Mutations of the transcription factor PU.1 are not associated with acute lymphoblastic leukaemia

The transcription factor PU.1 plays a crucial role during normal haematopoiesis in both myeloid cells and B-lymphocytes. Mice with a disruption in both alleles of the PU.1 locus were found to lack macrophages and B cells and had delayed appearance of neutrophils. In addition, critical decrease of PU.1 expression is sufficient to cause acute myeloid leukaemia (AML) and lymphomas in mice. Recently, we reported that heterozygous mutations in the PU.1 gene are present in some patients with AML. Thus, we hypothesised that PU.1 mutations might also contribute to the development of acute leukaemias of the B-cell lineage. Here, we screened 62 patients with B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis for genomic mutations by direct sequencing of all five exons of the PU.1 gene. We found no genomic alteration of the PU.1 gene suggesting that PU.1 mutations are not likely to be common in B-ALL

Posterior reversible encephalopathy syndrome in a child with cyclical vomiting and hypertension: a case report

<p>Abstract</p> <p>Introduction</p> <p>Posterior reversible encephalopathy syndrome is characterized by headache, nausea and vomiting, seizures and visual disturbances. It has certain characteristic radiological features, which allow diagnosis in the appropriate clinical setting and enable appropriate clinical therapy to be instituted.</p> <p>Case presentation</p> <p>A 10-year-old Caucasian girl who was hospitalized due to recurrent vomiting was diagnosed as having posterior reversible encephalopathy syndrome after an initial diagnosis of cyclical vomiting and hypertension was made.</p> <p>Conclusion</p> <p>Posterior reversible encephalopathy syndrome is a rare disorder in children. Early recognition of characteristic radiological features is key to the diagnosis as clinical symptoms may be non-specific or mimic other neurological illnesses. To the best of our knowledge this is the first case to report an association between posterior reversible encephalopathy syndrome, cyclical vomiting and hypertension. Furthermore, in this case, the resolution of the abnormalities found on magnetic resonance imaging over time did not appear to equate with clinical recovery.</p

Mechanical properties and fracture patterns of graphene (graphitic) nanowiggles

publisher: Elsevier articletitle: Mechanical properties and fracture patterns of graphene (graphitic) nanowiggles journaltitle: Carbon articlelink: http://dx.doi.org/10.1016/j.carbon.2017.04.018 content_type: article copyright: © 2017 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Mechanical properties and fracture patterns of graphene (graphitic) nanowiggles journaltitle: Carbon articlelink: http://dx.doi.org/10.1016/j.carbon.2017.04.018 content_type: article copyright: © 2017 Elsevier Ltd. All rights reserved.This work was supported in part by the Brazilian Agencies CNPq, CAPES and FAPESP. The authors would like to thank the Center for Computational Engineering and Sciences at Unicamp for financial support through the FAPESP/CEPID Grant 2013/08293-7. N.M.P. is supported by the European Research Council PoC 2015 “Silkene” No. 693670, by the European Commission H2020 under the Graphene Flagship Core 1 No. 696656 (WP14 “Polymer Nanocomposites”) and under the Fet Proactive “Neurofibres” No. 732344

Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of cancer among children in Malawi - preliminary findings

<p>Abstract</p> <p>Background</p> <p>The impact of infection with HIV on the risk of cancer in children is uncertain, particularly for those living in sub-Saharan Africa. In an ongoing study in a paediatric oncology centre in Malawi, children (aged ≤ 15 years) with known or suspected cancers are being recruited and tested for HIV and their mothers or carers interviewed. This study reports findings for children recruited between 2005 and 2008.</p> <p>Methods</p> <p>Only children with a cancer diagnosis were included. Odds ratios (OR) for being HIV positive were estimated for each cancer type (with adjustment for age (<5 years, ≥ 5 years) and sex) using children with other cancers and non-malignant conditions as a comparison group (excluding the known HIV-associated cancers, Kaposi sarcoma and lymphomas, as well as children with other haematological malignancies or with confirmed non-cancer diagnoses).</p> <p>Results</p> <p>Of the 586 children recruited, 541 (92%) met the inclusion criteria and 525 (97%) were tested for HIV. Overall HIV seroprevalence was 10%. Infection with HIV was associated with Kaposi sarcoma (29 cases; OR = 93.5, 95% CI 26.9 to 324.4) and with non-Burkitt, non-Hodgkin lymphoma (33 cases; OR = 4.4, 95% CI 1.1 to 17.9) but not with Burkitt lymphoma (269 cases; OR = 2.2, 95% CI 0.8 to 6.4).</p> <p>Conclusions</p> <p>In this study, only Kaposi sarcoma and non-Burkitt, non-Hodgkin lymphoma were associated with HIV infection. The endemic form of Burkitt lymphoma, which is relatively frequent in Malawi, was not significantly associated with HIV. While the relatively small numbers of children with other cancers, together with possible limitations of diagnostic testing may limit our conclusions, the findings may suggest differences in the pathogenesis of HIV-related malignancies in different parts of the world.</p

Transgenic Expression of P1A Induced Thymic Tumor: A Role for Onco-Fetal Antigens in Tumorigenesis

