Artificial 'spin ice' in a geometrically frustrated lattice of nanoscale ferromagnetic islands.

Frustration, defined as a competition between interactions such that not all of them can be satisfied, is important in systems ranging from neural networks to structural glasses. Geometrical frustration, which arises from the topology of a well-ordered structure rather than from disorder, has recently become a topic of considerable interest. In particular, geometrical frustration among spins in magnetic materials can lead to exotic low-temperature states, including 'spin ice', in which the local moments mimic the frustration of hydrogen ion positions in frozen water. Here we report an artificial geometrically frustrated magnet based on an array of lithographically fabricated single-domain ferromagnetic islands. The islands are arranged such that the dipole interactions create a two-dimensional analogue to spin ice. Images of the magnetic moments of individual elements in this correlated system allow us to study the local accommodation of frustration. We see both ice-like short-range correlations and an absence of long-range correlations, behaviour which is strikingly similar to the low-temperature state of spin ice. These results demonstrate that artificial frustrated magnets can provide an uncharted arena in which the physics of frustration can be directly visualized.

Encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: real-life data from an Italian multicenter experience.

BACKGROUND: Encorafenib plus cetuximab with or without binimetinib showed increased objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared with chemotherapy plus anti-EGFR in previously treated patients with BRAF V600E-mutated (mut) metastatic colorectal cancer (mCRC). Although no formal comparison was planned, addition of binimetinib to encorafenib plus cetuximab did not provide significant efficacy advantage. PATIENTS AND METHODS: This real-life study was aimed at evaluating safety, activity, and efficacy of encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mut mCRC treated at 21 Italian centers within a nominal use program launched in May 2019. RESULTS: Out of 133 patients included, 97 (73%) received encorafenib plus cetuximab (targeted doublet) and 36 (27%) the same therapy plus binimetinib (targeted triplet). Most patients had Eastern Cooperative Group Performance Status (ECOG-PS) of 0 or 1 (86%), right-sided primary tumor (69%), and synchronous disease (66%). Twenty (15%) tumors were DNA mismatch repair deficiency (dMMR)/microsatellite instability (MSI)-high. As many as 44 (34%) patients had received two or more prior lines of therapy, 122 (92%) were previously exposed to oxaliplatin, and 109 (82%) to anti-vascular endothelial growth factor (anti-VEGF). Most frequent adverse events were asthenia (62%) and anti-EGFR-related skin rash (52%). Any grade nausea (P = 0.03), vomiting (P = 0.04), and diarrhea (P = 0.07) were more frequent with the triplet therapy, while melanocytic nevi were less common (P = 0.06). Overall, ORR and disease control rate (DCR) were 23% and 69%, respectively, with numerically higher rates in the triplet group (ORR 31% versus 17%, P = 0.12; DCR 78% versus 65%, P = 0.23). Median PFS and OS were 4.5 and 7.2 months, respectively. Worse ECOG-PS, peritoneal metastases, and more than one prior treatment were independent poor prognostic factors for PFS and OS. Clonality of BRAF mutation measured as adjusted mutant allele fraction in tumor tissue was not associated with clinical outcome. CONCLUSIONS: Our real-life data are consistent with those from the BEACON trial in terms of safety, activity, and efficacy. Patients in good general condition and not heavily pretreated are those more likely to derive benefit from the targeted treatment.

Nanoscale reversible mass transport for archival memory.

We report on a simple electromechanical memory device in which an iron nanoparticle shuttle is controllably positioned within a hollow nanotube channel. The shuttle can be moved reversibly via an electrical write signal and can be positioned with nanoscale precision. The position of the shuttle can be read out directly via a blind resistance read measurement, allowing application as a nonvolatile memory element with potentially hundreds of memory states per device. The shuttle memory has application for archival storage, with information density as high as 10(12) bits/in(2), and thermodynamic stability in excess of one billion years.

[Drug use among workers: an update]. / Aggiornamenti in tema di abuso di sostanze stupefacenti e psicotrope.

We present data coming from two years of surveillance of drug use among workers, as provided for by the recent law. Urine samples have been collected either by our lab or by the firm; procedures and investigated substances followed the law. Self-reported information on job duties and history of drug use have also been collected. Between September 2008 and April 2010, n = 2745 workers (age 40.5 +/- 9.5, 98% men, 43% handling workers) were screened, for a total number of 3002 urine samples. Among the samples with creatinine > = 20 mg/dl (n = 2878), 46 were positive (1.6%); no temporal trends were detected. Cannabis e cocaine were the two most spread substances. Positivity was associated with young age and presence of another positive sample in the same firm. Furthermore, we present the results of the analysis (urine and hair samples) on 146 suspected drug abuser selected by the SERT Varese in the same time period.

