Ziconotide is commonly used for intrathecal (IT) therapy of chronic pain, and has been recently indicated as a first-line IT drug. It is also extremely useful for patients intolerant or refractory to ...the common IT drugs (such as morphine). The literature, excluding registration studies, mostly includes small samples, and gives only fragmentary evidence on the long-term risks and benefits of ziconotide.
To collect data on safety and efficacy of long-term ziconotide IT infusion in Italian pain centers.
Retrospective cohort study on the use of ziconotide in Italy. The study was designed and coordinated by the Foundation ISAL (Algological Sciences Research and Training Institute). Patients treated with ziconotide from several pain therapy and neurosurgery units were included in the study, allowing the creation of the first Italian Registry of Ziconotide.
Seventeen Italian public and private pain and neurosurgery centers.
Patients suffering from cancer or non-cancer intractable chronic pain who had been treated with ziconotide IT infusion for at least one month. Efficacy was analyzed considering changes on the visual analog scale of pain intensity from baseline observation. Safety was assessed by monitoring the number and intensity of adverse events.
Currently, 104 patients are included in the Italian Registry of Ziconotide. Ziconotide was administered as the first IT drug choice to 55 patients. Seventy-two patients reported at least a 30% pain intensity reduction with a mean dose of 4.36 ug/d. The sustained analgesic effect (P < 0.001) of the ziconotide IT therapy was observed in a group of 45 patients who remained in the study over 6 months without treatment interruptions and with relatively stable doses. Sixty-six patients reported at least one side effect related to ziconotide. However, adverse events have not always been decisive for treatment interruptions.
Data were collected retrospectively from different pain centers that used different methods for ziconotide treatment and clinical forms for its data collection; for this reason there is an absence of standardized methodologies and a placebo-controlled group, and some data were missing.
Ziconotide IT therapy is a treatment option commonly used for clinical practice in 17 Italian pain therapy and neurosurgery units. It might give relief to patients with refractory chronic pain, and it seems to have a safe profile. Long-term studies and controlled trials are required.
Abstract
Time-dependent energy spectra of galactic cosmic rays (GCRs) carry crucial information regarding their origin and propagation throughout the interstellar environment. When observed at the ...Earth, after traversing the interplanetary medium, such spectra are heavily affected by the solar wind and the embedded solar magnetic field permeating the inner sectors of the heliosphere. The activity of the Sun changes significantly over an 11 yr solar cycle—and so does the effect on cosmic particles; this translates into a phenomenon called solar modulation. Moreover, GCR spectra during different epochs of solar activity provide invaluable information for a complete understanding of the plethora of mechanisms taking place in various layers of the Sun’s atmosphere and how they evolve over time. The High-Energy Particle Detector (HEPD-01) has been continuously collecting data since 2018 August, during the quiet phase between solar cycles 24 and 25; the activity of the Sun is slowly but steadily rising and is expected to peak around 2025/2026. In this paper, we present the first spectra for ∼50–250 MeV galactic protons measured by the HEPD-01 instrument—placed on board the CSES-01 satellite—from 2018 August to 2022 March over a one-Carrington-rotation time basis. Such data are compared to the ones from other spaceborne experiments, present (e.g., EPHIN, Parker Solar Probe) and past (PAMELA), and to a state-of-the-art three-dimensional model describing the GCRs propagation through the heliosphere.
We describe the use of a transverse field RF surface coil that improves 1.5 T proton MR spectroscopy in the human calf. A 2-element figure-of-eight (FO8) transverse field RF surface coil (diameter ...2R=10 cm; separation between the two linear current elements 2s=1cm) and a circular loop (CL) coil of equal diameter where built and tested with proton PRESS spectra at 1.5 T. The super(1H PRESS spectra obtained in the resting calf muscle of healthy volunteers showed that the FO8 coil allows a higher PRESS SNR (up to a factor 4.5) within a region of about 20 mm centred at about 12 mm from the coil plane, as compared to a standard CL coil. We found also a faster PRESS SNR decrease in the muscle tissue for anterior/posterior distance 20 mm using the FO8 coil. The measured PRESS SNR in the fat tissues of the calf showed a signal mostly localised within 10 mm from the coils surface and with an improved SNR (up to 5.5 times) observed in the presence of the FO8 coil as compared to the CL coil of equal diameter. The FO8 coil design can be advantageous for MRS applications, since it allows higher SNR from a small VOI positioned centrally within a relatively narrow region at a given depth in the human calf. The reported spatial SNR features of the FO8 coil design should also be useful for ) super(1)H and 31P MRS metabolites quantification in the human brain.
