Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia.

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In vivo dose delivery verification in proton therapy can be performed by positron emission tomography (PET) of the positron-emitting nuclei produced by the proton beam in the patient. A PET scanner installed in the treatment position of a proton therapy facility that takes data with the beam on will see very short-lived nuclides as well as longer-lived nuclides. The most important short-lived nuclide for proton therapy is N (Dendooven et al 2015 Phys. Med. Biol. 60 8923-47), which has a half-life of 11 ms. The results of a proof-of-principle experiment of beam-on PET imaging of short-livedN nuclei are presented. The Philips Digital Photon Counting Module TEK PET system was used, which is based on LYSO scintillators mounted on digital SiPM photosensors. A 90 MeV proton beam from the cyclotron at KVI-CART was used to investigate the energy and time spectra of PET coincidences during beam-on. Events coinciding with proton bunches, such as prompt gamma rays, were removed from the data via an anti-coincidence filter with the cyclotron RF. The resulting energy spectrum allowed good identification of the 511 keV PET counts during beam-on. A method was developed to subtract the long-lived background from the N image by introducing a beam-off period into the cyclotron beam time structure. We measured 2D images and 1D profiles of theN distribution. A range shift of 5 mm was measured as 6  ±  3 mm using the N profile. A larger, more efficient, PET system with a higher data throughput capability will allow beam-onN PET imaging of single spots in the distal layer of an irradiation with an increased signal-to-background ratio and thus better accuracy. A simulation shows that a large dual panel scanner, which images a single spot directly after it is delivered, can measure a 5 mm range shift with millimeter accuracy: 5.5  ±  1.1 mm for 1  ×  10 protons and 5.2  ±  0.5 mm for 5  ×  10 protons. This makes fast and accurate feedback on the dose delivery during treatment possible.

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Captopril improves cardiopulmonary morphology and function by reducing acute cardiac damage, a risk factor in the development of radiation-induced cardiopulmonary toxicity. ACE inhibition should be evaluated as a strategy to reduce cardiopulmonary complications induced by radiotherapy to the thoracic area.

Summary1 Invasive annual grasses introduced by European settlers have largely displaced native grassland vegetation in California and now form dense stands that constrain the establishment of native perennial bunchgrass seedlings. Bunchgrass seedlings face additional pressures from both livestock grazing and barley and cereal yellow dwarf viruses (B/CYDVs), which infect both young and established grasses throughout the state. 2 Previous work suggested that B/CYDVs could mediate apparent competition between invasive exotic grasses and native bunchgrasses in California. 3 To investigate the potential significance of virus-mediated mortality for early survivorship of bunchgrass seedlings, we compared the separate and combined effects of virus infection, competition and simulated grazing in a field experiment. We infected two species of young bunchgrasses that show different sensitivity to B/CYDV infection, subjected them to competition with three different densities of exotic annuals crossed with two clipping treatments, and monitored their growth and first-year survivorship. 4 Although virus infection alone did not reduce first-year survivorship, it halved the survivorship of bunchgrasses competing with exotics. Within an environment in which competition strongly reduces seedling survivorship (as in natural grasslands), virus infection therefore has the power to cause additional seedling mortality and alter patterns of establishment.5 Surprisingly, clipping did not reduce bunchgrass survivorship further, but rather doubled it and disproportionately increased survivorship of infected bunchgrasses. 6 Together with previous work, these findings show that B/CYDVs can be potentially powerful elements influencing species interactions in natural grasslands. 7 More generally, our findings demonstrate the potential significance of multitrophic interactions in virus ecology. Although sometimes treated collectively as plant 'predators', viruses and herbivores may exert influences that are distinctly different, even counteracting.

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