Microscopic fractional anisotropy outperforms multiple sclerosis lesion assessment and clinical outcome associations over standard fractional anisotropy tensor.

We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.

First Evidence of Purely Extreme-Ultraviolet Four-Wave Mixing.

The extension of nonlinear optical techniques to the extreme-ultraviolet (EUV), soft and hard x-ray regime represents one of the open challenges of modern science since it would combine chemical specificity with background-free detection and ultrafast time resolution. We report on the first observation of a four-wave-mixing (FWM) response from solid-state samples stimulated exclusively by EUV pulses. The all-EUV FWM signal was generated by the diffraction of high-order harmonics of the FERMI free-electron laser (FEL) from the standing wave resulting from the interference of two crossed FEL pulses at the fundamental wavelength. From the intensity of the FWM signal, we are able to extract the first-ever estimate of an effective value of ∼6×10^{-24} m^{2} V^{-2} for the third-order nonlinear susceptibility in the EUV regime. This proof of principle experiment represents a significant advance in the field of nonlinear optics and sets the starting point for a manifold of techniques, including frequency and phase-resolved FWM methods, that are unprecedented in this photon-energy regime.

Four-wave-mixing experiments with seeded free electron lasers.

The development of free electron laser (FEL) sources has provided an unprecedented bridge between the scientific communities working with ultrafast lasers and extreme ultraviolet (XUV) and X-ray radiation. Indeed, in recent years an increasing number of FEL-based applications have exploited methods and concepts typical of advanced optical approaches. In this context, we recently used a seeded FEL to demonstrate a four-wave-mixing (FWM) process stimulated by coherent XUV radiation, namely the XUV transient grating (X-TG). We hereby report on X-TG measurements carried out on a sample of silicon nitride (Si3N4). The recorded data bears evidence for two distinct signal decay mechanisms: one occurring on a sub-ps timescale and one following slower dynamics extending throughout and beyond the probed timescale range (100 ps). The latter is compatible with a slower relaxation (time decay > ns), that may be interpreted as the signature of thermal diffusion modes. From the peak intensity of the X-TG signal we could estimate a value of the effective third-order susceptibility which is substantially larger than that found in SiO2, so far the only sample with available X-TG data. Furthermore, the intensity of the time-coincidence peak shows a linear dependence on the intensity of the three input beams, indicating that the measurements were performed in the weak field regime. However, the timescale of the ultrafast relaxation exhibits a dependence on the intensity of the XUV radiation. We interpreted the observed behaviour as the generation of a population grating of free-electrons and holes that, on the sub-ps timescale, relaxes to generate lattice excitations. The background free detection inherent to the X-TG approach allowed the determination of FEL-induced electron dynamics with a sensitivity largely exceeding that of transient reflectivity and transmissivity measurements, usually employed for this purpose.

The use of ciclosporin in paediatric inflammatory bowel disease: an Italian experience.

AIM: To asses the efficacy and safety of ciclosporin in a paediatric population with inflammatory bowel disease. PATIENTS AND METHODS: Twenty-three Italian children treated with ciclosporin were studied retrospectively. The indications for treatment were severe unresponsive colitis, chronic active colitis or severe fistulizing Crohn's disease. The treatment duration, follow-up and causes of drug discontinuation were assessed. RESULTS: Sixteen patients were treated intravenously for a mean time of 10 +/- 7 days (1-24 days) and 19 orally for a mean time of 133 days (17-660 days). The mean follow-up of all patients was 13.2 months. Ciclosporin was totally ineffective, being discontinued for surgery, in nine of 23 patients (39%); it was discontinued for partial response in three patients (13%). During treatment, clinical remission was achieved in eight children (35%) and maintained after drug withdrawal in four (17%). In severe unresponsive colitis, urgent colectomy was avoided in 12 (85%) of 14 patients who tolerated the drug. Side-effects appeared in six of 23 patients (26%), and three (13%) required ciclosporin to be discontinued due to neurotoxicity. CONCLUSIONS: Ciclosporin shows disappointing long-term results in the treatment of refractory inflammatory bowel disease, but can play an important role in preventing urgent surgery in unresponsive severe colitis. Severe side-effects can occur.

Effect of passive smoking during pregnancy on selected perinatal parameters.

A prospective study of 1004 consecutive deliveries was carried out to investigate the effect of passive smoking during pregnancy on a set of perinatal parameters. The data set was a cooperative study involving 11 Italian cities, distributed nationally. The study group was divided in three categories according to the mother's cigarette smoke exposure during pregnancy, ie, not smokers, passive smokers, direct smokers. Potential confounders, including paternal characteristics, were adjusted for by multiple linear regression analysis. A mean reduction of 16 g (p less than 0.07) in birthweight and a decrease in birth length of 0.05 cm (p less than 0.08) were found for each hour of antenatal passive smoke exposure. No or slight effects were reported for the other perinatal parameters considered.

Bloodstream infections can develop late (after day 100) and/or in the absence of neutropenia in children receiving allogeneic bone marrow transplantation.

