Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry

The clinical significance of detecting minimal residual disease (MRD) in B-lineage acute lymphoblastic leukaemia (ALL) was evaluated by quantitative flow cytometry using a combination of TdT with CD10 and CD19. 53 patients with B-cell precursor ALL were followed during and after completion of treatment (median follow-up 23 months). Nine patients relapsed and MRD had been detected in six of them, 5–15 weeks before relapse despite morphological complete remission. 43 patients remain in clinical remission and in none of these was MRD detected. Disease-free survival based on the detection of MRD by flow cytometry showed a statistically significant difference between both groups ( P  < 0.0001). The absence of MRD correlates with a low relapse rate, whereas the presence of MRD predicted early relapse. This study has shown that flow cytometry can improve the morphologic assessment of bone marrow (BM) remission status in B-lineage ALL. The finding of < 5% blasts in BM aspirates did not correlate with 'true' remission in a proportion of cases as residual leukaemic blasts were detected by flow cytometry in nine samples from six patients. On the other hand, the presence of > 5% blasts assessed by morphology was not necessarily a feature of relapse in five patients as these cells were shown to have a phenotype identical to normal TdT-negative B-cell precursors. Quantitative flow cytometry was more informative than conventional morphology to assess remission status and showed a strong correlation with clinical outcome. This methodology is useful to define MRD in the majority of patients with B-lineage ALL and should be tested in prospective clinical trials.     

Environment, wealth, inequality and the burden of disease in the Accra metropolitan area, Ghana

The study examines environmental problems and adverse impacts on the health of urban households in the Accra metropolitan area, Ghana. Accra is faced with severe inadequacy of urban infrastructure in the face of rapid population growth in the metropolis. More than half of the city's population do not have access to solid waste collection services. Only 39.8% of households have indoor pipe and over 35.0% of households depend on unsanitary public latrines whilst 2.5% do not have access to toilet facilities. Human excrement, garbage and wastewater are usually deposited in surface drains, open spaces and streams in poor neighbourhoods. The resultant poor sanitation has serious health impacts as more than half of reported diseases are related to poor environmental sanitation. The majority of households depend on solid fuels for cooking and this leads to indoor air pollution and high incidence of respiratory infections. Poor households bear a disproportionately large share of the burden of environmental health hazards than their wealthy counterparts, due to their particular vulnerability resulting from inadequate access to environmental health facilities and services.     

Proteomic identification of an MHC-binding peptidome from pancreas and breast cancer cell lines

Peptides bound to cell surface MHC class I molecules allow the immune system to recognize intracellular pathogens and tumor-derived peptides. Our goal was to learn what the immune system “sees” on the surfaces of tumor cells by acid-eluting peptides from HLA molecules for extended time periods. We determined how long peptides would continue to elute over time from a pancreatic tumor cell line, Panc-1, and a breast cancer cell line, MCF-7, at pH 3.0 in citrate buffer while monitoring viability. Both cell lines demonstrated greater than 90% viability after 25 min at pH 3.0. Panc-1 remained >90% intact after 45 min at pH 3.0. Acid eluted peptide sequences were identified using LC–MS/MS and searching the NCBI refseq database. The total number of peptides eluted peaked between 40 and 45 min for Panc-1, but continued to increase over time from MCF-7. A total of 131 peptides were identified from Panc-1 while 101 peptides were identified from MCF-7 elutions. Two classes of peptides were eluted: (1) 8–10 amino acid peptides fitting the HLA-binding motifs of each cell line, and (2) peptides longer than 10 amino acids containing HLA-binding motifs of each cell line. W6/32 antibody affinity purification of intact MHC molecules after papain cleavage of MHC class I from tumor cell surfaces also indicated that peptides longer than 10 amino acids bind to class I proteins. A peptide–MHC-refolding assay further substantiated the binding of longer peptides to HLA-A*0201. Our findings provide sequences and gene names of peptides presented by MHC class I molecules from common pancreas and breast cancer cell lines. We utilized a novel refolding assay to demonstrate that peptides longer than the canonical 8–10 amino acids commonly bind in MHC class I cell surface molecules.     

