The mutation R107Q alters mtSSB ssDNA compaction ability and binding dynamics.

Mitochondrial single-stranded DNA-binding protein (mtSSB) is essential for mitochondrial DNA (mtDNA) replication. Recently, several mtSSB variants have been associated with autosomal dominant mitochondrial optic atrophy and retinal dystrophy. Here, we have studied at the molecular level the functional consequences of one of the most severe mtSSB variants, R107Q. We first studied the oligomeric state of this variant and observed that the mtSSBR107Q mutant forms stable tetramers in vitro. On the other hand, we showed, using complementary single-molecule approaches, that mtSSBR107Q displays a lower intramolecular ssDNA compaction ability and a higher ssDNA dissociation rate than the WT protein. Real-time competition experiments for ssDNA-binding showed a marked advantage of mtSSBWT over mtSSBR107Q. Combined, these results show that the R107Q mutation significantly impaired the ssDNA-binding and compacting ability of mtSSB, likely by weakening mtSSB ssDNA wrapping efficiency. These features are in line with our molecular modeling of ssDNA on mtSSB showing that the R107Q mutation may destabilize local interactions and results in an electronegative spot that interrupts an ssDNA-interacting-electropositive patch, thus reducing the potential mtSSB-ssDNA interaction sites.

Positive psychology interventions in the United Arab Emirates: boosting wellbeing - and changing culture?

As the science of wellbeing has grown, universities have adopted the challenge of prioritizing the wellbeing of students. Positive psychology interventions (PPIs), activities designed to increase the frequency of positive emotions and experiences, which help to facilitate the use of actions and thoughts that lead to human flourishing, are being increasingly used worldwide. Known to boost wellbeing and a number of other variables, it nonetheless remains unknown whether their use can influence other variables in non-Western cultures. In this study, we determined the impact of PPIs on a variety of wellbeing outcomes. The 6-week PPI program was conducted in the United Arab Emirates on Emirati university students (n = 120) who reported more positive emotion and overall balance of feelings that favored positivity over time relative to a control group. Yet, there was no effect found on negative emotions, life satisfaction, perceived stress, fear of happiness, locus of control, or somatic symptoms, and no effect on levels of collectivism or individualism. Our findings nonetheless support the use of PPIs in higher education as they show an increase in the experience of positive emotion, with this in itself bringing positive life outcomes, and no negative impact on culture. Our findings serve to build a foundation for understanding for whom PPIs work best - and least - around the world.

The effects of positive psychology interventions in Arab countries: A systematic review.

While there is evidence for the effects of positive psychology interventions (PPIs) in the Western world, we know little about their effects on Arab cultures. This review aimed to assess the effects of PPIs on well-being and mental health across Arab countries. Systematic searches of randomised controlled trials (RCTs) and quasi-experimental studies investigating PPIs in Arabia were conducted in six English and Arabic databases from the inception of positive psychology in 1998 to 28 February 2022. The quality of the studies was assessed using the Cochrane risk-of-bias tools. The protocol was published in the BMJ Open. Forty-four studies from 10 Arab countries (n = 3598 participants) were included. Of these, 12 were RCTs and 32 were quasi-experimental. The studies mainly focused on adults (73%) and healthy populations (86%). PPIs included mindfulness, positive thinking, strengths, hope, optimism, self-compassion, positive traits, and multiple PPIs. Nearly all studies (91%) mentioned cultural adaptation; however, little detail was given. This is the first review in Arabia. PPIs appear to be effective for promoting well-being and reducing mental health issues. However, there were some risks of bias concerns. Future research should include younger and clinical populations, using larger samples and providing more details about adaptation.

Geographic, Socio-Demographic and School Type Variation in Adolescent Wellbeing and Mental Health and Links with Academic Competence in the United Arab Emirates.

