Search

Purpose: Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer–specific mortality (BCM) and overall mortality (OM) in TNBC.Experimental Design: Data on treatments and diagnostic tests from electronic medical records of two health care systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data available, we explored the relationship between TILs and peripheral lymphocyte counts.Results: A total of 1,463 stage I–III TNBC patients were diagnosed from 2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1 year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC n = 70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy.Conclusions: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment. Clin Cancer Res; 24(12); 2851–8. ©2018 AACR.

Supplemental Table S1, Figure S1, and Figure Legends for Figure S2 - S5 Table S1. Number of potential allelic methylation sites identified per sample Figure S1. Flow diagram summarizing the strategy for study cohort selection consisting of high-risk breast cancer family index patients.

Purpose:BRCA1/2-mutated and some sporadic triple-negative breast cancers (TNBC) have DNA repair defects and are sensitive to DNA-damaging therapeutics. Recently, three independent DNA-based measures of genomic instability were developed on the basis of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST).Experimental Design: We assessed a combined homologous recombination deficiency (HRD) score, an unweighted sum of LOH, TAI, and LST scores, in three neoadjuvant TNBC trials of platinum-containing therapy. We then tested the association of HR deficiency, defined as HRD score ≥42 or BRCA1/2 mutation, with response to platinum-based therapy.Results: In a trial of neoadjuvant platinum, gemcitabine, and iniparib, HR deficiency predicted residual cancer burden score of 0 or I (RCB 0/I) and pathologic complete response (pCR; OR = 4.96, P = 0.0036; OR = 6.52, P = 0.0058). HR deficiency remained a significant predictor of RCB 0/I when adjusted for clinical variables (OR = 5.86, P = 0.012). In two other trials of neoadjuvant cisplatin therapy, HR deficiency predicted RCB 0/I and pCR (OR = 10.18, P = 0.0011; OR = 17.00, P = 0.0066). In a multivariable model of RCB 0/I, HR deficiency retained significance when clinical variables were included (OR = 12.08, P = 0.0017). When restricted to BRCA1/2 nonmutated tumors, response was higher in patients with high HRD scores: RCB 0/I P = 0.062, pCR P = 0.063 in the neoadjuvant platinum, gemcitabine, and iniparib trial; RCB 0/I P = 0.0039, pCR P = 0.018 in the neoadjuvant cisplatin trials.Conclusions: HR deficiency identifies TNBC tumors, including BRCA1/2 nonmutated tumors more likely to respond to platinum-containing therapy. Clin Cancer Res; 22(15); 3764–73. ©2016 AACR.

Purpose:Understanding and explaining hereditary predisposition to cancer has focused on the genetic etiology of the disease. However, mutations in known genes associated with breast cancer, such as BRCA1 and BRCA2, account for less than 25% of familial cases of breast cancer. Recently, specific epigenetic modifications at BRCA1 have been shown to promote hereditary breast cancer, but the broader potential for epigenetic contribution to hereditary breast cancer is not yet well understood.Experimental Design:We examined DNA methylation through deep bisulfite sequencing of CpG islands and known promoter or regulatory regions in peripheral blood DNA from 99 patients with familial or early-onset breast or ovarian cancer, 6 unaffected BRCA mutation carriers, and 49 unaffected controls.Results:In 9% of patients, we observed altered methylation in the promoter regions of genes known to be involved in cancer, including hypermethylation at the tumor suppressor PTEN and hypomethylation at the proto-oncogene TEX14. These alterations occur in the form of allelic methylation that span up to hundreds of base pairs in length.Conclusions:Our observations suggest a broader role for DNA methylation in early-onset, familial risk breast cancer. Further studies are warranted to clarify these mechanisms and the benefits of DNA methylation screening for early risk prediction of familial cancers.

List of regions identified as having potential allelic methylation

Genomic instability is a major feature of neoplastic development in colorectal carcinoma and other cancers. Specific genomic instability events, such as deletions in chromosomes and other alterations in gene copy number, have potential utility as biologically relevant prognostic biomarkers. For example, genomic deletions on chromosome arm 18q are an indicator of colorectal carcinoma behavior and potentially useful as a prognostic indicator. Adapting a novel genomic technology called molecular inversion probes which can determine gene copy alterations, such as genomic deletions, we designed a set of probes to interrogate several hundred individual exons of >200 cancer genes with an overall distribution covering all chromosome arms. In addition, >100 probes were designed in close proximity of microsatellite markers on chromosome arm 18q. We analyzed a set of colorectal carcinoma cell lines and primary colorectal tumor samples for gene copy alterations and deletion mutations in exons. Based on clustering analysis, we distinguished the different categories of genomic instability among the colorectal cancer cell lines. Our analysis of primary tumors uncovered several distinct categories of colorectal carcinoma, each with specific patterns of 18q deletions and deletion mutations in specific genes. This finding has potential clinical ramifications given the application of 18q loss of heterozygosity events as a potential indicator for adjuvant treatment in stage II colorectal carcinoma. (Cancer Res 2006; 66(16): 7910-9)

