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Background This paper describes the development of an eight-week Compassion Focused Therapy for Pain Management (CFT-PM) group. This group was specifically designed for ‘strivers’ a sub-group of people with persistent pain who tend to engage in over-activity and resist making reasonable adjustments to their activity levels to accommodate their persistent pain. ‘Strivers’ tend to cope by ignoring their pain and pushing on through, in the shorter term leading to ‘boom and bust’ activity-related exacerbations of their pain. They also risk the development of additional persistent fatigue and burnout in the longer term. Method 117 people completed the CFT-PM group; The group was delivered in person ( n = 84) but in online format from July 2020 ( n = 33). 162 people started the CFT-PM group but 45 dropped-out (27.43%). Results There was a significant effect for time across all measures: significant improvement was found for depression, self-compassion, pain-related disability, pain-related anxiety and pain self-efficacy. Pain numeric rating scores were approaching significance. There was a significant main effect of diagnosis; post-hoc t-test analysis found significant improvement for all diagnoses on all measures with the exception of spinal. There was also a significant interaction between time and format: post-hoc t-test analysis found greater improvement for virtual format on self-compassion and pain-related anxiety. Discussion Findings suggests that CFT-PM may be a clinically effective group intervention with virtual format showing superior improvement. This approach might be less suitable for certain diagnoses; the spinal group may benefit more from traditional CBT-based PMPs. Limitations include the lack of random selection or allocation to treatment group. Future studies should adopt an experimental design to be able to draw firm conclusions regarding causation and efficacy. Despite these limitations, present findings suggest that CFT-PM may be an effective group intervention worthy of further investigation and clinical application.

Many brain insults and injuries are "epileptogenic": they increase the risk of developing epilepsy. It is desirable to identify treatments that are "antiepileptogenic": treatments that prevent the development of epilepsy, if administered after the occurrence of an epileptogenic insult. Current antiepileptic drugs are not antiepileptogenic, but evidence of antiepileptogenic efficacy is accumulating for a growing number of other compounds. From among these candidate compounds, statins are deserving of particular attention because statins are reported to be antiepileptogenic in more published studies and in a wider range of brain insults than any other individual or class of compounds. Although many studies report the antiepileptogenic effect of statins, it is unclear how many studies provide evidence that statins exhibit the following two essential features of a clinically viable antiepileptogenic drug: the drug must exert an antiepileptogenic effect even if it is initiated after the epileptogenic brain insult has already occurred, and the antiepileptogenic effect must endure even after the drug has been discontinued. In the current work, we interrogate published preclinical and clinical studies, to determine if statins fulfill these essential requirements. There are eight different statins in clinical use. To enable the clinical use of one of these statins for antiepileptogenesis, its antiepileptogenic effect will have to be established through future time- and resource-intensive clinical trials. Therefore, it is desirable to review the published literature to determine which of the statins emerges as the most promising candidate for antiepileptogenic therapy. Hence, in the current work, we also collate and analyze published data-clinical and pre-clinical, direct and indirect-that help to answer the question: Which statin is the most promising candidate to take forward into an antiepileptogenesis clinical trial?

This study investigates the role of populism in the growing prominence of the far-right and will address a research gap by specifically focusing on the Australian context – a national setting often overlooked in this field of study. A fresh approach is taken that seeks to understand the new far-right landscape in in terms of discourse, messaging and appeals, rather than trying to group together people and parties. This lens will be used to establish how three components of framing and disseminating far-right discourse have been crucial in the contemporary popularisation of far-right appeals. Firstly, the use of populism to mobilise the ethno-cultural majority who are feeling threatened and hostile due to historical, political and contextual factors. The fluid and pragmatic changing of discourses will then be identified as a decisive strategy in appealing to a wider audience, with specific consideration given to the far-right’s utilisation of Islamophobic messaging. The final component is the evolution and widespread dissemination of far-right messaging. It will be argued that the populist far-right have transformed and achieved mainstream success because these three components have come together at this time in history and provided a great deal of strength to the operation of the far-right.

Photodynamic therapy (PDT) is a medicinal tool that uses a photosensitiser and a light source to treat several conditions, including cancer. PDT uses reactive oxygen species (ROS) such as cytotoxic singlet oxygen (1 O2 ) to induce cell death in cancer cells. Chemotherapy has historically utilized the cytotoxic effects of many metals, especially transition-metal complexes. However, chemotherapy is a systemic treatment so all cells in a patient's body are exposed to the same cytotoxic effects. Transition metal complexes have also shown high cytotoxicity as PDT agents. PDT is a potential localized method for treating several cancer types by using inorganic complexes as photosensitizing agents. This review covers several in vitro and in vivo studies, as well as clinical trials that reported on the anti-cancer properties of inorganic pharmaceuticals used in PDT against different types of cancer.

