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Abstract The combination of radiotherapy/chemoradiotherapy and immune checkpoint blockade can result in poor outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Here, we show that combining ATR inhibition (ATRi) with radiotherapy (RT) increases the frequency of activated NKG2A+PD-1+ T cells in animal models of HNSCC. Compared with the ATRi/RT treatment regimen alone, the addition of simultaneous NKG2A and PD-L1 blockade to ATRi/RT, in the adjuvant, post-radiotherapy setting induces a robust antitumour response driven by higher infiltration and activation of cytotoxic T cells in the tumour microenvironment. The efficacy of this combination relies on CD40/CD40L costimulation and infiltration of activated, proliferating memory CD8+ and CD4+ T cells with persistent or new T cell receptor (TCR) signalling, respectively. We also observe increased richness in the TCR repertoire and emergence of numerous and large TCR clonotypes that cluster based on antigen specificity in response to NKG2A/PD-L1/ATRi/RT. Collectively, our data point towards potential combination approaches for the treatment of HNSCC.

Background: Poor sleep can contribute to poorer health and socioemotional outcomes. Sleep health can be influenced by a range of individual and other socioecological factors. Perceptions of neighborhood physical and social characteristics reflect broader social-level factors that may influence sleep, which have not been well studied in the Australian context. This study examined the association between perceived neighborhood characteristics and sleep in a large sample of Australians. Methods: Data were from 9,792 people aged 16 years or older, from Waves 16 and 17 of the nationally representative Household, Income and Labour Dynamics in Australia Survey. Associations between perceived neighborhood characteristics (neighborly interaction and support, environmental noise, physical condition, and insecurity) and self-reported sleep duration, sleep disturbance, and napping were examined using multiple logistic regression models. Results: "Neighborhood interaction and support" and "neighborhood physical condition" were not significantly associated with any sleep outcomes after adjusting for relevant covariates. However, "environmental noise" and "neighborhood insecurity" remained significantly associated with sleep duration and sleep disturbance. None of the neighborhood characteristics were associated with napping. Furthermore, associations did not significantly vary by gender. Conclusions: This study highlights the potential benefit of public health policies to address noise and safety in neighborhoods to improve sleep.

Understanding and predicting individual responses to common stressors is essential for optimising performance in high-stress environments. This article outlines a protocol for a study to identify biomarkers that predict performance under heat, musculoskeletal, psychosocial and sleep stress, for future integration into a wearable sensor system. In Phase I, healthy adults aged between 18 and 45 years (n=104) will be recruited for an intervention trial that involves exposure to one of the four stressors: heat, musculoskeletal, psychosocial or sleep deprivation. Biomarkers will be identified from molecular markers in biological samples (eg, blood, saliva, sweat and stool), physiological measures and psychological assessments to predict cognitive and physical performance under stress. A within-subjects design will determine changes in molecular and non-molecular markers before and after stress exposure. In Phase II, we will use the biomarkers identified in Phase I to develop a wearable sensor to predict and monitor human performance under stress.

Small-scale inland and coastal fisheries improve physical and economic access to food for communities in Malawi, Tanzania and Uganda, according to analyses of nationally representative data.

Measurement(s) Perception • Threats • Adaptive capacity Technology Type(s) Survey Factor Type(s) Fishery location • Demographics Sample Characteristic - Organism Homo sapiens • fish Sample Characteristic - Environment freshwater environment • lake • stream • wetland ecosystem Sample Characteristic - Location Europe • Asia • Oceania • Africa • South America • North America • Australia Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14749161

Rice and fish are preferred foods, critical for healthy and nutritious diets, and provide the foundations of local and national economies across Asia. Although transformations, or “revolutions,” in agriculture and aquaculture over the past half-century have primarily relied upon intensified monoculture to increase rice and fish production, agroecological approaches that support biodiversity and utilize natural processes are particularly relevant for achieving a transformation toward food systems with more inclusive, nutrition-sensitive, and ecologically sound outcomes. Rice and fish production are frequently integrated within the same physical, temporal, and social spaces, with substantial variation amongst the types of production practice and their extent. In Cambodia, rice field fisheries that strongly rely upon natural processes persist in up to 80% of rice farmland, whereas more input and infrastructure dependent rice-shrimp culture is expanding within the rice farmland of Vietnam. We demonstrate how a diverse suite of integrated production practices contribute to sustainable and nutrition-sensitive food systems policy, research, and practice. We first develop a typology of integrated production practices illustrating the nature and degree of: (a) fish stocking, (b) water management, (c) use of synthetic inputs, and (d) institutions that control access to fish. Second, we summarize recent research and innovations that have improved the performance of each type of practice. Third, we synthesize data on the prevalence, outcomes, and trajectories of these practices in four South and Southeast Asian countries that rely heavily on fish and rice for food and nutrition security. Focusing on changes since the food systems transformation brought about by the Green Revolution, we illustrate how integrated production practices continue to serve a variety of objectives to varying degrees: food and nutrition security, rural livelihood diversification and income improvement, and biodiversity conservation. Five shifts to support contemporary food system transformations [i.e., disaggregating (1) production practices and (2) objectives, (3) utilizing diverse metrics, (4) valuing emergent, place-based innovation, (5) building adaptive capacity] would accelerate progress toward Sustainable Development Goal 2, specifically through ensuring ecosystem maintenance, sustainable food production, and resilient agricultural practices with the capacity to adapt to global change.

Human adults can optimally combine vision with self-motion to facilitate navigation. In the absence of visual input (e.g., dark environments and visual impairments), sensory substitution devices (SSDs), such as The vOICe or BrainPort, which translate visual information into auditory or tactile information, could be used to increase navigation precision when integrated together or with self-motion. In Experiment 1, we compared and assessed together The vOICe and BrainPort in aerial maps task performed by a group of sighted participants. In Experiment 2, we examined whether sighted individuals and a group of visually impaired (VI) individuals could benefit from using The vOICe, with and without self-motion, to accurately navigate a three-dimensional (3D) environment. In both studies, 3D motion tracking data were used to determine the level of precision with which participants performed two different tasks (an egocentric and an allocentric task) and three different conditions (two unisensory conditions and one multisensory condition). In Experiment 1, we found no benefit of using the devices together. In Experiment 2, the sighted performance during The vOICe was almost as good as that for self-motion despite a short training period, although we found no benefit (reduction in variability) of using The vOICe and self-motion in combination compared to the two in isolation. In contrast, the group of VI participants did benefit from combining The vOICe and self-motion despite the low number of trials. Finally, while both groups became more accurate in their use of The vOICe with increased trials, only the VI group showed an increased level of accuracy in the combined condition. Our findings highlight how exploiting non-visual multisensory integration to develop new assistive technologies could be key to help blind and VI persons, especially due to their difficulty in attaining allocentric information.