Water mass properties in the Amundsen Sea, Antarctica, using seal-borne tags

Global attention is focused on the melting of the West Antarctic Ice Sheet and the impacts of associated sea level rise. Glaciers in the Amundsen Sea Embayment are some of the biggest contributors, yet difficulty collecting data in this area, especially during winter when harsh weather and ice cover prevent many traditional observation techniques, means detailed understanding of the relevant processes is limited. This thesis presents a dataset of >11,000 new seal-borne hydrographic profiles from the summer, autumn and winter seasons of 2014, enabling seasonal comparisons of deep water, and for the first time, the upper ocean. A through evaluation of the quality of the seal tag dataset is presented, along with details of the appropriate corrections. The magnitude of corrections derived from pre-deployment tests suggest that some tag datasets lacking these pre-deployment tests might not meet the stated accuracies. One of the drivers of increased glacial melt in this region is warm Circumpolar Deep Water (CDW) increasingly crossing the continental shelf, and contributing to increased ice mass loss. Seasonal analysis reveals a CDW layer on average 49 db thicker in late winter (August to October) than in late summer (February to April), the reverse seasonality of that seen at moorings in the western trough. This layer contains more heat in winter. In the upper ocean, salinification, cooling and the deepening of the mixed layer begins in or before February, and continues until June/July. The distance to which mooring-top observations can be extrapolated upward into the upper ocean is examined, and found to be between 110 and 230 m, although dependent on local conditions and the depth of the mooring. These observations form a crucial building block for future study on seasonality and variability in the area, and are essential for verifying model simulations of ice shelf melt

The application of long‑read sequencing in clinical settings

Long-read DNA sequencing technologies have been rapidly evolving in recent years, and their ability to assess large and complex regions of the genome makes them ideal for clinical applications in molecular diagnosis and therapy selection, thereby providing a valuable tool for precision medicine. In the third-generation sequencing duopoly, Oxford Nanopore Technologies and Pacific Biosciences work towards increasing the accuracy, throughput, and portability of long-read sequencing methods while trying to keep costs low. These trades have made long-read sequencing an attractive tool for use in research and clinical settings. This article provides an overview of current clinical applications and limitations of long-read sequencing and explores its potential for point-of-care testing and health care in remote settings

Birt-Hogg-Dubé Syndrome and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome: An Effective Multidisciplinary Approach to Hereditary Renal Cancer Predisposing Syndromes

Aim: We aimed to describe and analyse clinical features, characteristics, and adherence to surveillance guidelines in an Australian Birt-Hogg-Dubé syndrome (BHD) and hereditary leiomyomatosis and renal cell cancer (HLRCC) cohort. Methods: All identified patients with a diagnosis of BHD or HLRCC at RBWH 01/01/2014-01/09/2019 were included (HREC/17/QRBW/276). All patients were initially assessed and counselled by a clinical geneticist and then referred to an adult nephrologist. Baseline and incidental clinical variables were extracted and analysed. Results: Fifty-seven patients were identified (28 BHD, 29 HLRCC) with a median age of 47 years. The median and cumulative follow-up were 1 and 99 years, respectively. Baseline renal MRI occurred in 40/57 patients, and 33/57 had regular MRI as per the national guidelines (eviQ). Of 18/57 without baseline imaging, nine were yet to have imaging, seven were lost follow-up, and two patients had logistic difficulties. RCC was diagnosed in 11/57 patients: two of 28 with BHD were diagnosed with RCC aged 73 and 77, both prior to commencement of surveillance. Nine of 29 patients with HLRCC were diagnosed with RCC (one of 29 during surveillance at 47 years of age) and eight of 29 prior to commencement of surveillance (11–55 years). Amongst BHD patients, cutaneous fibrofolliculomas were noted in 15 patients, lung cysts were detected in seven patients, spontaneous pneumothoraces in five patients, and parotid oncocytoma in two of 28. Amongst those with HLRCC, cutaneous leiomyomas were noted in 19/29, cutaneous leiomyosarcoma diagnosed in one of 29, and uterine fibroids in 13 female patients. Conclusion: Evidence-based RCC screening in BHD and HLRCC cohort is feasible and able to identify incidental renal lesions. Multidisciplinary patient management enables expedited genetic counselling, diagnosis, longitudinal screening, and RCC management. The success of this clinical model warrants consideration of undertaking longitudinal screening of BHD and HLRCC patients by nephrologists

Cellular milieu in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is globally the most prevalent renal cancer. The cells of origin in ccRCC have been identified as proximal tubular epithelial cells (PTEC); however, the transcriptomic pathways resulting in the transition from normal to malignant PTEC state have remained unclear. Immunotherapy targeting checkpoints have revolutionized the management of ccRCC, but a sustained clinical response is achieved in only a minority of ccRCC patients. This indicates that our understanding of the mechanisms involved in the malignant transition and resistance to immune checkpoint therapy in ccRCC is unclear. This review examines recent single-cell transcriptomics studies of ccRCC to clarify the transition of PTEC in ccRCC development, and the immune cell types, states, and interactions that may limit the response to targeted immune therapy, and finally suggests stromal cells as key drivers in recurrent and locally invasive ccRCC. These and future single-cell transcriptomics studies will continue to clarify the cellular milieu in the ccRCC microenvironment, thus defining actional clinical, therapeutic, and prognostic characteristics of ccRCC

The prevalence of Fabry disease in a statewide chronic kidney disease cohort – Outcomes of the aCQuiRE (Ckd.Qld fabRy Epidemiology) study

Background: Prevalence of Fabry disease amongst Chronic Kidney Disease (CKD) patients on haemodialysis has been shown to be approximately 0.2%. Methods: We undertook a cross-sectional study employing a cascade screening strategy for Fabry Disease amongst 3000 adult, male and female patients affected by CKD stage 1-5D/T at public, specialty renal practices within participating Queensland Hospital and Health Services from October 2017 to August 2019. A multi-tiered FD screening strategy, utilising a combination of dried blood spot (DBS) enzymatic testing, and if low, then lyso-GB3 testing and DNA sequencing, was used. Results: Mean (SD) age was 64.0 (15.8) years (n = 2992), and 57.9% were male. Eight participants withrew out of the 3000 who consented. Of 2992 screened, 6 (0.20%) received a diagnosis of FD, 2902 (96.99%) did not have FD, and 84 (2.81%) received inconclusive results. Of the patients diagnosed with FD, mean age was 48.5 years; 5 were male (0.29%) and 1 was female (0.08%); 4 were on kidney replacement therapy (2 dialysis and 2 transplant); 3 were new diagnoses. Conclusions: Estimated overall FD prevalence was 0.20%. Screening of the broader CKD population may be beneficial in identifying cases of FD. Trial registration: The aCQuiRE Study has been prospectively registered with the Queensland Health Database of Research Activity (DORA, https://dora.health.qld.gov.au) as pj09946 (Registered 3rd July 2017)

Serum Creatinine and Tacrolimus Assessment With VAMS Finger-Prick Microsampling: A Diagnostic Test Study

Rationale & Objective: Kidney transplant recipients require frequent venipunctures. Microsampling methods that use a finger-prick draw of capillary blood, like volumetric absorptive microsamplers (VAMS), have the potential to reduce the pain, inconvenience, and volume of blood loss associated with venipuncture. This study aimed to provide diagnostic accuracy using VAMS for measurement of tacrolimus and creatinine compared to gold standard venous blood in adult kidney transplant recipients. Study Design: Diagnostic test study. Prospective blood samples for measurement of tacrolimus and creatinine were collected using Mitra VAMS and venipuncture immediately before and 2 hours after tacrolimus dosing. Setting & Participants: A convenience sample of 40 adult kidney transplant participants in the outpatient setting. Tests Compared: Method comparison was assessed by Passing-Bablok regression and Bland-Altman analysis. The predictive performance of VAMS measurement compared to venipuncture was also assessed through estimation of the median prediction error and median absolute percentage prediction error. Results: A total of 74 tacrolimus samples and 70 creatinine samples were analyzed from 40 participants. Passing-Bablok regression showed a systematic difference between VAMS and venipuncture when measuring tacrolimus and creatinine with a slope of 1.08 (95% CI, 1.03-1.13) and a slope of 0.65 (95% CI, 0.6-0.7), respectively. These values were then corrected for the systematic difference. When used for Bland-Altman analysis, corrected values of tacrolimus and creatinine showed a bias of -0.1 μg/L and 0.04 mg/dL, respectively. Tacrolimus (corrected) and creatinine (corrected) microsampling values when compared to corresponding venipuncture values met median prediction error and median absolute percentage prediction error predefined acceptability limits of <15%. Limitations: This study was conducted in a controlled environment using a trained nurse to collect VAMS samples. Conclusions: In this study, VAMS was used to reliably measured tacrolimus and creatinine. This represents a clear opportunity for more frequent and less invasive sampling for patients

Between the Devil and the Deep Blue Sea: The Role of the Amundsen Sea Continental Shelf in Exchanges Between Ocean and Ice Shelves

