Punzi-loss:: a non-differentiable metric approximation for sensitivity optimisation in the search for new particles.

We present the novel implementation of a non-differentiable metric approximation and a corresponding loss-scheduling aimed at the search for new particles of unknown mass in high energy physics experiments. We call the loss-scheduling, based on the minimisation of a figure-of-merit related function typical of particle physics, a Punzi-loss function, and the neural network that utilises this loss function a Punzi-net. We show that the Punzi-net outperforms standard multivariate analysis techniques and generalises well to mass hypotheses for which it was not trained. This is achieved by training a single classifier that provides a coherent and optimal classification of all signal hypotheses over the whole search space. Our result constitutes a complementary approach to fully differentiable analyses in particle physics. We implemented this work using PyTorch and provide users full access to a public repository containing all the codes and a training example.

Addition of Sn to TiNb alloys to improve mechanical performance and surface properties conducive to enhanced cell activity.

Titanium (Ti) alloys with Niobium (Nb) and Tin (Sn) were prepared in order to conduct a systematic study on the bulk and surface properties of as-cast c.p.Ti, binary Ti-40Nb and Ti-10Sn, and ternary Ti-10Nb-5Sn (at.%) to ascertain whether Sn content can be used as an enhancer for cell activity. From a metallurgy viewpoint, a range of binary and ternary alloys displaying distinctive Ti phases (i.e. ß, α', α") were achieved at room temperature. Their surface (oxide thickness and composition, roughness, contact angle) and bulk (compressive stiffness, strength, elongation, microhardness, electrical resistance) features were characterised. The same surface roughness was imparted on all the alloys, therefore substrate-cell interactions were evaluated independently from this variable. The physico-mechanical properties of the ternary alloy presented the highest strength to stiffness ratio and thereby proved the most suitable for load-bearing orthopaedic applications. From a cellular response viewpoint, their cytotoxicity, ability to adsorb proteins, to support cell growth and to promote proliferation were studied. Metabolic activity using a mouse model was monitored for a period of 12 days to elucidate the mechanism behind an enhanced proliferation rate observed in the Sn-containing alloys. It was hypothesised that the complex passivating surface oxide layer and the bulk inhomogeneity with two dominant Ti phases were responsible for this phenomenon.

No evidence for long-term carrier status of pigs after African swine fever virus infection.

This study targeted the assessment of a potential African swine fever virus (ASFV) carrier state of 30 pigs in total which were allowed to recover from infection with ASFV "Netherlands'86" prior exposure to six healthy sentinel pigs for more than 2 months. Throughout the whole trial, blood and swab samples were subjected to routine virological and serological investigations. At the end of the trial, necropsy of all animals was performed and viral persistence and distribution were assessed. Upon infection, a wide range of clinical and pathomorphological signs were observed. After an initial acute phase in all experimentally inoculated pigs, 66.6% recovered completely and seroconverted. However, viral genome was detectable in blood samples for up to 91 days. Lethal outcomes were observed in 33.3% of the pigs with both acute and prolonged courses. No ASFV transmission occurred over the whole in-contact phase from survivors to sentinels. Similarly, infectious ASFV was not detected in any of the tissue samples from ASFV convalescent and in-contact pigs. These findings indicate that the suggested role of ASFV survivors is overestimated and has to be reconsidered thoroughly for future risk assessments.

Simplifying sampling for African swine fever surveillance: Assessment of antibody and pathogen detection from blood swabs.

