Medicine and Health Sciences Commons^™

First-In-Human Phase I Study Of Infusional And Bolus Schedules Of Deflexifol, A Novel 5-Fluorouracil And Leucovorin Formulation, After Failure Of Standard Treatment, Phillip R. Clingan, Stephen Ackland, Daniel Brungs, Paul De Souza, Morteza Aghmesheh, Madhu Garg, Richard Ranson, Suzanne Parker, Rebecca Jokela, Marie Ranson

Illawarra Health and Medical Research Institute

Background: 5‐Fluorouracil (5‐FU) is administered with leucovorin (LV) to enhance clinical activity. However, simultaneous administration is not feasible due to their chemical incompatibility, so conditions for the maximum possible beneficial interaction cannot be met. To overcome this, we developed a novel all‐in‐one, pH neutral stable solution of 5‐FU plus LV with β‐cyclodextrin (termed Deflexifol) and assessed its safety and tolerability in a first‐in‐human phase I trial.

Methods: Patients with advanced solid malignancy received Deflexifol as weekly bolus (375–575 mg/m²) or two‐weekly 46 h infusion (1200–3600 mg/m²) for six cycles in a 3+3 dose escalation design. …

Intimate Moments: Dispelling The Cancer Myth With Real Life - Summer Rain By Nanna Hauge Kristensen., Sophie Townsend

RadioDoc Review

Nanna Hauge Kristensen’s Summer Rain is a small piece in length and in scope. It is intimate, almost fragmentary. It is simply a story of a woman, who is a mother, and a daughter, and who has cancer; a woman undergoing treatment, and raising her child, and dealing with the ramifications of what cancer treatment means. An anthropologist by training, Kristensen’s observational, almost distanced approach style, allows us to glimpse her life, but also to feel it. There is something very empirical about what she’s doing in this piece, and she allows us no room to pretend that her cancer …

Effects Of Short- And Long-Term Aripiprazole Treatment On Group I Mglurs In The Nucleus Accumbens: Comparison With Haloperidol, Jeremy Lum, Bo Pan, Chao Deng, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell

Illawarra Health and Medical Research Institute

The D2 receptor partial agonist, aripiprazole, has shown increased therapeutic efficacy for schizophrenia, autism and Tourette's syndrome compared to traditional antipsychotics such as the D2 receptor antagonist, haloperidol. Recent evidence suggests this superior profile may be associated with downstream effects on glutamatergic synapses. Group 1 metabotropic glutamate receptors (mGluRs) and their endogenous modulators, Norbin and Homer1, are regulated by D2 receptor activity, particularly within the nucleus accumbens (NAc), a target region of aripiprazole and haloperidol. This study sought to evaluate the effects of aripiprazole on Group 1 mGluRs, Norbin and Homer1 in the NAc, in comparison to haloperidol. Sprague-Dawley rats …

Detection Of Kinetic Change Points In Piece-Wise Linear Single Molecule Motion, Flynn R. Hill, Antoine M. Van Oijen, Karl E. Duderstadt

Illawarra Health and Medical Research Institute

Single-molecule approaches present a powerful way to obtain detailed kinetic information at the molecular level. However, the identification of small rate changes is often hindered by the considerable noise present in such single-molecule kinetic data. We present a general method to detect such kinetic change points in trajectories of motion of processive single molecules having Gaussian noise, with a minimum number of parameters and without the need of an assumed kinetic model beyond piece-wise linearity of motion. Kinetic change points are detected using a likelihood ratio test in which the probability of no change is compared to the probability of …

Cyclic Analogues Of Α-Conotoxin Vc1.1 Inhibit Colonic Nociceptors And Provide Analgesia In A Mouse Model Of Chronic Abdominal Pain, Joel Castro, Luke Grundy, Annemie Deiteren, Andrea M. Harrington, Tracey O'Donnell, Jessica Maddern, Jessi Moore, Sonia Garcia-Caraballo, Grigori Rychkov, Rilei Yu, Quentin Kaas, David J. Craik, David J. Adams, Stuart Brierley

Illawarra Health and Medical Research Institute

Background and Purpose: Patients with irritable bowel syndrome suffer from chronic visceral pain (CVP) and limited analgesic therapeutic options are currently available. We have shown that α-conotoxin Vc1.1 induced activation of GABA_B receptors on the peripheral endings of colonic afferents and reduced nociceptive signalling from the viscera. However, the analgesic efficacy of more stable, cyclized versions of Vc1.1 on CVP remains to be determined.

Experimental Approach: Using ex vivo colonic afferent preparations from mice, we determined the inhibitory actions of cyclized Vc1.1 (cVc1.1) and two cVc1.1 analogues on mouse colonic nociceptors in healthy and chronic visceral hypersensitivity …

Attaching Nora Efflux Pump Inhibitors To Methylene Blue Enhances Antimicrobial Photodynamic Inactivation Of Escherichia Coli And Acinetobacter Baumannii In Vitro And In Vivo, Ardeshir Rineh, John B. Bremner, Michael R. Hamblin, Anthony R. Ball, George P. Tegos, Michael J. Kelso

Illawarra Health and Medical Research Institute

Resistance of bacteria to antibiotics is a public health concern worldwide due to the increasing failure of standard antibiotic therapies. Antimicrobial photodynamic inactivation (aPDI) is a promising non-antibiotic alternative for treating localized bacterial infections that uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species and kill microbes. Phenothiazinium photosensitizers like methylene blue (MB) and toluidine blue O are hydrophobic cations that are naturally expelled from bacterial cells by multidrug efflux pumps, which reduces their effectiveness. We recently reported the discovery of a NorA efflux pump inhibitor-methylene blue (EPI-MB) hybrid compound INF55-(Ac)en-MB that shows enhanced photodynamic inactivation of …

Development And Optimization Of Ciprofloxacin-Loaded Gelatin Microparticles By Single-Step Spray-Drying Technique, Dina M. Morais Da Silva, Heema Vyas, Martina L. Sanderson-Smith, Vitor Sencadas

Illawarra Health and Medical Research Institute

Polymeric particles are a versatile class of local or systemic drug delivery systems, used to improve drugs pharmacokinetics and pharmacodynamics along with patient compliance. Herein, we report a rapid, scalable, and optimized method to encapsulate ciprofloxacin (CP_x), a poor water soluble antimicrobial agent, in gelatin microparticles by single step processing via spray-drying of an aqueous solution. The developed particles show mainly a wrinkle morphology with a unimodal distribution, with mean diameters ranging between 2 and 4 μm, depending on the processing conditions. The encapsulation of 1, 2 and 5 wt% CPx narrows the size distribution (1-3 μm). In …

The Impact Of Caller Gender On Telephone Crisis-Helpline Workers' Interpretation Of Suicidality In Caller Vignettes, Tara Hunt, Coralie J. Wilson, Peter Caputi, Ian G. Wilson, Alan Woodward

Illawarra Health and Medical Research Institute

Telephone crisis-line workers (TCWs) are trained in a variety of techniques and skills to facilitate the identification of suicidal callers. One factor that may influence the implementation of these skills is gender. This study used an experimental design to explore whether helpline callers being identified as male or female is associated with TCWs' ratings of callers' potential for suicide risk and TCWs' intention to use support- or intervention-oriented skills with callers. Data were collected using an online self-report survey in an Australian sample of 133 TCWs. The results suggest that under some circumstances the callers' gender might influence TCWs' intention …

The Transcription-Repair Coupling Factor Mfd Associates With Rna Polymerase In The Absence Of Exogenous Damage, Han Ngoc Ho, Antoine M. Van Oijen, Harshad Ghodke

Illawarra Health and Medical Research Institute

During transcription elongation, bacterial RNA polymerase (RNAP) can pause, backtrack or stall when transcribing template DNA. Stalled transcription elongation complexes at sites of bulky lesions can be rescued by the transcription terminator Mfd. The molecular mechanisms of Mfd recruitment to transcription complexes in vivo remain to be elucidated, however. Using single-molecule live-cell imaging, we show that Mfd associates with elongation transcription complexes even in the absence of exogenous genotoxic stresses. This interaction requires an intact RNA polymerase-interacting domain of Mfd. In the presence of drugs that stall RNAP, we find that Mfd associates pervasively with RNAP. The residence time of …

Single-Molecule Characterization Of The Interactions Between Extracellular Chaperones And Toxic Α-Synuclein Oligomers, Daniel Whiten, Dezerae Cox, Mathew H. Horrocks, Christopher Taylor, Suman De, Patrick Flagmeier, Laura Tosatto, Janet R. Kumita, Heath Ecroyd, Christopher M. Dobson, David Klenerman, Mark R. Wilson

Illawarra Health and Medical Research Institute

The aberrant aggregation of α-synuclein is associated with several human diseases, collectively termed the α-synucleinopathies, which includes Parkinson's disease. The progression of these diseases is, in part, mediated by extracellular α-synuclein oligomers that may exert effects through several mechanisms, including prion-like transfer, direct cytotoxicity, and pro-inflammatory actions. In this study, we show that two abundant extracellular chaperones, clusterin and α2-macroglobulin, directly bind to exposed hydrophobic regions on the surface of α-synuclein oligomers. Using single-molecule fluorescence techniques, we found that clusterin, unlike α2-macroglobulin, exhibits differential binding to α-synuclein oligomers that may be related to structural differences between two previously described forms …

Chronic Adolescent Cdppb Treatment Alters Short-Term, But Not Long-Term, Glutamatergic Receptor Expression, Jeremy Lum, Samuel Millard, Elisabeth T. Frank, Natalie Matosin, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell

Illawarra Health and Medical Research Institute

Dysfunction of the glutamatergic system is believed to underlie many neurodevelopmental disorders including autism, Rett syndrome and schizophrenia. Metabotropic glutamate receptor (mGluR5) positive allosteric modulators (PAM) potentiate glutamatergic signaling, particularly indirectly via the NMDA receptor. Preclinical studies report mGluR5 PAMs can improve schizophrenia-relevant behaviours. Furthermore, adolescent administration has shown to prevent cognitive induced deficits in adult rodents. However, there is limited understanding of the short- and long-term neurochemical effects of mGluR5 PAMs, which may underlie their therapeutic effects. We examined the effect of 7-day adolescent (PN28-34) treatment with the mGluR5 PAM, CDDPB (30 mg/kg), on glutamatergic receptor expression at adolescence …

Identifying Usual Food Choices At Meals In Overweight And Obese Study Volunteers: Implications For Dietary Advice, Vivienne Guan, Yasmine Probst, Elizabeth Neale, Marijka Batterham, Linda C. Tapsell

Illawarra Health and Medical Research Institute

Understanding food choices made for meals in overweight and obese individuals may aid strategies for weight loss tailored to their eating habits. However, limited studies have explored food choices at meal occasions. The aim of this study was to identify the usual food choices for meals of overweight and obese volunteers for a weight-loss trial. A cross-sectional analysis was performed using screening diet history data from a 12-month weight-loss trial (the HealthTrack study). A descriptive data mining tool, the Apriori algorithm of association rules, was applied to identify food choices at meal occasions using a nested hierarchical food group classification …

Inhibition Of Human N- And T-Type Calcium Channels By An Ortho-Phenoxyanilide Derivative, Moniro-1, Jeffrey R. Mcarthur, Leonid Motin, Ellen Gleeson, Sandro Spiller, Richard J. Lewis, Peter J. Duggan, Kellie L. Tuck, David J. Adams

Illawarra Health and Medical Research Institute

Background and Purpose: Voltage-gated calcium channels are involved in nociception in the CNS and in the periphery. N-type (Ca_v2.2) and T-type (Ca_v3.1, Ca_v3.2 and Ca_v3.3) voltage-gated calcium channels are particularly important in studying and treating pain and epilepsy. Experimental Approach: In this study, whole-cell patch clamp electrophysiology was used to assess the potency and mechanism of action of a novel ortho-phenoxylanilide derivative, MONIRO-1, against a panel of voltage-gated calcium channels including Ca_v1.2, Ca_v1.3, Ca_v2.1, Ca_v2.2, Ca_v2.3, Ca_v3.1, Ca …

