Invertibility Conditions for Floating-Point Formulae

Automated reasoning procedures are essential for a number of applications that involve bit-exact floating-point computations. This paper presents conditions that characterize when a variable in a floating-point constraint has a solution, which we call invertibility conditions. We describe a novel workflow that combines human interaction and a syntax-guided synthesis (SyGuS) solver that was used for discovering these conditions. We verify our conditions for several floating-point formats. One implication of this result is that a fragment of floating-point arithmetic admits compact quantifier elimination. We implement our invertibility conditions in a prototype extension of our solver CVC4, showing their usefulness for solving quantified constraints over floating-points

Diffusion MRI Findings in Encephalopathy Induced by Immunosuppressive Therapy after Liver Transplantation

Neurological complications are common after liver transplantation, as they affect up to one-third of the transplanted patients and are associated with significant morbidity. The introduction of calcineurin inhibitors, cyclosporine A and tacrolimus, in immunosuppressive regimens significantly improved the outcome of solid-organ transplantation even though immunosuppression-associated neurotoxicity remains a significant complication, particularly occurring in about 25% of cases after liver transplantation. The immunosuppressant cyclosporine A and tacrolimus have been associated with the occurrence of major neurological complications, diffuse encephalopathy being the most common. The biochemical and pathogenetic basis of calcineurin inhibitors-induced neurotoxicity are still unclear although several mechanisms have been suggested. Early recognition of symptoms could help reduce neurotoxic event. The aim of the study was to evaluate cerebral changes through MRI, in particular with diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps, in two patients undergoing liver transplantation after immunosuppressive therapy. We describe two patients in which clinical pictures, presenting as a severe neurological condition, early after orthotopic liver transplantation during immunosuppression therapy, showed a different evolution in keeping with evidence of focal-multifocal lesions at DWI and ADC maps. At clinical onset, DWI showed hyperintensity of the temporo-parieto-occipital cortex with normal ADC values in the patient with following good clinical recovery and decreased values in the other one; in the latter case, MRI abnormalities were still present after ten days, until the patient's exitus. The changes in DWI with normal ADC may be linked to brain edema with a predominant vasogenic component and therefore reversible, while the reduction in ADC is due to cytotoxic edema and linked to more severe, nonreversible, clinical picture. Brain MRI and particularly DWI and ADC maps provide not only a good and early representation of neurological complications during immunosuppressant therapy but can also provide a useful prognostic tool on clinical outcome of the patient

Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients.

C-fibres probably represent the common final pathway in both ACE inhibitors and neoplastic cough. A recent report demonstrated that inhaled sodium cromoglycate is an effective treatment for ACE inhibitors' cough; this effect might be due to the suppression of afferent unmyelinated C-fibres. We tested the hypothesis that inhaled sodium cromoglycate might also be effective in lung cancer patients who presented with irritative neoplastic cough. Twenty non-small-cell lung cancer (NSCLC) patients complaining of cough resistant to conventional treatment were randomised to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. Patients recorded cough severity daily, before and during treatment, on a 0 to 4 scale. The efficacy of treatment was tested with the Mann-Whitney U-test for non-parametric measures, comparing the intergroup differences in the measures of summary of symptom scores calculated in each patient before and after treatment. We report that inhaled sodium cromoglycate can reduce cough, also in NSCLC patients and that such reduction, observed in all patients treated, is statistically significant (P < 0.001). Inhaled sodium cromoglycate appears to be a cost-effective and safe treatment for lung cancer-related cough

Should the visceral peritoneum at the bladder flap closed at caesarean sections a post partum sonographic and clinical assessment?

