Modelling burning thermonuclear plasma.

Considerable progress towards the achievement of thermonuclear burn using inertial confinement fusion has been achieved at the National Ignition Facility in the USA in the last few years. Other drivers, such as the Z-machine at Sandia, are also making progress towards this goal. A burning thermonuclear plasma would provide a unique and extreme plasma environment; in this paper we discuss (a) different theoretical challenges involved in modelling burning plasmas not currently considered, (b) the use of novel machine learning-based methods that might help large facilities reach ignition, and (c) the connections that a burning plasma might have to fundamental physics, including quantum electrodynamics studies, and the replication and exploration of conditions that last occurred in the first few minutes after the Big Bang. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 1)'.

A mathematical model of muscle containing heterogeneous half-sarcomeres exhibits residual force enhancement.

A skeletal muscle fiber that is stimulated to contract and then stretched from L1 to L2 produces more force after the initial transient decays than if it is stimulated at L2. This behavior has been well studied experimentally, and is known as residual force enhancement. The underlying mechanism remains controversial. We hypothesized that residual force enhancement could reflect mechanical interactions between heterogeneous half-sarcomeres. To test this hypothesis, we subjected a computational model of interacting heterogeneous half-sarcomeres to the same activation and stretch protocols that produce residual force enhancement in real preparations. Following a transient period of elevated force associated with active stretching, the model predicted a slowly decaying force enhancement lasting >30 seconds after stretch. Enhancement was on the order of 13% above isometric tension at the post-stretch muscle length, which agrees well with experimental measurements. Force enhancement in the model was proportional to stretch magnitude but did not depend strongly on the velocity of stretch, also in agreement with experiments. Even small variability in the strength of half-sarcomeres (2.1% standard deviation, normally distributed) was sufficient to produce a 5% force enhancement over isometric tension. Analysis of the model suggests that heterogeneity in half-sarcomeres leads to residual force enhancement by storing strain energy introduced during active stretch in distributions of bound cross-bridges. Complex interactions between the heterogeneous half-sarcomeres then dissipate this stored energy at a rate much slower than isolated cross-bridges would cycle. Given the variations in half-sarcomere length that have been observed in real muscle preparations and the stochastic variability inherent in all biological systems, half-sarcomere heterogeneity cannot be excluded as a contributing source of residual force enhancement.

UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy.

The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.

Automation and control of laser wakefield accelerators using Bayesian optimization.

Laser wakefield accelerators promise to revolutionize many areas of accelerator science. However, one of the greatest challenges to their widespread adoption is the difficulty in control and optimization of the accelerator outputs due to coupling between input parameters and the dynamic evolution of the accelerating structure. Here, we use machine learning techniques to automate a 100 MeV-scale accelerator, which optimized its outputs by simultaneously varying up to six parameters including the spectral and spatial phase of the laser and the plasma density and length. Most notably, the model built by the algorithm enabled optimization of the laser evolution that might otherwise have been missed in single-variable scans. Subtle tuning of the laser pulse shape caused an 80% increase in electron beam charge, despite the pulse length changing by just 1%.

Hypofractionated Radiotherapy in Oesophageal Cancer for Patients Unfit for Systemic Therapy: A Retrospective Single-Centre Analysis.

