Open scholarship in Australia: A review of needs, barriers, and opportunities

Wed 28 Sep 2022 10:43:59 AEST

Open scholarship encompasses open access, open data, open source software, open educational resources, and all other forms of openness in the scholarly and research environment, using digital or computational techniques, or both. It can change how knowledge is created, preserved, and shared, and can better connect academics with communities they serve. Yet, the movement toward open scholarship has encountered significant challenges. This article begins by examining the history of open scholarship in Australia. It then reviews the literature to examine key barriers hampering uptake of open scholarship, with emphasis on the humanities. This involves a review of global, institutional, systemic, and financial obstacles, followed by a synthesis of how these barriers are influenced at diverse stakeholder levels: policymakers and peak bodies, publishers, senior university administrators, researchers, librarians, and platform providers. The review illustrates how universities are increasingly hard-pressed to sustain access to publicly funded research as journal, monograph, and open scholarship costs continue to rise. Those in academia voice concerns about the lack of appropriate open scholarship infrastructure and recognition for the adoption of open practices. Limited access to credible research has led, in some cases, to public misunderstanding about legitimacy in online sources. This article, therefore, represents an urgent call for more empirical research around ‘missed opportunities’ to promote open scholarship. Only by better understanding barriers and needs across the university landscape can we address current challenges to open scholarship so research can be presented in usable and understandable ways, with data made more freely available for reuse by the broader public.

Acceptability and feasibility of cognitive assessments with adults with primary brain cancer and brain metastasis: A systematic review

Wed 28 Feb 2024 15:08:37 AEDT

Routine cognitive assessment for adults with brain cancers is seldom completed but vital for guiding daily living, maintaining quality of life, or supporting patients and families. This study aims to identify cognitive assessments which are pragmatic and acceptable for use in clinical settings. MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane were searched to identify studies published in English between 1990 and 2021. Publications were independently screened by two coders and included if they: (1) were peer-reviewed; (2) reported original data relating to adult primary brain tumor or brain metastases; (3) used objective or subjective assessments; (4) reported assessment acceptability or feasibility. The Psychometric And Pragmatic Evidence Rating Scale was used. Consent, assessment commencement and completion, and study completion were extracted along with author-reported acceptability and feasibility data. PROSPERO Registration: CRD42021234794. Across 27 studies, 21 cognitive assessments had been assessed for feasibility and acceptability; 15 were objective assessments. Acceptability data were limited and heterogeneous, particularly consent (not reported in 23 studies), assessment commencement (not reported in 19 studies), and assessment completion (not reported in 21 studies). Reasons for non-completion could be grouped into patient-factors, assessment-factors, clinician-factors, and system-factors. The three cognitive assessments with the most acceptability and feasibility data reported were the MMSE, MoCA, and NIHTB-CB. Further acceptability and feasibility data are needed including consent, commencement and completion rates. Cost, length, time, and assessor burden are needed for the MMSE, MoCA, and NIHTB-CB, along with potentially new computerized assessments suited for busy clinical settings.

Neurovascular coupling mechanisms in health and neurovascular uncoupling in Alzheimer's disease

Wed 27 Sep 2023 09:54:11 AEST

To match the metabolic demands of the brain, mechanisms have evolved to couple neuronal activity to vasodilation, thus increasing local cerebral blood flow and delivery of oxygen and glucose to active neurons. Rather than relying on metabolic feedback signals such as the consumption of oxygen or glucose, the main signalling pathways rely on the release of vasoactive molecules by neurons and astrocytes, which act on contractile cells. Vascular smooth muscle cells and pericytes are the contractile cells associated with arterioles and capillaries, respectively, which relax and induce vasodilation. Much progress has been made in understanding the complex signalling pathways of neurovascular coupling, but issues such as the contributions of capillary pericytes and astrocyte calcium signal remain contentious. Study of neurovascular coupling mechanisms is especially important as cerebral blood flow dysregulation is a prominent feature of Alzheimer’s disease. In this article we will discuss developments and controversies in the understanding of neurovascular coupling and finish by discussing current knowledge concerning neurovascular uncoupling in Alzheimer’s disease.

Disability and madness in colonial asylum records in Australia and New Zealand

Wed 24 May 2023 12:08:33 AEST

Case records examined here are those of inmates in two public institutions for the insane in colonial Victoria, Australia, and in Auckland, New Zealand, between 1870 and 1910. In the international field of mental health studies and histories of psychiatry, intellectual disability has been the subject of detailed historical inquiry and forms part of the critical discussion about how institutions for the “insane” housed a range of inmates in the nineteenth century. Yet the archival records of mental hospitals have rarely been examined in any sustained way for their detail about the physically disabled or those whose records denote bodily difference. References to the physical manifestations of various forms of intellectual or emotional disability, as well as to bodily difference and “deformity,” were part of the culture of the colonial institution, which sought to categorize, label, and ascribe identities to institutional inmates.

Corporate Bankruptcy Prediction: An Approach Towards Better Corporate World

Wed 14 Jun 2023 16:06:00 AEST

The area of corporate bankruptcy prediction attains high economic importance, as it affects many stakeholders. The prediction of corporate bankruptcy has been extensively studied in economics, accounting and decision sciences over the past two decades. The corporate bankruptcy prediction has been a matter of talk among academic literature and professional researchers throughout the world. Different traditional approaches were suggested based on hypothesis testing and statistical modeling. Therefore, the primary purpose of the research is to come up with a model that can estimate the probability of corporate bankruptcy by evaluating its occurrence of failure using different machine learning models. As the dataset was not well prepared and contains missing values, various data mining and data pre-processing techniques were utilized for data preparation. Within this research, the task of resolving the issues induced by the imbalance between the two classes is approached by applying different data balancing techniques. We address the problem of imbalanced data with the random undersampling and Synthetic Minority Over Sampling Technique (SMOTE). We used five machine learning models (support vector machine, J48 decision tree, Logistic model tree, random forest and decision forest) to predict corporate bankruptcy earlier to the occurrence. We use data from 2009 to 2013 on Poland manufacturing corporates and selected the 64 financial indicators to be broken down. The main finding of the study is a significant improvement in predictive accuracy using machine learning techniques. We also include other economic indicators ratios, along with Altman’s Z-score variables related to profitability, liquidity, leverage and solvency (short/long term) to propose an efficient model. Machine learning models give better results while balancing the data through SMOTE as compared to random undersampling. The machine learning technique related to decision forest led to 99% accuracy, whereas support vector machine (SVM), J48 decision tree, Logistic Model Tree (LMT) and Random Forest (RF) led to 92%, 92.3%, 93.8% and 98.7% accuracy, respectively, with all predictive financial indicators. We find that the decision forest outperforms the other techniques and previous techniques discussed in the literature. The proposed method is also deployed on the web to assist regulators, investors, creditors and scholars to predict corporate bankruptcy.

