KRAS are associated with a lack of sensitivity to either drug. CONCLUSION: Our results suggest that treatment decisions regarding use of these kinase inhibitors might be improved by determining the mutational status of both EGFR and KRAS

Structural insights into what glycan arrays tell us about how glycan-binding proteins interact with their ligands

Screening of glycan arrays represents a powerful, high-throughput approach to defining oligosaccharide ligands for glycan-binding receptors, commonly referred to as lectins. Correlating results from such arrays with structural analysis of receptor–ligand complexes provide one way to validate the arrays. Using examples drawn from the family of proteins that contain C-type carbohydrate-recognition domains, this review illustrates how information from the arrays reflects the way that selectivity and affinity for glycan ligands is achieved. A range of binding profiles is observed, from very restricted binding to a small set of structurally similar ligands to binding of broad classes of ligands with related terminal sugars and even to failure to bind any of the glycans on an array. These outcomes provide insights into the importance of multiple factors in defining the selectivity of these receptors, including the presence of conformationally defined units in some oligosaccharide ligands, local and extended interactions between glycans and the surfaces of receptors, and steric factors that exclude binding of some ligands

The economic impact of the Green Certificate market through the Macro Multiplier approach

In the last decade, as many other European countries, the Italian Government adopted several reforms in order to increase the use of Renewable Energy Sources (RES). The liberalization of the electricity market that represent one of these reforms aims to reach environmental benefits from the substitution of fossil fuel with renewable sources.The Italian Green Certificate market was introduced in 2002 in order to accomplish this objective and represents a mechanism where a quota of renewable electricity is imposed to suppliers in proportion to their sales. The electricity industries are obliged to meet this condition by producing the quantity of renewable electricity by means of a change in their production process, otherwise they must buy a number of certificates corresponding to the quota. This mechanism changes the importance of the electricity industry first in promoting climate protection, than in terms of the impact in the economy as a whole. A policy aimed to develop the market of green certificates may lead to environmental improvement by switching the energy production process to renewable resources. But above all an increase in demand for green certificates, resultant from a reform on the quota of renewable electricity, can generate positive change in all components of the industrial production. For this purpose, the paper aims to quantify the economic impact of a reform on Green Certificate market for the Italian system by means of the Macro Multiplier (MM) approach. The analysis is performed through the Hybrid Input-Output (I-O) model that allows expressing the energy flows in physical terms (GWh) while all other flows are expressed in monetary terms (e). Moreover, through the singular value decomposition of the inverse matrix of the model, which reveals the set of key structures of the exogenous change of final demand, we identify the appropriate key structure able to obtain both the expected positive total output change and the increase of electricity production from RES

Structure and Functions of Pediatric Aerodigestive Programs: A Consensus Statement

Aerodigestive programs provide coordinated interdisciplinary care to pediatric patients with complex congenital or acquired conditions affecting breathing, swallowing, and growth. Although there has been a proliferation of programs, as well as national meetings, interest groups and early research activity, there is, as of yet, no consensus definition of an aerodigestive patient, standardized structure, and functions of an aerodigestive program or a blueprint for research prioritization. The Delphi method was used by a multidisciplinary and multi-institutional panel of aerodigestive providers to obtain consensus on 4 broad content areas related to aerodigestive care: (1) definition of an aerodigestive patient, (2) essential construct and functions of an aerodigestive program, (3) identification of aerodigestive research priorities, and (4) evaluation and recognition of aerodigestive programs and future directions. After 3 iterations of survey, consensus was obtained by either a supermajority of 75% or stability in median ranking on 33 of 36 items. This included a standard definition of an aerodigestive patient, level of participation of specific pediatric disciplines in a program, essential components of the care cycle and functions of the program, feeding and swallowing assessment and therapy, procedural scope and volume, research priorities and outcome measures, certification, coding, and funding. We propose the first consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. We hope that this may provide an initial framework to further standardize care, develop clinical guidelines, and improve outcomes for aerodigestive patients