Environmental risk assessment of GE plants under low-exposure conditions

The requirement for environmental risk assessment (ERA) of genetically engineered (GE) plants prior to large scale or commercial introduction into the environment is well established in national laws and regulations, as well as in international agreements. Since the first introductions of GE plants in commercial agriculture in the 1990s, a nearly universal paradigm has emerged for conducting these assessments based on a few guiding principles. These include the concept of case-by-case assessment, the use of comparative assessments, and a focus of the ERA on characteristics of the plant, the introduced trait, and the receiving environment as well as the intended use. In practice, however, ERAs for GE plants have frequently focused on achieving highly detailed characterizations of potential hazards at the expense of consideration of the relevant levels of exposure. This emphasis on exhaustive hazard characterization can lead to great difficulties when applied to ERA for GE plants under low-exposure conditions. This paper presents some relevant considerations for conducting an ERA for a GE plant in a low-exposure scenario in the context of the generalized ERA paradigm, building on discussions and case studies presented during a session at ISBGMO 12

Can Global Variation of Nasopharynx Cancer Be Retrieved from the Combined Analyses of IARC Cancer Information (CIN) Databases?

BACKGROUND: The international nasopharynx cancer (NPC) burdens are masked due to the lack of integrated studies that examine epidemiological data based on up-to-date international disease databases such as the Cancer Information (CIN) databases provided by the International Agency for Research on Cancer (IARC). METHODS: By analyzing the most recently updated NPC epidemiological data available from IARC, we tried to retrieve the worldwide NPC burden and patterns from combined analysis with GLOBOCAN2008 and the Cancer Incidence in Five Continents (CI5) databases. We provide age-standardized rates (ASR) for NPC mortality in 20 highest cancer registries from GLOBOCAN2008 and the World Health Organization (WHO) mortality databases, respectively. However, NPC incidence data can not be retrieved since it is not individually listed in CI5 database. The trend of NPC mortality was investigated with Joinpoint analysis in the selected countries/regions with high ASR. RESULTS: GLOBOCAN 2008 revealed that the highest NPC incidence rates in 2008 were in registries from South-Eastern Asia, Micronesia and Southern Africa with Malaysia, Indonesia and Singapore ranking the top 3. WHO mortality database analysis revealed that China Hong Kong, Singapore and Malta ranks the top 3 regions with the highest 5-year mortality rates. CONCLUSIONS: NPC mortality rate is about 2-3 times higher in male than that in female, and shows decrease tendency in those selected countries/regions during the analyzed periods. However, the integrated analyses of the current IARC CIN databases may not be suitable to retrieve epidemiological data of NPC. Much effort is required to improve the local cancer entry and regional death-reporting systems so as to aid similar studies

Trends in prenatal cares settings: association with medical liability

<p>Abstract</p> <p>Background</p> <p>Medical liability concerns centered around maternity care have widespread public health implications, as restrictions in physician scope of practice may threaten quality of and access to care in the current climate. The purpose of this study was to examine national trends in prenatal care settings based on medical liability climate.</p> <p>Methods</p> <p>Analysis of prenatal visits in the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, 1997 to 2004 (N = 21,454). To assess changes in rates of prenatal visits over time, we used the linear trend test. Multivariate logistic regression modeling was developed to determine characteristics associated with visits made to hospital outpatient departments.</p> <p>Results</p> <p>In regions of the country with high medical liability (N = 11,673), the relative number, or proportion, of all prenatal visits occurring in hospital outpatient departments increased from 11.8% in 1997–1998 to 19.4% in 2003–2004 (p < .001 for trend); the trend for complicated obstetrical visits (N = 3,275) was more pronounced, where the proportion of prenatal visits occurring in hospital outpatient departments almost doubled from 22.7% in 1997–1998 to 41.6% in 2003–2004 (p = .004 for trend). This increase did not occur in regions of the country with low medical liability (N = 9,781) where the proportion of visits occurring in hospital outpatient departments decreased from 13.3% in 1997–1998 to 9.0% in 2003–2004.</p> <p>Conclusion</p> <p>There has been a shift in prenatal care from obstetrician's offices to safety net settings in regions of the country with high medical liability. These findings provide strong indirect evidence that the medical liability crisis is affecting patterns of obstetric practice and ultimately patient access to care.</p

Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total

Can Global Variation of Nasopharynx Cancer Be Retrieved from the Combined Analyses of IARC Cancer Information (CIN) Databases?

BACKGROUND: The international nasopharynx cancer (NPC) burdens are masked due to the lack of integrated studies that examine epidemiological data based on up-to-date international disease databases such as the Cancer Information (CIN) databases provided by the International Agency for Research on Cancer (IARC). METHODS: By analyzing the most recently updated NPC epidemiological data available from IARC, we tried to retrieve the worldwide NPC burden and patterns from combined analysis with GLOBOCAN2008 and the Cancer Incidence in Five Continents (CI5) databases. We provide age-standardized rates (ASR) for NPC mortality in 20 highest cancer registries from GLOBOCAN2008 and the World Health Organization (WHO) mortality databases, respectively. However, NPC incidence data can not be retrieved since it is not individually listed in CI5 database. The trend of NPC mortality was investigated with Joinpoint analysis in the selected countries/regions with high ASR. RESULTS: GLOBOCAN 2008 revealed that the highest NPC incidence rates in 2008 were in registries from South-Eastern Asia, Micronesia and Southern Africa with Malaysia, Indonesia and Singapore ranking the top 3. WHO mortality database analysis revealed that China Hong Kong, Singapore and Malta ranks the top 3 regions with the highest 5-year mortality rates. CONCLUSIONS: NPC mortality rate is about 2-3 times higher in male than that in female, and shows decrease tendency in those selected countries/regions during the analyzed periods. However, the integrated analyses of the current IARC CIN databases may not be suitable to retrieve epidemiological data of NPC. Much effort is required to improve the local cancer entry and regional death-reporting systems so as to aid similar studies