Interest in adolescents' wellbeing and mental health is growing worldwide, but little research in this area has been conducted in certain world regions and countries such as the United Arab Emirates (UAE). Geographic, socio-demographic and school type differences in adolescent wellbeing and mental health are commonly observed in the field, and the UAE is a diverse country where these types of differences have been found for other outcomes (notably, academic). Yet, no prior national study has explored these differences in terms of wellbeing and mental health in the nation. We address this gap by investigating differences across emirates, gender, socio-economic status, immigrant status, school sector and school curriculum for overall life satisfaction, positive affect, negative affect, meaning and purpose in life, and internalizing difficulties. We use linear regression to analyse cross-sectional data from the Programme for International Student Assessment (PISA) study from 2015 and 2018. We find substantial geographic, socio-demographic and school type differences in levels (2018) of wellbeing and mental health -which vary across distinct domains- and declines (2015-2018) of wellbeing. Better wellbeing and mental health are observed in the northern emirates and among boys. Better wellbeing and poorer mental health are observed among nationals (compared to expatriates) and in public schools (compared to private schools). Despite presenting the best academic outcomes, British schools present the worst wellbeing and mental health outcomes. However, results show the absence of a trade-off between academic competence and wellbeing and mental health, with evidence of a small positive association with wellbeing.

An ecological approach to predict areas with established populations of Ixodes scapularis in Quebec, Canada.

Public health management of Lyme disease (LD) is a dynamic challenge in Canada. Climate warming is driving the northward expansion of suitable habitat for the tick vector, Ixodes scapularis. Information about tick population establishment is used to inform the risk of LD but is challenged by sampling biases from surveillance data. Misclassifying areas as having no established tick population underestimates the LD risk classification. We used a logistic regression model at the municipal level to predict the probability of I. scapularis population establishment based on passive tick surveillance data during the period of 2010-2017 in southern Quebec. We tested for the effect of abiotic and biotic factors hypothesized to influence tick biology and ecology. Additional variables controlled for sampling biases in the passive surveillance data. In our final selected model, tick population establishment was positively associated with annual cumulative degree-days > 0°C, precipitation and deer density, and negatively associated with coniferous and mixed forest types. Sampling biases from passive tick surveillance were controlled for using municipal population size and public health instructions on tick submissions. The model performed well as indicated by an area under the curve (AUC) of 0.92, sensitivity of 86% and specificity of 81%. Our model enables prediction of I. scapularis population establishment in areas which lack data from passive tick surveillance and may improve the sensitivity of LD risk categorization in these areas. A more sensitive system of LD risk classification is important for increasing awareness and use of protective measures employed against ticks, and decreasing the morbidity associated with LD.

Validation study of a wellbeing scale (SPANE) in the Arab Gulf region: A multicountry study.

The Scale of Positive and Negative Experience (SPANE) is an emerging wellbeing scale to measure the frequency of positive and negative emotions. This study explores the psychometric properties of SPANE on a sample from the Arab Gulf region. The Arab Gulf region shares cultural elements with the broader Muslim and Arab world, but maintains distinct features that warrants validation studies for psychological instruments. There were 1393 participants from Saudi Arabia, Oman, Kuwait and other Arab Gulf countries. The factorial structure of SPANE was examined using a principal axis factor analysis, followed up with a confirmatory factor analysis. The convergent validity was examined by correlating SPANE with the Satisfaction with Life Scale (SWLS). The findings confirmed a two-factor structure of SPANE, and demonstrated adequate psychometric properties and convergent validity. In conclusion, this study indicates that SPANE shows sufficient validity for use as a measure of wellbeing in the Arab Gulf region.

Upfront DPYD Genotyping and Toxicity Associated with Fluoropyrimidine-Based Concurrent Chemoradiotherapy for Oropharyngeal Carcinomas: A Work in Progress.

Background: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk DPYD polymorphisms. Methods: The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the implementation of upfront DPYD*2A genotyping. We aimed to determine the effect of DPYD genotyping on grade ≥3 toxicities. Results: 181 patients were analyzed (87 patients before and 94 patients following DPYD*2A screening). Of the patients, 91% (n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% (n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Extended genotyping of DPYD*2A-negative patients later allowed for the retrospective identification of six additional patients with alternative DPYD variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before DPYD*2A screening versus 62% following upfront genotyping (p = 0.18). When retrospectively analyzing additional non-DPYD*2A variants, the relative risks for mucositis (RR 2.36 [1.39-2.13], p = 0.0063), dysphagia (RR 2.89 [1.20-5.11], p = 0.019), and aspiration pneumonia (RR 13 [2.42-61.5)], p = 0.00065) were all significantly increased. Conclusion: The DPYD*2A, c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can identify patients in whom 5-FU-related toxicity should be avoided.

Foraging efficiency in temporally predictable environments: is a long-term temporal memory really advantageous?

