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.

Physical performance in kidney transplanted patients: a study on desert trekking.

Physical performance of kidney transplanted patients in challenging environments, such as deserts, has been poorly studied. Six kidney transplanted (T: 5 males, 1 female; 45±6 yrs) and 8 control (C: 5 males, 3 females; 49±13 yrs) subjects participated in a 5-day desert trek. Blood pressure, hydration status (Height2/Rz by bioimpedance), heart rate, energy expenditure (by SenseWear Pro Armband) and walking velocities were recorded during each daily trekking stage (GPS-assisted wearable devices). Systo-diastolic blood pressure did not differ between C (119/77±12/8 mmHg) and T (121/77±10/6 mmHg) groups throughout the study. The hydration status was stable from day 1 (Ht2/Rz: 64±13 cm2/Ohm in T and 59±12 cm2/Ohm in C subjects) to day 5 (66±11 cm2/Ohm in T and 61±13 cm2/Ohm in C subjects) in both groups. Two patients on steroid treatment showed a relative hyperhydration. Mean heart rate did not differ between T (135±10 bpm) and C (136±5 bpm) subjects throughout the study, although a reduction from day 1 to day 5 was observed in T subjects only (p<0.05 vs C group). No differences were found between T and C group in walking velocity (1.7±0.6 km/h in T and 1.7±0.5 km/h in C group); mean intensity of physical activity was 3.4±0.5 METs in T and 3.3±0.6 METs in C group during each trekking stage. Negligible differences were observed in cardiovascular, metabolic and hydration status adaptations to desert trekking between selected T and C individuals. T subjects with creatinine clearance > 55 ml/min showed acceptable physical performance and acclimatization to desert environment, suggesting a good long-term outcome of transplantation.

Air pollution ultrafine particles: toxicity beyond the lung.

BACKGROUND: Ultrafine particles or nanoparticles (UFPs or PM0.1) are the fraction of ambient particulates with an aerodynamic diameter smaller than 0.1 microm. Currently UFPs are emerging as the most abundant particulate pollutants in urban and industrial areas, as their exposures have increased dramatically because of anthropogenic sources such as internal combustion engines, power plants, incinerators and many other sources of thermo-degradation. Ultrafine particles have been less studied than PM2.5 and PM10 particulates, mass concentrations of particles smaller than 2.5 and 10 microm, respectively. OBJECTIVE, EVIDENCE AND INFORMATION SOURCES: We examined the current scientific literature about the health effects of ultrafine particles exposure. STATE OF THE ART: UFPs are able to inhibit phagocytosis, and to stimulate inflammatory responses, damaging epithelial cells and potentially gaining access to the interstitium. They could be responsible for consistent reductions in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in patients with asthma. Chronic exposure to UFPs can produce deleterious effects on the lung, also causing oxidative stress and enhancing pro-inflammatory effects in airways of COPD patients. Cardiovascular detrimental consequences due to UFPs exposure have observed in epidemiological studies, and could likely be explained by translocation of UFPs from the respiratory epithelium towards circulation and subsequent toxicity to vascular endothelium; alteration of blood coagulation; triggering of autonomic nervous system reflexes eventually altering the cardiac frequency and function. Once deposited deeply into the lung, UFPs--in contrast to larger-sized particles--appear to access to the blood circulation by different transfer routes and mechanisms, resulting in distribution throughout the body, including the brain, with potential neurotoxic consequences. PERSPECTIVES AND CONCLUSIONS: UFPs represent an area of toxicology of emerging concern. A new concept of environmental medicine would help in understanding not only the environmental mechanisms of disease, but also in developing specific preventive or therapeutic strategies for minimizing the dangerous influence of pollution on health.

Brittle asthma.

Brittle asthma is a rare form of severe asthma characterized by a wide variation of Peak Expiratory Flow (PEF), in spite of heavy doses of steroides. Brittle asthmatic patients had very serious and often, life threatening, attacks. Type 1 brittle asthma is characterized by a mantained PEF variability despite therapy, and it affected mostly female, aged between 15 and 55 years. Type 1 is associated to skin prick tests positivity and food intolerance. Several studies have referred a correlation with personality disorders. The patients affected with type 1 have high morbidity, and frequently they have hospital admission for assessment and stabilitation their asthmatic condition. Type 2 brittle asthma is characterized by acute attacks that are very severe and could led to death or mechanical ventilation for respiratory insufficiency. Brittle asthma is very difficult to recognize and to treat. In type 1 brittle asthma, the therapy is based on inhaled and/or oral steroids, and beta2-agonists, used with an inhaler or with subcutaneous infusion. The patients affected with type 1 had to be nearly monitered and treated. Patients affected with type 2 brittle asthma, are mostly free by simptoms, but they have severe attacks that led them to emergency treatment. Brittle asthma is a rare form of severe asthma, that the clinicians may recognize and treat very strictly, because of high morbidity and mortality.

