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Figure S1. BrPA inhibits MUC1-mediated nucleotide metabolism. Figure S2. Immunohistochemical staining for MUC1 in tumor sections.

Purpose: MUC1, an oncogene overexpressed in multiple solid tumors, including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth-promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models.Experimental Design: We used MUC1-knockdown and -overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response, and metabolomic evaluations. We also investigated whether inhibition of glycolysis could revert MUC1-mediated metabolic alterations and radiation resistance by using in vitro and in vivo models.Results: MUC1 expression diminished radiation-induced cytotoxicity and DNA damage in pancreatic cancer cells by enhancing glycolysis, pentose phosphate pathway, and nucleotide biosynthesis. Such metabolic reprogramming resulted in high nucleotide pools and radiation resistance in in vitro models. Pretreatment with the glycolysis inhibitor 3-bromopyruvate abrogated MUC1-mediated radiation resistance both in vitro and in vivo, by reducing glucose flux into nucleotide biosynthetic pathways and enhancing DNA damage, which could again be reversed by pretreatment with nucleoside pools.Conclusions: MUC1-mediated nucleotide metabolism plays a key role in facilitating radiation resistance in pancreatic cancer and targeted effectively through glycolytic inhibition. Clin Cancer Res; 23(19); 5881–91. ©2017 AACR.

Non-white people are more likely to develop systemic lupus erythematosus (SLE), yet are underrepresented in SLE clinical trials. The efficacy and safety of drugs may be influenced by ancestry, and ancestrally diverse study populations are necessary to optimize treatments across the full spectrum of patients. However, barriers to entry into clinical trials are amplified in non-white populations. To address these issues, a conference was held in Bethesda, Maryland from October 15th -16th , 2019 entitled "Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies: Overcoming the Barriers." Participants included people with lupus, lupus physicians, lupus clinical trialists, treatment developers from biotechnology, social scientists, patient advocacy groups, and United States government representatives (the Office of Minority Health, Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration). For all of these groups, the organizers purposefully included people of non-white ancestry. Decreased participation of non-white SLE patients in clinical research was evaluated through historical, societal, experiential, and pragmatic perspectives, and several interventional programs to increase non-white patient participation in SLE and non-SLE research were described and discussed. The presentations and discussions highlighted the need for changes at the societal, institutional, research team, referring physician, and patient education levels to achieve equitable ancestral representation in SLE clinical studies.

Objectives: To develop and assess the measurement properties of self-report measures of accumulation of sitting time. Methods: Seven candidate measures were collected in 51 workers from three office environments (79% women) via online questionnaire administered immediately before and after 7-day monitoring periods (activPAL3 24-hour protocol with diary recorded work hours). Results: Three measures had some validity (P

Background Extended contact interventions delivered via text messaging are a low-cost option for promoting the long-term continuation of behavior change. This secondary analysis of a text message–delivered extended contact intervention (‘Get Healthy, Stay Healthy’ (GHSH)) explores the extent to which changes in physical activity, dietary behaviors and body weight were associated with the frequency of text messages (dose) and contact between the health coach and participant (engagement). Methods Following a telephone coaching program, participants were randomised to receive extended contact via tailored text messages (GHSH, n = 114) or no additional contact (n = 114) over a 6-month period. Message dose, timing, and content were based on participant preferences, ascertained during two tailoring telephone calls. All incoming and outgoing messages were recorded. At baseline and 6 months, participants self-reported body weight and dietary behaviors (fruit and vegetable servings/day). Moderate-vigorous physical activity (MVPA) was assessed via accelerometry. Results Median dose (25th, 75th percentile) was 53 (33, 72) text messages in total across six months. Mean fortnightly dose in weeks 1–2 was 5.5 (95 % CI: 4.3, 6.6) text messages, and remained stable (with the exception of planned decreases in weeks involving additional intervention contacts). Offset against the average fortnightly dose of goal checks (1.6, 95 % CI: 1.3, 2.0 and 1.5, 95 % CI: 1.2, 1.8, for physical activity and diet respectively), mean replies to goal checks were highest in weeks 1–2 (1.4, 95 % CI: 1.4, 1.5 and 1.3, 95 % CI: 1.2, 1.4, respectively) and tended to become lower in most weeks thereafter. Greater weight loss was positively associated with text message dose (P = 0.022), with a difference of 1.9 kg between participants receiving the most and fewest texts. There was no association between engagement and changes in outcome measures. Conclusions A fixed dose of texts does not seem suitable to meet participants’ individual preferences. Higher self-selected text doses predicted better weight outcomes. However, greater participant engagement through text replies does not predict more favourable outcomes, despite being a suggested facilitator of successful behavior change maintenance. Trial registration Australian New Zealand Clinical Trials Registry number: ACTRN12613000949785. Date registered: 27 August 2013. Retrospectively registered. http://www.anzctr.org.au/.

Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used for safe retrieval of traumatic memories of experiences that occurred elsewhere. However, it is unknown whether indirectly retrieved traumatic memories are sensitive to disruption. Here we used a backward (BW) conditioning procedure to indirectly retrieve and manipulate a hippocampus (HPC)-dependent contextual fear engram in male rats. We show that conditioned freezing to a BW conditioned stimulus (CS) is mediated by fear to the conditioning context, activates HPC ensembles that can be covertly captured and chemogenetically activated to drive fear, and is impaired by post-retrieval protein synthesis inhibition. These results reveal that indirectly retrieved contextual fear memories reactivate HPC ensembles and undergo protein synthesis-dependent reconsolidation. Clinical interventions that rely on indirect retrieval of traumatic memories, such as imaginal exposure, may open a window for editing or erasure of neural representations that drive pathological fear.

A computerized tomography (CT) scan is the current advanced imaging standard of care for evaluation and preoperative planning for tibial plateau fractures, but magnetic resonance imaging (MRI) is emerging as a better method to identify soft tissue injuries. This study compares MRI and CT for fracture classification, associated soft tissue injuries, and preoperative planning for tibial plateau fractures. MRI offers lack of radiation and enhanced soft tissue evaluation, and as a result improved preoperative planning. MRI was favored among survey respondents for preoperative planning, Schatzker classification, and surgical approach planning.

Translation of an effective research intervention into a program able to be implemented in practice typically requires adaptations to ensure the outcomes can be achieved within the applied setting. User centred design (UCD) methodologies can support these iterative adaptations, with this approach being particularly well suited to peer-led interventions, due to a focus on usability. We describe and reflect on the UCD approach that was applied to optimise an online, peer-led workplace health promotion initiative (BeUpstanding: ACTRN12617000682347) to be suitable for wide-scale implementation and evaluation. Optimisation was aligned against the indicators of the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, with UCD methodologies (discovery interviews, persona and scenario mapping, facilitated workshops, surveys and prototyping) employed to enhance the program according to all RE-AIM dimensions. The core team (content experts, implementation scientist, interaction designer, software developer, business developer) worked closely with policy and practice partners and end users (workplace champions, management and staff) to iteratively develop and test across the RE-AIM indicators. This description and reflection of the process of applying UCD and the RE-AIM framework to the optimisation of BeUpstanding is intended to provide guidance for other behaviour change research adaptations into practice.

The hippocampus and its extended network contribute to encoding and recall of episodic experiences. Drawing from recent anatomical, physiological, and behavioral studies, we propose that hippocampal engrams function as indices to mediate memory recall. We broaden this idea to discuss potential relationships between engrams and hippocampal place cells, as well as the molecular, cellular, physiological and circuit determinants of engrams that permit flexible routing of information to intra- and extra-hippocampal circuits for re-instatement, a feature critical to memory indexing. Incorporating indexing into frameworks of memory function opens new avenues of study and even therapies for hippocampal dysfunction.

Highlights • Workplaces varied in the number of activity-supportive characteristics present. • Spatial characteristics were more common than resource or policy characteristics. • Characteristics absent in most workplaces were likely to be modifiable or low cost (“easy wins”). • Almost all workplaces had some room for improvement in terms of activity-supportive factors., Desk-based workers are highly sedentary; this has been identified as an emerging work health and safety issue. To reduce workplace sitting time and promote physical activity it is important to understand what factors are already present within workplaces to inform future interventions. This cross-sectional study examined the prevalence of supportive environmental factors, prior to workplaces taking part in a ‘sit less, move more’ initiative (BeUpstanding). Participants were 291 Australian-based workplace champions (representing 230 organisations) who unlocked the BeUpstanding program’s online toolkit between September 2017 and mid-November 2020, and who completed surveys relating to champion characteristics, organisation and workplace characteristics, and the availability of environmental factors to support sitting less and moving more. Factors were characterized using descriptive statistics and compared across key sectors and factor categories (spatial; resources/initiatives; policy/cultural) using mixed logistic regression models. Of the 42 factors measured, only 11 were present in > 50% of workplaces. Spatial design factors were more likely to be present than resources/initiatives or policy/cultural factors. Centralised printers were the most commonly reported attribute (94%), while prompts to encourage stair use were the least common (4%). Most workplace factors with