AIMS: Chemoradiotherapy (CRT) is established as a superior treatment option to definitive radiotherapy in the non-surgical management of oesophageal cancer. For patients precluded from CRT through choice or comorbidity there is little evidence to guide delivery of single-modality radiotherapy. In this study we outline outcomes for patients unfit for CRT who received a hypofractionated radiotherapy (HRT) regimen. MATERIALS AND METHODS: A retrospective UK single-centre analysis of 61 consecutive patients with lower- or middle-third adenocarcinoma (OAC; 61%) or squamous cell carcinoma of the oesophagus managed using HRT with radical intent between April 2009 and 2014. Treatment consisted of 50 Gy in 16 fractions (n = 49, 80.3%) or 50-52.5 Gy in 20 fractions (n = 12, 19.7%). Outcomes were referenced against a contemporaneous comparator cohort of 80 (54% OAC) consecutive patients managed with conventionally fractionated CRT within the same centre. RESULTS: Three-year and median overall survival were, respectively, 56.9% and 29 months with HRT compared with 55.5% and 26 months for CRT; adjusted hazard ratio 0.79 (95% confidence interval 0.48-1.28). Grade 3 and 4 toxicity rates were low at 16.4% (n = 10) for those receiving HRT and 40.2% (n = 32) for the CRT group. In patients with OAC, CRT delivered superior overall survival (hazard ratio 0.46; 95% confidence interval 0.25-0.85) and progression-free survival (hazard ratio 0.45; 95% confidence interval 0.23-0.88) when compared with HRT. CONCLUSIONS: The HRT regimen described here was safe and tolerable in patients unable to receive CRT, and delivered promising survival outcomes. The use of HRT for the treatment of oesophageal cancer, both alone and as a sequential or concurrent treatment with chemotherapy, requires further study. New precision radiotherapy technologies may provide additional scope for improving outcomes in oesophageal cancer using HRT-based approaches and should be evaluated.

The immune system--is it relevant to cancer development, progression and treatment?

The ability of the immune system to effectively respond to human tumours is a matter of long-term controversy. There is an increasing body of recent evidence to support a role for the immune system in eliminating pre-clinical cancers, an old concept termed 'immunosurveillance'. 'Immunoediting' is an updated hypothesis, in which selection pressures applied by the immune response to tumours modulate tumour immunogenicity and growth. Tumour infiltration by immune cells has been shown to have powerful prognostic significance in a host of cancer types. Paradoxically, in some circumstances the immune system can promote tumour development. Cytotoxic therapies, including radiotherapy and chemotherapy, induce potentially immunogenic cell death, releasing tumour-associated antigens in the context of a 'danger' signal to the immune system. An understanding of the interaction between immune cells, tumour cells and treatment modalities will therefore guide the future combination of immunotherapy with conventional therapy to achieve optimal anti-tumour effects.

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy.

Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different locations in the body. Members of all the trial management groups collaborated to generate a consensus document on appropriate organ at risk dose constraints. Values from existing but older reviews were updated using data from current studies. It is hoped that this unified approach will facilitate standardised implementation of SABR across the UK and will allow meaningful toxicity comparisons between SABR studies and internationally.

Superiority of Deformable Image Co-registration in the Integration of Diagnostic Positron Emission Tomography-Computed Tomography to the Radiotherapy Treatment Planning Pathway for Oesophageal Carcinoma.

AIMS: To investigate the use of image co-registration in incorporating diagnostic positron emission tomography-computed tomography (PET-CT) directly into the radiotherapy treatment planning pathway, and to describe the pattern of local recurrence relative to the PET-avid volume. MATERIALS AND METHODS: Fourteen patients were retrospectively identified, six of whom had local recurrence. The accuracy of deformable image registration (DIR) and rigid registration of the diagnostic PET-CT and recurrence CT, to the planning CT, were quantitatively assessed by comparing co-registration of oesophagus, trachea and aorta contours. DIR was used to examine the correlation between PET-avid volumes, dosimetry and site of recurrence. RESULTS: Positional metrics including the dice similarity coefficient (DSC) and conformity index (CI), showed DIR to be superior to rigid registration in the co-registration of diagnostic and recurrence imaging to the planning CT. For diagnostic PET-CT, DIR was superior to rigid registration in the transfer of oesophagus (DSC=0.75 versus 0.65, P<0.009 and CI=0.59 versus 0.48, P<0.003), trachea (DSC=0.88 versus 0.65, P<0.004 and CI=0.78 versus 0.51, P<0.0001) and aorta structures (DSC=0.93 versus 0.86, P<0.006 and CI=0.86 versus 0.76, P<0.006). For recurrence imaging, DIR was superior to rigid registration in the transfer of trachea (DSC=0.91 versus 0.66, P<0.03 and CI=0.83 versus 0.51, P<0.02) and oesophagus structures (DSC=0.74 versus 0.51, P<0.004 and CI=0.61 versus 0.37, P<0.006) with a non-significant trend for the aorta (DSC=0.91 versus 0.75, P<0.08 and CI=0.83 versus 0.63, P<0.06) structure. A mean inclusivity index of 0.93 (range 0.79-1) showed that the relapse volume was within the planning target volume (PTVPET-CT); all relapses occurred within the high dose region. CONCLUSION: DIR is superior to rigid registration in the co-registration of PET-CT and recurrence CT to the planning CT, and can be considered in the direct integration of PET-CT to the treatment planning process. Local recurrences occur within the PTVPET-CT, suggesting that this is a suitable target for dose-escalation strategies.