Boron nitride nanotubes.

The successful synthesis of pure boron nitride (BN) nanotubes is reported here. Multi-walled tubes with inner diameters on the order of 1 to 3 nanometers and with lengths up to 200 nanometers were produced in a carbon-free plasma discharge between a BN-packed tungsten rod and a cooled copper electrode. Electron energy-loss spectroscopy on individual tubes yielded B:N ratios of approximately 1, which is consistent with theoretical predictions of stable BN tube structures.

Synthesis and Electronic Transport of Single Crystal K3C60.

Sizable single crystals of C(6O) have been synthesized and doped with potassium. Above the superconducting transition temperature T(c), the electrical resistivity p(T) displays a classic metal-like temperature dependence. The transition to the superconducting state at T(c) = 19.8 K is extremely sharp, with a transition width DeltaT < 200 mK. In contrast to transport behavior of doped polycrystalline and granular thin films, no anomalous fluctuations are observed near T(c) in single crystal specimens.

Comparative HPLC and ELISA studies for CDT isoform characterization in subjects with alcohol related problems. Prospective application in workplace risk-prevention policy.

Serum carbohydrate-deficient transferrin (CDT) is the most specific marker of chronic alcohol abuse so far. The performance of commercial HPLC over the ELISA method for measurement of CDT was evaluated on a series of 105 serum samples obtained from subjects referred to the Toxicology Laboratory of Salvatore Maugeri Hospital for alcohol-related problems. Compared to ELISA, HPLC analysis was more valuable for determining alcohol-related patterns of CDT isoforms and quantifying serum levels of disialotransferrin that better reflect chronic heavy drinking. Other significant advantages of the HPLC method included reproducible separation and easier detection of glycoform types and genetic transferrin variants that are known to cause falsely high or low results in sera examined by immunoassay. Current scientific evidence indicates that disialotransferrin is the target analyte for CDT determination and HPLC the current CDT analysis reference method. Systematic studies for early assessment of excessive alcohol intake or abuse of alcoholic substances in workers are recommended by the Italian legislation in accordance with the European Alcohol Action Plan (EAAP) launched by the WHO Regional Committee for Europe. These studies are advisable given their potential role in preventing negative effects of alcohol abuse in workplace. A research strategy combining CDT and other laboratory markers with questionnaire and physician interview is recommended for examining subjects with alcohol related problems and the diagnosis of alcoholism. This approach can be applied for alcohol abuse in workplace surveillance.

Unusual morphological features in a presumably Neolithic individual from Riparo della Rossa, Serra San Quirico (Ancona, Italy).

The present study describes human skeletal remains from Riparo della Rossa, a rock shelter in the Marche region (Central Italy). The remains consist of a cranial vault and a few non-articulated postcranial bones, possibly belonging to the same adult individual. As the cranial vault showed some morphological features that are unusual for a modern human (marked prominence of the supraorbital region, very prominent nasal bones and rather high thickness of the vault), an accurate anthropological analysis and quantification of the antiquity of the bones were required. The remains were dated with two different absolute dating methods, AMS (14)C and (235)U-(231)Pa non-destructive gamma-ray spectrometry (NDGRS), which produced discordant results: the uncalibrated (14)C dating produced 5690 +/- 80 BP for the cranial vault and 6110 +/- 80 BP for the clavicle; the NDGRS dating produced 10,000 +/- 3000 BP for the cranial vault. The sex discriminant morphological characters on the skull are not unequivocal, though the masculine ones appear more evident. The aims of the present paper are: to provide a morphological and metric description of the remains; to interpret their unusual morphological features; to attempt to attribute them to male or female sex and to one of the possible prehistoric cultural groups, according to dating results (Upper Palaeolithic, Mesolithic or Neolithic). The attribution was obtained by a Bayesian procedure taking into account the reliability of the combined information of morphological/metric features and absolute dating results. The results suggest that the Riparo della Rossa remains are best attributed to a male individual of the Neolithic age.

[Diagnostic agreement between two different analytic methods for in vitro measurement of specific IgE and comparison with clinical evaluation and in vivo test for ubiquitarian and professional allergens]. / Concordanza diagnostica tra due differenti metodi analitici per la determinazione in vitro di IgE specifiche e confronto con valutazione clinica e test in vivo per allergeni ubiquitari e professionali.

This study surveys the diagnostic agreement between two different analytic systems for the measurement of serum specific IgE (sLgE), Immulite 2000 (IML) and ImmunoCap (CAP), with clinic evaluation and in vivo test. Our sample is represented by 33 adults (27 females and 6 males), with suspect of immediate allergic disease and suspect of sensitization to at least one allergen of the study panel (18 allergens: inhalant, alimentary and professional). All patients have been subjected to Skin Prick Test (SPT) for all the studied allergens, therefore sIgE measurement with IML and CAP systems has been executed (twice for each method) only for the allergens which resulted positive to the diagnostic suspect and to SPT, and for an equal number of allergens chosen by bound randomisation. In vitro methods (IML and CAP), evaluated by K Cohen statistics, give good diagnostic agreement. In the same way, the diagnostic agreement of the used analytic systems both with clinical suspect and with in vivo test is satisfying, with higher K values for IML.

Neurotoxicity and ototoxicity of cisplatin plus paclitaxel in comparison to cisplatin plus cyclophosphamide in patients with epithelial ovarian cancer.

PURPOSE: To compare the neurotoxicity and ototoxicity of combination cisplatin plus paclitaxel versus cisplatin plus cyclophosphamide using extensive clinical and instrumental evaluation. PATIENTS AND METHODS: Forty-six of 51 consecutive patients affected by-epithelial ovarian cancer seen in our institution between October 1994 and August 1995 entered the study. After randomization, they were assigned to receive cisplatin 75 mg/m2 every 3 weeks associated with cyclophosphamide 750 mg/m2 (CC group, n = 22) or paclitaxel 175 mg/m2 over a 3-hour infusion (CP group, n = 24). Treatment was repeated six times in 43 patients and nine times in 25. Before treatment and after three, six, and nine courses of chemotherapy, patients underwent clinical and instrumental neurologic and otologic examinations. RESULTS: Mild sensory impairment was evident even after only three courses of both treatments and signs and symptoms were more severe at the end of treatment. On clinical grounds only, it was possible to demonstrate after six and nine courses a difference between CC and CP treatment, due to the involvement in some CP patients of pain and thermal sensory modalities. However, the overall severity of the neuropathy was similar. Audiometric parameters demonstrated a more negative outcome after treatment in CC compared with CP patients. However, the different severity of the involvement was closely correlated to this initial difference in audiologic performance. CONCLUSION: Up to nine courses of chemotherapy, the CC and CP schedules are similar in terms of severity of neurotoxicity and ototoxicity when patients are evaluated during and immediately after treatment. With the doses used in our study, these toxicities are not dose-limiting. Our results suggest that most of the toxic effects observed during the treatment were due to cisplatin.

Risk factors for the development of severe cisplatin neurotoxicity.

Cisplatin sensory neuropathy is not equally severe in all patients and may progress even after drug withdrawal. A major goal in cisplatin chemotherapy would be the identification of early predictors of an unfavorable neurological outcome in order to adjust the schedules of administration. The final neurological outcome of 63 women treated with the same schedule of cisplatin (CDDP) was compared with the general demographic and oncological parameters and with the baseline neurological results. No definite association could be drawn between any of the parameters evaluated and peripheral neuropathy. Further studies are needed to investigate the individual factors which are at the basis of the remarkable variability of this severe side effect of CDDP.

Electrophysiological findings in workers exposed to N-heptane fumes.

Electrophysiological examination of the peroneal nerve was performed in a group of individuals exposed for professional reasons to vapours of n-heptane. The results suggest a probably specific role of this hydrocarbon compound in provoking "minimal" peripheral nerve damage.

Rational use of EEG in adults in clinical practice.

The electroencephalogram (EEG) is still widely used for the diagnosis of several clinical conditions and symptoms. To assess the information provided by the EEG in relation to its duration, and to identify the shortest recording providing a conclusive report, the tracing was tested in 290 adult patients seen in a hospital neurophysiology unit for epilepsy (definite or uncertain), headache, head trauma, fainting, syncope, undefined loss of consciousness, vertigo, and cerebrovascular disease. Two neurophysiologists participating in the study read the same EEG independently. The record was based on a standardized timed sequence of montages. At each step any changes from the previous step were noted. Sixty-seven percent of the EEGs were coded as normal or aspecific, 24.1% were slow, and 8.6% were epileptiform. Normal tracings ranged from 38.8% (definite epilepsy) to 87.5% (vertigo), and epileptiform EEG from 0 (uncertain epilepsy) to 28.6% (definite epilepsy). The final report was clear in 80% of cases at the end of a 2-minute reading and almost 90% after 4 minutes. Hyperventilation and intermittent photic stimulation contributed little to the final report. Only for definite epilepsy were there changes along the whole sequence of montages. Thus, only for epilepsy need the EEG recordings last more than 20 minutes, whereas for the other clinical indications the total recording time could be limited to 4 minutes at most.

