An Introduction to Glaciated Margins::The Sedimentary and Geophysical Archive

A glaciated margin is a continental margin that has been occupied by a large ice mass, such that glacial processes and slope processes conspire to produce a thick sedimentary record. Ice masses take an active role in sculpting, redistributing and reorganizing the sediment that they erode on the continental shelf, and act as a supply route to large fan systems (e.g. trough mouth fans, submarine fans) on the continental slope and continental rise. To many researchers, the term ‘glaciated margin’ is synonymous with modern day areas fringing Antarctica and the Arctic shelf systems, yet the geological record contains ancient examples ranging in age from Precambrian to Cenozoic. In the pre-Pleistocene record, there is a tendency for the configuration of the tectonic plates to become increasingly obscure with age. For instance, in the Neoproterozoic record, not everyone agrees on the location of rift margins and some fundamental continental boundaries remain unclear. Given these issues, this introductory paper has two simple aims: (1) to provide a brief commentary of relevant Geological Society publications on glaciated margins, with the landmark papers highlighted and (2) to explain the contents of this volume

The effect of early diagnosis and treatment on maternal and fetal outcomes in patients with HELLP syndrome

Uvod: Sindrom HELLP, težak oblik preeklampsije kojega klinički karakterizira hemoliza, povišeni jetreni enzimi, te mali broj trombocita, prvi je put opisan 1982. godine. Materijali i metode: Kako bismo procijenili utjecaj identificiranja ovoga sin-droma na ishode liječenja rodilja i fetusa, proveli smo retrospektivnu studiju i pregledali dokumentaciju bolesnica s preeklampsijom liječenih u Klinici Mayo prije i nakon 1982. godine. Načinili smo retrospektivnu dijagnozu sindroma HELLP u 11 od 146 bolesnica liječenih zbog preeklampsije prije 1982. godine. Usporedili smo ishode trudnoće u nasumce odabranoj skupini 24 žene sa sin-dromom HELLP koje su liječene u Klinici Mayo između 1986. i 1994. godine. Rezultati: Nismo zapazili statistički značajnu razliku među demografskim podatcima o rodiljama ili dijagnostičkim laboratorijskim nalazima. Smrtnost fetusa je bila značajno viša prije 1982. godine. Pojavnost i težina akutnog zatajenja bubrega i drugih skupnih komplikacija kod rodilja (uključujući plućni edem, pleuralni izljev, perikardijski izljev, unutarmoždano krvarenje, konvulzi-je, hepatičku nekrozu, te odignuće mrežnice) bili su značajno veći prije 1982. godine. Nakon te godine vrijeme od dijagnoze do porođaja bilo je značajno kraće (2,5 u odnosu na 14 dana), a za bolesnice je bilo vjerojatnije da će pri-miti profilaksu protiv konvulzija magnezijevim sulfatom. Zabilježena je i tendencija većega broja carskih rezova i poticanja trudova u žena liječenih nakon 1982. godine. Zaključci: Navedena zapažanja ukazuju da je prepoznavanje sindroma HELLP kao zasebnoga kliničkog sindroma dovelo do poboljšanih ishoda trudnoće vjerojatno zbog pravodobnije dijagnoze i ranijeg završetka trudnoće.Background: HELLP syndrome, a severe form of preeclampsia clinically characterized by hemolysis, elevated liver enzymes, and low platelet count, was first described in 1982. Materials and Methods: To assess the impact of recognition of this syndrome on fetal and maternal outcomes, we conducted a retrospective study and reviewed the records of patients with preeclampsia treated at Mayo Clinic before and after 1982. We made a retrospective diagnosis of HELLP in 11 of 146 patients treated for preeclampsia prior to 1982. We compared pregnancy outcomes to a randomly selected group of 24 women with HELLP syndrome treated at Mayo Clinic between 1986 and 1994. Results: We did not observe a statistically significant difference in maternal demographics or diagnostic laboratory findings. Priorto 1982, fetal mortality was significantly higher. The incidence and severity of acute renal failure and other cumulative maternal complications (including pulmonary edema, pleural effusion, pericardial effusion, intracerebral hemorrhage, seizure, hepatic necrosis, and retinal detachment) were significantly higher priorto 1982. After 1982, the time from diagnosis to delivery was significantly shorter (2.5 vs. 14 days), and patients were more likely to receive seizure prophylaxis with magnesium sulfate. There was a trend towards more Caesarian sections and labor induction in women treated after 1982. Conclusions: These observations suggest that recognition of HELLP as a distinct clinical syndrome has led to improved outcomes of pregnancies, probably due to more timely diagnosis and earlier termination of pregnancy

Developing a patient-centred tool for pain measurement and evaluation in autosomal dominant polycystic kidney disease.

