Identifying biochemical changes in the kidney using proton nuclear magnetic resonance in an adenine diet chronic kidney disease mouse model.

This study aimed to investigate the metabolic changes in the kidneys in a murine adenine-diet model of chronic kidney disease (CKD). Kidney fibrosis is the common pathological manifestation across CKD aetiologies. Sustained inflammation and fibrosis cause changes in preferred energy metabolic pathways in the cells of the kidney. Kidney cortical tissue from mice receiving a control or adenine-supplemented diet for 8 weeks (late inflammation and fibrosis) and 12 weeks (8 weeks of treatment followed by 4 weeks recovery) were analysed by 2D-correlated nuclear magnetic resonance spectroscopy and compared with histopathology and biomarkers of kidney damage. Tissue metabolite and lipid levels were assessed using the MestreNova software. Expression of genes related to inflammation, fibrosis, and metabolism were measured using quantitative polymerase chain reaction. Animals showed indicators of severely impaired kidney function at 8 and 12 weeks. Significantly increased fibrosis was present at 8 weeks but not in the recovery group suggesting some reversal of fibrosis and amelioration of inflammation. At 8 weeks, metabolites associated with glycolysis were increased, while lipid signatures were decreased. Genes involved in fatty acid oxidation were decreased at 8 weeks but not 12 weeks while genes associated with glycolysis were significantly increased at 8 weeks but not at 12 weeks. In this murine model of CKD, kidney fibrosis was associated with the accumulation of triglyceride and free lactate. There was an up-regulation of glycolytic enzymes and down-regulation of lipolytic enzymes. These metabolic changes reflect the energy demands associated with progressive kidney disease where there is a switch from fatty acid oxidation to that of glycolysis.

Prevalence of alcohol use disorders documented in electronic health records in primary care across intersections of race or ethnicity, sex, and socioeconomic status.

BACKGROUND: Diagnosis of alcohol use disorder (AUD) in primary care is critical for increasing access to alcohol treatment. However, AUD is underdiagnosed and may be inequitably diagnosed due to societal structures that determine access to resources (e.g., structural racism that limits opportunities for some groups and influences interpersonal interactions in and beyond health care). This study described patterns of provider-documented AUD in primary care across intersections of race, ethnicity, sex, and community-level socioeconomic status (SES). METHODS: This cross-sectional study used EHR data from a regional healthcare system with 35 primary care clinics that included adult patients who completed alcohol screenings between 3/1/2015 and 9/30/2020. The prevalence of provider-documented AUD in primary care based on International Classification of Diseases-9 (ICD-9) and ICD-10 diagnoses was compared across intersections of race, ethnicity, sex, and community-level SES. RESULTS: Among 439,375 patients, 6.6% were Latine, 11.0% Asian, 5.4% Black, 1.3% Native Hawaiian/Pacific Islander (NH/PI), 1.5% American Indian/Alaska Native (AI/AN), and 74.2% White, and 58.3% women. The overall prevalence of provider-documented AUD was 1.0% and varied across intersecting identities. Among women, the prevalence was highest for AI/AN women with middle SES, 1.5% (95% CI 1.0-2.3), and lowest for Asian women with middle SES, 0.1% (95% CI 0.1-0.2). Among men, the prevalence was highest for AI/AN men with high and middle SES, 2.0% (95% CI 1.1-3.4) and 2.0% (95% CI 1.2-3.2), respectively, and lowest for Asian men with high SES, 0.5% (95% CI 0.3-0.7). Black and Latine patients tended to have a lower prevalence of AUD than White patients, across all intersections of sex and SES except for Black women with high SES. There were no consistent patterns of the prevalence of AUD diagnosis that emerged across SES. CONCLUSION: The prevalence of provider-documented AUD in primary care was highest in AI/AN men and women and lowest in Asian men and women. Findings of lower prevalence of provider-documented AUD in Black and Hispanic than White patients across most intersections of sex and SES differed from prior studies. Findings may suggest that differences in access to resources, which vary in effects across these identity characteristics and lived experiences, influence the diagnosis of AUD in clinical care.

Heat hardening improves thermal tolerance in abalone, without the trade-offs associated with chronic heat exposure.