Supplementary Table 1 from Oncogenic BRAF Mutation with CDKN2A Inactivation Is Characteristic of a Subset of Pediatric Malignant Astrocytomas

Supplementary Methods. Description of additional methods and procedures used in the study.

Supplementary Figure Legends 1-3 from Synergistic Chemosensitivity of Triple-Negative Breast Cancer Cell Lines to Poly(ADP-Ribose) Polymerase Inhibition, Gemcitabine, and Cisplatin

The basal-like subtype of breast cancer is characterized by a triple-negative (TN) phenotype (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2/neu negative). TN breast cancers share similar gene expression profiles and DNA repair deficiencies with BRCA1-associated breast cancers. BRCA1-mutant cells exhibit sensitivity to gemcitabine, cisplatin, and poly(ADP-ribose) polymerase (PARP) inhibition; therefore, we hypothesized that TN cancer cells may also exhibit sensitivity to these drugs. In this study, we report that TN breast cancer cells are more sensitive to these drugs compared with non-TN breast cancer cells. Moreover, combination treatments indicated that PARP inhibition by the small-molecule inhibitor PJ34 or siRNA knockdown synergized with gemcitabine and cisplatin in TN cells but not in luminal cancer cells. TN cells exhibited reduced repair of UV-induced cyclobutane pyrimidine dimers after PARP inhibition, suggesting that the synergistic effect of PJ34 and gemcitabine or cisplatin reflected inefficient nucleotide excision repair. Mechanistic investigations revealed that in TN cells, PJ34 reduced the levels of ΔNp63α with a concurrent increase in p73 and its downstream target p21. Thus, the sensitivity to combination treatment seemed to be mediated by sustained DNA damage and inefficient DNA repair triggering p63/p73–mediated apoptosis. Our results suggest a novel therapeutic strategy to treat women with TN breast cancer, an aggressive disease that presently lacks effective treatment options. Cancer Res; 70(20); 7970–80. ©2010 AACR.

Supplementary Figures S1-S5. SUM149PT cell line meets the screening criteria (S1); A preliminary screen identified BrdU as a small-molecule positive control (S2); Optimization of conditions for HT-screening (S3); Validation of the HT screening protocol (S4); DNA repair-activating agents exhibit minimal cytotoxicity at concentrations that enhance BER of ODD (S5).

Supplementary Table 2 from Oncogenic BRAF Mutation with CDKN2A Inactivation Is Characteristic of a Subset of Pediatric Malignant Astrocytomas

Supplementary Data 1 from Molecular Inversion Probe Analysis of Gene Copy Alterations Reveals Distinct Categories of Colorectal Carcinoma

Malignant astrocytomas are a deadly solid tumor in children. Limited understanding of their underlying genetic basis has contributed to modest progress in developing more effective therapies. In an effort to identify such alterations, we performed a genome-wide search for DNA copy number aberrations (CNA) in a panel of 33 tumors encompassing grade 1 through grade 4 tumors. Genomic amplifications of 10-fold or greater were restricted to grade 3 and 4 astrocytomas and included the MDM4 (1q32), PDGFRA (4q12), MET (7q21), CMYC (8q24), PVT1 (8q24), WNT5B (12p13), and IGF1R (15q26) genes. Homozygous deletions of CDKN2A (9p21), PTEN (10q26), and TP53 (17p3.1) were evident among grade 2 to 4 tumors. BRAF gene rearrangements that were indicated in three tumors prompted the discovery of KIAA1549-BRAF fusion transcripts expressed in 10 of 10 grade 1 astrocytomas and in none of the grade 2 to 4 tumors. In contrast, an oncogenic missense BRAF mutation (BRAFV600E) was detected in 7 of 31 grade 2 to 4 tumors but in none of the grade 1 tumors. BRAFV600E mutation seems to define a subset of malignant astrocytomas in children, in which there is frequent concomitant homozygous deletion of CDKN2A (five of seven cases). Taken together, these findings highlight BRAF as a frequent mutation target in pediatric astrocytomas, with distinct types of BRAF alteration occurring in grade 1 versus grade 2 to 4 tumors. Cancer Res; 70(2); 512–9

Supplementary Table and Figure Legends. Legend for Supplementary Table S1 and Supplementary Figures S1-S5.

