Responses of intraspecific metabolic scaling to temperature and activity differ between water- and air-breathing ectothermic vertebrates.

Metabolism underpins all life-sustaining processes and varies profoundly with body size, temperature and locomotor activity. A current theory explains some of the size-dependence of metabolic rate (its mass exponent, b) through changes in metabolic level (L). We propose two predictive advances that: (a) combine the above theory with the evolved avoidance of oxygen limitation in water-breathers experiencing warming, and (b) quantify the overall magnitude of combined temperatures and degrees of locomotion on metabolic scaling across air- and water-breathers. We use intraspecific metabolic scaling responses to temperature (523 regressions) and activity (281 regressions) in diverse ectothermic vertebrates (fish, reptiles and amphibians) to show that b decreases with temperature-increased L in water-breathers, supporting surface area-related avoidance of oxygen limitation, whereas b increases with activity-increased L in air-breathers, following volume-related influences. This new theoretical integration quantitatively incorporates different influences (warming, locomotion) and respiration modes (aquatic, terrestrial) on animal energetics.

ssVERDICT: Self-supervised VERDICT-MRI for enhanced prostate tumor characterization.

PURPOSE: Demonstrating and assessing self-supervised machine-learning fitting of the VERDICT (vascular, extracellular and restricted diffusion for cytometry in tumors) model for prostate cancer. METHODS: We derive a self-supervised neural network for fitting VERDICT (ssVERDICT) that estimates parameter maps without training data. We compare the performance of ssVERDICT to two established baseline methods for fitting diffusion MRI models: conventional nonlinear least squares and supervised deep learning. We do this quantitatively on simulated data by comparing the Pearson's correlation coefficient, mean-squared error, bias, and variance with respect to the simulated ground truth. We also calculate in vivo parameter maps on a cohort of 20 prostate cancer patients and compare the methods' performance in discriminating benign from cancerous tissue via Wilcoxon's signed-rank test. RESULTS: In simulations, ssVERDICT outperforms the baseline methods (nonlinear least squares and supervised deep learning) in estimating all the parameters from the VERDICT prostate model in terms of Pearson's correlation coefficient, bias, and mean-squared error. In vivo, ssVERDICT shows stronger lesion conspicuity across all parameter maps, and improves discrimination between benign and cancerous tissue over the baseline methods. CONCLUSION: ssVERDICT significantly outperforms state-of-the-art methods for VERDICT model fitting and shows, for the first time, fitting of a detailed multicompartment biophysical diffusion MRI model with machine learning without the requirement of explicit training labels.

Medications and cognitive risk in Aboriginal primary care: a cross-sectional study.

BACKGROUND: Aboriginal and Torres Strait Islander people are ageing with high rates of comorbidity, yet little is known about suboptimal prescribing in this population. AIM: The prevalence of potentially suboptimal prescribing and associated risk factors were investigated among older patients attending primary care through Aboriginal Community Controlled Health Services (ACCHSs). METHODS: Medical records of 420 systematically selected patients aged ≥50 years attending urban, rural and remote health services were audited. Polypharmacy (≥ 5 prescribed medications), potentially inappropriate medications (PIMs) as per Beers Criteria and anticholinergic burden (ACB) were estimated and associated risk factors were explored with logistic regression. RESULTS: The prevalence of polypharmacy, PIMs and ACB score ≥3 was 43%, 18% and 12% respectively. In multivariable logistic regression analyses, polypharmacy was less likely in rural (odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.24-0.77) compared to urban patients, and more likely in those with heart disease (OR = 2.62, 95% CI = 1.62-4.25), atrial fibrillation (OR = 4.25, 95% CI = 1.08-16.81), hypertension (OR = 2.14, 95% CI = 1.34-3.44), diabetes (OR = 2.72, 95% CI = 1.69-4.39) or depression (OR = 1.91, 95% CI = 1.19-3.06). PIMs were more frequent in females (OR = 1.88, 95% CI = 1.03-3.42) and less frequent in rural (OR = 0.41, 95% CI = 0.19-0.85) and remote (OR = 0.58, 95% CI = 0.29-1.18) patients. Factors associated with PIMs were kidney disease (OR = 2.60, 95% CI = 1.37-4.92), urinary incontinence (OR = 3.00, 95% CI = 1.02-8.83), depression (OR = 2.67, 95% CI = 1.50-4.77), heavy alcohol use (OR = 2.83, 95% CI = 1.39-5.75) and subjective cognitive concerns (OR = 2.69, 95% CI = 1.31-5.52). High ACB was less common in rural (OR = 0.10, 95% CI = 0.03-0.34) and remote (OR = 0.51, 95% CI = 0.25-1.04) patients and more common in those with kidney disease (OR = 3.07, 95% CI = 1.50-6.30) or depression (OR = 3.32, 95% CI = 1.70-6.47). CONCLUSION: Associations between potentially suboptimal prescribing and depression or cognitive concerns highlight the importance of considering medication review and deprescribing for these patients.