Marine animals are challenged by chronically raised temperatures alongside an increased frequency of discrete, severe warming events. Exposure to repeated heat shocks could result in heat hardening, where sub-lethal exposure to thermal stress temporarily enhances thermotolerance, and may be an important mechanism by which marine species will cope with future thermal challenges. However, we have relatively little understanding of the effects of heat hardening in comparison to chronic exposure to elevated temperatures. Therefore, we compared the effects of heat hardening from repeated exposure to acute heat shocks and chronic exposure to elevated temperatures on thermal tolerance in the European abalone, Haliotis tuberculata. Adult abalones were exposed to either control temperature (15 °C), chronic warming (20 °C) or a regime of two events of repeated acute heat shock cycles (23-25 °C) during six months, and their thermal tolerance and performance, based upon cardiac activity, compared using a dynamic ramping assay. The cost associated with each treatment was also estimated via measurements of condition index (CI). Abalone exposed to both temperature treatments had higher upper thermal limits than the control, but heat-hardened individuals had significantly higher CI values, indicating an enhancement in condition status. Differences in the shape of the thermal performance curve suggest different mechanisms may be at play under different temperature exposure treatments. We conclude that heat hardening can boost thermal tolerance in this species, without performance trade-offs associated with chronic warming.

Receipt of Medications for Alcohol Use Disorder in the Veterans Health Administration: Comparison of Rates at the Intersections of Racialized and Ethnic Identity With Both Sex and Transgender Status.

OBJECTIVES: Medications for alcohol use disorder (MAUDs) are recommended for patients with alcohol use disorder yet are underprescribed. Consistent with Minority Stress and Intersectionality theories, persons with multiple sociodemographically marginalized identities (eg, Black women) often experience greater barriers to care and have poorer health outcomes. We use data from the Veterans Health Administration to assess disparities in Federal Drug Administration (FDA)-approved MAUDs and all effective MAUDs between the following groups: racialized and ethnic identity, sex, transgender status, and their intersections. METHODS: Among all Veterans Health Administration outpatients between August 1, 2015, and July 31, 2017, with documented alcohol screenings and an International Classification of Diseases diagnosis for alcohol use disorder in the 0-365 days prior (N = 308,238), we estimated the prevalence and 95% confidence intervals of receiving FDA-approved MAUDs and any MAUDs in the following year and compared them using χ2 or Fisher's exact test. Analyses are unadjusted to present true prevalence and group differences. RESULTS: The overall prevalence for MAUDs was low (FDA-MAUDs = 8.7%, any MAUDs = 20.0%). Within sex, Black males had the lowest rate of FDA-MAUDs (7.3%, [7.1-7.5]), whereas American Indian/Alaskan Native females had the highest (18.4%, [13.8-23.0]). Among those identified as transgender, Asian and Black transgender persons had the lowest rates of FDA-MAUDs (0%; 4.3%, [1.8-8.5], respectively), whereas American Indian/Alaskan Native transgender patients had the highest (33.3%, [2.5-64.1]). Similar patterns were observed for any MAUDs, with higher rates overall. CONCLUSIONS: Substantial variation exists in MAUD prescribing, with marginalized veterans disproportionately receiving MAUDs at lower and higher rates than average. Implementation and quality improvement efforts are needed to improve MAUD prescribing practices and reduce disparities.

Analysis of risk factors for late arteriovenous fistula failure and patency rates after angioplasty in hemodialysis patients: a retrospective cohort study.