Supplementary Figure 1 from Oncogenic BRAF Mutation with CDKN2A Inactivation Is Characteristic of a Subset of Pediatric Malignant Astrocytomas

Supplementary Figure Legend from Defective Repair of Oxidative DNA Damage in Triple-Negative Breast Cancer Confers Sensitivity to Inhibition of Poly(ADP-Ribose) Polymerase

Subtypes of breast cancer that represent the two major types of epithelial cells in the breast (luminal and basal) carry distinct histopathologic profiles. Breast cancers of the basal-like subtype, which include the majority of hereditary breast cancers due to mutations in the breast cancer susceptibility gene 1 (BRCA1), frequently assume triple-negative status, i.e., they lack expression of estrogen receptor-α and progesterone receptor, and lack overexpression or amplification of the HER2/NEU oncogene. Defects in DNA damage response pathways result in genome instability and lead to carcinogenesis, but may also be exploited for therapeutic purposes. We analyzed repair of oxidative DNA damage by the base-excision repair (BER) pathway, which when aberrant leads to genomic instability and breast carcinogenesis, in cell lines that represent the different subtypes of breast cancer and in the presence of BRCA1 deficiency. We found that basal-like and BRCA1-mutated breast cancer cells were defective in BER of oxidative DNA damage, and that this defect conferred sensitivity to inhibition of poly(ADP-ribose) polymerase, a DNA repair enzyme. The defect may be attributed, at least in part, to a novel role for BRCA1 in the BER pathway. Overall, these data offer preventive, prognostic, and therapeutic usefulness. [Cancer Res 2009;69(8):3589–96]

Supplementary Figure 1 from Defective Repair of Oxidative DNA Damage in Triple-Negative Breast Cancer Confers Sensitivity to Inhibition of Poly(ADP-Ribose) Polymerase

HIV infection occlusive arteriopathies may result in neurological symptoms. We report a case of bilateral complete occlusion of the extracranial portions of the internal carotid arteries in a HIV+ve patient who presented with a syncopal episode due to intraventricular haemorrhage. Compensatory blood flow from the posterior cerebral circulation via the circle of Willis resulted in small telangiectatic vessels arising from the posterior cerebral circulation which probably accounted for this rare haemorrhagic complication of an occlusive arteriopathy.&nbsp

A middle-aged lady who presented with headaches and sudden onset of left cavernous sinus syndrome was found to have a left persistent primitive trigeminal artery (PPTA) on scans. The syndrome uniquely resolved spontaneously after a few days. Vascular variations in the region of the cavernous sinus should be actively sought in cross-sectional imaging performed for cavernous sinus syndrome.

BackgroundMismatch negativity (MMN) reductions are among the most reliable biomarkers for schizophrenia and have been associated with increased risk for conversion to psychosis in individuals at clinical high risk for psychosis (CHR-P). Here, we adopt a computational approach to develop a mechanistic model of MMN reductions in CHR-P individuals and patients early in the course of schizophrenia (ESZ).MethodsElectroencephalography (EEG) was recorded in 38 CHR-P individuals (15 converters), 19 ESZ patients (≤5 years), and 44 healthy controls (HC) during three different auditory oddball MMN paradigms including 10% duration-, frequency-, or double-deviants, respectively. We modelled sensory learning with the hierarchical Gaussian filter and extracted precision-weighted prediction error trajectories from the model to assess how the expression of hierarchical prediction errors modulated EEG amplitudes over sensor space and time.ResultsBoth low-level sensory and high-level volatility precision-weighted prediction errors were altered in CHR-P and ESZ groups compared to HC. Furthermore, low-level precision-weighted prediction errors were significantly different in CHR-P that later converted to psychosis compared to non-converters.ConclusionsOur results implicate altered processing of hierarchical prediction errors as a computational mechanism in early psychosis consistent with predictive coding accounts of psychosis. This computational model appears to capture pathophysiological mechanisms relevant to early psychosis and the risk for future psychosis in CHR-P individuals, and may serve as a predictive biomarker and mechanistic target for novel treatment development.

