Social support among English learners with disabilities and other adolescents.

INTRODUCTION: Social support is important for many youth but may be particularly important for English learners (ELs) with disabilities, a population that has historically faced barriers accessing resources to meet their educational needs. The current study investigates social support from parents, peers, teachers, and schools in a nationally representative sample of adolescents. METHOD: Data from the National Longitudinal Transition Study 2012 was used to evaluate potential group differences in social support among participants that included ELs with (n = 440) and without disabilities (n = 100) and non-ELs with (n = 4890) and without disabilities (n = 1090). A multivariate analysis of covariance was conducted to evaluate potential between-group variations in social support among these student groups after controlling for variations in background demographic characteristics. RESULTS AND CONCLUSIONS: Results showed between group differences in parental support and peer connectedness but not in teacher or school support. Parents of students with disabilities reported the highest levels of support, whereas parents of ELs without disabilities reported the lowest levels of support. Students with disabilities reported the lowest levels of peer connectedness among the four groups. Overall, levels of teacher and school supports were high across all four groups of students. These patterns contribute to our understanding of the social support network of ELs with disabilities in comparison to other students. Further investigation is needed to examine the mechanisms that contribute to these differences.

LED-pumped eye-safe pulse laser with an extracavity optical parametric oscillator.

An LED-side-pumped Nd:YAG/Cr4+:YAG passively Q-switched (PQS) laser containing an extracavity optical parametric oscillator (EOPO) is demonstrated. As far as we know, it is the first LED-pumped eye-safe laser. The Nd:YAG pump module is optimized to increase the PQS pulse energy to 24 mJ at 1064 nm. By using a single-pass EOPO design, the output energy of the signal pulse at 1573 nm is 7.44 mJ with a pulse width of 16 ns, the peak power is 434 kW, and the pump-to-signal conversion efficiency is 31%. For double-pass EOPO operation, the pump-to-signal conversion efficiency increases to 45.8%, the output energy of signal pulse is up to 10.98 mJ with a pulse width of 23.5 ns, and the peak power is 459 kW.

Improving stroke pathways using an adhesive ambulatory ECG patch: reducing time for patients to ECGs and subsequent results.

Three south-London hospital trusts undertook a feasibility study, comparing data from 93 patients who received the 14-day adhesive ambulatory electrocardiography (ECG) patch Zio XT with retrospective data from 125 patients referred for 24-hour Holter for cryptogenic stroke and transient ischaemic attack following negative 12-lead ECG. As the ECG patch was fitted the same day as the clinical decision for ambulatory ECG monitoring was made, median time to the patient having the monitor fitted was significantly reduced in all three hospital trusts compared with 24-hour Holter being ordered and fitted. Hospital visits reduced by a median of two for patients receiving Zio XT. This project supports that it is feasible to use a patch as part of routine clinical care with a positive impact on care pathways.

SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes.

SF3B1 is the most frequently mutated RNA splicing factor in cancer, including in ∼25% of myelodysplastic syndromes (MDS) patients. SF3B1-mutated MDS, which is strongly associated with ringed sideroblast morphology, is characterized by ineffective erythropoiesis, leading to severe, often fatal anemia. However, functional evidence linking SF3B1 mutations to the anemia described in MDS patients harboring this genetic aberration is weak, and the underlying mechanism is completely unknown. Using isogenic SF3B1 WT and mutant cell lines, normal human CD34 cells, and MDS patient cells, we define a previously unrecognized role of the kinase MAP3K7, encoded by a known mutant SF3B1-targeted transcript, in controlling proper terminal erythroid differentiation, and show how MAP3K7 missplicing leads to the anemia characteristic of SF3B1-mutated MDS, although not to ringed sideroblast formation. We found that p38 MAPK is deactivated in SF3B1 mutant isogenic and patient cells and that MAP3K7 is an upstream positive effector of p38 MAPK. We demonstrate that disruption of this MAP3K7-p38 MAPK pathway leads to premature down-regulation of GATA1, a master regulator of erythroid differentiation, and that this is sufficient to trigger accelerated differentiation, erythroid hyperplasia, and ultimately apoptosis. Our findings thus define the mechanism leading to the severe anemia found in MDS patients harboring SF3B1 mutations.