Oral glucose tolerance test-The imperfect gold standard for gestational diabetes screening: A qualitative study involving clinicians in regional, rural and remote areas of Western Australia.

ISSUE ADDRESSED: The oral glucose tolerance test is the 'gold standard' for detecting gestational diabetes in Australian and International guidelines. Test completion in regional, rural and remote regions may be as low as 50%. We explored challenges and enablers for regional, rural and remote antenatal clinicians providing gestational diabetes screening to better understand low oral glucose tolerance test completion. METHODS: We conducted a qualitative descriptive study using semi-structured interviews. Participants eligible for the study were doctors or midwives providing antenatal care in regional, rural and remote Western Australia, between August 2019 and November 2020. Interviews were recorded digitally and transcribed into a Word document. We conducted a thematic analysis after initial categorisation and deduction of themes through workshops involving the research team. RESULTS: We found a diversity of viewpoints on oral glucose tolerance test reliability for detecting gestational diabetes. Themes that emerged were; good collaboration between antenatal clinicians is required for successful screening; screening occurs throughout pregnancy using various tests; clinicians make significant efforts to address barriers; clinicians prioritise therapeutic relationships. CONCLUSIONS: Effective universal screening for gestational diabetes in regional, rural and remote Western Australia is difficult and more complex in practice than guidelines imply. Detecting gestational diabetes requires creative solutions, early identification of at risk women and trust and collaboration between clinicians and women. SO WHAT?: Detection of gestational diabetes in regional, rural and remote Western Australia remains poorly completed. New strategies are required to adequately identify women at risk of adverse birth outcomes relating to hyperglycaemia in pregnancy.

Prevalence of functional limitations in older remote-living Aboriginal Australians.

INTRODUCTION: To better tailor prevention and care strategies, there is a need to identify modifiable factors associated with functional impairment in older Aboriginal people, and related service needs. OBJECTIVE: To investigate the prevalence and associated factors for functional impairment in older Aboriginal people, and related service needs. DESIGN: Cross-sectional survey of 289 Aboriginal people aged ≥45 years living in the remote Kimberley region of Western Australia. Factors associated with functional impairment were explored with logistic regression. FINDINGS: 41.2% (95% CI 35.6%-47.0%) of participants required assistance with at least one I/ADL, and 26.0% (95% CI 21.2%-31.3%) required assistance with two or more I/ADLs. A core activity limitation (required assistance with showering, dressing or cooking) was reported by 15.9% (95% CI 12.1%-20.6%). In multivariable logistic regression analyses, older age, diabetes, difficulty walking, head injury, higher depression score and worse cognition were associated with needing help with two or more I/ADLs, while older age, history of stroke, higher depression score and worse cognition were associated with the presence of a core activity limitation. The proportion of participants receiving support with I/ADLs ranged from 71.2% to 97.6%. Support was generally provided by family and friends rather than service providers. DISCUSSION: The key modifiable factors associated with functional impairment in older Aboriginal people living in remote regions are diabetes, depression and cognitive impairment. Services required are transport and socio-cultural activities, and ensuring support for family providing the majority of care. CONCLUSIONS: This study highlights the need for holistic prevention strategies and care for older Aboriginal people with functional limitations and their families.