In search of interventions targeting brain dysfunction and underlying cognitive impairment in schizophrenia, we look at the brain and beyond to the potential role of dysfunctional systemic metabolism on neural network instability and insulin resistance in serious mental illness. We note that disrupted insulin and cerebral glucose metabolism are seen even in medication-naïve first-episode schizophrenia, suggesting that people with schizophrenia are at risk for Type 2 diabetes and cardiovascular disease, resulting in a shortened life span. Although glucose is the brain's default fuel, ketones are a more efficient fuel for the brain. We highlight evidence that a ketogenic diet can improve both the metabolic and neural stability profiles. Specifically, a ketogenic diet improves mitochondrial metabolism, neurotransmitter function, oxidative stress/inflammation, while also increasing neural network stability and cognitive function. To reverse the neurodegenerative process, increasing the brain's access to ketone bodies may be needed. We describe evidence that metabolic, neuroprotective, and neurochemical benefits of a ketogenic diet potentially provide symptomatic relief to people with schizophrenia while also improving their cardiovascular or metabolic health. We review evidence for KD side effects and note that although high in fat it improves various cardiovascular and metabolic risk markers in overweight/obese individuals. We conclude by calling for controlled clinical trials to confirm or refute the findings from anecdotal and case reports to address the potential beneficial effects of the ketogenic diet in people with serious mental illness.

Background Multidrug-resistant organisms (MDRO) in long-term care facilities are prevalent and pose a major health concern for their residents. During the COVID-19 pandemic, infection control measures were justifiably heightened in every aspect of health care, including nursing homes. There are reports depicting decreasing prevalence of MDRO in hospital settings during the pandemic. We compared the prevalence of MDRO in our facility’s nursing homes in the two-year period before vs. the two years of the pandemic. Methods Northport Veterans Affairs Medical Center provides long-term nursing home care structured as community living centers including mental health and hospice care; a 139 total bed capacity. A retrospective review of culture data collected by infection control preventionists comparing the prevalence of MDROs between 1 March 2018 to 28 February 2022 was performed. Data included: Nasopharyngeal MRSA swabs, urine, wound, blood, sputum cultures, C. difficile toxin and PCR assays. MDRO included ESBL E. coli, K. pneumoniae, P. mirabilis, MDR Pseudomonas spp (resistance to 2/3 antibiotics: cefepime/piperacillin-tazobactam/ciprofloxacin), carbapenem-resistant Pseudomonas spp, and vancomycin-resistant Enterococcus spp. Results There were 75209 bed days of care from 1 March 2018 to 28 February 2020 vs. 77531 from 1 March 2020 to 28 February 2022. The MRSA rate per 1000 patient days decreased from 4.98 pre-COVID to 2.70 during-COVID, P < 0.001. Similarly, there was a decrease in C. difficile 0.69 vs. 0.13, P< 0.001, ESBL E. coli 0.53 vs. 0.51, P< 0.001 and S. maltophilia (no cases during COVID). There was an increase in ESBL K. pneumoniae 0.51 vs. 0.63, P< 0.001, MDR Pseudomonas 0.05 vs. 0.49, P< 0.001, carbapenem-resistant Pseudomonas 0.026 vs. 0.077, P< 0.001 and VRE 0.22 vs. 0.31, P< 0.001. There were no Candida auris or Acinetobacter spp detected in the study period. MDRO occurrences before and during COVID-19 pandemic Conclusion While increased awareness and implementation of infection control measures during the years of the COVID-19 pandemic led to decrease in certain infections in our nursing homes, like C. difficile, a surprising uptick in ESBL K. pneumoniae and MDR Pseudomonas was noted. This is a concerning trend that merits further study to identify molecular factors and increase stewardship efforts in diligent use of carbapenems. Disclosures All Authors: No reported disclosures.

Background COVID-19 (C-19) vaccines have demonstrated effectiveness in reducing SARS-CoV-2 related morbidity/mortality. The duration of protection in the general population is showing a waning immunity over time. Variable antibody responses to C-19 vaccines have been shown in persons living with HIV. We followed the anti-SARS-CoV-2 receptor biding domain (RBD) antibody titers, after 2 and 3 (booster) C-19 vaccinations, in US Veterans living with HIV (USVLH). Methods Retrospective chart review of USVLH who had received C-19 vaccinations at Northport VAMC. Testing was done with the © Beckman Coulter enzyme immunoassay measuring total IgG antibody to the RBD, a critical target of neutralizing antibodies within the spike protein encoded in the mRNA vaccines. Titers were drawn after the 2nd and 3rd doses C-19 vaccines in variable timing. Demographic data, CD4+ T cell counts nadir and current, HIV viral load, comorbid conditions were reviewed. Results We analyzed the SARS CoV-2 RBD IgG titers in 50 vaccinated USVLH. The median age is 65 years (range 36-75). 50% were Black, Caucasian 40%, Hispanic 10%. Risk factor for HIV infection, Heterosexual 52%, IVDU 18%, MSM 26%, needle stick 2%, blood transfusion 2%. The median CD4 nadir was 200/µL (5- 600), median current CD4 656 (174-1529). All USVLH were on HAART, 92% on INSTI-based therapy. 45 had undetectable HIV viral load (< 20), 5 had viremia from 22 to 563 copies. Medical conditions: diabetes 30%, CAD 18%, HTN 60%, COPD 8%, HLD 66%, smokers 18%. Six USV had C-19 prior to vaccination, and six had C-19 after vaccination with median 102 days (90-148) from last vaccine dose. Vaccines given: Janssen in 3 USVLH: Moderna (MOD)- 2 doses: 4; MOD-3 doses:5; Pfizer (PFZ)-2: 6; PFZ-3: 32. IgG titers decrease with time after 2nd vaccine dose and increase after booster dose. IgG titers checked after 2nd dose median days 120 (11-392) {titers: median 4.63 S/CO [0.17 – 53.66]}, 91 days (5-181) after 3rd dose {titers: median 16.22 [1.15-73.92]}. Titers were higher in MOD-2 vs. PFZ-2, median 25.7 vs. 4.63, P: 0.039, MOD-3 vs. PFZ-3 33.89 vs. 15.5, P: 0.117. No death due to C-19 was seen. SARS-CoV-2 RBD IgG titers in US Veterans living with HIV after 2nd dose of COVID vaccine. COVID-19 VACCINATED IN US VETERANS LIVING WITH HIV N=50 Conclusion In a cohort of USVLH, well controlled on HAART, C-19 vaccinations produced a serologic response that decayed over time and increased after booster dose. MOD vaccine may have achieved higher titers than PFZ. Disclosures All Authors: No reported disclosures.

Sleep problems are widely reported among children and adolescents on the autism spectrum. There is emerging evidence of the effectiveness and social validity of parent-implemented behavioral sleep interventions for children and adolescents on the autism spectrum. However, most research is focused on multi-component interventions that include the use of extinction, and questions remain about the effectiveness of modification to antecedent variables (including sleep/wake rescheduling) alone. This systematic review aims to summarize and appraise the literature examining the effectiveness of antecedent-based modifications for treating sleep problems among children on the autism spectrum. Eligible studies included one or more participants aged 2 to 18 years with autism and treated sleep problems using modification to antecedent variables as standalone treatments. Data were identified from PsycINFO, Cochrane Library, Scopus, and MEDLINE databases and extracted according to participant characteristics and sleep problems, study design, characteristics of the intervention, dependent variables and sleep measures, treatment outcomes, and social validity. Study quality was evaluated using a standardized rubric and was classified as “strong,” “adequate,” or “weak.” Overall, 12 studies met inclusion criteria. All studies reported improvements in sleep problems for most or all participants following antecedent-based modifications. Improvements were maintained at follow-up for all participants for whom this data was collected. Only 3 studies met criteria reflecting strong methodological rigor. Modification to antecedent variables can reduce or eliminate sleep problems; however, there is a need for more rigorous evaluation and systematic extension of these findings. Minimally sufficient modification of antecedent variables may be implemented as a less restrictive alternative to consequence-based interventions. Systematic review registration: PROSPERO CRD42021240539.

Practice change is essential if environmental agencies are to incorporate diverse values in decision making, but little is currently known about what constrains or enables such change. Over a 19-month period, we observed how environmental professionals responded to an agency request that they consider a wider range of values in strategic bushfire management planning than had been considered in past practice. Through participant observation, interviews and document analysis, we examined how practices did and did not change and what contributed to these outcomes. Practices for assessing well understood values (e.g. towns and houses, ecological resilience) were refined, while practices for handling less familiar values (e.g. animal welfare, economic values and Indigenous cultural heritage) were either maintained, adapted or transformed, with outcomes varying across values and regions. The findings partly confirm expected biases toward values that can be spatially located and quantified, and point to other conditions supporting change to incorporate new types of values: alignment between policy and planning guidance, alignment between a value and priorities of professionals and agencies involved in planning, collaboration that supported input from cross-agency actors, and scope for experimentation. We discuss the practical implications of these findings for agencies seeking to incorporate values in environmental planning.