Early-career general practitioners’ antibiotic prescribing for acute infections: a systematic review

Wed 05 Jun 2024 09:37:21 AEST

Background: Antimicrobial resistance is a worldwide threat, exacerbated by inappropriate prescribing. Most antibiotic prescribing occurs in primary care. Early-career GPs are important for the future of antibiotic prescribing and curbing antimicrobial resistance. Objectives: To determine antibiotic prescribing patterns by early-career GPs for common acute infections. Methods: A systematic literature search was conducted using PubMed, Embase and Scopus. Two authors independently screened abstracts and full texts for inclusion. Primary outcomes were antibiotic prescribing rates for common acute infections by GPs with experience of 10 years or less. Secondary outcomes were any associations between working experience and antibiotic prescribing. Results: Of 1483 records retrieved, we identified 41 relevant studies. Early-career GPs were less likely to prescribe antibiotics compared with their more experienced colleagues (OR range 0.23–0.67). Their antibiotic prescribing rates for ‘any respiratory condition’ ranged from 14.6% to 52%, and for upper respiratory tract infections from 13.5% to 33%. Prescribing for acute bronchitis varied by country, from 15.9% in Sweden to 26% in the USA and 63%–73% in Australia. Condition-specific data for all other included acute infections, such as sinusitis and acute otitis media, were limited to the Australian context. Conclusions: Early-career GPs prescribe fewer antibiotics than later-career GPs. However, there are still significant improvements to be made for common acute conditions, as their prescribing is higher than recommended benchmarks. Addressing antimicrobial resistance requires an ongoing worldwide effort and early-career GPs should be the target for long-term change.

Differences in Falls and Physical Activity in Older Women From Two Generations

Wed 03 Apr 2024 13:22:37 AEDT

Background: Falls and physical inactivity increase with age. However, physical activity, falls and their associations in older people born at different times are unclear. Methods: Women born 1921–26 and 1946–51 who completed follow-up questionnaires in 1999 (n = 8 403, mean (SD) age: 75 (1) years) and 2019 (n = 7 555; 71 (1) years) in the Australian Longitudinal Study on Women’s Health. Self-reported noninjurious and injurious falls in the previous 12 months and weekly amounts and types of physical activity (brisk walking, moderate- and vigorous-intensity) were compared between the cohorts using Chi-square tests. Associations between physical activity, and noninjurious and injurious falls were estimated using multinomial logistic regressions informed by a directed acyclic graph. Results: A greater proportion of the later (1946–51) cohort (59%) reached 150–300 minutes of weekly physical activity, as recommended by the World Health Organization, compared to the earlier (1921–26) cohort (43%, p < .001). A greater proportion of the later cohort reported noninjurious falls (14% vs 8%). Both cohorts reported similar proportions of injurious falls (1946–51:15%, 1921–26:14%). In both cohorts, participation in 150–300 minutes of physical activity was associated with lower odds of noninjurious falls (adjusted Odds Ratio, 95% CI: 1921–26: 0.66, 0.52–0.84; 1946–51: 0.78, 0.63–0.97) and injurious falls (1921–26: 0.72, 0.60–0.87; 1946–51: 0.78, 0.64–0.96). Conclusions: Participation in recommended levels of physical activity was associated with reduced falls in both cohorts. However, generational differences were found with more falls and more physical activities in the women born later. Future studies could examine the reasons contributing to the generational differences.

Diversity and Evolution of Frog Visual Opsins: Spectral Tuning and Adaptation to Distinct Light Environments

Wed 01 May 2024 10:39:30 AEST

Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception. Here, we analyze the diversity and evolution of visual opsin genes from 93 new eye transcriptomes plus published data for a combined dataset spanning 122 frog species and 34 families. We find that most species express the four visual opsins previously identified in frogs but show evidence for gene loss in two lineages. Further, we present evidence of positive selection in three opsins and shifts in selective pressures associated with differences in habitat and life history, but not activity pattern. We identify substantial novel variation in the visual opsins and, using microspectrophotometry, find highly variable spectral sensitivities, expanding known ranges for all frog visual pigments. Mutations at spectral-tuning sites only partially account for this variation, suggesting that frogs have used tuning pathways that are unique among vertebrates. These results support the hypothesis of adaptive evolution in photoreceptor physiology across the frog tree of life in response to varying environmental and ecological factors and further our growing understanding of vertebrate visual evolution.

Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis

Tue 27 Feb 2024 13:58:29 AEDT

Background: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. Methods: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. Results: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI], .59–1.19]; P = .33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI, .64–1.68]; P = .88). Conclusions: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.

Legal translation as comparative law: the case of the Brazilian contract law

Tue 24 Sep 2019 14:06:54 AEST

Legal translation is a tool of comparative law so long as the translator conforms to the methodological rigours of the comparatist scholar. Comparative law serves the purpose of justice when it allows lawyers in one jurisdiction to examine critically domestic legal solutions in light of diverse solutions from other jurisdictions. If these solutions are expressed in different languages, the task of translation becomes essential to these comparative undertakings. A case in point is the expert witness in judicial proceedings involving foreign law applicable under conflict of law rules, whose mission is to enlighten the local judge on how to apply the law as the foreign judge would have done. This article presents the task of legal translation as a tool of comparative law in the quest for justice by reporting a sample of the translation of the contract law of the Brazilian Civil Code from Portuguese into English. In order to express the source legal concepts transparently, the comparatist-translator needs to find functional equivalents in the target language inviting the foreign lawyer to accommodate the source concept sensibly in their own legal system. This means that in some cases this translation departs from reputable international instruments in the English language that fall short of crossing the divide between the civil and common legal traditions. By disclosing the logic behind the choice of words or legal equivalents, this article locates legal translation within the realm of the discipline of comparative contract law in the search for commonalities between diverse jurisdictions.