Human apoA-I[Lys107del] mutation affects lipid surface behavior of apoA-I and its ability to form large nascent HDL.

Population studies have found that a natural human apoA-I variant, apoA-I[K107del], is strongly associated with low HDL-C but normal plasma apoA-I levels. We aimed to reveal properties of this variant that contribute to its unusual phenotype associated with atherosclerosis. Our oil-drop tensiometry studies revealed that compared to WT, recombinant apoA-I[K107del] adsorbed to surfaces of POPC-coated triolein drops at faster rates, remodeled the surfaces to a greater extent, and was ejected from the surfaces at higher surface pressures on compression of the lipid drops. These properties may drive increased binding of apoA-I[K107del] to and its better retention on large triglyceride-rich lipoproteins, thereby increasing the variant's content on these lipoproteins. While K107del did not affect apoA-I capacity to promote ABCA1-mediated cholesterol efflux from J774 cells, it impaired the biogenesis of large nascent HDL particles resulting in the formation of predominantly smaller nascent HDL. Size-exclusion chromatography of spontaneously reconstituted 1,2-dimyristoylphosphatidylcholine-apoA-I complexes showed that apoA-I[K107del] had a hampered ability to form larger complexes but formed efficiently smaller-sized complexes. CD analysis revealed a reduced ability of apoA-I[K107del] to increase α-helical structure on binding to 1,2-dimyristoylphosphatidylcholine or in the presence of trifluoroethanol. This property may hinder the formation of large apoA-I[K107del]-containing discoidal and spherical HDL but not smaller HDL. Both factors, the increased content of apoA-I[K107del] on triglyceride-rich lipoproteins and the impaired ability of the variant to stabilize large HDL particles resulting in reduced lipid:protein ratios in HDL, may contribute to normal plasma apoA-I levels along with low HDL-C and increased risk for CVD.

Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1-13 C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade.

BACKGROUND: Three-dimensional (3D) multiecho balanced steady-state free precession (ME-bSSFP) has previously been demonstrated in preclinical hyperpolarized (HP) 13 C-MRI in vivo experiments, and it may be suitable for clinical metabolic imaging of prostate cancer (PCa). PURPOSE: To validate a signal simulation framework for the use of sequence parameter optimization. To demonstrate the feasibility of ME-bSSFP for HP 13 C-MRI in patients. To evaluate the metabolism in PCa measured by ME-bSSFP. STUDY TYPE: Retrospective single-center cohort study. PHANTOMS/POPULATION: Phantoms containing aqueous solutions of [1-13 C] lactate (2.3 M) and [13 C] urea (8 M). Eight patients (mean age 67 ± 6 years) with biopsy-confirmed Gleason 3 + 4 (n = 7) and 4 + 3 (n = 1) PCa. FIELD STRENGTH/SEQUENCES: 1 H MRI at 3 T with T2 -weighted turbo spin-echo sequence used for spatial localization and spoiled dual gradient-echo sequence used for B0 -field measurement. ME-bSSFP sequence for 13 C MR spectroscopic imaging with retrospective multipoint IDEAL metabolite separation. ASSESSMENT: The primary endpoint was the analysis of pyruvate-to-lactate conversion in PCa and healthy prostate regions of interest (ROIs) using model-free area under the curve (AUC) ratios and a one-directional kinetic model (kP ). The secondary objectives were to investigate the correlation between simulated and experimental ME-bSSFP metabolite signals for HP 13 C-MRI parameter optimization. STATISTICAL TESTS: Pearson correlation coefficients with 95% confidence intervals and paired t-tests. The level of statistical significance was set at P < 0.05. RESULTS: Strong correlations between simulated and empirical ME-bSSFP signals were found (r > 0.96). Therefore, the simulation framework was used for sequence optimization. Whole prostate metabolic HP 13 C-MRI, observing the conversion of pyruvate into lactate, with a temporal resolution of 6 seconds was demonstrated using ME-bSSFP. Both assessed metrics resulted in significant differences between PCa (mean ± SD) (AUC = 0.33 ± 012, kP  = 0.038 ± 0.014) and healthy (AUC = 0.15 ± 0.10, kP  = 0.011 ± 0.007) ROIs. DATA CONCLUSION: Metabolic HP 13 C-MRI in the prostate using ME-bSSFP allows for differentiation between aggressive PCa and healthy tissue. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Avoiding Unnecessary Biopsy after Multiparametric Prostate MRI with VERDICT Analysis: The INNOVATE Study.

