'With great power comes great responsibility': An impetus for quality and safety in radiation oncology.

Strict quality control and vigilance at every step is essential to maintain rigour and ensure quality and safety in radiation oncology. The scientific knowledge and technological capabilities we possess give us enormous power to deliver specialised and complex treatments and improve health outcomes for our cancer patients. However, this requires development of whole system performance and its evaluation against established standards and benchmarks. It calls for organisational commitment and active participation of managers and clinical teams in quality improvement initiatives. In addition to medical physicists and radiation therapist, radiation oncologists, including trainees, must accept important leadership responsibilities to maintain a positive safety culture.

The changing radiation oncology landscape in New Zealand.

INTRODUCTION: This paper outlines the New Zealand (NZ) responses to the biennial facilities surveys of The Royal Australian and New Zealand College of Radiologists (RANZCR), Faculty of Radiation Oncology (FRO) from 2011 to 2019. METHODS: The facilities survey is conducted by the FRO Economics and Workforce Committee (FROEWC) and focuses on equipment, treatment activities and staffing. RESULTS: The number of facilities increased by two to 10, both in the private sector. The total number of linear accelerators (linacs) increased by four; one in public and three in private. The majority of linacs were over 8 years old (62.5%). Treatment courses have increased by 19% and fraction numbers by 13.7%. Courses per linac have remained relatively constant. There was growth in IMRT, orthovoltage, high dose rate brachytherapy and paediatric treatments. There was a slow increase in number of radiation oncologists and trainees. The number of radiation therapists was unchanged with a 20% increase in treatment courses per radiation therapist. Physicist numbers have increased but 61.4% of physicists are overseas-trained and vacancies persist. CONCLUSION: The survey results indicate a rapidly changing radiation oncology landscape in NZ between 2011 and 2019. The challenges of increases in cancer numbers, treatment courses and complexity of treatments and a need to focus on quality standards against a set of minimal increase in machine numbers, ageing machines, static or slowly increasing staffing numbers and heavy reliance on overseas staffing require a national review of radiation oncology services to ensure a sustainable future.

Correction: Widespread mortality of trembling aspen (Populus tremuloides) throughout interior Alaskan boreal forests resulting from a novel canker disease.

[This corrects the article DOI: 10.1371/journal.pone.0250078.].

Widespread mortality of trembling aspen (Populus tremuloides) throughout interior Alaskan boreal forests resulting from a novel canker disease.

Over the past several decades, growth declines and mortality of trembling aspen throughout western Canada and the United States have been linked to drought, often interacting with outbreaks of insects and fungal pathogens, resulting in a "sudden aspen decline" throughout much of aspen's range. In 2015, we noticed an aggressive fungal canker causing widespread mortality of aspen throughout interior Alaska and initiated a study to quantify potential drivers for the incidence, virulence, and distribution of the disease. Stand-level infection rates among 88 study sites distributed across 6 Alaska ecoregions ranged from <1 to 69%, with the proportion of trees with canker that were dead averaging 70% across all sites. The disease is most prevalent north of the Alaska Range within the Tanana Kuskokwim ecoregion. Modeling canker probability as a function of ecoregion, stand structure, landscape position, and climate revealed that smaller-diameter trees in older stands with greater aspen basal area have the highest canker incidence and mortality, while younger trees in younger stands appear virtually immune to the disease. Sites with higher summer vapor pressure deficits had significantly higher levels of canker infection and mortality. We believe the combined effects of this novel fungal canker pathogen, drought, and the persistent aspen leaf miner outbreak are triggering feedbacks between carbon starvation and hydraulic failure that are ultimately driving widespread mortality. Warmer early-season temperatures and prolonged late summer drought are leading to larger and more severe wildfires throughout interior Alaska that are favoring a shift from black spruce to forests dominated by Alaska paper birch and aspen. Widespread aspen mortality fostered by this rapidly spreading pathogen has significant implications for successional dynamics, ecosystem function, and feedbacks to disturbance regimes, particularly on sites too dry for Alaska paper birch.

Adjuvant external beam radiotherapy after therapeutic groin lymphadenectomy for patients with melanoma: a dosimetric comparison of three-dimensional conformal and intensity-modulated radiotherapy techniques.

Radiotherapy after lymph node dissection is recommended in high-risk melanoma cases. The aim of this study is to assess whether intensity-modulated radiotherapy (IMRT) offers advantages over three-dimensional conformal radiotherapy (3DCRT) in the groin nodal basin. Fifteen consecutively treated patients (5 3DCRT and 10 IMRT) were selected. Optimized theoretical plans using the other modality were created - enabling direct comparisons of 3DCRT and IMRT. Target volume and organs at risk constraints were assessed as achieved or as having minor (≤5%) or major (>5%) deviations. The Wilcoxon signed-rank test was used to compare the dose received from each patient plan (3DCRT vs. IMRT), whereas the Mann-Whitney U-test was used to compare clinical plans with theoretical plans. Fisher's exact test was used to compare categorical data. Target coverage was achievable in most patients (major deviations - 1 IMRT and 3 3DCRT). Conformity index improved with IMRT - median 0.65, range 0.48-0.81, versus median 0.44, range 0.29-0.60 for 3DCRT; P value less than 0.001. All 3DCRT plans had major deviations for femoral head/neck constraints. Twelve and 13 IMRT plans achieved the high (V42<5%) and low (V36<35%) constraints; P value less than 0.001. IMRT delivered statistically significant lower doses to small bowel volumes up to 40 ml. There were no differences in beam numbers used nor dosimetric endpoints measured when clinical plans were compared with theoretical plans. IMRT appears to allow superior conformity of dose to the target volume while relatively sparing the adjacent the bowel and femoral head/neck. This may reduce toxicity while maintaining control rates.

Recommendations of generic names in Diaporthales competing for protection or use.

In advancing to one name for fungi, this paper treats generic names competing for use in the order Diaporthales (Ascomycota, Sordariomycetes) and makes a recommendation for the use or protection of one generic name among synonymous names that may be either sexually or asexually typified. A table is presented that summarizes these recommendations. Among the genera most commonly encountered in this order, Cytospora is recommended over Valsa and Diaporthe over Phomopsis. New combinations are introduced for the oldest epithet of important species in the recommended genus. These include Amphiporthe tiliae, Coryneum lanciforme, Cytospora brevispora, C. ceratosperma, C. cinereostroma, C. eugeniae, C. fallax, C. myrtagena, Diaporthe amaranthophila, D. annonacearum, D. bougainvilleicola, D. caricae-papayae, D. cocoina, D. cucurbitae, D. juniperivora, D. leptostromiformis, D. pterophila, D. theae, D. vitimegaspora, Mastigosporella georgiana, Pilidiella angustispora, P. calamicola, P. pseudogranati, P. stromatica, and P. terminaliae.

Outcomes after primary chemoradiotherapy for N3 (>6 cm) head and neck squamous cell carcinoma after an FDG-PET--guided neck management policy.

BACKGROUND: The purpose of this study was to assess whether a positron emission tomography (PET)-directed policy remains appropriate for managing neck nodes (N3; >6 cm) in head and neck squamous cell carcinoma (HNSCC). METHODS: All patients with N3 (>6 cm) HNSCC treated with definitive chemoradiotherapy (CRT) at our institution between 2005 and 2012 were included in the analysis. Patients underwent PET assessment before and 12 weeks after CRT. Neck dissections were performed for PET-avid residual nodal abnormalities after complete response at the primary site. Rate of isolated nodal failure (INF) was the primary outcome. RESULTS: Median follow-up from diagnosis for 33 patients was 30 months (range, 6-76 months). INF occurred in 2 patients (6%) with neck dissections performed in 4 cases (12%). First failure was predominantly distant metastatic (10; 30%). CONCLUSION: The rate of INF remains low when following a PET-directed neck management policy after definitive CRT for N3 (>6 cm) HNSCC.

Does fluorodeoxyglucose PET add to the management of the neck following curative radiotherapy in head and neck cancer compared with computed tomography?

In recent times, metabolic response to chemoradiotherapy has become possible due to the clinical application of 18F-fluorodeoxyglucose PET. Its utility in the initial staging of head and neck cancer is becoming widely accepted, however, its role in the post-therapy management of the neck following chemoradiotherapy in node-positive head and neck cancer remains unresolved. This article examines the role of PET in the restaging of patients who achieve a complete response at the primary site following radiotherapy. In particular, the authors examine its potential use in the assessment of post-therapy residual nodes and its role in sparing patients from an unnecessary neck dissection in order to minimize treatment-related morbidity.

Objective and subjective changes in voice quality after radiotherapy for early (T1 or T2, N0) laryngeal cancer: a pilot prospective cohort study.

