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.

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.

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.

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.

Phase I/II trial of Durvalumab plus Tremelimumab and stereotactic body radiotherapy for metastatic head and neck carcinoma.

BACKGROUND: The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway has previously been demonstrated in metastatic head and neck squamous cell carcinoma (HNSCC). Stereotactic Body Radiotherapy (SBRT) aims at ablating metastatic lesions and may play a synergistic role with immunotherapy. The purpose of this study is to assess the safety and efficacy of triple treatment combination (TTC) consisting of the administration of durvalumab and tremelimumab in combination with SBRT in metastatic HNSCC. METHOD: This is a phase I/II single arm study that will include 35 patients with 2-10 extracranial metastatic lesions. Patients will receive durvalumab (1500 mg IV every 4 weeks (Q4W)) and tremelimumab (75 mg IV Q4W for a total of 4 doses) until progression, unacceptable toxicity or patient withdrawal. SBRT to 2-5 metastases will be administered between cycles 2 and 3 of immunotherapy. The safety of the treatment combination will be evaluated through assessment of TTC-related toxicities, defined as grade 3-5 toxicities based on Common Terminology Criteria for Adverse Events (v 4.03), occurring within 6 weeks from SBRT start, and that are definitely, probably or possibly related to the combination of all treatments. We hypothesize that dual targeting of PD-L1 and CTLA-4 pathways combined with SBRT will lead to < 35% grade 3-5 acute toxicities related to TTC. Progression free survival (PFS) will be the primary endpoint of the phase II portion of this study and will be assessed with radiological exams every 8 weeks using the RECIST version 1.1 criteria. DISCUSSION: The combination of synergistic dual checkpoints inhibition along with ablative radiation may significantly potentiate the local and systemic disease control. This study constitutes the first clinical trial combining effects of SBRT with dual checkpoint blockade with durvalumab and tremelimumab in the treatment of metastatic HNSCC. If positive, this study would lead to a phase III trial testing this treatment combination against standard of care in metastatic HNSCC. TRIAL REGISTRATION: NCT03283605 . Registration date: September 14, 2017; version 1.

Habitat-dependent movement rate can determine the efficacy of marine protected areas.

Theoretical studies of marine protected areas (MPAs) suggest that more mobile species should exhibit reduced local effects (defined as the ratio of the density inside vs. outside of the MPA). However, empirical studies have not supported the expected negative relationship between the local effect and mobility. We propose that differential, habitat-dependent movement (i.e., a higher movement rate in the fishing grounds than in the MPA) might explain the disparity between theoretical expectations and empirical results. We evaluate this hypothesis by building two-patch box and stepping-stone models and show that increasing disparity in the habitat-specific movement rates shifts the relationship between the local effect and mobility from negative (the previous theoretical results) to neutral or positive (the empirical pattern). This shift from negative to positive occurs when differential movement offsets recruitment and mortality differences between the two habitats. Thus, local effects of MPAs might be caused by behavioral responses via differential movement rather than by, or in addition to, reductions in mortality. In addition, the benefits of MPAs, in terms of regional abundance and fishing yields, can be altered by the magnitude of differential movement. Thus, our study points to a need for empirical investigations that disentangle the interactions among mobility, differential movement, and protection.

Pre-irradiation dental care: Ready-to-use templates for oropharyngeal cancers.