Background In men suspected of having prostate cancer (PCa), up to 50% of men with positive multiparametric MRI (mpMRI) findings (Prostate Imaging Reporting and Data System [PI-RADS] or Likert score of 3 or higher) have no clinically significant (Gleason score ≤3+3, benign) biopsy findings. Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) MRI analysis could improve the stratification of positive mpMRI findings. Purpose To evaluate VERDICT MRI, mpMRI-derived apparent diffusion coefficient (ADC), and prostate-specific antigen density (PSAD) as determinants of clinically significant PCa (csPCa). Materials and Methods Between April 2016 and December 2019, men suspected of having PCa were prospectively recruited from two centers and underwent VERDICT MRI and mpMRI at one center before undergoing targeted biopsy. Biopsied lesion ADC, lesion-derived fractional intracellular volume (FIC), and PSAD were compared between men with csPCa and those without csPCa, using nonparametric tests subdivided by Likert scores. Area under the receiver operating characteristic curve (AUC) was calculated to test diagnostic performance. Results Among 303 biopsy-naive men, 165 study participants (mean age, 65 years ± 7 [SD]) underwent targeted biopsy; of these, 73 had csPCa. Median lesion FIC was higher in men with csPCa (FIC, 0.53) than in those without csPCa (FIC, 0.18) for Likert 3 (P = .002) and Likert 4 (0.60 vs 0.28, P < .001) lesions. Median lesion ADC was lower for Likert 4 lesions with csPCa (0.86 × 10-3 mm2/sec) compared with lesions without csPCa (1.12 × 10-3 mm2/sec, P = .03), but there was no evidence of a difference for Likert 3 lesions (0.97 × 10-3 mm2/sec vs 1.20 × 10-3 mm2/sec, P = .09). PSAD also showed no difference for Likert 3 (0.17 ng/mL2 vs 0.12 ng/mL2, P = .07) or Likert 4 (0.14 ng/mL2 vs 0.12 ng/mL2, P = .47) lesions. The diagnostic performance of FIC (AUC, 0.96; 95% CI: 0.93, 1.00) was higher (P = .02) than that of ADC (AUC, 0.85; 95% CI: 0.79, 0.91) and PSAD (AUC, 0.74; 95% CI: 0.66, 0.82) for the presence of csPCa in biopsied lesions. Conclusion Lesion fractional intracellular volume enabled better classification of clinically significant prostate cancer than did apparent diffusion coefficient and prostate-specific antigen density. Clinical trial registration no. NCT02689271 © RSNA, 2022 Online supplemental material is available for this article.

Termites have wider thermal limits to cope with environmental conditions in savannas.

The most diverse and abundant family of termites, the Termitidae, evolved in African tropical forests. They have since colonised grassy biomes such as savannas. These open environments have more extreme conditions than tropical forests, notably wider extremes of temperature and lower precipitation levels and greater temporal fluctuations (of both annual and diurnal variation). These conditions are challenging for soft-bodied ectotherms, such as termites, to survive in, let alone become as ecologically dominant as termites have. Here, we quantified termite thermal limits to test the hypothesis that these physiological limits are wider in savanna termite species to facilitate their existence in savanna environments. We sampled termites directly from mound structures, across an environmental gradient in Ghana, ranging from wet tropical forest through to savanna. At each location, we quantified both the Critical Thermal Maxima (CTmax ) and the Critical Thermal Minima (CTmin ) of all the most abundant mound-building Termitidae species in the study areas. We modelled the thermal limits in two separate mixed-effects models against canopy cover at the mound, temperature and rainfall, as fixed effects, with sampling location as a random intercept. For both CTmax and CTmin , savanna species had significantly more extreme thermal limits than forest species. Between and within environments, areas with higher amounts of canopy cover were significantly associated with lower CTmax values of the termite colonies. CTmin was significantly positively correlated with rainfall. Temperature was retained in both models; however, it did not have a significant relationship in either. Sampling location explained a large proportion of the residual variation, suggesting there are other environmental factors that could influence termite thermal limits. Our results suggest that savanna termite species have wider thermal limits than forest species. These physiological differences, in conjunction with other behavioural adaptations, are likely to have enabled termites to cope with the more extreme environmental conditions found in savanna environments and facilitated their expansion into open tropical environments.