High prevalence of medical conditions and unhealthy lifestyle behaviours in women with PCOS during preconception: findings from the Australian Longitudinal Study on Women's Health

Tue 21 Nov 2023 10:30:35 AEDT

Study Question: What are the pre-existing medical conditions and lifestyle behaviours of women with and without PCOS during the preconception period? Summary Answer: During the preconception period, medical conditions of obesity, depression, anxiety, and a history of infertility were more highly prevalent in women with than without PCOS, and more women with than without PCOS were engaged in unhealthy lifestyle behaviours. What Is Known Already: Women with PCOS are predisposed to infertility and pregnancy complications. Optimizing preconception medical health and lifestyle behaviours can improve maternal and pregnancy outcomes but, to the best of our knowledge, no study has examined the preconception medical conditions and lifestyle behaviours of women with PCOS. Study Design, Size Duration: This is a cross-sectional study on 942 women with PCOS and 7024 women without PCOS, aged 24-30 years from the Australian Longitudinal Study of Women's Health, an ongoing, national survey-based prospective cohort study. Participants/Materials, Setting, Methods: The current study analysed self-reported data from Survey 6 collected in 2019 of the cohort of women born between 1989 and 1995. Explored outcomes included BMI, pre-existing medical conditions, and modifiable lifestyle behaviours, including smoking, recreational drug use, alcohol intake, and physical activity level, during the preconception period. Differences between subgroups were tested using Student's t-test, χ2 test, or Fisher's exact test as appropriate. The associations of pregnancy intention with medical conditions and lifestyle behaviours were examined using logistic regression. Main Results and The Role Of Chance: Obesity, depression, anxiety, and infertility were highly prevalent in women actively planning for pregnancy. Among women with PCOS, the prevalence of obesity was 47.02%, followed by depression at 32.70%, anxiety at 39.62%, and infertility at 47.17%. Conversely among women without PCOS, the corresponding prevalence was lower, at 22.33% for obesity, 18.98% for depression, 23.93% for anxiety, and 16.42% for infertility. In women actively planning for pregnancy, only those without PCOS demonstrated a lower prevalence of unhealthy lifestyle behaviours compared to non-planning women. The prevalence of unhealthy lifestyle behaviours was similar in women with PCOS regardless of their pregnancy intentions. Multivariable logistic regression revealed that only moderate/high stress with motherhood/children (adjusted odds ratio (OR) 3.31, 95% CI 1.60-6.85) and history of infertility (adjusted OR 9.67, 95% CI 5.02-18.64) were significantly associated with active pregnancy planning in women with PCOS. Limitations, Reasons For Caution: The findings were based on self-reported data. The cohort of women surveyed may have a higher level of education than women in the community, therefore our findings may underestimate the true prevalence of pre-existing medical conditions and lifestyle challenges faced by the broader population. Wider Implications Of The Findings: A higher proportion of women with than without PCOS had pre-existing medical conditions and engaged in potentially modifiable unhealthy lifestyle behaviours during preconception despite their risk for subfertility and pregnancy complications. Healthcare professionals play a pivotal role in guiding this high-risk group of women during this period, offering counselling, education, and support for the adoption of healthy lifestyles to improve fertility, pregnancy outcomes, and intergenerational health.

Conceptualizing harmonization: the case for contract law

Tue 21 Mar 2023 13:45:39 AEDT

Legal harmonization is a fundamental notion of comparative contract law that has been on the international and national agendas for at least six decades. There have been a number of endeavours seeking for similarity between legal rules from different jurisdictions; however, their achievements remain contested since there is no comprehensive understanding of the nature and extent of harmonization. This article examines different facets of harmonization by looking at it as a legal phenomenon instead of a distinct process of drafting similar rules. This article discusses that, conceptually, harmonization is better understood as encompassing the meanings given, and the goals pursued, by the various agents promoting its implementation. Four cases of harmonization show that the different meanings of harmonization converge on the same multifaceted referent irrespective of operating at the supranational, international, or federal level. This article brings together at least four explanatory models responding to different approaches to the same phenomenon as they focus on inputs and outcomes, the greater or lesser diversity between rules, the sources of the law, and the processes of harmonization themselves. Adopting a comprehensive understanding of harmonization as a legal phenomenon may help to better assess the strengths and weaknesses of the implementation processes as well as to formulate adequately new endeavours.

Impact of the solid Earth mass adjustment by the 2011 Tohoku-Oki earthquake on the regional sea level and hydrological mass change recovery from GRACE

Tue 20 Feb 2024 16:26:49 AEDT

For more than a decade, GRACE data have provided global mass redistribution measurements due to water cycles, climate change and giant earthquake events. Large earthquakes can yield gravity changes over thousands of kilometres from the epicentre for years to decades, and those solid Earth deformation signals can introduce significant biases in the estimate of regional-scale water and ice mass changes around the epicentres. We suggest a modelling scheme to understand their contribution to the estimates of water and ice mass changes and to remove the earthquake-related solid mass signals from GRACE data. This approach is composed of physics-based earthquake modelling, GRACE data correction and high-resolution surface mass change recovery. In this study, we examined the case of the 2011 Tohoku–Oki earthquake to better estimate the regional sea level and hydrological mass changes in the East Asia. The co- and post-seismic changes from GRACE observations were used to constrain the earthquake model parameters to obtain optimal self-consistent models for the earthquake source and the asthenosphere rheology. The result demonstrated that our earthquake correction model significantly reduced the mass change signals by solid Earth deformation from the time-series of regional surface mass changes on both land and oceans. For example, the apparent climate-related ocean mass increase over the East Sea was 1.59 ± 0.11 mm yr−1 for 2003–2016, significantly lower than the global mean ocean mass trend (2.04 ± 0.10 mm yr−1) due to contamination of the earthquake signals. After accounting for the solid mass changes by the earthquake, the estimate was revised to 1.87 ± 0.11 mm yr−1, that is increased by 20 per cent and insignificantly different from the global estimate.