BACKGROUND: Limited data exist on long-term voice quality after treatment for early laryngeal cancer. We report on the feasibility of establishing a dedicated service to assess changes after radiotherapy. METHODS: From June 1999 to December 2005, all patients referred for radical radiotherapy for early laryngeal cancers were invited to join a prospective cohort study. Subjective and objective voice quality tests were performed before and after treatment and at 3, 6, 12, and 24 months after treatment. RESULTS: Twenty-seven patients were screened for the study. Sufficient data were available for 15 (56%) patients. Both subjective and objective assessments improved significantly. CONCLUSIONS: This pilot study shows that it is possible to collect prospective voice quality data. There are both subjective and objective improvements in voice that persist to at least 2 years after radiotherapy. We propose the use of the methods described here to study voice outcomes in a lager cohort of patients treated with both surgery and radiotherapy.

Strong genetic differentiation between North American and European populations of Phytophthora alni subsp. uniformis.

Alder decline caused by Phytophthora alni has been one of the most important diseases of natural ecosystems in Europe during the last 20 years. The emergence of P. alni subsp. alni -the pathogen responsible for the epidemic-is linked to an interspecific hybridization event between two parental species: P. alni subsp. multiformis and P. alni subsp. uniformis. One of the parental species, P. alni subsp. uniformis, has been isolated in several European countries and, recently, in North America. The objective of this work was to assess the level of genetic diversity, the population genetic structure, and the putative reproduction mode and mating system of P. alni subsp. uniformis. Five new polymorphic microsatellite markers were used to contrast both geographical populations. The study comprised 71 isolates of P. alni subsp. uniformis collected from eight European countries and 10 locations in North America. Our results revealed strong differences between continental populations (Fst = 0.88; Rst = 0.74), with no evidence for gene flow. European isolates showed extremely low genetic diversity compared with the North American collection. Selfing appears to be the predominant mating system in both continental collections. The results suggest that the European P. alni subsp. uniformis population is most likely alien and derives from the introduction of a few individuals, whereas the North American population probably is an indigenous population.

Enhanced intrinsic radiosensitivity after treatment with stereotactic radiosurgery for an acoustic neuroma.

Enhanced radiosensitivity is an uncommon phenomenon attributable to deficient DNA repair after radiotherapy which can be assessed with the γ-H2AX assay. Reports of radiosensitivity after stereotactic radiosurgery (SRS) are uncommon. We describe a case where the clinical, radiological and laboratory findings suggest enhanced radiosensitivity after SRS for an acoustic neuroma.

PET in Decision Making for Neck Dissection After Radiation Treatment.

This article summarizes the controversies around surgical management of the neck following definitive chemoradiation. It explains how policies have evolved and how changes in the biology of the disease, effectiveness of treatment, and the assessment of results have contributed to this. The focus of the article is on the use of positron emission tomography (PET) in deciding the appropriate management of the neck following treatment. It summarizes available evidence on the clinical usefulness and cost-effectiveness of PET compared with other available strategies.

Heterokaryotic nuclear conditions and a heterogeneous nuclear population are observed by flow cytometry in Phytophthora infestans.

A simple and reliable method for preparation of whole nuclei of a common oomycete, Phytophthora infestans, is described for laser flow cytometry. The ease of preparation, the absence of detectable debris and aggregates, and the precision in determinations of DNA content per nucleus improve interpretation and understanding of the genetics of the organism. Phytophthora infestans is the pathogen that causes potato and tomato late blight. The genetic flexibility of P. infestans and other oomycete pathogens has complicated understanding of the mechanisms of variation contributing to shifts in race structure and virulence profiles on important agricultural crops. Significant phenotypic and genotypic changes are being reported in the apparent absence of sexual recombination in the field. Laser flow cytometry with propidium iodide is useful in investigating the nuclear condition of the somatic colony of field strains of P. infestans. The majority of the studied strains contain a single population of nuclei in nonreplicated diplophase. However, mean DNA content per nucleus varies considerably among isolates confirming the heterogeneity of the nuclear population in regard to C-value, for field isolates. Nuclear DNA content varies from 1.75x to 0.75x that of nuclei in a standard strain from central Mexico. Some strains contain two to three populations of nuclei with differing DNA contents in the mycelium and are heterokaryons. Such a range in DNA content suggests DNA-aneuploidy, but direct confirmation of aneuploidy will require microscopy of chromosomes. Heterokaryosis and populations of nuclei of differing DNA content necessarily confound standardized assays used worldwide in crop breeding programs for determination of race profiles and virulence phenotypes of this important pathogen.