Novel natural products from soil DNA libraries in a streptomycete host.

As a route to accessing the potential chemical diversity of uncultivable microbes from the soil, combinatorial biosynthetic libraries were constructed by cloning large fragments of DNA isolated from soil into a Streptomyces lividans host. Four novel compounds, terragines A (1), B (2), C (3), and D (4), were isolated from recombinant 436-s4-5b1, and another novel compound, terragine E (5), was isolated from 446-s3-102g1. The structures were determined by a combination of spectroscopic techniques, primarily 2D NMR.

Macrolide biosynthesis: a single cytochrome P450, PicK, is responsible for the hydroxylations that generate methymycin, neomethymycin, and picromycin in Streptomyces venezuelae.

The final step in the biosynthesis of methymycin, neomethymycin, and picromycin is an hydroxylation, shown to be carried out by the cytochrome P-450 monooxygenase, PicK. Direct comparison of the relative Kcat/K(m) values for the two substrates, YC-17 and narbomycin, showed a threefold rate preference of picK for narbomycin.

Respiratory allergy to Cupressus sempervirens in Rome.

Mediterranean Cypress pollen is the major aerospore component in winter and early spring. Several recent studies have assessed the incidence of respiratory allergy to this pollen. A personal series of patients encountered in 1994-96 revealed a 9.33% incidence of positive prick-test responses to Cypress pollen among a population with atopical status. That series included 16 (19.05%) single and 68 (80.95%) multiple allergy sufferers. Among the former the symptoms encountered were rhinitis (62.5%) and asthma (37.5%). Given the ever-increasing incidence of Cypress pollen allergy, there is a need to restrict the planting of the tree for ornamental purposes, especially in areas with a high pollen count.

[Study of spontaneous resolution of bronchial spasm after methacholine challenge. Comparison of patients with different degree of hyperreactivity]. / Studio della risoluzione spontanea del broncospasmo dopo PD con metacolina. Confronto tra pazienti con iperreattività di diverso grado.

The study was designed to assess the spontaneous recovery of bronchial spasm induced by methacholine in bronchial challenge tests and to examine the mechanisms and the modalities involved as well as the influence of dosage. The phenomenon was analysed in 32 hyperreactive patients diagnosed as asthmatics by measuring FEV1 as soon as maximum bronchial constriction (PD20) had been achieved and after 5, 10, 15, 30 and 60 minutes. The data obtained were subjected to variance analysis. Results show: 1) as regards duration of spontaneous recovery, that FEV1 returned to pre-challenge levels after 60 minutes in both the severely and moderately hyperreactive patients; 2) as regards onset of regression, that onset depended on the level of sensitivity, occurring after 30 minutes in the severely affected, after 15 minutes in the mild cases; 3) as regards recovery intensity, that in the moderated cases the recovery was more pronounced in the first 15 minutes than subsequently. Data show that the onset and intensity of the spontaneous recovery change according to the degree of sensitivity. That might reflect a greater affinity and/or bonding of methacholine in the muscarinic receptors of the severely affected, but the possibility of a difference in mediator metabolization speed cannot be excluded. In conclusion, research into the recovery of bronchial spasm may contribute to a better understanding of bronchial hypersensitivity and provide new information of value on the diagnosis, pathogenesis and treatment of the condition.

Respiratory allergy to parietaria pollen in 348 subjects.

We have revisited 348 records of allergic outpatients to Parietaria, ratio M/F 1:1 and mean age 29.46 +/- 12.49 yrs. 97 of them were skin positive to Parietaria only (A-group: M/F 37/60); 251 patients were skin positive also to other allergens (B-group: M/F 137/114). Mean age of A-group patients (35.41 +/- 12.91) was higher than B-group (27.16 +/- 11.54; p < 001). Dividing mono and polysensitized subjects by age decade, a different distribution was found between the two groups (p < 001): monosensitized patients showed an increasing number of subjects from the 3rd to the 4th decade and a decreasing trend in the following decades; polysensitized patients showed a prevalence in age < 20 yrs and a decreasing trend in the other decades. In B-group Gramineae were the most frequent allergens associated to Parietaria (84.8%) followed by Olea Europaea (41.1%), Dermatophagoides farinae (37.4%) and Dermatophagoides pteronyssinus (36.2%). Main symptoms were rhinoconjunctivitis (187 cases), rhinitis + asthma (141 cases) and bronchial asthma (20 cases). Comparing the clinical features of the two groups, we have found that monosensitized patients showed a female prevalence, a prevalence of rhinitis with late onset of symptoms while in patients suffering from isolated asthma the onset was early.

