Tailored stereotactic radiotherapy technique using deep inspiration breath-hold to reduce stomach dose for cardiac radioablation

PURPOSE: To provide a new insight on a novel safe cardiac radioablation using deep inspiration breath-hold (DIBH) to reduce gastrointestinal dose. MATERIALS AND METHODS: For treating incessant ventricular tachycardia (VT) originated from left ventricle inferior scar abutting the stomach, a target delineation and treatment planning for cardiac radioablation was performed. With four different computed tomography (CT) scan protocols-DIBH, full expiration breath-hold, four-dimensional (4D) CT without and with abdominal compression, the distances between the target and the stomach were compared. RESULTS: Among the protocols, the CT scan with DIBH showed largest distance between the target and the stomach and selected for the treatment planning. The prescribed dose was 25 Gy in a single fraction, and satisfactory dosimetric parameters were achieved with the DIBH. The patient was successfully treated with the DIBH, and experienced no acute toxicity. CONCLUSION: To gain the best benefit from cardiac radioablation, understanding the possible toxicity in the adjacent organs is crucial. By moving the heart with thoraco-diaphragmatic movement by DIBH, the target could be physically separated from the stomach

Hidden Gibbs random fields model selection using Block Likelihood Information Criterion

Performing model selection between Gibbs random fields is a very challenging task. Indeed, due to the Markovian dependence structure, the normalizing constant of the fields cannot be computed using standard analytical or numerical methods. Furthermore, such unobserved fields cannot be integrated out and the likelihood evaluztion is a doubly intractable problem. This forms a central issue to pick the model that best fits an observed data. We introduce a new approximate version of the Bayesian Information Criterion. We partition the lattice into continuous rectangular blocks and we approximate the probability measure of the hidden Gibbs field by the product of some Gibbs distributions over the blocks. On that basis, we estimate the likelihood and derive the Block Likelihood Information Criterion (BLIC) that answers model choice questions such as the selection of the dependency structure or the number of latent states. We study the performances of BLIC for those questions. In addition, we present a comparison with ABC algorithms to point out that the novel criterion offers a better trade-off between time efficiency and reliable results

Gaps and barriers in the control of blood glucose in people with type 2 diabetes

Background: Glycaemic control is suboptimal in a large proportion of people with type 2 diabetes who are consequently at an increased and avoidable risk of potentially severe complications. We sought to explore attitudes and practices among healthcare professionals that may contribute to suboptimal glycaemic control through a review of recent relevant publications in the scientific literature. Methods: An electronic search of the PubMed database was performed to identify relevant publications from January 2011 to July 2015. The electronic search was complemented by a manual search of abstracts from key diabetes conferences in 2014/2015 available online. Results: Recently published data indicate that glycaemic control is suboptimal in a substantial proportion (typically 40%-60%) of people with diabetes. This is the case across geographic regions and in both low- and higher-income countries. Therapeutic inertia appears to be an important contributor to poor glycaemic control in up to half of people with type 2 diabetes. In particular, prescribers are often willing to tolerate extended periods of 'mild' hyperglycaemia as well as having low expectations for their patients. There are often delays of 3 years or longer in initiating or intensifying glucose-lowering therapy when needed. Conclusion: Many people with type 2 diabetes are failed by current management, with approximately half not achieving or maintaining appropriate target blood glucose levels, leaving these patients at increased and avoidable risk of serious complications. Review criteria: The methodology of this review article is detailed in the 'Methods' section

High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

Mannose-binding lectin (MBL) targets diverse microorganisms for phagocytosis and complement-mediated lysis by binding specific surface glycans. Although recombinant human MBL (rhMBL) trials have focused on reconstitution therapy, safety studies have identified no barriers to its use at higher levels. Ebola viruses cause fatal hemorrhagic fevers for which no treatment exists and that are feared as potential biothreat agents. We found that mice whose rhMBL serum concentrations were increased ≥7-fold above average human levels survived otherwise fatal Ebola virus infections and became immune to virus rechallenge. Because Ebola glycoproteins potentially model other glycosylated viruses, rhMBL may offer a novel broad-spectrum antiviral approach

Invited Commentary: Secondhand Smoke-an Underrecognized Risk Factor for Cognitive Decline.