Isotopologue fractionation during N(2)O production by fungal denitrification.

Identifying the importance of fungi to nitrous oxide (N2O) production requires a non-intrusive method for differentiating between fungal and bacterial N2O production such as natural abundance stable isotopes. We compare the isotopologue composition of N2O produced during nitrite reduction by the fungal denitrifiers Fusarium oxysporum and Cylindrocarpon tonkinense with published data for N2O production during bacterial nitrification and denitrification. The fractionation factors for bulk nitrogen isotope values for fungal denitrification were in the range -74.7 to -6.6 per thousand. There was an inverse relationship between the absolute value of the fractionation factors and the reaction rate constant. We interpret this in terms of variation in the relative importance of the rate constants for diffusion and enzymatic reduction in controlling the net isotope effect for N2O production during fungal denitrification. Over the course of nitrite reduction, the delta(18)O values for N2O remained constant and did not exhibit a relationship with the concentration characteristic of an isotope effect. This probably reflects isotopic exchange with water. Similar to the delta(18)O data, the site preference (SP; the difference in delta(15)N between the central and outer N atoms in N2O) was unrelated to concentration during nitrite reduction and, therefore, has the potential to act as a conservative tracer of production from fungal denitrification. The SP values of N2O produced by F. oxysporum and C. tonkinense were 37.1 +/- 2.5 per thousand and 36.9 +/- 2.8 per thousand, respectively. These SP values are similar to those obtained in pure culture studies of bacterial nitrification but quite distinct from SP values for bacterial denitrification. The large magnitude of the bulk nitrogen isotope fractionation and the delta(18)O values associated with fungal denitrification are distinct from bacterial production pathways; thus multiple isotopologue data holds much promise for resolving bacterial and fungal production. Our work further provides insight into the role that fungal and bacterial nitric oxide reductases have in determining site preference during N2O production.

Fulminating fungal sinusitis caused by Valsa sordida, a plant pathogen, in a patient immunocompromised by acute myeloid leukemia.

We describe a case in which a patient immunocompromised by acute myeloid leukemia experienced acute fulminating invasive fungal sinusitis followed by pneumonia and then death. Though the microbiology of the pneumonia could not be directly investigated, nasal lesions revealed fungal mycelium. Valsa sordida was consistently cultured from a biopsied sample. The fungus was identified to the genus level based on morphology in culture and DNA sequence homology, and then was placed at species level by means of phylogenetic analysis of the nuclear ribosomal internal transcribed spacer region. The fungus is in the order Diaporthales, family Valsaceae in the Ascomycota and is distributed worldwide as a pathogen of trees in the genera Populus and Salix. Koch's postulates were demonstrated to apply in a neutropenic rat model. The fungus was susceptible to antifungals with MIC-0 scores of 0.0313 microg/ml for amphotericin B, 0.25 microg/ml for voriconazole, 0.0313 microg/ml for caspofungin, and MIC-2 of 16 microg/ml for fluconazole. This is the first substantiated report of an isolate in the genus Valsa (anamorph Cytospora) being identified in human disease.

Taxonomy and toxicity of Conocybe lactea and related species.

Conocybe lactea was examined as part of a larger study on the distribution of amatoxins and phallotoxins in fungi, and the taxonomic relationships between these fungi. As amatoxins are present in the congener C. filaris, the locally abundant C. lactea was examined using HPLC and mass spectroscopy. Amatoxins were not found in C. lactea, but the related phallotoxins were present in small quantities making it the first fungus outside of the genus Amanita in which phallotoxins have been detected. Despite the presence of a related toxin, C. lactea was found not to be taxonomically close to C. filaris. Phylogenetic analyses using nuclear ribosomal RNA genes indicated that North American specimens of C. lactea were conspecific with North American specimens of C. crispa in Conocybe sect. Candidae. European C. crispa was a distinct taxon. The implications of the use of the name C. albipes for these taxa are discussed. Nucleotide data confirmed placement of the sequestrate taxon Gastrocybe lateritia in sect. Candidae, but as a distinct taxon. It is hypothesized that the unique sequestrate morphology of G. lateritia may be caused by a bacterial infection.