Objective. To compare cesarean section (CS) using open or closed visceral peritoneum of the bladder flap (BF) in relation to fluid collection in vesico-uterine space (VUS) by ultrasound (US) and clinical outcome. Material and methods. A prospective cohort of repeat CS in 474 in advanced first and second stage of labor was studied. All women underwent a Misgav Ladach CS, in local combined anesthesia. These were divided into two groups by surgical management of the BF at the time of CS: Group I (n?262), with visceral peritoneum left open and Group II (n?212), with visceral peritoneum closed. An US check for the fluid collections in the VUS was done in the third post-operative day. The two groups were also clinically compared for: intra-operative estimated blood loss, the need for post-CS pain killers, febrile morbidity and duration of hospital stay. Results. Visceral peritoneum (VP) closure resulted in a significant increase blood collections in the VUS (p50.05). VP closure resulted in a significantly higher morbidity in all the following parameters. Rate of BFHs, post-operative fever, need for post-operative analgesia, require antibiotic administration and prolonged hospitalisation (p50.05). Conclusions. VP suturing of women requiring CS for dystocia is associated to increased rate of blood collection in the VUS, which could possibly explain the higher rate of puerperal complications in these patients. These data clearly indicate that suturing the VP of the BF in women undergoing CS for dystocia is contraindicated. This data could be probably extrapolated to all cesarean deliveries

The Biological Relevance of NHERF1 Protein in Gynecological Tumors

Gynecological cancer management remains challenging and a better understanding of molecular mechanisms that lead to carcinogenesis and development of these diseases is needed to improve the therapeutic approaches. The Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein that contains modular protein-interaction domains able to interact with molecules with an impact on carcinogenesis and cancer progression. During recent years, its involvement in gynecological cancers has been explored, suggesting that NHERF1 could be a potential biomarker for the development of new targeted therapies suitable to the management of these tumors. This comprehensive review provides an update on the recent study on NHERF1 activity and its pathological role in cervical and ovarian cancer, as well as on its probable involvement in the therapeutic landscape of these cancer types

Auditory time thresholds in the range of milliseconds but not seconds are impaired in ADHD

The literature on time perception in individuals with ADHD is extensive but inconsistent, probably reflecting the use of different tasks and performances indexes. A sample of 40 children/adolescents (20 with ADHD, 20 neurotypical) was engaged in two identical psychophysical tasks measuring auditory time thresholds in the milliseconds (0.25–1 s) and seconds (0.75–3 s) ranges. Results showed a severe impairment in ADHD for milliseconds thresholds (Log10BF = 1.9). The deficit remained strong even when non-verbal IQ was regressed out and correlation with age suggests a developmental delay. In the seconds range, thresholds were indistinguishable between the two groups (Log10BF = − 0.5) and not correlated with milliseconds thresholds. Our results largely confirm previous evidence suggesting partially separate mechanisms for time perception in the ranges of milliseconds and seconds. Moreover, since the evidence suggests that time perception of milliseconds stimuli might load relatively less on cognitive control and working memory, compared to longer durations, the current results are consistent with a pure timing deficit in individuals with ADHD

The economic benefit of timely, adequate, and adherence to Parkinson's disease treatment: the Value of Treatment Project 2

Background: Parkinson's disease (PD) is a chronic progressive neurological disorder with a high psychosocial and economic burden. As part of the European Brain Council (EBC)-led Value of Treatment project, this study aimed to capture the economic benefit of timely, adequate, and adherence to PD treatment. Methods: The EBC Value of Treatment Initiative combined different stakeholders to identify unmet needs in the patients’ journey according to Rotterdam methodology. The economic evaluation focused on three major topics identified as major gaps: start of treatment; best treatment for advanced disease; and adherence to treatment. Two separate healthcare systems (Germany and the UK) were chosen. Cost-effectiveness was determined by using decision-analytical modelling approaches. Effectiveness was expressed as quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio (ICER). Results: Treatment intervention in PD was found to be cost-effective regardless of the initial health state of the patient receiving the treatment. Cost savings were between -€1000 and −€5400 with 0.10 QALY gain and -€1800 and -€7600 with 0.10 QALY gain for Germany and the UK, respectively. Treatment remains cost-effective within the National Institute for Health and Care Excellence thresholds. Availability of adequate treatment to more patients was also found to be cost-effective, with an ICER of €15,000–€32,600 across country settings. Achieving the target adherence to treatment would generate cost-savings of €239,000–€576,000 (Germany) and €917,000–€2,980.000 (UK) for every 1,000 patients treated adequately. Conclusions: The analyses confirmed that timely, adequate, and adherence to PD treatment will not only improve care of the patients but is also cost-effective across healthcare systems. Further studies with a distinct identification of gaps in care are necessary to develop better and affordable care