Background: The incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is increasing worldwide. Hemodialysis (HD) is the mainstay of renal replacement therapy for patients with ESKD. Risk factors associated with late arteriovenous fistula (AVF) failure in HD patients are poorly investigated. Therefore, the aim of this study was to identify factors associated with late AVF failure in HD patients. Methods: Patients with end-stage renal disease (ESRD) who underwent forearm or upper arm AVF angioplasty at Second Affiliated Hospital of Chongqing Medical University between September 2009 and August 2018 were included. Patients were followed up for 36 months. Baseline characteristics were collected using electronic medical records (EMRs). Variables associated with late AVF failure were identified using Cox proportional hazards models. Results: There were 137 patients (64% male, 36% female) included in this study, with 50 (36.5%) experiencing AVF failure. Univariable log-rank analysis showed that age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), intact parathyroid hormone (iPTH), albumin (ALB), and AVF patency rate were significantly different between patients who did and did not experience AVF failure. Cox regression analysis showed that CRP [P=0.002, hazard ratio (HR) =2.719, 95% confidence interval (CI) for HR: 1.432-5.164], ESR (P=0.030, HR =2.431, 95% CI: 1.088-5.434), iPTH (P=0.013, HR =0.325, 95% CI: 0.133-0.793), and ALB (P=0.040, HR =0.539, 95% CI: 0.299-0.972) were independently associated with AVF failure. Kaplan-Meier survival analysis showed that the cumulative patency rates of AVF at 6, 12, 18, 24, 30, and 36 months were 84%, 74%, 69%, 64%, 64%, and 64%, respectively. Conclusions: CRP, ESR, iPTH, and ALB were associated with AVF failure and should be used as reference in clinical practice.

A proposed multi-domain, digital model for capturing functional status and health-related quality of life in oncology.

Whereas traditional oncology clinical trial endpoints remain key for assessing novel treatments, capturing patients' functional status is increasingly recognized as an important aspect for supporting clinical decisions and assessing outcomes in clinical trials. Existing functional status assessments suffer from various limitations, some of which may be addressed by adopting digital health technologies (DHTs) as a means of collecting both objective and self-reported outcomes. In this mini-review, we propose a device-agnostic multi-domain model for oncology capturing functional status, which includes physical activity data, vital signs, sleep variables, and measures related to health-related quality of life enabled by connected digital tools. By using DHTs for all aspects of data collection, our proposed model allows for high-resolution measurement of objective data as patients navigate their daily lives outside of the hospital setting. This is complemented by electronic questionnaires administered at intervals appropriate for each instrument. Preliminary testing and practical considerations to address before adoption are also discussed. Finally, we highlight multi-institutional pre-competitive collaborations as a means of successfully transitioning the proposed digitally enabled data collection model from feasibility studies to interventional trials and care management.

Predictive accuracy of risk prediction models for recurrence, metastasis and survival for early-stage cutaneous melanoma: a systematic review.

OBJECTIVES: To identify prognostic models for melanoma survival, recurrence and metastasis among American Joint Committee on Cancer stage I and II patients postsurgery; and evaluate model performance, including overall survival (OS) prediction. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Searched MEDLINE, Embase, CINAHL, Cochrane Library, Science Citation Index and grey literature sources including cancer and guideline websites from 2000 to September 2021. ELIGIBILITY CRITERIA: Included studies on risk prediction models for stage I and II melanoma in adults ≥18 years. Outcomes included OS, recurrence, metastases and model performance. No language or country of publication restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Two pairs of reviewers independently screened studies, extracted data and assessed the risk of bias using the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies checklist and the Prediction study Risk of Bias Assessment Tool. Heterogeneous predictors prevented statistical synthesis. RESULTS: From 28 967 records, 15 studies reporting 20 models were included; 8 (stage I), 2 (stage II), 7 (stages I-II) and 7 (stages not reported), but were clearly applicable to early stages. Clinicopathological predictors per model ranged from 3-10. The most common were: ulceration, Breslow thickness/depth, sociodemographic status and site. Where reported, discriminatory values were ≥0.7. Calibration measures showed good matches between predicted and observed rates. None of the studies assessed clinical usefulness of the models. Risk of bias was high in eight models, unclear in nine and low in three. Seven models were internally and externally cross-validated, six models were externally validated and eight models were internally validated. CONCLUSIONS: All models are effective in their predictive performance, however the low quality of the evidence raises concern as to whether current follow-up recommendations following surgical treatment is adequate. Future models should incorporate biomarkers for improved accuracy. PROSPERO REGISTRATION NUMBER: CRD42018086784.

High risk clear cell renal cell carcinoma microenvironments contain protumour immunophenotypes lacking specific immune checkpoints.

Perioperative immune checkpoint inhibitor (ICI) trials for intermediate high-risk clear cell renal cell carcinoma (ccRCC) have failed to consistently demonstrate improved patient outcomes. These unsuccessful ICI trials suggest that the tumour infiltrating immunophenotypes, termed here as the immune cell types, states and their spatial location within the tumour microenvironment (TME), were unfavourable for ICI treatment. Defining the tumour infiltrating immune cells may assist with the identification of predictive immunophenotypes within the TME that are favourable for ICI treatment. To define the immunophenotypes within the ccRCC TME, fresh para-tumour (pTME, n = 2), low-grade (LG, n = 4, G1-G2) and high-grade (HG, n = 4, G3-G4) tissue samples from six patients with ccRCC presenting at a tertiary referral hospital underwent spatial transcriptomics sequencing (ST-seq). Within the generated ST-seq datasets, immune cell types and states, termed here as exhausted/pro-tumour state or non-exhausted/anti-tumour state, were identified using multiple publicly available single-cell RNA and T-cell receptor sequencing datasets as references. HG TMEs revealed abundant exhausted/pro-tumour immune cells with no consistent increase in expression of PD-1, PD-L1 and CTLA4 checkpoints and angiogenic genes. Additional HG TME immunophenotype characteristics included: pro-tumour tissue-resident monocytes with consistently increased expression of HAVCR2 and LAG3 checkpoints; an exhausted CD8+ T cells sub-population with stem-like progenitor gene expression; and pro-tumour tumour-associated macrophages and monocytes within the recurrent TME with the expression of TREM2. Whilst limited by a modest sample size, this study represents the largest ST-seq dataset on human ccRCC. Our study reveals that high-risk ccRCC TMEs are infiltrated by exhausted/pro-tumour immunophenotypes lacking specific checkpoint gene expression confirming that HG ccRCC TME are immunogenic but not ICI favourable.

Self-reported and digital-trace measures of computer science students' self-regulated learning in blended course designs.

This study investigated the extent to which self-report and digital-trace measures of students' self-regulated learning in blended course designs align with each other amongst 145 first-year computer science students in a blended "computer systems" course. A self-reported Motivated Strategies for Learning Questionnaire was used to measure students' self-efficacy, intrinsic motivation, test anxiety, and use of self-regulated learning strategies. Frequencies of interactions with six different online learning activities were digital-trace measures of students' online learning interactions. Students' course marks were used to represent their academic performance. SPSS 28 was used to analyse the data. A hierarchical cluster analysis using self-reported measures categorized students as better or poorer self-regulated learners; whereas a hierarchical cluster analysis using digital-trace measures clustered students as more active or less active online learners. One-way ANOVAs showed that: 1) better self-regulated learners had higher frequencies of interactions with three out of six online learning activities than poorer self-regulated learners. 2) More active online learners reported higher self-efficacy, higher intrinsic motivation, and more frequent use of positive self-regulated learning strategies, than less active online learners. Furthermore, a cross-tabulation showed significant (p < .01) but weak association between student clusters identified by self-reported and digital-trace measures, demonstrating self-reported and digital-trace descriptions of students' self-regulated learning experiences were consistent to a limited extent. To help poorer self-regulated learners improve their learning experiences in blended course designs, teachers may invite better self-regulated learners to share how they approach learning in class.

SNP discovery and genetic structure in blue mussel species using low coverage sequencing and a medium density 60 K SNP-array.

Blue mussels from the genus Mytilus are an abundant component of the benthic community, found in the high latitude habitats. These foundation species are relevant to the aquaculture industry, with over 2 million tonnes produced globally each year. Mussels withstand a wide range of environmental conditions and species from the Mytilus edulis complex readily hybridize in regions where their distributions overlap. Significant effort has been made to investigate the consequences of environmental stress on mussel physiology, reproductive isolation, and local adaptation. Yet our understanding on the genomic mechanisms underlying such processes remains limited. In this study, we developed a multi species medium-density 60 K SNP-array including four species of the Mytilus genus. SNPs included in the platform were called from 138 mussels from 23 globally distributed mussel populations, sequenced using a whole-genome low coverage approach. The array contains polymorphic SNPs which capture the genetic diversity present in mussel populations thriving across a gradient of environmental conditions (~59 K SNPs) and a set of published and validated SNPs informative for species identification and for diagnosis of transmissible cancer (610 SNPs). The array will allow the consistent genotyping of individuals, facilitating the investigation of ecological and evolutionary processes in these taxa. The applications of this array extend to shellfish aquaculture, contributing to the optimization of this industry via genomic selection of blue mussels, parentage assignment, inbreeding assessment and traceability. Further applications such as genome wide association studies (GWAS) for key production traits and those related to environmental resilience are especially relevant to safeguard aquaculture production under climate change.