The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models

Tue 20 Aug 2024 16:11:19 AEST

Background: Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated. Methods: The production of functional viruses was assessed by immunoblotting and replication assays. The antitumor effect was evaluated in a panel of human and murine pHGG and DMG cell lines. RNAseq, the seahorse stress test, mitochondrial DNA content, and γH2A.X immunofluorescence were used to perform mechanistic studies. Mouse models of both diseases were used to assess the efficacy of the combination in vivo. The tumor immune microenvironment was evaluated using flow cytometry, RNAseq, and multiplexed immunofluorescence staining. Results: The Delta-24-RGD/ONC201 combination did not affect the virus replication capability in human pHGG and DMG models in vitro. Cytotoxicity analysis showed that the combination treatment was either synergistic or additive. Mechanistically, the combination treatment increased nuclear DNA damage and maintained the metabolic perturbation and mitochondrial damage caused by each agent alone. Delta-24-RGD/ONC201 cotreatment extended the overall survival of mice implanted with human and murine pHGG and DMG cells, independent of H3 mutation status and location. Finally, combination treatment in murine DMG models revealed a reshaping of the tumor microenvironment to a proinflammatory phenotype. Conclusions: The Delta-24-RGD/ONC201 combination improved the efficacy compared to each agent alone in in vitro and in vivo models by potentiating nuclear DNA damage and in turn improving the antitumor (immune) response to each agent alone.

Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma

Tue 11 Oct 2022 19:42:45 AEDT

Background: Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brainstem tumor for which radiation is the only treatment. Case studies report a clinical response to ONC201 for patients with H3K27M-mutant gliomas. Oncoceutics (ONC201) is only available in the United States and Japan; however, in Germany, DIPG patients can be prescribed and dispensed a locally produced compound—ONC201 German-sourced ONC201 (GsONC201). Pediatric oncologists face the dilemma of supporting the administration of GsONC201 as conjecture surrounds its authenticity. Therefore, we compared GsONC201 to original ONC201 manufactured by Oncoceutics Inc. Methods: Authenticity of GsONC201 was determined by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Biological activity was shown via assessment of on-target effects, in vitro growth, proliferation, and apoptosis analysis. Patient-derived xenograft mouse models were used to assess plasma and brain tissue pharmacokinetics, pharmacodynamics, and overall survival (OS). The clinical experience of 28 H3K27M+ mutant DIPG patients who received GsONC201 (2017–2020) was analyzed. Results: GsONC201 harbored the authentic structure, however, was formulated as a free base rather than the dihydrochloride salt used in clinical trials. GsONC201 in vitro and in vivo efficacy and drug bioavailability studies showed no difference compared to Oncoceutics ONC201. Patients treated with GsONC201 (n = 28) showed a median OS of 18 months (P = .0007). GsONC201 patients who underwent reirradiation showed a median OS of 22 months compared to 12 months for GsONC201 patients who did not (P = .012). Conclusions: This study confirms the biological activity of GsONC201 and documents the OS of patients who received the drug; however, GsONC201 was never used as a monotherapy.

Prediction of general practice licensure/certification examination performance by a measure of 'questionable' activities in clinical practice: a retrospective cohort study

Tue 11 Jun 2024 18:44:30 AEST

Purpose: ‘Low-value’ clinical care and medical services are ‘questionable’ activities, being more likely to cause harm than good or with disproportionately low benefit relative to cost. This study examined the predictive ability of the QUestionable In Training Clinical Activities Index (QUIT-CAI) for general practice (GP) registrars’ (trainees’) performance in Australian GP Fellowship examinations (licensure/certification examinations for independent GP). Methods: The study was nested in ReCEnT, an ongoing cohort study in which Australian GP registrars document their in-consultation clinical practice. Outcome factors in analyses were individual registrars’ scores on the three Fellowship examinations (‘AKT’, ‘KFP’, and ‘OSCE’ examinations) and pass/fail rates during 2012–21. Analyses used univariable and multivariable regression (linear or logistic, as appropriate). The study factor in each analysis was ‘QUIT-CAI score percentage’—the percentage of times a registrar performed a QUIT-CAI clinical activity when ‘at risk’ (i.e. when managing a problem where performing a QUIT-CAI activity was a plausible option). Results: A total of 1265, 1145, and 553 registrars sat Applied Knowledge Test, Key Features Problem, and Objective Structured Clinical Exam examinations, respectively. On multivariable analysis, higher QUIT-CAI score percentages (more questionable activities) were significantly associated with poorer Applied Knowledge Test scores (P = .001), poorer Key Features Problem scores (P = .003), and poorer Objective Structured Clinical Exam scores (P = .005). QUIT-CAI score percentages predicted Royal Australian College of General Practitioner exam failure [odds ratio 1.06 (95% CI 1.00, 1.12) per 1% increase in QUIT-CAI, P = .043]. Conclusion: Performing questionable clinical activities predicted poorer performance in the summative Fellowship examinations, thereby validating these examinations as measures of actual clinical performance (by our measure of clinical performance, which is relevant for a licensure/certification examination).

The Impact of Dietary Interventions on the Microbiota in Inflammatory Bowel Disease: A Systematic Review

Tue 11 Jun 2024 16:02:37 AEST

Background and Aims: Diet plays an integral role in the modulation of the intestinal environment, with the potential to be modified for management of individuals with inflammatory bowel disease [IBD]. It has been hypothesised that poor ‘Western-style’ dietary patterns select for a microbiota that drives IBD inflammation and, that through dietary intervention, a healthy microbiota may be restored. This study aimed to systematically review the literature and assess current available evidence regarding the influence of diet on the intestinal microbiota composition in IBD patients, and how this may affect disease activity. Methods: MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library were searched from January 2013 to June 2023, to identify studies investigating diet and microbiota in IBD. Results: Thirteen primary studies met the inclusion criteria and were selected for narrative synthesis. Reported associations between diet and microbiota in IBD were conflicting due to the considerable degree of heterogeneity between studies. Nine intervention studies trialled specific diets and did not demonstrate significant shifts in the diversity and abundance of intestinal microbial communities or improvement in disease outcomes. The remaining four cross-sectional studies did not find a specific microbial signature associated with habitual dietary patterns in IBD patients. Conclusions: Diet modulates the gut microbiota, and this may have implications for IBD; however, the body of evidence does not currently support clear dietary patterns or food constituents that are associated with a specific microbiota profile or disease marker in IBD patients. Further research is required with a focus on robust and consistent methodology to achieve improved identification of associations.