Cognitive abilities enabling animals that feed on ephemeral but yearly renewable resources to infer when resources are available may have been favoured by natural selection, but the magnitude of the benefits brought by these abilities remains poorly known. Using computer simulations, we compared the efficiencies of three main types of foragers with different abilities to process temporal information, in spatially and/or temporally homogeneous or heterogeneous environments. One was endowed with a sampling memory, which stores recent experience about the availability of the different food types. The other two were endowed with a chronological or associative memory, which stores long-term temporal information about absolute times of these availabilities or delays between them, respectively. To determine the range of possible efficiencies, we also simulated a forager without temporal cognition but which simply targeted the closest and possibly empty food sources, and a perfectly prescient forager, able to know at any time which food source was effectively providing food. The sampling, associative and chronological foragers were far more efficient than the forager without temporal cognition in temporally predictable environments, and interestingly, their efficiencies increased with the level of temporal heterogeneity. The use of a long-term temporal memory results in a foraging efficiency up to 1.16 times better (chronological memory) or 1.14 times worse (associative memory) than the use of a simple sampling memory. Our results thus show that, for everyday foraging, a long-term temporal memory did not provide a clear benefit over a simple short-term memory that keeps track of the current resource availability. Long-term temporal memories may therefore have emerged in contexts where short-term temporal cognition is useless, i.e. when the anticipation of future environmental changes is strongly needed.

Individual-Level Memory Is Sufficient to Create Spatial Segregation among Neighboring Colonies of Central Place Foragers.

AbstractCentral place foragers often segregate in space, even without signs of direct agonistic interactions. Using parsimonious individual-based simulations, we show that for species with spatial cognitive abilities, individual-level memory of resource availability can be sufficient to cause spatial segregation in the foraging ranges of colonial animals. The shapes of the foraging distributions are governed by commuting costs, the emerging distribution of depleted resources, and the fidelity of foragers to their colonies. When colony fidelity is weak and foragers can easily switch to colonies located closer to favorable foraging grounds, this leads to space partitioning with equidistant borders between neighboring colonies. In contrast, when colony fidelity is strong-for example, because larger colonies provide safety in numbers or individuals are unable to leave-it can create a regional imbalance between resource requirements and resource availability. This leads to nontrivial space-use patterns that propagate through the landscape. Interestingly, while better spatial memory creates more defined boundaries between neighboring colonies, it can lower the average intake rate of the population, suggesting a potential trade-off between an individual's attempt for increased intake and population growth rates.

Effects of positive psychology interventions in Arab countries: a protocol for a systematic review.

INTRODUCTION: Despite the growing volume of published studies on the effects of positive psychology interventions (PPIs), little is known about their effectiveness outside of Western countries, particularly in Arab countries. As the effectiveness of PPIs in this region remains unclear, a systematic review focusing on this area of research can offer a valuable contribution. Here, we present a protocol for the first systematic review that aims to examine the effects of PPIs on increasing well-being, quality of life and resilience and decreasing depression, anxiety and stress for both health and clinical, child and adult populations in Arab countries. METHODS AND ANALYSIS: This protocol is carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. A systematic literature search for studies up to 30 April 2021 will be conducted in the following electronic databases: PsycINFO, PubMed, Scopus, ProQuest, Dar Al Mandumah and Al Manhal. Experimental/quasi-experimental quantitative studies evaluating the effects of PPIs on healthy and clinical participants of all ages in the 22 Arab countries will be included. Outcomes will include psychological effects of PPIs on dimensions related to well-being (eg, happiness), quality of life, resilience, depression, anxiety and stress. The risk of bias will be evaluated using the Cochrane risk-of-bias tool. A narrative synthesis with tables of study characteristics will be provided. A meta-analysis will be included if outcomes allow; in this instance, subgroups analysis will be conducted, depending on the data gathered, to examine differences in effect sizes based on age group, population type, duration of intervention and type of intervention. ETHICS AND DISSEMINATION: Ethical approval was not required for the performance of this systematic review. We intend to publish the study in a peer-reviewed journal and share the findings at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020198092.

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial.

BACKGROUND: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC. METHODS: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice. DISCUSSION: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.

Drivers of site fidelity in ungulates.

