The Paraprofessional Conundrum: Why We Need Alternative Support Strategies

This four-page article describes a conundrum facing schools utilizing paraprofessionals to support students receiving special education. It considers three factors: (a) asked to engage in teacher-type instructional roles, (b) trained and supervised for teacher-type instructional roles, and (c) compensation commensurate with teacher-type instructional roles across six combinations. Regardless of whether or not the factors are present or not it often leads to series of undesirable outcomes. The article suggest a series of alternatives

Guidelines for Selecting Alternatives to Overreliance on Paraprofessionals

The Guidelines for Selecting Alternatives to Overreliance on Paraprofessionals is a field-tested schhol-based planning process. Support for the preparation of this article was provided by the United States Department of Education, Office of Special Education and Rehabilitative Services under the funding category, Model Demonstration Projects for Children and Youth with Disabilities, CFDA 84.324M (H324M02007), awarded to the Center on Disability and Community Inclusion at the University of Vermont. The contents of this document reflect the ideas and positions of the authors and do not necessarily reflect the ideas or positions of the U.S. Department of Education; therefore, no official endorsement should be inferred

Alternatives to Overreliance or Inappropriate Utilization of Paraprofessionals in Special Education

This article describes 12 alternatives to overreliance or Inappropriate utilization of paraprofessionals in special education based utilization in American schools. Support for the preparation of this article was provided by the United States Department of Education, Office of Special Education Programs, under the funding category, Model Demonstration Projects for Children and Youth with Disabilities, CFDA 84.324M (Project EVOLVE, H324M02007), awarded to the Center on Disability and Community Inclusion at the University of Vermont. The contents of this paper reflect the ideas and positions of the authors and do not necessarily reflect the ideas or positions of the U.S. Department of Education; therefore, no official endorsement should be inferred

Developing a Shared Understanding: Paraeducator Supports for Students with Disabilities in General Education

In order for groups of people to become effective teams it is vital that they develop a shared understanding of the underlying beliefs, values, and principles that will guide their work together. This shared understanding evolves over time as members learn about each other, spend time together, and engage in the work of their group. Having a shared understanding provides a basic structure within which teams: • develop common goals; determine actions that will lead toward the attainment of their goals; ensure that their actions are consistent with their beliefs; and judge whether their efforts have been successful

A Guide to Schoolwide Planning for Paraeducator Supports

A Guide to Schoolwide Planning for Paraeducator Supports is a field-tested, schoolwide planning tool designed to improve the quality of paraprofessional supports offered in public schools to supports students with disabilities and other identified support needs. Support for the preparation of this article was provided by the United States Department of Education, Office of Special Education and Rehabilitative Services under the funding category, Model Demonstration Projects for Children and Youth with Disabilities, CFDA 84.324M (H324M980229), awarded to the Center on Disability and Community Inclusion at the University of Vermont. The contents of this paper reflect the ideas and positions of the authors and do not necessarily reflect the ideas or positions of the U.S. Department of Education; therefore, no official endorsement should be inferred

Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites

Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family—the Novel Putative Transporters (NPTs)—play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites

The Concise Guide to PHARMACOLOGY 2023/24:Transporters

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16182. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.</p

Toll-Like Receptor 1 Locus Re-examined in a Genome-Wide Association Study Update on Anti–Helicobacter pylori IgG Titers

