Conjunctions of Among Constraints

Many existing global constraints can be encoded as a conjunction of among constraints. An among constraint holds if the number of the variables in its scope whose value belongs to a prespecified set, which we call its range, is within some given bounds. It is known that domain filtering algorithms can benefit from reasoning about the interaction of among constraints so that values can be filtered out taking into consideration several among constraints simultaneously. The present pa- per embarks into a systematic investigation on the circumstances under which it is possible to obtain efficient and complete domain filtering algorithms for conjunctions of among constraints. We start by observing that restrictions on both the scope and the range of the among constraints are necessary to obtain meaningful results. Then, we derive a domain flow-based filtering algorithm and present several applications. In particular, it is shown that the algorithm unifies and generalizes several previous existing results.Comment: 15 pages plus appendi

Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study

Background: The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing). Methods: We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800–0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50–138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants. Findings: Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53–68]; median follow-up 7·0 years [IQR 4·7–10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19–1·94) and autonomous cortisol secretion (1·77, 1·20–2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93–9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values <0·001). Interpretation: Cortisol autonomy is associated with increased all-cause mortality, particularly in women younger than 65 years. However, until results from randomised interventional trials are available, a conservative therapeutic approach seems to be justified in most patients with adrenal incidentaloma. Funding: Deutsche Forschungsgemeinschaft, Associazione Italiana per la Ricerca sul Cancro, Università di Torino

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC

Toll-like receptor evolution in birds: gene duplication, pseudogenisation and diversifying selection

Toll-like receptors (TLRs) are key sensor molecules in vertebrates triggering initial phases of immune responses to pathogens. The avian TLR family typically consists of ten receptors, each adapted to distinct ligands. To understand the complex evolutionary history of each avian TLR, we analysed all members of the TLR family in the whole genome assemblies and target sequence data of 63 bird species covering all major avian clades. Our results indicate that gene duplication events most probably occurred in TLR1 before synapsids diversified from sauropsids. Unlike mammals, ssRNA-recognising TLR7 has duplicated independently in several avian taxa, while flagellin-sensing TLR5 has pseudogenised multiple times in bird phylogeny. Our analysis revealed stronger positive, diversifying selection acting in TLR5 and the three-domain TLRs (TLR10 [TLR1A], TLR1 [TLR1B], TLR2A, TLR2B, TLR4) that face the extracellular space and bind complex ligands than in single-domain TLR15 and endosomal TLRs (TLR3, TLR7, TLR21). In total, 84 out of 306 positively selected sites were predicted to harbour substitutions dramatically changing the amino acid physicochemical properties. Furthermore, 105 positively selected sites were located in the known functionally-relevant TLR regions. We found evidence for convergent evolution acting between birds and mammals at 54 of these sites. Our comparative study provides a comprehensive insight into the evolution of avian TLR genetic variability. Besides describing the history of avian TLR gene gain and gene loss, we also identified candidate positions in the receptors that have been likely shaped by direct molecular host-pathogen co-evolutionary interactions and most probably play key functional roles in birds

An automatic footshape plantograms analysis based on a new shape-measure

In this note we present a method for recognition of flatfoot abnormality with the help of some new shape-measure describing numerically this abnormality efficient enough. The proposed measure can be easily implemented and used for automatic flatfoot level diagnosis. Experiments carried out on a number of the plantograms, analysed using the computer programme prepared by first of the authors, proved the usefulness of this new approach

Automatic plantography footprint database searching method

In this note we present a very simple database searching method for footprints of the desired flatfoot abnormality. The method is based on the new shape-measure introduced in [7]. The used measure describes flatfoot abnormalities very well, do not use reference points determined manually, so is it easily implemented for fully automatic footprints comparison task. Experiments carried out on a number of plantograms, with the help of the software prepared by the first author, approved good searching results of the described method

Fourier analysis in classification of blood cells

In the paper we present some results concerning the usage of Fourier analysis which we can successfully apply to distinguish between normal and pathological blood cells. We use special area function and different number of Fourier descriptors that are automatically calculated for all objects pointed out in an image. Calculations are performed with the help of the software made by the first author. Experiments performed on the same set of tested images as in [3] and [5] draw as to the same conclusions as there in [3] where the fractal analysis to shape has been used and in [5] where simple geometrical shape parameters have been applied. Other application of Fourier analysis one can find in [9]

Computing stable loads for pallets

This paper describes an Integer Programming model for generating stable loading patterns for the Pallet Loading Problem under several stability criteria. The results obtained during evaluation show great improvement in the number of stable patterns in comparison with results reported earlier. Moreover, most of the solved cases also ensure optimality in terms of utilization of a pallet.Logistics Distribution Packing Pallet loading

Dynamics of wheel-tyre subjected to moving oscillating force

The subject of the paper is analysis of wheel of a moving railway vehicle which is subjected to a moving oscillating force. Rail ring is treated as a beam of small curvature connected to wheel axle with a Winkler foundation. Bernoulli-Euler and Timoshenko beam model is used. Results are gained using Fourier transformation. Space and space-time graphs, showing wave propagation in subcritical and supercritical zones of excitation, concerning resonance of transverse vibrations, are included