While the tendency to return to previously visited locations-termed 'site fidelity'-is common in animals, the cause of this behaviour is not well understood. One hypothesis is that site fidelity is shaped by an animal's environment, such that animals living in landscapes with predictable resources have stronger site fidelity. Site fidelity may also be conditional on the success of animals' recent visits to that location, and it may become stronger with age as the animal accumulates experience in their landscape. Finally, differences between species, such as the way memory shapes site attractiveness, may interact with environmental drivers to modulate the strength of site fidelity. We compared inter-year site fidelity in 669 individuals across eight ungulate species fitted with GPS collars and occupying a range of environmental conditions in North America and Africa. We used a distance-based index of site fidelity and tested hypothesized drivers of site fidelity using linear mixed effects models, while accounting for variation in annual range size. Mule deer Odocoileus hemionus and moose Alces alces exhibited relatively strong site fidelity, while wildebeest Connochaetes taurinus and barren-ground caribou Rangifer tarandus granti had relatively weak fidelity. Site fidelity was strongest in predictable landscapes where vegetative greening occurred at regular intervals over time (i.e. high temporal contingency). Species differed in their response to spatial heterogeneity in greenness (i.e. spatial constancy). Site fidelity varied seasonally in some species, but remained constant over time in others. Elk employed a 'win-stay, lose-switch' strategy, in which successful resource tracking in the springtime resulted in strong site fidelity the following spring. Site fidelity did not vary with age in any species tested. Our results provide support for the environmental hypothesis, particularly that regularity in vegetative phenology shapes the strength of site fidelity at the inter-annual scale. Large unexplained differences in site fidelity suggest that other factors, possibly species-specific differences in attraction to known sites, contribute to variation in the expression of this behaviour. Understanding drivers of variation in site fidelity across groups of organisms living in different environments provides important behavioural context for predicting how animals will respond to environmental change.

Quality of Life: A Prospective Randomized Trial of Palliative Volumetric Arc Therapy Versus 3-Dimensional Conventional Radiation Therapy.

PURPOSE: Volumetric arc therapy (VMAT) is a radiation therapy (RT) technique that spares normal tissues from high and intermediate RT doses but increases the volume of tissues receiving low doses of RT compared with 3-dimensional conformal RT (3DCRT). We hypothesized that palliative VMAT would reduce the detriment to patient quality of life (QOL) compared with palliative 3DCRT. METHODS AND MATERIALS: This phase 2 trial randomized patients to palliative RT using VMAT or 3DCRT to 1 painful site of metastatic disease in the trunk. Treating physicians could choose 8 Gy in 1 fraction or 20 Gy in 5 fractions to stratify randomization. The primary endpoint was the change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30) global health status QOL subscale at 1 week after RT. Repeated measures analysis of variance was used to assess the relationship of patient QOL over time with other factors. RESULTS: From July 2014 to November 2017, 37 patients who underwent 3DCRT and 32 patients who underwent VMAT were randomized into the study. Median overall survival was 9 months. Overall pain responses to RT were equivalent (P = .53) between the techniques. Patient compliance in returning QOL questionnaires was 94%, 81%, and 69% at baseline, 1 week after RT, and 1 month after RT, respectively. At 1 week after RT, change in global QOL was not significantly (P = .31) different between VMAT versus 3DCRT. At 4 weeks after RT, VMAT induced significantly (P = .049) less global QOL deterioration than 3DCRT did. Patients who underwent VMAT maintained better physical (P = .012), role (P = .041), and social (P = .025) functioning, but they reported more diarrhea symptoms (P = .017) than in the 3DCRT group. CONCLUSIONS: Palliative VMAT and 3DCRT did not differ in their ability to control pain; however, palliative VMAT induced fewer QOL detriments than 3DCRT did at 4 weeks after RT.

Phase II study of de-intensified intensity-modulated radiotherapy and concurrent carboplatin/5-fluorouracil in lateralized p16-associated oropharyngeal carcinoma.

PURPOSE: To assess cancer control and patient-reported outcomes (PROs) after de-intensified intensity-modulated radiotherapy (IMRT) in lateralized p16-associated oropharyngeal cancer (p16-OPC). METHODS: Lateralized p16-OPC treated with radiotherapy and concurrent Carboplatin/5-fluorouracil between 2011 and 2014 were enrolled. De-intensified IMRT consisted in elective neck dose of 43.2 Gy/24 fractions and omission of contralateral retropharyngeal/level IV nodes. PROs were assessed using the EORTC QLC-C30 and QLQ-HN35 scales. RESULTS: Twenty-nine patients were included. Median follow-up was 44 months. As per AJCC 7th Ed, 7%, 83% and 10% of patients had stage III, IVa and IVb. 5-year locoregional control and overall survival rates were 100% and 100%, respectively. Rates of acute were 52% and 35%, respectively. At 2 years post-treatment, 50% and 14% of patients had grade 1 xerostomia and dysgueusia, respectively. Most PROs scores returned to baseline within 8 months post-treatment. CONCLUSION: De-intensified IMRT was associated with excellent cancer outcomes, and rapid recovery of PROs in lateralized p16-OPC.