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies.

PURPOSE: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies. MATERIALS AND METHODS: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7-21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging. RESULTS: Eight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441-404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%-100%). There were no significant changes in perfusion imaging parameters after TACE. CONCLUSIONS: BTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.

Planning of gamma knife radiosurgery (GKR) for brain arteriovenous malformations using triple magnetic resonance angiography (triple-MRA).

PURPOSE: Intra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR). METHODS: Fifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported. RESULTS: AVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6-13.9%; SD:7.14%; p = .003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2-76; range: 65-80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7-21.3; range: 7-30%). CONCLUSION: The technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects.

Female fruit flies cannot protect stored sperm from high temperature damage.

Recently, it has been demonstrated that heat-induced male sterility is likely to shape population persistence as climate change progresses. However, an under-explored possibility is that females may be able to successfully store and preserve sperm at temperatures that sterilise males, which could ameliorate the impact of male infertility on populations. Here, we test whether females from two fruit fly species can protect stored sperm from a high temperature stress. We find that sperm carried by female Drosophila virilis are almost completely sterilised by high temperatures, whereas sperm carried by female Zaprionus indianus show only slightly reduced fertility. Heat-shocked D. virilis females can recover fertility when allowed to remate, suggesting that the delivered heat-shock is damaging stored sperm and not directly damaging females in this species. The temperatures required to reduce fertility of mated females are substantially lower than the temperatures required to damage mature sperm in males, suggesting that females are worse than males at protecting mature sperm. This suggests that female sperm storage is unlikely to ameliorate the impacts of high temperature fertility losses in males, and instead exacerbates fertility costs of high temperatures, representing an important determinant of population persistence during climate change.

Advances in Implantable Microelectrode Array Insertion and Positioning.

OBJECTIVES: Microelectrode arrays offer a means to probe the functional circuitry of the brain and the promise of cortical neuroprosthesis for individuals suffering from paralysis or limb loss. These devices are typically comprised of one or more shanks incorporating microelectrode sites, where the shanks are positioned by inserting the devices along a straight path that is normal to the brain surface. The lack of consistent long-term chronic recording technology has driven interest in novel probe design and approaches that go beyond the standard insertion approach that is limited to a single velocity or axis. This review offers a description of typical approaches and associated limitations and surveys emergent methods for implantation of microelectrode arrays, in particular those new approaches that leverage embedded microactuators and extend the insertion direction beyond a single axis. MATERIALS AND METHODS: This review paper surveys the current technologies that enable probe implantation, repositioning, and the capability to record/stimulate from a tissue volume. A comprehensive literature search was performed using PubMed, Web of Science, and Google Scholar. RESULTS: There has been substantial innovation in the development of microscale and embedded technology that enables probe repositioning to maintain quality recordings in the brain. Innovations in material science have resulted in novel strategies for deployable structures that can record from or stimulate a tissue volume. Moreover, new developments involving magnetically steerable catheters and needles offer an alternative approach to "pull" rather than "push" a probe into the tissue. CONCLUSION: We envision the emergence of a new generation of probes and insertion methodologies for neuromodulation applications that enable reliable chronic performance from devices that can be positioned virtually anywhere in the brain.

Early childhood development practices in a remote Aboriginal Community Controlled Health Services setting.