Radiation-induced cell death and dendritic cells: potential for cancer immunotherapy?

Dendritic cells are key orchestrators of the immune system. There is considerable interest in their use for treating cancer. Whether they initiate an effective cytotoxic response against antigen-bearing cells, or produce tolerance, depends on the context in which those antigens are presented. Ionising radiation, and the cell death it causes, has several properties that may facilitate such an effective response. A range of in-vitro and in-vivo data supports this, although potential problems exist that may require concurrent strategies.

Nucleic acid related compounds. 47. Synthesis and biological activities of pyrimidine and purine "acyclic" nucleoside analogues.

Various acyclic, i.e., (2-hydroxyethoxy)methyl and (2-acetoxyethoxy)methyl, analogues of pyrimidine and purine nucleosides have been prepared and evaluated for their antiviral, antimetabolic, and cytotoxic properties. All of the pyrimidine analogues, including (E)-5-(2-bromovinyl)-1-[(2-hydroxyethoxy)methyl]uracil (12) and its O-acetyl derivative (13), were virtually devoid of antiviral, cytotoxic, and antimetabolic activities. However, several of the 8-substituted derivatives of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) had higher antiviral specificity in vitro than the parent drug. The 8-methyl-, 8-amino-, 8-bromo-, and 8-iodoacyclovir derivatives have activities worthy of further investigation.

Ectopic pelvic spleen.

We are reporting the first, to our knowledge, ectopic pelvic spleen demonstrated preoperatively by means of a liver-spleen scan and a selective splenic arteriogram. Symptoms, consisting of crampy pain in the lower part of the abdomen exacerbated by standing or stooping, were relieved by splenectomy in this 19-year-old woman. Splenopexy, which has been advocated in the past, has no place in the management of this rare and interesting congenital variant. Laxity or failure of development of the phrenicosplenic and gastrosplenic ligaments is thought to account for the splenic descensus.

Role of liver scanning in the diagnosis of hepatic metastases.

Liver scanning is quite useful in detecting metastases, particularly when none are suspected clinically, and obviates the need for more elaborate and expensive examinations in about half the cases in the series analyzed here.

An analysis of the hypertension journals.

There are now at least nine medical journals which are exclusively related to the topic of hypertension, of which two started publication in 1992. We have conducted an analysis of the impact of these journals in the published body of medical research into hypertension as well as the reports published in 1993 by the hypertension management 'guidelines' committees in the UK, USA, New Zealand, Canada and the WHO. Finally an analysis was conducted of the contents of the four established hypertension journals (Hypertension, Journal of Hypertension, Journal of Human Hypertension and American Journal of Hypertension) in 1992 in relation to the country of origin of the papers and the topics covered. Only 19% of all the hypertension papers listed in Index Medicus in 1992 were from the four established journals and only 12.6% of papers quoted in the 'guidelines' reports were from these journals. Most papers, and particularly the important ones, tend to be published in the weekly or monthly general medical journals. In the contents of the four journals, Hypertension and Journal of Hypertension tended to take more papers devoted to basic science than the Journal of Human Hypertension and American Journal of Hypertension which favoured more clinically relevant papers. American papers tended to go to American journals while European and Japanese papers appeared in all journals, although the Japanese bias towards basic science meant that their contributions also appeared in the two basic science orientated journals.(ABSTRACT TRUNCATED AT 250 WORDS)

On-site field sampling and analysis of fragrance from living lavender (Lavandula angustifolia L.) flowers by solid-phase microextraction coupled to gas chromatography and ion-trap mass spectrometry.