Mobility and its sensitivity to fitness differences determine consumer-resource distributions.

An animal's movement rate (mobility) and its ability to perceive fitness gradients (fitness sensitivity) determine how well it can exploit resources. Previous models have examined mobility and fitness sensitivity separately and found that mobility, modelled as random movement, prevents animals from staying in high-quality patches, leading to a departure from an ideal free distribution (IFD). However, empirical work shows that animals with higher mobility can more effectively collect environmental information and better sense patch quality, especially when the environment is frequently changed by human activities. Here, we model, for the first time, this positive correlation between mobility and fitness sensitivity and measure its consequences for the populations of a consumer and its resource. In the absence of consumer demography, mobility alone had no effect on system equilibria, but a positive correlation between mobility and fitness sensitivity could produce an IFD. In the presence of consumer demography, lower levels of mobility prevented the system from approaching an IFD due to the mixing of consumers between patches. However, when positively correlated with fitness sensitivity, high mobility led to an IFD. Our study demonstrates that the expected covariation of animal movement attributes can drive broadly theorized consumer-resource patterns across space and time and could underlie the role of consumers in driving spatial heterogeneity in resource abundance.

Do Women Have Equal Chances for an Academic Career in Radiation Oncology in Canada? A Comparison With Related Specialties.

PURPOSE: The progress of women in academic medicine appears to be curtailed. We evaluated gender differences in academia for residents in radiation oncology compared with 2 of its related specialties, radiology and medical oncology, across Canada. METHODS AND MATERIALS: We analyzed abstracts presented between 2013 and 2016 at the annual meetings of the Canadian Association of Radiation Oncologists and compared it to the corresponding data for the meetings of the Canadian Association of Radiologists and Canadian Association of Medical Oncology. We further evaluated gender composition of abstracts, presentations, and publications available on PubMed. Conversion rates according to gender and to medical specialties were assessed. Proportions were compared using Fisher exact test or the chi-squared test. RESULTS: Among the 198 presented abstracts, 103 (52%) were published. Radiation oncology had the highest publishing rate with 90% (oncology 56%, radiology 40%). The publication rate between the medical specialties was significantly different (P < .001).Fifty-seven percent of abstracts presented by women were published versus 48% of abstracts presented by men. Overall, there was no significant difference between genders in terms of subsequent conversions into a scientific publication within each specialty (P = .25-1.0).In radiation oncology, women presented 67% of abstracts and published 95% of their presented abstracts, and in medical oncology, 66% of abstracts were from women and 57% of the presented abstracts were published. Among the published abstracts, 83% had the same first author in the abstract and the publication. Among those who lost their first-authorship status, 59% were women. However, there was no statistically significant difference between specialties for loss of first-author status. CONCLUSIONS: We observed that from 2013 to 2016, women had the highest presentation and publication rate in radiation oncology. More prospective data are needed to monitor the progress of women in all specialties and their specific needs.

To Biopsy or Not to Biopsy?: A Matched Cohort Analysis of Early-Stage Lung Cancer Treated with Stereotactic Radiation with or Without Histologic Confirmation.

PURPOSE: For nonoperable stage I non-small cell lung cancer, stereotactic body radiation therapy (SBRT) has emerged as a standard treatment option. We aimed to compare the clinical outcomes of lung SBRT between patients with versus without pathologic cancer diagnosis. METHODS AND MATERIALS: We included patients treated by SBRT for a single pulmonary lesion between July 2009 and July 2017. Patients in the clinical diagnosis group had a positron emission tomography/computed tomography scan showing hypermetabolism, growth of the mass on sequential computed tomography, and were not eligible for biopsy, refused biopsy, or had an inconclusive biopsy. For each of those patients, a matched pair in the pathologic diagnosis group was identified by matching for patient, treatment, and tumoral characteristics. We performed a power calculation to estimate the sample size required to detect a difference arising from a 5% or 15% rate of benign processes in the group without pathology. RESULTS: A total of 924 lung SBRT treatments were performed among 878 patients from 2009 to 2017. Within this population, 131 patients were treated based on clinical findings. They were matched with 131 patients with a pathologic diagnosis who received treatment. At 3 years, no significant differences were observed in overall survival (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.7-2.1), local control (HR, 0.9; 95% CI, 0.4-2), or regional (HR, 0.5; 95% CI, 0.2-1.4) or distant recurrence (HR, 0.6; 95% CI, 0.3-1.1). CONCLUSIONS: In our population, we found no clinically significant difference in patterns of recurrence or survival after lung SBRT for patients who had received clinical versus pathological diagnoses. There was, however, a trend toward more distant recurrences in the pathologic diagnosis group. Our power calculation suggests that data from multiple institutions would be required to rule out a difference in outcomes due to 5% to 15% of clinically diagnosed cases being treated for benign processes.