OBJECTIVE: Supporting Early Childhood Development (ECD) is an Australian national priority. Aboriginal children in Western Australia's Kimberley region have much higher rates of developmental concerns at school entry than non-Aboriginal children. We aimed to describe ECD practices in the participating service; document follow-up of identified developmental concerns; and identify barriers and enablers to incorporating ECD practices into clinic activity. DESIGN: Mixed-method design incorporating clinical audit and staff interviews. SETTING: An Aboriginal Community Controlled Health Service (ACCHS) in the Kimberley region. PARTICIPANTS: A total of 176 children receiving primary health care through the participating ACCHS; interviews with five ACCHS staff members. MAIN OUTCOME MEASURES: Frequency of developmental enquiry by age and domain; follow-up of identified developmental concerns; and barriers and enablers to ECD practices. RESULTS: Developmental enquiry was documented for 114 of 176 eligible children (65%), including in 80% of ACCHS child health assessments. Standardised ECD assessments were less common. Staff were aware of the importance of developmental enquiry, however, barriers to increasing ECD practices included a lack of resources and structured staff education, time pressures and a lack of role clarity between the ACCHS and government community health clinic. CONCLUSIONS: This study provides insight into ECD practices in an ACCHS setting, highlighting the potential of primary health care to have an enhanced role in ECD if appropriate systems, training and tools are provided. A lack of role clarity across services, combined with poor communication between services, creates a potential risk for missed opportunities to support ECD.

Utility of diffusion MRI characteristics of cervical lymph nodes as disease classifier between patients with head and neck squamous cell carcinoma and healthy volunteers.

Diffusion MRI characteristics assessed by apparent diffusion coefficient (ADC) histogram analysis in head and neck squamous cell carcinoma (HNSCC) have been reported as helpful in classifying tumours based on diffusion characteristics. There is little reported on HNSCC lymph nodes classification by diffusion characteristics. The aim of this study was to determine whether pretreatment nodal microstructural diffusion MRI characteristics can classify diseased nodes of patients with HNSCC from normal nodes of healthy volunteers. Seventy-nine patients with histologically confirmed HNSCC prior to chemoradiotherapy, and eight healthy volunteers, underwent diffusion-weighted (DW) MRI at a 1.5-T MR scanner. Two radiologists contoured lymph nodes on DW (b = 300 s/m2 ) images. ADC, distributed diffusion coefficient (DDC) and alpha (α) values were calculated by monoexponential and stretched exponential models. Histogram analysis metrics of drawn volume were compared between patients and volunteers using a Mann-Whitney test. The classification performance of each metric between the normal and diseased nodes was determined by receiver operating characteristic (ROC) analysis. Intraclass correlation coefficients determined interobserver reproducibility of each metric based on differently drawn ROIs by two radiologists. Sixty cancerous and 40 normal nodes were analysed. ADC histogram analysis revealed significant differences between patients and volunteers (p ≤0.0001 to 0.0046), presenting ADC distributions that were more skewed (1.49 for patients, 1.03 for volunteers; p = 0.0114) and 'peaked' (6.82 for patients, 4.20 for volunteers; p = 0.0021) in patients. Maximum ADC values exhibited the highest area under the curve ([AUC] 0.892). Significant differences were revealed between patients and volunteers for DDC and α value histogram metrics (p ≤0.0001 to 0.0044); the highest AUC were exhibited by maximum DDC (0.772) and the 25th percentile α value (0.761). Interobserver repeatability was excellent for mean ADC (ICC = 0.88) and the 25th percentile α value (ICC = 0.78), but poor for all other metrics. These results suggest that pretreatment microstructural diffusion MRI characteristics in lymph nodes, assessed by ADC and α value histogram analysis, can identify nodal disease.

Fine sediment and flow velocity impact bacterial community and functional profile more than nutrient enrichment.