Astrocytic Modulation Of Cortical Oscillations, Alba Bellot-Saez, Greg Cohen, Andre Van Schaik, Lezanne Ooi, John W. Morley, Yossi Buskila

Illawarra Health and Medical Research Institute

Brain waves are rhythmic voltage oscillations emerging from the synchronization of individual neurons into a neuronal network. These oscillations range from slow to fast fluctuations, and are classified by power and frequency band, with different frequency bands being associated with specific behaviours. It has been postulated that at least ten distinct mechanisms are required to cover the frequency range of neural oscillations, however the mechanisms that gear the transition between distinct oscillatory frequencies are unknown. In this study, we have used electrophysiological recordings to explore the involvement of astrocytic K⁺ clearance processes in modulating neural oscillations at both network …

Transcription Factor Tbx18 Induces The Differentiation Of C-Kit+Canine Mesenchymal Stem Cells (Cmscs) Into San-Like Pacemaker Cells In A Co-Culture Model In Vitro, Hua Xiao, Yong-Jun Yang, Yi-Zhang Lin, Song Peng, Shu Lin, Zhi-Yuan Song

Illawarra Health and Medical Research Institute

Bone mesenchymal stem cells (MSCs), as well as cardiomyocytes, are derived from early mesoderm, becoming committed to their fate under the influence of different differentiation factors. We examined whether the overexpression of Tbx18 can induce the differentiation of c-kit⁺ cMSCs into a phenotype similar to that of native pacemaker cells and whether these transfected cells can couple to adjacent atrial cells with functional consequences. The c-kit⁺ cMSCs were first sorted, then transfected with different lentiviral vectors. Tbx18-c-kit⁺ cMSCs represented the experimental group, while EYFP-c-kit⁺ cMSCs and canine sinoatrial node (SAN) cells were used as controls. Within …

A Systematic Benchmarking Of Computational Vibrational Spectroscopy With Dftb3: Normal Mode Analysis And Fast Fourier Transform Dipole Autocorrelation Function, Venkatasaisandeep Inakollu, Haibo Yu

Illawarra Health and Medical Research Institute

Computational vibrational spectroscopy serves as an important tool in the interpretation of experimental infrared (IR) spectra. In this article, we present a systematic benchmarking study of DFTB3 with two different computational vibrational spectroscopic methods, based on either normal mode analysis (NMA) or fast Fourier transform dipole autocorrelation function (FT‐DAC). The results were compared with experimental data and theoretical calculations with B3LYP/cc‐pVTZ. The empirical scaling factors for DFTB3/NMA, DFTB3‐freq/NMA, and DFTB3/FT‐DAC methods are 0.9993, 1.0059, and 0.9982, respectively. We also demonstrate the significance of anharmonicity and conformational sampling in vibrational spectroscopic calculations on flexible molecules. As expected, DFTB3/FT‐DAC predicted the anharmonic …

Modelling The Dorsal Root Ganglia Using Human Pluripotent Stem Cells: A Platform To Study Peripheral Neuropathies, Serena Viventi, Mirella Dottori

Illawarra Health and Medical Research Institute

Sensory neurons of the dorsal root ganglia (DRG) are the primary responders to stimuli inducing feelings of touch, pain, temperature, vibration, pressure and muscle tension. They consist of multiple subpopulations based on their morphology, molecular and functional properties. Our understanding of DRG sensory neurons has been predominantly driven by rodent studies and using transformed cell lines, whereas less is known about human sensory DRG neurons simply because of limited availability of human tissue. Although these previous studies have been fundamental for our understanding of the sensory system, it is imperative to profile human DRG subpopulations as it is becoming evident …

6-Substituted Hexamethylene Amiloride (Hma) Derivatives As Potent And Selective Inhibitors Of The Human Urokinase Plasminogen Activator For Use In Cancer, Benjamin J. Buckley, Ashraf Abdel A. Aboelela, Elahe Minaei, Longguang Jiang, Zhihong Xu, Umar Ali, Karen J. Fildes, Chen Cheung, Simon M. Cook, Darren Johnson, Daniel Bachovchin, Gregory Cook, Minoti Apte, Mingdong Huang, Marie Ranson, Michael J. Kelso

Illawarra Health and Medical Research Institute

Metastasis is the cause of death in the majority (∼90%) of malignant cancers. The oral potassium-sparing diuretic amiloride and its 5-substituted derivative 5-N,N-(hexamethylene)amiloride (HMA) reportedly show robust antitumor/metastasis effects in multiple in vitro and animal models. These effects are likely due, at least in part, to inhibition of the urokinase plasminogen activator (uPA), a key protease determinant of cell invasiveness and metastasis. This study reports the discovery of 6-substituted HMA analogs that show nanomolar potency against uPA, high selectivity over related trypsin-like serine proteases, and minimal inhibitory effects against epithelial sodium channels (ENaC), the diuretic and antikaliuretic target of amiloride. …

The Effect Of Dna Backbone On The Triplet Mechanism Of Uv-Induced Thymine-Thymine (6-4) Dimer Formation, Xingyong Wang, Haibo Yu

Illawarra Health and Medical Research Institute

Density functional theory calculations have been carried out to investigate the formation mechanism of the thymine-thymine (6-4) dimer ((6-4)TT), which is one of the main DNA lesions induced by ultraviolet radiation and is closely related to skin cancers. The DNA backbone was found to have nonnegligible effects on the triplet reaction pathway, particularly the reaction steps involving substantial base rotations. The mechanism for the isomerisation from (6-4)TT to its Dewar valence isomer (DewarTT) was also explored, confirming the necessity of absorbing a second photon. In addition, the solvation effects were examined and showed considerable influence on the potential energy surface.

Targeting Of N-Type Calcium Channels Via Gabab-Receptor Activation By Α-Conotoxin Vc1.1 Variants Displaying Improved Analgesic Activity, Fengtao Cai, Ning Xu, Zhuguo Liu, Rong Ding, Shuo Yu, Mingxin Dong, Shuo Wang, Jintao Shen, Han Shen Tae, David J. Adams, Xuerong Zhang, Qiuyun Dai

Illawarra Health and Medical Research Institute

α-Conotoxins exhibiting analgesic activity, such as Vc1.1, have been shown to inhibit α9α10 nicotinic acetylcholine receptors (nAChRs) and GABA_B-receptor (GABA_BR) coupled N-type (Ca_V2.2) calcium channels. Here, we report two Vc1.1 variants, Vc1.1[N9R] and benzoyl-Vc1.1[N9R], that selectively inhibit Ca_V2.2 channels via GABA_BR activation but exhibit reduced inhibitory activity at α9α10 and other neuronal nAChR subtypes compared with Vc1.1. Surprisingly, the analgesic activity of Vc1.1[N9R] and benzoyl-Vc1.1[N9R] was more potent than that of Vc1.1 when tested in partial sciatic nerve ligation injury and chronic constriction injury models. Vc1.1[N9R] and benzoyl-Vc1.1[N9R] exhibited either …

Exposure To High-Frequency Electromagnetic Field Triggers Rapid Uptake Of Large Nanosphere Clusters By Pheochromocytoma Cells, Palalle G. Tharushi Perera, The Hong Phong Nguyen, Chaitali Dekiwadia, Jason V. Wandiyanto, I Sbarski, Olga Bazaka, Kateryna Bazaka, Russell Crawford, Rodney J. Croft, Elena Ivanova

Illawarra Health and Medical Research Institute

Background: Effects of man-made electromagnetic fields (EMF) on living organisms potentially include transient and permanent changes in cell behaviour, physiology and morphology. At present, these EMF-induced effects are poorly defined, yet their understanding may provide important insights into consequences of uncontrolled (e.g., environmental) as well as intentional (e.g., therapeutic or diagnostic) exposure of biota to EMFs. In this work, for the first time, we study mechanisms by which a high frequency (18 GHz) EMF radiation affects the physiology of membrane transport in pheochromocytoma PC 12, a convenient model system for neuro-toxicological and membrane transport studies.

Methods and results: …

A High-Throughput Method For The Analysis Of Erythrocyte Fatty Acids And The Omega-3 Index, Ayedh Alqarni, Kiara Mcintyre, Simon H. J Brown, Barbara J. Meyer, Todd W. Mitchell

Illawarra Health and Medical Research Institute

Omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) have several health benefits. In particular, low n-3 LCPUFA status is associated with cardiovascular disease (CVD) and led to the development of the omega-3 index that is the proportion of eicosapentaenoic acid and docosahexaenoic acid in the erythrocyte membranes, as a marker of CVD risk. Most methods used to measure the omega-3 index are laborious and time consuming. Therefore, the aim of this study was to develop a high-throughput method for the extraction and measurement of erythrocyte fatty acids and the omega-3 index. For sample extraction and quantification, two methods were used; a …

Could An Allied Health Care Approach Reduce The Unacceptable Incidence Of Suicide After Psychiatric Hospital Discharge?, Katrina Weston-Green, Ashleigh L. Osborne, Kelly A. Newell

Illawarra Health and Medical Research Institute

We propose that an allied care model could assist to reduce the unacceptably high incidence of suicide after psychiatric hospital discharge. A designated care coordinator is needed to provide holistic discharge planning that incorporates medical, functional and social support for the patient. At a minimum, this approach must include assessment of suicide means access and modifications to the home environment to reduce risk of injury as a standard management procedure.

Defining And Developing A Generic Framework For Monitoring Data Quality In Clinical Research, Lauren Houston, Ping Yu, Allison Martin, Yasmine Probst

Illawarra Health and Medical Research Institute

Evidence for the need for high data quality in clinical research is well established. The rigor of clinical research conclusions rely heavily on good quality data, which relies on good documentation practices. Little attention has been given to clear guidelines and definitions to monitor data quality. To address this, a "fit-for-use" data quality monitoring framework (DQMF) for clinical research was developed based on a holistic design-oriented approach. An integrated literature review and feasibility study underpinned the framework development. Ontology of key terms, concepts, methods, and standards were recorded using a consensus approach and mind mapping technique. The DQMF is presented …

Antibacterial Properties Of Four Novel Hit Compounds From A Methicillin-Resistant Staphylococcus Aureus-Caenorhabditis Elegans High-Throughput Screen, Nagendran Tharmalingam, Rajmohan Rajmuthiah, Wooseong Kim, Beth Fuchs, Elamparithi Jeyamani, Michael J. Kelso, Eleftherios Mylonakis

Illawarra Health and Medical Research Institute

There is an urgent need for the discovery of effective new antimicrobial agents to combat the rise of bacterial drug resistance. High-throughput screening (HTS) in whole-animal infection models is a powerful tool for identifying compounds that show antibacterial activity and low host toxicity. In this report, we characterize the activities of four novel antistaphylococcal compounds identified from an HTS campaign conducted using Caenorhabditis elegans nematodes infected with methicillin-resistant Staphylococcus aureus (MRSA). The hit compounds included an Nhydroxy indole-1, a substituted melamine derivative-2, N-substituted indolic alkyl isothiocyanate-3, and pdifluoromethylsulfide analog-4 of the well-known protonophore carbonyl cyanide m-chlorophenyl hydrazone. Minimal inhibitory concentrations …

Plasma Cortisol And Oxytocin Levels Predict Help-Seeking Intentions For Depressive Symptoms, Susan J. Thomas, Theresa A. Larkin

Faculty of Science, Medicine and Health - Papers: part A

Background: Depressed individuals often refuse or withdraw from help, a phenomenon termed help-negation, which is a risk factor for poor outcomes. Most previous research has investigated psychosocial factors including stigma as causes of low help-seeking intentions for depression, however these do not adequately explain the problem. We hypothesised that because help-negation worsens with symptom severity, it might be linked to important biological changes associated with depression itself. We investigated the relative contributions of cortisol, a stress hormone linked to depression, and oxytocin, a hormone which mediates social behaviours, alongside psychosocial factors, to help-seeking intentions among depressed and non-depressed individuals. Methods: …

Repeated Megafloods From Glacial Lake Vitim, Siberia, To The Arctic Ocean Over The Past 60,000 Years, Martin Margold, John D. Jansen, Alexandru Tiberiu Codilean, Frank Preusser, Artem L. Gurinov, Toshiyuki Fujioka, David Fink

Faculty of Science, Medicine and Health - Papers: part A

Cataclysmic outburst floods transformed landscapes and caused abrupt climate change during the last deglaciation. Whether such events have also characterized previous deglaciations is not known. Arctic marine cores hint at megafloods prior to Oxygen Isotope Stage (OIS) 2, but the overprint of successive glaciations means that geomorphological traces of ancient floods remain scarce in Eurasia and North America. Here we present the first well-constrained terrestrial megaflood record to be linked with Arctic archives. Based on cosmogenic-nuclide exposure dating and optically stimulated luminescence dating applied to glacial-lake sediments, a 300-m deep bedrock spillway, and giant eddy-bars > 200-m high, we reconstruct a …

Biological And Geophysical Feedbacks With Fire In The Earth System, Sally Archibald, Caroline E. R Lehmann, C Belcher, William J. Bond, Ross A. Bradstock, A-L Daniau, K Dexter, E Forrestel, M Greve, T He, S I. Higgins, W Hoffmann, B B. Lamont, D J. Mcglinn, G Moncrieff, C P. Osborne, Juli G. Pausas, Owen F. Price, B Ripley, B Rogers, D Schwilk, M Simon, M Turetsky, G R. Van Der Werf, A E. Zanne

Faculty of Science, Medicine and Health - Papers: part A

Roughly 3% of the Earth's land surface burns annually, representing a critical exchange of energy and matter between the land and atmosphere via combustion. Fires range from slow smouldering peat fires, to low-intensity surface fires, to intense crown fires, depending on vegetation structure, fuel moisture, prevailing climate, and weather conditions. While the links between biogeochemistry, climate and fire are widely studied within Earth system science, these relationships are also mediated by fuels-namely plants and their litter-that are the product of evolutionary and ecological processes. Fire is a powerful selective force and, over their evolutionary history, plants have evolved traits that …

Discovery Of Ancient Roman "Highway" Reveals Geomorphic Changes In Karst Environments During Historic Times, Federico Bernardini, Giacomo Vinci, Emanuele Forte, Stefano Furlani, Michele Pipan, Sara Biolchi, Angelo De Min, Andrea Fragiacomo, Roberto Micheli, Paola Ventura, Claudio Tuniz

Faculty of Science, Medicine and Health - Papers: part A

Sinkholes are a well-known geologic hazard but their past occurrence, useful for subsidence risk prediction, is difficult to define, especially for ancient historic times. Consequently, our knowledge about Holocene carbonate landscapes is often limited. A multidisciplinary study of Trieste Karst (Italy), close to early Roman military fortifications, led to the identification of possible ancient road tracks, cut by at least one sinkhole. Electrical Resistivity Tomography through the sinkhole has suggested the presence of a cave below its bottom, possibly responsible of the sinkhole formation, while Ground Penetrating Radar has detected no tectonic disturbances underneath the tracks. Additionally, archaeological surveys led …

Packaging Data Analytical Work Reproducibly Using R (And Friends), Ben Marwick, Carl Boettiger, Lincoln Mullen

Faculty of Science, Medicine and Health - Papers: part A

Computers are a central tool in the research process, enabling complex and large-scale data analysis. As computer-based research has increased in c omplexity, so have the challenges of ensuring that this research is reproducible. To address this challenge, we review the concept of the research compendium as a solution for providing a standard and easily recognizable way for organizing the digital materials of a research project to enable other researchers to inspect, reproduce, and extend the research. We investigate how the structure and tooling of software packages of the R programming language are being used to produce research compendia in …