Working Effectively with People who are Blind or Visually Impaired

This brochure on peoples who are blind or visually impaired and The Americans with Disabilities Act (ADA) is one of a series on human resources practices and workplace accommodations for persons with disabilities edited by Susanne M. Bruyère, Ph.D., CRC, SPHR, Director, Program on Employment and Disability, School of Industrial and Labor Relations – Extension Division, Cornell University

Working Effectively with People who are Blind or Visually Impaired

This brochure on peoples who are blind or visually impaired and The Americans with Disabilities Act (ADA) is one of a series on human resources practices and workplace accommodations for persons with disabilities edited by Susanne M. Bruyère, Ph.D., CRC, SPHR, Director, Program on Employment and Disability, School of Industrial and Labor Relations – Extension Division, Cornell University. Cornell University was funded in the early 1990’s by the U.S. Department of Education National Institute on Disability and Rehabilitation Research as a National Materials Development Project on the employment provisions (Title I) of the ADA (Grant #H133D10155). These updates, and the development of new brochures, have been funded by Cornell’s Program on Employment and Disability

Metal Abundances in the Magellanic Stream

We report on the first metallicity determination for gas in the Magellanic Stream, using archival HST GHRS data for the background targets Fairall 9, III Zw 2, and NGC 7469. For Fairall 9, using two subsequent HST revisits and new Parkes Multibeam Narrowband observations, we have unequivocally detected the MSI HI component of the Stream (near its head) in SII1250,1253 yielding a metallicity of [SII/H]=-0.55+/-0.06(r)+/-0.2(s), consistent with either an SMC or LMC origin and with the earlier upper limit set by Lu et al. (1994). We also detect the saturated SiII1260 line, but set only a lower limit of [SiII/H]>-1.5. We present serendipitous detections of the Stream, seen in MgII2796,2803 absorption with column densities of (0.5-1)x10^13 cm^-2 toward the Seyfert galaxies III Zw 2 and NGC 7469. These latter sightlines probe gas near the tip of the Stream (80 deg down-Stream of Fairall 9). For III Zw 2, the lack of an accurate HI column density and the uncertain MgIII ionization correction limits the degree to which we can constrain [Mg/H]; a lower limit of [MgII/HI]>-1.3 was found. For NGC 7469, an accurate HI column density determination exists, but the extant FOS spectrum limits the quality of the MgII column density determination, and we conclude that [MgII/HI]>-1.5. Ionization corrections associated with MgIII and HII suggest that the corresponding [Mg/H] may range lower by 0.3-1.0 dex. However, an upward revision of 0.5-1.0 dex would be expected under the assumption that the Stream exhibits a dust depletion pattern similar to that seen in the Magellanic Clouds. Remaining uncertainties do not allow us to differentiate between an LMC versus SMC origin to the Stream gas.Comment: 30 pages, 8 figures, LaTeX (aaspp4), also available at http://casa.colorado.edu/~bgibson/publications.html, accepted for publication in The Astronomical Journa

A comparison of pneumolysin activity and concentration in vitro and in vivo in a rabbit endophthalmitis model

The purpose of this study was to determine whether the in vitro activity and concentration of Streptococcus pneumoniae pneumolysin correlated to the pathogenesis of S. pneumoniae endophthalmitis. Five S. pneumoniae clinical endophthalmitis strains were grown in media to similar optical densities (OD), and extracellular milieu was tested for pneumolysin activity by hemolysis of rabbit red blood cells. Pneumolysin concentration was determined using a sandwich ELISA. Rabbit vitreous was injected with 102 colony-forming units (CFU) of 1 of 2 different strains with low hemolytic activity (n = 10 and 12 for strains 4 and 5, respectively) or 1 of 3 different strains with high hemolytic activity (n = 12 per strain). Pathogenesis of endophthalmitis infection was graded by slit lamp examination (SLE) at 24 hours post-infection. Bacteria were recovered from infected vitreous and quantitated. The SLE scores of eyes infected with strains having high hemolytic activity were significantly higher than the scores of those infected with strains having low hemolytic activity (P < 0.05). Pneumolysin concentration in vitro, however, did not correlate with hemolysis or severity of endophthalmitis. Bacterial concentrations from the vitreous infected with 4 of the strains were not significantly different (P > 0.05). These data suggest that pneumolysin hemolytic activity in vitro directly correlates to the pathogenesis of S. pneumoniae endophthalmitis. The protein concentration of pneumolysin, however, is not a reliable indicator of pneumolysin activity

A Novel Combination of Serum Markers in a Multivariate Model to Help Triage Patients Into “Low-” and “High-Risk” Categories for Prostate Cancer

BACKGROUND: Almost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies. MATERIALS AND METHODS: Serum samples and clinical information were collected from N = 125 age-matched patients (n = 61 non-PCa and n = 64 PCa) and analyzed using Biochip Array Technology on high-sensitivity cytokine array I (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, TNFα, MCP-1, INFγ, EGF, and VEGF), cerebral array II (CRP, D-dimer, neuron-specific enolase, and sTNFR1), and tumor PSA oncology array (fPSA, tPSA, and CEA). RESULTS: The data showed that 11/19 (68.8%) markers were significantly different between the non-PCa and the PCa patients. A combination of EGF, log(10) IL-8, log(10) MCP-1, and log(10) tPSA significantly improved the predictive potential of tPSA alone to identify patients with PCa (DeLong, p < 0.001). This marker combination had an increased area under the receiver operator characteristic (0.860 vs. 0.700), sensitivity (78.7 vs. 68.9%), specificity (76.5 vs. 67.2%), PPV (76.2 vs. 66.7%), and NPV (79.0 vs. 69.4%) compared with tPSA. CONCLUSIONS: The novel combination of serum markers identified in this study could be employed to help triage patients into “low-” and “high-risk” categories, allowing general practitioners to improve the management of patients in primary care settings and potentially reducing the number of referrals for unnecessary, invasive, and costly treatments

