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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2012
    In:  Neuro-Oncology Vol. 14, No. suppl 3 ( 2012-09-01), p. iii1-iii94
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 14, No. suppl 3 ( 2012-09-01), p. iii1-iii94
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
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  • 2
    In: BJS Open, Oxford University Press (OUP), Vol. 6, No. 1 ( 2022-01-06)
    Abstract: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Methods The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study (‘IMAGINE’) of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study (‘Tayside’) in major abdominal surgery (2011–2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Results In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655–0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323–0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specificity range 0.881–0.890 (Tayside 95 per cent c.i. 0.853 to 0.905; IMAGINE 95 per cent c.i. 0.881 to 0.899). Conclusion The OAKS prognostic model can identify patients who are not at high risk of postoperative AKI after gastrointestinal surgery with high specificity. Presented to Association of Surgeons in Training (ASiT) International Conference 2018 (Edinburgh, UK), European Society of Coloproctology (ESCP) International Conference 2018 (Nice, France), SARS (Society of Academic and Research Surgery) 2020 (Virtual, UK).
    Type of Medium: Online Resource
    ISSN: 2474-9842
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
    In: BJS Open, Oxford University Press (OUP), Vol. 5, No. 6 ( 2021-11-09)
    Abstract: The intermediate-term impact of acute kidney injury (AKI) in patients after major gastrointestinal and liver surgery has not been well characterized. This study aimed to evaluate the 1-year mortality rate and renal outcomes associated with postoperative AKI in a national prospective cohort. Methods This prospective multicentre, observational cohort with 1-year postoperative follow-up included adults undergoing major gastrointestinal and liver surgery across the UK and Ireland between 23 September and 18 November 2015. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The primary outcome was death at 1-year after surgery, and the secondary outcome was Major Adverse Kidney Events (MAKE-365). Cox proportionate and multilevel logistic regression were used to account for case mix. Results Of 5745 patients across 173 centres, 1-year follow-up data was completed for 3504 patients (62.2 per cent, 126 centres), with attrition largely explained by centre non-participation (63.1 per cent). Some 13.6 per cent (475 of 3504) patients developed AKI by 7 days after surgery (stage 1: 9.2 per cent; stage 2/3: 4.3 per cent). At 1 year, 10.8 per cent (378 patients) experienced a MAKE-365 endpoint (303 patients had died, 61 had renal replacement therapy and 78 had renal dysfunction). Patients who experienced AKI by 7 days after surgery had a higher hazard of death at 1 year for KDIGO stage 1 (hazard ratio 1.50 (95 per cent c.i. 1.08 to 2.08), P = 0.016) and KDIGO stage 2/3 (hazard ratio 2.96 (95 per cent c.i. 2.02 to 4.33), P & lt; 0.001). Both KDIGO stage 1 (odds ratio 2.09 (95 per cent c.i. 1.50 to 2.92), P & lt; 0.001) and stage 2/3 (odds ratio 9.26 (95 per cent c.i. 6.31 to 13.59), P & lt; 0.001) AKI were independently associated with MAKE-365. Conclusion AKI events within 7 days after gastrointestinal or liver surgery are associated with significantly worse survival and renal outcomes at 1 year.
