Critical Structure Sparing in Stereotactic Ablative Radiotherapy for Central Lung Lesions: Helical Tomotherapy vs. Volumetric Modulated Arc Therapy

Background

Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are both advanced techniques of delivering intensity-modulated radiotherapy (IMRT). Here, we conduct a study to compare HT and partial-arc VMAT in their ability to spare organs at risk (OARs) when stereotactic ablative radiotherapy (SABR) is delivered to treat centrally located early stage non-small-cell lung cancer or lung metastases.

Methods

12 patients with centrally located lung lesions were randomly chosen. HT, 2 & 8 arc (Smart Arc, Pinnacle v9.0) plans were generated to deliver 70 Gy in 10 fractions to the planning target volume (PTV). Target and OAR dose parameters were compared. Each technique’s ability to meet dose constraints was further investigated.

Results

HT and VMAT plans generated essentially equivalent PTV coverage and dose conformality indices, while a trend for improved dose homogeneity by increasing from 2 to 8 arcs was observed with VMAT. Increasing the number of arcs with VMAT also led to some improvement in OAR sparing. After normalizing to OAR dose constraints, HT was found to be superior to 2 or 8-arc VMAT for optimal OAR sparing (meeting all the dose constraints) (p = 0.0004). All dose constraints were met in HT plans. Increasing from 2 to 8 arcs could not help achieve optimal OAR sparing for 4 patients. 2/4 of them had 3 immediately adjacent structures.

Conclusion

HT appears to be superior to VMAT in OAR sparing mainly in cases which require conformal dose avoidance of multiple immediately adjacent OARs. For such cases, increasing the number of arcs in VMAT cannot significantly improve OAR sparing.     

Limited contemporary gene flow and high self‐replenishment drives peripheral isolation in an endemic coral reef fish

Extensive ongoing degradation of coral reef habitats worldwide has lead to declines in abundance of coral reef fishes and local extinction of some species. Those most vulnerable are ecological specialists and endemic species. Determining connectivity between locations is vital to understanding recovery and long‐term persistence of these species following local extinction. This study explored population connectivity in the ecologically‐specialized endemic three‐striped butterflyfish (Chaetodon tricinctus) using mt and msatDNA (nuclear microsatellites) to distinguish evolutionary versus contemporary gene flow, estimate self‐replenishment and measure genetic diversity among locations at the remote Australian offshore coral reefs of Middleton Reef (MR), Elizabeth Reef (ER), Lord Howe Island (LHI), and Norfolk Island (NI). Mt and msatDNA suggested genetic differentiation of the most peripheral location (NI) from the remaining three locations (MR, ER, LHI). Despite high levels of mtDNA gene flow, there is limited msatDNA gene flow with evidence of high levels of self‐replenishment (≥76%) at all four locations. Taken together, this suggests prolonged population recovery times following population declines. The peripheral population (NI) is most vulnerable to local extinction due to its relative isolation, extreme levels of self‐replenishment (95%), and low contemporary abundance.     

Placebo Use in the United Kingdom: Results from a National Survey of Primary Care Practitioners

Objectives

Surveys in various countries suggest 17% to 80% of doctors prescribe ‘placebos’ in routine practice, but prevalence of placebo use in UK primary care is unknown.

Methods

We administered a web-based questionnaire to a representative sample of UK general practitioners. Following surveys conducted in other countries we divided placebos into ‘pure’ and ‘impure’. ‘Impure’ placebos are interventions with clear efficacy for certain conditions but are prescribed for ailments where their efficacy is unknown, such as antibiotics for suspected viral infections. ‘Pure’ placebos are interventions such as sugar pills or saline injections without direct pharmacologically active ingredients for the condition being treated. We initiated the survey in April 2012. Two reminders were sent and electronic data collection closed after 4 weeks.

Results

We surveyed 1715 general practitioners and 783 (46%) completed our questionnaire. Our respondents were similar to those of all registered UK doctors suggesting our results are generalizable. 12% (95% CI 10 to 15) of respondents used pure placebos while 97% (95% CI 96 to 98) used impure placebos at least once in their career. 1% of respondents used pure placebos, and 77% (95% CI 74 to 79) used impure placebos at least once per week. Most (66% for pure, 84% for impure) respondents stated placebos were ethical in some circumstances.

Conclusion and implications

Placebo use is common in primary care but questions remain about their benefits, harms, costs, and whether they can be delivered ethically. Further research is required to investigate ethically acceptable and cost-effective placebo interventions.     