AIM: To develop a tool in order to guide pre-irradiation dental care (PIDC) for patients with oropharyngeal cancers. BACKGROUND: Osteoradionecrosis of the jaws is a potential complication of radiotherapy (RT) for head and neck cancers. To prevent this complication, PIDC can involve multiple dental extractions as a preventative measure to avoid post-RT complications. However, there is no standardized tool to guide PIDC. MATERIALS AND METHODS: From January 2005 to October 2015, 120 head and neck cancer patients were prospectively included in a study investigating dysgeusia after RT. From this cohort, patients were enrolled according to the following inclusion criteria: histopathological confirmation of oropharyngeal squamous cell carcinoma; stage T1-4 N1-3 M0; ≤10 missing teeth. Individual teeth were retrospectively delineated on planning computed tomography and doses to dentition were assessed to generate templates. RESULTS: Thirty-three patients were included. Molars received highest doses with a mean dose of 50 Gy (range; 19-75 Gy). Ipsi-lateral and contralateral wisdom teeth received RT dose superior to 50 Gy in 92% and 56% of cases, respectively. Patients with advanced disease (T4 or N2c-3) received higher mean doses on inferior and ipsi-lateral dental arches compared to other patients (T1-3 N0-2b): 42 Gy vs. 39 Gy and 44 Gy vs. 39 Gy (p < 0.05), respectively. CONCLUSION: Pre-RT dose distribution templates are an objective way to prepare PIDC. Further studies with a larger cohort are needed to validate these templates.

Spatial memory shapes density dependence in population dynamics.

Most population dynamics studies assume that individuals use space uniformly, and thus mix well spatially. In numerous species, however, individuals do not move randomly, but use spatial memory to visit renewable resource patches repeatedly. To understand the extent to which memory-based foraging movement may affect density-dependent population dynamics through its impact on competition, we developed a spatially explicit, individual-based movement model where reproduction and death are functions of foraging efficiency. We compared the dynamics of populations of with- and without-memory individuals. We showed that memory-based movement leads to a higher population size at equilibrium, to a higher depletion of the environment, to a marked discrepancy between the global (i.e. measured at the population level) and local (i.e. measured at the individual level) intensities of competition, and to a nonlinear density dependence. These results call for a deeper investigation of the impact of individual movement strategies and cognitive abilities on population dynamics.

How memory-based movement leads to nonterritorial spatial segregation.

Home ranges (HRs) are a remarkably common form of animal space use, but we still lack an integrated view of the individual-level processes that can lead to their emergence and maintenance, particularly when individuals are in competition for resources. We built a spatially explicit mechanistic movement model to investigate how simple memory-based foraging rules may enable animals to establish HRs and to what extent this increases their foraging efficiency compared to individuals that do not base foraging decisions on memory. We showed that these simple rules enable individuals to perform better than individuals using the most efficient strategy that does not rely on memory and drive them to spatially segregate through avoidance of resource patches used by others. This striking result questions the common assumption that low HR overlaps are indicators of territorial behavior. Indeed, it appears that, by using an information-updating system, individuals can keep their environment relatively predictable without paying the cost of defending an exclusive space. However, memory-based foraging strategies leading to HR emergence seem unable to prevent the disruptive effects of the arrival of new individuals. This calls for further research on the mechanisms that can stabilize HR spatial organization in the long term.

Lyme disease: Knowledge and practices of family practitioners in southern Quebec.

BACKGROUND: Public health authorities in Quebec have responded to the progressive emergence of Lyme disease (LD) with surveillance activities and education for family physicians (FPs) who are key actors in both vigilance and case management. OBJECTIVES: To describe FPs' clinical experience with LD, their degree of knowledge, and their practices in two areas, one with known infected tick populations (Montérégie) and one without (regions nearby Montérégie). METHODS: In the present descriptive cross-sectional study, FPs were recruited during educational sessions. They were asked to complete a questionnaire assessing their clinical experience with Lyme disease, their knowledge of signs and symptoms of LD, and their familiarity with accepted guidelines for diagnosing and treating LD in two clinical scenarios (tick bite and erythema migrans). RESULTS: A total of 201 FPs participated, mostly from Montérégie (n=151). Overall, results revealed a moderate lack of knowledge and suboptimal practices rather than systematically insufficient knowledge or inadequate practices. A majority of participants agreed to more education on LD. As expected, FPs from Montérégie had a higher clinical experience with tick bites (57% versus 25%), better knowledge of LD endemic areas in Canada and erythema migrans characteristics, and better management of erythema migrans (72% versus 50%). CONCLUSION: The present study documented the inappropriate intention to order serology tests for tick bites and the unjustified intention to use tick analysis for diagnostic purposes. Such practices should be discouraged because they are unnecessary and overuse collective laboratory and medical resources. In addition, public health authorities must pursue their education efforts regarding FPs to optimize case management.