    Type of Medium: Online Resource
    ISSN: 2474-9842
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 4
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 107, No. 8 ( 2020-06-15), p. 1023-1032
    Abstract: This study aimed to determine the impact of preoperative exposure to intravenous contrast for CT and the risk of developing postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. Methods This prospective, multicentre cohort study included adults undergoing gastrointestinal resection, stoma reversal or liver resection. Both elective and emergency procedures were included. Preoperative exposure to intravenous contrast was defined as exposure to contrast administered for the purposes of CT up to 7 days before surgery. The primary endpoint was the rate of AKI within 7 days. Propensity score-matched models were adjusted for patient, disease and operative variables. In a sensitivity analysis, a propensity score-matched model explored the association between preoperative exposure to contrast and AKI in the first 48 h after surgery. Results A total of 5378 patients were included across 173 centres. Overall, 1249 patients (23·2 per cent) received intravenous contrast. The overall rate of AKI within 7 days of surgery was 13·4 per cent (718 of 5378). In the propensity score-matched model, preoperative exposure to contrast was not associated with AKI within 7 days (odds ratio (OR) 0·95, 95 per cent c.i. 0·73 to 1·21; P = 0·669). The sensitivity analysis showed no association between preoperative contrast administration and AKI within 48 h after operation (OR 1·09, 0·84 to 1·41; P = 0·498). Conclusion There was no association between preoperative intravenous contrast administered for CT up to 7 days before surgery and postoperative AKI. Risk of contrast-induced nephropathy should not be used as a reason to avoid contrast-enhanced CT.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 5
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 103, No. 9 ( 2016-07-18), p. 1157-1172
    Abstract: There is currently conflicting evidence surrounding the effects of obesity on postoperative outcomes. Previous studies have found obesity to be associated with adverse events, but others have found no association. The aim of this study was to determine whether increasing body mass index (BMI) is an independent risk factor for development of major postoperative complications. Methods This was a multicentre prospective cohort study across the UK and Republic of Ireland. Consecutive patients undergoing elective or emergency gastrointestinal surgery over a 4-month interval (October–December 2014) were eligible for inclusion. The primary outcome was the 30-day major complication rate (Clavien–Dindo grade III–V). BMI was grouped according to the World Health Organization classification. Multilevel logistic regression models were used to adjust for patient, operative and hospital-level effects, creating odds ratios (ORs) and 95 per cent confidence intervals (c.i.). Results Of 7965 patients, 2545 (32·0 per cent) were of normal weight, 2673 (33·6 per cent) were overweight and 2747 (34·5 per cent) were obese. Overall, 4925 (61·8 per cent) underwent elective and 3038 (38·1 per cent) emergency operations. The 30-day major complication rate was 11·4 per cent (908 of 7965). In adjusted models, a significant interaction was found between BMI and diagnosis, with an association seen between BMI and major complications for patients with malignancy (overweight: OR 1·59, 95 per cent c.i. 1·12 to 2·29, P = 0·008; obese: OR 1·91, 1·31 to 2·83, P = 0·002; compared with normal weight) but not benign disease (overweight: OR 0·89, 0·71 to 1·12, P = 0·329; obese: OR 0·84, 0·66 to 1·06, P = 0·147). Conclusion Overweight and obese patients undergoing surgery for gastrointestinal malignancy are at increased risk of major postoperative complications compared with those of normal weight.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
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  • 6
    In: World Journal of Surgery, Wiley, Vol. 41, No. 1 ( 2017-01), p. 47-55
    Abstract: Significant safety concerns remain surrounding the use of nonsteroidal anti‐inflammatory drugs (NSAIDs) following gastrointestinal surgery, leading to wide variation in their use. This study aimed to determine the safety profile of NSAIDs after major gastrointestinal surgery. Methods Consecutive patients undergoing elective or emergency abdominal surgery with a minimum one‐night stay during a 3‐month study period were eligible for inclusion. The administration of any NSAID within 3 days following surgery was the main independent variable. The primary outcome measure was the 30‐day postoperative major complication rate, as defined by the Clavien–Dindo classification (Clavien–Dindo III–V). Propensity matching with multivariable logistic regression was used to produce odds ratios (OR) and 95 % confidence intervals. Results From 9264 patients, 23.9 % ( n = 2212) received postoperative NSAIDs. The overall major complication rate was 11.5 % ( n = 1067). Following propensity matching and adjustment, use of NSAIDs were not significantly associated with any increase in major complications (OR 0.90, 0.60–1.34, p = 0.560). Conclusions Early use of postoperative NSAIDs was not associated with an increase in major complications following gastrointestinal surgery.
