High sensitivity tool for geophysical applications: a geometrically locked ring laser gyroscope.

We demonstrate that a middle sized ring laser gyroscope (RLG) can be a very sensitive and robust instrument for rotational seismology, even if it operates in a quite noisy environment. The RLG has a square cavity, 1.60×1.60m 2, and it lies in a plane orthogonal to the Earth's rotational axis. The Fabry-Perot optical cavities along the diagonals of the square were accessed, and their lengths were locked to a reference laser. Through a quite simple locking circuit, we were able to keep the sensor fully operative for 14 days. We verified that the prototype properties are compatible with the seismic requirements. The obtained long term stability is of the order of 3 nanorad/s, and the short term sensitivity is close to 2n a n o r a d/s⋅H z -1/2. These results are limited only by the noisy environment; our laboratory is located in a building downtown.

Analysis of 90 day operation of the GINGERINO gyroscope.

Gyroscopes IN GEneral Relativity (GINGER) is a proposed experiment with the aim of measuring in a ground laboratory the gravitoelectric and gravitomagnetic effects foreseen by general relativity through an array of ring laser gyroscopes. GINGERINO is a square ring-laser prototype that has been built to investigate the level of noise inside the Gran Sasso underground laboratory. GINGERINO has shown the advantage of the underground location. Now it provides suitable data for geophysics and seismology. Since May 2017, it has continuously acquired data. The analysis of the first 90 days shows that the duty cycle is higher than 95%, and the quantum shot noise limit is of the order of 10-10(rad/s)/Hz. It is located in a seismically active area, and it recorded part of the central Italy earthquakes. Its high sensitivity in the frequency band of fraction of hertz makes it suitable for seismology studies. The main purpose of the present analysis is to investigate the long-term response of the apparatus. Simple and fast routines to suppress the disturbances coming from the laser have been developed. The Allan deviation of the raw data reaches some 10-6 after about 106 s of integration time, while the processed data show an improvement of 1 order of magnitude. Disturbances at the daily time scale are present in the processed data, and the expected signal induced by polar motion and solid Earth tides is covered by those disturbances.

Analysis of 90 day operation of the GINGERINO gyroscope: publisher's note.

This publisher's note identifies a figure error in Appl. Opt.57, 5844 (2018)APOPAI0003-693510.1364/AO.57.005844.

Acquired partial lower urinary tract obstruction caused by intravesical ureterocele in an adult dog.

Ureterocele is an uncommon condition in dogs characterised by a cystic dilation of the submucosal portion of the distal ureter. A 4-year-old intact male Siberian husky with a 4-month previous diagnosis of ureterocele was presented for pollakiuria. Abdominal ultrasound showed increased dimensions of the ureterocele, and a retrograde positive contrast urethrocystography detected a filling defect of the bladder neck lumen. The position of ureterocele was considered responsible for the partial urinary obstruction. This hypothesis is supported by the resolution of pollakiuria after surgical ureterocele resection. Based on a literature search, this is the first case of an intravesical ureterocele causing partial urinary obstruction in dogs. Ureterocele should be considered as a differential diagnosis in patients with pollakiuria.

Patients with profuse hair shedding may reveal anagen hair dystrophy: a diagnostic clue of alopecia areata incognita.

BACKGROUND: Several patients, especially women, seek advice because of hair loss. They may be diagnosed clinically as having telogen effluvium (TE) or androgenetic alopecia (AGA), but histopathology may reveal that a proportion of them have in fact alopecia areata incognita (AAI). OBJECTIVES: To detect dystrophic anagen hairs in such patients. METHODS: We studied 1932 patients with hair loss and no signs of classical alopecia areata. They were submitted to the modified wash test (which counts the total number of telogen hairs lost and the percentage of vellus hairs) and divided into patients having pure TE (403), patients with AGA+TE (1235) and patients with pure AGA (294). Dystrophic hairs were detected with a low magnification microscope. RESULTS: Dystrophic hairs were observed in 13 patients with TE (3.2%), in 54 with AGA+TE (4.4%) and in none with AGA. In addition, 7 patients with TE and 32 with AGA+TE developed small patches of alopecia areata in 6 to 9 weeks. No patches developed in patients with AGA. CONCLUSIONS: The presence of dystrophic hairs and the development of patches of alopecia areata (and their absence in pure AGA) provide a first evidence of the possibility that within the heterogenous condition named TE some patients have in fact AAI.