BACKGROUND: Pain affects 60% of the autosomal dominant polycystic kidney disease (ADPKD) population. Despite being an early and debilitating symptom, it is poorly characterized and management is suboptimal. This study aimed to develop an ADPKD-specific pain assessment tool (APAT) to facilitate pain research. METHODS: Following a systematic review of PATs used in ADPKD studies and against international recommendations for pain trials, our multi-disciplinary team of clinical experts and patients constructed an ADPKD-pain conceptual framework of key pain evaluation themes. We compiled a new APAT covering domains prioritized within our framework using components of questionnaires validated in other chronic pain disorders. The APAT was administered longitudinally within a randomized high-water intake trial (NCT02933268) to ascertain feasibility and provide pilot data on ADPKD pain. RESULTS: Thirty-nine ADPKD participants with chronic kidney disease Stages 1-4 provided 129 APAT responses. Each participant completed a median of 3 (range 1-10) assessments. Respondents' mean ± standard deviation age was 47 ± 13 years; 59% (23) were female; and 69% (27) had enlarged kidneys with median time from diagnosis 14.2 (interquartile range 7.0-25.9) years. Pain (52%) and associated analgesic use (29%) were common. Pain severity was associated with increasing age [odds ratio (OR) = 1.07, P = 0.009], female gender (OR = 4.34, P = 0.018), estimated glomerular filtration rate <60 mL/min/1.73 m2 (OR = 5.45, P = 0.021) and hypertension (OR = 12.11, P = 0.007), but not with kidney size (P = 0.23). The APAT achieved good internal consistency (Cronbach's alpha coefficient = 0.91) and test-retest reliability (domain intra-class correlation coefficients ranging from 0.62 to 0.90). CONCLUSIONS: The APAT demonstrated good acceptability and reliability, and following further validation in a larger cohort could represent an invaluable tool for future ADPKD pain studies.Addenbrookes Charitable Trust Kidney Care UK British Renal Society Kidney Research U

Strategy and rationale for urine collection protocols employed in the NEPTUNE study

Abstract Background Glomerular diseases are potentially fatal, requiring aggressive interventions and close monitoring. Urine is a readily-accessible body fluid enriched in molecular signatures from the kidney and therefore particularly suited for routine clinical analysis as well as development of non-invasive biomarkers for glomerular diseases. Methods The Nephrotic Syndrome Study Network (NEPTUNE; ClinicalTrials.gov Identifier NCT01209000) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes standardized urine collections across all participating centers for the purpose of discovering non-invasive biomarkers for patients with nephrotic syndrome due to minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Here we describe the organization and methods of urine procurement and banking procedures in NEPTUNE. Results We discuss the rationale for urine collection and storage conditions, and demonstrate the performance of three experimental analytes (neutrophil gelatinase-associated lipocalin [NGAL], retinol binding globulin, and alpha-1 microglobulin) under these conditions with and without urine preservatives (thymol, toluene, and boric acid). We also demonstrate the quality of RNA and protein collected from the urine cellular pellet and exosomes. Conclusions The urine collection protocol in NEPTUNE allows robust detection of a wide range of proteins and RNAs from urine supernatant and pellets collected longitudinally from each patient over 5 years. Combined with the detailed clinical and histopathologic data, this provides a unique resource for exploration and validation of new or accepted markers of glomerular diseases. Trial registration ClinicalTrials.gov Identifier NCT01209000http://deepblue.lib.umich.edu/bitstream/2027.42/116023/1/12882_2015_Article_185.pd

Patient-reported outcome measures for pain in autosomal dominant polycystic kidney disease: A systematic review.

Pain is a common symptom in people with autosomal dominant polycystic kidney disease (ADPKD), but it is assessed and reported inconsistently in research, and the validity of the measures remain uncertain. The aim of this study was to identify the characteristics, content, and psychometric properties of measures for pain used in ADPKD. We conducted a systematic review including all trials and observational studies that reported pain in people with ADPKD. Items from all measures were categorized into content and measurement dimensions of pain. We assessed the general characteristics and psychometric properties of all measures. 118 studies, we identified 26 measures: 12 (46%) measures were developed for a non-ADPKD population, 1 (4%) for chronic kidney disease, 2 (8%) for polycystic liver disease and 11 (42%) specifically for ADPKD. Ten anatomical sites were included, with the lower back the most common (10 measures [39%]), four measurement dimensions (intensity (23 [88%]), frequency (3 [12%]), temporality (2 [8%]), and sensory (21 [81%]), two pain types, nociceptive including visceral (15 [58%]) and somatic (5 [20%]), and neuropathic (2 [8%]), and twelve impact dimensions, where the most frequent was work (5 [31%]). The validation data for the measures were variable and only the ADPKD Impact Scale reported all psychometric domains. The measures for pain in ADPKD varied in terms of content and length, and most had not been validated in ADPKD. A standardized psychometrically robust measure that captures patient-important dimensions of pain is needed to evaluate and manage this debilitating complication of ADPKD