Comparison of spherical cap and rectangular harmonic analysis of airborne vector gravity data for high-resolution (1.5 km) local geopotential field models over Tanzania

Thu 13 Apr 2023 09:38:45 AEST

This study examines local geopotential field modeling over a mountainous region in Tanzania using vector airborne gravity data. We use the adjusted spherical cap and rectangular harmonic analyses. Both methods are based on expansion of gravitational potential into a series of orthogonal harmonic basis functions of local support in such a way that the expansion coefficients are determined by gravity observations. All three components of gravity vector are simultaneously inverted to derive the geopotential coefficients. In order to evaluate the accuracy of the local models, independent checkpoints are selected within the study region and around its boundary and the computed gravity vectors are compared with the independent gravity observations. The results show an excellent agreement with root mean square error (RMSE) of < 1.6 mGal over the study area. On the contrary, the RMSEs of global geopotential models against the checkpoints data are 7 mGal for the models up to the maximum degree of 2190 (a resolution of ∼9.1 km) and 5 mGal to 5399 (∼3.7 km). Our local models are significantly more accurate than the state-of-the-art global models and fully exploit the airborne vector data with the measurement error of ∼1 mGal. We also present the regional models constrained only by radial (vertical) or by lateral (horizontal) gravity observations. Those models are considerably less accurate than the one from 3D gravity data inversion. Lastly, the regional models are validated against topography data. It is found that the gravity-topography correlation is 0.8–0.9 at 100 km, 0.5 at 20 km, and higher than the correlations of the global models at all frequencies. The gravity-topography admittances estimated from our regional models indicate ∼130 mGal/km and imply the effective density of 2500 kg/m3 for topographical mass.

Sources of Cervicogenic Headache among the Upper Cervical Synovial Joints

Sat 05 Nov 2022 12:28:10 AEDT

Objectives: The study sought to assess the utility of controlled diagnostic blocks in patients with probable cervicogenic headache by determining the prevalence of sources of pain among the upper and lower synovial joints of the cervical spine. Methods: Controlled diagnostic blocks were performed in 166 consecutive patients who clinically exhibited features consistent with a diagnosis of probable cervicogenic headache. Data were collected on how often a particular source of pain could be pinpointed and how often particular diagnostic blocks provided a positive yield. Results: In patients in whom headache was the dominant complaint, diagnostic blocks succeeded in establishing the source of pain in 75% of patients. The C2-3 joint was the source of pain in 62%, followed by the C1-2 (7%) and C3-4 (6%). In patients in whom headache was less severe than neck pain, blocks were successful in 67%. C2-3 was the source of pain in 42%, followed by lower cervical joints in 18% and the C3-4 joint in 7%. Conclusions: Controlled diagnostic blocks can establish the source of pain in the majority of patients presenting with probable cervicogenic headache, with C2-3 being the most common source. On the basis of pretest probability, diagnostic algorithms should commence investigations at C2-3. Second and third steps in the algorithm should differ according to whether headache is the dominant or nondominant complaint.

Understanding Transportation difficulty Among older adults in Ghana from the Perspective of World Health Organisation's Healthy Ageing framework: Lessons for Improving Social Work Practice with Older Adults

Sat 05 Nov 2022 12:28:03 AEDT

Social work profession can be useful in addressing the transportation needs of older adults. However, there is a paucity of knowledge concerning this need in Ghana. The purpose of the study was to investigate the factors relating to transportation difficulty among older adults in Ghana, employing the World Health Organisation (WHO) Healthy Ageing framework. The implications of the findings on social work practice with older adults in Ghana are herein discussed. Data for 5,107 adults aged fifty years or more came from the WHO Study on global AGEing and adult health Ghana Wave 1. Transportation difficulty was assessed using the self-reported question. In the last thirty days, how much difficulty did you have with getting to where you want to go using private or public transport if needed?” Logistic regression tested associations between transportation difficulty and other independent variables. About 31 per cent of the participants, mostly women (54.7 per cent), experienced transportation difficulty. Associated factors included (not exhaustive) advanced age, lower household income, chronic diseases and lack of trust for others. A high prevalence of transportation difficulty exists among older adults in Ghana and is holistically related. Social work’s intervention to address the transportation needs of older adults in Ghana should be holistic; incorporating the significant factors identified affecting older adults’ well-being.

Enhancing the relevance of social work education in Nigeria

Mon 24 Oct 2022 09:52:51 AEDT

Quality locally relevant social work education is essential in social workers’ professional development and, in Nigeria, in the profession’s struggle for legitimacy and connection with local families and communities. It is also pivotal to efficient and effective service delivery in the contemporary digitally connected world, where myriad social issues warrant the professional intervention of skilled practitioners in diverse fields. Social workers’ responsiveness and effectiveness depend crucially on the quality and relevance of the education and training they receive at the start of and throughout their professional careers. This article examines social work education, its relatively recent origins and issues in contemporary Nigerian society highlighting the ongoing need for socio-cultural relevance in the interests of professional recognition. It proposes that social work educators and administrators have a crucial role to play in enhancing the profession’s relevance and suggests a way forward.

Developing a reproducible protocol for culturing functional confluent monolayers of differentiated equine oviduct epithelial cells

Mon 24 Oct 2022 09:45:31 AEDT

We describe the development of two methods for obtaining confluent monolayers of polarized, differentiated equine oviduct epithelial cells (EOEC) in Transwell inserts and microfluidic chips. EOECs from the ampulla were isolated post-mortem and seeded either (1) directly onto a microporous membrane as differentiated EOECs (direct seeding protocol) or (2) first cultured to a confluent de-differentiated monolayer in conventional wells, then trypsinized and seeded onto a microporous membrane (re-differentiation protocol). Maintenance or induction of EOEC differentiation in these systems was achieved by air–liquid interface introduction. Monolayers cultured via both protocols were characterized by columnar, cytokeratin 19-positive EOECs in Transwell inserts. However, only the re-differentiation protocol could be transferred successfully to the microfluidic chips. Integrity of the monolayers was confirmed by transepithelial resistance measurements, tracer flux, and the demonstration of an intimate network of tight junctions. Using the direct protocol, 28% of EOECs showed secondary cilia at the apical surface in a diffuse pattern. In contrast, re-differentiated polarized EOECs rarely showed secondary cilia in either culture system (>90% of the monolayers showed <1% ciliated EOECs). Occasionally (5–10%), re-differentiated monolayers with 11–27% EOECs with secondary cilia in a diffuse pattern were obtained. Additionally, nuclear progesterone receptor expression was found to be inhibited by simulated luteal phase hormone concentrations, and sperm binding to cilia was higher for re-differentiated EOEC monolayers exposed to estrogen–progesterone concentrations mimicking the follicular rather than luteal phase. Overall, a functional equine oviduct model was established with close morphological resemblance to in vivo oviduct epithelium.