HISTORIQUE: Les autorités en santé publique du Québec ont répondu à l'émergence progressive de la maladie de Lyme (ML) par des activités de surveillance et des formations pour les médecins de famille (MF), qui sont des acteurs majeurs en matière de vigilance et de prise en charge. OBJECTIFS: Décrire l'expérience clinique des MF à l'égard de la ML, leur degré de connaissances et leurs pratiques dans deux régions, l'une comptant des populations connues de tiques infectées (Montérégie) et l'autre n'en comptant pas (régions à proximité de la Montérégie). MÉTHODOLOGIE: Dans la présente étude transversale descriptive, les MF ont été recrutés pendant des séances de formation. Ils ont été invités à remplir un questionnaire visant à évaluer leur expérience clinique de la ML, leurs connaissances des signes et symptômes de cette maladie et leurs connaissances des directives acceptées pour diagnostiquer et traiter la ML pour deux scénarios cliniques (piqûre de tique et érythème migrant). RÉSULTATS: Au total, 201 MF ont participé, la plupart provenant de la Montérégie (n=151). Dans l'ensemble, les résultats ont révélé un manque modéré de connaissances et des pratiques sous-optimales plutôt que des connaissances systématiquement insuffisantes ou des pratiques inadéquates. La majorité des participants ont convenu avoir besoin de plus de formation sur la ML. Comme prévu, les MF de la Montérégie avaient une plus grande expérience clinique des piqûres de tique (57 % par rapport à 25 %), connaissaient mieux les régions endémiques de la ML au Canada et les caractéristiques de l'érythème migrant et prenaient mieux en charge l'érythème migrant (72 % par rapport à 50 %). CONCLUSION: La présente étude a permis de constater l'intention inappropriée de demander des tests sérologiques après une piqûre de tique et d'analyser les tiques pour corroborer le diagnostic de ML. Il faut décourager ces pratiques, car elles sont inutiles et favorisent la surutilisation collective des laboratoires et des ressources médicales. Par ailleurs, les autorités en santé publique doivent poursuivre leurs efforts de formation auprès des MF pour optimiser la prise en charge des cas.

Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421.

ACE2 (angiotensin converting enzyme 2) plays a critical role in the local tissue RAS (renin-angiotensin system) by hydrolysing the potent hypertensive and mitogenic peptide AngII (angiotensin II). Changes in the levels of ACE2 have been observed in a number of pathologies, including cardiovascular disease, but little is known of the mechanisms regulating its expression. In the present study, therefore, the potential role of miRNAs in the regulation of ACE2 expression in primary human cardiac myofibroblasts was examined. Putative miRNA-binding sites were identified in the 3'-UTR of the ACE2 transcript using online prediction algorithms. Two of these, miR-200b and miR-421, were selected for further analysis. A reporter system using the 3'-UTR of ACE2 fused to the coding region of firefly luciferase was used to determine the functionality of the identified binding sites in vitro. This identified miR-421, but not miR-200b, as a potential regulator of ACE2. The ability of miR-421, an miRNA implicated in the development of thrombosis, to down-regulate ACE2 expression was subsequently confirmed by Western blot analysis of both primary cardiac myofibroblasts and transformed cells transfected with a synthetic miR-421 precursor. Real-time PCR analysis of miR-421 revealed widespread expression in human tissues. miR-421 levels in cardiac myofibroblasts showed significant inter-patient variability, in keeping with the variability of ACE2 expression we have observed previously. In conclusion, the present study is the first to demonstrate that ACE2 may be subject to post-transcriptional regulation and reveals a novel potential therapeutic target, miR-421, which could be exploited to modulate ACE2 expression in disease.

Do naive juvenile seabirds forage differently from adults?

Foraging skills of young individuals are assumed to be inferior to those of adults. The reduced efficiency of naive individuals may be the primary cause of the high juvenile mortality and explain the deferment of maturity in long-lived species. However, the study of juvenile and immature foraging behaviour has been limited so far. We used satellite telemetry to compare the foraging movements of juveniles, immatures and breeding adult wandering albatrosses Diomedea exulans, a species where foraging success is positively influenced by the distance covered daily. We showed that juveniles are able to use favourable winds as soon as the first month of independence, but cover shorter distances daily and spend more time sitting on water than adults during the first two months after fledging. These reduced movement capacities do not seem to be the cause of higher juvenile mortality. Moreover, juveniles almost never restrict their movement to specific areas, as adults and immatures frequently do over shelf edges or oceanic zones, which suggest that the location of appropriate areas is learned through experience. Immatures and adults have equivalent movement capacities, but when they are central place foragers, i.e. when adults breed or immatures come to the colony to display and pair, immatures make shorter trips than adults. The long duration of immaturity in this species seems to be related to a long period of learning to integrate the foraging constraints associated with reproduction and central place foraging. Our results indicate that foraging behaviour of young albatrosses is partly innate and partly learned progressively over immaturity. The first months of learning appear critical in terms of survival, whereas the long period of immaturity is necessary for young birds to attain the skills necessary for efficient breeding without fitness costs.

Periodicity analysis of movement recursions.

Many animals adaptively use their environments by adjusting how long and how often they use specific areas of their home range. Whereas questions about residence times have been addressed for a long time, the study of movement recursions has only recently received due interest. A key question concerns the potential periodicity of such recursions, as many potential drivers of movement behaviour such as light, climate or plant-herbivore interactions can be periodic. We propose here to build upon well-established Fourier and wavelet analyses to extract periodic patterns from time-series of presence/absence, arrival or departure from areas of interest, and introduce reliable null models for assessing the statistical significance of the periods detected. We provide an illustrative example which shows how an impala (Aepyceros melampus) expressed periodic use of the main open area of its home range. The significant periods found (12 h using arrival times; 24h, 7 days, and 30 days using presence/absence records) were consistent with a use of this area linked to predation and disturbance, as the area was used more at night, closer to dark moon, and during week-days. Our approach is a further step towards building up a wider analytical framework for the study of movement ecology.

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.

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.

Differential movement and movement bias models for marine protected areas.

Marine protected areas (MPAs) are promoted as a tool to protect overfished stocks and increase fishery yields. Previous models suggested that adult mobility modified effects of MPAs by reducing densities of fish inside reserves, but increasing yields (i.e., increasing densities outside of MPAs). Empirical studies contradicted this prediction: as mobility increased, the relative density of fishes inside MPAs (relative to outside) increased or stayed constant. We hypothesized that this disparity between theoretical and empirical results was the result of differential movement of fish inside versus outside the MPA. We, therefore, developed a model with unequal and discontinuous diffusion, and analyzed its steady state and stability. We determined the abundance in the fishing grounds, the yield, the total abundance and the log ratio at steady-state and examined their response to adult mobility (while keeping the relative inequity in the diffusion constant). Abundance in the fishing grounds and yield increased, while total abundance and log-ratio decreased, as mobility increased. These results were all qualitatively consistent with the previous models assuming uniform diffusivity. Thus, the mismatch between empirical and theoretical results must result from other processes or other forms of differential movement. Therefore, we modified our original model by assuming that species located on the boundary of the MPA will preferentially move towards the MPA. This localized movement bias model gives rise to steady state profiles that can differ radically from the profiles in the unbiased model, especially when the bias is large. Moreover, for sufficiently large bias values, the monotonicity of the four measures with increased mobility is reversed, when compared with our original model. Thus, the movement bias model reconciles empirical data and theoretical results.

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.