Subjectively adapted high capacity lossless image data hiding based on prediction errors

This article reports on a lossless data hiding scheme for digital images where the data hiding capacity is either determined by minimum acceptable subjective quality or by the demanded capacity. In the proposed method data is hidden within the image prediction errors, where the most well-known prediction algorithms such as the median edge detector (MED), gradient adjacent prediction (GAP) and Jiang prediction are tested for this purpose. In this method, first the histogram of the prediction errors of images are computed and then based on the required capacity or desired image quality, the prediction error values of frequencies larger than this capacity are shifted. The empty space created by such a shift is used for embedding the data. Experimental results show distinct superiority of the image prediction error histogram over the conventional image histogram itself, due to much narrower spectrum of the former over the latter. We have also devised an adaptive method for hiding data, where subjective quality is traded for data hiding capacity. Here the positive and negative error values are chosen such that the sum of their frequencies on the histogram is just above the given capacity or above a certain quality.

Free-breathing T2 mapping at 3T for the monitoring of cardiac allograft rejection: initial results

rejection can lead to loss of function. Histological reading of endomyocardial biopsy remains the "gold standard" for guiding immunosuppression, despite its methodological limitations (sampling error and interobserver variability). The measurement of the T2 relaxation time has been suggested for detection of allograft rejection, on the pathophysiological basis that the T2 relaxation time prolongs with local edema resulting from acute allograft rejection. Using breath-held cardiac magnetic resonance T2 mapping at 1.5 T, Usman et al. (CircCardiovascImaging2012) detected moderate allograft rejection (grade 2R, ISHLT 2004). With modern immunosuppression grade 2R rejection has become a rare event, but the need remains for a technique that permits the discrimination of absent (grade 0R) and mild rejection (grade 1R). We therefore investigated whether an increase of magnetic field strength to 3T and the use of real-time navigator-gated respiration compensation allow for an increase in the sensitivity of T2 relaxation time detection that is necessary to achieve this discrimination. Methods: Eighteen patients received EMB (Tan et al., ArchPatholLabMed2007) and cardiac T2 mapping on the same day. Reading of T2 maps was blinded to the histological results. For final analysis, 3 cases with known 2R rejection at the time of T2 mapping were added, yielding 21 T2 mapping sessions. A respiration-navigator-gated radial gradient-recalled-echo pulse sequence (resolution 1.17 mm2, matrix 2562, trigger time 3 heartbeats, T2 preparation duration TET2 Prep = 60/30/0 ms) was applied to obtain 3 short-axis T2 maps (van Heeswijk et al., JACCCardiovascImaging2012), which were segmented according to AHA guidelines (Cerqueira et al, Circulation2001). The highest segmental T2 values were grouped according to histological rejection grade and differences were analyzed by Student's t-test, except for the non-blinded cases with 2R rejection. The degree of discrimination was determined using the Spearman's ranked correlation test. Results: The high-quality T2 maps allowed for visual differentiation of the rejection degrees (Figure 1), and the correlation of T2 mapping with the histological grade of acute cellular rejection was significant (Spearman's r = 0.56, p = 0.007). The 0R (n = 15) and 1R (n = 3) degrees demonstrated significantly different T2 values (46.9 ± 5.0 and 54.3 ± 3.0 ms, p = 0.02, Figure 2). Cases with 2R rejection showed clear T2 elevation (T2 = 60.3 ± 16.2 ms). Conclusions: This pilot study demonstrates that non-invasive free-breathing cardiac T2 mapping at 3T discriminates between no and mild cardiac allograft rejection. Confirmation of these encouraging results in a larger cohort should consider a study able to show equivalency or superiority of T2 mapping.

Oral rivaroxaban for symptomatic venous thromboembolism.

BACKGROUND: Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring. METHODS: We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study. RESULTS: The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11). CONCLUSIONS: Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).