Disease-Causing Mutations in SF3B1 Alter Splicing by Disrupting Interaction with SUGP1.

SF3B1, which encodes an essential spliceosomal protein, is frequently mutated in myelodysplastic syndromes (MDS) and many cancers. However, the defect of mutant SF3B1 is unknown. Here, we analyzed RNA sequencing data from MDS patients and confirmed that SF3B1 mutants use aberrant 3' splice sites. To elucidate the underlying mechanism, we purified complexes containing either wild-type or the hotspot K700E mutant SF3B1 and found that levels of a poorly studied spliceosomal protein, SUGP1, were reduced in mutant spliceosomes. Strikingly, SUGP1 knockdown completely recapitulated the splicing errors, whereas SUGP1 overexpression drove the protein, which our data suggest plays an important role in branchsite recognition, into the mutant spliceosome and partially rescued splicing. Other hotspot SF3B1 mutants showed similar altered splicing and diminished interaction with SUGP1. Our study demonstrates that SUGP1 loss is a common defect of spliceosomes with disease-causing SF3B1 mutations and, because this defect can be rescued, suggests possibilities for therapeutic intervention.

Evaluation of a Pharmacist-Managed Antidiabetic Deprescribing Program in an Integrated Health Care System.

BACKGROUND: In the elderly, use of medications may increase the propensity for adverse drug events due to alterations in pharmacokinetic and pharmacodynamic profiles from normal aging processes. Deprescribing is the planned and supervised process of dose reduction or discontinuation of medications that may lead to harm or are no longer beneficial. While there are studies detailing strategies to deprescribe medications such as benzodiazepines and antipsychotics in nursing homes or for patients with dementia, there is a lack of guidance to safely deprescribe chronic medications, such as antidiabetics, for older patients in the community setting. OBJECTIVE: To evaluate the risk of hypoglycemia and other outcomes of pharmacist-managed deprescribing on selected antidiabetic medications under the guidance of a standardized program compared with usual care within an integrated health care system. METHODS: This was a retrospective propensity score-matched cohort study. The pharmacist-managed deprescribing group included patients who were enrolled in the deprescribing program between July 1, 2016, and June 30, 2017. The usual care group included eligible patients who did not receive the deprescribing intervention and were matched to the deprescribing group using propensity score matching (PSM). Baseline demographics and clinical variables were used for matching. Patients were followed for 6 months or the end of membership or death, whichever occurred first. Primary outcome was the risk of hypoglycemia. Secondary outcomes included risk of hyperglycemia, proportion of patients at goal (A1c), change in A1c, change in monthly antidiabetic drug cost, and all-cause mortality. Outcomes were analyzed using descriptive statistics and multivariant regression or Cox proportional hazard models when appropriate. RESULTS: After PSM, 685 patients in the deprescribing group and 2,055 patients in the usual care group were similar in age, gender, weight, and comorbidity burden (mean [SD] age 82.4 [5.4] years, 48% female, mean [SD] weight 81.7 [19.2] kg, mean [SD] Charlson Comorbidity Index score 3.2 [1.6]). Compared with the usual care group, the deprescribing group had a lower risk of hypoglycemia (1.5% vs. 3.1%, P < 0.02; adjusted odds ratio 0.42, P < 0.01). As for the secondary outcomes, the deprescribing group had a greater change (SD) in A1c (0.3 [0.6] vs. 0.2 [0.7] P < 0.01) and lower all-cause mortality (2.3% vs 5.6%, P < 0.01; adjusted hazard ratio 0.35, P < 0.01). There were no differences observed in the risk of hyperglycemia, proportion of patients at goal A1c < 7%, and change in monthly antidiabetic drug costs between the 2 groups. CONCLUSIONS: There are currently no studies to our knowledge that evaluate the outcomes of a pharmacist-managed deprescribing program targeting antidiabetic medications. The results of our study showed that deprescribing of selected antidiabetics reduced the risk of hypoglycemia and may have mortality benefit in elderly patients with well-controlled type 2 diabetes, who are taking medications that can cause hypoglycemia. Further and longer studies are needed to validate these benefits. DISCLOSURES: No outside funding was provided to support this research study. The authors of this study have no actual or potential conflicts of interest to report. Parts of this study were presented in a nonreviewed resident poster at the Academy of Managed Care Pharmacy Managed Care and Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Integrated in silico and in vitro genotoxicity assessment of thirteen data-poor substances.

