NIS2+ as a screening tool to optimize patient selection in metabolic dysfunction-associated steatohepatitis clinical trials.

Background & Aims: Strategies to reduce liver biopsy (LB) screen failures through better patient selection are needed for clinical trials. Standard fibrosis biomarkers were not derived to detect "at-risk" metabolic dysfunction-associated steatohepatitis (MASH; MASH with metabolic dysfunction-associated steatotic liver disease score ≥4 and fibrosis stage ≥2). We compared the performance of screening pathways that incorporate NIS2+™, an optimized version of the blood-based NIS4® technology designed to identify at-risk MASH, with those incorporating fibrosis (FIB)-4 within the RESOLVE-IT clinical trial (NCT02704403), aiming for optimized selection of patients for LB.

NIS2+™, an effective blood-based test for the diagnosis of at-risk nonalcoholic steatohepatitis in adults 65 years and older.

Background: Older patients are at increased risk for at-risk NASH, defined as NASH with NAFLD activity scores (NAS) ≥4 and significant fibrosis (F ≥ 2). The aim of this study was to compare the performance of 2 new blood tests, NIS4® and NIS2+™, with FIB-4, NFS, ELF™, and alanine aminotransferase (ALT) for the diagnosis of at-risk NASH in a cohort of patients aged ≥65 years.

Methods: The clinical performance of multiple blood-based tests was assessed for their ability to detect at-risk NASH using the RESOLVE-IT diag cohort, a large population of patients with metabolic risk who were screened for potential inclusion in the RESOLVE-IT phase 3 trial.

NIS2+™, an optimisation of the blood-based biomarker NIS4® technology for the detection of at-risk NASH: A prospective derivation and validation study.

Background & Aims: NIS4® is a blood-based non-invasive test designed to effectively rule in/rule out at-risk non-alcoholic steatohepatitis (NASH), defined as non-alcoholic fatty liver disease activity score ≥4 and significant fibrosis (stage ≥2), among patients with metabolic risk factors. Robustness of non-invasive test scores across characteristics of interest including age, type 2 diabetes mellitus, and sex, and optimised analytical aspects are critical for large-scale implementation in clinical practice. We developed and validated NIS2+™, an optimisation of NIS4®, specifically designed to improve score robustness.

Crowded skies: Conflicts between expanding goose populations and aviation safety.

We here review the collision risks posed by large-bodied, flocking geese to aircraft, exacerbated by recent major increases in northern hemisphere goose populations and air traffic volume. Mitigation of goose-aircraft strike risks requires knowledge of local goose movements, global goose population dynamics and ecology. Airports can minimise goose strikes by managing habitats within the airport property, applying deterrents to scare geese away and lethal control, but goose migration and movements at greater spatial scales present greater challenges.

Long acting analogue of the calcitonin gene-related peptide induces positive metabolic effects and secretion of the glucagon-like peptide-1.

The pharmacological potential of Calcitonin gene-related peptide (CGRP) beyond vasodilation is not completely understood and studies are limited by the potent vasodilatory effect and the short half-life of CGRP. In particular, the effects of CGRP on metabolic diseases are not clarified. A peptide analogue of the α form of CGRP (αAnalogue) with prolonged half-life (10.

Electrophysiological correlates of stimulus equivalence processes.

Research reported here concerns neural processes relating to stimulus equivalence class formation. In Experiment 1, two types of word pairs were presented successively to normally capable adults. In one type, the words had related usage in English (e.

EXCLUSION LEARNING AND EMERGENT SYMBOLIC CATEGORY FORMATION IN INDIVIDUALS WITH SEVERE LANGUAGE IMPAIRMENTS AND INTELLECTUAL DISABILITIES.

We evaluated formation of simple symbolic categories from initial learning of specific dictated word-picture relations through emergence of untaught or derived relations. Participants were 10 individuals with severe intellectual and language limitations. Three experimental categories were constructed, each containing 1 spoken word (Set A), 1 photograph (Set B), and 1 visual-graphic "lexigram" (Set C).

Improving memory span in children with Down syndrome.