    Type of Medium: Online Resource
    ISSN: 0364-2313 , 1432-2323
    Language: English
    Publisher: Wiley
    Publication Date: 2017
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  • 7
    In: Diabetes Care, American Diabetes Association, Vol. 41, No. 9 ( 2018-09-01), p. 1887-1894
    Abstract: We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients’ relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8] , 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial–Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables. RESULTS Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06–1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS & gt;0.295, 95% CI 1.47–3.51; P = 0.0002). CONCLUSIONS The T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 8
    In: Oncogenesis, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2023-06-19)
    Abstract: Collectively, the MYC family of oncoprotein transcription factors is overexpressed in more than half of all malignancies. The ability of MYC proteins to access chromatin is fundamental to their role in promoting oncogenic gene expression programs in cancer and this function depends on MYC–cofactor interactions. One such cofactor is the chromatin regulator WDR5, which in models of Burkitt lymphoma facilitates recruitment of the c-MYC protein to chromatin at genes associated with protein synthesis, allowing for tumor progression and maintenance. However, beyond Burkitt lymphoma, it is unknown whether these observations extend to other cancers or MYC family members, and whether WDR5 can be deemed as a “universal” MYC recruiter. Here, we focus on N-MYC amplified neuroblastoma to determine the extent of colocalization between N-MYC and WDR5 on chromatin while also demonstrating that like c-MYC, WDR5 can facilitate the recruitment of N-MYC to conserved WDR5-bound genes. We conclude based on this analysis that N-MYC and WDR5 colocalize invariantly across cell lines at predicted sites of facilitated recruitment associated with protein synthesis genes. Surprisingly, we also identify N-MYC-WDR5 cobound genes that are associated with DNA repair and cell cycle processes. Dissection of chromatin binding characteristics for N-MYC and WDR5 at all cobound genes reveals that sites of facilitated recruitment are inherently different than most N-MYC-WDR5 cobound sites. Our data reveals that WDR5 acts as a universal MYC recruiter at a small cohort of previously identified genes and highlights novel biological functions that may be coregulated by N-MYC and WDR5 to sustain the neuroblastoma state.
    Type of Medium: Online Resource
    ISSN: 2157-9024
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 9
    In: Bulletin of Spanish Studies, Informa UK Limited, Vol. 87, No. 2 ( 2010-03), p. 253-285
    Type of Medium: Online Resource
    ISSN: 1475-3820 , 1478-3428
    RVK:
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2010
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    detail.hit.zdb_id: 280520-0
    SSG: 5,3
    SSG: 7,34
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  • 10
    Online Resource
    Online Resource
    Wiley ; 2012
    In:  Journal of the Society for Information Display Vol. 20, No. 1 ( 2012-01), p. 22-27
    In: Journal of the Society for Information Display, Wiley, Vol. 20, No. 1 ( 2012-01), p. 22-27
    Abstract: Abstract— A procedure is described for perceptually assessing the effects of laser speckle on target discrimination in the context of developing a laser‐display measurement standard. The perceptual approach avoids the difficulties inherent in assessing speckle contrast photometrically. Size thresholds for triangular test stimuli were obtained using an orientation discrimination task. Data were obtained for both a laser display and an LCD monitor using both a method of constant stimuli and a QUEST procedure. The identification threshold was 29% higher for the laser display. Given that the measured spatial resolutions of the displays were similar, the difference in threshold was attributed to the effects of laser speckle. Laser‐speckle size was also estimated as part of the display calibration. For a chosen camera f ‐number, speckle‐size data are necessary to determine the sensor pixel density required to photometrically estimate speckle contrast, and they may be useful for comparison with the data obtained using the perceptual procedure described here. Mean speckle size was estimated by scaling and normalizing the laser‐speckle luminance and then determining the width of the associated autocorrelation function. It is proposed that a laser‐display standard be developed based in part upon a comparison of task performance on the laser display to be evaluated and on a standard display.
    Type of Medium: Online Resource
    ISSN: 1071-0922 , 1938-3657
    Language: English
    Publisher: Wiley
    Publication Date: 2012
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