Hydraulisen kuristinmallin ja liikealustan ohjauksen kehittäminen reaaliaikasimulointiin

Diplomityön ensimmäisessä vaiheessa tutkittiin hydraulisen kuristimen ominaisuuksia ja esiteltiin numeerisesti tehokas kuristinmalli käyttäenpolynomifunktiota virtauksen laminaarisen ja transitioalueen kuvaukseen. Puoliempiirisen mallin paremmuus tulee esille siinä, että kuristimen geometriatietoja ei tarvita laskettaessa virtausta paine-eron perusteella. Reaaliaikasimuloinnissa esiintyy kompromisseja tarkkuuden ja laskentanopeuden välillä. Tätä asiaa tutkittiin kahden virtausalueen kuristinmallilla. Transition paine-eron ja integrointiaika-askelen valinnan vaikutus tarkkuuteen ja laskentanopeuteen tutkittiin. Toisessa vaiheessa tutkittiin mahdollisimman hyvän liiketuntuman tuottamista liikealustalla ohjaussignaalia kehittämällä. Liikealustan liikeradan rajallisuudesta johtuen ohjauksessa on perinteisesti käytetty washout-suodatusta, joka erottelee simuloitavan järjestelmän kiihtyvyyssignaalista vain nopeatkiihtyvyydet. Tässä työssä tutkittiin hitaiden kiihtyvyyksien ottamista mukaan liikealustan ohjaukseen liikealustan liikeradan puitteissa. Tämä toteutettiin kuvaamalla hitaat kiihtyvyydet kallistamalla liikealustaa, jolloin käyttäjään kohdistuva voima saatiin kuvattua gravitaatiota hyväksi käyttäen.

Early high-dose treatment: SCT results from the European High Risk Neuroblastoma Study

Aims: The HR-NBL1 Study of the European SIOP Neuroblastoma Group (SIOPEN) randomised two high dose regimens to learn about potential superiority and toxicity profiles.Patients and Methods: At interim analysis 1483 high risk neuroblastoma patients (893 males) were included since 2002 with either INSS stage 4 disease (1383 pts) above 1 year, or as infants (59 pts) and stage 2&3 of any age (145 pts) with MYCN amplification. The median age at diagnosis was 2.9 years (1 month-19.9 years) with a median follow up of 3 years. Response eligibility criteria prior randomisation after Rapid Cojec Induction (J Clin Oncol, 2010) ± 2 courses of TVD (Cancer, 2003) included complete bone marrow remission and at least partial response at skeletal sites with no more than 3, but improved mIBG positive spots and a PBSC harvest of at least 3x10E6 CD34/kgBW. The randomised regimens were BuMel [busulfan oral till 2006, 4x150mg/m² in 4 ED; or intravenous use according to body weight as licenced thereafter; melphalan 140mg/m²/day) and CEM [carboplatinum ctn. infusion (4x AUC 4.1mg/ml.min/day, etoposid ctn. infusion (4x 338mg/m²/day or [4x 200mg/m²/day]*, melphalan (3x70mg/m²/day; 3x60mg/m²/day*;*reduced dosis if GFR< 100ml/min/1.73m²). Supportive care followed institutional guidelines. VOD prophylaxis included ursadiol, but randomised patients were not eligible for the prophylactic defibrotide trial. Local control included surgery and radiotherapy of 21Gy.Results: Of 1483 patients, 584 were being randomised for the high dose question at data lock. A significant difference in event free survival (3-year EFS 49% vs. 33%, p<0.001) and overall survival (3-year OS 61% vs. 48%, p=0.003) favouring the BuMel regimen over the CEM regimen was demonstrated. The relapse/progression rate was significantly higher after CEM (0.60±0.03) than after BuMel (0.48±0.03)(p<0.001). Toxicity data had reached 80% completeness at last analysis. The severe toxicity rate up to day 100 (ICU and toxic deaths) was below 10%, but was significantly higher for CEM (p= 0.014). The acute toxic death rate was 3% for BuMel and 5% for CEM (NS). The acute HDT toxicity profile favours the BuMel regimen in spite of a total VOD incidence of 18% (grade 3:5%).Conclusions: The Peto rule of P<0.001 at interim analysis on the primary endpoint, EFS was met. Hence randomization was stopped with BuMel as recommended standard treatment in the HR-NBl1/SIOPEN trial which is still accruing for the randomised immunotherapy question.

Epistemología y cibernética

Si el observador y el observado forman parte del mismo objeto descrito, la convergencia entre el sujeto cognoscente y el objeto por conocer no puede sustraerse del principio de reflexividad, que propicia una mejor y más profunda solidez del corpus científico generado. La superioridad del principio de reflexividad se fundamenta en la naturaleza autorreferente de los sistemas sociales, esto es, en la capacidad que desarrollan los sistemas para tomar conciencia de sí y delimitarse respecto a un entorno o ambiente. A través de tal delimitación los sistemas acceden a la autoobservación, sin ella los sistemas no son capaces de generar todos los componentes que precisan para sus operaciones, esto es, no son capaces de llevar a cabo sus procesos autopoiéticos.

MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial.

PURPOSE: Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen. EXPERIMENTAL DESIGN: Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m(2) per day)/one week off] or Arm B [3 weeks on (80 mg/m(2) per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR. RESULTS: Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8-3.2 vs. B: 2.0 months; 95% CI, 1.8-3.5] and overall survival [A: 9.8 months (95% CI, 6.7-13.0) vs. B: 10.6 months (95% CI, 8.1-11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8-7.4) versus 1.8 months (95% CI, 1.8-2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation. CONCLUSIONS: Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation.

Méta-analyses d'essais randomisés sur données individuelles dans le traitement des cancers ORL non métastatiques : principes, résultats, perspectives [Individual patient data meta-analyses of randomized trials for the treatment of non-metastatic head and neck squamous cell carcinomas: Principles, results and perspectives].

Meta-analyses are considered as an important pillar of evidence-based medicine. The aim of this review is to describe the main principles of a meta-analysis and to use examples of head and neck oncology to demonstrate their clinical impact and methodological interest. The major role of individual patient data is outlined, as well as the superiority of individual patient data over meta-analyses based on published summary data. The major clinical breakthrough of head and neck meta-analyses are summarized, regarding concomitant chemotherapy, altered fractionated chemotherapy, new regimens of induction chemotherapy or the use of radioprotectants. Recent methodological developments are described, including network meta-analyses, the validation of surrogate markers. Lastly, the future of meta-analyses is discussed in the context of personalized medicine.

Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review.

CONTEXT: The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound-guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging-ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. OBJECTIVE: Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. EVIDENCE SYNTHESIS: Fourteen papers reporting the outcomes of 15 studies (n=2293; range: 13-582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2-50% vs 4.8-52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7-82.1% vs 14.3-59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5-16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). CONCLUSIONS: Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. PATIENT SUMMARY: We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.

Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis.

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression. Comment in The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlEfficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis--results to be interpreted with caution.

A mouse peritonitis model for the study of glycopeptide efficacy in GISA infections

In recent years, the emergence of Staphylococcus aureus strains with reduced susceptibility to glycopeptides has raised considerable concern. We studied the efficacy of vancomycin and teicoplanin, as well as cloxacillin and cefotaxime, against the infection caused by four S. aureus strains with different glycopeptide and β-lactam susceptibilities (strains A, B, C, and D; MICs for vancomycin of 1, 2, 4, and 8 µg/ml respectively), using a modified model of mouse peritonitis. This optimized model appeared to be straightforward and reproducible, and was able to detect low differences in bacterial killing between antibiotics and also between different S. aureus strains. Bactericidal activities in peritoneal fluid for vancomycin, teicoplanin, cloxacillin, and cefotaxime decreased from -2.98, -2.36, -3.22, and -3.57 log10 cfu/ml, respectively, in infection by strain A (MICs for vancomycin and cloxacillin of 1 and 0.38 µg/ml, respectively) to -1.22, -0.65, -1.04, and +0.24 in peritonitis due to strain D (MICs for vancomycin and cloxacillin of 8 and 1,024 µg/ml). Our data confirm the superiority of β-lactams against methicillin-susceptible S. aureus and show that bactericidal activity of glycopeptides decreases significantly with slight increases in MICs; this finding suggests a reduced efficacy of glycopeptides in the treatment of serious glycopeptide-intermediate S. aureus infections

A mouse peritonitis model for the study of glycopeptide efficacy in GISA infections

In recent years, the emergence of Staphylococcus aureus strains with reduced susceptibility to glycopeptides has raised considerable concern. We studied the efficacy of vancomycin and teicoplanin, as well as cloxacillin and cefotaxime, against the infection caused by four S. aureus strains with different glycopeptide and β-lactam susceptibilities (strains A, B, C, and D; MICs for vancomycin of 1, 2, 4, and 8 µg/ml respectively), using a modified model of mouse peritonitis. This optimized model appeared to be straightforward and reproducible, and was able to detect low differences in bacterial killing between antibiotics and also between different S. aureus strains. Bactericidal activities in peritoneal fluid for vancomycin, teicoplanin, cloxacillin, and cefotaxime decreased from -2.98, -2.36, -3.22, and -3.57 log10 cfu/ml, respectively, in infection by strain A (MICs for vancomycin and cloxacillin of 1 and 0.38 µg/ml, respectively) to -1.22, -0.65, -1.04, and +0.24 in peritonitis due to strain D (MICs for vancomycin and cloxacillin of 8 and 1,024 µg/ml). Our data confirm the superiority of β-lactams against methicillin-susceptible S. aureus and show that bactericidal activity of glycopeptides decreases significantly with slight increases in MICs; this finding suggests a reduced efficacy of glycopeptides in the treatment of serious glycopeptide-intermediate S. aureus infections

Making SENSE - Sustained Effort Network for treatment of Status Epilepticus as a multicenter prospective registry.