Background: Down syndrome (DS) is characterized by impaired memory span, particularly auditory verbal memory span. Memory span is linked developmentally to several language capabilities, and may be a basic capacity that enables language learning. If children with DS had better memory span, they might benefit more from language intervention.

Demonstration of a method for assessing semantic organization and category membership in individuals with autism spectrum disorders and receptive vocabulary limitations.

A recognized challenge in the field of augmentative and alternative communication (AAC) is the assessment of the individual skills and preferences of potential users of AAC. Particularly in cognitive assessment, many traditional methods are inappropriate because they require the participant to produce a verbal response and/or involve complex verbal instructions. For individuals with limited verbal forms of language, failure at such tasks is relatively uninstructive, either for revealing their functional intellectual status or for developing effective interventions.

Computer-aided detection of breast cancer: a cost-effectiveness study.

Purpose: To analyze the cost-effectiveness of adding computer-aided detection (CAD) to a screening mammography program.

Materials And Methods: A Markov model was developed to compare three hypothetical groups of women aged 40-79 years. The first group was composed of women undergoing mammographic screening without CAD; the second, of women undergoing mammographic screening with CAD; and the third, of women undergoing observation without screening.

Phonological reading skills acquisition by children with mental retardation.

Twenty children with mental retardation (MR), age 7-12, completed a phonological reading skills program over approximately 10 weeks. As a result of the instruction, they were better able to sound out learned and transfer words compared to a control group matched on age, IQ, nonword reading, language comprehension, and phonemic awareness. Final sounding out was predicted by beginning reading skill in both groups, by phonemic awareness and articulation speed in the control group only, and by general language ability in the instruction group only.

Phonological and visuo-spatial working memory in individuals with intellectual disability.

Differences in the storage and rehearsal components of the phonological loop and visuo-spatial sketchpad were investigated in individuals with and without intellectual disability matched on memory span. The group with intellectual disability had specific difficulty in the rehearsal component of the phonological loop, as demonstrated by a weak word length effect compared to the group without intellectual disability. Groups did not differ in the storage component of the phonological loop as indexed by the phonological similarity effect.

Predicting treatment choice for patients with pelvic organ prolapse.

Objective: To evaluate which clinical factors were predictive of treatment choice for patients with pelvic organ prolapse.

Methods: One hundred fifty-two patients were enrolled in this cross-sectional study to collect clinical data on potential predictors of treatment choice. Continuous parametric, continuous nonparametric (ordinal), and categoric data were compared with chosen management plan (expectant, pessary, surgery) using analysis of variance, the Kruskal-Wallis test, and the chi(2) test for association, respectively.

Is pelvic organ prolapse a cause of pelvic or low back pain?

Objective: To test the null hypothesis that there is no association between pelvic organ prolapse and pelvic or low back pain.

Methods: A total of 152 consecutive patients with pelvic organ prolapse completed a visual faces scale to quantify the amount of pelvic or low back pain present. Pelvic organ prolapse severity was graded by three techniques: 1) pelvic organ prolapse quantification staging; 2) descent of the leading edge of prolapse; and 3) dynamic cystoproctography.

Memory training for children with Down syndrome.

One well-established fact concerning cognitive and language development in individuals with Down syndrome is that working memory is particularly poor, with auditory working memory worse than visual working memory. Working memory serves the functions of control, regulation, and active maintenance of information and is critical in daily complex cognitive activities. Thus, there is a strong need to find effective and practical interventions targeted at improving working memory in individuals with Down syndrome.

Collagen type II C-telopeptide fragments as an index of cartilage degradation.

We report the development of an assay for measurement of the urinary concentration of collagen type II C-telopeptide fragments. This assay was developed for providing a specific marker of joint metabolism. A monoclonal antibody, recognizing a linear six amino acid epitope from the middle region of the collagen type II C-telopeptide was used in a competitive enzyme-linked immunoassay (ELISA) format for measurement of urine samples.

Laparoscopic versus open gastric bypass: a randomized study of outcomes, quality of life, and costs.

Objective: To compare outcomes, quality of life (QOL), and costs of laparoscopic and open gastric bypass (GBP).

Summary Background Data: Laparoscopic GBP has been reported to be a safe and effective approach for the treatment of morbid obesity. The authors performed a prospective randomized trial to compare outcomes, QOL, and costs of laparoscopic GBP with those of open GBP.