Solid-phase microextraction coupled to gas chromatography and mass spectrometry has been applied as a simple alternative method for the analysis of essential oil directly from lavender intact flowering spikes and genuine oils. All recognised major oil constituents were detected by this procedure, with results comparable to those given by a conventional method (organic solvent extraction). Distinctive chromatographic profiles were found for various species.

Experimental crystal nephropathy (one year study in the pig).

An acute crystal nephropathy was produced in pigs by feeding a mixture of guanine and allopurinol. The pathogenesis of the lesion produced was studied by serial histology and renal function tests over 12 months. Tubular blockage by the crystals produced erosion of the basement membrane and an accompanying interstitial nephritis. Tubular degeneration around the crystal mass transferred the crystals to the interstitium. Despite rapid subsequent disappearance of these crystals the interstitial nephritis was still evident nine months later. An early return of renal function to near normal was not sustained beyond nine months. It was shown that even brief periods of intratubular crystal deposition caused irreversible changes, resulting eventually in a reduction in kidney size, nephron population and renal function.

Reproductive performance of ewe lambs from ewes from different selection practices with or without induced estrus.

Three groups of ewe lambs born in May (experiment 1; n=211) or April (experiment 2; n=174) were used to evaluate the effects of selection line and induction of estrus on pregnancy rate. Experiment 1 was a single factor experiment with induction of estrus as the main effect. In early December, May-born Targhee (n=82) and Rambouillet x Targhee (n=129) ewes were randomly assigned within body weight to one of two treatment groups: control or induction of estrus. Experiment 2 was designed in a 2x2 factorial array with the main effects of induction of estrus or selection line. In early November, April-born Targhee lambs (n=174) from two distinct selection lines were either treated as controls or received an estrus induction treatment. The two lines included an unselected control line of randomly bred ewes and a line that had been selected since 1976, based on the weight of lamb weaned. Ewes from each line were randomly assigned within body weight to one of the treatment groups. In experiments 1 and 2, estrus was induced using MAP pessaries. Pessaries were inserted for 12 days. At the time of pessary removal, ewe lambs received 400 IU eCG i.m. All ewe lambs were bred in multi-sire pens. Pregnancy rate and fetal numbers were determined either by lambing data or real-time ultrasound. Body weight, lambing date and fetal numbers were analyzed by GLM, and remaining variables were analyzed by CATMOD. For experiment 1, estrus induction increased (P<0.01) pregnancy rates (61 versus 31%) and number of fetuses estimated by real-time ultrasound (79 versus 35%) compared to control ewe lambs. Pregnancy rate and fetal number were increased (P<0.01) for the 1st year compared to the 2nd year. For experiment 2, estrus induction tended to increase (P<0.07) pregnancy rate, and pregnancy rate differed (P<0.01) between selection lines. Estrus induction increased (P<0.05) fetal numbers (0.96) compared to controls (0.77). Fetal numbers were greater (P<0.01) for the selected line (1.06) compared to random bred controls (0.67). Average date of lambing was earlier in both experiments for the estrus-induced ewe lambs compared to controls. These results indicate that induction of estrus can be recommended if increased reproduction is desired for ewe lambs.

Renal biopsy in the pig.

In the pig, needle renal biopsy proved a safe and simple procedure which caused little discomfort to the animal. It proved a valuable method for following serial changes in renal histology and can therefore be applied to the study of both spontaneous and experimental renal diseases in pigs.

Osteitis fibrosa cystica (brown tumor) in a patient with renal transplantation. Report of a case with aspiration cytodiagnosis.