The Canadian Domestic Substances List (DSL) contains chemicals that have not been tested for genotoxicity as their use pre-dates regulatory requirements. In the present study, (quantitative) structure-activity relationships ((Q)SAR) model predictions and in vitro tests were conducted for genotoxicity assessment of 13 data-poor chemicals from the DSL (i.e. CAS numbers 19286-75-0, 13676-91-0, 2478-20-8, 6408-20-8, 74499-36-8, 26694-69-9, 29036-02-0, 120-24-1, 84696-48-9, 4051-63-2, 5718-26-3, 632-51-9, and 600-14-6). First, chemicals were screened by (Q)SAR models in Leadscope® and OASIS TIMES; two chemicals were excluded from (Q)SAR as they are complex mixtures. Six were flagged by (Q)SAR as potentially mutagenic and were subsequently confirmed as mutagens using the Ames assay. Of nine chemicals with clastogenic (Q)SAR flags, eight induced micronuclei in TK6 cells. Benchmark dose analysis was used to evaluate the potency of the chemicals. Four chemicals were bacterial mutagens with similar potencies. Three chemicals were more potent in micronuclei induction than the prototype alkylating agent methyl methanesulfonate and three were equipotent to the mutagenic carcinogen benzo[a]pyrene in the presence of rat liver S9. Overall, 11 of the 13 DSL chemicals demonstrated at least one type of genotoxicity in vitro. This study demonstrates the application of genotoxic potency analysis for prioritizing further investigations.

Effects of Maturity at Harvest and Fermentation Conditions on Bioactive Compounds of Cocoa Beans.

Cocoa beans and cocoa products contain considerable amounts of bioactive compounds. Harvesting cocoa fruit too early or too late may have effects on the phenolic and alkaloid concentrations of the cocoa powder. Fermentation, a primary processing used to transform cocoa beans to cocoa powder, may also influence the contents of bioactive compounds. In this study, proanthocyanidins, the major compounds in cocoa polyphenols, caffeine and theobromine of cocoa beans, were evaluated at different maturities at harvest, and with different fermentation durations, with and without the addition of a commercial enzyme, Pectinex® Ultra SP-L. The amounts of proanthocyanidins, caffeine and theobromine, and the antioxidant capacities of the unfermented cocoa beans increased as the fruits matured. The values ranged from 16.12-27.28 g catechin equivalents (CE)/100 g dry weight (DW); 99.66-173.61 mg/100 g DW; 556.39-948.84 mg/100 g DW; 23.23-26.32 mol Trolox equivalents (TE)/100 g DW, respectively. Prolonged fermentation with or without the addition of pectinase, from three to seven days, significantly reduced the amounts of these compounds present. Fermentation using the enzyme significantly reduced the proanthocyanidin content and antioxidant capacity of the cocoa powder, with the overall means decreasing from 8.93-4.93 g CE/100 g DW and from 15.81-12.95 g mol TE/100 g DW, respectively. Two-way ANOVA analyses showed that the proanthocyanidins, caffeine, theobromine contents and the antioxidant capacity of cocoa beans were strongly dependet to their stages of maturity, fermentation methods and fermentation duration.

c-myb hyperactivity leads to myeloid and lymphoid malignancies in zebrafish.

The c-MYB transcription factor is a key regulator of hematopoietic cell proliferation and differentiation, and dysregulation of c-MYB activity often associates with various hematological disorders. Yet, its pathogenic role remains largely unknown due to lack of suitable animal models. Here, we report a detail characterization of a c-myb-gfp transgenic zebrafish harboring c-Myb hyperactivity (named c-mybhyper). This line exhibits abnormal granulocyte expansion that resembles human myelodysplastic syndrome (MDS) from embryonic stage to adulthood. Strikingly, a small portion of c-mybhyper adult fish develops acute myeloid leukemia-like or acute lymphoid leukemia-like disorders with age. The myeloid and lymphoid malignancies in c-mybhyper adult fish are likely caused by the hyperactivity of c-myb, resulting in the dysregulation of a number of cell-cycle-related genes and hyperproliferation of hematopoietic precursor cells. Finally, treatment with c-myb target drug flavopiridol can relieve the MDS-like symptoms in both c-mybhyper embryos and adult fish. Our study establishes a zebrafish model for studying the cellular and molecular mechanisms underlying c-Myb-associated leukemogenesis as well as for anti-leukemic drug screening.