Freshwater ecosystems face many simultaneous pressures due to human activities. Consequently, there has been a rapid loss of freshwater biodiversity and an increase in biomonitoring programs. Our study assessed the potential of benthic stream bacterial communities as indicators of multiple-stressor impacts associated with urbanization and agricultural intensification. We conducted a fully crossed four-factor experiment in 64 flow-through mesocosms fed by a pristine montane stream (21 d of colonization, 21 d of manipulations) and investigated the effects of nutrient enrichment, flow-velocity reduction and added fine sediment after 2 and 3 weeks of stressor exposure. We used high-throughput sequencing and metabarcoding techniques (16S rRNA genes), as well as curated biological databases (METAGENassit, MetaCyc), to identify changes in bacterial relative abundances and predicted metabolic functional profile. Sediment addition and flow-velocity reduction were the most pervasive stressors. They both increased α-diversity and had strong taxon-specific effects on community composition and predicted functions. Sediment and flow velocity also interacted frequently, with 88% of all bacterial response variables showing two-way interactions and 33% showing three-way interactions including nutrient enrichment. Changes in relative abundances of common taxa were associated with shifts in dominant predicted functions, which can be extrapolated to underlaying stream-wide mechanisms such as carbon use and bacterial energy production pathways. Observed changes were largely stable over time and occurred after just 2 weeks of exposure, demonstrating that bacterial communities can be well-suited for early detection of multiple stressors. Overall, added sediment and reduced flow velocity impacted both bacterial community structure and predicted function more than nutrient enrichment. In future research and stream management, a holistic approach to studying multiple-stressor impacts should include multiple trophic levels with their functional responses, to enhance our mechanistic understanding of complex stressor effects and promote establishment of more efficient biomonitoring programs.

Prevalence and sites of pain in remote-living older Aboriginal Australians, and associations with depressive symptoms and disability.

BACKGROUND: Pain is a growing public health problem associated with significant health and functional implications. Limited data exist for Aboriginal Australians. AIMS: To describe the prevalence, severity and sites of pain, analgesic use and associated factors, including depression and disability, in remote-living Aboriginal Australians. METHODS: Cross-sectional study of 263 Aboriginal Australians aged ≥45 years from six remote Indigenous communities and the town of Derby in the Kimberley region of Western Australia between 2011 and 2013. Pain was assessed using a culturally adapted pain scale. Factors associated with pain were investigated with binary logistic regression. RESULTS: One hundred and seventy (64.6%) participants reported having pain and 53 (20.2%) reported persistent pain. Of those reporting pain, 61 (35.9%) rated it as moderate and 70 (41.2%) as severe. The most common sites of pain were back and knee, and 38 (22.4%) participants with pain indicated three or more sites of pain. Only 70 (41.2%) participants with pain were on some type of analgesic medication. After adjustment, poor vision (odds ratio (OR) = 2.21; 95% confidence interval (CI) 1.22-4.00), hypertension (OR = 1.89; 95% CI 1.03-3.45) and heart problems (OR = 2.05; 95% CI 1.01-4.14) were associated with pain. Higher depression scores were associated with more persistent pain, but pain was not significantly associated with clinically relevant depressive symptoms, or requiring assistance with two or more personal and/or instrumental activities of daily living. CONCLUSION: High levels of pain were reported, although the prevalence of persistent pain was comparable to the general population. Identifying risk factors, improving pain recognition and assessment and evaluating culturally tailored management approaches should be a priority.

Risk and resilience: a mixed methods investigation of Aboriginal Australian women's perinatal mental health screening assessments.

PURPOSE: To describe the psychosocial protective and risk factors for perinatal mental health identified in a sample of Aboriginal women's Kimberley Mum's Mood Scale (KMMS) assessments and explore the role of these factors in their screening assessment and diagnostic outcome. METHODS: We used a mixed methods approach to retrospectively analyse a cross-sectional study dataset of 91 completed KMMS assessments. This included: categorising the clinical notes from the KMMS psychosocial yarn into 'risk' and 'protective' factors and describing these categories, describing the number and type of risk and protective factors associated with different KMMS risk assessment categories (no, low, medium, high), and exploring relationships between these risk and protective factors and diagnosis of perinatal depression and/or anxiety. RESULTS: Protective factors were recorded for the vast majority of the women; the most prominent was positive family relationships. When protective and risk factors were stratified by KMMS risk category, women in the higher risk group less commonly had specific protective factors (11-33% high vs 61-100% no risk) and more commonly had risk factors (22-67% high vs 6-28% no risk) than women with lower KMMS assessed risk. The average number of protective factors decreased with increasing KMMS risk category (4.9 ± 1.1 to 1.6 ± 1.3), with the inverse pattern for risk factors (1.1 ± 1.1 to 3.8 ± 1.0). Having protective factors also appeared to reduce the risk of developing clinical depression or anxiety. CONCLUSION: Assessing protective factors in mental health screening for perinatal Aboriginal women increases the effectiveness of screening and provides a foundation for the delivery of local structured psychosocial care.