Developing accessible cyberinfrastructure-enabled knowledge communities in the national disability community: theory, practice, and policy

Since publication of the Atkins Commission report in 2003, the national scientific community has placed significant emphasis on developing cyberinfrastructure-enabled knowledge communities, which are designed to facilitate enhanced efficiency and collaboration in geographically distributed networks of researchers. This article suggests that the new cyberinfrastructure movement may not fully benefit those participants with disabilities, unless closer attention is paid to legal mandates and universal design principles. Many technology-enhanced learning communities provide geographically distributed collaboration opportunities that expand the inclusion of diverse peoples and help close the digital divide. However, to date, most collaboratory efforts have not emphasized the need for access among people with disabilities nor meeting minimum standards for technological accessibility. To address these concerns, this article reports on two pilot collaboratory studies that explore the role advanced information, communication, and collaboration technologies play in enhancing geographically distributed collaboration among specific research and applied networks within the national disability community. Universal design principles inform the design of the collaboratory and its use and our efforts to ensure access for all. Data for this article come from Web-based surveys, interviews, observations, computer logs, and detailed, mixed-methods accessibility testing. Emerging results suggest that with deliberate and systematic efforts, cyberinfrastructure can be more accessible and generate benefits among persons with disabilities. The authors provide lessons learned and recommendations for future research, policy, law, and practice.     

Increasing the uptake of prevention of mother-to-child transmission of HIV services in a resource-limited setting

Background  

As in other resource limited settings, the Ministry of Health in Zambia is challenged to make affordable and acceptable PMTCT interventions accessible and available. With a 14.3% HIV prevalence, the MOH estimates over one million people are HIV positive in Zambia. Approximately 500,000 children are born annually in Zambia and 40,000 acquire the infection vertically each year if no intervention is offered. This study sought to review uptake of prevention of mother-to-child (PMTCT) services in a resource-limited setting following the introduction of context-specific interventions.     

Adherence to On-Time ART Drug Pick-Up and Its Association with CD4 Changes and Clinical Outcomes Amongst HIV Infected Adults on First-Line Antiretroviral Therapy in Nigerian Hospitals

Medication adherence is a major determinant of antiretroviral treatment (ART) success. Promptness in medication refill pick-ups may give an indication of medication adherence. This study determined medication refill adherence among HIV positive patients on ART and its association with treatment outcomes in HIV treatment centers in Nigeria. This retrospective multi-center cohort study involved a review of ART refill records for 3534 HIV-positive patients aged 18–60 years who initiated first-line ART between January 2008 and December 2009 and were on therapy for ≥18 months after ART initiation. Drug refill records of these patients for 10 consecutive refill visits after ART initiation were analyzed. The first ten consecutive refill appointment-keeping rates after ART initiation ranged from 64.3 % to 76.1 % which decreased with successive visits. Altogether, 743 (21.1 %) patients were deemed adherent, meaning they picked up their drugs within 7 days of the drug refill appointment date on at least nine out of ten refill visits. The adherent group of patients had a mean CD4 cells increase of 206 ± 6.1 cells/dl after 12 months of ART compared to 186 ± 7.1 cells/dl reported among the nonadherent group (p = 0.0145). The proportion of patients in the adherent category who showed no OIs after 12 months on ART (81 %) was significantly higher when compared to the proportion in the non-adherent category (23.5 %), (p = 0.008). The multivariate analysis showed that the odds of being adherent was 2–3 times more in patients who had a baseline CD4 count of less than 200 cells/dl compared to those with a baseline CD4 of >350 cells/dl. (AOR 2.43, 95 % CI 1.62–3.66). In addition, for patients with baseline CD4 cell count of 201–350 cells/dl, the odds of being adherent was found to be 1.9 compared to those with baseline CD4 of greater than 350 cells/dl (AOR 1.93, 95 % CI 1.27–2.94). Pharmacy refill data can serve as an adherence measure. Adherence to on-time drug pickup on ≥90 % of refill appointments was associated with a better CD4 count response and a reduction in the presence of opportunistic infections in ART patients after 12 months of treatment.