Video-based Simulations: Considerations for Teaching Students with Developmental Disabilities

The use of video-based multimedia simulations for teaching functional skills to persons with developmental disabilities remains an unexplored application of technology for this group. This article examines the historical literature in this area, and discusses future considerations, design issues, and implications of using multimedia simulations. Implementation issues are presented, and suggestions regarding design, development, and application of multimedia simulations are offered. Considerations address the importance of appropriate role modeling and the combination of video-based simulation and in vivo training to foster generalization and maintenance in the context of transition to the real world.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Towards imaging metabolic pathways in tissues

Molecular tumour pathology - and tumour genetic

Elevated glycated haemoglobin (HbA1c) is associated with an increased risk of pancreatic ductal adenocarcinoma: a UK Bi-obank cohort study

Background: the role of dysglycaemia as a risk marker for Pancreatic Ductal Adenocarcinoma (PDAC) is uncertain. We investigated the relationship between glycated haemoglobin (HbA1c) and incident PDAC using a retrospective cohort study within the UK Biobank. Methods: a study involving 499,804 participants from the UK Biobank study was undertaken. Participants were stratified by diabetes mellitus (DM) status, and then by HbA1c values < 42 mmol/mol, 42–47 mmol/mol, or ≥48 mmol/mol. Cox proportional hazard models were used to describe the association between HbA1c category (with time-varying interactions) and incident PDAC. Results: PDAC occurred in 1157 participants during 11.6 (10.9–12.3) years follow up [(median (interquartile range)]. In subjects without known DM at baseline, 12 months after recruitment, the adjusted hazard ratios (aHR, 95% CI) for incident PDAC for HbA1c 42–47 mmol/mol compared to HbA1c < 42 mmol/mol (reference group) was 2.10 (1.31–3.37, p = 0.002); and was 8.55 (4.58–15.99, p < 0.001) for HbA1c ≥ 48 mmol/mol. The association between baseline HbA1c and incident PDAC attenuated with increasing duration of time of follow-up to PDAC diagnosis. Conclusions: dysglycaemia detected by elevated HbA1c is associated with an increased risk of PDAC. The strength of the association between elevated HbA1c and incident PDAC is inversely proportional to the time from detecting dysglycaemia but remains significant for at least 60 months following HbA1c testing

N-glycosylation of colorectal cancer tissues: a liquid chromatography and mass spectrometry-based investigation

Colorectal cancer is the third most common cancer worldwide with an annual incidence of ~1 million cases and an annual mortality rate of ~655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers.Surgical oncolog

Investigations on Aberrant Glycosylation of Glycosphingolipids in Colorectal Cancer Tissues Using Liquid Chromatography and Matrix-Assisted Laser Desorption Time-of-Flight Mass Spectrometry (MALDI-TOF-MS)

Surgical oncolog

Multicenter Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI MSI) identifies proteomic differences in breast-cancer-associated stroma.

MALDI mass spectrometry imaging (MSI) has rapidly established itself as a powerful biomarker discovery tool. To date, no formal investigation has assessed the center-to-center comparability of MALDI MSI experiments, an essential step for it to develop into a new diagnostic method. To test such capabilities, we have performed a multicenter study focused on biomarkers of stromal activation in breast cancer. MALDI MSI experiments were performed in two centers using independent tissue banks, infrastructure, methods, and practitioners. One of the data sets was used for discovery and the other for validation. Areas of intra- and extratumoral stroma were selected, and their protein signals were compared. Four protein signals were found to be significantly associated with tumor-associated stroma in the discovery data set measured in Munich. Three of these peaks were also detected in the independent validation data set measured in Leiden, all of which were also significantly associated with intratumoral stroma. Hierarchical clustering displayed 100% accuracy in the Munich MSI data set and 80.9% accuracy in the Leiden MSI data set. The association of one of the identified mass signals (PA28) with stromal activation was confirmed with immunohistochemistry performed on 20 breast tumors. Independent and international MALDI MSI investigations could identify validated biomarkers of stromal activation

Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section

On-tissue digestion matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can be used to record spatially correlated molecular information from formalin-fixed, paraffin-embedded (FFPE) tissue sections. In this work, we present the in situ multimodal analysis of N-linked glycans and proteins from the same FFPE tissue section. The robustness and applicability of the method are demonstrated for several tumors, including epithelial and mesenchymal tumor types. Major analytical aspects, such as lateral diffusion of the analyte molecules and differences in measurement sensitivity due to the additional sample preparation methods, have been investigated for both N-glycans and proteolytic peptides. By combining the MSI approach with extract analysis, we were also able to assess which mass spectral peaks generated by MALDI-MSI could be assigned to unique N-glycan and peptide identities.Surgical oncolog

Psychosocial barriers to the reintegration of homeless

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging is a rapidly evolving field in which mass spectrometry techniques are applied directly on tissues to characterize the spatial distribution of various molecules such as lipids, protein/peptides, and recently also N-glycans. Glycans are involved in many biological processes and several glycan changes have been associated with different kinds of cancer, making them an interesting target group to study. An important analytical challenge for the study of glycans by MALDI mass spectrometry is the labile character of sialic acid groups which are prone to in-source/postsource decay, thereby biasing the recorded glycan profile. We therefore developed a linkage-specific sialic acid derivatization by dimethylamidation and subsequent amidation and transferred this onto formalin-fixed paraffin-embedded (FFPE) tissues for MALDI imaging of N-glycans. Our results show (i) the successful stabilization of sialic acids in a linkage specific manner, thereby not only increasing the detection range, but also adding biological meaning, (ii) that no noticeable lateral diffusion is induced during to sample preparation, (iii) the potential of mass spectrometry imaging to spatially characterize the N-glycan expression within heterogeneous tissues.Surgical oncolog

Tropospheric ozone: respiratory effects and Australian air quality goals.

OBJECTIVE--To review the health effects of tropospheric ozone and discuss the implications for public health policy. DESIGN--Literature review and consultation with scientists in Australia and overseas. Papers in English or with English language abstracts were identified by Medline search from the international peer reviewed published reports. Those from the period 1980-93 were read systematically but selected earlier papers were also considered. Reports on ozone exposures were obtained from environmental agencies in the region. RESULTS--Exposure to ozone at concentrations below the current Australian air quality goal (0.12 ppm averaged over one hour) may cause impaired respiratory function. Inflammatory changes in the small airways and respiratory symptoms result from moderate to heavy exercise in the presence of ozone at levels of 0.08-0.12 ppm. The changes in respiratory function due to ozone are short lived, vary with the duration of exposure, may be modified by levels of other pollutants (such as sulphur dioxide and particulates), and differ appreciably between individuals. Bronchial lavage studies indicate that inflammation and other pathological changes may occur in the airways before reductions in air flow are detectable, and persist after respiratory function has returned to normal. It is not known whether exposures to ozone at low levels (0.08-0.12 ppm) cause lasting damage to the lung or, if such damage does occur, whether it is functionally significant. At present, it is not possible to identify confidently population subgroups with heightened susceptibility to ozone. People with asthma may be more susceptible to the effects of ozone than the general population but the evidence is not consistent. Recent reports suggest that ozone increases airway reactivity on subsequent challenge with allergens and other irritants. Animal studies are consistent with the findings in human populations. CONCLUSION--A new one hour air quality ozone goal of 0.08 ppm for Australia, and the introduction of a four hour goal of 0.06 ppm are recommended on health grounds