ORCID Profile
0009-0005-5269-8003
Current Organisations
Albert-Ludwigs-Universität Freiburg
,
Institute for the Study of Christianity in an Age of Science and Technology (ISCAST)
,
Monash University
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Publications
‘Good culture, bad culture’: polygyny, cultural change and structural drivers of HIV in Papua New Guinea
Publisher: Informa UK Limited
Date: 16-02-2017
DOI: 10.1080/13691058.2017.1287957
Abstract: Culture is often problematised as a key structural driver of HIV transmission in Papua New Guinea. Official HIV programmes, as well as church teachings, tend to focus on customary marital practices of polygyny and bride price payments as 'harmful traditions'. This focus can oversimplify the effects of current and historical nuances of cultural, political and economic change on sexual concurrency and gender inequality. Community-based healthcare workers in Southern Highlands Province explain that customary marital practices are now highly reconfigured from their traditional forms. A recent mining boom has financially advantaged local and travelling men, who are driving an increase of sexual concurrency, transactional sex and inflation of bride price payments. Healthcare workers suggest that the erosion of important social relationships and kinship obligations by the expanding cash economy has caused an intensification of in idual male power while enhancing the vulnerability of women. Yet without the means to challenge the effects of uneven economic development, healthcare workers are left to target 'culture' as the central influence on in idual behaviours. A commitment to address structural inequality by political leadership and in HIV prevention programmes and a careful contextualisation of cultural change is needed.
Reverse transcriptase mutations in sequential HIV‐1 isolates in a patient with AIDS
Publisher: Wiley
Date: 07-1995
Abstract: Sequential human immunodeficiency virus type 1 (HIV-1) isolates were obtained over a 29-month period from a person before, during, and after AZT therapy. DNA sequence analysis of polymerase chain- lified reverse-transcriptase gene showed a gradual accumulation of mutations to peak resistance (IC50 2.13 microM AZT) in association with mutations at codons 44, 210, and 369, as well as at 41, 67, 70, and 215. Eight months after cessation of AZT therapy, when an HIV-1 isolate from the patient was again sensitive to AZT, these mutations had all returned to the pretherapy sequence.
Alternatively spliced RNAs encode several isoforms of CD46 (MCP), a regulator of complement activation
Publisher: Springer Science and Business Media LLC
Date: 05-1991
DOI: 10.1007/BF00216692
Hepatitis C seropositivity is not a risk factor for sensory neuropathy among patients with HIV
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-05-2010
An in vivo mutation from leucine to tryptophan at position 210 in human immunodeficiency virus type 1 reverse transcriptase contributes to high-level resistance to 3'-azido-3'-deoxythymidine
Publisher: American Society for Microbiology
Date: 11-1996
DOI: 10.1128/JVI.70.11.8010-8018.1996
Abstract: Sequencing of the reverse transcriptase (RT) region of 26 human immunodeficiency virus type 1 (HIV-1) isolates from eight patients treated with 3'-azido-3'-deoxythymidine (AZT) revealed a mutation at codon 210 from TTG (leucine) to TGG (tryptophan) exclusively in association with resistance to AZT. The mutation Trp-210 was observed in 15 of the 20 isolates phenotypically resistant to AZT, being more commonly observed than resistance-associated mutations at codons 67, 70, and 219. Trp-210 was never observed before the emergence of resistance-associated mutations Leu-41 and Tyr-215, and in a sequential series of five isolates from one patient the order of emergence of mutations was found to be Tyr-215, Leu-41, and then Trp-210. Trp-210 was also found in association with the Leu-41, Asn-67, Arg-70, and Tyr-215 resistance genotype. To define the role of Trp-210 in AZT resistance, molecular HIV-1 clones were constructed with various combinations of RT mutations at codons 41, 67, 70, 210, and 215 and tested for susceptibility to AZT. In clones with polymerase genes derived either from HXB2-D or clinical isolates, Trp-210 alone did not increase AZT resistance, whereas in conjunction with Leu-41 and Tyr-215, Trp-210 contributed to high-level resistance (50% inhibitory concentration of microM). In HXB2-D, Trp-210 with Tyr-215 generated a virus with resistance comparable to one with Leu-41, Tyr-215, and Trp-210. Inserting Trp-210 into the genetic context of mutations at codons 41, 67, 70, and 215 further enhanced resistance from a 50% inhibitory concentration of 1.44 microM to 8.41 microM. Molecular modeling of the tertiary structure of HIV-1 RT revealed that the distance between the side chains of Trp-210 (in helix alphaF) and Tyr-215 (in strand beta11a) approximated 4 A (1 A = 0.1 nm), sufficiently close to result in significant energetic interaction between these two aromatic side chains. In conclusion, Trp-210 contributes significantly to phenotypic AZT resistance of HIV-1 by augmenting resistance at least three- to sixfold in the context of two resistant genotypes, and its effect may require an interaction with an aromatic amino acid at position 215.