Pan et al. (Am J Epidemiol. 2018;187(5):911-918) reported findings that exposure to secondhand smoke (SHS) was associated with cognitive decline over the course of 2 years among middle-aged and older Chinese women who never smoked, and they also reported a dose-response relationship. SHS exposure affects vulnerable people disproportionately because they have less control or choice over their living and working environment. Smoking is an established risk factor for dementia, but recent evidence reports on dementia-risk increase have not included SHS. Many epidemiologic studies collect data on smoking but not SHS exposure. SHS may be one of the most prevalent and modifiable risk factors for cognitive decline and therefore represents a major potential target for reduction of dementia risk. Given the high prevalence of smoking in China and other parts of the world, there is an urgent need to raise awareness of SHS reduction as part of global and national strategies to reduce cognitive decline and dementia and to introduce legislation that protects nonsmokers and vulnerable children and adults from SHS

Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.

The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom's 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia

How well do blood folate concentrations predict dietary folate intakes in a sample of Canadian lactating women exposed to high levels of folate? An observational study

<p>Abstract</p> <p>Background</p> <p>In 1998, mandatory folic acid fortification of white flour and select cereal grain products was implemented in Canada with the intention to increase dietary folate intakes of reproducing women. Folic acid fortification has produced a dramatic increase in blood folate concentrations among reproductive age women, and a reduction in neural tube defect (NTD)-affected pregnancies. In response to improved blood folate concentrations, many health care professionals are asking whether a folic acid supplement is necessary for NTD prevention among women with high blood folate values, and how reliably high RBC folate concentrations predict folate intakes shown in randomized controlled trials to be protective against NTDs. The objective of this study was to determine how predictive blood folate concentrations and folate intakes are of each other in a sample of well-educated lactating Canadian women exposed to high levels of synthetic folate.</p> <p>Methods</p> <p>The relationship between blood folate concentrations and dietary folate intakes, determined by weighed food records, were assessed in a sample of predominantly university-educated lactating women (32 ± 4 yr) at 4-(n = 53) and 16-wk postpartum (n = 55).</p> <p>Results</p> <p>Median blood folate concentrations of all participants were well above plasma and RBC folate cut-off levels indicative of deficiency (6.7 and 317 nmol/L, respectively) and all, except for 2 subjects, were above the cut-off for NTD-risk reduction (>906 nmol/L). Only modest associations existed between total folate intakes and plasma (r = 0.46, <it>P </it>< 0.001) and RBC (r = 0.36, <it>P </it>< 0.01) folate concentrations at 16-wk postpartum. Plasma and RBC folate values at 16-wk postpartum correctly identified the quartile of folate intake of only 26 of 55 (47%) and 18 of 55 (33%) of subjects, respectively. The mean RBC folate concentration of women consuming 151–410 μg/d of synthetic folate (2^ndquartile of intake) did not differ from that of women consuming >410 μg/d (3^rdand 4^thquartile).</p> <p>Conclusion</p> <p>Folate intakes, estimated by food composition tables, and blood folate concentrations are not predictive of each other in Canadian lactating women exposed to high levels of folate. Synthetic intakes > 151–410 μg/d in these women produced little additional benefit in terms of maximizing RBC content. More studies are needed to examine the relationship between blood folate concentration and NTD risk. Until data from such studies are available, women planning a pregnancy should continue to consume a daily folic acid supplement of 400 μg.</p

Negative Regulation of EGFR/MAPK Pathway by Pumilio in Drosophila melanogaster

In Drosophila melanogaster, specification of wing vein cells and sensory organ precursor (SOP) cells, which later give rise to a bristle, requires EGFR signaling. Here, we show that Pumilio (Pum), an RNA-binding translational repressor, negatively regulates EGFR signaling in wing vein and bristle development. We observed that loss of Pum function yielded extra wing veins and additional bristles. Conversely, overexpression of Pum eliminated wing veins and bristles. Heterozygotes for Pum produced no phenotype on their own, but greatly enhanced phenotypes caused by the enhancement of EGFR signaling. Conversely, over-expression of Pum suppressed the effects of ectopic EGFR signaling. Components of the EGFR signaling pathway are encoded by mRNAs that have Nanos Response Element (NRE)–like sequences in their 3’UTRs; NREs are known to bind Pum to confer regulation in other mRNAs. We show that these NRE-like sequences bind Pum and confer repression on a luciferase reporter in heterologous cells. Taken together, our evidence suggests that Pum functions as a negative regulator of EGFR signaling by directly targeting components of the pathway in Drosophila