Prick and intradermal tests compared with specific IgE in allergic assessment.

Allergic assessment in symptomatic patients often requires more tests and they can be conflicting. Sixty outpatients, suffering from seasonal or periannal respiratory symptoms, underwent prick tests, intradermal reactions and specific IgE (IgEs) determination by enzime immunoassay for eight common allergens; in addition total IgE were measured. At the end of the study 512 tests were performed. Total serum IgE levels had no significance in the results. There was a statistically different behaviour among three methods; a positive or negative concordance was found in 64.1% of tests whereas in the others (35.9%) results were conflicting. In particular it was seen that a prick test positive was confirmed by intradermal reaction and a test prick and intradermal negative was not probably confirmed by IgEs. Serum specific IgE levels were higher in subjects prick and intradermal positive than in prick negative and intradermal or IgEs positive subjects. Intradermal reactions were found positive especially in mites and often they were not confirmed by prick or IgEs. So prick test is always the routine test; intradermal test ought to be used if there were prick tests negative and patient's history positive. If prick and intradermal test were found negative it is plausible that the measurement of specific IgE will be negative circumscribing even more the number of individuals where determination of serum specific antibody is necessary.

[Custom mouthguards: indications and construction]. / Paradenti individuale: indicazioni e realizzazione.

Dealing with the personal endoral protections today it is possible to choose between different methods, which present various difficulties in application, but result in being more functional and comfortable than semi-individual protections. The cost shouldn't be a determining factor in athletes wanting maximum performances. In addition, in the case of athletes with cranium-mandibular diseases, articular clicks, and other problems, the personal endoral protection, represents not only an efficient method of prevention, but serves as a therapy.

[Biochemical aspects of orthodontic movement: recent findings and trends]. / Aspetti biochimici del movimento ortodontico: recenti acquisizioni e prospettive future.

The orthodontic tooth movement produces physical and biochemical reactions in the periodontium. Tooth movements can be expressed by cell activation inducing bone resorption and remodelling. Substances as cAMP, cGMP, neuropeptides, prostaglandins and ormons play a basic role in this mechanism as mediators and modulators of the cellular responses. The Authors review the possibility to control the degree of the tooth movement acting on this biochemical process.

Superoxide anion production by circulating polymorphonuclear leucocytes in rheumatoid arthritis.

In twelve rheumatoid arthritis (RA) patients, receiving only nonsteroid anti-inflammatory therapy, superoxide anion (02-) generation by polymorphonuclear leucocytes (PMNs) was assessed by Cytochrome C reduction. The 02- production by non-activated PMNs in RA patients was significantly higher than in healthy controls. The 02- production by PMNs activated by zymosan and phorbol myristate acetate was significantly lower than in controls. PMNs from controls preincubated with rheumatoid sera generated higher 02- levels than the same PMNs incubated in normal sera.

Ultrastructural changes of collagen and elastin in human gingiva during orthodontic tooth movement.

After 15 days of mesializing or distalizing orthodontic treatment, 10 permanent premolars of young patients were extracted with the interdental gingiva. The connective tissues of the compressed or stretched interdental papillae were compared to that of untreated samples by light and transmission electron microscope. Large collagen fibres bundles represented by fibrils with a banding pattern of 64 nm and a mean diameter of 75 nm were observed in compressed interdental gingiva. Several elastic fibres with a mean diameter of 950 nm were also present. In some central areas of compressed gingiva collagen fibrils longitudinally split into widely spaced microfibrils were often observed in proximity to the elastic fibres. In stretched and untreated interdental papillae the collagen fibrils presented a mean diameter of 66 nm and 57 nm respectively. In both groups, few elastic fibres ranging in diameter 600 nm were seen. The increased size of the gingival collagen fibrils undergoing pressure and tension is indicative of remodelling of the fibrous collagen system. The fair increase in number and size of elastic fibres in compressed gingiva suggests that the elastic fibre system takes over the place whenever a collapse of the collagenous framework occurs.

The effect of general and regional anesthesia on oxygen-dependent microbicidal mechanisms of polymorphonuclear leukocytes in children.

The microbicidal activity of polymorphonuclear leukocytes (PMNL) was investigated in two groups of children undergoing hernia repair surgery. Group 1, after short general halothane anesthesia, received caudal analgesia, whereas group 2 received halothane anesthesia alone. Both groups showed a decrease in singlet oxygen production as demonstrated using chemiluminescence method. However, 24 hours after the end of surgery singlet oxygen production was fully recovered in the caudal analgesia group (group 1), whereas in the general anesthesia group (group 2), production was still significantly (P less than 0.01) depressed. It is concluded that halothane may be associated with PMNL impairment, perhaps in a time-dependent manner.