Golgi-Located NTPDase1 of Leishmania major Is Required for Lipophosphoglycan Elongation and Normal Lesion Development whereas Secreted NTPDase2 Is Dispensable for Virulence
Publisher: Public Library of Science (PLoS)
Date: 18-12-2014
Syncytium-inducing phenotype and zidovudine susceptibility of HIV-1 isolated from post-mortem tissue
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1996
DOI: 10.1097/00002030-199601000-00007
Abstract: To establish the syncytium-inducing (SI) phenotype and zidovudine (ZDV) susceptibility of HIV-1 isolates obtained from autopsy specimens. Isolation of HIV was attempted from autopsy specimens obtained from 76 AIDS patients. Specimens of lymph node, spleen, spinal cord, brain and cerebrospinal fluid (CSF) were processed and cultured with peripheral blood mononuclear cells (PBMC) from seronegative donors. Biological phenotype was determined in a T-lymphocyte line (MT-2). ZDV susceptibility was evaluated in a PBMC-based assay. Sequencing of amino-acid codons in the reverse transcriptase gene previously shown to be associated with ZDV resistance was carried out on a subgroup of isolates. HIV was recovered from tissue specimens and CSF up to 5 days post-mortem, but recovery rate of infectious virus decreased as the time between autopsy and specimen processing increased. There was a lack of concordance between PBMC isolates and isolates from different tissue sites with respect to SI phenotype. ZDV-resistant virus was isolated from post-mortem specimens of patients who had received long-term ZDV therapy up until or shortly before their death. ZDV-sensitive virus re-emerged in the lymph node of patients who ceased treatment several months prior to death. Phenotypically sensitive virus obtained from lymph node tissue of three patients after a relatively short time off ZDV (4-6 months) retained some of the amino-acid substitutions known to be associated with resistance. The data suggests that ZDV resistance and re-emergence of sensitive virus does not originate in peripheral cells, and that these cells and tissues are seeded with virus present elsewhere, possibly in the germinal centres of the lymph node.
Use of electronic cigarettes in the perioperative period: A mixed-method study exploring perceptions of cardiothoracic patients in Australia
Publisher: E.U. European Publishing
Date: 12-11-2018
DOI: 10.18332/TID/98957
Assessment of fitness and vector competence of a New Caledonia wMel Aedes aegypti strain before field-release.
Publisher: Public Library of Science (PLoS)
Date: 07-09-2021
DOI: 10.1371/JOURNAL.PNTD.0009752
Abstract: Biological control programs involving Wolbachia -infected Aedes aegypti are currently deployed in different epidemiological settings. New Caledonia (NC) is an ideal location for the implementation and evaluation of such a strategy as the only proven vector for dengue virus (DENV) is Ae . aegypti and dengue outbreaks frequency and severity are increasing. We report the generation of a NC Wolbachia- infected Ae . aegypti strain and the results of experiments to assess the vector competence and fitness of this strain for future implementation as a disease control strategy in Noumea, NC. The NC Wolbachia strain (NC- w Mel) was obtained by backcrossing Australian AUS- w Mel females with New Caledonian Wild-Type (NC-WT) males. Blocking of DENV, chikungunya (CHIKV), and Zika (ZIKV) viruses were evaluated via mosquito oral feeding experiments and intrathoracic DENV challenge. Significant reduction in infection rates were observed for NC- w Mel Ae . aegypti compared to WT Ae . aegypti . No transmission was observed for NC- w Mel Ae . aegypti . Maternal transmission, cytoplasmic incompatibility, fertility, fecundity, wing length, and insecticide resistance were also assessed in laboratory experiments. Ae . aegypti NC- w Mel showed complete cytoplasmic incompatibility and a strong maternal transmission. Ae . aegypti NC- w Mel fitness seemed to be reduced compared to NC-WT Ae . aegypti and AUS- w Mel Ae . aegypti regarding fertility and fecundity. However further experiments are required to assess it accurately. Our results demonstrated that the NC- w Mel Ae . aegypti strain is a strong inhibitor of DENV, CHIKV, and ZIKV infection and prevents transmission of infectious viral particles in mosquito saliva. Furthermore, our NC- w Mel Ae . aegypti strain induces reproductive cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, supporting field-releases in Noumea, NC.