Sural nerve bioptic findings in essential cryoglobulinemic patients with and without peripheral neuropathy.

Peripheral neuropathy often occurs in cryoglobulinemia but the pathogenesis of the peripheral nerve involvement is not completely understood, so that the relation between the reported endoneural changes and neuropathy is not clear. In this study we compared the sural nerve biopsies of 6 cryoglobulinemic patients with or without signs of peripheral neuropathy and all affected by the essential mixed type II form (ECII) and, moreover, of 8 age-matched controls. We found that in all the patients with neuropathy, axonopathy occurred and it was invariably associated with endoneural vessel damage. Moreover, the fiber losses were patchily distributed within the nerve fascicles. On the contrary both nerve fibers and vessels were normal in the patients without clinical and neurophysiological evidence of neuropathy and in controls. Our results support the hypothesis that the endoneural damage observed during ECII is not simply coincidental, but is relevant in the pathogenesis of cryoglobulinemic neuropathy. They also favor the assumption that ischemic damage of the nerve fibers occurs during ECII.

Stroke care in young patients.

The aims of this study were (i) to evaluate the clinical features of a consecutive series of young patients with ischemic stroke and (ii) to assess the changes in the clinical management of these patients over the study period. All consecutive cases of young adults aged 16 to 44 years, with ischemic stroke, that were admitted between 2000 and 2005 in 10 Italian hospitals were included. We retrospectively identified 324 patients. One or more vascular risk factors were present in 71.5% of the patients. With respect to the diagnostic process, an increase in the frequency of cerebral noninvasive angiographic studies and a decrease in the use of digital subtraction angiography were observed (P < 0.001 and P = 0.03, resp.). Undetermined causes decreased over 5-year period of study (P < 0.001). The diagnosis of cardioembolism increased. Thrombolysis was performed for 7.7% of the patients. PFO closure (8%) was the most frequently employed surgical procedure. In conclusion, the clinical care that is given to young patients with ischemic stroke changed over the study period. In particular, we detected an evolution in the diagnostic process and a reduction in the number of undetermined cases.

Incidence and predictors of acute symptomatic seizures after stroke.

OBJECTIVE: To assess incidence and predictors of acute symptomatic seizures in a prospective cohort of patients with first stroke. METHODS: Patients with first stroke hospitalized in 31 Italian centers were recruited. Relevant demographic data, disease characteristics, and risk factors were collected. Acute symptomatic seizures (≤7 days) were recorded and correlated to age, gender, family history of epilepsy, and vascular risk factors. RESULTS: A total of 714 patients (315 women, 399 men; age 27-97 years) were enrolled. A total of 609 (85.3%) had cerebral infarction (32 cerebral infarction with hemorrhagic transformation [CIHT]) and 105 (14.7%) primary intracerebral hemorrhage (PIH). A total of 141 (19.7%) had a large lesion (>3 cm) and 296 (41.5%) cortical involvement. Twelve patients reported family history of seizures. Forty-five patients (6.3%) presented acute symptomatic seizures, 24 with cerebral infarction (4.2%), 4 with CIHT (12.5%), and 17 (16.2%) with PIH. In multivariate analysis, compared to cerebral infarction, PIH carried the highest risk (odds ratio [OR] 7.2; 95% confidence interval [CI] 3.5-14.9) followed by CIHT (OR 2.7; 95% CI 0.8-9.6). Cortical involvement was a risk factor for PIH (OR 6.0; 95% CI 1.8-20.8) and for CI (OR 3.1; 95% CI 1.3-7.8). Hyperlipidemia (OR 0.2; 95% CI 0.03-0.8) was a protective factor for IPH. CONCLUSION: The incidence of acute symptomatic seizures is the highest reported in patients with first stroke with prospective follow-up. Hemorrhagic stroke and cortical lesion were independent predictors of acute symptomatic seizures. Hyperlipidemia was a protective factor for hemorrhagic stroke.