The Effects of Prebiotics, Synbiotics, and Short-Chain Fatty Acids on Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis

Mon 24 Oct 2022 09:38:51 AEDT

Prebiotics, synbiotics, and SCFAs have been shown to decrease systemic inflammation and play a protective role in chronic respiratory conditions. However, their effects on infection and immune function are unclear. The objective of this systematic review was to summarize the current evidence for prebiotic, synbiotic, and SCFA supplementation on respiratory tract infections (RTIs) and immune function. The protocol for this systematic review was registered with PROSPERO (National Institute for Health Research, University of York, UK), accessed online at https://www.crd.york.ac.uk/prospero (CRD42019118786). Relevant English-language articles up to May 2021 were identified via online databases: MEDLINE, EMBASE, CINAHL, and Cochrane Library. Included studies (n = 58) examined the effect of prebiotics, synbiotics, or SCFA, delivered orally, on the incidence, severity, or duration of RTIs and/or markers of immune function (e.g., peripheral blood immunophenotyping, NK cell activity). The majority of studies were randomized controlled trials reporting on RTIs in infants and children. The meta-analysis indicated that the numbers of subjects with ≥1 RTI were reduced with prebiotic (OR, 0.73; 95% CI: 0.62-0.86; P = 0.0002; n = 17) and synbiotic (OR, 0.75; 95% CI: 0.65-0.87; P = 0.0001; n = 9) supplementation compared to placebo. Further, NK cell activity was increased with synbiotic (standardized mean difference, 0.74; 95% CI: 0.42-1.06; P < 0.0001, n = 3) supplementation. This review provides evidence that prebiotic, specifically oligosaccharide, supplementation may play a protective role in RTIs in infants and children. There is less evidence for this effect in adults. Supplementation with prebiotic and synbiotic treatment may alter immune function by increasing NK cell activity, though effects on immunophenotype were less clear.

Shorter Contextual Timescale Rather Than Memory Deficit in Aging

Mon 24 Oct 2022 09:38:40 AEDT

Many aspects of cognitive ability and brain function that change as we age look like deficits on account of measurable differences in comparison to younger adult groups. One such difference occurs in auditory sensory responses that index perceptual learning. Meta-analytic findings show reliable age-related differences in auditory responses to repetitive patterns of sound and to rare violations of those patterns, variously attributed to deficits in auditory sensory memory and inhibition. Here, we determine whether proposed deficits would render older adults less prone to primacy effects, robustly observed in young adults, which present as a tendency for first learning to have a disproportionate influence over later perceptual inference. The results confirm this reduced sensitivity to primacy effects but do not support impairment in auditory sensory memory as the origin of this difference. Instead, the aging brain produces data consistent with shorter timescales of contextual reference. In conclusion, age-related differences observed previously for perceptual inference appear highly context-specific necessitating reconsideration of whether and to what function the notion of deficit should be attributed, and even whether the notion of deficit is appropriate at all.

Associations between older African academics' physical activity, walkability and mental health: a social distancing perspective

Mon 24 Oct 2022 09:38:25 AEDT

This study aimed to assess the moderating influence of neighborhood walkability on the association between physical activity (PA) and mental health among older African academics aged 50 years or more in cities with social distancing protocols in response to the Coronavirus disease 2019 (COVID-19). A total of 905 volunteer academics participated in the study. A hierarchical linear regression analysis was employed to conduct sensitivity analyses and test the study hypotheses. After controlling for sex, education and age, there was a positive association between PA and mental health. Neighborhood walkability moderated the relationship between PA and mental health, which suggests that during the pandemic PA was associated with higher mental health scores in more walkable neighborhoods. The study concludes that PA was beneficial to mental health in the social distancing context and was associated with higher mental health in more walkable neighborhoods, particularly in a social distancing context.

Short-chain fatty acids as anti-inflammatory agents in overweight and obesity: A systematic review and meta-analysis

Mon 24 Oct 2022 09:24:48 AEDT

Context: Short-chain fatty acids (SCFAs) derived from microbial fermentation of prebiotic soluble fibers are noted for their anti-inflammatory benefits against obese systemic inflammation. Objective: A systematic review and meta-analysis were undertaken to investigate the effect of SCFAs and prebiotic interventions on systemic inflammation in obesity. Data Sources: Relevant studies from 1947 to August 2019 were collected from the Cumulative Index to Nursing and Allied Health Literature, Embase, Medline, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Study Selection: Of 61 included studies, 29 were of humans and 32 of animals. Data Extraction: Methodological quality of studies was assessed using the critical appraisal checklist of the Academy of Nutrition and Dietetics. Data pertaining to population, intervention type and duration, and markers of systemic inflammation were extracted from included studies. Results: Of 29 included human studies, 3 of 4 SCFA interventions and 11 of 25 prebiotic interventions resulted in a significant decrease in ≥1 biomarker of systemic inflammation. Of 32 included animal studies, 10 of 11 SCFA interventions and 18 of 21 prebiotic interventions resulted in a significant reduction of ≥1 biomarker of systemic inflammation. Meta-analysis revealed that prebiotics in humans reduced levels of plasma high-sensitivity C-reactive protein (standard mean difference [SMD], −0.83; 95%CI: −1.56 to −0.11; I2: 86%; P = 0.02) and plasma lipopolysaccharide (SMD, −1.20; 95%CI: −1.89 to −0.51; I2: 87%; P = 0.0006), and reduced TNF−α levels in animals (SMD, −0.63; 95%CI: −1.19 to −0.07; P = 0.03). Heterogeneity among supplement types, duration, and dose across studies was significant. Conclusion: Evidence from this review and meta-analysis supports the use of SCFAs and prebiotics as novel aids in treatment of obese systemic inflammation. Systematic Review Registration: PROSPERO registration no. CRD42020148529.