Post-traumatic stress disorder: A biopsychosocial case-control study investigating peripheral blood protein biomarkers

Experiencing traumatic events is unfortunately commonplace and, in some cases, may lead to the onset of debilitating mental health disorders, such as post-traumatic stress disorder (PTSD). Current diagnostic criteria for PTSD results in high depression and anxiety comorbidity. Better understanding of biological mechanisms and pathways underlying PTSD could aid in more accurate case identification and stratification of treatments. Recent meta-analysis has identified chronic PTSD to be associated with increased expression of pro-inflammatory cytokines and alterations in neuronal structures which contribute to an overall reduction in brain volume. Despite this, there are currently no biological markers in clinical use to identify PTSD or monitor treatment. This case-control study (n = 40) aimed to identify differences in peripheral blood biomarkers, and biomarker combinations, able to distinguish PTSD participants from controls, and examine in a biopsychosocial framework. The levels of 5/37 biomarkers investigated were significantly altered in the serum of PTSD participants: HDL and LDL cholesterol, tPA, IL-8 and EGF. Biomarkers could be used in combination with psychological criteria, in a biopsychosocial model, to support clinical management decisions and ensure appropriate individual treatment pathways

PolyQ Tract Toxicity in SCA1 is Length Dependent in the Absence of CAG Repeat Interruption

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by an expansion of a polyglutamine tract within the ATXN1 gene. Normal alleles have been reported to range from 6 to 35 repeats, intermediate alleles from 36 to 38 repeats and fully penetrant pathogenic alleles have at least 39 repeats. This distribution was based on relatively few samples and the narrow intermediate range makes the accuracy of the repeat sizing crucial for interpreting and reporting diagnostic tests, which can vary between laboratories. Here, we examine the distribution of 6378 SCA1 chromosomes and identify a very late onset SCA1 family with a fully penetrant uninterrupted pathogenic allele containing 38 repeats. This finding supports the theory that polyQ toxicity is related to the increase of the length of the inherited tracts and not as previously hypothesized to the structural transition occurring above a specific threshold. In addition, the threshold of toxicity shifts to a shorter polyQ length with the increase of the lifespan in SCA1. Furthermore, we show that SCA1 intermediate alleles have a different behavior compared to the other polyglutamine disorders as they do not show reduced penetrance when uninterrupted. Therefore, the pathogenic mechanism in SCA1 is distinct from other cytosine-adenine-guanine (CAG) repeat disorders. Accurately sizing repeats is paramount in precision medicine and can be challenging particularly with borderline alleles. We examined plasmids containing cloned CAG repeat tracts alongside a triplet repeat primed polymerase chain reaction (TP PCR) CAG repeat ladder to improve accuracy in repeat sizing by fragment analysis. This method accurately sizes the repeats irrespective of repeat composition or length. We also improved the model for calculating repeat length from fragment analysis sizing by fragment analyzing 100 cloned repeats of known size. Therefore, we recommend these methods for accurately sizing repeat lengths and restriction enzyme digestion to identify interruptions for interpretation of a given allele’s pathogenicity

Epigenetic Mechanisms Regulate MHC and Antigen Processing Molecules in Human Embryonic and Induced Pluripotent Stem Cells

Background Human embryonic stem cells (hESCs) are an attractive resource for new therapeutic approaches that involve tissue regeneration. hESCs have exhibited low immunogenicity due to low levels of Mayor Histocompatibility Complex (MHC) class-I and absence of MHC class-II expression. Nevertheless, the mechanisms regulating MHC expression in hESCs had not been explored. Methodology/Principal Findings We analyzed the expression levels of classical and non-classical MHC class-I, MHC class-II molecules, antigen-processing machinery (APM) components and NKG2D ligands (NKG2D-L) in hESCs, induced pluripotent stem cells (iPSCs) and NTera2 (NT2) teratocarcinoma cell line. Epigenetic mechanisms involved in the regulation of these genes were investigated by bisulfite sequencing and chromatin immunoprecipitation (ChIP) assays. We showed that low levels of MHC class-I molecules were associated with absent or reduced expression of the transporter associated with antigen processing 1 (TAP-1) and tapasin (TPN) components in hESCs and iPSCs, which are involved in the transport and load of peptides. Furthermore, lack of β2-microglobulin (β2m) light chain in these cells limited the expression of MHC class I trimeric molecule on the cell surface. NKG2D ligands (MICA, MICB) were observed in all pluripotent stem cells lines. Epigenetic analysis showed that H3K9me3 repressed the TPN gene in undifferentiated cells whilst HLA-B and β2m acquired the H3K4me3 modification during the differentiation to embryoid bodies (EBs). Absence of HLA-DR and HLA-G expression was regulated by DNA methylation. Conclusions/Significance Our data provide fundamental evidence for the epigenetic control of MHC in hESCs and iPSCs. Reduced MHC class I and class II expression in hESCs and iPSCs can limit their recognition by the immune response against these cells. The knowledge of these mechanisms will further allow the development of strategies to induce tolerance and improve stem cell allograft acceptance