"When I got the news": Aboriginal fathers in the Kimberley region yarning about their experience of the antenatal period.

ISSUE ADDRESSED: Paternal involvement during the antenatal period is recognised as a positive contributor to a child's health and developmental outcomes. Little is known about Aboriginal Australian men's experiences and perceptions during their partner's antenatal period. METHODS: A qualitative yarning methodology was used to explore the experiences of ten Aboriginal Australian fathers during their partner's antenatal period, in a remote Northern Australian town. RESULTS: The study found the participants valued supporting their partners through pregnancy, making positive changes to their lifestyles, and having access to information on pregnancy. Participants described experiencing multiple stressors during the antenatal period that impacted on their social and emotional wellbeing. This is despite the range of protective factors identified by them. Participants had diverse experiences with health care providers during the antenatal period. CONCLUSIONS: This study demonstrated that these Aboriginal men valued engagement with antenatal care (ANC) services and highlighted strategies to improve Aboriginal paternal involvement with ANC services. SO WHAT?: Enhancing ANC to be inclusive of fathers, through a local co-design process, could strengthen and support Aboriginal families to achieve improved health and wellbeing outcomes across the family system.

Parent perceptions of minimally invasive dental treatment of Australian Aboriginal pre-school children in rural and remote communities.

INTRODUCTION: Aboriginal* children in rural and remote communities in Australia have a higher burden of dental decay and poorer access to dental services than their non-Aboriginal counterparts. In the Kimberley region of Western Australia (WA), Aboriginal children experience six times the rate of untreated dental decay of non-Aboriginal children. Access to dental care is challenged by the availability and appropriate delivery of services in remote locations. This study elicited the experiences and perceptions of parents and carers who participated in a project that tested the minimally invasive atraumatic restorative treatment and the Hall technique approaches (ART-HT) to manage early childhood dental caries among Australian Aboriginal preschool children. METHODS: The core study design was a stepped-wedge, cluster-community-randomised controlled trial. Consenting communities in the Kimberley region of WA were randomised into early and delayed intervention groups. Children were clinically examined at study commencement; the early intervention group was offered dental treatment using the ART-HT approach, and the delayed group was advised to seek dental care from their usual service provider. At the 12-month follow-up, children in both groups were re-examined and offered care using the minimally invasive model of care, and parents and carers were invited to take part in focus group or one-to-one interviews. Semistructured interviews, guided by the yarning approach, were conducted with consenting parents and carers in community locations of convenience to participants. The same open-ended questions were asked of all participants, and the interviews were audio-recorded with permission and transcribed by an independent agency. Thematic analysis was undertaken, the transcripts were coded by NVivo software, and emergent themes were identified and developed. RESULTS: One-to-one interviews were conducted with 29 parents and carers (10 from five test communities; 19 from eight control communities). Interview participants consisted of 3 males and 26 females. Following thematic analysis, three main themes (and subthemes) were identified: (1) access to care (barriers, service availability, impact on family due to lack of access); (2) experience of care (cultural safety, child-centred care, comprehensiveness of care); (3) community engagement (service information, engagement, oral health education). Structural and system factors as well as geography were identified as barriers by parents and carers in accessing timely and affordable dental care in culturally safe environments; parents and carers also identified the impacts from lack of access to care. They valued comprehensive care delivered within community, underpinned by child- and family-centred care. Of equal importance was the holistic approach adopted through the building of community engagement and trusting relationships. CONCLUSION: A high level of satisfaction was reported by parents and carers with their experience of dental care for their children with the minimally invasive approach. Satisfaction was expressed around ease of accessing services delivered in a child- and family-centred manner, and that were well supported by appropriate engagement between service providers, communities and families. The findings from this study suggest a minimally invasive dental care model can be considered effective and culturally acceptable and should be considered in delivering oral health services for young children in rural and remote locations. * The term Aboriginal is inclusive of Aboriginal and Torres Strait Islander peoples.