Intuitive control of rolling sound synthesis

International audienceThis paper presents a rolling sound synthesis model which can be intuitively controlled. To propose this model, different aspects of the rolling phenomenon are explored : physical modeling, perceptual attributes and signal morphology. A source-filter model for rolling sounds synthesis is presented with associated intuitive controls

Talking quiescence: a rigorous theory that supports parallel composition, action hiding and determinisation

The notion of quiescence - the absence of outputs - is vital in both behavioural modelling and testing theory. Although the need for quiescence was already recognised in the 90s, it has only been treated as a second-class citizen thus far. This paper moves quiescence into the foreground and introduces the notion of quiescent transition systems (QTSs): an extension of regular input-output transition systems (IOTSs) in which quiescence is represented explicitly, via quiescent transitions. Four carefully crafted rules on the use of quiescent transitions ensure that our QTSs naturally capture quiescent behaviour. We present the building blocks for a comprehensive theory on QTSs supporting parallel composition, action hiding and determinisation. In particular, we prove that these operations preserve all the aforementioned rules. Additionally, we provide a way to transform existing IOTSs into QTSs, allowing even IOTSs as input that already contain some quiescent transitions. As an important application, we show how our QTS framework simplifies the fundamental model-based testing theory formalised around ioco.Comment: In Proceedings MBT 2012, arXiv:1202.582

Test Model Coverage Analysis under Uncertainty

In model-based testing (MBT) we may have to deal with a non-deterministic model, e.g. because abstraction was applied, or because the software under test itself is non-deterministic. The same test case may then trigger multiple possible execution paths, depending on some internal decisions made by the software. Consequently, performing precise test analyses, e.g. to calculate the test coverage, are not possible. This can be mitigated if developers can annotate the model with estimated probabilities for taking each transition. A probabilistic model checking algorithm can subsequently be used to do simple probabilistic coverage analysis. However, in practice developers often want to know what the achieved aggregate coverage, which unfortunately cannot be re-expressed as a standard model checking problem. This paper presents an extension to allow efficient calculation of probabilistic aggregate coverage, and moreover also in combination with k-wise coverage

Systematic model forecast error in Rossby wave structure

Diabatic processes can alter Rossby wave structure; consequently errors arising from model processes propagate downstream. However, the chaotic spread of forecasts from initial condition uncertainty renders it difficult to trace back from root mean square forecast errors to model errors. Here diagnostics unaffected by phase errors are used, enabling investigation of systematic errors in Rossby waves in winter-season forecasts from three operational centers. Tropopause sharpness adjacent to ridges decreases with forecast lead time. It depends strongly on model resolution, even though models are examined on a common grid. Rossby wave amplitude reduces with lead time up to about five days, consistent with under-representation of diabatic modification and transport of air from the lower troposphere into upper-tropospheric ridges, and with too weak humidity gradients across the tropopause. However, amplitude also decreases when resolution is decreased. Further work is necessary to isolate the contribution from errors in the representation of diabatic processes

Implants in the severely resorbed mandibles: whether or not to augment? What is the clinician’s preference?

Contains fulltext : 96000.pdf (publisher's version ) (Open Access)INTRODUCTION: The aim of this study is to inventory in the Netherlands which therapy is the clinician's first choice when restoring the edentulous mandible. MATERIAL AND METHODS: A questionnaire was sent to all Dutch Oral and Maxillofacial surgeons. As part of this, the surgeons were invited to treat five virtual edentulous patients, differing only in mandibular residual height. RESULTS: In cases of a sufficient residual height of 15 mm, all surgeons were in favour to insert solely two implants to anchor an overdenture. In case of a residual height of 12 mm, 10% of the surgeons choose for an augmentation procedure. If a patient was presented with a mandibular height of 10 mm, already 40% of the OMF surgeons executed an augmentation procedure. Most (80%) surgeons prefer the (anterior) iliac crest as donor site. The choice of 'whether or not to augment' was not influenced by the surgeon's age; however, the hospital, where he was trained, did. Surgeons trained in Groningen were more in favour of installing short implants in mandibles with reduced vertical height. DISCUSSION: As the option overdenture supported on two interforaminal implants is reimbursed by the Dutch health assurance, this treatment modality is very popular in the Netherlands. From a point of costs and to minimize bypass comorbidity, surgeons should be more reluctant in executing augmentation procedures to restore the resorbed edentulous mandible as it is dated in literature that also in mandibles with a residual height of 10 mm or less, solely placing implants, thus without an augmentation procedure in advance, is a reliable treatment option

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy

Background &amp; Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.</p

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy

Background &amp; Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.</p

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Background &amp; Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). Conclusions: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. Trial registration number: #NCT02900443.</p

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Background &amp; Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). Conclusions: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. Trial registration number: #NCT02900443.</p