Environmental Predictability as a Cause and Consequence of Animal Movement.

The impacts of environmental predictability on the ecology and evolution of animal movement have been the subject of vigorous speculation for several decades. Recently, the swell of new biologging technologies has further stimulated their investigation. This advancing research frontier, however, still lacks conceptual unification and has so far focused little on converse effects. Populations of moving animals have ubiquitous effects on processes such as nutrient cycling and seed dispersal and may therefore shape patterns of environmental predictability. Here, we synthesise the main strands of the literature on the feedbacks between environmental predictability and animal movement and discuss how they may react to anthropogenic disruption, leading to unexpected threats for wildlife and the environment.

Risk-adapted stereotactic ablative radiotherapy for central and ultra-central lung tumours.

BACKGROUND: SABR is a widely accepted treatment for early-stage lung cancer but there are safety concerns for central and ultra-central tumours. Herein we report our experience using risk-adapted fractionation (prescribed doses: 40-60 Gy in 3-8 fractions) with prioritization of dose to organs at risk. METHODS: Patient declining or unsuitable for surgery with primitive or recurrent lung cancer were included. Tumours inside a 2 cm area around proximal bronchial tree (PBT) were classified as central while tumours with PTV overlapping PBT, oesophagus, great vessels and pericardial pleura were classified as ultra-central. We assessed overall survival (OS), disease-free survival (DFS), local control (LC) and toxicities. RESULTS: From 2009 to 2016, 137 patients were treated (median age: 75 years), with 60 central and 77 ultra-central tumours. Median follow-up was 36 months. Median tumour size, GTV and PTV were 2.5 cm (0.9-7), 7.8 cm3 (0.7-94.2) and 30.6 cm3 (6.5-274.3), respectively. For the whole population, median OS and DFS were 46 months and 33 months. One- and 2-years LC rates were 95% and 81%. Median OS between central and ultra-central tumours was statistically different with 57 vs 37 months (HR 0.48, p = 0.017), but LC was not different among them. We observed 4 Grade 3 and 6 Grade 5 toxicities (no grade 4). CONCLUSIONS: SABR for central and ultra-central tumours is associated with good OS, DFS and LC rates, with 7.3% grade 3-5 toxicities. Central tumours had a better prognosis in our cohort.

Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials.

BACKGROUND: Radiation Therapy Oncology Group (RTOG)-0129 recursive partitioning analysis was the basis for risk-based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors' knowledge, the question of whether RTOG-0129 overall survival (OS) estimates for low-risk, intermediate-risk, and high-risk groups are similar in other data sets or applicable to progression-free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG-0129 risk groups persist at 5 years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups. METHODS: Prospective randomized clinical trials were analyzed retrospectively. RTOG-0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG-0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible. RESULTS: There was a total of 260 patients and 287 patients, respectively, from RTOG-0129 and RTOG-0522, with median follow-ups for surviving patients of 7.9 years (range, 1.7-9.9 years) and 4.7 years (range, 0.1-7.0 years), respectively. Previous OS differences in RTOG-0129 persisted at 5 years. In RTOG-0522, the 5-year OS rates for the low-risk, intermediate-risk, and high-risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5-year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG-0522 among a subgroup of patients considered to be at very good risk (p16-positive disease, smoking history of ≤10 pack-years, and classified with T1-T2 disease with ipsilateral lymph nodes measuring ≤6 cm or T3 disease without contralateral or >6 cm lymph nodes), the 5-year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group. CONCLUSIONS: RTOG-0129 risk groups persisted at 5 years and were reproducible in RTOG-0522. However, there was variability in the estimates. These data underscore the importance of long-term follow-up and appropriate patient selection in therapeutic deintensification trials.