Measuring and monitoring apoptosis and drug toxicity in HIV patients by ligation-mediated polymerase chain reaction
Publisher: Wiley
Date: 05-2009
Genomic Structure of an Attenuated Quasi Species of HIV-1 from a Blood Transfusion Donor and Recipients
Publisher: American Association for the Advancement of Science (AAAS)
Date: 10-11-1995
DOI: 10.1126/SCIENCE.270.5238.988
Abstract: A blood donor infected with human immunodeficiency virus-type 1 (HIV-1) and a cohort of six blood or blood product recipients infected from this donor remain free of HIV-1-related disease with stable and normal CD4 lymphocyte counts 10 to 14 years after infection. HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). Full-length sequencing of one isolate genome and lification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1.
A new way of measuring apoptosis by absolute quantitation of inter-nucleosomally fragmented genomic DNA
Publisher: Oxford University Press (OUP)
Date: 28-04-2012
DOI: 10.1093/NAR/GKS334
A novel Cas9 fusion protein promotes targeted genome editing with reduced mutational burden in primary human cells
Publisher: Oxford University Press (OUP)
Date: 18-04-2023
DOI: 10.1093/NAR/GKAD255
Abstract: Precise genome editing requires the resolution of nuclease-induced DNA double strand breaks (DSBs) via the homology-directed repair (HDR) pathway. In mammals, this is typically outcompeted by non-homologous end-joining (NHEJ) that can generate potentially genotoxic insertion/deletion mutations at DSB sites. Because of higher efficacy, clinical genome editing has been restricted to imperfect but efficient NHEJ-based approaches. Hence, strategies that promote DSB resolution via HDR are essential to facilitate clinical transition of HDR-based editing strategies and increase safety. Here we describe a novel platform that consists of a Cas9 fused to DNA repair factors to synergistically inhibit NHEJ and favor HDR for precise repairing of Cas-induced DSBs. Compared to canonical CRISPR/Cas9, the increase in error-free editing ranges from 1.5-fold to 7-fold in multiple cell lines and in primary human cells. This novel CRISPR/Cas9 platform accepts clinically relevant repair templates, such as oligodeoxynucleotides (ODNs) and adeno-associated virus (AAV)-based vectors, and has a lower propensity to induce chromosomal translocations as compared to benchmark CRISPR/Cas9. The observed reduced mutational burden, resulting from diminished indel formation at on- and off-target sites, provides a remarkable gain in safety and advocates this novel CRISPR system as an attractive tool for therapeutic applications depending on precision genome editing.
The struggle of translating science into action: Foundational concepts of implementation science
Publisher: Wiley
Date: 31-03-2017
DOI: 10.1111/JEP.12741
Molecular cloning and partial nucleotide sequence of a 3.5 kb HLA-B27-associated fragment of genomic DNA.
Publisher: Springer Science and Business Media LLC
Date: 10-1985
DOI: 10.1007/BF00430923
Pastoral power in HIV prevention: Converging rationalities of care in Christian and medical practices in Papua New Guinea
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.SOCSCIMED.2017.09.049
Abstract: In his conceptualisation of pastoral power, Michel Foucault argues that modern healthcare practices derive a specific power technique from pastors of the early Christian church. As experts in a position of authority, pastors practise the care of others through implicitly guiding them towards thoughts and actions that effect self-care, and towards a predefined realm of acceptable conduct, thus having a regulatory effect. This qualitative study of healthcare workers from two Christian faith-based organisations in Papua New Guinea examines the pastoral rationalities of HIV prevention practices which draw together globally circulated modern medical knowledge and Christian teachings in sexual morality for implicit social regulation. Community-based HIV awareness education, voluntary counselling and testing services, mobile outreach, and economic empowerment programs are standardised by promoting behavioural choice and in idual responsibility for health. Through pastoral rationalities of care, healthcare practices become part of the social production of negative differences, and condemn those who become ill due to perceived immorality. This emphasis assumes that all in iduals are equal in their ability to make behavioural choices, and downplays social inequality and structural drivers of HIV risk that are outside in idual control. Given healthcare workers' recognition of the structural drivers of HIV, yet the lack of language and practical strategies to address these issues, political commitment is needed to enhance structural competency among HIV prevention programs and healthcare workers.