Vicilin from Anadenanthera colubrina Seeds: An alternative tool to combat Callosobruchus maculatus.

Vicilins are seed proteins, and they constitute 70-80% of the total protein in leguminous seeds; with amolecular mass between 150 and 190 kDa, they are composed of subunits without disulfide bridges, with high affinity for chitin-binding. They are also associated with seed defense against insect pests. The chitin-binding vicilin from Anadenanthera colubrina seeds was purified by ammonium sulfate, followed by affinity chromatography on a chitin column, molecular exclusion on Superdex 75 Tricorn in FPLC system and Phenomenex C8 chromatography in HPLC system. The A. colubrina vicilin, named AcV, is a tetrameric glycoprotein composed of 1.55% carbohydrates and molecular weight determined by SDS-PAGE, consisting of 70, 73, 43 and 41 kDa. The AcV homogeneity was confirmed in native PAGE, where it was observed to be a unique band with slow mobility in this gel, with approximately 230 kDa. AcV added to the Callosobruchus maculatus diet in the bioassays resulted in a strong effect on adult emergence (ED50 of 0.096%), and in larvae caused a marked reduction in mass (WD50 of 0.32%) and lethality (LD50 of 0.33%) (w:w). The digestibility of AcV was evaluated in vitro with the digestive enzymes of larvae of C. maculatus of fourth instar, showing major fragments of 10 and 30 kDa. AcV showed reactivity against the anti-EvV antibody from Erythrina velutina vicilin. The deleterious effects of AcV are likely to be associated with the chitin-binding fragments generated by proteolysis in the bruchid gut, similarly to that found for vicilins from other leguminous plant species, Enterolobium contortisiliquum and Vigna unguiculata. AcV might be a candidate protein for a possible bioinsecticidal control of the bruchid weevil, C. maculatus.

Effects of sub-chronic exposure to palladium (as potassium hexachloro-palladate) on cytokines in male Wistar rats.

Palladium (Pd) is a heavy metal belonging to the platinum group elements. It has been shown that Pd and its compounds can cause sensitization, asthma and dermatologic disorders. In this study, Wistar rats were exposed for 3 months to 0, 1, 10, 100, and 250 ng/ml of Pd (as potassium hexachloro-palladate) in drinking water. At the end of exposure, possible changes in two type-1 cytokines [interleukin (IL)-2, interferon (INF)-gamma] and one type-2 cytokine (IL-4) in the serum were measured. After the sub-chronic exposure, analysis of variance of IL-2 and INF-gamma response shows that the difference between mean values in the groups of animals exposed reaches statistical significance for IL-2 (P = 0.001), showing a J-shaped dose-response relationship. At the higher dose of 250 ng/ml Pd, it was observed a significant increase in IL-2 production when compared with the controls. Furthermore at 1 and 10 ng/ml of Pd we observed an increase of INF-gamma production that was significant at 100 ng/ml of Pd, while at the higher dose of 250 ng/ml of Pd the response was indistinguishable from the control. At the doses investigated, Pd has been shown not to determine a modification of IL-4 response (P = 0.10). These preliminary findings indicate the need to carry out further investigations regarding the effect of other Pd compounds and the measurement of other types of cytokines both in the animal model used in our study and other models.

Detection and quantification of Anaplasma marginale DNA in blood samples of cattle by real-time PCR.

A TaqMan-based real-time PCR assay was developed for the diagnosis of Anaplasma marginale infection of cattle. The established assay was proven to be highly specific, since no cross-reactions were observed with other Anaplasma species of ruminants, including the closely related Anaplasma centrale, or other haemoparasites of ruminants (Anaplasma bovis, Anaplasma ovis, Anaplasma phagocytophilum, Babesia bovis, Babesia bigemina, Theileria annulata and Theileria buffeli). The detection limit was equal to that of nested (n)PCR (10(1) copies of standard DNA and 3 x 10(1) infected erythrocytes ml(-1) of blood). The assay was also reproducible, as shown by satisfactory low intra-assay and inter-assay coefficients of variation. Fifty-four blood samples of ruminants (cattle, n = 51; sheep, n = 2; goats, n = 1), that had been tested previously by reverse line blot (RLB) hybridisation, were subjected to an nPCR assay and the newly established real-time PCR assay. By using real-time PCR, A. marginale DNA was detected in 39/51 bovine samples, with DNA titres ranging from 3.60 x 10(3) to 5.70 x 10(8) copies ml(-1) of blood, whereas sheep and goat samples tested negative. The concordance with nPCR was 100%, whereas a unique sample that had tested negative by RLB gave positive results by nPCR and real-time PCR. The established assay could overcome the limitations of existing diagnostic methods, allowing for simultaneous detection and quantification of the A. marginale DNA in bovine blood, that is essential to support the clinical diagnosis, to assess the carrier status of the animals and to evaluate the efficacy of vaccines and antirickettsial drugs.

Are FPCIs a source of increased risk for children? Results of a multicenter, experimental study comparing children's behaviour with FPCIs and toys.

INTRODUCTION: Food Products Containing Inedibles (FPCIs) are believed to represent a source of higher choking risk in children. The aim of this study was to set up a controlled study, conducted on children aged 3-6 in a laboratory setting, in order to understand their behavior when interacting with FPCIs (with reference to mouthing activities, double nature recognition, and toy assembling ability). METHOD: The experimental phase was divided into two sessions: a FPCI session and a Toy session, to which 247 children were randomly assigned. During these sessions children were observed in order to catch their mouthing activity according to the two types of objects available to them (FPCIs and Toys). RESULTS: This study shows that: (a) children's behavior with respect to toys contained in FPCIs and toys presented alone is not significantly different; (b) children's ability to distinguish between the edible and non-edible part of the FPCI was very high; and (c) mouthing episodes of the inedible parts were negligible and comparable between FPCIs and toys presented alone. This strongly suggests that, with respect to choking risk, FPCIs are not per se distinguishable from toys containing small parts. IMPACT ON INDUSTRY: Restrictions on the sale of FPCIs with small toys exist in the U.S. market. In Europe, FPCIs are allowed to be on sale, under the condition that, in case, they will follow the general regulatory requirements of small toys packaged and sold alone. In this case, they must provide age warnings and labels. Our findings do not justify the different attention that toys in FPCIs are at times afforded by regulators when compared to "stand alone" toys.

The effects of sub-acute exposure to palladium on cytokines in male Wistar rats.

Palladium (Pd) and its compounds can cause sensitization, asthma and skin disorders. Sensitization to Pd is increasing in the European general population. In this study, Wistar rats were exposed for two weeks to 0, 1, 10,100 and 250 ng ml-1 of Pd as potassium hexachloro-palladate in drinking water. At the end of exposure, possible changes in two type-1 cytokines (IL-2, INF-gamma) and one type-2 cytokine (IL-4) in the serum were measured. Our findings suggest that, after a sub-acute exposure, a moderate level of Pd causes a strong Th2 response. This also occurs at higher concentrations. Although no effect on Th1 cells is observed up to a concentration of 250 ng/ml, a significant increase in IL-2 production is reported thereafter. These results therefore suggest that in sub-acute exposure, Pd exerts a significant immuno-modulating effect, altering the Th1/Th2 cytokine balance, even at low exposure doses. Our preliminary results indicate the need to carry out further studies to observe the effect of different types of Pd compounds and to measure other types of cytokines both in the animal model used in our study and in other models.

Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice.

We report results from a replication in second and third generation female mice of accelerated time to puberty associated with low Pb exposure levels . Mice in the 2nd generation study are offspring of mice from the initial study; the 3rd generation mice are offspring from mice in the 2nd generation study. For each generation the time to puberty onset was markedly influenced by exposure to dietary lead. Modest increases in blood lead concentration from a normal background of 2-3 to 8-13 micro g/dl delayed the onset of puberty by 10-20% from a normal of 33-35 days to about 40-43 days; reducing blood lead from 2-3 to 0.7 micro g/dl was associated with profound acceleration of puberty to 21 days, an enhancement by over 30%. This dose-response relationship, which replicates previous novel findings, has possible ecological as well as public health significance and indicates that lead is able to induce biologically significant changes at blood lead levels previously thought to be without effect.