Purpose: Hematopoietic cell transplantation (HCT) is associated with significant risk prior to hematopoietic engraftment. Endurance exercise can modify the bone marrow microenvironment, alter hematopoiesis and accelerate hematopoietic regeneration in mouse models of transplantation. Methods: A systematic review was conducted to clarify the impact of exercise on clinically relevant hemato-logical outcomes in patients following HCT. Results: A systematic search of the literature identified 13 studies (total of 615 participants; 313 in study arms). Studies included exercise regimens that were primarily low-to-moderate intensity. A total of five studies re-ported on engraftment and length of stay, which were largely unchanged with intervention. Rates of graft-ver-sus host disease were reported in six studies whereas red cell and platelet transfusion needs were reported in four studies, neither of which was different with exercise. Survival was reported in four studies and was significantly improved by exercise in one study. Conclusions: Exercise in patients receiving HCT appears feasible and safe. Heterogeneity in type and intensity of exercise was observed and few studies examined high intensity exercise. Outcome reporting was inconsis-tent regarding transplant-related outcomes. Standardized hematological outcome measures are needed to clarify the impact of higher intensity exercise on HCT.

Natural products are a bountiful source of bioactive molecules. Unfortunately, discovery of novel bioactive natural products is challenging due to cryptic biosynthetic gene clusters, low titers, and arduous purifications. Herein, we describe SNaPP (Synthetic Natural Product Inspired Cyclic Peptides), a method for identifying NP-inspired bioactive peptides. SNaPP expedites bioactive molecule discovery by combining bioinformatics predictions of nonribosomal peptide synthetases with chemical synthesis of the predicted natural products (pNPs). SNaPP utilizes a recently discovered cyclase, the penicillin binding protein-like cyclase, as the lynchpin for the development of a library of head-to-tail cyclic peptide pNPs. Analysis of 500 biosynthetic gene clusters allowed for identification of 131 novel pNPs. Fifty-one diverse pNPs were synthesized using solid phase peptide synthesis and solution-phase cyclization. Antibacterial testing revealed 14 pNPs with antibiotic activity, including activity against multidrug-resistant Gram-negative bacteria. Overall, SNaPP demonstrates the power of combining bioinformatics predictions with chemical synthesis to accelerate the discovery of bioactive molecules.

Author(s): Rogers, Thomas F; Zhao, Fangzhu; Huang, Deli; Beutler, Nathan; Burns, Alison; He, Wan-Ting; Limbo, Oliver; Smith, Chloe; Song, Ge; Woehl, Jordan; Yang, Linlin; Abbott, Robert K; Callaghan, Sean; Garcia, Elijah; Hurtado, Jonathan; Parren, Mara; Peng, Linghang; Ricketts, James; Ricciardi, Michael J; Rawlings, Stephen A; Smith, Davey M; Nemazee, David; Teijaro, John R; Voss, James E; Andrabi, Raiees; Briney, Bryan; Landais, Elise; Sok, Devin; Jardine, Joseph G; Burton, Dennis R | Abstract: The development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate serum and monoclonal antibody responses, adapted our high throughput antibody isolation, production and characterization pipeline to rapidly screen over 1000 antigen-specific antibodies, and established an animal model to test protection. We report multiple highly potent neutralizing antibodies (nAbs) and show that passive transfer of a nAb provides protection against high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.

This paper documents the analysis of the circumstances surrounding fatalities due to flooding in Australia between 1900 and 2015. This longitudinal investigation is important to understand changing trends in social vulnerability and to inform efficient and strategic risk reduction strategies. The basis of this analysis was PerilAUS, Risk Frontiers’ database of historical natural hazard impacts in Australia. This data was augmented and verified using coronial inquest records which provide detailed data concerning the social, demographic and environmental circumstances of each fatality. A statistical analysis of the data was undertaken, examining demographics (age, gender), location (state), seasonality, circumstances surrounding the fatality, environmental factors (e.g. the event intensity) and social factors (e.g. the decisions or actions which led to death). Overall there have been 1859 fatalities identified, with distinct trends in relation to gender, age, activity and reason behind the activity. Flood deaths have been declining. The majority of the fatalities are male (79.3%): however, since the 1960s the proportion of female to male fatalities has increased. Children and young adults (, This research was funded by a research grant from the Bushfire and Natural Hazards Cooperative Research Centre (BNHCRC). Ethical approval for the project was granted from the Macquarie University Human Research Ethics Committee, reference no. 5201400073.