Relationship between cortical and medullary thickness and glomerular filtration rate among living kidney donors.

The relationship between the kidney cortex and medulla is not well understood in healthy populations. This study characterised the relationship between cortical/medullary thickness and measured glomerular filtration rate (GFR) in 390 living kidney donors. A positive relationship was observed between medullary, but not cortical, thickness and GFR. We propose that this reflects a correlation between juxtamedullary nephron number and GFR.

Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134.

PURPOSE: Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAFV600-mutant metastatic melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy. PATIENTS AND METHODS: In a phase III trial, patients with treatment-naive BRAFV600-mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D). The primary end point was 2-year overall survival (OS). Secondary end points were 3-year OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety. RESULTS: A total of 265 patients were enrolled, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped early by the independent Data Safety Monitoring Committee because of a clinically significant end point being achieved. The 2-year OS for those starting on arm A was 71.8% (95% CI, 62.5 to 79.1) and arm B 51.5% (95% CI, 41.7 to 60.4; log-rank P = .010). Step 1 progression-free survival favored arm A (P = .054). Objective response rates were arm A: 46.0%; arm B: 43.0%; arm C: 47.8%; and arm D: 29.6%. Median duration of response was not reached for arm A and 12.7 months for arm B (P < .001). Crossover occurred in 52% of patients with documented disease progression. Grade ≥ 3 toxicities occurred with similar frequency between arms, and regimen toxicity profiles were as anticipated. CONCLUSION: Combination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.

Factors associated with hospitalisations and deaths of residential aged care residents with COVID-19 during the Omicron (BA.1) wave in Queensland.

OBJECTIVE: To identify characteristics associated with the hospitalisation and death of people with COVID-19 living in residential aged care facilities (RACFs). DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: All confirmed (polymerase chain reaction testing) or probable SARS-CoV-2 infections (rapid antigen tests) in residents of the 86 RACFs in the Metro South Hospital and Health Service area (southeast Queensland), 13 December 2021 - 24 January 2022. MAIN OUTCOME MEASURES: Hospitalisation within 14 days or death within 28 days of COVID-19 diagnosis. RESULTS: Of 1071 RACF residents with COVID-19, 151 were hospitalised within 14 days and 126 died within 28 days of diagnosis. Likelihood of death increased with age (per five years: adjusted odds ratio [aOR], 1.38; 95% confidence interval [CI], 1.21-1.57), but not that of hospitalisation. Men were more likely to be hospitalised (aOR, 1.7; 95% CI, 1.2-2.4) or die (aOR, 2.5; 95% CI, 1.7-3.6) than women. The likelihood of hospitalisation was greater for those with dementia (aOR, 1.9; 95% CI, 1.2-3.0), heart failure (aOR, 1.7; 95% CI, 1.1-2.7), chronic kidney disease (aOR, 1.7; 95% CI, 1.1-2.5), or asthma (aOR, 2.2; 95% CI, 1.2-3.8). The likelihood of death was greater for residents with dementia (aOR, 2.2; 95% CI, 1.3-3.7), diabetes mellitus (aOR, 1.9; 95% CI, 1.3-3.0), heart failure (aOR, 2.0; 95% CI, 1.1-3.3), or chronic lung disease (aOR, 1.7; 95% CI, 1.1-2.7). The likelihood of hospitalisation and death were each higher for residents who had received two or fewer vaccine doses than for those who had received three doses. CONCLUSIONS: Most characteristics that influenced the likelihood of hospitalisation or death of RACF residents with COVID-19 were non-modifiable factors linked with frailty and general health status. Having received three COVID-19 vaccine doses was associated with much lower likelihood of hospitalisation or death.

The relations between self-reported perceptions of learning environment, observational learning strategies, and academic outcome.

