Evidences for a quasi 60-year North Atlantic Oscillation since 1700 and its meaning for global climate change

The North Atlantic Oscillation (NAO) obtained using instrumental and documentary proxy predictors from Eurasia is found to be characterized by a quasi 60-year dominant oscillation since 1650. This pattern emerges clearly once the NAO record is time integrated to stress its comparison with the temperature record. The integrated NAO (INAO) is found to well correlate with the length of the day (since 1650) and the global surface sea temperature record HadSST2 and HadSST3 (since 1850). These findings suggest that INAO can be used as a good proxy for global climate change, and that a 60-year cycle exists in the global climate since at least 1700. Finally, the INAO ~60-year oscillation well correlates with the ~60- year oscillations found in the historical European aurora record since 1700, which suggests that this 60-year dominant climatic cycle has a solar-astronomical origin

Azacitidine prolongs overall survival and reduces infections and hospitalizations in patients with WHO-defined acute myeloid leukaemia compared with conventional care regimens: an update

Azacitidine (AZA), as demonstrated in the phase III trial (AZA-001), is the first MDS treatment to significantly prolong overall survival (OS) in higher risk MDS pts ((2007) Blood 110 817). Approximately, one-third of the patients (pts) enrolled in AZA-001 were FAB RAEB-T (≥20–30% blasts) and now meet the WHO criteria for acute myeloid leukaemia (AML) ((1999) Blood 17 3835). Considering the poor prognosis (median survival <1 year) and the poor response to chemotherapy in these pts, this sub-group analysis evaluated the effects of AZA versus conventional care regimens (CCR) on OS and on response rates in pts with WHO AML

Long-term safety of Mometasone Furoate administered via a dry powder inhaler in children: Results of an open-label study comparing Mometasone Furoate with Beclomethasone Dipropionate in children with persistent asthma

<p>Abstract</p> <p>Background</p> <p>To assess the long-term pediatric safety of 2 doses of mometasone furoate administered via a dry powder inhaler (MF-DPI) for mild-to-moderate persistent asthma and compare them with that of beclomethasone dipropionate administered via a metered dose inhaler (BDP-MDI) in the treatment of persistent asthma. Both MF-DPI doses tested are twice the approved pediatric dosage of 100 μg once-daily (QD) for children aged 4–11 years.</p> <p>Methods</p> <p>Children (N = 233) aged 4–11 years were randomized to 52 weeks of treatment with MF-DPI 200 μg QD AM, MF-DPI 100 μg twice daily (BID), or BDP-MDI 168 μg BID. Patients had used inhaled corticosteroids (ICSs) daily for ≥ 30 days before the screening visit and were on stable ICS doses for ≥ 2 weeks before screening. The primary safety variable was the incidence of adverse events. Secondary safety variables were laboratory tests (including cortisol concentrations), vital signs, and physical examination.</p> <p>Results</p> <p>The incidence of adverse events was similar in all 3 treatment groups. The most frequently reported adverse event was upper respiratory tract infection, reported by 47%–49% of the MF-DPI-treated patients and 51% of the BPD-treated patients. Most adverse events were considered unrelated to study drug. The most frequently reported related adverse events were headache (MF-DPI 200 μg QD AM, 8%; MF-DPI 100 μg BID, 4%; BDP-MDI 168 μg BID, 2%) and oral candidiasis (4% in each treatment group). No clinically relevant changes in laboratory values, including plasma cortisol, vital signs, or physical examinations were noted in any treatment group.</p> <p>Conclusion</p> <p>Both MF-DPI doses were well tolerated, with no unusual or unexpected adverse events or safety concerns, and had a similar adverse event profile to that of BDP-MDI 168 μg BID.</p

Expression of therapeutic misconception amongst Egyptians: a qualitative pilot study