Forest edges are an important legacy of natural and anthropogenic disturbances. Edges of intact forest fragments are influenced by adjacent non-forested ecosystems, resulting in compositional and structural differences at the edge and into the intact forest. Edge influence (EI) is the altered biotic and abiotic interactions that occur along the edge-to-interior gradient in disturbed forests. Few studies have analyzed natural disturbance created edges, particularly in woodland structures, which contain fewer trees per hectare and are typically less light-limited than forests. The goal of our study was to examine the EI of a tornado-created edge in a Pinus palustris Mill. (longleaf pine) woodland in Alabama. In 2011, an EF-3 tornado impacted a restored P. palustris woodland, resulting in a distinct edge. We installed transects perpendicular to the edge to quantify biotic and abiotic response variables and calculate the distance of EI. Reduced structural forest complexity and basal area (negative EI) were evident 70 m into the interior woodland. Ground flora richness and diversity experienced a positive EI, with higher richness and diversity at the edge. Results of this study add to our understanding of EI on woodland composition and structure and naturally created edges and may help guide natural disturbance based silvicultural systems.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been established. We show that, to our surprise, suppression of KRAS increased autophagic flux, as did pharmacological inhibition of its effector ERK MAPK. Furthermore, we demonstrate that either KRAS suppression or ERK inhibition decreased both glycolytic and mitochondrial functions. We speculated that ERK inhibition might thus enhance PDAC dependence on autophagy, in part by impairing other KRAS- or ERK-driven metabolic processes. Accordingly, we found that the autophagy inhibitor chloroquine and genetic or pharmacologic inhibition of specific autophagy regulators synergistically enhanced the ability of ERK inhibitors to mediate antitumor activity in KRAS-driven PDAC. We conclude that combinations of pharmacologic inhibitors that concurrently block both ERK MAPK and autophagic processes that are upregulated in response to ERK inhibition may be effective treatments for PDAC. Blockade of ERK signaling in KRAS-mutant pancreatic cancer increases the dependence on autophagic flux through different mechanisms and provides a rationale for combinatorial targeting with autophagy inhibitors.

The endovascular aneurysm repair-2 (EVAR-2) trial suggested that EVAR in patients unfit for open surgical repair (OSR) failed to provide a significant overall survival advantage compared with conservative management. The aim is to compare survival and cost-effectiveness in patients with poor cardiopulmonary exercise test (CPET) metrics who underwent EVAR or were managed conservatively.A prospective database of all CPETs (1435 patients) performed to assess preoperative fitness for abdominal aortic aneurysm repair was maintained. A total of 350 patients deemed unfit for OSR underwent EVAR or were managed conservatively. A 1:1 propensity-matched analysis incorporating age, gender, anaerobic threshold, and aneurysm size was used to compare survival. Cost-effectiveness analysis was based on the economic model for the National Institute for Health and Care Excellence clinical guideline on abdominal aortic aneurysm treatment.Propensity matching produced 122 pairs of patients in the EVAR and conservative management groups. The median overall survival for the EVAR group was significantly longer than that for the conservative management group (84 vs 30 months, P .001). One-, three-, and five-year mortality in the EVAR group was 7%, 40%, and 68%, respectively, compared with 25%, 68%, and 82% in the conservative management group, all P .001. The increment cost-effectiveness ratio for EVAR was £8023 (US$11,644) per quality-adjusted life year gained compared with £430,602 (US$624,967) in the National Institute for Health and Care Excellence guideline, which is based on EVAR-2 results.EVAR offers a survival advantage and is cost-effective in selected patients deemed unfit for OSR based on CPET compared with conservative management.

This explanatory sequential mixed-method study explored the factors associated with the investment (or not) in sit-stand workstations (SSWs) and alternative initiatives to reduce prolonged sitting at work from the perspective of furniture purchasing decision-makers in Australian workplaces. Participants (n = 270) from >200 organisations across 19 industry sectors completed an online survey. Seven interviews were conducted in a sub-sample of participants from organisations without SSWs. The majority (80%) of workplaces reported having invested in SSWs. Workplaces without SSWs, opposed to those with SSWs, were more likely to be private (79.6% vs. 43.5%), of small/medium size (70.4% vs. 35.6%) and without a wellness program (57.4% vs. 22.2%) (all p < 0.05). Financial implications were the main reason for not investing in SSWs. Exercise and stretch breaks were alternative initiatives to reducing sedentary behaviour at work. Better evidence on the return on investment is needed to support purchasing decisions on SSWs.

Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used for safe retrieval of traumatic memories of experiences that occurred elsewhere. However, it is unknown whether indirectly retrieved traumatic memories are sensitive to disruption. Here we used a backward (BW) conditioning procedure to indirectly retrieve and manipulate a hippocampus (HPC)-dependent contextual fear engram in male rats. We show that conditioned freezing to a BW conditioned stimulus (CS) is mediated by fear to the conditioning context, activates HPC ensembles that can be covertly captured and chemogenetically activated to drive fear, and is impaired by post-retrieval protein synthesis inhibition. These results reveal that indirectly retrieved contextual fear memories reactivate HPC ensembles and undergo protein synthesis-dependent reconsolidation. Clinical interventions that rely on indirect retrieval of traumatic memories, such as imaginal exposure, may open a window for editing or erasure of neural representations that drive pathological fear.

Background Healthy Living after Cancer (HLaC) was a national dissemination and implementation study of an evidence-based lifestyle intervention for cancer survivors. The program was imbedded into existing telephone cancer information and support services delivered by Australian state-based Cancer Councils (CC). We report here the reach, effectiveness, adoption, implementation, and maintenance of the program. Methods In this phase IV study (single-group, pre-post design) participants - survivors of any type of cancer, following treatment with curative intent - received up to 12 nurse/allied health professional-led telephone health coaching calls over 6 months. Intervention delivery was grounded in motivational interviewing, with emphasis on evidence-based behaviour change strategies. Using the RE-AIM evaluation framework, primary outcomes were reach, indicators of program adoption, implementation, costs and maintenance. Secondary (effectiveness) outcomes were participant-reported anthropometric, behavioural and psychosocial variables including: weight; physical activity; dietary intake; quality-of-life; treatment side-effects; distress; and fear of cancer recurrence and participant satisfaction. Changes were evaluated using linear mixed models, including terms for timepoint (0/6 months), strata (Cancer Council), and timepoint x strata. Results Four of 5 CCs approached participated in the study. In total, 1183 cancer survivors were referred (mostly via calls to the Cancer Council telephone information service). Of these, 90.4% were eligible and 88.7% (n = 791) of those eligible consented to participate. Retention rate was 63.4%. Participants were mostly female (88%), aged 57 years and were overweight (BMI = 28.8 ± 6.5 kg/m2). Improvements in all participant-reported outcomes (standardised effect sizes of 0.1 to 0.6) were observed (p Conclusions This telephone-delivered lifestyle intervention, which was feasibly implemented by Cancer Councils, led to meaningful and statistically significant improvements in cancer survivors’ health and quality-of-life at a relatively low cost. Trial registration Australian and New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12615000882527 (registered on 24/08/2015).

Information and material biological legacies that persist after catastrophic forest disturbance collectively constitute the ecological memory of the system and may strongly influence future stand development. Catastrophic disturbances often result in an influx of coarse woody debris (CWD), and this material legacy may provide beneficial microsites that affect successional and structural developmental pathways. We examined how microenvironmental characteristics influence the regeneration of woody plants in a subtropical woodland that experienced a large influx of CWD from a catastrophic wind disturbance. Specifically, we asked (1) what microenvironmental factors best explain woody plant density, richness, and height in the regeneration layer and (2) does woody plant density, richness, and height benefit from the large influx of CWD to a degree that competition dynamics and succession may be modified? Data were collected in a Pinus palustris woodland that had experienced an EF3 tornado and was subjected to a four-year prescribed fire rotation. We documented live woody plants &lt, 5 cm diameter at breast height, soil, and site characteristics and tested for differences in seedling and sapling density, species richness, and height in relation to CWD proximity. We used a random forest machine learning algorithm to examine the influence of microenvironmental conditions on the characteristics of woody plants in the regeneration layer. Woody plant density and species richness were not significantly different by proximity to CWD, but plants near CWD were slightly taller than plants away from CWD. The best predictors of woody plant density, richness, and height were abiotic site characteristics including slope gradient and azimuth, organic matter depth and weight, and soil water content. Results indicated that the regeneration of woody plants in this P. palustris woodland was not strongly influenced by the influx of CWD, but by other biological legacies such as existing root networks and soil characteristics. Our study highlights the need to consider ecological memory in forest management decision-making after catastrophic disturbance. Information and material legacies shape recovery patterns, but, depending on the system, some legacies will be more influential on successional and developmental pathways than others.