This study investigated the relations between students' self-reported perceptions of the blended learning environment, their observed online learning strategies, and their academic learning outcomes. The participants were 310 undergraduates enrolled in an introductory course on computer systems in an Australian metropolitan university. A Likert-scale questionnaire was used to examine students' perceptions. The digital traces recorded in a bespoke learning management system were used to detect students' observed online learning strategies. Using the data mining algorithms, including the Hidden Markov Model and an agglomerative hierarchical sequence clustering, four types of online learning strategies were found. The four strategies not only differed in the number of online learning sessions but also showed differences in the proportional distribution with regard to different online learning behaviors. A one-way ANOVA revealed that students adopting different online learning strategies differed significantly on their final course marks. Students who employed intensive theory application strategy achieved the highest whereas those used weak reading and weak theory application scored the lowest. The results of a cross-tabulation showed that the four types of observed online learning strategies were significantly associated with the better and poorer perceptions of the blended learning environment. Specially, amongst students who adopted the intensive theory application strategy, the proportion of students who self-reported better perceptions was significantly higher than those reporting poorer perceptions. In contrast, amongst students using the weak reading and weak theory application strategy, the proportion of students having poorer perceptions was significantly higher than those holding better perceptions.

Two-dimensional correlated spectroscopy distinguishes clear cell renal cell carcinoma from other kidney neoplasms and non-cancer kidney.

Background: Routinely used clinical scanners, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US), are unable to distinguish between aggressive and indolent tumor subtypes in masses localized to the kidney, often leading to surgical overtreatment. The results of the current investigation demonstrate that chemical differences, detected in human kidney biopsies using two-dimensional COrrelated SpectroscopY (2D L-COSY) and evaluated using multivariate statistical analysis, can distinguish these subtypes. Methods: One hundred and twenty-six biopsy samples from patients with a confirmed enhancing kidney mass on abdominal imaging were analyzed as part of the training set. A further forty-three samples were used for model validation. In patients undergoing radical nephrectomy, biopsies of non-cancer kidney cortical tissue were also collected as a non-cancer control group. Spectroscopy data were analyzed using multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection to latent structures with discriminant analysis (OPLS-DA), to identify biomarkers in kidney cancer tissue that was also classified using the gold-standard of histopathology. Results: The data analysis methodology showed good separation between clear cell renal cell carcinoma (ccRCC) versus non-clear cell RCC (non-ccRCC) and non-cancer cortical tissue from the kidneys of tumor-bearing patients. Variable Importance for the Projection (VIP) values, and OPLS-DA loadings plots were used to identify chemical species that correlated significantly with the histopathological classification. Model validation resulted in the correct classification of 37/43 biopsy samples, which included the correct classification of 15/17 ccRCC biopsies, achieving an overall predictive accuracy of 86%, Those chemical markers with a VIP value >1.2 were further analyzed using univariate statistical analysis. A subgroup analysis of 47 tumor tissues arising from T1 tumors revealed distinct separation between ccRCC and non-ccRCC tissues. Conclusions: This study provides metabolic insights that could have future diagnostic and/or clinical value. The results of this work demonstrate a clear separation between clear cell and non-ccRCC and non-cancer kidney tissue from tumor-bearing patients. The clinical translation of these results will now require the development of a one-dimensional (1D) magnetic resonance spectroscopy (MRS) protocol, for the kidney, using an in vivo clinical MRI scanner.

Sensor Verification and Analytical Validation of Algorithms to Measure Gait and Balance and Pronation/Supination in Healthy Volunteers.

Numerous studies have sought to demonstrate the utility of digital measures of motor function in Parkinson's disease. Frameworks, such as V3, document digital measure development: technical verification, analytical and clinical validation. We present the results of a study to (1) technically verify accelerometers in an Apple iPhone 8 Plus and ActiGraph GT9X versus an oscillating table and (2) analytically validate software tasks for walking and pronation/supination on the iPhone plus passively detect walking measures with the ActiGraph in healthy volunteers versus human raters. In technical verification, 99.4% of iPhone and 91% of ActiGraph tests show good or excellent agreement versus the oscillating table as the gold standard. For the iPhone software task and algorithms, intraclass correlation coefficients (ICCs) > 0.75 are achieved versus the human raters for measures when walking distance is >10 s and pronation/supination when the arm is rotated more than two times. Passively detected walking start and end time was accurate to approx. 1 s and walking measures were accurate to one unit, e.g., one step. The results suggest that the Apple iPhone and ActiGraph GT9X accelerometers are fit for purpose and that task and passively collected measures are sufficiently analytically valid to assess usability and clinical validity in Parkinson's patients.