<p>Abstract</p> <p>Background</p> <p>Studies have shown that research participants fail to appreciate the difference between research and medical care, labeling such phenomenon as a "therapeutic misconception" (TM). Since research activity involving human participants is increasing in the Middle East, qualitative research investigating aspects of TM is warranted. Our objective was to assess for the existence of therapeutic misconception amongst Egyptians.</p> <p>Methods</p> <p><it>Study Tool: </it>We developed a semi-structured interview guide to elicit the knowledge, attitudes, and perspectives of Egyptians regarding medical research.</p> <p><it>Setting: </it>We recruited individuals from the outpatient settings (public and private) at Ain Shams University in Cairo, Egypt.</p> <p><it>Analysis: </it>Interviews were taped, transcribed, and translated. We analyzed the content of the transcribed text to identify the presence of a TM, defined in one of two ways: TM₁= inaccurate beliefs about how individualized care can be compromised by the procedures in the research and TM₂= inaccurate appraisal of benefit obtained from the research study.</p> <p>Results</p> <p>Our findings showed that a majority of participants (11/15) expressed inaccurate beliefs regarding the degree with which individualized care will be maintained in the research setting (TM₁) and a smaller number of participants (5/15) manifested an unreasonable belief in the likelihood of benefits to be obtained from a research study (TM₂). A total of 12 of the 15 participants were judged to have expressed a TM on either one of these bases.</p> <p>Conclusion</p> <p>The presence of TM is not uncommon amongst Egyptian individuals. We recommend further qualitative studies investigating aspects of TM involving a larger sample size distinguished by different types of illnesses and socio-economic variables, as well as those who have and have not participated in clinical research.</p

Modeling Mechanisms of In Vivo Variability in Methotrexate Accumulation and Folate Pathway Inhibition in Acute Lymphoblastic Leukemia Cells

Methotrexate (MTX) is widely used for the treatment of childhood acute lymphoblastic leukemia (ALL). The accumulation of MTX and its active metabolites, methotrexate polyglutamates (MTXPG), in ALL cells is an important determinant of its antileukemic effects. We studied 194 of 356 patients enrolled on St. Jude Total XV protocol for newly diagnosed ALL with the goal of characterizing the intracellular pharmacokinetics of MTXPG in leukemia cells; relating these pharmacokinetics to ALL lineage, ploidy and molecular subtype; and using a folate pathway model to simulate optimal treatment strategies. Serial MTX concentrations were measured in plasma and intracellular MTXPG concentrations were measured in circulating leukemia cells. A pharmacokinetic model was developed which accounted for the plasma disposition of MTX along with the transport and metabolism of MTXPG. In addition, a folate pathway model was adapted to simulate the effects of treatment strategies on the inhibition of de novo purine synthesis (DNPS). The intracellular MTXPG pharmacokinetic model parameters differed significantly by lineage, ploidy, and molecular subtypes of ALL. Folylpolyglutamate synthetase (FPGS) activity was higher in B vs T lineage ALL (p<0.005), MTX influx and FPGS activity were higher in hyperdiploid vs non-hyperdiploid ALL (p<0.03), MTX influx and FPGS activity were lower in the t(12;21) (ETV6-RUNX1) subtype (p<0.05), and the ratio of FPGS to γ-glutamyl hydrolase (GGH) activity was lower in the t(1;19) (TCF3-PBX1) subtype (p<0.03) than other genetic subtypes. In addition, the folate pathway model showed differential inhibition of DNPS relative to MTXPG accumulation, MTX dose, and schedule. This study has provided new insights into the intracellular disposition of MTX in leukemia cells and how it affects treatment efficacy

Follicular thyroid carcinoma invades venous rather than lymphatic vessels

Follicular thyroid carcinoma (FTC) tends to metastasize to remote organs rather than local lymph nodes. Separation of FTC from follicular thyroid adenoma (FTA) relies on detection of vascular and/or capsular invasion. We investigated which vascular markers, CD31, CD34 and D2-40 (lymphatic vessel marker), can best evaluate vascular invasion and why FTC tends to metastasize via blood stream to remote organs. Thirty two FTCs and 34 FTAs were retrieved for evaluation. The average age of patients with FTA was 8 years younger than FTC (p = 0.02). The female to male ratio for follicular neoplasm was 25:8. The average size of FTC was larger than FTA (p = 0.003). Fourteen of 32 (44%) FTCs showed venous invasion and none showed lymphatic invasion, with positive CD31 and CD34 staining and negative D2-40 staining of the involved vessels. The average number of involved vessels was 0.88 ± 1.29 with a range from 0 to 5, and the average diameter of involved vessels was 0.068 ± 0.027 mm. None of the 34 FTAs showed vascular invasion. CD31 staining demonstrated more specific staining of vascular endothelial cells than CD34, with less background staining. We recommended using CD31 rather than CD34 and/or D2-40 in confirming/excluding vascular invasion in difficult cases. All identified FTCs with vascular invasions showed involvement of venous channels, rather than lymphatic spaces, suggesting that FTCs prefer to metastasize via veins to distant organs, instead of lymphatic vessels to local lymph nodes, which correlates with previous clinical observations

Long-Term Health Outcomes in Children Born to Mothers with Diabetes: A Population-Based Cohort Study