The Amundsen Sea is a key region of Antarctica where ocean, atmosphere, sea ice, and ice sheet interact. For much of Antarctica, the relatively warm water of the open Southern Ocean (a few degrees above freezing) does not reach the Antarctic continental shelf in large volumes under current climate conditions. However, in the Amundsen Sea, warm water penetrates onto the continental shelf and provides heat that can melt the underside of the area’s floating ice shelves, thinning them. Here, we discuss how the ocean’s role in melting has come under increased scrutiny, present 2014 observations from the Amundsen Sea, and discuss their implications, highlighting aspects where understanding is still incomplete

Engaging and supporting women with chronic kidney disease with pre‐conception decision‐making (including their experiences during COVID 19): A mixed‐methods study protocol

Aim To report a protocol for a qualitative study to better understand the key factors that influence decision making about pregnancy from women's perspectives and to use these data to develop a theoretical model for shared decision-making tools for the multiple stakeholders. Design Mixed-method design using online surveys (with validated components) and purposively sampled follow-up semi structured interviews. Methods Funded from September 2020 for 12 months. Online surveys of adult women (aged 18–50) identified via all Wales kidney database (n ≥ 500), additional recruitment through multidisciplinary healthcare professionals, relevant third sector organizations and social media. Follow-up in-depth qualitative interviews with n = 30 women. Linear regression models to identify associations between shared decision-making preferences and clinical and psychosocial variables. Qualitative interviews will use a visual timeline task to empower women in taking control over their narratives. Qualitative data will be fully transcribed and analysed thematically, based around a chronological and theoretical (theoretical domains framework) structure that maps out key challenges and opportunities for improved decision support in the care pathway. Visual timelines will be used during stakeholder consultation activities, to enable us to co-create a map of current support, gaps in provision, and opportunities for interventions. Quantitative data will be analysed descriptively to characterize our cohort. We will assemble a multidisciplinary shared decision-making intervention development group and provide ongoing stakeholder consultation activities with patient and public representatives. Discussion Outcomes will support new learning into; the ways women's knowledge of kidney disease may affect family planning and pregnancy, their needs in terms of psychological and social support, and how they weigh up the pros and cons of starting a family. Impact Evidence will inform the design of new shared decision-making tools to better support women with the complex and often emotional decisions about having children while living with kidney disease

Utility of Phase Angle to Identify Cachexia and Assess Mortality in End-Stage Renal Disease

© 2020 American Society for Nutrition. Published by Elsevier Inc. This is an Open access article under the CC-BY-NC-ND license. https://creativecommons.org/licenses/by-nc-nd/4.0/Objectives This cross-sectional analysis sought to identify cachexia and assess survival using phase angle (PA) in patients with end-stage renal disease (ESRD) receiving haemodialysis. Methods Patients receiving haemodialysis (n = 87, mean age 65.9 +/– 13.0) completed a Phase Angle (PA; 50 khz) measurement using bioelectrical impedance analysis. Cachexia variables were recorded according to Evans et al. definition (2008) including nutritional and functional measures (weight, Body Mass Index (BMI), Hand Grip Strength (HGS), Lean Tissue Mass (LTM), C-Reative Protein (CRP), serum albumin, haemoglobin, appetite (Functional Assessment of Anorexia/Cachexia Treatment (FAACT)) and fatigue (Functional Assessment of Chronic Illness Therapy (FACIT)). Survival was assessed at 12 months. Mann Whitney-U and Spearman correlation coefficient were conducted. Results The majority of patients completed follow up (n = 76). Eleven patients had died. Mean PA was not statistically different between those identified as cachectic and non-cachectic according to Evans et al. (2008) definition or between those patients that survived and died. However, patients that survived had better mean scores of weight, BMI, HGS, CRP, serum albumin and fatigue (FACIT). In addition, LTM scores were significantly better in patients that survived (P < .01). Appetite scores were also significantly better in patients that survived (P < .01) and those without cachexia (P = .01). Conclusions This study was part of a larger effort to clarity a phenotype of cachexia in ESRD. Unlike previous research, this study did not find PA useful in identifying patients at a higher risk of cachexia or death. However overall these patients had a very low mean PA. FAACT did discriminate between groups indicating self-reporting measurement tools of nutritional status were useful in identifying patients at a higher risk of cachexia and death. A larger sample and longer follow up is required to balance the limitations of this small study. Timing the administration of PA also requires consideration in future studies. Funding Sources Public Health Agency; Northern Ireland Kidney Research Fund.Peer reviewe