Abilities underlying decoding differences in children with intellectual disability.

Researchers in recent years have made much progress towards understanding why some children struggle to learn to read. However, little of this research has involved children with intellectual disability associated with an IQ < 70 (ID, also called mental retardation). In the present analysis, the authors examined cognitive similarities and differences between stronger and weaker decoders, all of whom have ID.

Influence of feature training on the formation of exemplar-specific representations in children with mental retardation.

Whether exemplar-specific or prototype representations were primarily used by children with mild mental retardation in a categorization task consisting of two groups of make-believe animals whose features were ill-defined was examined. Categorization performance of familiar, prototypic, and novel test phase exemplars indicated that these children were able to acquire and use both types of representations. A feature-labeling training procedure, expected to promote the formation of exemplar-specific representations prior to exemplar classification, was also incorporated within the current study's design.

Clinical evaluation of the Serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides.

The Serum CrossLaps One Step ELISA is a sandwich assay using two monoclonal antibodies specific for a beta-aspartate form of the epitope EKAHDGGR derived from the carboxy-terminal telopeptide region of type I collagen alpha1-chain. Our objective was to assess the clinical value of the Serum CrossLaps assay for monitoring antiresorptive therapy in osteoporosis treatment. Samples obtained from postmenopausal women treated with different doses of cyclic or continuous hormone replacement therapy (HRT) with an estrogen analog (tibolone) or with a bisphosphonate (ibandronate) were measured in the Serum CrossLaps One Step ELISA at baseline and at various time points during therapy.

Serum CrossLaps One Step ELISA. First application of monoclonal antibodies for measurement in serum of bone-related degradation products from C-terminal telopeptides of type I collagen.

We have developed a two-site ELISA for measurement in serum of bone-related degradation products derived from C-terminal telopeptides of type I collagen. The assay is based on the application of two highly specific monoclonal antibodies against the amino acid sequence of AHD-beta-GGR, where the aspartic acid residue (D) is beta-isomerized. In a one-step incubation procedure, the degradation products containing cross-linked diisomerized EKAHD-beta-GGR peptides are captured by a biotinylated antibody and a peroxidase-conjugated antibody.

Screening mammography beginning at age 40 years: a reappraisal of cost-effectiveness.

Background: Several recent studies have added significant information regarding the benefit of screening mammography, especially in the 40-49-years age group. This new information makes it important to reassess the cost-effectiveness of screening.

Methods: A Markov model was used to study the cost-effectiveness of 4 age-related screening strategies: 1) annually from ages 40-79 years; 2) annually from ages 40-64 years and biennially from ages 65-79 years; 3) annually from ages 40-49 years and biennially from ages 50-79 years; and 4) annually from ages 40-79 years in high risk women (10%) and biennially from ages 40-49 years followed by annually from ages 50 -79 years in normal risk women (90%).

Purification and characterization of bone-specific alkaline phosphatase from a human osteosarcoma cell line.

Bone-specific alkaline phosphatase (bone ALP) levels are considered to reflect osteoblastic activity and can therefore be used as a marker of bone formation. However, bone ALP is difficult to distinguish from other ALP isoforms since the kidney, liver, and bone isoenzymes are encoded by the same gene and only differ because of post-translational modification of their carbohydrate side chains. The aim of this study was to purify and separate bone ALP which could be used to raise specific antisera against human bone ALP, from Saos-2, a human osteogenic sarcoma cell line.

High bone turnover is associated with low bone mass in both pre- and postmenopausal women.

In 979 healthy women, aged 30-75 years, bone mass was measured by DXA in the lumbar spine and proximal femur, and by SXA in the distal forearm. Bone turnover was assessed by urinary CrossLaps (CrossLaps ELISA), a new assay which measures type I collagen degradation products in urine and by osteocalcin (two-site N-Mid hOsteocalcin ELISA), a new assay which measures the N-terminal-mid fragment (1-43) as well as the intact (1-49) osteocalcin (OCN-Mid) in serum. For comparison data on urinary hydroxyproline (fU Hpr/Cr) and serum, total alkaline phosphatase were included (AP).