P1A is the first known tumor rejection antigen. It is expressed in embryonic stem cells and multiple tumors but is silent in adult tissues except for the testis and placenta. Therefore, P1A represents a prototype for onco-fetal antigens. To test the potential function of P1A in tumorigenesis, we used a transgenic mouse expressing P1A in lymphoid cells. We observed that immunodeficient host P1A transgenic mice developed thymic tumors after 7 months of age and had shorter survival rates compared to control groups. Most of the 7 examined tumors displayed B cell lineage markers. The P1A transgenic bone marrow cells had higher proliferation ability and more potential progenitors compared to control bone marrow cells. To our knowledge, our data provided the first example that onco-fetal antigen can promote tumorigenesis

Consensus Paper—ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia

The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients—the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life

Long-term outcome of radiological-guided insertion of implanted central venous access port devices (CVAPD) for the delivery of chemotherapy in cancer patients: institutional experience and review of the literature

Central venous access port devices (CVAPD) are necessary for delivery of prolonged infusional chemotherapy or in patients with poor peripheral venous access. Previous studies of Hickman catheters report complication rates in about 45% of patients. Our aim was to assess the early and late complication rate, and duration that the CVAPD remained functional, following insertion by interventional radiologists in patients with solid tumours. A prospective study was undertaken in 110 consecutive patients who had insertion of 111 subclavian CVAPD. The median age of patients was 57 years (range 17–83), 64 were females; 68 patients (61%) had gastrointestinal tumours and 25 (23%) had breast cancer. CVAPD were successfully implanted in all but one patient. There were four (4%) immediate major complications: thrombosis 2 and pneumothorax 2. Nine patients (8%) had bruising or pain. Four devices (4%) became infected. In total, 100 CVAPD (90%) were either removed as planned at the end of treatment (n=23) after a median 203 days, or remained in situ for a median of 237 days (7–1133). Premature removal occurred in eight patients due to infection (n=4), thrombosis (n=3) or faulty device (n=1). Four patients were lost to follow-up. Radiological insertion of CVAPD is safe and convenient with low rates of complications

Spatial patterns of microbial diversity and activity in an aged creosote-contaminated site

Restoration of polluted sites via in situ bioremediation relies heavily on the indigenous microbes and their activities. Spatial heterogeneity of microbial populations, contaminants and soil chemical parameters on such sites is a major hurdle in optimizing and implementing an appropriate bioremediation regime. We performed a grid-based sampling of an aged creosote-contaminated site followed by geostatistical modelling to illustrate the spatial patterns of microbial diversity and activity and to relate these patterns to the distribution of pollutants. Spatial distribution of bacterial groups unveiled patterns of niche differentiation regulated by patchy distribution of pollutants and an east-to-west pH gradient at the studied site. Proteobacteria clearly dominated in the hot spots of creosote pollution, whereas the abundance of Actinobacteria, TM7 and Planctomycetes was considerably reduced from the hot spots. The pH preferences of proteobacterial groups dominating in pollution could be recognized by examining the order and family-level responses. Acidobacterial classes came across as generalists in hydrocarbon pollution whose spatial distribution seemed to be regulated solely by the pH gradient. Although the community evenness decreased in the heavily polluted zones, basal respiration and fluorescein diacetate hydrolysis rates were higher, indicating the adaptation of specific indigenous microbial populations to hydrocarbon pollution. Combining the information from the kriged maps of microbial and soil chemistry data provided a comprehensive understanding of the long-term impacts of creosote pollution on the subsurface microbial communities. This study also highlighted the prospect of interpreting taxa-specific spatial patterns and applying them as indicators or proxies for monitoring polluted sites

Research note: Investor perceptions of comparable-to-industry versus higher-than-industry pay ratio disclosures

The usefulness of the CEO-to-employee pay ratio disclosure to investors is subject to significant debate. Our experiment examines participant responses to higher-than-industry and comparable-to-industry pay ratio disclosures in a company. A prior experiment by Kelly and Seow (2016) (hereafter KS) found that incrementally disclosing a higher-than-industry pay ratio on top of higher-than-industry CEO pay had indirect negative effects on the company\u27s perceived investment potential, via negative perceptions about the fairness of the CEO pay and workplace climate. We find that the negative indirect effects of pay ratio disclosures on perceived investment potential in KS are replicable in our study, and for a less extreme comparable-to-industry pay ratio. We do not find evidence that the effects of incremental pay ratio disclosure on investor perceptions are stronger when the pay ratio is higher-than-industry than when it is comparable-to-industry. Our study suggests that the ability of pay ratio disclosures to impact investor perceptions extends across a range of pay ratios

The International Limits and Population at Risk of Plasmodium vivax Transmission in 2009

Growing evidence shows that Plasmodium vivax malaria is clinically less benign than has been commonly believed. In addition, it is the most widely distributed species of human malaria and is likely to cause more illness in certain regions than the more extensively studied P. falciparum malaria. Understanding where P. vivax transmission exists and measuring the number of people who live at risk of infection is a fundamental first step to estimating the global disease toll. The aim of this paper is to generate a reliable map of the worldwide distribution of this parasite and to provide an estimate of how many people are exposed to probable infection. A geographical information system was used to map data on the presence of P. vivax infection and spatial information on climatic conditions that impede transmission (low ambient temperature and extremely arid environments) in order to delineate areas where transmission was unlikely to take place. This map was combined with population distribution data to estimate how many people live in these areas and are, therefore, exposed to risk of infection by P. vivax malaria. The results show that 2.85 billion people were exposed to some level of risk of transmission in 2009