BACKGROUND: To examine whether prenatal exposure to parental type 1 diabetes, type 2 diabetes, or gestational diabetes is associated with an increased risk of malignant neoplasm or diseases of the circulatory system in the offspring. METHODS/PRINCIPAL FINDINGS: We conducted a population-based cohort study of 1,781,576 singletons born in Denmark from 1977 to 2008. Children were followed for up to 30 years from the day of birth until the onset of the outcomes under study, death, emigration, or December 31, 2009, whichever came first. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the outcomes under study while adjusting for potential confounders. An increased risk of malignant neoplasm was found in children prenatally exposed to maternal type 2 diabetes (HR = 2.2, 95%CI: 1.5-3.2). An increased risk of diseases of the circulatory system was found in children exposed to maternal type 1 diabetes (HR = 2.2, 95%CI: 1.6-3.0), type 2 diabetes (HR = 1.4, 95%CI: 1.1-1.7), and gestational diabetes (HR = 1.3, 95%CI: 1.1-1.6), but results were attenuated after excluding children with congenital malformations. An increased risk of diseases of the circulatory system was also found in children exposed to paternal type 2 diabetes (HR = 1.5, 95%CI: 1.1-2.2) and the elevated risk remained after excluding children with congenital malformations. CONCLUSIONS: This study suggests that susceptibility to malignant neoplasm is modified partly by fetal programming. Diseases of the circulatory system may be modified by genetic factors, other time-stable family factors, or fetal programming

How do firms comply with international sustainability standards? Processes and consequences of adopting the global reporting initiative

This paper addresses the issue of the influence of global governance institutions, particularly international sustainability standards, on a firm’s intra-organizational practices. More precisely, we provide an exploratory empirical view of the impact of the Global Reporting Initiative (GRI) on a multinational corporation’s (MNC) corporate social responsibility (CSR) management practices. We investigate standard compliance by comparing the stated intention of the use of the GRI with its actual use and the consequent effects within the firm. Based on an in-depth case study, our findings illustrate the processes and consequences of the translation of the GRI within the organization. We show that substantive standard adoption can lead to unintended consequences on CSR management practices, specifically it can influence the management structure and CSR committee function; the choice of CSR activities, the relationships between subsidiaries, the temporal dimension of CSR management, and the interpretation of CSR performance. We also highlight the need to look at the relationship dynamics (or lack of) between standards. Finally we illustrate and discuss the role of reporting and its influence on management in order to better understand the internal issues arising from compliance with standards

Daptomycin antimicrobial activity tested against methicillin-resistant staphylococci and vancomycin-resistant enterococci isolated in European medical centers (2005)

BACKGROUND: Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gram-positive bacteria currently used for the treatment of complicated skin and skin structure infections and bacteremia, including right sided endocarditis. We evaluated the in vitro activity of this compound and selected comparator agents tested against clinical strains of staphylococci and enterococci collected in European medical centers in 2005. METHODS: A total of 4,640 strains from 23 medical centers located in 10 European countries, Turkey and Israel (SENTRY Program platform) were tested for susceptibility by reference broth microdilution methods according to Clinical and Laboratory Standards Institute guidelines and interpretative criteria. Mueller-Hinton broth was supplemented to 50 mg/L Ca(++ )for testing daptomycin. Results for oxacillin (methicillin)-resistant staphylococci and vancomycin-resistant enterococci were analyzed separately. RESULTS: Oxacillin resistance rates among Staphylococcus aureus varied from 2.1% in Sweden to 42.5% in the United Kingdom (UK) and 54.7% in Ireland (29.1% overall), while vancomycin resistance rates varied from 0.0% in France, Sweden and Switzerland to 66.7% in the UK and 71.4% in Ireland among Enterococcus faecium (17.9% overall). All S. aureus strains were inhibited at daptomycin MIC of 1 mg/L (MIC(50/90), 0.25/0.5 mg/L; 100.0% susceptible) and only one coagulase-negative staphylococci strain (0.1%) showed an elevated (>1 mg/L) daptomycin MIC value (4 mg/L). Among E. faecalis (MIC(50/90), 0.5/1 mg/L; 100% susceptible) the highest daptomycin MIC value was 2 mg/L; while among E. faecium (MIC(50/90), 2/4 mg/L; 100% susceptible) the highest MIC result was 4 mg/L. CONCLUSION: Daptomycin showed excellent in vitro activity against staphylococci and enterococci collected in European medical centers in 2005 and resistance to oxacillin, vancomycin or quinupristin/dalfopristin did not compromise its activity overall against these pathogens. Based on these results and those of previous publications, daptomycin appears to be an excellent therapeutic option for serious infections caused by oxacillin-resistant staphylococci and vancomycin-resistant enterococci in Europe