Ocean stratification and low melt rates at the Ross Ice Shelf grounding zone

Ocean‐driven melting of ice shelves is a primary mechanism for ice loss from Antarctica. However, due to the difficulty in accessing the sub‐ice shelf ocean cavity, the relationship between ice shelf melting and ocean conditions is poorly understood, particularly near the grounding zone, where the ice transitions from grounded to floating. We present the first borehole oceanographic observations from the grounding zone of the Ross Ice Shelf, Antarctica's largest ice shelf by area. Contrary to predictions that tidal currents near grounding zones mix the water column, we found that Ross Ice Shelf waters were vertically stratified. Current velocities at middepth in the ocean cavity did not change significantly over measurement periods at two different parts of the tidal cycle. The observed stratification resulted in low melt rates near this portion of the grounding zone, inferred from phase‐sensitive radar observations. These melt rates were generally <10 cm/year, which is lower than average for the Ross Ice Shelf (∼20 cm/year). Melt rates may be higher at portions of the grounding zone that experience higher subglacial discharge or stronger tidal mixing. Stratification in the cavity at the borehole site was prone to diffusive convection as a result of ice shelf melting. Since diffusive convection influences vertical heat and salt fluxes differently than shear‐driven turbulence, this process may affect ice shelf melting and merits further consideration in ocean models of sub‐ice shelf circulation

Isolation of Primary Human Hepatocytes from Normal and Diseased Liver Tissue: A One Hundred Liver Experience

Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples

Normal kidney size and its influencing factors - a 64-slice MDCT study of 1.040 asymptomatic patients

<p>Abstract</p> <p>Background</p> <p>Normal ultrasound values for pole-to-pole kidney length (LPP) are well established for children, but very little is known about normal kidney size and its influencing factors in adults. The objectives of this study were thus to establish normal CT values for kidney dimensions from a group of unselected patients, identify potential influencing factors, and to estimate their significance.</p> <p>Methods</p> <p>In multiphase thin-slice MDCTs of 2.068 kidneys in 1.040 adults, the kidney length pole to pole (LPP), parenchymal (PW) and cortical width (CW), position and rotation status of the kidneys, number of renal arteries, pyelon width and possible influencing factors that can be visualized, were recorded from a volume data set. For length measurements, axes were adjusted individually in double oblique planes using a 3D-software. Analyses of distribution, T-tests, ANOVA, correlation and multivariate regression analyses were performed.</p> <p>Results</p> <p>LPP was 108.5 ± 12.2 mm for the right, and 111.3 ± 12.6 mm for the left kidney (p < 0.0001 each). PW on the right side was 15.4 ± 2.8 mm, slightly less than 15.9 ± 2.7 mm on the left side (p < 0.0001), the CW was the same (6.6 ± 1.9 mm). The most significant independent predictors for LPP, CW, and PW were body size, BMI, age, and gender (p < 0.001 each). In men, the LPP increases up to the fifth decade of life (p < 0.01). It is also influenced by the position of the kidneys, stenoses and number of renal arteries (SRA/NRA), infarctions suffered, parapelvic cysts, and absence of the contralateral kidney; CW is influenced by age, position, parapelvic cysts, NRA and SRA, and the PW is influenced in addition by rotation status (p < 0.05 each). Depending on the most important factors, gender-specific normal values were indicated for these dimensions, the length and width in cross section, width of the renal pelvis, and parenchyma-renal pyelon ratio.</p> <p>Conclusions</p> <p>Due to the complex influences on kidney size, assessment should be made individually. The most important influencing factors are BMI, height, gender, age, position of the kidneys, stenoses and number of renal arteries.</p

Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies

Sonographic assessment of renal length in children: A reappraisal

Ultrasonography (US) has largely replaced the intravenous urogram as the first modality for the evaluation of the kidneys in children suspected of having urinary tract abnormalities. Because many renal disorders are associated with changes in the sizes of the kidneys, normative standards for assessing renal size have been developed. These standards rely upon comparison of the renal lengths or calculated volumes or both, with various assessments of overall body size, including body surface area, weight, height, and chronological age. We discuss some of the limitations of US in assessing renal size in children. Practical recommendations are offered for optimizing the measurement and interpretation of sonographic renal sizes in children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46703/1/247_2005_Article_BF02020164.pd

Cognitive behavioral therapy of socially phobic children focusing on cognition: a randomised wait-list control study

BACKGROUND: Although literature provides support for cognitive behavioral therapy (CBT) as an efficacious intervention for social phobia, more research is needed to improve treatments for children. METHODS: Forty four Caucasian children (ages 8-14) meeting diagnostic criteria of social phobia according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; APA, 1994) were randomly allocated to either a newly developed CBT program focusing on cognition according to the model of Clark and Wells (n = 21) or a wait-list control group (n = 23). The primary outcome measure was clinical improvement. Secondary outcomes included improvements in anxiety coping, dysfunctional cognitions, interaction frequency and comorbid symptoms. Outcome measures included child report and clinican completed measures as well as a diagnostic interview. RESULTS: Significant differences between treatment participants (4 dropouts) and controls (2 dropouts) were observed at post test on the German version of the Social Phobia and Anxiety Inventory for Children. Furthermore, in the treatment group, significantly more children were free of diagnosis than in wait-list group at post-test. Additional child completed and clinician completed measures support the results. DISCUSSION: The study is a first step towards investigating whether CBT focusing on cognition is efficacious in treating children with social phobia. Future research will need to compare this treatment to an active treatment group. There remain the questions of whether the effect of the treatment is specific to the disorder and whether the underlying theoretical model is adequate. CONCLUSION: Preliminary support is provided for the efficacy of the cognitive behavioral treatment focusing on cognition in socially phobic children. Active comparators should be established with other evidence-based CBT programs for anxiety disorders, which differ significantly in their dosage and type of cognitive interventions from those of the manual under evaluation (e.g. Coping Cat)

Cognitive Behavior Therapy for Anxious Adolescents: Developmental Influences on Treatment Design and Delivery

Anxiety disorders in adolescence are common and disruptive, pointing to a need for effective treatments for this age group. Cognitive behavior therapy (CBT) is one of the most popular interventions for adolescent anxiety, and there is empirical support for its application. However, a significant proportion of adolescent clients continue to report anxiety symptoms post-treatment. This paper underscores the need to attend to the unique developmental characteristics of the adolescent period when designing and delivering treatment, in an effort to enhance treatment effectiveness. Informed by the literature from developmental psychology, developmental psychopathology, and clinical child and adolescent psychology, we review the ‘why’ and the ‘how’ of developmentally appropriate CBT for anxious adolescents. ‘Why’ it is important to consider developmental factors in designing and delivering CBT for anxious adolescents is addressed by examining the age-related findings of treatment outcome studies and exploring the influence of developmental factors, including cognitive capacities, on engagement in CBT. ‘How’ clinicians can developmentally tailor CBT for anxious adolescents in six key domains of treatment design and delivery is illustrated with suggestions drawn from both clinically and research-oriented literature. Finally, recommendations are made for research into developmentally appropriate CBT for anxious adolescents

A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

BACKGROUND: Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. METHODS AND FINDINGS: We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding. CONCLUSIONS: A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors

Lipid Composition of the Human Eye: Are Red Blood Cells a Good Mirror of Retinal and Optic Nerve Fatty Acids?

International audienceBACKGROUND: The assessment of blood lipids is very frequent in clinical research as it is assumed to reflect the lipid composition of peripheral tissues. Even well accepted such relationships have never been clearly established. This is particularly true in ophthalmology where the use of blood lipids has become very common following recent data linking lipid intake to ocular health and disease. In the present study, we wanted to determine in humans whether a lipidomic approach based on red blood cells could reveal associations between circulating and tissue lipid profiles. To check if the analytical sensitivity may be of importance in such analyses, we have used a double approach for lipidomics. METHODOLOGY AND PRINCIPAL FINDINGS: Red blood cells, retinas and optic nerves were collected from 9 human donors. The lipidomic analyses on tissues consisted in gas chromatography and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS). Gas chromatography did not reveal any relevant association between circulating and ocular fatty acids except for arachidonic acid whose circulating amounts were positively associated with its levels in the retina and in the optic nerve. In contrast, several significant associations emerged from LC-ESI-MS analyses. Particularly, lipid entities in red blood cells were positively or negatively associated with representative pools of retinal docosahexaenoic acid (DHA), retinal very-long chain polyunsaturated fatty acids (VLC-PUFA) or optic nerve plasmalogens. CONCLUSIONS AND SIGNIFICANCE: LC-ESI-MS is more appropriate than gas chromatography for lipidomics on red blood cells, and further extrapolation to ocular lipids. The several individual lipid species we have identified are good candidates to represent circulating biomarkers of ocular lipids. However, further investigation is needed before considering them as indexes of disease risk and before using them in clinical studies on optic nerve neuropathies or retinal diseases displaying photoreceptors degeneration