BACKGROUND: Evidence regarding the different treatment options of status epilepticus (SE) in adults is scarce. Large randomized trials cover only one treatment at early stage and suggest the superiority of benzodiazepines over placebo, of intravenous lorazepam over intravenous diazepam or over intravenous phenytoin alone, and of intramuscular midazolam over intravenous lorazepam. However, many patients will not be treated successfully with the first treatment step. A large randomized trial covering the treatment of established status (ESETT) has just been funded recently by the NIH and will not start before 2015, with expected results in 2018; a trial on the treatment of refractory status with general anesthetics was terminated early due to insufficient recruitment. Therefore, a prospective multicenter observational registry was set up; this may help in clinical decision-making until results from randomized trials are available. METHODS/DESIGN: SENSE is a prospective, multicenter registry for patients treated for SE. The primary objective is to document patient characteristics, treatment modalities and in-house outcome of consecutive adults admitted for SE treatment in each of the participating centres and to identify predictors of outcome. Pre-treatment, treatment-related and outcome variables are documented systematically. To allow for meaningful multivariate analysis in the patient subgroups with refractory SE, a cohort size of 1000 patients is targeted. DISCUSSION: The results of the study will provide information about risks and benefits of specific treatment steps in different patient groups with SE at different points of time. Thus, it will support clinical decision-making and, furthermore, it will be helpful in the planning of treatment trials. TRIAL REGISTRATION: DRKS00000725.

The Influence of Chronic and Situational Social Status on Stereotype Susceptibility

We tested whether stereotypical situations would affect low-status group members' performance more strongly than high-status group members'. Experiment 1 and 2 tested this hypothesis using gender as a proxy of chronic social status and a gender-neutral task thathas been randomly presented to favor boys (men superiority condition), favor girls (women superiority condition), or show no gender preference (control condition). Both experiments found that women's (Experiment 1) and girls' performance (Experiment 2) suffered more from the evoked stereotypes than did men's and boys' ones. This result was replicated in Experiment 3, indicating that short men (low-status group) were more affected compared to tallmen (high-status group). Additionally, men were more affected compared to women when they perceived height as a threat. Hence, individuals are more or less vulnerable to identity threats as a function of the chronic social status at play; enjoying a high status provides protection and endorsing a low one weakens individual performance in stereotypical situations.

Trimodal therapy for invasive bladder cancer: is it really equal to radical cystectomy?

PURPOSE OF REVIEW: Trimodal therapy (TMT) is considered the most effective bladder-sparing approach for muscle-invasive urothelial carcinoma of the bladder (MIBC) and an alternative to radical cystectomy. The purpose of this article was to review and summarize the current knowledge on the equivalence of TMT and radical cystectomy based on the recent literature. RECENT FINDINGS: TMT consists of a maximal transuretral resection of the bladder, followed by a concurrent radiotherapy and chemotherapy, limiting salvage radical cystectomy to nonresponder tumors or muscle-invasive recurrence. In large population studies, less than 6% of the patients with nonmetastatic MIBC receive a chemoradiation therapy and this rate is stable. A growing body of evidence exists that TMT provides good oncologic outcomes with low morbidity when compared with radical cystectomy. TMT requires, however, a close follow-up because of the high risk of local recurrence and salvage radical cystectomy in up to 30% of the patients. Salvage radical cystectomy can be performed with adequate results but does not offer the same opportunity of reconstruction and functional outcomes than primary radical cystectomy. SUMMARY: Although radical cystectomy is still the treatment of reference for most of the patients with localized MIBC, TMT represents a reasonable alternative in highly selected patients. Any firm conclusion on the equivalence or superiority of one treatment to the other is still limited by the lack of randomized controlled trials and the heterogeneity of the available literature. Future studies and multidisciplinary approach are mandatory to optimize the patient selection and regimen of TMT.