Immunohistochemical studies and fluorodeoxyglucose uptake on positron emission tomography in pharyngeal cancer for predicting radiotherapy-based treatment outcomes.

OBJECTIVES: This study correlated immunohistochemical studies with fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) and identified prognostic factors for radiotherapy (RT)-based treatment outcomes in patients with squamous cell carcinoma of the oropharynx and hypopharynx. METHODS: Genomic data from pre-treatment biopsy specimens (Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met and p16) of 76 patients were analysed using tissue microarrays. FDG uptake was evaluated using the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG). RESULTS: The overexpression of Glut1 positively associated with increased values of the SUVmax, MTV and TLG, whereas VEGF and HIF-1α expression with the MTV and TLG, respectively. A VEGF immunoreactive score (IRS) >2 (P = 0.001, hazard ratio [HR] = 3.94) and an MTV defined by an SUV of 2.5 (MTV2.5) >14.5 mL (P = 0.004, HR = 3.31) were prognostic factors for low cause-specific survival, whereas a VEGF IRS >2 (P = 0.02, HR = 2.83) for low primary relapse-free survival. CONCLUSION: The overexpression of Glut1, VEGF and HIF-1α associated with increased FDG uptake. For patients with pharyngeal cancer requiring RT, the treatment outcome can be stratified by VEGF and MTV2.5.

DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling.

Although the majority of patients with acute myeloid leukemia (AML) initially respond to chemotherapy, many of them subsequently relapse, and the mechanistic basis for AML persistence following chemotherapy has not been determined. Recurrent somatic mutations in DNA methyltransferase 3A (DNMT3A), most frequently at arginine 882 (DNMT3AR882), have been observed in AML and in individuals with clonal hematopoiesis in the absence of leukemic transformation. Patients with DNMT3AR882 AML have an inferior outcome when treated with standard-dose daunorubicin-based induction chemotherapy, suggesting that DNMT3AR882 cells persist and drive relapse. We found that Dnmt3a mutations induced hematopoietic stem cell expansion, cooperated with mutations in the FMS-like tyrosine kinase 3 gene (Flt3ITD) and the nucleophosmin gene (Npm1c) to induce AML in vivo, and promoted resistance to anthracycline chemotherapy. In patients with AML, the presence of DNMT3AR882 mutations predicts minimal residual disease, underscoring their role in AML chemoresistance. DNMT3AR882 cells showed impaired nucleosome eviction and chromatin remodeling in response to anthracycline treatment, which resulted from attenuated recruitment of histone chaperone SPT-16 following anthracycline exposure. This defect led to an inability to sense and repair DNA torsional stress, which resulted in increased mutagenesis. Our findings identify a crucial role for DNMT3AR882 mutations in driving AML chemoresistance and highlight the importance of chromatin remodeling in response to cytotoxic chemotherapy.

Humanin: Functional Interfaces with IGF-I.

Humanin is the first newly discovered peptide encoded in the mitochondrial genome in over three decades. It is the first member of a novel class of mitochondrial derived peptides. This small, 24 amino acid peptide was initially discovered to have neuroprotective effects and subsequent experiments have shown that it is beneficial in a diverse number of disease models including stroke, cardiovascular disease, and cancer. Over a decade ago, our lab found that humanin bound IGFBP-3 and more recent studies have found it to decrease circulating IGF-I levels. In turn, IGF-I also seems to regulate humanin levels and in this review, we cover the known interaction between humanin and IGF-I. Although the exact mechanism for how humanin and IGF-I regulate each other still needs to be elucidated, it is clear that humanin is a new player in IGF-I signaling.

IDH mutations in cancer and progress toward development of targeted therapeutics.

