Peri-operative adrenocortical response to low-dose (1 microg) ACTH and relation to postoperative complications in patients undergoing elective abdominal surgery

BACKGROUND: To test the hypothesis that reduced responsiveness to adrenocorticotropin (ACTH) stimulation before elective major abdominal surgery is associated with an increased incidence of postoperative complications. METHODS: A low-dose (1 microg) ACTH test was performed the day before surgery, during the operation, on the first postoperative day, and before discharge from the hospital in 77 patients undergoing major abdominal surgery (age 62 [47;69] yrs [median, quartiles]; 30 female). Thirty-one patients undergoing minor, non-abdominal surgery (mostly inguinal hernia repair) (age 57 [40;66] yrs; 14 female) served as controls with minor surgical stress. A stimulated plasma cortisol concentration >or=500 nmol/l or an increment of >or=200 nmol/l in response to 1 microg ACTH was defined as normal. Scores for surgical stress and comprehensive risk, postoperative complications, and length of hospital stay (LOS) were assessed. RESULTS: On the day before major abdominal surgery, basal and stimulated plasma cortisol were 242 (165;299) nmol/l and 497 (404;568) nmol/l, respectively. Eighteen (23%) patients had an abnormal ACTH test, and 7 of these (39%) had complications versus 25 (42%) of the 59 patients with normal ACTH tests (P = .992). Surgical stress, comprehensive risk, and intra- and postoperative basal cortisol levels were higher and the response to ACTH stimulation smaller in patients with major abdominal compared to minor surgery. The peri-operative course of ACTH responses was not associated with complications or LOS in abdominal surgery patients. CONCLUSION: In patients scheduled for abdominal surgery, pre-operatively reduced adrenal response to stimulation with 1 microg ACTH is common but not associated with postoperative complications.

A Hybrid Model for Multimodal Brain Tumor Segmentation

We present a fully automatic segmentation method for multi-modal brain tumor segmentation. The proposed generative-discriminative hybrid model generates initial tissue probabilities, which are used subsequently for enhancing the classi�cation and spatial regularization. The model has been evaluated on the BRATS2013 training set, which includes multimodal MRI images from patients with high- and low-grade gliomas. Our method is capable of segmenting the image into healthy (GM, WM, CSF) and pathological tissue (necrotic, enhancing and non-enhancing tumor, edema). We achieved state-of-the-art performance (Dice mean values of 0.69 and 0.8 for tumor subcompartments and complete tumor respectively) within a reasonable timeframe (4 to 15 minutes).

Coordination-directed self-assembly of a simple benzothiadiazole-fused tetrathiafulvalene to low-bandgap metallogels

Coordination-driven gelation of a benzothiadiazole-fused tetrathiafulvalene (TTF) is demonstrated. This is the first work reporting highly stable metallogels based on a donor-acceptor conjugate with such a simple structure for the construction of new low-bandgap materials with various functional properties and novel nanostructures.

Environmental control on the occurrence of high-coercivity magnetic minerals and formation of iron sulfides in a 640 ka sediment sequence from Lake Ohrid (Balkans)

The bulk magnetic mineral record from Lake Ohrid, spanning the past 637 kyr, reflects large-scale shifts in hydrological conditions, and, superimposed, a strong signal of environmental conditions on glacial–interglacial and millennial timescales. A shift in the formation of early diagenetic ferrimagnetic iron sulfides to siderites is observed around 320 ka. This change is probably associated with variable availability of sulfide in the pore water. We propose that sulfate concentrations were significantly higher before  ∼  320 ka, due to either a higher sulfate flux or lower dilution of lake sulfate due to a smaller water volume. Diagenetic iron minerals appear more abundant during glacials, which are generally characterized by higher Fe / Ca ratios in the sediments. While in the lower part of the core the ferrimagnetic sulfide signal overprints the primary detrital magnetic signal, the upper part of the core is dominated by variable proportions of high- to low-coercivity iron oxides. Glacial sediments are characterized by high concentration of high-coercivity magnetic minerals (hematite, goethite), which relate to enhanced erosion of soils that had formed during preceding interglacials. Superimposed on the glacial–interglacial behavior are millennial-scale oscillations in the magnetic mineral composition that parallel variations in summer insolation. Like the processes on glacial–interglacial timescales, low summer insolation and a retreat in vegetation resulted in enhanced erosion of soil material. Our study highlights that rock-magnetic studies, in concert with geochemical and sedimentological investigations, provide a multi-level contribution to environmental reconstructions, since the magnetic properties can mirror both environmental conditions on land and intra-lake processes.

On the theory of high and low pressure areas: The significance of divergence in pressure areas

This is the edited and translated version of the article by Richard Scherhag “Zur Theorie der Hoch- und Tiefdruckgebiete. Die Bedeutung der Divergenz in Druckfeldern” (On the theory of high and low pressure areas: The significance of divergence in pressure areas), which was published in Meteorologische Zeitschrift 51, 129–138.