African swine fever (ASF) is a notifiable disease with serious socio-economic consequences that has been present in wild boar in the Baltic States and Poland since 2014. An introduction of ASF is usually accompanied by increased mortality, making fallen wild boar and hunted animals with signs of disease the main target for early warning and passive surveillance. It is difficult, however, to encourage hunters and foresters to report and take samples from these cases. A pragmatic and easy sampling approach with quick-drying swabs could facilitate this. In this study, we further evaluated the use of dry blood swabs for the detection of ASFV antibody and genome with samples from animal trials and diagnostic submissions (blood, bone and organs) from Estonia. Compared to serum samples, dried blood swabs yielded 93.1% (95% confidence interval: [83.3, 98.1]) sensitivity and 100% [95.9, 100.0] specificity in a commercial ASFV antibody ELISA. Similarly, the swabs gave a sensitivity of 98.9% [93.4, 100.0] and a specificity of 98.1% [90.1, 100.0] for genome detection by a standard ASFV p72 qPCR when compared to EDTA blood. The same swabs were tested in a VP72-antibody lateral flow device, with a sensitivity of 94.7% [85.4, 98.9] and specificity of 96.1% [89.0, 99.2] compared to the serum ELISA. When GenoTube samples tested in ELISA and LFD were compared, the sensitivity was 96.3% [87.3, 99.5] and the specificity was 93.8% [86.0, 97.9]. This study demonstrates reliable detection of ASFV antibody and genome from swabs. A field test of the swabs with decomposed wild boar carcasses in an endemic area in Estonia also gave promising results. Thus, this technique is a practical approach for surveillance of ASF in both free and endemic areas.

Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies.

Porcine epidemic diarrhea (PED) has caused tremendous losses to the United States pig industry since 2013. From 2014, outbreaks were also reported from Central Europe. To characterize the Central European PEDV strains regarding their virulence in suckling piglets, and to assess the protective effect of maternally derived antibodies (MDA), four trial groups were randomly assigned, each consisting of two pregnant sows and their litter. To induce MDA in a subset of piglets, two sows received a cell culture-adapted PEDV strain, and another two sows were inoculated with field material from German PED outbreaks. Four sows stayed naïve. Subsequently, all piglets were inoculated with the corresponding PEDV strains at an age of 3 to 6 days, and virus shedding, clinical signs and occurrence of specific antibodies were assessed. Piglets without MDA showed a morbidity of 100% and low lethality, while almost all MDA-positive piglets stayed clinically healthy and showed considerably lower virus shedding. Taken together, the Central European PEDV strains showed rather low virulence under experimental conditions, and pre-inoculation of sows led to a solid protection of their offspring. The latter is the prerequisite for a sow vaccination concept that could help to prevent PED induced losses in the piglet sector.

Biological characterization of African swine fever virus genotype II strains from north-eastern Estonia in European wild boar.

Due to its impact on animal health and pig industry, African swine fever (ASF) is regarded as one of the most important viral diseases of pigs. Following the ongoing epidemic in the Transcaucasian countries and the Russian Federation, African swine fever virus was introduced into the Estonian wild boar population in 2014. Epidemiological investigations suggested two different introductions into the southern and the north-eastern part of Estonia. Interestingly, outbreak characteristics varied considerably between the affected regions. While high mortality and mainly virus-positive animals were observed in the southern region, mortality was low in the north-eastern area. In the latter, clinically healthy, antibody-positive animals were found in the hunting bag and detection of virus was rare. Two hypotheses could explain the different behaviour in the north-east: (i) the frequency of antibody detections combined with the low mortality is the tail of an older, so far undetected epidemic wave coming from the east, or (ii) the virus in this region is attenuated and leads to a less severe clinical outcome. To explore the possibility of virus attenuation, a re-isolated ASFV strain from the north-eastern Ida-Viru region was biologically characterized in European wild boar. Oronasal inoculation led to an acute and severe disease course in all animals with typical pathomorphological lesions. However, one animal recovered completely and was subsequently commingled with three sentinels of the same age class to assess disease transmission. By the end of the trial at 96 days post-initial inoculation, all animals were completely healthy and neither virus nor viral genomes were detected in the sentinels or the survivor. The survivor, however, showed high antibody levels. In conclusion, the ASFV strain from north-eastern Estonia was still highly virulent but nevertheless, one animal recovered completely. Under the experimental conditions, no transmission occurred from the survivor to susceptible sentinel pigs.

