How hot? How often? Getting the fire frequency and timing right for optimal management of woody cover and pasture composition in northern Australian grazed tropical savannas. Kidman Springs Fire Experiment 1993-2013

Abstract. A long-term (1993-2013) experiment in grazed semiarid tropical savannas in northern Australia tested the impact of varying the frequency (every 2, 4 and 6 years) and season (June -EDS versus October -LDS) of fire compared with unburnt controls on woody cover and pasture composition, in grassland and open woodland. Over an 18-year period, woody cover increased by 4% (absolute) in the woodland even with the most severe (i.e. frequent, late dry season) fire treatments. With less severe or no fire, woody cover increased by 12-17%. In the grassland, woody cover remained static when subjected to LDS fires every 2 or 4 years, but increased by 3-6% under other fire treatments, and by 8% when unburnt. Major shifts in understorey species composition occurred at both sites regardless of fire regime. The effect of fire on herbage mass and composition was compounded by higher grazing after fires. The herbage mass of perennial grasses declined and that of annual grasses and forbs increased following early or frequent fires. Brachyachne convergens, Gomphrena canescens and Flemingia pauciflora increased in response to fire while Aristida latifolia and Heteropogon contortus decreased. Four-yearly LDS fire provided the most effective management of woody cover and pasture composition. Although EDS fire is recommended for biodiversity management and reducing greenhouse gas emissions in wet tropical savannas, on grazed pastoral land, it can promote woodland thickening and pasture degradation. Optimal fire management, therefore, depends on vegetation type, land use and the prevailing seasonal timing and frequency of fire. Additional keywords: fire management, fire season, rangeland management, time since fire

Promoting independence, health and well-being for older people: : a feasibility study of computer-aided health and social risk appraisal system in primary care

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Walters et al, BMC Family Practice (2017), 18:47, DOI: 10.1186/s12875-017-0620-6Abstract Background: With population ageing, research is needed into new low-cost, scalable methods of effective promotion of health and wellbeing for older people. We aimed to assess feasibility, reach and costs of implementing a new tailored computer-aided health and social risk appraisal system in primary care. Methods: Design: Feasibility study. Setting: Five General Practices in London (Ealing) and Hertfordshire, United Kingdom (UK) Participants: Random sample of patients aged 65+years. Intervention: The Multi-dimensional Risk Appraisal for Older people (MRA-O) system includes: 1) Postal questionnaire including health, lifestyle, social and environmental domains; 2) Software system generating a personalised feedback report with advice on health and wellbeing; 3) Follow-up of people with new concerning or complex needs by GPs or practice nurses. Evaluation: Feasibility of implementation; participant wellbeing, functional ability and quality of life; social needs, health risks, potential lifestyle changes; and costs of implementation. Results: Response rates to initial postal invitations were low (526/1550, 34%). Of these, 454/526 (86%) completed MRA-O assessments. Compared to local UK Census data on older people, participants were younger, more were owner-occupiers and fewer were from ethnic minority groups than expected. A range of problems was identified by participants, including pain in last week (269/438, 61.4%), low physical activity (173/453, 38.2%), sedentary lifestyle (174/447, 38.3%), falls (117/439, 26.7%), incontinence (111/441 25.2%), impaired vision 116/451 (25.7%), impaired hearing (145/431, 33.6%), depressed mood (71/451, 15.7%), impaired memory (44/444 9.9%), social isolation (46/449, 10.2%) and loneliness (31/442, 7.0%). Self-rated health was good/excellent in 312/437 (71.4%), and quality of life and well-being were slightly above age-specific population norms. Implementation costs were low. Practices reviewed medical records of 143/454 (31.5%) of participants as a consequence of their responses, and actively followed up 110/454 (24.2%) of their patients. Conclusions: A computer-aided risk appraisal system was feasible for General Practices to implement, yields useful information about health and social problems, and identifies individual needs. Participation rates were however low, particularly for the oldest old, the poorest, and ethnic minority groups, and this type of intervention may increase inequalities in access. Widespread implementation of this approach would require work to address potential inequalities.Peer reviewedFinal Published versio

Two-way communication with neural networks in vivo using focused light

Neuronal networks process information in a distributed, spatially heterogeneous manner that transcends the layout of electrodes. In contrast, directed and steerable light offers the potential to engage specific cells on demand. We present a unified framework for adapting microscopes to use light for simultaneous in vivo stimulation and recording of cells at fine spatiotemporal resolutions. We use straightforward optics to lock onto networks in vivo, to steer light to activate circuit elements and to simultaneously record from other cells. We then actualize this 'free' augmentation on both an 'open' two-photon microscope and a leading commercial one. By following this protocol, setup of the system takes a few days, and the result is a noninvasive interface to brain dynamics based on directed light, at a network resolution that was not previously possible and which will further improve with the rapid advance in development of optical reporters and effectors. This protocol is for physiologists who are competent with computers and wish to extend hardware and software to interface more fluidly with neuronal networks.National Institutes of Health (U.S.) (Postdoctoral Fellowship)Simons Foundation (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Predoctoral Fellowship)National Institutes of Health (U.S.)Simons Foundatio

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy