Purpose To characterize the stacked and staggered dual‐layer multileaf collimator (MLC) on the HalcyonTM system. Methods The novel MLC assembly was reviewed and compared to the widely used MillenniumTM 120‐leaf MLC system. We investigated the MLC positioning stability over 70 days using Machine Performance Check (MPC) data. We evaluated the leaf transmission, penumbra, leaf end effect, and leaf edge effect. Leaf transmission through distal, proximal, and both MLC layers was measured with a Farmer chamber, by comparing an open and a closed field. Leaf penumbra was measured using film for three different MLC‐defined field sizes. The leaf end effect was measured with sweeping gap fields of varying gap sizes defined by the distal MLC. The leaf edge effect was evaluated using the Electronic Portal Imaging Device (EPID) for the different banks, gantry positions, and collimator angles. Point dose measurements for 10 test plans were compared to dose predictions of two dose calculation model versions. Results From MPC data, the largest measured MLC positioning accuracy deviation was within 0.1 mm. The proximal MLC exhibited greater deviations compared to the distal MLC. The distal‐and‐proximal‐combination had reduced inter‐leaf and intra‐leaf transmission compared to delivery with distal‐only. The measured leaf transmission was 0.41% for distal‐only, 0.40% for proximal‐only, and negligible for distal‐and‐proximal‐combination. The leaf end penumbra was wider compared to the leaf edge penumbra. The leaf end effect was measured to be −0.2 mm. The leaf edge effect showed minimal bank, gantry position, and collimator angle dependence. However, a systematic deviation between measurements and treatment planning system handling of the leaf edge effect was observed. The discrepancy between the measured and predicted dose in the 10 test plans improved with the latest version of the dose calculation algorithm. Conclusion The characteristics of the stacked and staggered dual‐layer MLC on the HalcyonTM system were presented.

The learning curve in prostate tumor detection largely reflected self-directed learning. Continual feedback had a lesser effect. Clinical prostate MRI interpretation by novice radiologists warrants caution.

The macronuclear genome of hypotrichous ciliates consists of DNA molecules of gene-sized length. A macronuclear DNA molecule contains a single coding region. We have analyzed the many hypotrich macronuclear DNA sequences sequenced by us and others. No highly conserved promoter sequences nor replication initiation sequences have been identified in the 5' nor in the 3' non-translated regions, suggesting that promoter function in hypotrichs may differ from other eukaryotes. The macronuclear genes are intron-poor; approximately 19% of the genes sequenced to date have one to three introns. Not all macronuclear DNA molecules may be transcribed; some macronuclear molecules may not have any coding function. Codon bias in hypotrichs is different in many respects from other ciliates and from other eukaryotes.

Specific recognition of nucleotide cofactors by RNA may be important in engineering new RNA enzymes (ribozymes). Although in vitro selections (SELEX) have identified nucleic acid motifs ("aptamers") that bind a variety of adenosine cofactors, none of these recognizes coenzyme A (CoA), the primary biological cofactor used in acyltransfer reactions. We used SELEX experiments with two random RNA pools to identify aptamers that bind CoA. Functional boundary determination and extensive comparative sequence analysis (including reselection of a mutagenized, circularly permuted RNA) led to the identification of a 52 nucleotide minimal aptamer ("min52"). The RNA structural motif contains a large internal loop with 26 unpaired nucleotides flanked by helices of any base-paired sequence. Twenty loop nucleotides are specifically required for binding activity, 12 of which are derived from the original primer binding sequences. Specificity studies with CoA analogues demonstrated that the aptamer recognizes many adenosine analogues, including ATP, and that recognition is predominantly through the Höogsteen face of adenine. Binding activity is greatest at acidic pH (optimum near 5.0), in low or no monovalent salt, and at high concentrations of either Mg2+ or Mn2+. Strong binding activity (86% of maximum) is observed at pH 4.0, suggesting that at least some extreme conditions (acidic pH) may be compatible with RNA World theories of the origin and early evolution of life. In the presence of 10 mM Mg2+, binding is unaffected by the addition of 1 mM Ca2+, but it is mildly inhibited by 1 mM Zn2+ or Co2+ or by 0.1 mM Cu2+ or Ni2+. The dissociation constant (Kd) for the association of min52 RNA with ATP in solution was measured to be 2.4 +/- 0.4 microM under the conditions of the selection and 0.5 +/- 0.1 microM under optimized conditions. Finally, we show that the selected CoA aptamer populations contain other RNAs at low frequencies that preferentially recognize intact CoA and are not eluted from the resin by AMP alone.