The cytologic findings from fine needle aspiration of a left shoulder mass are described for a woman who had undergone renal transplantation and on whom an orthopedic consultation suggested the clinical possibility of a soft tissue sarcoma. The aspirate samples from multiple sites in the mass showed several multinucleate, osteoclast-type giant cells, spindly or fibrillary cells with ovoid nuclei and a significant amount of granular calcium. The needle aspiration cytodiagnosis was of critical importance since it saved the patient from invasive surgical intervention. This case emphasizes the role of needle aspiration cytology in providing a rapid cytodiagnosis of osteitis fibrosa cystica with a minimally invasive method.

Relationships among ewe milk production and ewe and lamb forage intake in Suffolk and Targhee ewes nursing single or twin lambs.

Suffolk and Targhee ewes (30 each) with single or twin lambs were used in four periods beginning in late gestation and continuing through weaning to evaluate breed differences in milk production, lamb BW, and DMI by ewes and lambs. In Periods 1 (late gestation) and 2 (early lactation), ewes (Period 1) and ewes with lambs (Period 2) were individually penned, fed .45 kg of barley x ewe(-1) x d(-1) and allowed ad libitum access to chopped alfalfa. Ewes and lambs grazed native range in Periods 3 and 4. Grazed forage DMI was estimated using chromic oxide. Estimates of milk production were obtained by handmilking. Average lamb age was 4, 45, and 73 d at the beginning of Periods 2, 3, and 4, respectively. Milk production tended (P = .20) to be greater for Suffolk than for Targhee ewes. Targhee ewes produced 85% more (P = .001) wool than Suffolk ewes. From 33 d prepartum to 89 d postpartum, Suffolk ewes consistently weighed more (P = .001) than Targhee ewes. Suffolk ewe BW loss (-.15 kg/d) was greater (P = .01) than Targhee ewe BW loss (-.02 kg/d) from 33 d prepartum to 6 d postpartum. From 6 to 89 d postpartum BW gain did not differ (P = .69; .05 kg/d) between breeds. From birth to 89 d postpartum, Suffolk lambs consistently weighed more than Targhee lambs (P = .003). From birth to 89 d postpartum, ADG was greater for Suffolk than for Targhee lambs (P = .006). Targhee ewes consumed 25% more (P = .01) feed over the course of the study than did Suffolk ewes. Grazed forage DMI by Targhee lambs was 26% greater (P = .01) than DMI by Suffolk lambs. When meat production is the primary income from sheep, one potential advantage of Suffolks compared with Targhees is more rapid gain with less feed intake.

The effects of different methods of estimating fecal output on plasma cortisol, fecal output, forage intake, and weight change in free-ranging and confined wethers.

Thirty-four white-face wethers (avg BW 56 kg) were used in two experiments to investigate differences in plasma cortisol, forage intake, fecal output, and BW change associated with two methods of estimating fecal output. The methods were fecal collection bags (B) and marker estimates of fecal output (U). A control treatment (C) was included in each experiment in which wethers were not bagged or dosed with the marker. Experiment 1 was conducted with wethers grazing dormant sagebrush-bunchgrass range. Experiment 2 was conducted with wethers housed in metabolism crates. In Exp. 1, the following differences were detected: 1) basal and mean integrated (following ACTH challenge) plasma cortisol levels were higher (P < .05) for U wethers than for C wethers, 2) no differences (P > .05) between B and C wethers were detected for basal or mean integrated plasma cortisol, 3) both B and U wethers gained (P < .05) weight, whereas C wethers lost weight, and 4) no differences (P > .05) between B and U wethers were detected for cortisol measurements, weight change, or fecal output. No differences (P > .05) were noted for any of the variables tested in Exp. 2. When treatments were combined within experiment to test Exp. 1 vs 2, time to peak cortisol levels was longer (P < .05) and mean integrated cortisol levels and weight change were lower (P < .05) for wethers in confinement than for wethers on range. No difference (P > .05) was detected for basal cortisol levels.(ABSTRACT TRUNCATED AT 250 WORDS)