In vivo conditioning of acid-base equilibrium by crystalloid solutions: an experimental study on pigs.

PURPOSE: Large infusion of crystalloids may induce acid-base alterations according to their strong ion difference ([SID]). We wanted to prove in vivo, at constant PCO(2), that if the [SID] of the infused crystalloid is equal to baseline plasma bicarbonate, the arterial pH remains unchanged, if lower it decreases, and if higher it increases. METHODS: In 12 pigs, anesthetized and mechanically ventilated at PCO(2) ≈40 mmHg, 2.2 l of crystalloids with a [SID] similar to (lactated Ringer's 28.3 mEq/l), lower than (normal saline 0 mEq/l), and greater than (rehydrating III 55 mEq/l) baseline bicarbonate (29.22 ± 2.72 mEq/l) were infused for 120 min in randomized sequence. Four hours of wash-out were allowed between the infusions. Every 30 min up to minute 120 we measured blood gases, plasma electrolytes, urinary volume, pH, and electrolytes. Albumin, hemoglobin, and phosphates were measured at time 0 and 120 min. RESULTS: Lactated Ringer's maintained arterial pH unchanged (from 7.47 ± 0.06 to 7.47 ± 0.03) despite a plasma dilution around 12%. Normal saline caused a reduction in pH (from 7.49 ± 0.03 to 7.42 ± 0.04) and rehydrating III induced an increase in pH (from 7.46 ± 0.05 to 7.49 ± 0.04). The kidney reacted to the infusion, minimizing the acid-base alterations, by increasing/decreasing the urinary anion gap, primarily by changing sodium and chloride concentrations. Lower urine volume after normal saline infusion was possibly due to its greater osmolarity and chloride concentration as compared to the other solutions. CONCLUSIONS: Results support the hypothesis that at constant PCO(2), pH changes are predictable from the difference between the [SID] of the infused solution and baseline plasma bicarbonate concentration.

Accuracy of finite element predictions in sideways load configurations for the proximal human femur.

Subject-specific finite element models have been used to predict stress-state and fracture risk in individual patients. While many studies analysed quasi-axial loading configurations, only few works simulated sideways load configurations, such as those arising in a fall. The majority among these latter directly predicted bone strength, without assessing elastic strain prediction accuracy. The aim of the present work was to evaluate if a subject-specific finite element modelling technique from CT data that accurately predicted strains in quasi-axial loading configurations is suitable to accurately predict strains also when applying low magnitude loads in sideways configurations. To this aim, a combined numerical-experimental study was performed to compare finite element predicted strains with strain-gauge measurements from three cadaver proximal femurs instrumented with sixteen strain rosettes and tested non-destructively under twelve loading configurations, spanning a wide cone (0-30° for both adduction and internal rotation angles) of sideways fall scenarios. The results of the present study evidenced a satisfactory agreement between experimentally measured and predicted strains (R(2) greater than 0.9, RMSE% lower than 10%) and displacements. The achieved strain prediction accuracy is comparable to those obtained in state of the art studies in quasi-axial loading configurations. Still, the presence of the highest strain prediction errors (around 30%) in the lateral neck aspect would deserve attention in future studies targeting bone failure.

Optimized biogas-fermentation by neural network control.

In this work several feed-forward back-propagation neural networks (FFBP) were trained in order to model, and subsequently control, methane production in anaerobic digesters. To produce data for the training of the neural nets, four anaerobic continuous stirred tank reactors (CSTR) were operated in steady-state conditions at organic loading rates (Br) of about 2 kg x m(-3) x d(-1) chemical oxygen demand (COD), and disturbed by pulse-like increase of the organic loading rate. For the pulses additional carbon sources were added to the basic feed (surplus- and primary sludge) to simulate cofermentation and to increase the COD. Measured parameters were: gas composition, methane production rate, volatile fatty acid concentration, pH, redox potential, volatile suspended solids and COD of feed and effluent. A hierarchical system of neural nets was developed and embedded in a Decision Support System (DSS). A 3-3-1 FFBP simulated the pH with a regression coefficient of 0.82. A 9-3-3 FFBP simulated the volatile fatty acid concentration in the sludge with a regression coefficient of 0.86. And a 9-3-2 FFBP simulated the gas production and gas composition with a regression coefficient of 0.90 and 0.80 respectively. A lab-scale anaerobic CSTR controlled by this tool was able to maintain a methane concentration of about 60% at a rather high gas production rate of between 5 to 5.6 m3 x m(-3) x d(-1).

Modelling of the production of gaseous by-products in anaerobic digestion.

Goal of the EU-Project AMONCO (Advanced Prediction, Monitoring and Controlling of Anaerobic Digestion Processes Behaviour towards Biogas Usage in Fuel Cells) is demonstration of the practical use of biogas in fuel cells. The right precondition is a biogas quality which fits into the fuel cells tolerances. Therefore the mission of the workgroup Environmental biotechnology is to control anaerobic digestion in a way that production of potential harmful by-products for fuel cells is reduced. A good understanding of the production of these by products is essential for an applicable decision support tool. This poster presents the modelling of hydrogen sulfide by means of hierarchical neural networks and a classical mathematical method.

A fuzzy logic approach to control anaerobic digestion.

One of the goals of the EU-Project AMONCO (Advanced Prediction, Monitoring and Controlling of Anaerobic Digestion Process Behaviour towards Biogas Usage in Fuel Cells) is to create a control tool for the anaerobic digestion process, which predicts the volumetric organic loading rate (Bv) for the next day, to obtain a high biogas quality and production. The biogas should contain a high methane concentration (over 50%) and a low concentration of components toxic for fuel cells, e.g. hydrogen sulphide, siloxanes, ammonia and mercaptanes. For producing data to test the control tool, four 20 l anaerobic Continuously Stirred Tank Reactors (CSTR) are operated. For controlling two systems were investigated: a pure fuzzy logic system and a hybrid-system which contains a fuzzy based reactor condition calculation and a hierachial neural net in a cascade of optimisation algorithms.

Replacing oxamniquine by praziquantel against Schistosoma mansoni infection in a rural community from the sugar-cane zone of Northeast Brazil: an epidemiological follow-up.

A group of 52 villagers was followed-up for three years regarding Schistosoma mansoni infection. All villagers were periodically surveyed by the Kato-Katz method. In March 1997 and March 1998 the positives were treated with oxamniquine (15-20 mg/kg), and in March 1999, with praziquantel (60 mg/kg). All infection indices decreased substantially between March 1999 and March 2000: prevalence of infection (from 32.7% to 21.2%), prevalence of moderate/heavy infection (from 7.7% to 1.9%), intensity of infection (from 23.1 epg to 7.4 epg) and reinfection (from 35.7% to 14.3%). Negativation increased from 53.8 to 82.4. An optimistic prognostic is assumed in the short term for the introduction of praziquantel in the study area.

Oxidative metabolism in cultured fibroblasts derived from sporadic Alzheimer's disease (AD) patients.

Fibroblasts from Alzheimer's disease (AD) patients displayed decreased cytochrome c oxidase (complex IV) activity (P < 0.05). The basal oxygen consumption rate (QO2) and the response to an uncoupler of oxidative phosphorylation did not differ between AD and control fibroblasts. The QO2 of AD fibroblasts was more susceptible (P < 0.05) to inhibition by azide in the range 0.5-5 mM. The basal intracellular pH (pHi) in AD fibroblasts was significantly more acidic than in control ones. The results support the hypothesis that subtle dysfunctions of oxidative energy-producing processes are present in fibroblasts from sporadic AD patients. The alterations observed scantly influence the fibroblasts functioning even in stressful conditions; however in tissues, such as the brain, that rely heavily on oxidative metabolism for their function, similar alterations may trigger molecular mechanisms leading to cell damage.

Endoscopic ultrasonography in the diagnosis of gastric submucosal tumor.

Endoscopic ultrasonography contributed to a correct diagnosis in 24 of 25 patients with gastric submucosal tumor, including 10 extrinsic compressions and 14 intraparietal growths. Leiomyoma and lipoma were easily recognized. In one case, an unusual group of gastric varices was clearly differentiated from a pedunculated polyp prior to polypectomy. In gastric submucosal tumors, endoscopic ultrasonography can greatly reduce the need for aggressive and risky biopsy techniques or exploratory laparotomy.

Primary gastric lymphoma versus gastric carcinoma: endoscopic US evaluation.

Endoscopic ultrasonography (US) enables high-resolution imaging of the stomach and can demonstrate the different layers of the gastric wall. It has therefore been proposed for use in evaluating the extension of gastric neoplasms. It was performed in nine patients with primary gastric non-Hodgkin lymphoma and in 36 with gastric carcinoma. The US and pathologic findings were correlated in three surgical specimens of gastric lymphoma. Three different US patterns were found in gastric lymphomas: a polypoid pattern (two cases), localized (two cases) or extended (five cases) hypoechoic infiltration, and thickening with superficial ulcerations. Infiltration was confined to the second and third layers of the gastric wall in six cases and was transmural in three. The study of the gastric lymphoma specimens confirmed the accuracy of US in demonstrating the extent of infiltration. Gastric carcinomas had a more echogenic pattern and a different trend of diffusion, with no extended longitudinal hypoechoic infiltration of the superficial layers or extended hypoechoic transmural infiltration.

Sonographic evaluation of the portal venous system after elective endoscopic sclerotherapy of esophageal varices.

In order to evaluate possible changes in the portal venous system after endoscopic sclerosis of esophageal varices, 25 cirrhotic patients underwent abdominal ultrasonography before the first session of sclerotherapy and after eradication of esophageal varices had been achieved. The caliber of the portal, splenic, and superior mesenteric veins was measured sonographically in each case. Sonographic results were compared statistically before and after sclerotherapy. Neither evidence of significant variations in the caliber of the portal veins nor thrombotic obliteration was seen. These results support the view that sclerotherapy has no significant negative side effects on the portal venous system.

Technique of endoscopic ultrasonography investigation: esophagus, stomach and duodenum.

Endoscopic ultrasonography (EUT) allows a better sonographic image of the internal organs. Moreover, it is possible for the first time to explore the upper GI tract wall. To achieve this, three methods are available: 1) direct apposition of the transducer on the mucosa; 2) contact of a small balloon filled with water over the tip of the ultrasonic probe; 3) direct instillation of water. The esophageal wall is explored with the first and second method; the gastric wall is best explored with the third method; the duodenal wall is explored with the second or the third method. Exploration of esophagus and stomach has been achieved in 100% of cases, duodenal exploration in 72% of cases. No complications occurred in this study.

Detection of portal hypertension and esophageal varices by means of endoscopic ultrasonography.

Endoscopic ultrasonography (EUT) enables not only the visualization of the portal system and of the esophageal varices, as obtained by transabdominal ultrasonography and fiberoptic endoscopy, but also the visualization of intramural and periesophageal collateral veins. Fifteen cirrhotic patients were examined by EUT without complications. When present, esophageal or gastric varices were always detected. In all cases enlarged extrinsic periesophageal veins were visualized, and in 14 of 15 their caliber was correlated with the size of esophageal varices. In three patients examined after sclerotherapy the submucosal veins had disappeared, but extrinsic collateral vessels were patent. EUT will probably become a fundamental technique in the study of portal hypertension and esophageal varices, before and after therapy.