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to α-ketoglutarate (αKG).IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here we provide an overview of the function of normal and mutated IDH, discuss the role of IDH mutations in tumorigenesis and progression and review the key clinical considerations when treating IDH-mutated tumors based on emerging clinical data from mutant IDH1/2 inhibitor trials. IDH1 and IDH2 mutations confer neomorphic activity in the mutant protein, resulting in the conversion of αKG to the oncometabolite, D-2-hydroxyglutarate (2-HG). The subsequent accumulation of 2-HG results in epigenetic dysregulation via inhibition of αKG-dependent histone and DNA demethylases, and a block in cellular differentiation. There is growing preclinical and clinical evidence suggesting that IDHmutations are involved in neoplasia. Furthermore, preclinical studies assessing small molecule inhibitors of mutant IDH1/2 enzymes have provided proof of concept that this approach decreases intracellular 2-HG levels, reverses epigenetic dysregulation and induces cellular differentiation. Phase I studies of mutant IDH inhibitors are currently ongoing in patients with IDH-mutant hematologic and solid tumors, with early data in hematologic tumors suggesting a manageable safety profile as well as clinical benefit, with a mechanism of action based on differentiation of malignant cells. Inhibition of mutant IDH shows promise as a treatment approach in hematologic malignancies, with further development ongoing in solid tumors and glioma. The mutant IDH inhibitors may have clinical utility both as single agents and in combination strategies that target additional oncogenic pathways.

Prominent coronary artery flow with normal coronary artery anatomy is a rare but ominous harbinger of poor outcome in the fetus.

OBJECTIVES: "Heart sparing" refers to prominent antegrade fetal coronary artery (CA) blood flow readily visualized by color Doppler and is a harbinger of poor outcome in growth restricted fetus, but little is known of the features and presentation of heart sparing in normally grown fetuses. Our objective was to describe heart sparing effects in normally grown fetuses, and compare the presentation and outcome of heart sparing between fetuses with growth restriction and those who were normally grown. METHODS: In a series of fetuses with prominent antegrade CA flow, we assessed Doppler flow profiles in the aortic isthmus, ductus venosus (DV), umbilical vein (UV), umbilical artery (UA) and middle cerebral artery (MCA). We calculated MCA and UA systolic/diastolic ratios and the cerebral placental ratio, and measured fetal biometry. We evaluated cardiac function using the myocardial performance index (MPI) and the cardiovascular profile score (CVPS). RESULTS: Ten fetuses with heart sparing had normal DV flow at 24-36.6 (mean 30.9) weeks of gestation. Five had growth restriction (Group 1); 4/5 had normal MPI and CVPS, and one died. Five were normally grown (Group 2); 5/5 had elevated MPI and decreased CVPS, of these 2 died in utero and one died immediately after birth despite urgent delivery. Coronary arteries were normal after birth or autopsy. CONCLUSIONS: Heart sparing confers a poor prognosis in fetal growth restriction and in normally grown fetuses with cardiac dysfunction. We suggest CA flow be assessed in all high-risk fetuses.

[Clinical forensic imaging. Detection and documentation of internal injuries in living victims of violence]. / Klinisch-forensische Bildgebung. Erfassung und Dokumentation innerer Verletzungsbefunde bei lebenden Gewaltopfern.

External examination of the body surface with documentation of all visible findings can still be regarded as the status quo of clinical forensic injury assessment. It is obvious that internal findings cannot be detected using this technique. For obtaining such findings accessible well-established radiological techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI) should be used. Especially MRI with no damaging radiation exposure for the examined person allows the detection of internal soft tissue and organ damage and offers a great potential regarding new techniques for allowing insights into tissue composition and function. Furthermore, imaging data collected in clinical institutions before the patient was transferred to the department of legal medicine will play a major role in the future. Although these data were obtained based on a different approach, they provide excellent and recent information on injuries in the respective (current) case und can therefore be of high value for the forensic expertise.

Disease-associated mutation in SRSF2 misregulates splicing by altering RNA-binding affinities.