Contribution of Genetic Background and Clinical Risk Factors to Low-Trauma Fractures in Human Immunodeficiency Virus (HIV)-Positive Persons: The Swiss HIV Cohort Study.

Background.  The impact of human genetic background on low-trauma fracture (LTF) risk has not been evaluated in the context of human immunodeficiency virus (HIV) and clinical LTF risk factors. Methods.  In the general population, 6 common single-nucleotide polymorphisms (SNPs) associate with LTF through genome-wide association study. Using genome-wide SNP arrays and imputation, we genotyped these SNPs in HIV-positive, white Swiss HIV Cohort Study participants. We included 103 individuals with a first, physician-validated LTF and 206 controls matched on gender, whose duration of observation and whose antiretroviral therapy start dates were similar using incidence density sampling. Analyses of nongenetic LTF risk factors were based on 158 cases and 788 controls. Results.  A genetic risk score built from the 6 LTF-associated SNPs did not associate with LTF risk, in both models including and not including parental hip fracture history. The contribution of clinical LTF risk factors was limited in our dataset. Conclusions.  Genetic LTF markers with a modest effect size in the general population do not improve fracture prediction in persons with HIV, in whom clinical LTF risk factors are prevalent in both cases and controls.

Spectral biases in tree-ring climate proxies

External forcing and internal dynamics result in climate system variability ranging from sub-daily weather to multi-centennial trends and beyond1, 2. State-of-the-art palaeoclimatic methods routinely use hydroclimatic proxies to reconstruct temperature (for example, refs 3, 4), possibly blurring differences in the variability continuum of temperature and precipitation before the instrumental period. Here, we assess the spectral characteristics of temperature and precipitation fluctuations in observations, model simulations and proxy records across the globe. We find that whereas an ensemble of different general circulation models represents patterns captured in instrumental measurements, such as land–ocean contrasts and enhanced low-frequency tropical variability, the tree-ring-dominated proxy collection does not. The observed dominance of inter-annual precipitation fluctuations is not reflected in the annually resolved hydroclimatic proxy records. Likewise, temperature-sensitive proxies overestimate, on average, the ratio of low- to high-frequency variability. These spectral biases in the proxy records seem to propagate into multi-proxy climate reconstructions for which we observe an overestimation of low-frequency signals. Thus, a proper representation of the high- to low-frequency spectrum in proxy records is needed to reduce uncertainties in climate reconstruction efforts.

Transformative deliberative moments among ex-combattants in Colombia

This dissertation presents the concept of Deliberative Transformative Moment and the instrument to identify it, in a further attempt to bridge the gap between deliberation theory and practice. A transformative moment in the deliberative process occurs when the level of deliberation is either lifted from low to high or drops from high to low. In order to identify such a moment, one has to look at the context and dynamics of the group discussion. This broadening of the unit of analysis is a big difference from other existing instruments to measure the level of deliberation, such as the Deliberative Quality Index –DQI, which focuses primarily on the individual speech acts. Consistent with the theoretical framework of consociational and deliberation approaches, the observed discussions took place among two deeply divided groups, Colombian ex-combatants from both the extreme left and the extreme right. Moving beyond a pure Habermasian perspective, this study finds that besides pure rational arguments, there are some contexts in which personal stories, jokes and self-interests, acting as justification of arguments, have either a positive or a negative impact on deliberative transformative moments. Although this research has a strongly qualitative orientation, reliability tests scored high, giving it strength as a reliable and valid research method that shedding some light on the sort of speech acts that enhance deliberation and those that detract from it.

Plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, e-selectin and C-reactive protein levels in response to 4-week very-high-fructose or -glucose diets.

BACKGROUND/OBJECTIVES High intake of added sweeteners is considered to have a causal role in the pathogenesis of cardiometabolic disorders. Especially, high-fructose intake is regarded as potentially harmful to cardiometabolic health. It may cause not only weight gain but also low-grade inflammation, which represents an independent risk factor for developing type 2 diabetes and cardiovascular disease. In particular, fructose has been suggested to induce plasminogen activator inhibitor-1 (PAI-1) expression in the liver and to increase circulating inflammatory cytokines. We therefore aimed to investigate, whether high-fructose diet has an impact on PAI-1, monocyte chemoattractant protein-1 (MCP-1), e-selectin and C-reactive protein (CRP) concentrations in healthy humans. SUBJECTS/METHODS We studied 20 participants (12 males and 8 females) of the TUebingen FRuctose Or Glucose study. This is an exploratory, parallel, prospective, randomized, single-blinded, outpatient, hypercaloric, intervention study. The participants had a mean age of 30.9 ± 2.1 years and a mean body mass index of 26.0 ± 0.5 kg/m(2) and they received 150 g of either fructose or glucose per day for 4 weeks.Results:There were neither significant changes of PAI-1, MCP-1, e-selectin and CRP after fructose (n=10) and glucose (n=10) intervention nor treatment effects (all P>0.2). Moreover, we did not observe longitudinal associations of the inflammatory parameters with triglycerides, liver fat, visceral fat and body weight in the fructose group. CONCLUSIONS Temporary high-fructose intake does not seem to cause inflammation in apparently healthy people in this secondary analysis of a small feeding trial.