Introduction: High risk behaviors, such as aggression, criminality, sexual promiscuity, drug use, and gambling, are often associated with psychopathic traits. Such behaviors might arise due to a lack of fear of the consequences (boldness) or due to impulsive actions (disinhibition). We examined risk taking behavior in the laboratory setting using the Balloon Analogue Risk Task (BART), where an individual can inflate a balloon to earn a reward, but will lose this accumulated reward if the balloon bursts. The task reflects the willingness to take risks under conditions where the risk-taking behavior is understood and is made clear to the individual. Method: BART performance was measured in a mixed community and offender sample, and psychopathy was characterized via the triarchic conceptualization of psychopathy, which proposes that psychopathy is a combination of boldness, meanness, and disinhibition. Results: Total psychopathy score was correlated with greater risk taking on the BART, and this effect was mainly due to the Boldness scale rather than the Meanness or Disinhibition scales. These relationships were not moderated by the nature of the sample (offender vs. community) or by gender. Conclusions: Individuals with high psychopathy scores appear more willing to take risks on this simple laboratory task, and this behavior appears due to boldness rather than being related to an impulsive disposition.

Pancreatic cancer affects both male and female individuals with higher incidences and death rates among the male population. Detection of this malignancy is delayed due to the lack of symptoms in the early-stage cancer, which makes it extremely difficult to treat. Identifying effective strategies has been a challenge for improving the survival rates in pancreatic cancer patients. Resistance to chemotherapy is often developed in pancreatic cancer treatment. Although many strategies are under clinical trials to target certain markers associated with cancer, immunotherapeutic approaches are currently gaining importance. Immunotherapy for pancreatic cancer is in the limelight after preclinical research showed some promise. Immunotherapy approaches were tested along with other treatment options to enhance the treatment effect. Adoptive cell transfer and immune checkpoint inhibitors are currently in clinical trials. The Food and Drug Administration approved pembrolizumab in a fast-tracked review for advanced pancreatic cancer patients. Pembrolizumab blocks the checkpoint protein, programmed cell death protein 1 (PD-1), on T cells to boost the response of the immune system against cancer cells, thereby shrinking tumors. The recent developments in immunotherapy and the early success in other cancers are encouraging to further test immunotherapy in pancreatic cancer. The combination of pembrolizumab and pelareorep, an isolate of human reovirus, is in phase II clinical study in metastatic disease. Depending on the results of current clinical trials and testing, the strategies in the pipeline are expected to increase the use of immunotherapy in the clinical testing setting. Success in immunotherapy is urgently needed to address the side-effects, treating patients with advanced disease and reducing metastasis for increasing the survival rate in pancreatic cancer patients.

Food insecurity is associated with high body weight for women but not men in affluent Western societies. However, it is not currently known what behavioural or psychological mechanisms drive this association. Moreover, it is also unknown whether only current experience of food insecurity in adulthood is important, or there are lasting effects of childhood experience. We carried out a mock ‘taste test’ where 126 adult volunteers had the opportunity to consume and rate senergy-dense snack foods. Current food insecurity was measured using the standard USDA measure, and in addition, we used a novel measure that also captures childhood experience of food insecurity. As well as the expected gender-specific association between current food insecurity and body weight, we found some evidence for associations between food insecurity and calorie consumption in the taste test, and liking of one of the foods, chocolate. However, associations between current food insecurity and the outcomes were moderated by childhood experience of food insecurity, with greater childhood food insecurity enhancing the positive effect of current food insecurity on body weight, but attenuating the positive effect of food insecurity on calorie consumption and liking for chocolate. These findings are exploratory, but they suggest that any effects of food insecurity in adulthood on eating and the hedonic value of foods may be moderated by childhood experience.

The focus for this thesis for the LLM by Research is Family Law Mediation in England and\ud Wales. The research is looking at the system both as it stands currently as well as past\ud changes made by the government. It starts by looking at where mediation stands within\ud alternative dispute resolution and what the history of alternative dispute resolution entails. It\ud then moves on to look at the place of mediation in the family law system. It is mainly looking\ud at four major parts the first one being the introduction of The Family Law Act in 1996 and\ud what impact this had on the stance of mediation. The second part is looking at the\ud introduction of Mediation Information and Assessment Meetings and how successful they\ud were at meeting increasing the mediation intake. Thirdly the research looks at the\ud introduction of the Legal Aid, Sentencing and Punishment of Offenders Act 2012 and how\ud this changed the legal aid available for family law and what this did for mediation. Finally the\ud research also looks at what stance children have in the mediation process and whether\ud mediation is a beneficial process for them. Throughout the thesis is critique and analysis of\ud these aspects of mediation concluding with whether or not the current system meets the\ud aims the government have for alternative dispute resolution and what the future of mediation\ud holds.