Funding Information: Funding The Rotterdam Study I-II was supported by the Netherlands Organization of Scientific Research (NWO; 175.010.2005.011, 911-03-012), Research Institute for Diseases in the Elderly (RIDE; 014-93-015), Genomics Initiative/NWO (project no. 050-060-810), Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), Ministry of Education, Culture, and Science and Ministry for Health, Welfare, and Sports, European Commission, and the Municipality of Rotterdam. GenerationR was supported by Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, ZonMw (907.00303, 916.10159), NWO, and the Ministry for Health, Welfare and Sports. The Study of Health in Pomerania (SHIP) and SHIP-TREND were supported by Deutsche Krebshilfe/Dr Mildred-Scheel-Stiftung (109102), Deutsche Forschungsgemeinschaft (DFG GRK840-D2/E3/E4, MA 4115/1-2/3), Federal Ministry of Education and Research (BMBF GANI-MED 03IS2061A and BMBF 0314107, 01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012), the European Union (EU-FP-7-EPCTM and EU-FP7-REGPOT-2010-1), AstraZeneca (unrestricted grant), the Federal Ministry of Education and Research, Siemens Healthcare, the Federal State of Mecklenburg–West Pomerania, and the University of Greifswald. The Framingham Heart Study was supported by National Institutes of Health grants N01-HC-25195, HHSN268201500001I, and 75N92019D00031 (to Boston University) and the Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI). The Multi-Ethnic Study of Atherosclerosis (MESA) and the MESA SHARe projects were supported by the NHLBI (75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420. Funding for SHARe genotyping was provided by NHLBI grant N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, CA) and the Broad Institute of Harvard and MIT (Boston, MA) using the Affymetrix Genome-Wide Human SNP Array 6.0. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Epidemiological Investigations on Chances of Preventing Recognizing Early and Optimally Treating Chronic Diseases in an Elderly Population were supported by the State Ministry of Science, Research and Arts, Baden-Württemberg, Federal Ministry of Education and Research, and Federal Ministry of Family Affairs, Senior Citizens, Women and Youth. LATVIA was supported by the European Regional Development Fund (ERDF; 009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016), National Program for Research in Latvia, Ministry of Health (6-1396-2016), and Fundamental and Applied Research Projects Program in Latvia (project no. lzp-2018/1-0135). Funding Information: Conceptualization: Linda Broer, Manon C.W. Spaander, Fabian Frost, Stefan Weiss, Georg Homuth, Henry Völzke, Markus M. Lerch, Ben Schöttker, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, Edmond K. Kabagambe, Marcis Leja, Janis Klovins, Raitis Peculis, Dace Rudzite, Liene Nikitina-Zake, Girts Skenders, Vita Rovite, André Uitterlinden, Ernst J. Kuipers, Maikel P. Peppelenbosch, and additional members of Rotterdam Study I-II, GenerationR, Study of Health in Pomerania, Framingham Heart Study, Multi-Ethnic Study of Atherosclerosis, Epidemiological Investigations on Chances of Preventing Recognizing Early and Optimally Treating Chronic Diseases in an Elderly Population, and LATVIA cohorts not directly involved in this manuscript. Methodology: all authors. Investigation: all authors. Formal analysis of discovery: Linda Broer, Fabian Frost, Stefan Weiss, Georg Homuth, Henry Völzke, Markus M. Lerch, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, and Edmond K. Kabagambe. Formal analysis of replication: Yan Zhang, Hannah Stocker, Hermann Brenner, Marcis Leja, Janis Klovins, and Raitis Peculis. Formal analysis of meta-analysis: Linda Broer. Project administration: Suk Yee Lam and Gwenny M. Fuhler. Resources: Fabian Frost, Stefan Weiss, Georg Homuth, Henry Völzke, Markus M. Lerch, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, Edmond K. Kabagambe, Marcis Leja, Janis Klovins, Dace Rudzite, Liene Nikitina-Zake, Girts Skenders, Vita Rovite, Ernst J. Kuipers, and Maikel P. Peppelenbosch. Supervision: Manon C.W. Spaander, Fabian Frost, Stefan Weiss, Georg Homuth, Henry Völzke, Markus M. Lerch, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, Edmond K. Kabagambe, Marcis Leja, Janis Klovins, Gwenny M. Fuhler, Maikel P. Peppelenbosch, and André Uitterlinden. Visualization: Suk Yee Lam, Michiel C. Mommersteeg, Bingting Yu, Linda Broer, and Gwenny M. Fuhler. Writing—original draft: Suk Yee Lam, Michiel C. Mommersteeg, and Gwenny M. Fuhler. Writing—reviewing and editing: all authors. Publisher Copyright: © 2022 The Author(s)Background & Aims: A genome-wide significant association between anti–Helicobacter pylori (H pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigated this association in an updated genome-wide association study (GWAS) meta-analysis for populations with low gastric cancer incidence, address potential causes of cohort heterogeneity, and explore functional implications of genetic variation at the TLR1/6/10 locus. Methods: The dichotomous GWAS (25% individuals exhibiting highest anti–H pylori IgG titers vs remaining 75%) included discovery and replication sampls of, respectively, n = 15,685 and n = 9676, all of European ancestry. Longitudinal analysis of serologic data was performed on H pylori–eradicated subjects (n = 132) and patients under surveillance for premalignant gastric lesions (n = 107). TLR1/6/10 surface expression, TLR1 mRNA, and cytokine levels were measured in leukocyte subsets of healthy subjects (n = 26) genotyped for TLR1/6/10 variants. Results: The association of the TLR1/6/10 locus with anti–H pylori IgG titers (rs12233670; β = −0.267 ± SE 0.034; P = 4.42 × 10−15) presented with high heterogeneity and failed replication. Anti–H pylori IgG titers declined within 2–4 years after eradication treatment (P = 0.004), and decreased over time in patients with premalignant gastric lesions (P < 0.001). Variation at the TLR1/6/10 locus affected TLR1-mediated cytokine production and TLR1 surface expression on monocytes (P = 0.016) and neutrophils (P = 0.030), but not mRNA levels. Conclusions: The association between anti–H pylori IgG titers and TLR1/6/10 locus was not replicated across cohorts, possibly owing to dependency of anti–H pylori IgG titers on therapy, clearance, and antibody decay. H pylori–mediated immune cell activation is partly mediated via TLR1 signaling, which in turn is affected by genetic variation.publishersversionPeer reviewe

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.Peer reviewe