A primary assembly of a bovine haplotype block map based on a 15,036-single-nucleotide polymorphism panel genotyped in holstein-friesian cattle

Analysis of data on 1000 Holstein-Friesian bulls genotyped for 15,036 single-nucleotide polymorphisms (SNPs) has enabled genomewide identification of haplotype blocks and tag SNPs. A final subset of 9195 SNPs in Hardy-Weinberg equilibrium and mapped on autosomes on the bovine sequence assembly (release Btau 3.1) was used in this study. The average intermarker spacing was 251.8 kb. The average minor allele frequency (MAF) was 0.29 (0.05-0.5). Following recent precedents in human HapMap studies, a haplotype block was defined where 95% of combinations of SNPs within a region are in very high linkage disequilibrium. A total of 727 haplotype blocks consisting of > or =3 SNPs were identified. The average block length was 69.7 +/- 7.7 kb, which is approximately 5-10 times larger than in humans. These blocks comprised a total of 2964 SNPs and covered 50,638 kb of the sequence map, which constitutes 2.18% of the length of all autosomes. A set of tag SNPs, which will be useful for further fine-mapping studies, has been identified. Overall, the results suggest that as many as 75,000-100,000 tag SNPs would be needed to track all important haplotype blocks in the bovine genome. This would require approximately 250,000 SNPs in the discovery phase.     

Congenital defects among liveborn infants with Down syndrome

BACKGROUND: Many infants with Down syndrome (DS) have co-occurring congenital malformations requiring intensive surgical and medical management. To anticipate the care needed by these infants, providers and parents require accurate information about birth defects that may be present. This article uses a unique national hospital discharge dataset to identify the rate at which structural birth defects are identified among liveborn infants with DS. METHODS: ICD-9-CM diagnosis codes for data from the Healthcare Cost and Utilization Project were used to identify infants with and without DS, and to classify birth defects. The study population consisted of liveborn infants discharged from the hospital from 1993 through 2002. ORs for the association between the occurrence of congenital malformations and the presence of DS were computed using logistic regression models for survey data. RESULTS: Discharge data included 11,372 DS and 7,884,209 non-DS births, representing national estimates of 43,463 DS and 39,716,469 non-DS births respectively. In addition to congenital heart defects that co-occurred most often in DS infants compared to infants without DS, the risks for gastrointestinal malformations (OR 67.07), genitourinary malformations (OR 3.62), orofacial malformations (OR 5.63), and abdominal wall malformations (OR 3.25) were also elevated in infants with DS. There was no difference in the risk of spina bifida between infants with and without DS. CONCLUSIONS: This is the first nationally representative compilation of the co-occurrence of congenital malformations associated with DS. This information may assist providers and parents in their attempts to understand and prepare for the true burden of this condition.     

Identification of a novel species of Eimeria Schneider, 1875 from the woylie,Bettongia penicillata Gray (Diprotodontia: Potoroidae) and the genetic characterisation of three Eimeria spp. from other potoroid marsupials

Faecal samples (n = 1,093) collected from the woylie Bettongia penicillata Gray, in south-western Australia were examined for the presence of coccidian parasites. Eimeria sp. oöcysts were detected in 15.2% of samples. Faecal samples obtained from the eastern bettong Bettongia gaimardi (Desmarest) (n = 4) and long-nosed potoroo Potorous tridactylus (Kerr) (n = 12) in Tasmania, were also screened for the presence of Eimeria spp. (prevalence 50% and 41.7%, respectively). Morphological and genetic comparison with other known species of Eimeria indicates that the material identified in woylies is novel. This study aimed to (i) morphologically describe and genetically characterise Eimeria woyliei n. sp. found in woylies; and (ii) genetically characterise Eimeria gaimardi Barker, O’Callaghan & Beveridge, 1988, Eimeria potoroi Barker, O’Callaghan & Beveridge, 1988, and Eimeria mundayi Barker, O’Callaghan & Beveridge, 1988, from other potoroid marsupials. Molecular phylogenetic analyses conducted at the 18S rDNA and mitochondrial cytochrome c oxidase subunit 1 (cox1) loci revealed that E. woyliei n. sp. was most closely related to Eimeria setonicis Barker, O’Callaghan & Beveridge, 1988, at the 18S rDNA locus, and Eimeria trichosuri O’Callaghan & O’Donoghue, 2001, at the cox1 locus. Eimeria woyliei n. sp. is the sixth species of Eimeria to be formally described from potoroid marsupials.