Clinical MRI/MRS applications require radio frequency (RF) surface coils positioned at an arbitrary angle alpha with respect to B(0). In these experimental conditions the standard circular loop (CL) ...coil, producing an axial RF field, shows a large signal loss in the central region of interest (ROI). We demonstrate that transverse-field figure-of-eight (FO8) RF surface coils design are not subject to the same amount of signal loss in the central ROI as loop coils when their orientations are changed. The 1.5-T CL and FO8 prototypes (diameter = 10 cm) were built on Plexiglas using copper strips (width = 4 mm, thickness = 100 mum). The two linear elements of the FO8 coil were 1 cm apart. Axial spoiled gradient echo (SPGR) images of a phantom containing doped water were acquired with the coil plane at alpha=0 degrees , 45 degrees , and 90 degrees . As alpha increases, the CL images show, in the central ROI, a signal that decreases from a maximum value to zero. Whereas the FO8 images show, in the same ROI, a signal that varies little from the maximum value (20%). Optimized FO8 coils can be oriented with the coil plane positioned along any direction with respect to B(0) without significant signal loss. Transverse RF coil design should be useful for clinical MRS studies and also for parallel imaging techniques where versatile RF coils disposed along arbitrary directions are required.
Abstract
We present a study of the solar-cycle variations of >80 MeV proton flux intensities in the lower edge of the inner radiation belt, based on the measurements of the Payload for Antimatter ...Matter Exploration and Light-nuclei Astrophysics (PAMELA) mission. The analyzed data sample covers an ∼8 yr interval from 2006 July to 2014 September, thus spanning from the decaying phase of the 23rd solar cycle to the maximum of the 24th cycle. We explored the intensity temporal variations as a function of drift shell and proton energy, also providing an explicit investigation of the solar modulation effects at different equatorial pitch angles. PAMELA observations offer new important constraints for the modeling of low-altitude particle radiation environment at the highest trapping energies.
One of the most fascinating possibilities of Additive Manufacturing technologies is their capability to realize objects that include various types of joints and moving parts. The research presented ...in this paper proposes to embed elastic elements in these joints in order to control their compliance. Two applications are also presented, in order to demonstrate, firstly, the practical feasibility of this innovative joint, and, secondly, the possibility to control joint elastic behavior in order to force the connected parts to automatically return to their initial positions when the actuating load is removed.
An ω-space adaptive acquisition technique for MRI from projections is presented. It is based on the evaluation of the information content of a set composed of four initial projections, measured at ...angles 0°, 45°, 90°, and 135°, followed by the selection of new angles where the information content is maximum. An entropy function is defined on the power spectrum of the projections that is useful for evaluating the information content of each projection. The method makes it possible to reduce the total acquisition time with little degradation of the reconstructed image and it adapts to the arbitrary shape of the sample. For this reason, it can be particularly useful in those applications where acquisition from projections is strongly recommended to save acquisition time, such as functional MRI, imaging of species having very short T2, or angiography. The method has been tested both on simulated data and on experimental data collected by a commercial MRI apparatus. The method has also been compared to the regular acquisition method, that is, the standard acquisition method in MRI from projections.
A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for ~40% of familial amyotrophic ...lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic lateral sclerosis cases (21 of Sardinian ancestry) and 41 German index familial amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On average, children developed disease 7.0 years earlier than their parents children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation 10.9); P = 0.003. Parental phenotype influenced the type of clinical symptoms manifested by the child: of the 13 cases where the affected parent had an amyotrophic lateral sclerosis-frontotemporal dementia or frontotemporal dementia, the affected child also developed amyotrophic lateral sclerosis-frontotemporal dementia in nine cases. When compared with patients carrying mutations of other amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non-C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6-7.2) and longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7-2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most frequent mutation in our large cohort of patients with familial amyotrophic lateral sclerosis of Italian, Sardinian and German ancestry. Together with mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for ~60% of familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72 hexanucleotide repeat expansions present some phenotypic differences compared with patients with mutations of other genes or with unknown mutations, namely a high incidence of bulbar-onset disease and comorbidity with frontotemporal dementia. Their pedigrees typically display a high frequency of cases with pure frontotemporal dementia, widening the concept of familial amyotrophic lateral sclerosis.
The qualitative equivalence between the Fourier reconstruction (FR) algorithm and the filtered back projection (FBP) algorithm is demonstrated when all the different phase errors that can occur in FR ...are eliminated. The causes of phase errors are underlined and methods to eliminate them are presented. The practical comparison between FR and FBP has been evaluated on a numerical test image and the results are reported, demonstrating the qualitative equivalence. FR has the advantage of being very computationally efficient. In fact, the time spent to obtain the FR image was 1/20 of that used to obtain the FBP image. Because of the computational efficiency of FR and the good quality of the results obtained, an iterative version of FR has been used to implement the spectral–spatial imaging (SSI) algorithm in the field of electron paramagnetic resonance imaging (EPRI). An experimental example, demonstrating its good performance, is reported.
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