Percutaneous endovascular aneurysm repair (PEVAR) has been shown to have high success rates, shorter operating times and length of stay compared to open access. However, there exists a lack of long-term follow-up data on these patients, and questions remain regarding longer-term outcomes. This study aims to assess the long-term complications and evolution of accessed vessels post-PEVAR. Sixty-one cases of bilateral PEVAR (122 groins) with > 36 months follow-up were analysed. Vessel diameter, calcification, dissection, lymphocele, pseudoaneurysm and thrombus formation were reviewed at 30th day and at the most recent follow-up CT. Notes were reviewed for groin infections, haematomas and nerve injury. Complications were considered ‘major’ if they required intervention or treatment. Mean follow-up time from procedure to most recent scan was 49.9 months. There were no major short- or long-term complications. The early complication rate was 9.8%, with six pseudoaneurysms, four dissections, one thrombus, one nerve injury and no lymphoceles, haematomas or groin infections. The long-term complication rate was 0.8%, with only one pseudoaneurysm. The remainder of early complications resolved naturally without intervention. Accessed vessel showed significantly (P ≤ 0.05) increased diameter and calcification between 30th day and last follow-up scan. This study provides the largest clinical cohort and the longest mean follow-up time reported in the literature and demonstrates the long-term safety of PEVAR. PEVAR has a very low long-term complication rate, without any major complications in our cohort. The accessed common femoral arteries do not show stenosis or thrombosis. Minor short-term complications appear to gradually resolve without intervention. Larger multi-centre studies are recommended.

Background Comorbidity of anxiety disorders, stressor- and trauma-related disorders, and substance use disorders is extremely common. Moreover, therapies that reduce pathological fear and anxiety on the one hand, and drug-seeking on the other, often prove short-lived and are susceptible to relapse. Considerable advances have been made in the study of the neurobiology of both aversive and appetitive extinction, and this work reveals shared neural circuits that contribute to both the suppression and relapse of conditioned responses associated with trauma or drug use. Objectives The goal of this review is to identify common neural circuits and mechanisms underlying relapse across domains of addiction biology and aversive learning in preclinical animal models. We focus primarily on neural circuits engaged during the expression of relapse. Key findings After extinction, brain circuits involving the medial prefrontal cortex and hippocampus come to regulate the expression of conditioned responses by the amygdala, bed nucleus of the stria terminalis, and nucleus accumbens. During relapse, hippocampal projections to the prefrontal cortex inhibit the retrieval of extinction memories resulting in a loss of inhibitory control over fear- and drug-associated conditional responding. Conclusions The overlapping brain systems for both fear and drug memories may explain the co-occurrence of fear and drug-seeking behaviors.

The amygdala and, more recently, also the bed nucleus of the stria terminalis, have been widely implicated in fear and anxiety. Much of our current knowledge is derived from animal studies and suggests an intricate convergence and divergence in functions related to defensive responding. In a recent paper, Klumpers and colleagues set out to examine these functions in a human fear learning procedure using functional magnetic resonance imaging. Their main findings were a role for the bed nucleus of the stria terminalis in threat anticipation, and for the amygdala in threat confrontation. Here, we provide a critical summary of this interesting study and point out some important issues that were not addressed by its authors. In particular, we first take a closer look at the striking differences between both samples that were combined for the study, and, secondly, we provide an in-depth discussion of their findings in relation to existing neurobehavioral models. ispartof: Neuropsychology Review vol:29 issue:2 pages:181-185 ispartof: location:United States status: published