Current retinal prostheses (RPs) have not achieved useful vision restoration, as their resolution is limited by power dissipation and complexity of interconnect. This article presents an inductively powered wireless system on a chip (SoC) for an electrically controlled, optically addressed retinal prosthetic system. The SoC interfaces to a co-fabricated nanoengineered photosensitive electrode array using only two wires. To reduce the thermal dissipation near sensitive retinal tissue, the proposed design pushes voltage regulation and charge-balanced stimulation control off the implant via a duty-cycled wireless charge metering technique. A calibration technique compensating for power fluctuation caused by eye movement is also presented. Implemented in 180-nm CMOS and delivering up to $3~\mu \text{C}$ of charge at 20-nC resolution, the SoC achieves 73% RF-to-stimulation power efficiency.

Environmental decision-making is recognised as requiring integration of biophysical and social knowledge, but integration of knowledges based in different epistemic assumptions is challenging. We used an action research approach to observe integration in the development of a landscape decision support system (DSS) for forest and fire management in Victoria, Australia. We found two different knowledge integration processes, conceptually-driven to shape the structure of the DSS and technically-driven through modelling. Project framing dominated by biophysical sciences and technically-driven integration presented a barrier to many potential social science contributions that could connect a DSS with the surrounding social and decision contexts. Nonetheless, some conceptually-driven integration occurred when social researchers contributed their analysis of values of the public to the DSS design. The need for this integration emerged through initial conflict over disciplinary understandings of ‘value’. While initially uncomfortable, this opened the way to differentiate knowledge related to the term and to negotiate some conceptual synthesis and an agreed multidisciplinary list of values to structure the DSS. Technically-driven integration occurred through incorporation of social and biophysical metrics in model software. Our research highlights that bridging concepts such as values and related frameworks act as boundary objects that help in overcoming barriers to integration between social and biophysical knowledge. Integration is itself a potential boundary object and early discussions to differentiate and clarify how the term is understood can help in designing interdisciplinary processes. Critically, projects need adequate time for interdisciplinary differentiation, tolerance amongst the team for uncomfortable conversations, and leadership that fosters interdisciplinary interactions to achieve a high degree of knowledge integration.

There are calls to consider the views of the diverse public in bushfire policy, planning, and management, yet those who do not typically participate in social research and/or government community engagement activities are generally under-represented. A mixed method research design was used, including a survey, intercept and in-depth interviews to study a diversity of views. Concepts of social values, knowledge and practices were drawn on first to examine participants’ relationship to bushfire and second to discuss bushfire engagement. We identified and analyzed three relationships to bushfire: Irrelevant to me; Terror at my door; A rural concern. Participants’ values were more focused on people, pets, and special things than in earlier research and they generally perceived bushfire as solely a domain for experts. There is an opportunity to find ways to resonate with their values and relationships to bushfire, and to shape bushfire research and practice.

Chemotactic bacteria sense and respond to temporal and spatial gradients of chemical cues in their surroundings. This phenomenon plays a critical role in many microbial processes such as groundwater bioremediation, microbially enhanced oil recovery, nitrogen fixation in legumes, and pathogenesis of the disease. Chemical heterogeneity in these natural systems may produce numerous competing signals from various directions. Predicting the migration behavior of bacterial populations under such conditions is necessary for designing effective treatment schemes. In this study, experimental studies and mathematical models are reported for the chemotactic response of Escherichia coli to a combination of attractant (α-methylaspartate) and repellent (NiCl2 ), which bind to the same transmembrane receptor complex. The model describes the binding of chemoeffectors and phosphorylation of the kinase in the signal transduction mechanism. Chemotactic parameters of E. coli (signaling efficiency σ , stimuli sensitivity coefficient γ , and repellent sensitivity coefficient κ ) were determined by fitting the model with experimental results for individual stimuli. Interestingly, our model naturally identifies NiCl2 as a repellent for κ>1 . The model is capable of describing quantitatively the response to the individual attractant and repellent, and correctly predicts the change in direction of bacterial population migration for competing stimuli with a twofold increase in repellent concentration.