Ribosomal DNA sequence divergence and group I introns within the Leucostoma species L. cinctum, L. persoonii, and L. parapersoonii sp. nov., ascomycetes that cause Cytospora canker of fruit trees.

Leucostoma species that are the causal agents of Cytospora canker of stone and pome fruit trees were studied in detail. DNA sequence of the internal transcribed spacer regions and the 5.8S of the nuclear ribosomal DNA operon (ITS rDNA) supplied sufficient characters to assess the phylogenetic relationships among species of Leucostoma, Valsa, Valsella, and related anamorphs in Cytospora. Parsimony analysis of the aligned sequence divided Cytospora isolates from fruit trees into clades that generally agreed with the morphological species concepts, and with some of the phenetic groupings (PG 1-6) identified previously by isozyme analysis and cultural characteristics. Phylogenetic analysis inferred that isolates of L. persoonii formed two well-resolved clades distinct from isolates of L. cinctum. Phylogenetic analysis of the ITS rDNA, isozyme analysis, and cultural characteristics supported the inference that L. persoonii groups PG 2 and PG 3 were populations of a new species apparently more genetically different from L. persoonii PG 1 than from isolates representative of L. massariana, L. niveum, L. translucens, and Valsella melastoma. The new species, L. parapersoonii, was described. A diverse collection of isolates of L. cinctum, L. persoonii, and L. parapersoonii were examined for genetic variation using restriction fragment length polymorphism (RFLP) analysis of the ITS rDNA and the five prime end of the large subunit of the rDNA (LSU rDNA). HinfI and HpaII endonucleases were each useful in dividing the Leucostoma isolates into RFLP profiles corresponding to the isozyme phenetic groups, PG 1-6. RFLP analysis was more effective than isozyme analysis in uncovering variation among isolates of L. persoonii PG 1, but less effective within L. cinctum populations. Isolates representative of seven of the L. persoonii formae speciales proposed by G. Défago in 1935 were found to be genetically diverse isolates of PG 1. Two large insertions, 415 and 309 nucleotides long, in the small subunit (SSU) of the nuclear rDNA of L. cinctum were identified as Group 1 introns; intron 1 at position 943 and intron 2 at position 1199. The two introns were found to be consistently present in isolates of L. cinctum PG 4 and PG 5 and absent from L. cinctum PG 6 isolates, despite the similarity of the ITS sequence and teleomorph morphology. Intron 1 was of subgroup 1C1 whereas intron 2 was of an unknown subgroup. RFLP patterns and presence/absence of introns were useful characters for expediting the identification of cultures of Leucostoma isolated from stone and pome fruit cankers. RFLP patterns from 13 endonucleases provided an effective method for selecting an array of diverse PG 1 isolates useful in screening plant germplasm for disease-resistance.

Shoot dieback during prolonged drought in Ceanothus (Rhamnaceae) chaparral of California: a possible case of hydraulic failure.

Progressive diebacks of outer canopy branchlets of Ceanothus crassifolius were repeatedly observed after rainless periods up to 9 mo in duration in the Santa Monica Mountains of southern California. Mean xylem pressures of branchlets near the end of drought were as low as -11.2 MPa (N = 22) with a mean of about 60 dead branchlets per shrub. Inoculation (N = 15) with three species of fungi previously isolated from the same population of C. crassifolius did not promote dieback, suggesting that the observed decline was not fungal induced, as had been proposed. Further, at least 50% of healthy-appearing twigs, without symptoms of dieback, contained isolatible endophytic fungi. We used a centrifugal force method to determine the range of xylem pressure causing cavitation (vulnerability curves) for branchlets (N = 12) and roots (N = 16). We combined vulnerability curves with soil texture data (N = 6) into a water transport model that estimated the critical values (P(Lcrit)) of leaf xylem pressure associated with the loss of water from soil to foliage. Maximum P(Lcrit) was between -10 and -11 MPa and within the range of minimum measured xylem pressures of branchlets during drought and dieback. Branchlet dieback correlated with seasonal declines in xylem pressure in concert with declining safety margins from hydraulic failure. Symptoms of dieback were duplicated in the field by partially severing stem xylem that normally supplied branchlets with water. Taken together, these results indicate that loss of hydraulic conductance to foliage was the probable cause of the observed dieback in C. crassifolius. Partial dieback of peripheral branchlets, and its attendant reduction in evaporative surface area, may be a last-resort mechanism for whole-plant water conservation and drought survival in this species.