Stand structural complexity enhancement is an increasingly popular management objective, especially on public lands. Complex stand structures are hypothesized to support a relatively high degree of native forest diversity and be more resistant and resilient to disturbances. Complex structures are characterized by the presence of deadwood and heterogeneity of tree-size classes and tree architecture. Relatively little is known about how discrete disturbance events affect structural complexity and compositional diversity in Quercus-dominated stands at fine spatial scales (i.e. neighborhoods). We established 20 0.05 ha fixed-radius plots on the Sipsey Wilderness of William B. Bankhead National Forest in northern Alabama to quantify woody plant species composition and structure. Trees were mapped on each plot to quantify overstory structural complexity and compositional diversity. We extracted two cores from all canopy Quercus spp. ≥ 5 cm diameter at breast height to quantify age, recruitment pulses, and reconstruct canopy disturbance history. Shannon species diversity in the sampled area was 1.75 for trees, 2.08 for saplings, and 1.69 for seedlings. Quercus alba had the greatest basal area, and Ostrya virginiana had the highest density. The stand exhibited a reverse J-shaped distribution with a q-factor of 1.72. The oldest Quercus dated to 1795, and the largest recruitment pulse occurred in the 1870s. The mean return interval for intermediate-severity disturbance was 38 years. Although we documented no relationships between disturbance frequency and compositional diversity at the neighborhood scale (0.05 ha), less frequent disturbance was associated with higher structural complexity (r2 = 0.258, p = 0.026) at the neighborhood scale. We suggest that localized disturbance increases species diversity and structural complexity, but these processes are manifest at the stand level and not at the neighborhood scale. We conclude that the spatial variability (i.e. size, shape, orientation, microsite conditions) is likely more influential on diversity and complexity than the temporal variation (frequency) of these processes at the neighborhood scale.

Purpose: MUC1, an oncogene overexpressed in multiple solid tumors, including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth-promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models. Experimental Design: We used MUC1-knockdown and -overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response, and metabolomic evaluations. We also investigated whether inhibition of glycolysis could revert MUC1-mediated metabolic alterations and radiation resistance by using in vitro and in vivo models. Results: MUC1 expression diminished radiation-induced cytotoxicity and DNA damage in pancreatic cancer cells by enhancing glycolysis, pentose phosphate pathway, and nucleotide biosynthesis. Such metabolic reprogramming resulted in high nucleotide pools and radiation resistance in in vitro models. Pretreatment with the glycolysis inhibitor 3-bromopyruvate abrogated MUC1-mediated radiation resistance both in vitro and in vivo, by reducing glucose flux into nucleotide biosynthetic pathways and enhancing DNA damage, which could again be reversed by pretreatment with nucleoside pools. Conclusions: MUC1-mediated nucleotide metabolism plays a key role in facilitating radiation resistance in pancreatic cancer and targeted effectively through glycolytic inhibition. Clin Cancer Res; 23(19); 5881–91. ©2017 AACR.

Retrieving fear memories just prior to extinction has been reported to effectively erase fear memories and prevent fear relapse. The current study examined whether the type of retrieval procedure influences the ability of extinction to impair fear renewal, a form of relapse in which responding to a conditional stimulus (CS) returns outside of the extinction context. Rats first underwent Pavlovian fear conditioning with an auditory CS and footshock unconditional stimulus (US); freezing behavior served as the index of conditioned fear. Twenty-four hours later, the rats underwent a retrieval-extinction procedure. Specifically, 1 h prior to extinction (45 CS-alone trials; 44 for rats receiving a CS reminder), fear memory was retrieved by either a single exposure to the CS alone, the US alone, a CS paired with the US, or exposure to the conditioning context itself. Over the next few days, conditional freezing to the extinguished CS was tested in the extinction and conditioning context in that order (i.e., an ABBA design). In the extinction context, rats that received a CS+US trial before extinction exhibited higher levels of conditional freezing than animals in all other groups, which did not differ from one another. In the renewal context, all groups showed renewal, and none of the reactivation procedures reduced renewal relative to a control group that did not receive a reactivation procedure prior to extinction. These data suggest retrieval-extinction procedures may have limited efficacy in preventing fear renewal.

In developed and developing countries, social, economic, and environmental transitions have led to physical inactivity and large amounts of time spent sitting. Research is now unraveling the adverse public health consequences of too much sitting. We describe improvements in device-based measurement that are providing new insights into sedentary behavior and health. We consider the implications of research linking evidence from epidemiology and behavioral science with mechanistic insights into the underlying biology of sitting time. Such evidence has led to new sedentary behavior guidelines and initiatives. We highlight ways that this emerging knowledge base can inform public health strategy: First, we consider epidemiologic and experimental evidence on the health consequences of sedentary behavior; second, we describe solutions-focused research from initiatives in workplaces and schools. To inform a broad public health strategy, researchers need to pursue evidence-informed collaborations with occupational health, education, and other sectors. Refereed/Peer-reviewed