Determination of histopathological tumor grade in neuroepithelial brain tumors by using spectral pattern analysis of in vivo spectroscopic data

OBJECT: In this study, 1H magnetic resonance (MR) spectroscopy was prospectively tested as a reliable method for presurgical grading of neuroepithelial brain tumors. METHODS: Using a database of tumor spectra obtained in patients with histologically confirmed diagnoses, 94 consecutive untreated patients were studied using single-voxel 1H spectroscopy (point-resolved spectroscopy; TE 135 msec, TE 135 msec, TR 1500 msec). A total of 90 tumor spectra obtained in patients with diagnostic 1H MR spectroscopy examinations were analyzed using commercially available software (MRUI/VARPRO) and classified using linear discriminant analysis as World Health Organization (WHO) Grade I/II, WHO Grade III, or WHO Grade IV lesions. In all cases, the classification results were matched with histopathological diagnoses that were made according to the WHO classification criteria after serial stereotactic biopsy procedures or open surgery. Histopathological studies revealed 30 Grade I/II tumors, 29 Grade III tumors, and 31 Grade IV tumors. The reliability of the histological diagnoses was validated considering a minimum postsurgical follow-up period of 12 months (range 12-37 months). Classifications based on spectroscopic data yielded 31 tumors in Grade I/II, 32 in Grade III, and 27 in Grade IV. Incorrect classifications included two Grade II tumors, one of which was identified as Grade III and one as Grade IV; two Grade III tumors identified as Grade II; two Grade III lesions identified as Grade IV; and six Grade IV tumors identified as Grade III. Furthermore, one glioblastoma (WHO Grade IV) was classified as WHO Grade I/II. This represents an overall success rate of 86%, and a 95% success rate in differentiating low-grade from high-grade tumors. CONCLUSIONS: The authors conclude that in vivo 1H MR spectroscopy is a reliable technique for grading neuroepithelial brain tumors.

Combined alpha-methylacyl coenzyme A racemase/p53 analysis to identify dysplasia in inflammatory bowel disease

Identification of dysplasia in inflammatory bowel disease represents a major challenge for both clinicians and pathologists. Clear diagnosis of dysplasia in inflammatory bowel disease is sometimes not possible with biopsies remaining "indefinite for dysplasia." Recent studies have identified molecular alterations in colitis-associated cancers, including increased protein levels of alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2. In order to analyze the potential diagnostic use of these parameters in biopsies from inflammatory bowel disease, a tissue microarray was manufactured from colons of 54 patients with inflammatory bowel disease composed of 622 samples with normal mucosa, 78 samples with inflammatory activity, 6 samples with low-grade dysplasia, 12 samples with high-grade dysplasia, and 66 samples with carcinoma. In addition, 69 colonoscopic biopsies from 36 patients with inflammatory bowel disease (28 low-grade dysplasia, 8 high-grade dysplasia, and 33 indefinite for dysplasia) were included in this study. Immunohistochemistry for alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2 was performed on both tissue microarray and biopsies. p53 and alpha-methylacyl coenzyme A racemase showed the most discriminating results, being positive in most cancers (77.3% and 80.3%) and dysplasias (94.4% and 94.4%) but only rarely in nonneoplastic epithelium (1.6% and 9.4%; P < .001). Through combining the best discriminators, p53 and alpha-methylacyl coenzyme A racemase, a stronger distinction between neoplastic tissues was possible. Of all neoplastic lesions, 75.8% showed a coexpression of alpha-methylacyl coenzyme A racemase and p53, whereas this was found in only 4 of 700 nonneoplastic samples (0.6%). alpha-methylacyl coenzyme A racemase/p53 coexpression was also found in 10 of 33 indefinite for dysplasia biopsies (30.3 %), suggesting a possible neoplastic transformation in these cases. Progression to dysplasia or carcinoma was observed in 3 of 10 p53/alpha-methylacyl coenzyme A racemase-positive, indefinite-for-dysplasia cases, including 1 of 7 cases without and 2 of 3 cases with p53 mutation. It is concluded that combined alpha-methylacyl coenzyme A racemase/p53 analysis may represent a helpful tool to confirm dysplasia in inflammatory bowel disease.

Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways

Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra- and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low- to high-grade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, β-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P=0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenoma-carcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.