There are many different RNA sequences that can bind Cam. The Cam aptamers that we examined have a well-defined secondary structure with a binding pocket that appears to be stabilized by Cam. This RNA motif superficially resembles the Cam-binding site in 23S rRNA, although further work is needed to establish the significance of these similarities.

Background The treatment of lung lesions with stereotactic body radiation therapy calls for highly conformal dose, which is evaluated by a number of metrics. Lung stereotactic body radiation therapy clinical trials constrain a plans gradient index. The purpose of this work is to describe the dependence of clinically achievable dose gradient on planning target volume. Methods Three hundred seventy-four lung stereotactic body radiation therapy treatment plans were retrospectively reviewed and selected for this study. The relationship between R50% and planning target volume size was observed and compared against the RTOG 0915 and 0813 constraints noting minor and major deviations. Then a least squares regression was used to determine the coefficients for a power functional form of the dependence of gradient measure (GM) on planning target volume size. Results Of the 317 peripheral lung SBRT plans, 142 exhibited no deviation, 135 exhibited a minor deviation, and 40 exhibited a major deviation according to the RTOG 0915 dosimetric. conformality and dose fall-off constraints. A plot of gradient measure versus planning target volume size for peripheral lesions, excluding RTOG 0915 major deviations, is fit with an power function of GM = 0.564 V 0.215 . Conclusions Using the PTV size and GM relationship we have characterized, treatment plans with PTV < 85 cm 3 can be evaluated subjectively to our previously plans, and given a percentile GM. This relationship and evaluation is useful for volumetric modulated arc therapy lung stereotactic body radiation therapy treatment planning and quality control. Electronic supplementary material The online version of this article (10.1186/s13014-019-1334-9) contains supplementary material, which is available to authorized users.

This study supports the previous GWAS findings and is the first to suggest a role for FOXE1, ABCA4, and MAFB in orofacial clefting in two separate Hispanic populations.

Roughly half the attacks underwent spontaneous remission during the two periods, but the medical mortality was 4-8% in the former and 0-7% in the latter, the operative mortality 20-0 and 7.0%, and the overall mortality 11.3 and 4.5% respectively. The lowering of the mortality was particularly striking in severe first attacks and in severe attacks in-patients over 60 years of age.Perforation of the colon was found in 21 cases, or nearly 20% of 112 patients coming to operation during attacks, being commoner in the first period (32-5%) than in the second (11-1%).°The immediate mortality of all such operations was 11.6%; in cases with perforation it was 28-6%.Acute colonic dilatation was observed in 28 cases. All but one were treated by emergency colectomy, at which the colon was noted to be perforated in 11. The mortality of these operations was 18.5%.Follow-up of the 140 patients who survived without coming to operation during their attacks shows that 52 (37-1%) subsequently underwent surgical treatment either during further attacks or electively.Though all 258 attacks were thought at the time to be due to ordinary ulcerative colitis, subsequent pathological examination of operative specimens derived from 98 patients who came to urgent or subsequent operation during the 1964-9 period revealed that the lesion in the large bowel was Crohn's disease in 17 instances. IsitroductionThe dangers to life posed by ulcerative colitis are largely concentrated in the phases of acute exacerbations or relapse which so frequently characterize the course of this disease. Fortunately these severe attacks often show a considerable tendency towards spontaneous remission, which can be to some extent encouraged by corticosteroid therapy and possibly other medical measures. In quite a proportion of cases, however, the attacks fail to remit on conservative management, and surgical treatment is urgently required if a fatal outcome is to be avoided, though surgery itself undertaken in these circumstances has often carried considerable risks. There has been much controversy among physicians and surgeons about the frequency with which operative intervention is really needed in these acute conditions and regarding its optimal timing.