Investigations of compound disturbances that alter forest resilience (i.e., recovery time or trajectory) have escalated over the past two decades. We used a systematic approach to identify and describe the ecological consequences of discrete forest disturbance events involved in compound interactions. Fire, wind disturbance, and salvage logging were the most common disturbance types investigated. Most compound interactions occurred in North America and involved five or fewer years between disturbances. Common and interrelated disturbance legacies that facilitated compound interactions included reduced seed source availability, deadwood deposition and extraction, and increased light and growing space availability. Forest recovery was assessed with a diversity of metrics including woody and herbaceous plants, soil properties, and carbon stocks, which sometimes determined whether and what kind of compound interaction was detected. Distinctions between recovery time and trajectory, forest succession and development, and species‐specific and community‐level responses also influenced the detection and direction of compound interactions. Moving forward, we advocate a more holistic approach to quantify ecosystem recovery that considers multiple response variables. Other opportunities to improve compound disturbance ecology include increased emphasis on understudied disturbance types, regions, and forest types. We also encourage more research on buffering interactions that increase forest resilience, which were underrepresented in this review.

Recent work indicates that the bed nucleus of the stria terminalis (BNST) is critically involved in the regulation of conditioned fear responses to unpredictable threats. Here we examined whether the involvement of the BNST in contextual fear conditioning in male rats depends on the imminence of shock after placement in the conditioning chamber. Specifically, we hypothesized that the BNST supports contextual freezing after conditioning with delayed, but not imminent, footshock (relative to placement in the context). Rats were implanted with cannulae targeting the BNST and underwent a contextual fear conditioning procedure in which a single footshock unconditioned stimulus (US) was delivered either 1 min or 9 min after the rat was placed in the context; the rats received a total of four identical conditioning sessions over two days, all with equivalent exposure to the context. Contexts associated with either imminent or delayed US onsets produced distinct patterns of freezing and shock-induced activity but freezing in each case was context-dependent. Reversible inactivation of the BNST reduced the expression of contextual freezing in the context paired with delayed (9 min), but not imminent (1 min), footshock onset. Implications of these data are discussed in the light of recent conceptualizations of BNST function, as well as for anxiety behaviors.

BACKGROUND The web-based BeUpstanding Champion Toolkit was developed to support work teams in addressing the emergent work health and safety issue of excessive sitting. It provides a step-by-step guide and associated resources that equip a workplace representative—the champion—to adopt and deliver the 8-week intervention program (BeUpstanding) to their work team. The evidence-informed program is designed to raise awareness of the benefits of sitting less and moving more, build a supportive culture for change, and encourage staff to take action to achieve this change. Work teams collectively choose the strategies they want to implement and promote to stand up, sit less, and move more, with this bespoke and participative approach ensuring the strategies are aligned with the team’s needs and existing culture. BeUpstanding has been iteratively developed and optimized through a multiphase process to ensure that it is fit for purpose for wide-scale implementation. OBJECTIVE The study aimed to describe the current version of BeUpstanding, and the methods and protocol for a national implementation trial. METHODS The trial will be conducted in collaboration with five Australian workplace health and safety policy and practice partners. Desk-based work teams from a variety of industries will be recruited from across Australia via partner-led referral pathways. Recruitment will target sectors (small business, rural or regional, call center, blue collar, and government) that are of priority to the policy and practice partners. A minimum of 50 work teams will be recruited per priority sector with a minimum of 10,000 employees exposed to the program. A single-arm, repeated-measures design will assess the short-term (end of program) and long-term (9 months postprogram) impacts. Data will be collected on the web via surveys and toolkit analytics and by the research team via telephone calls with champions. The Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework will guide the evaluation, with assessment of the adoption/reach of the program (the number and characteristics of work teams and participating staff), program implementation (completion by the champion of core program components), effectiveness (on workplace sitting, standing, and moving), and maintenance (sustainability of changes). There will be an economic evaluation of the costs and outcomes of scaling up to national implementation, including intervention affordability and sustainability. RESULTS The study received funding in June 2018 and the original protocol was approved by institutional review board on January 9, 2017, with national implementation trial consent and protocol amendment approved March 12, 2019. The trial started on June 12, 2019, with 48 teams recruited as of December 2019. CONCLUSIONS The implementation and multimethod evaluation of BeUpstanding will provide the practice-based evidence needed for informing the potential broader dissemination of the program. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12617000682347; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372843&isReview=true. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/15756

Background The web-based BeUpstanding Champion Toolkit was developed to support work teams in addressing the emergent work health and safety issue of excessive sitting. It provides a step-by-step guide and associated resources that equip a workplace representative—the champion—to adopt and deliver the 8-week intervention program (BeUpstanding) to their work team. The evidence-informed program is designed to raise awareness of the benefits of sitting less and moving more, build a supportive culture for change, and encourage staff to take action to achieve this change. Work teams collectively choose the strategies they want to implement and promote to stand up, sit less, and move more, with this bespoke and participative approach ensuring the strategies are aligned with the team’s needs and existing culture. BeUpstanding has been iteratively developed and optimized through a multiphase process to ensure that it is fit for purpose for wide-scale implementation. Objective The study aimed to describe the current version of BeUpstanding, and the methods and protocol for a national implementation trial. Methods The trial will be conducted in collaboration with five Australian workplace health and safety policy and practice partners. Desk-based work teams from a variety of industries will be recruited from across Australia via partner-led referral pathways. Recruitment will target sectors (small business, rural or regional, call center, blue collar, and government) that are of priority to the policy and practice partners. A minimum of 50 work teams will be recruited per priority sector with a minimum of 10,000 employees exposed to the program. A single-arm, repeated-measures design will assess the short-term (end of program) and long-term (9 months postprogram) impacts. Data will be collected on the web via surveys and toolkit analytics and by the research team via telephone calls with champions. The Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework will guide the evaluation, with assessment of the adoption/reach of the program (the number and characteristics of work teams and participating staff), program implementation (completion by the champion of core program components), effectiveness (on workplace sitting, standing, and moving), and maintenance (sustainability of changes). There will be an economic evaluation of the costs and outcomes of scaling up to national implementation, including intervention affordability and sustainability. Results The study received funding in June 2018 and the original protocol was approved by institutional review board on January 9, 2017, with national implementation trial consent and protocol amendment approved March 12, 2019. The trial started on June 12, 2019, with 48 teams recruited as of December 2019. Conclusions The implementation and multimethod evaluation of BeUpstanding will provide the practice-based evidence needed for informing the potential broader dissemination of the program. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12617000682347; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372843&isReview=true. International Registered Report Identifier (IRRID) DERR1-10.2196/15756

The aim of this cross-sectional mixed-method study was to understand the current use, and practices to support the implementation, of sit-stand workstations (SSWs) from the perspective of furniture purchasing decision makers in Australian organisations. An online survey, and in-depth interviews with a purposive sub-sample were conducted. A total of 216 eligible participants from 150 organisations across 18 sectors completed the survey with 17 interviews conducted. 40% of organisations provided SSWs on request while 41% reported not using them appropriately. Over half provided no training on the appropriate use of SSWs (n = 109, 51%) nor used any strategies to enhance their use (n = 163, 84%). From the interviews, SSWs were perceived effective in reducing discomforts and increasing employees’ satisfaction and productivity. Lack of resources and guidelines to support SSW usage, and lack of wellbeing knowledge, were identified as barriers. Education and ongoing monitoring are important to enhance the appropriate use and uptake of SSWs.

Providing effective weight management services to the growing number of overweight or obese hospital patients necessitates long-term service provision; however, it is arguably not within the acute-care hospital remit to provide such extended services. Referral to community-based programs is required to provide continuing weight management services. The Get Healthy Service is a free six-month, telephone-delivered lifestyle program, now offered in several states of Australia with potential for wide population reach. However, health practitioner referral into the service has been low. The study aimed to examine awareness and suitability of the Get Healthy Service for referral of hospital outpatients for weight management, among key health-care decision-makers. Nine key decision-makers from metropolitan and rural Queensland Health hospitals took part in semi-structured telephone interviews that were audio-recorded (January-July 2014), transcribed verbatim and thematically analysed. Interviews revealed that most decision-makers had limited awareness of the Get Healthy Service but perceived the telephone service to be suitable for patient referrals. Incorporating Get Healthy Service referrals into patient care was seen to be potentially valuable and relatively easy to implement, with most interviewees suggesting that they would provide a Get Healthy Service brochure to patients who could then self-refer into the service. The Get Healthy Service provides a referral model for weight management service provision that appears feasible for use in Queensland hospital settings. Increased awareness and a more integrated approach to referrals would likely result in improved enrolment to the service, with future research needed to demonstrate this.