Serine/arginine-rich splicing factor 2 (SRSF2) is an RNA-binding protein that plays important roles in splicing of mRNA precursors. SRSF2 mutations are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how these mutations affect SRSF2 function has only begun to be examined. We used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease to introduce the P95H mutation to SRSF2 in K562 leukemia cells, generating an isogenic model so that splicing alterations can be attributed solely to mutant SRSF2. We found that SRSF2 (P95H) misregulates 548 splicing events (<1% of total). Of these events, 374 involved the inclusion of cassette exons, and the inclusion was either increased (206) or decreased (168). We detected a specific motif (UCCA/UG) enriched in the more-included exons and a distinct motif (UGGA/UG) in the more-excluded exons. RNA gel shift assays showed that a mutant SRSF2 derivative bound more tightly than its wild-type counterpart to RNA sites containing UCCAG but bound less tightly to UGGAG sites. Thus in most cases the pattern of exon inclusion or exclusion correlated with stronger or weaker RNA binding, respectively. We further show that the P95H mutation does not affect other functions of SRSF2, i.e., protein-protein interactions with key splicing factors. Our results thus demonstrate that the P95H mutation positively or negatively alters the binding affinity of SRSF2 for cognate RNA sites in target transcripts, leading to misregulation of exon inclusion. Our findings shed light on the mechanism of the disease-associated SRSF2 mutation in splicing regulation and also reveal a group of misspliced mRNA isoforms for potential therapeutic targeting.

Identification and characterisation of a novel heat shock protein 90 inhibitor ONO4140.

Heat shock protein (Hsp) 90 is a key component of the super-chaperone complex that maintains functionally active conformation of various client proteins. Many of these client proteins regulate important nodal points in multiple signalling pathways that promote cancer cell growth and survival. Inhibitors of Hsp90, therefore, have the potential of functioning as anti-cancer agents with pleiotropic effects. Identification of novel Hsp90 inhibitors with more favourable pharmacological properties is a priority in cancer therapy. To achieve this goal, we screened a compound library using a biochemical assay based on refolding of denatured firefly luciferase. The assay revealed high sensitivity, reliability and reproducibility with a Z-factor of 0.81 ± 0.17. Six Hsp90 inhibitory compounds identified by this screening with IC50 values between 1.0 and 6 µM were further characterised for anti-proliferative activity by Cell Titer-Blue Cell Viability Assay using multiple tumour cell lines. Of particular interest was ONO4140 with lowest GI50 values in three different cancer cell lines viz; DU-145, BT-474 and K562 cell lines. This study also revealed that short-term exposure of tumour cells with ONO4140 is sufficient to inhibit the catalytic activity of Hsp90, evaluated through disruption of Hsp90-p23 association by immunoprecipitation. This short term exposure appears to initiate events like degradation of Hsp90 client proteins such as ErbB2/Her-2 and Akt with concomitant inhibition of survival signalling leading to the apoptotic death of tumour cells as seen by western blotting and Caspase Glow-3,7 assay. The study also reveals that apoptosis following Hsp90 inhibition with ONO4140 occurs via Caspase9-Caspase3 intrinsic apoptotic pathway, a process that is likely triggered by inactivation of Akt. In conclusion, we have identified a novel class of synthetic compounds which show potent Hsp90 inhibitory action in preclinical studies. The discovery of this novel class of synthetic Hsp90 inhibitors with simple chemical backbone allows us to conduct further structural modifications to improve their potency and pharmacokinetic properties for use in cancer therapy.

Impedance matched absorptive thermal blocking filters.

We have designed, fabricated, and characterized absorptive thermal blocking filters for cryogenic microwave applications. The transmission line filter's input characteristic impedance is designed to match 50 Ω and its response has been validated from 0 to 50 GHz. The observed return loss in the 0 to 20 GHz design band is greater than 20 dB and shows graceful degradation with frequency. Design considerations and equations are provided that enable this approach to be scaled and modified for use in other applications.

Measuring help-seeking behaviors: factor structure, reliability, and validity among youth with disabilities.

Existing measures of help-seeking focus on assessing attitudes and beliefs, rather than specific behaviors, toward help-seeking. This study described the development of a self-report measure of informal help-seeking behaviors (HSB). Participants were 228 high school students (148 males, 80 females) with disabilities from four states. Factor analyses revealed three underlying factors, each addressing a different source of help: parent, peer, and teacher. The HSB had good internal reliability and moderate validity. Results from regression analyses suggested that help-seeking behaviors toward parents and teachers contributed uniquely to students' self-ratings of school bonding, life satisfaction, and career outcome expectations. Help-seeking behaviors toward peers was a negative predictor of career outcome expectations. The value of the HSB as a research instrument was discussed.