Enhancing Credibility of Chemical Safety Studies: Emerging Consensus on Key Assessment Criteria

Objectives: We examined the extent to which consensus exists on the criteria that should be used for assessing the credibility of a scientific work, regardless of its funding source, and explored how these criteria might be implemented. Data sources: Three publications, all presented at a session of the 2009 annual meeting of the Society for Risk Analysis, have proposed a range of criteria for evaluating the credibility of scientific studies. At least two other similar sets of criteria have recently been proposed elsewhere. Data extraction/synthesis: In this article we review these criteria, highlight the commonalities among them, and integrate them into a list of 10 criteria. We also discuss issues inherent in any attempt to implement the criteria systematically. Con c l u s i o n s: Recommendations by many scientists and policy experts converge on a finite list of criteria for assessing the credibility of a scientific study without regard to funding source. These criteria should be formalized through a consensus process or a governmental initiative that includes discussion and pilot application of a system for reproducibly implementing them. Formal establishment of such a system should enable the debate regarding chemical studies to move beyond funding issues and focus on scientific merit

Changes in glycemic control from 1996 to 2006 among adults with type 2 diabetes: a longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Our objectives were to examine temporal changes in HbA1c and lipid levels over a 10-year period and to identify predictors of metabolic control in a longitudinal patient cohort.</p> <p>Methods</p> <p>We identified all adults within our hospital network with T2DM who had HbA1c's measured in both 1996 and 2006 (longitudinal cohort). For patients with no data in 2006, we used hospital and social security records to distinguish patients lost to follow-up from those who died after 1996. We compared characteristics of the 3 baseline cohorts (longitudinal, lost to f/u, died) and examined metabolic trends in the longitudinal cohort.</p> <p>Results</p> <p>Of the 4944 patients with HbA1c measured in 1996, 1772 (36%) had an HbA1c measured in 2006, 1296 (26%) were lost to follow-up, and 1876 (38%) had died by 2006. In the longitudinal cohort, mean HbA1c decreased by 0.4 ± 1.8% over the ten-year span (from 8.2% ± 1.7% to 7.8% ± 1.4%) and mean total cholesterol decreased by 49.3 (± 46.5) mg/dL. In a multivariate model, independent predictors of HbA1c decline included older age (OR 1.41 per decade, 95% CI: 1.3-1.6, p < 0.001), baseline HbA1c (OR 2.9 per 1% increment, 2.6 - 3.2, p < 0.001), and speaking English (OR 2.1, 1.4-3.1, p < 0.001).</p> <p>Conclusions</p> <p>Despite having had diabetes for an additional 10 years, patients in our longitudinal cohort had better glycemic and cholesterol control in 2006 than 1996. Greatest improvements occurred in patients with the highest levels in the baseline year.</p

Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

Myelofibrosis is a severe myeloproliferative neoplasm characterized by increased numbers of abnormal bone marrow megakaryocytes that induce fibrosis, destroying the hematopoietic microenvironment. To determine the cellular and molecular basis for aberrant megakaryopoiesis in myelofibrosis, we performed single-cell transcriptome profiling of 135,929 CD34+ lineage− hematopoietic stem and progenitor cells (HSPCs), single-cell proteomics, genomics, and functional assays. We identified a bias toward megakaryocyte differentiation apparent from early multipotent stem cells in myelofibrosis and associated aberrant molecular signatures. A sub-fraction of myelofibrosis megakaryocyte progenitors (MkPs) are transcriptionally similar to healthy-donor MkPs, but the majority are disease specific, with distinct populations expressing fibrosis- and proliferation-associated genes. Mutant-clone HSPCs have increased expression of megakaryocyte-associated genes compared to wild-type HSPCs, and we provide early validation of G6B as a potential immunotherapy target. Our study paves the way for selective targeting of the myelofibrosis clone and illustrates the power of single-cell multi-omics to discover tumor-specific therapeutic targets and mediators of tissue fibrosis

Treatment with intravenous pamidronate is a good alternative in case of gastrointestinal side effects or contraindications for oral bisphosphonates

<p>Abstract</p> <p>Background</p> <p>In case of contraindications or intolerance during treatment with oral bisphosphonates (OB), administration of pamidronate intravenously is a widely used alternative.</p> <p>In this study we compared the effect on change in bone mineral density (BMD) of the spine and hip during long term treatment with pamidronate iv in comparison to OB.</p> <p>Methods</p> <p>We studied 61 patients receiving treatment for at least two years. In case of contraindications or intolerance (within 3 months) of an OB, pamidronate iv was started. BMD was measured on a Hologic 4500 and a Lunar DPX-IQ at the spine (L1-L4) and total hip.</p> <p>Results</p> <p>Thirty-one patients were enrolled in the OB group and 30 in the intravenous pamidronate group. Mean follow-up duration (SD) was 4.3 (1.3) years. We observed a significant increase (p < 0.001) in spinal BMD, both in the OB group (8.3%) as well as in the pamidronate iv group (6.1%), but no significant difference in BMD change between the OB and pamidronate iv groups. At the hips, we observed a tendency to increased BMD in both groups, 1.1% in the OB and 1.4% in the pamidronate iv group.</p> <p>Conclusion</p> <p>We conclude that intravenous pamidronate is a good alternative for oral bisphosphonates in the treatment of osteoporosis in patients with contraindications or intolerance during treatment with oral bisphosphonates.</p