Kidney failure, CKD progression and mortality after nephrectomy.

PURPOSE: This study tested the hypothesis that progression of chronic kidney disease (CKD) is less aggressive in patients whose primary cause of CKD was nephrectomy, compared with non-surgical causes. METHODS: A sample of 5983 patients from five specialist nephrology practices was ascertained from the Queensland CKD Registry. Rates of kidney failure/death were compared on primary aetiology of CKD using multivariable Cox proportional hazards models. CKD progression was compared using multivariable linear and logistic regression analyses. RESULTS: Of 235 patients with an acquired single kidney as their primary cause of CKD, 24 (10%) and 38 (17%) developed kidney failure or died at median [IQR] follow-up times of 12.9 [2.5-31.0] and 33.6 [18.0-57.9] months after recruitment. Among patients with an eGFR < 45 mL/min per 1.73m2 at recruitment, patients with diabetic nephropathy and PCKD had the highest rates (per 1000 person-years) of kidney failure (107.8, 95% CI 71.0-163.8; 75.5, 95% CI 65.6-87.1); whereas, patients with glomerulonephritis and an acquired single kidney had lower rates (52.9, 95% CI 38.8-72.1; 34.6, 95% CI 20.5-58.4, respectively). Among patients with an eGFR ≥ 45 mL/min per 1.73m2, those with diabetic nephropathy had the highest rates of kidney failure (16.6, 95% CI 92.5-117.3); whereas, those with glomerulonephritis, PCKD and acquired single kidney had a lower risk (11.3, 95% CI 7.1-17.9; 11.7, 95% CI 3.8-36.2; 10.7, 95% CI 4.0-28.4, respectively). CONCLUSION: Patients who developed CKD after nephrectomy had similar rates of adverse events to most other causes of CKD, except for diabetic nephropathy which was consistently associated with worse outcomes. While CKD after nephrectomy is not the most aggressive cause of kidney disease, it is by no means benign, and is associated with a tangible risk of kidney failure and death, which is comparable to other major causes of CKD.

Optimal Surveillance Strategies for Early-Stage Cutaneous Melanoma Post Primary Tumor Excision: An Economic Evaluation.

Background. Consensus on standardized active surveillance or follow-up care by clinicians is lacking leading to considerable variation in practice across countries. An important structural modelling consideration is that self-examination by patients and their partners can detect melanoma recurrence outside of active surveillance regimes. Objectives. To identify candidate melanoma surveillance strategies for American Joint Committee on Cancer (AJCC) stage I disease and compare them with the current recommended practice in a cost-utility analysis framework. Methods. In consultation with UK clinical experts, a microsimulation model was built in TreeAge Pro 2019 R1.0 (Williamstown, MA, USA) to evaluate surveillance strategies for AJCC stage IA and IB melanoma patients separately. The model incorporated patient behaviors such as self-detection and emergency visits to examine suspicious lesions. A National Health Service (NHS) perspective was taken. Model input parameters were taken from the literature and where data were not available, local expert opinion was sought. Probabilistic sensitivity analysis, one-way sensitivity analysis on pertinent parameters and value of information was performed. Results. In the base-case probabilistic sensitivity analysis, less intensive surveillance strategies for AJCC stage IA and IB had lower total lifetime costs than the current National Institute for Health and Care Excellence (NICE) recommended strategy with similar effectiveness in terms of quality-adjusted life years and thereby likely to be cost-effective. Many strategies had similar effectiveness due to the relatively low chance of recurrence and the high rate of self-detection. Sensitivity and scenario analyses did not change these findings. Conclusions. Our model findings suggest that less resource intensive surveillance may be cost-effective compared with the current NICE surveillance guidelines. However, to advocate convincingly for changes, better evidence is required.