We retrospectively evaluated the incidence and time from transplantation of bloodstream infections occurring in children receiving bone marrow transplant (BMT) at G Gaslini Children's Hospital between September 1984 and December 1997. During this period the incidence was 35% after allogeneic and 26% after autologous BMT (P=0.08). Among these episodes, 38% after allogeneic BMT and 90% after autologous BMT were detected in the presence of neutropenia within the first 30 days from reinfusion (P < 0.001). Incidence of catheter-related bloodstream infections was 40% after allogeneic and 8% after autologous BMT (P < 0.001). Bloodstream infections in the absence of neutropenia were 55% after allogeneic BMT vs 10% after autologous BMT (P < 0.001) and occurred later after reinfusion (mean 199 vs 41 days, P <0.001). Among the episodes occurring after allogeneic BMT and in the absence of neutropenia, 61% were related to the presence of a central venous catheter, 15% were related to the presence of GVHD, but 23% were not associated with any of major risk factors for infection. Finally, 38% of episodes following allogeneic BMT were detected after day 100 vs 1% after autologous BMT. We concluded that patients receiving allogeneic BMT experience a high incidence of bloodstream infections in the absence of neutropenia and that a significant proportion of these episodes is not clearly associated with well known risk factors such as GVHD or central venous catheters. Moreover, many episodes develop a long time after the transplantation procedure. Therefore, any febrile episode following allogeneic BMT even late and/or in the absence of neutropenia should be intensively managed.

Bilateral breast involvement in a 71-year-old white man with lambda light chain disease. Regression after a new chemotherapy combination. A case report.

A rare case of lambda light chain disease with bilateral breast involvement is described. A complete regression after a new chemotherapy combination (peptichemio + teniposide + dexamethasone) was obtained. A previous treatment with prednisone + melphalan was ineffective.

[Hypothalamo-hypophyseal metastasis: a rare initial manifestation of adenocarcinoma of the jejunum. Description of a clinical case]. / Metastasi ipotalamo-ipofisaria: rara manifestazione iniziale di adenocarcinoma del digiuno. Descrizione di un caso clinico.

A rare case of jejunal adenocarcinoma is described in which the initial clinical sign was diabetes insipidus and hypopituitarism linked to hypothalamohypophyseal metastasis. The rarity of the intestinal neoplasm and the unusual site of the metastatic lesions are underlined.

[Incidence and treatment of local recurrences after conservative surgical treatment for cancer of the breast]. / Incidence et traitement des récidives locales après traitement chirurgical conservateur pour cancer du sein.

Long-term survival is comparable after total mastectomy or conservative surgery for early breast cancer. Our purpose was to evaluate the rate and therapy of breast relapse at the Regional Hospital of Varese (Italy) in a 10 years period. From 1/1/1980 to 31/12/1990 a total of 606 patients with early breast cancer (Stage I or II early) were evaluated. They all were submitted to quadrantectomy, axillary dissection and radiotherapy. In case of metastases to the axillary lymph nodes, hormono or chiotherapy were performed. 425 patients were regularly followed for a period of 2.5-13 years. In 15 patients (3.2%) a local recurrence was discovered. They were treated as follows, 8 patients: mastectomy, 4 patients: conservative surgery, 4 patients: no therapy. The surgical approach of the local recurrence, mastectomy or conservative surgery, does not influence long-term survival of patients treated with conservative surgery and radiotherapy for early stage breast cancer. Conservative surgery is often possible in treating local recurrence without interfering with complete removal of the tumor and long-term survival.

[Sepsis related to a permanent central venous catheter in children with neoplastic disease: practical implications of a continuous surveillance of the etiology]. / Sepsi correlate a catetere venoso centrale a permanenza in bambini affetti da malattia neoplastica: implicazioni pratiche di una sorveglianza continua dell'eziologia.

Indwelling central venous catheter-related bacteremias are an important complication in patients with cancer. In general they are due to Staphylococcus aureus and Candida, while bacteremias caused by Gram-negatives are less common and often related to infusate contaminans. We describe a survey of etiological surveillance of Broviac catheter-related infections at G. Gaslini Children's Hospital of Genoa, Italy. In the period 1989-1992 an increase of Broviac catheter-related bacteremias due to Gram-negatives was demonstrated as compared with previous years (1985-1988). At home parental management was suspected as an important risk factor, since this complication was frequently due to infusate contaminants and no epidemic cluster or positive surveillance culture was observed in the Hospital. Therefore at home management was changed, especially regarding heparin storage. The subsequent, prospective follow-up from July 1993 to December 1995 showed a significant decrease in catheter-related bacteremias due to Gram-negatives (P = 0.003, chi-square test). In conclusion, a strict control on at home catheter management procedures must be maintained in order to reduce the risk of indwelling central venous catheter-related infections in children with cancer.

A driving simulator study of driver performance on deceleration lanes.

Deceleration lanes are important because they help drivers transition from high-speed lanes to low-speed ramps. Although they are designed to allow vehicles to depart the freeway safely and efficiently, many studies report high accident rates on exit ramps with the highest percentage of crashes taking place in deceleration lanes. This paper describes the results of a driving simulator study that focused on driving performance while approaching a divergence area and decelerating during the exiting maneuver. Three different traffic scenarios were simulated to analyze the influence of traffic volume on driving performance. Thirty drivers drove in the simulator in these scenarios while data on their lateral position, speed and deceleration were collected. Our results indicate there are considerable differences between the main assumptions of models generally used to design deceleration lanes and actual driving performance. In particular, diverging drivers begin to decelerate before arriving at the deceleration lane, causing interference with the main flow. Moreover, speeds recorded at the end of the deceleration lane exceed those for which the ramp's curves are designed; this creates risky driving conditions that could explain the high crash rates found in studies of exit ramps. Finally, statistical analyses demonstrate significant influences of traffic volume on some aspects of exiting drivers' performance: lower traffic volume results in elevated exiting speed and deceleration, and diverging drivers begin to decelerate earlier along the main lane when traffic volume is low. However, speeds at the end of the deceleration lane and the site of lane changing are not significantly influenced by traffic volume.