Effects of Dietary Fat and Protein on Glucoregulatory Hormones in Adolescents and Young Adults with Type 1 Diabetes

Mon 24 Oct 2022 09:17:37 AEDT

Context: Dietary fat and protein impact postprandial hyperglycemia in people with type 1 diabetes, but the underlying mechanisms are poorly understood. Glucoregulatory hormones are also known to modulate gastric emptying and may contribute to this effect. Objective: Investigate the effects of fat and protein on glucagon-like peptide (GLP-1), glucagon-dependent insulinotropic polypeptide (GIP) and glucagon secretion. Methods: 2 crossover euglycemic insulin clamp clinical trials at 2 Australian pediatric diabetes centers. Participants were 12-21 years (n = 21) with type 1 diabetes for ≥1 year. Participants consumed a low-protein (LP) or high-protein (HP) meal in Study 1, and low-protein/low-fat (LPLF) or high-protein/high-fat (HPHF) meal in Study 2, all containing 30 g of carbohydrate. An insulin clamp was used to maintain postprandial euglycemia and plasma glucoregulatory hormones were measured every 30 minutes for 5 hours. Data from both cohorts (n = 11, 10) were analyzed separately. The main outcome measure was area under the curve of GLP-1, GIP, and glucagon. Results: Meals low in fat and protein had minimal effect on GLP-1, while there was sustained elevation after HP (80.3 ± 16.8 pmol/L) vs LP (56.9 ± 18.6), P = .016, and HPHF (103.0 ± 26.9) vs LPLF (69.5 ± 31.9) meals, P = .002. The prompt rise in GIP after all meals was greater after HP (190.2 ± 35.7 pmol/L) vs LP (152.3 ± 23.3), P = .003, and HPHF (258.6 ± 31.0) vs LPLF (151.7 ± 29.4), P < .001. A rise in glucagon was also seen in response to protein, and HP (292.5 ± 88.1 pg/mL) vs LP (182.8 ± 48.5), P = .010. Conclusion: The impact of fat and protein on postprandial glucose excursions may be mediated by the differential secretion of glucoregulatory hormones. Further studies to better understand these mechanisms may lead to improved personalized postprandial glucose management.

International comparison of guidelines for management of impetigo: a systematic review

Mon 24 Oct 2022 08:49:26 AEDT

Background: Impetigo is a common superficial skin infection that affects people worldwide and is usually treated with antibiotics; therefore, its management has implications for global antibiotic stewardship. Objective: This systematic review and narrative synthesis compares and contrasts international impetigo management guidelines. Methods: Guidelines for treatment of impetigo that were produced by a national authority; available to primary care physicians; and published since 2008 were included. Following a comprehensive search strategy, data extraction from eligible studies was performed independently in duplicate. Details of antiseptic and antibiotic treatment; methicillin-resistant Staphylococcus aureus treatment; and conservative management and preventative measures were tabulated and analysed descriptively. Results: Fifty-one guidelines were included from 42 different countries. All guidelines recommended systemic antibiotics, 78% of these only for widespread lesions or failure of topical antibiotic treatment. The first-line systemic antibiotic treatment was restricted to narrow-spectrum options in 21 (41%) whilst 7 (14%) recommended only broad-spectrum antibiotics first-line. Thirty-four (67%) guidelines included recommendations for topical antibiotic use. Twenty guidelines (39%) did not mention antiseptic treatment for impetigo. Guidelines did not always provide clear indications for different treatment options. Conclusions: Despite potentially equal efficacy to systemic antibiotics, only two-thirds of guidelines include topical antibiotic options. Many fail to include recommendations for non-antibiotic treatments such as antiseptics, preventative measures and conservative management, despite potential for antibiotic-sparing. Provision of clear definitions of disease severity and indications for treatment would enhance the ability of clinicians to adhere to recommendations. Systematic review registration: PROSPERO CRD42018117770.

Boundary Crossers: How Providers Facilitate Ethnic Minority Families' Access to Dementia Services

Mon 24 Oct 2022 08:28:26 AEDT

Objectives: Providers who work closely with ethnic minority people with dementia and their families are pivotal in helping them access services. However, few studies have examined how these providers actually do this work. Using the concept of “boundary crossers,” this article investigates the strategies applied by these providers to facilitate access to dementia services for ethnic minority people with dementia and their families. Methods: Between 2017 and 2020, in-depth video-recorded interviews were conducted with 27 health, aged care, and community service providers working with ethnic minority people living with dementia across Australia. Interviews were conducted in one of seven languages and/or in English, then translated and transcribed verbatim into English. The data were analyzed thematically. Results: Family and community stigma associated with dementia and extra-familial care were significant barriers to families engaging with services. To overcome these barriers, participants worked at the boundaries of culture and dementia, community and systems, strategically using English and other vernaculars, clinical and cultural terminology, building trust and rapport, and assisting with service navigation to improve access. Concurrently, they were cognizant of familial boundaries and were careful to provide services that were culturally appropriate without supplanting the families’ role. Discussion: In negotiating cultural, social, and professional boundaries, providers undertake multidimensional and complex work that involves education, advocacy, negotiation, navigation, creativity, and emotional engagement. This work is largely undervalued but offers a model of care that facilitates social and community development as well as service integration across health, aged care, and social services.

ITGB4 is essential for containing HDM-induced airway inflammation and airway hyperresponsiveness

Mon 23 Jan 2023 11:40:32 AEDT

Airway epithelial cells play a significant role in the pathogenesis of asthma. Although the structural and functional defects of airway epithelial cells have been postulated to increase asthma susceptibility and exacerbate asthma severity, the mechanism and implication of these defects remain uncertain. Integrin β4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. In this study, we demonstrated that ITGB4 deficiency leads to severe allergy-induced airway inflammation and airway hyper-responsiveness (AHR) in mice. After house dust mite (HDM) challenge, epithelial cell-specific ITGB4-deleted mice showed increased lymphocyte, eosinophil, and neutrophil infiltration into lung compared with that of the wild-type mice. ITGB4 deficiency also resulted in increased expression of the Th2 cytokine IL-4, IL-13, and the Th17 cytokine IL-17A in the lung tissue and in the T cells after HDM challenge. The aggravated inflammation in ITGB4 defect mice was partly caused by enhanced disrupted epithelial barrier integrity after HDM stress, which induced the increased thymic stromal lymphopoietin secretion from airway epithelial cells. This study therefore demonstrates that ITGB4 plays a pivotal role in containing allergen-mediated lung inflammation and airway hyper-responsiveness in allergic asthma.