[Biomonitoring of iridium in a urban population]. / Biomonitoraggio dell'iridio in una popolazione urbana.

Iridium (Ir) is one of the six elements collectively known as the platinum group metals. For its excellent catalytic properties, Ir was recently introduced into DeNOx, a new generation of automotive catalysts. The aim of our study was to evaluate urinary Ir levels in an urban population. A total of 122 healthy male subjects of Rome (Italy) were studied. Ir quantification in the urine samples of these subjects was carried out by sector field inductively coupled plasma mass spectrometry. The mean urinary Ir level was 10.41 ng/g creatinine (standard deviation: 9.67; 25th-75th percentile: 3,62-12,74 ng/g creatinine). The scientific community should respond to a potential increase in environmental exposure to Ir, due to its growing use as a catalyst, with very careful evaluation of the biological levels of this metal and monitoring of airborne particulate present in the life environment. Further investigation will enable researchers to confirm and integrate the findings of our present study undertaken in the context of surveillance.

First-night effect in normal subjects and psychiatric inpatients.

The goal of the present study was to evaluate the first-night effect in psychiatric inpatients using large subject samples (n > 30) in order to obtain a good statistical evaluation. Thirty-two normal subjects and 94 psychiatric inpatients (38 depressives and 56 insomniacs) were studied for three consecutive nights in the hospital sleep laboratory. Our results showed clearly that there was a first-night effect in normal subjects, similar to that reported in previously published data, characterized by a longer rapid eye movement (REM) sleep latency (p < 0.05), increased wakefulness (p < 0.01) and total sleep time (p < 0.02) and a decreased sleep efficiency (p < 0.01). REM sleep latency and stage REM in the first third of the night were still altered in the second night. Both clinical groups had a less marked first-night effect than normal subjects, showing alterations only observed in REM sleep (p < 0.01) (decreased REM sleep, longer REM sleep latency, increased REM sleep gravity center). However, the first-night effect was more pronounced in insomniacs than in depressed patients. No statistical differences between the second and third nights' recordings were found in sleep parameters. It is suggested that first-night data should not be simply discarded but could be used in subsequent analyses.

Changes in EEG power density during sleep laboratory adaptation.

First- and second-night effects on the electroencephalogram (EEG) were investigated by means of polygraphic sleep recordings and all-night spectral analysis. Eighteen normal subjects were studied for three consecutive nights in a hospital sleep laboratory. Visual sleep scoring showed that there was a first-night effect in normal subjects similar to that reported previously [increased wakefulness; decreased total sleep time, sleep efficiency, and rapid eye movement (REM) sleep]. Spectral analysis of the sleep EEG revealed important changes, most of which occurred in REM sleep. Increased delta, theta, and beta1 power densities accompanied by decreased mean frequency were seen in REM sleep in the second night. On the basis of REM sleep deprivation results previously published, our data suggest that the second night could be affected by partial REM sleep deprivation that occurred in the first night. Delta and theta power density values decreased in the first non-rapid eye movement episode of nights 1 and 2; this could result from increased REM sleep pressure. The overall consistency of spectral data in the first and second night with REM sleep findings derived from visual scoring in the first night lends further support to this hypothesis. The sleep disturbance experienced during the first night in a sleep laboratory may be a useful and valid model of transient insomnia. Therefore, we conclude that data from all nights recorded should be included in assessing a subject's sleep.

Sleep stage scoring using the neural network model: comparison between visual and automatic analysis in normal subjects and patients.

In this paper, we compare and analyze the results from automatic analysis and visual scoring of nocturnal sleep recordings. The validation is based on a sleep recording set of 60 subjects (33 males and 27 females), consisting of three groups: 20 normal controls subjects, 20 depressed patients and 20 insomniac patients treated with a benzodiazepine. The inter-expert variability estimated from these 60 recordings (61,949 epochs) indicated an average agreement rate of 87.5% between two experts on the basis of 30-second epochs. The automatic scoring system, compared in the same way with one expert, achieved an average agreement rate of 82.3%, without expert supervision. By adding expert supervision for ambiguous and unknown epochs, detected by computation of an uncertainty index and unknown rejection, the automatic/expert agreement grew from 82.3% to 90%, with supervision over only 20% of the night. Bearing in mind the composition and the size of the test sample, the automated sleep staging system achieved a satisfactory performance level and may be considered a useful alternative to visual sleep stage scoring for large-scale investigations of human sleep.

Tick-borne diseases (TBDs) of dairy cows in a Mediterranean environment: a clinical, serological, and hematological study.

A longitudinal study of tick-borne diseases (TBDs) in Southern Italy was carried out by monitoring two dairy farms (A and B) located in the Apulia Region. On each farm ten calves and ten heifers were observed monthly from May 1999 to February 2001 for clinical signs and blood parameters; antibodies against Babesia bigemina and Anaplasma marginale using an ELISA test were also monitored for the first eight months of the study. Totals of 28 and 14 cases of TBDs were observed in the complete herds of Farms A and B, respectively. Timing of disease appearance, categories of animals affected and changes in blood parameters are discussed.

In vitro and in vivo antitumor activity of the novel trinuclear platinum complex BBR 3464 in neuroblastoma.

PURPOSE: BBR 3464 is a promising new trinuclear platinum complex that has been shown to circumvent the resistance to cisplatin in a panel of tumor cell lines and xenografts with acquired or intrinsic resistance to cisplatin. The in vitro and in vivo antitumor activity of BBR 3464 was evaluated and compared with that of cisplatin in neuroblastoma. METHODS: In in vitro studies, the short- and long-term cytotoxicities, cell cycle perturbations, the ability to induce apoptosis, the intracellular platinum accumulation and DNA platination were evaluated in three neuroblastoma cell lines exposed to appropriate drug concentrations for 1 h. In in vivo studies, BBR 3464 was administered i.v. at doses of 0.30 and 0.35 mg/kg three times at intervals of 4 days (q4dx3), and cisplatin was administered i.v. according to two different schedules (at 2 and 4 mg/kg three times at intervals of 4 days and at 6 and 12 mg/kg as single doses). RESULTS: In a short-term growth inhibition assay, BBR 3464 was shown to be up to 100-fold more potent than cisplatin and it was even more potent in a clonogenic assay. The difference in the antitumor effect of BBR 3464 on the different cell lines was evident in both assays, while cisplatin exerted a comparable antitumor activity in all lines tested. Cell cycle analysis demonstrated a longer-lasting block in G2/M phase induced by BBR 3464 without the early S phase accumulation induced by cisplatin. The higher potency of BBR 3464 appeared to be unrelated to the induction of apoptosis, that was lower or at most comparable to cisplatin. Cellular platinum accumulation and platinum-DNA adduct formation following BBR 3464 exposure was higher than following cisplatin exposure. These differences may have resulted from a different mechanism of action and may explain the lack of cross-resistance with cisplatin. In xenografts of neuroblastoma, BBR 3464 was confirmed to be very potent as compared to cisplatin (MTD 0.35 mg/kg and 4 mg/kg for BBR 3464 and cisplatin, respectively). The efficacy of BBR 3464 was superior to that of cisplatin when both drugs were administered on a fractionated schedule (q4dx3), while BBR 3464 appeared equally active to 12 mg/kg cisplatin administered as a single dose. CONCLUSIONS: Our findings indicate that BBR 3464 has a definite antitumor effect in neuroblastoma lines and may be a candidate for early clinical trials in children with neuroblastoma.

Cerebrospinal fluid pharmacokinetics of carboplatin in children with brain tumors.

The pharmacokinetics of carboplatin in cerebrospinal fluid (CSF) and plasma was studied in five children with brain tumors (four medulloblastomas and one ependimoblastoma) who underwent preirradiation treatment with carboplatin. Carboplatin pharmacokinetics was studied following the administration of 600 mg/m2 as a 1-h infusion. Four children were treated a few weeks after surgery, whereas one child with an unresectable tumor was treated prior to surgery. All patients had a ventricular-peritoneal CSF shunt connected to a subcutaneous reservoir. Total platinum and free carboplatin were measured. The mean AUC values for free carboplatin in CSF and plasma were 2.29 +/- 1.20 and 8.18 +/- 1.27 mg ml-1 min, respectively. The mean ratio of CSF AUC to plasma AUC was 0.28 (range, 0.17-0.46). Both plasma peak levels and AUC values showed limited interpatient variability. On the other hand, carboplatin levels in CSF showed substantial interpatient variability, with a greater than 5-fold difference in peak levels and a 3-fold difference in AUC values being recorded. The interpatient difference in CSF pharmacokinetics may have been related at least in part to the different anatomical alterations induced by the surgical procedures or by the presence of a large tumor mass. In the four evaluable patients exhibiting macroscopic residual tumor, we observed one complete remission (CR) and two partial remissions (PR) following two cycles that consisted of two doses of 600 mg/m2 carboplatin given on 2 consecutive days (total dose, 1200 mg/m2) and were separated by a 1-month interval. These results may give some indication as to the optimal dose and schedule for carboplatin administration in the treatment of primitive neuroectodermic tumors (PNET).

Clinical pharmacokinetics of carboplatin in children.

The present study was undertaken to evaluate in children the plasma pharmacokinetics of free carboplatin given at different doses and schedules and to evaluate the inter- and intrapatient variability and the possible influence of schedule on drug exposure. A total of 35 children (age range, 1-17 years) with malignant tumors were studied. All patients had normal renal function (creatinine clearance corrected for surface body area, above 70 ml min-1 m-2; range, 71-151 ml min-1 m-2) and none had renal involvement by malignancy. Carboplatin was given at the following doses and schedules: 175, 400, 500, and 600 mg/m2 given as as a 1-h infusion; 1,200 mg/m2 divided into equal doses and infused over 1 h on 2 consecutive days; and 875 and 1,200 mg/m2 given as a 5-day continuous infusion. A total of 57 courses were studied. Carboplatin levels in plasma ultrafiltrate (UF) samples were measured both by high-performance liquid chromatography and by atomic absorption spectrophotometry. Following a 1-h infusion, carboplatin free plasma levels decayed biphasically; the disappearance half-lives, total body clearance, and apparent volume of distribution were similar for different doses. In children with normal renal function as defined by creatinemia and blood urea nitrogen (BUN) and creatinine clearance, we found at each dose studied a limited interpatient variability of the peak plasma concentration (Cmax) and the area under the concentration-time curve (AUC) and a linear correlation between the dose and both Cmax (r = 0.95) and AUC (r = 0.97). The mean value +/- SD for the dose-normalized AUC was 13 +/- 2 min m2 l-1 (n = 57).2+ The administration schedule does not seem to influence drug exposure, since prolonged i.v. infusion or bolus administration of 1,200 mg/m2 achieved a similar AUC (13.78 +/- 2.90 and 15.05 +/- 1.44 mg ml-1 min, respectively). In the nine children studied during subsequent courses a limited interpatient variability was observed and no correlation (r = 0.035) was found between AUC and subsequent courses by a multivariate analysis of dose, AUC, and course number. The pharmacokinetic parameters were similar to those previously reported in adults; however, a weak correlation (r = 0.52, P = 0.03) between carboplatin total body clearance and creatinine clearance varying within the normal range was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Altered cytokine production in mice exposed to lead acetate.

Previous investigations have shown that Pb exerts immunotoxic effects. Object of this study were Th1 and Th2-type immune responses of mice to Pb exposure. Adult Swiss male mice were administered 0, 40 and 400 mg/l of Pb (as acetate) in drinking water for 14 days. At the end of the treatment, blood Pb was determined and two Th1 cytokines (IL-2, INF-gamma) and one Th2 serum cytokine (IL-4) were measured. A significant increase in IL-4 production was observed in the mice exposed to 40 mg/l of Pb, while a further increase in IL-4 production was associated with a decrease in INF-gamma production in mice exposed to 400 mg/l of Pb. On the other hand, Pb exposure did not induce changes of serum IL-2 (involved also in the Th0 immune pattern). Our findings indicate that low level Pb exposure enhances a Th2 response. A high Pb does can either stimulate the Th2 immune activity or reduce the Th1 response; the result is an imbalance between Th1 and Th2 activation.