Women’s Perceptions of Journeying Toward an Unknown Future With Breast Cancer: The “Lives at Risk Study”
Publisher: SAGE Publications
Date: 22-09-2017
Abstract: Breast cancer risk classifications are useful for prognosis, yet little is known of their effect on patients. This study clarified women's understandings of risk as they "journeyed" through the health care system. Breast cancer patients and women undergoing genetic investigation were recruited ( N = 25) from a large UK Health Board, 2014-2015, completing a "Book of Experience," and Bio-photographic elicitation interviews. Stakeholder and Participant Feedback Forums were undertaken with key stakeholders, including patients, oncologists, funders, and policy developers, to inform team understanding. Thematic and visual frameworks from multidisciplinary analysis workshops uncovered two themes: "Subjective Understandings of Risk" and "Journeying Toward an Unknown Future." Breast cancer patients and women undergoing investigation experienced risk intuitively. Statistical formulations were often perplexing, erting attention away from concrete life-and-death facts. Following risk classification, care must be co-defined to reduce patients' foreboding about an unknown future, taking into consideration personal risk management strategies and aspirations for a cancer-free future.
Apoptosis: a clinically useful measure of antiretroviral drug toxicity?
Publisher: Informa UK Limited
Date: 28-09-2009
DOI: 10.1517/17425250903282781
Abstract: Antiretroviral therapy (ART) has improved life expectancy with HIV infection, but long-term toxicities associated with these medications are now a major global disease burden. There is a clear need to develop useful methods for monitoring patients on antiretroviral drugs for early signs of toxicity. Assays with predictive utility -- allowing therapy to be changed before serious end organ damage occurs -- would be ideal. Attempts to develop biochemical methods of monitoring ART toxicity have concentrated on the mitochondrial toxicity of nucleoside analogue reverse transcriptase inhibitors and have not generally lead to assays with widespread clinical applications. For ex le, plasma lactate and peripheral blood measurements of mitochondrial DNA associate with exposure to potentially toxic nucleoside analogue reverse transcriptase inhibitors but have not reliably predicted clinical toxicity. Better assays are needed, including markers of toxicity from additional drug classes. Apoptosis may be a potential marker of ART toxicity. Increased apoptosis has been demonstrated both in vitro and in vivo in association with various antiretroviral drug classes and a range of clinical toxicities. However, quantifying apoptosis on biopsy specimens of tissue (such as adipose tissue) is impractical for patient monitoring. Novel assays have been described that can quantify apoptosis using minute tissue s les and initial results from clinical s les suggest peripheral blood may have utility in predicting ART toxicities. The limitations and potential of such techniques for monitoring patients for drug side effects will be discussed.
Better evidence for earlier assessment and surgical intervention for refractory epilepsy (The BEST study)
Publisher: BMJ
Date: 08-2017
DOI: 10.1136/BMJOPEN-2017-017148
Abstract: One-third of patients with refractory epilepsy may be candidates for resective surgery, which can lead to positive clinical outcomes if efficiently managed. In Australia, there is currently between a 6-month and 2-year delay for patients who are candidates for respective epilepsy surgery from the point of referral for surgical assessment to the eventual surgical intervention. This is a major challenge for implementation of effective treatment for in iduals who could potentially benefit from surgery. This study examines implications of delays following the point of eligibility for surgery, in the assessment and treatment of patients, and the factors causing treatment delays. Mixed methods design: Observations of qualitative consultations, patient and healthcare professional interviews, and health-related quality of life assessments for a group of 10 patients and six healthcare professionals (group 1) quantitative retrospective medical records’ reviews examining longitudinal outcomes for 50 patients assessed for, or undergoing, resective surgery between 2014 and 2016 (group 2) retrospective epidemiological study of all in iduals hospitalised with a diagnosis of epilepsy in New South Wales (NSW) in the last 5 years (2012–2016 approximately 11 000 hospitalisations per year, total 55 000), examining health services’ use and treatment for in iduals with epilepsy, including refractory surgery outcomes (group 3). Ethical approval has been granted by the North Sydney Local Health District Human Research Ethics Committee (HREC/17/HAWKE/22) and the NSW Population & Health Services Research Ethics Committee (HREC/16/CIPHS/1). Results will be disseminated through publications, reports and conference presentations to patients and families, health professionals and researchers.
Characterisation of foscarnet-resistant strains of human immunodeficiency virus type 1.
Publisher: Elsevier BV
Date: 09-1995
Abstract: Foscarnet is a broad-spectrum viral DNA polymerase inhibitor active in vitro and in vivo against human immunodeficiency virus type 1 (HIV-1). Strains of HIV-1 resistant to foscarnet were selected by in vitro passage in increasing concentrations of drug. Reduced susceptibility to foscarnet was evident at the levels of both HIV-1 replication and reverse transcriptase. Biologically cloned, foscarnet-resistant strains with distinct genotypes were hypersensitive to zidovudine, azidodeoxyuridine, nevirapine, and R82913 but had unchanged susceptibility to zalcitibine and didanosine. The reverse transcriptase of foscarnet-resistant strains had unique substitutions Glu89-Lys, Leu92-Ile, or Ser156-Ala, the third being associated with six polymorphic changes. Introduction of these mutations into wild-type HIV-1 by site-directed mutagenesis confirmed their role in foscarnet resistance. In the three-dimensional structure of the reverse transcriptase enzyme these amino acids are located close to the template strand of the template primer and far away from the putative pyrophosphate binding site, suggesting that the mechanism by which HIV-1 becomes resistant to foscarnet is indirect. Foscarnet resistance is thus likely to be mediated through an altered interaction of the mutant enzyme with the template strand of the template primer which distorts the geometry of the polymerase active site and thereby decreases foscarnet binding.
Ubisol-Aqua™: Coenzyme Q10 prevents antiretroviral toxic neuropathy in an in vitro model
Publisher: Bentham Science Publishers Ltd.
Date: 04-2010
DOI: 10.2174/157016210791111106
Abstract: Peripheral neuropathy is the dose-limiting toxicity of stavudine and didanosine (nucleoside analogs used in HIV treatment) and is attributed to mitochondrial toxicity from these drugs. Acetyl L-carnitine (ALC) and co-enzyme Q(10) are proposed as neuropathy treatments, but evidence to support these is limited. We examined ALC and a water-soluble formulation of co-enzyme Q(10) (H(Q)O) for the prevention of d4T and ddI neurotoxicity using cultured fetal rat DRG as an in vitro model. DdI (33microM) and d4T (50microM) caused clear toxicity (impaired neurite growth) by day 8 of DRG culture. H(Q)O at concentrations 1-100microM completely prevented the toxicity of 33microM ddI in vitro and ALC at concentrations 1-100 microM substantially (but incompletely) prevented ddI toxicity in this model. In contrast, ALC was ineffective at all concentrations tested for preventing the toxicity of 50microM d4T. H(Q)O showed dose-dependent efficacy for preventing d4T toxicity. H(Q)O (1microM) partially prevented d4T toxicity while 10 and 100microM H(Q)O completely prevented d4T toxicity in this model. We find H(Q)O is superior to ALC for preventing the neurotoxicity of d4T (the HIV treatment most associated with neuropathy) and ddI in vitro. Further study is needed to clarify any clinical role for co-enzyme Q(10) co-administration with d4T and ddI and to assess whether this compound may have a role in treating established cases of neuropathy.
Communicating risk in active surveillance of localised prostate cancer: a protocol for a qualitative study
Publisher: BMJ
Date: 10-2017
DOI: 10.1136/BMJOPEN-2017-017372
Abstract: One in five men is likely to receive a diagnosis of prostate cancer (PCa) by the age of 85 years. Men diagnosed with low-risk PCa may be eligible for active surveillance (AS) to monitor their cancer to ensure that any changes are discovered and responded to in a timely way. Communication of risk in this context is more complicated than determining a numerical probability of risk, as patients wish to understand the implications of risk on their lives in concrete terms. Our study will examine how risk for PCa is perceived, experienced and communicated by patients using AS with their health professionals, and the implications for treatment and care. This is a proof of concept study, testing out a multimethod, qualitative approach to data collection in the context of PCa for the first time in Australia. It is being conducted from November 2016 to December 2017 in an Australian university hospital urology clinic. Participants are 10 men with a diagnosis of localised PCa, who are using an AS protocol, and 5 health professionals who work with this patient group (eg, urologists and Pca nurses). Data will be collected using observations of patient consultations with health professionals, patient questionnaires and interviews, and interviews with healthcare professionals. Analysis will be conducted in two stages. First, observational data from consultations will be analysed thematically to encapsulate various dimensions of risk classification and consultation dialogue. Second, interview data will be coded to derive meaning in text and analysed thematically. Overarching themes will represent patient and health professional perspectives of risk communication. Ethical approval for the study has been granted by Macquarie University Human Research Ethics Committee, approval 5201600638. Knowledge translation will be achieved through publications, reports and conference presentations to patients, families, clinicians and researchers.
Detecting wMel Wolbachia in field-collected Aedes aegypti mosquitoes using loop-mediated isothermal amplification (LAMP)
Publisher: Springer Science and Business Media LLC
Date: 15-08-2019
Related Organisations
Institute For The Study Of Christianity In An Age Of Science And Technology (ISCAST)
Location: Australia
Related Funding Activities
No related grants have been discovered for David James Hooker.