Effect of cinnamaldehyde on Rhizopus stolonifer and on the conservation of sweet potato

Mon 19 Aug 2024 18:14:44 AEST

Objectives: Rhizopus stolonifer, which causes soft rot of sweet potato, has resulted in substantial loss of economy postharvest. Materials and Methods: The antifungal effect and mechanism of cinnamaldehyde (CIN) against R. stolonifer were explored by biochemical analysis and RNA-sequencing in this research, and the edible quality of CIN-treated sweet potato was evaluated. Results: The results showed that CIN inhibited the growth of R. stolonifer and reduced the incidence of soft rot in sweet potato at a minimum inhibitory concentration of 1000 μL/L. The damage of the cell walls of R. stolonifer by CIN was associated with the upregulation of CHT1. Cytosolic leakage and malondialdehyde content increased following CIN-treatment, which was correlated with increased reactive oxygen species levels and decreased catalase activity. Upregulation of ERG genes and oxidative stress-related genes following CIN treatment was associated with impaired cell membrane integrity. The mitochondrial structure of R. stolonifer was damaged by CIN treatment resulting in decreased respiration rates and ATP production, which was correlated with lower expression levels of IDH1, COX4, and QCR7. Conclusions: Our research suggests that the inhibition of CIN on R. stolonifer was related to the disruption of its normal gene expression network, and CIN maintained the nutritional and edible quality of sweet potato. This study provides valuable insights into the antifungal mechanism of CIN on R. stolonifer and the maintenance of root quality, which contributes to the efficient use of CIN for controlling soft rot in sweet potato.

Factors influencing fertility rates in Australian women receiving kidney replacement therapy: analysis of linked Australia and New Zealand Dialysis and Transplant Registry and perinatal data over 22 years

Mon 17 Oct 2022 10:13:28 AEDT

Background: Pregnancy in women receiving kidney replacement therapy (KRT) is uncommon, and trends and factors influencing fertility rates remain poorly defined. Methods: The Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) was linked to mandatory perinatal data sets (all births from 1991 to 2013, ≥20 weeks’ gestation) in four Australian jurisdictions. Overall, age- and era-specific fertility rates were calculated based on general and KRT population denominators. Results: From 2 948 084 births, 248 babies were born to 168 mothers receiving KRT (37 babies born to 31 dialysed mothers; 211 babies born to 137 transplanted mothers). Substantial agreement between ANZDATA and perinatal data sets was observed for birth events and outcomes. Transplanted women had higher fertility rates than dialysed women in all analyses, with 21.4 live births/1000 women/year [95% confidence interval (CI) 18.6–24.6] in transplanted women, 5.8 (95% CI 4.1–8.1) in dialysed women and 61.9 (95% CI 61.8–62.0) in the non-KRT cohort. Fertility rates for dialysed women rose in recent years. After adjusting for maternal age and treatment modality, Caucasian women had higher fertility rates, while women with pre-existing diabetes, or transplanted women with exposure to KRT for ≤3.0 years had lower rates. As expected, transplanted women with a pre-conception estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m2 or transplant-to-pregnancy interval of <1.0 year had lower fertility rates. Geographical location, socioeconomic status and primary disease (glomerulonephritis versus other) did not affect fertility rates. Conclusions: Reporting of births to ANZDATA is sufficiently accurate to justify ongoing data collection. Rising fertility rates in dialysed women may indicate permissive attitudes towards pregnancy. Treatment modality, ethnicity, diabetes, pre-conception eGFR, transplant-to-pregnancy interval and duration of KRT exposure were associated with fertility rates. These factors should be considered when counselling women with kidney disease about parenthood.

Long-Term Efficacy of T3 Analogue Triac in Children and Adults with MCT8 Deficiency: A Real-Life Retrospective Cohort Study

Mon 07 Nov 2022 11:35:58 AEDT

Context: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. Objective: Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. Methods: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. Results: From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. Conclusions: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency.

Diffuse midline glioma, H3K27-altered: illuminating the dark side of the moon

Mon 03 Jun 2024 08:37:24 AEST

Despite the world-renown scientific achievement of Commander Neil Armstrong’s first moon walk, few will know of his daughter Karen “Muffie” Armstrong who was lost to the fatal brainstem malignancy, diffuse intrinsic pontine glioma (DIPG), at just 2 years of age. Muffie was diagnosed with this form of diffuse midline glioma (DMG) in 1962, received 6 weeks of palliative radiotherapy, and passed little more than 6 months following her diagnosis.

A subsidiary cell-localized glucose transporter promotes stomatal conductance and photosynthesis

Fri 28 Oct 2022 14:50:18 AEDT

It has long been recognized that stomatal movement modulates CO2 availability and as a consequence the photosynthetic rate of plants, and that this process is feedback-regulated by photoassimilates. However, the genetic components and mechanisms underlying this regulatory loop remain poorly understood, especially in monocot crop species. Here, we report the cloning and functional characterization of a maize (Zea mays) mutant named closed stomata1 (cst1). Map-based cloning of cst1 followed by confirmation with the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 system identified the causal mutation in a Clade I Sugars Will Eventually be Exported Transporters (SWEET) family gene, which leads to the E81K mutation in the CST1 protein. CST1 encodes a functional glucose transporter expressed in subsidiary cells, and the E81K mutation strongly impairs the oligomerization and glucose transporter activity of CST1. Mutation of CST1 results in reduced stomatal opening, carbon starvation, and early senescence in leaves, suggesting that CST1 functions as a positive regulator of stomatal opening. Moreover, CST1 expression is induced by carbon starvation and suppressed by photoassimilate accumulation. Our study thus defines CST1 as a missing link in the feedback-regulation of stomatal movement and photosynthesis by photoassimilates in maize.

When Law-And-Order Politics Fail: Media Fragmentation and Protective Factors That Limit the Politics of Fear

Fri 03 Nov 2023 15:58:28 AEDT

Law-and-order politics has long been a topic of scholarly work. The leveraging of fear of crime for political capital has been of particular concern. In the 2018 election in the Australian state of Victoria, crime and law-and-order became prominent political issues, particularly through racialized discourse about ‘African gangs’. That election provides a case study here. This article turns the traditional analysis of the politics of fear of crime around and considers some of the key reasons why law-and-order politics failed to gain decisive political traction in this instance. Media fragmentation and diversification continues to challenge the primacy of political primary definers in unpredictable ways. As such, electoral strategies that seek to leverage fear of crime and community insecurity need to be understood in the context of broader individual, community and social protective factors that might mitigate fear of crime.