Differences in Immunoglobulin Light Chain Species Found in Urinary Exosomes in Light Chain Amyloidosis (AL)

Renal involvement is a frequent consequence of plasma cell dyscrasias. The most common entities are light chain amyloidosis, monoclonal immunoglobulin deposition disease and myeloma cast nephropathy. Despite a common origin, each condition has its own unique histologic and pathophysiologic characteristic which requires a renal biopsy to distinguish. Recent studies have shown urinary exosomes containing kidney-derived membrane and cytosolic proteins that can be used to probe the proteomics of the entire urinary system from the glomerulus to the bladder. In this study, we analyzed urine exosomes to determine the differences between exosomes from patients with light chain amyloidosis, multiple myeloma, monoclonal gammopathy of undetermined significance, and non-paraproteinemia related kidney disease controls. In patients with light chain amyloidosis, multiple myeloma and monoclonal gammopathy of undetermined significance, immunoreactive proteins corresponding to monomeric light chains were found in exosomes by western blot. In all of the amyloidosis samples with active disease, high molecular weight immunoreactive species corresponding to a decamer were found which were not found in exosomes from the other diseases or in amyloidosis exosomes from patients in remission. Few or no light chains monomeric bands were found in non-paraproteinemia related kidney disease controls. Our results showed that urinary exosomes may have tremendous potential in furthering our understanding of the pathophysiology and diagnosis of plasma cell dyscrasia related kidney diseases

Analysis of baseline parameters in the HALT polycystic kidney disease trials

HALT PKD consists of two ongoing randomized trials with the largest cohort of systematically studied patients with autosomal dominant polycystic kidney disease to date. Study A will compare combined treatment with an angiotensin-converting inhibitor and receptor blocker to inhibitor alone and standard compared with low blood pressure targets in 558 early-stage disease patients with an eGFR over 60ml/min per 1.73m2. Study B will compare inhibitor-blocker treatment to the inhibitor alone in 486 late-stage patients with eGFR 25–60ml/min per 1.73m2. We used correlation and multiple regression cross-sectional analyses to determine associations of baseline parameters with total kidney, liver, or liver cyst volumes measured by MRI in Study A and eGFR in both studies. Lower eGFR and higher natural log-transformed urine albumin excretion were independently associated with a larger natural log–transformed total kidney volume adjusted for height (ln(HtTKV)). Higher body surface area was independently associated with a higher ln(HtTKV) and lower eGFR. Men had larger height-adjusted total kidney volume and smaller liver cyst volumes than women. A weak correlation was found between the ln(HtTKV) and natural log–transformed total liver volume adjusted for height or natural log liver cyst volume in women only. Women had higher urine aldosterone excretion and lower plasma potassium. Thus, our analysis (1) confirms a strong association between renal volume and functional parameters, (2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and (3) suggests an association between anthropomorphic measures reflecting prenatal and/or postnatal growth and disease severity

Mucosal associated invariant T cells are altered in patients with Hidradenitis Suppurativa and contribute to the inflammatory milieu

Mucosal Associated Invariant T cells are a population of “innate” T cells, which express the invariant T cell receptor (TCR) a chain Va7.2-Ja33 and are capable of robust rapid cytokine secretion, producing a milieu of cytokines including IFN-g and IL-17. MAIT cells have been reported in multiple human tissues including the gut, periphery and skin. On-going research has highlighted their involvement in numerous inflammatory diseases ranging from rheumatoid arthritis and obesity to psoriasis. Hidradenitis Suppurativa (H.S) is a chronic inflammatory disease of the hair follicles, resulting in painful lesions of apocrine-bearing skin. Several inflammatory cytokines have been implicated in the pathogenesis of H.S including IL-17. The role of MAIT cells in H.S is currently unknown. In this study we show for the first time, that MAIT cells are altered in the peripheral blood of patients with H.S, with reduced frequencies and an IL-17 cytokine bias. We show that CCL20 expression is elevated in lesions of patients with H.S, and MAIT cells can actively traffic towards lesions via CCL20. We show that MAIT cells can accumulate in the lesionsfrom patients with H.S. when compared to adjacent skin, with an IL-17 bias. We show that elevated IL-17, can be linked to the activation of dermal fibroblasts, promoting the expression of chemotactic signals including CCL20 and CXCL1. Finally, we show that targeting the IL-17A transcription factor RORyt robustly reduces IL-17 production by MAIT cells from patients with H.S. Collectively our data detailsIL-17 producing MAIT cells as a novel player in the pathogenesis of H.S and highlights the potential of RORyt inhibition as a novel therapeutic strategy

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy