Dynamics of magnetization at infinite temperature in a Heisenberg spin chain.

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

Stable quantum-correlated many-body states through engineered dissipation.

Engineered dissipative reservoirs have the potential to steer many-body quantum systems toward correlated steady states useful for quantum simulation of high-temperature superconductivity or quantum magnetism. Using up to 49 superconducting qubits, we prepared low-energy states of the transverse-field Ising model through coupling to dissipative auxiliary qubits. In one dimension, we observed long-range quantum correlations and a ground-state fidelity of 0.86 for 18 qubits at the critical point. In two dimensions, we found mutual information that extends beyond nearest neighbors. Lastly, by coupling the system to auxiliaries emulating reservoirs with different chemical potentials, we explored transport in the quantum Heisenberg model. Our results establish engineered dissipation as a scalable alternative to unitary evolution for preparing entangled many-body states on noisy quantum processors.

Nanowire Superinductance Fluxonium Qubit.

We characterize a fluxonium qubit consisting of a Josephson junction inductively shunted with a NbTiN nanowire superinductance. We explain the measured energy spectrum by means of a multimode theory accounting for the distributed nature of the superinductance and the effect of the circuit nonlinearity to all orders in the Josephson potential. Using multiphoton Raman spectroscopy, we address multiple fluxonium transitions, observe multilevel Autler-Townes splitting and measure an excited state lifetime of T_{1}=20 µs. By measuring T_{1} at different magnetic flux values, we find a crossover in the lifetime limiting mechanism from capacitive to inductive losses.

Survival of Mycobacterium avium subsp. paratuberculosis in the intermediate and final digestion products of biogas plants.

AIMS: To evaluate the survival of Mycobacterium avium subsp. paratuberculosis (MAP) during anaerobic digestion (AD), we studied two different biogas plants loaded with manure and slurry from paratuberculosis-infected dairy herds. METHODS AND RESULTS: Both plants were operating under mesophilic conditions, the first with a single digester and the second with a double digester. Mycobacterium avium subsp. paratuberculosis detection was performed by sampling each stage of the process, specifically the prefermenter, fermenter, liquid digestate and solid digestate stages, for 11 months. In both plants, MAP was isolated from the prefermenter stage. Only the final products, the solid and liquid digestates, of the one-stage plant showed viable MAP, while no viable MAP was detected in the digestates of the two-stage plant. CONCLUSIONS: Mycobacterium avium subsp. paratuberculosis showed a significant decrease during subsequent steps of the AD process, particularly in the two-stage plant. We suggest that the second digester maintained the digestate under anaerobic conditions for a longer period of time, thus reducing MAP survival and MAP load under the culture detection limit. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data are unable to exclude the presence of MAP in the final products of the biogas plants, particularly those products from the single digester; therefore, the use of digestates as fertilizers is a real concern related to the possible environmental contamination with MAP.

Early manifestation of arm-leg coordination during stepping on a surface in human neonates.

The accomplishment of mature locomotor movements relies upon the integrated coordination of the lower and upper limbs and the trunk. Human adults normally swing their arms and a quadrupedal limb coordination persists during bipedal walking despite a strong corticospinal control of the upper extremities that allows to uncouple this connection during voluntary activities. Here we investigated arm-leg coordination during stepping responses on a surface in human neonates. In eight neonates, we found the overt presence of alternating arm-leg oscillations, the arms moving up and down in alternation with ipsilateral lower limb movements. These neonates moved the diagonal limbs together, and the peak of the arm-to-trunk angle (i.e., maximum vertical excursion of the arm) occurred around the end of the ipsilateral stance phase, as it occurs during typical adult walking. Although episodes of arm-leg coordination were sporadic in our sample of neonates, their presence provides significant evidence for a neural coupling between the upper and lower limbs during early ontogenesis of locomotion in humans.

Corrigendum: Foot Placement Characteristics and Plantar Pressure Distribution Patterns during Stepping on Ground in Neonates.

[This corrects the article on p. 784 in vol. 8, PMID: 29066982.].

Foot Placement Characteristics and Plantar Pressure Distribution Patterns during Stepping on Ground in Neonates.

Stepping on ground can be evoked in human neonates, though it is rather irregular and stereotyped heel-to-toe roll-over pattern is lacking. Such investigations can provide insights into the role of contact- or load-related proprioceptive feedback during early development of locomotion. However, the detailed characteristics of foot placements and their association with motor patterns are still incompletely documented. We elicited stepping in 33 neonates supported on a table. Unilateral limb kinematics, bilateral plantar pressure distribution and EMG activity from up to 11 ipsilateral leg muscles were recorded. Foot placement characteristics in neonates showed a wide variation. In ~25% of steps, the swinging foot stepped onto the contralateral foot due to generally small step width. In the remaining steps with separate foot placements, the stance phase could start with forefoot (28%), midfoot (47%), or heel (25%) touchdowns. Despite forefoot or heel initial contacts, the kinematic and loading patterns markedly differed relatively to toe-walking or adult-like two-peaked vertical force profile. Furthermore, while the general stepping parameters (cycle duration, step length, range of motion of proximal joints) were similar, the initial foot contact was consistently associated with specific center-of-pressure excursion, range of motion in the ankle joint, and the center-of-activity of extensor muscles (being shifted by ~5% of cycle toward the end of stance in the "heel" relative to "forefoot" condition). In sum, we found a variety of footfall patterns in conjunction with associated changes in motor patterns. These findings suggest the potential contribution of load-related proprioceptive feedback and/or the expression of variations in the locomotor program already during early manifestations of stepping on ground in human babies.

The c.480C>G polymorphism of hOCT1 influences imatinib clearance in patients affected by chronic myeloid leukemia.

The aim of the study was to investigate any possible influence of polymorphisms of transmembrane transporters human organic cation transporter 1 (hOCT1), ABCB1, ABCG2 on imatinib pharmacokinetics in 33 men and 27 women (median age and range, 56 and 27-79 years, respectively) affected by chronic myeloid leukemia. A population pharmacokinetic analysis was performed to investigate imatinib disposition in every patient and the role of transporter polymorphisms. Results showed that the α1-acid glycoprotein and the c.480C>G genotype of hOCT1 had a significant effect on apparent drug clearance (CL/F) being responsible, respectively, for a 20% and 10% decrease in interindividual variability (IIV) of CL/F (from 50.1 up to 19.6%). Interestingly, 25 patients carrying at least one polymorphic c.480 G allele had a significant lower CL/F value with respect to the 35 c.480CC individuals (mean±s.d., 9.6±1.6 vs 12.1±2.3 l h(-1), respectively; P<0.001). In conclusion, the hOCT1 c.480C>G SNP may significantly influence imatinib pharmacokinetics, supporting further analyses in larger groups of patients.

Immune responses to tetanus vaccination in Italian healthy subjects and children with recurrent infections.

The ability of vaccine antigen to generate protection is a challenge that cannot be restricted to the antibody response; however, the contribution of T cell-mediated mechanisms has not been extensively analyzed. Age and administration to specific categories of patients, i.e. children with recurrent infections (RI), are some of the factors that might affect the vaccine immune response. We investigated the humoral and cellular response to tetanus toxoid (TT) vaccine in 104 healthy children (HC), 11 newborns and 22 healthy adults to characterize the status of immunity according to age and compared it to 118 RI children. Humoral and cellular responses varied in both groups according to age and doses of TT administered. The prevalence of antibody and cellular response was similar in both cohorts (HC 88 percent and 82 percent versus RI 86 percent and 85 percent), however, TT antibody values were significantly higher in 12-18 months old RI children compared to HC (median: 5 IU/ml vs 1.10 IU/ml) (p = 0.02). The lack of an efficient immune response was observed in 12-15 percent of children from both cohorts. Our data showed that specific antibodies were responsible for early protection, whereas cell-mediated mechanisms may contribute to the generation of long-term immunity after an appropriate vaccine recall. The occurrence of higher TT antibody values in 12-18 months old RI children deserves additional research to determine whether they are caused by different infectious agents and/or by other environmental factors. Clarification of this issue is important for categorizing patients into an optimal vaccine policy.

Breast-conserving surgery after neoadjuvant chemotherapy in patients with locally advanced cancer. Preliminary results.

Neoadjuvant chemotherapy (NACT) in locally advanced breast tumors may allow an adequate control of the disease impossible with surgery alone. Moreover, NACT increases the chance of breast-conserving surgery. Between 2008 and 2012, we treated with NACT 83 patients with locally advanced breast cancer. We report the preliminary results evaluating the impact of NACT on the type of surgery.

Combined thrombolytic therapy for atrial thrombus in a preterm infant.

Intracardiac thrombosis is a rare event in newborn (5.1 per 100000 live births). It is associated with an high morbidity and mortality. Most of intracardiac thrombi are related to intravascular catheterism. The use of thrombolytic therapy in neonates has rapidly improved in the last few years, particularly with the introduction of more clot-selective second-generation agents like urokinase and tissue plasminogen activator. In literature there is no therapeutic trial concerning the pharmacological approach of atrial thrombosis in newborns; different approaches are described in the case reports present in literature. In all of them, tissue plasminogen activator or urokinase are alternatively administered. In no case report urokinase and tissue plasminogen activator are administered in a combined thrombolytic therapy. Combined thrombolytic therapy with urokinase and tissue plasminogen activator, in association with low-dose heparin, allows the use of lower drug doses, less therapy's duration and a rapid resolution of thrombus. Thormbolytic therapy is sometimes complicated with hemorrhagic complications. This article describes the case of a preterm infant (25 weeks of gestational age) with peduncolate thrombus in the right atrium, treated with combined thrombolytic therapy. The authors noticed a rapid decrease in thrombus dimension, no thrombus replacement and no organ bleeding.

Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer.

BACKGROUND: The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC). METHODS: Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF: -2578A/C, -1498C/T, -1154A/G, -634C/G and 936C/T; and VEGFR-2: -604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients. RESULTS: Treatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found. CONCLUSION: Our study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies.

Three-times weekly teicoplanin as outpatient treatment of chronic osteoarticular infections.

Treatment of difficult-to-treat infections such as osteomyelitis or infections related to indwelling medical devices requires lengthy antibiotic therapy and adequate surgical debridement. Teicoplanin, a glycopeptide antibiotic with a long half-life, was used three-times weekly in the treatment of these infections. After a period of daily dosing with teicoplanin, patients were treated with an intravenous dose of 12 mg on mondays, wednesdays and fridays. A control group of patients were treated with teicoplanin daily. Teicoplanin levels were measured during the study. Thirty-six patients were enrolled in the study: 14 with vertebral osteomyelitis, 12 with infected orthopedic implants, 7 with osteomyelitis and 3 with arterial prosthetic infections. The duration of treatment ranged from 60 to 360 days. Cure was obtained in 21 (58%) patients and improvement in 15 (42%) patients. Trough and peak serum concentrations in three-time weekly patients were 16.2+/-7.2 mg/l and 58.7+/-14.4 mg/l. In the control group trough and peak serum concentrations were 18.9+/-13.6 mg/l and 52.2+/-27 mg/l. Adverse events occurred in 6 patients: mainly mild liver toxicity. Three times weekly teicoplanin seems to be a valuable option in the treatment of chronic infections.

Genetic polymorphisms of thiopurine S-methyltransferase in a cohort of patients with systemic autoimmune diseases.

OBJECTIVES: Azathioprine (AZA) is a purine antimetabolite, prodrug widely used as a disease modifying drug in several rheumatic conditions. The aim of the present study was to evaluate the prevalence of TPMT genetic polymorphisms in a cohort of Italian Caucasian patients affected by rheumatic diseases and treated with AZA, and to establish correlations with the tolerability of AZA treatment. RESULTS: Seventy-eight Caucasian patients, 16 males and 62 females, median age 41 years (min-max: 24-76) were enrolled. At the time of evaluation, the median duration of treatment with AZA was 8 months (min-max: 2-150 months); the median dose of AZA per kg of body weight was 1.42 mg (min-max: 0.5-2). Among the 78 patients evaluated, 76 presented a wild type genotype (TPMT *1), while polymorphic alleles were identified in 2 patients (2.6%). Twenty-five patients (32%) experienced different types of adverse events (AE) under AZA treatment. Eighteen patients (23.1%) discontinued AZA because of AE. No correlation was observed between polymorphic TPMT alleles and the development of AE. CONCLUSIONS: Our analysis supports the view that TPMT genotyping alone is not sufficient to adequately personalize the AZA dosage in rheumatic patients. Further studies based on phenotypic analysis of TPMT enzyme and assay of AZA metabolite appear to be required.

A dose finding and pharmacokinetic study of capecitabine in combination with oxaliplatin and irinotecan in metastatic colorectal cancer.

PURPOSE: The GONO-FOLFOXIRI regimen demonstrated higher activity and efficacy than FOLFIRI in metastatic colorectal cancer patients. The aim of this study was to determine the maximum tolerated dose of capecitabine, in substitution of 5-fluorouracil, combined with oxaliplatin and irinotecan and to evaluate the pharmacokinetics of the drugs. PATIENTS AND METHODS: We treated 15 patients with escalating doses of capecitabine (from day 1 to 7) and fixed doses of oxaliplatin (85 mg/m(2)) plus irinotecan (165 mg/m(2)) (both administered on day 1), repeated every 2 weeks. Pharmacokinetic analysis was performed on plasma samples collected at the first cycle of treatment. RESULTS: The maximum tolerated dose of capecitabine resulted 2,000 mg/m(2)/day, with diarrhea being the only dose-limiting toxicity. Large interpatient variability in the pharmacokinetic parameters of investigated drugs was observed. Results in terms of activity are promising. CONCLUSIONS: At the maximum tolerated dose of capecitabine of 2,000 mg/m(2)/day the combination is feasible with promising activity and deserves further investigations.

[The birth certificate as an instrument for pregnancy]. / Il Certificato di assistenza al parto come strumento informativo per una analisi del percorso nascita.

The birth certificate is a valid source of information on pregnancy, birth, the newborn and the parents: such information could be useful to identify and eventually to improve the sanitary, social and economic conditions in which this event takes place and which could have negative effects on pregnancy outcome. In this paper the authors present and analyze the results of a number of births in some sanitary structures in the Umbria region (Italy), carried out through the revision of data reported in the birth certificates during the year 2004.

Antiangiogenic and anticolorectal cancer effects of metronomic irinotecan chemotherapy alone and in combination with semaxinib.

Metronomic chemotherapy refers to the administration of chemotherapy at low, nontoxic doses on a frequent schedule with no prolonged breaks. The aim of the study is to rationally develop a CPT-11 metronomic regimen in preclinical settings of colon cancer. In vitro cell proliferation, apoptosis and thrombospondin-1/vascular endothelial growth factor (TSP-1/VEGF) expression analyses were performed on endothelial (HUVEC, HMVEC-d) and colorectal cancer (HT-29, SW620) cells exposed for 144 h to metronomic concentrations of SN-38, the active metabolite of CPT-11. HT-29 human colorectal cancer xenograft model was used, and tumour growth, microvessel density and VEGF/TSP-1 quantification was performed in tumours. In vitro and in vivo combination studies with the tyrosine inhibitor semaxinib were also performed. SN-38 preferentially inhibited endothelial cell proliferation alone and interacted synergistically with semaxinib; it induced apoptosis and increased the expression and secretion of TSP-1. Metronomic CPT-11 alone and combined with semaxinib significantly inhibits tumour growth in the absence of toxicity, which was accompanied by decreases in microvessel density and increases in TSP-1 gene expression in tumour tissues. In vitro results show the antiangiogenic properties of low-concentration SN-38, suggesting a key role of TSP-1 in this effect. In vivo, the CPT-11 metronomic schedule is effective against tumour and microvessel growth without toxic effect on mice.