the isolpharm project a new isol production method of high specific activity beta emitting radionuclides as radiopharmaceutical precursors

The ISOLPHARM project explores the feasibility of exploiting an innovative technology to produce extremely high specific activity beta-emitting radionuclides as radiopharmaceutical precursors. This technique is expected to produce radiopharmaceuticals that are virtually mainly impossible to obtain in standard production facilities, at lower cost and with less environmental impact than traditional techniques. The groundbreaking ISOLPHARM method investigated in this project has been granted an international patent (INFN). As a component of the SPES (Selective Production of Exotic Species) project at the Istituto Nazionale di Fisica Nucleare–Laboratori Nazionali di Legnaro (INFN–LNL), a new facility will produce radioactive ion beams of neutron-rich nuclei with high purity and a mass range of 80–160 amu. The radioactive isotopes will result from nuclear reactions induced by accelerating 40 MeV protons in a cyclotron to collide on a target of UC[Formula: see text]. The uranium in the target material will be [Formula: see text]U, yielding radioactive isotopes that belong to elements with an atomic number between 28 and 57. Isotope separation on line (ISOL) is adopted in the ISOLPHARM project to obtain pure isobaric beams for radiopharmaceutical applications, with no isotopic contaminations in the beam or subsequent trapping substrate. Isobaric contaminations may potentially affect radiochemical and radionuclide purity, but proper methods to separate chemically different elements can be developed

Pakistani children’s experiences of growing up with Beta-Thalassemia Major

In this study, we explored the lived experiences of children with beta-thalassemia major (β-TM). We considered children as experts on their experiences in contrast to the prevalent approach of asking parents or other adults about children’s perspectives. The sample consisted of 12 children aged 8 to12 years. There were two stages to data collection. In Stage 1 we employed two focus group discussions and two role plays and analyzed the data thematically. This directly informed Stage 2, consisting of 12 in-depth interviews subjected to interpretative phenomenological analysis. From our findings we show that living with β-TM involves a continuous struggle between feelings of being different and strategies to minimize these differences to strive for normalcy. We suggest that understanding the experiences of living with β-TM from children’s perspectives can provide unique insights into their experiences, which can fill the gap in the existing, predominantly adult-oriented research on chronic illness

Beta-thalassemia

Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta globin gene on chromosome 11, leading to reduced (beta+) or absent (beta0) synthesis of the beta chains of hemoglobin (Hb). Transmission is autosomal recessive; however, dominant mutations have also been reported. Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Differential diagnosis is usually straightforward but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemia). Genetic counseling is recommended and prenatal diagnosis may be offered. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. In some circumstances, spleen removal may be required. Bone marrow transplantation remains the only definitive cure currently available. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Prognosis for individuals with beta-thalassemia has improved substantially in the last 20 years following recent medical advances in transfusion, iron chelation and bone marrow transplantation therapy. However, cardiac disease remains the main cause of death in patients with iron overload

Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

<p>Abstract</p> <p>Background</p> <p>Beta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent.</p> <p>Discussion</p> <p>Thalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy or accept the high mortality risk of HSCT in the hope of obtaining complete recovery.</p> <p>Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome.</p> <p>Summary</p> <p>Only if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients.</p

Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with b-thalassemia

b-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with b-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non\u2013transfusion dependent (mean hemoglobin, &lt;10.0 g/dL; &lt;4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (\u20214 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for \u20215 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of \u20211.5 g/dL from baseline for \u202114 consecutive days (without RBC transfusions) for non\u2013transfusion-dependent patients or RBC transfusion burden reduction \u202120% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non\u2013transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase \u20211.5 g/dL over \u202114 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved \u202120% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of b-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409

Deferasirox (Exjade®) significantly improves cardiac T2* in heavily iron-overloaded patients with β-thalassemia major

Noninvasive measurement of tissue iron levels can be assessed using T2* magnetic resonance imaging (MRI) to identify and monitor patients with iron overload. This study monitored cardiac siderosis using T2* MRI in a cohort of 19 heavily iron-overloaded patients with β-thalassemia major receiving iron chelation therapy with deferasirox over an 18-month period. Overall, deferasirox therapy significantly improved mean ± standard deviation cardiac T2* from a baseline of 17.2 ± 10.8 to 21.5 ± 12.8 ms (+25.0%; P = 0.02). A concomitant reduction in median serum ferritin from a baseline of 5,497 to 4,235 ng/mL (−23.0%; P = 0.001), and mean liver iron concentration from 24.2 ± 9.0 to 17.6 ± 12.9 mg Fe/g dry weight (−27.1%; P = 0.01) was also seen. Improvements were seen in patients with various degrees of cardiac siderosis, including those patients with a baseline cardiac T2* of <10 ms, indicative of high cardiac iron burden. These findings therefore support previous observations that deferasirox is effective in the removal of myocardial iron with concomitant reduction in total body iron

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Attenuated total reflection infrared spectroscopy for studying adsorbates on planar model catalysts : CO adsorption on silica supported Rh nanoparticles

A sensitive method is presented for studying adsorption of gaseous species on metal surfaces in vacuum by attenuated total internal reflection Fourier transform IR spectroscopy (ATR). The method is illustrated by CO adsorption expts. on silica supported Rh nanoparticles. An exptl. setup and a procedure are described in detail to obtain a sensitivity of reflectance change of .apprx.5 * 10-5 absorbance units. Here, a silicon ATR crystal with a 50 nm layer of hydroxylated silica acts as the support for the Rh nanoparticles. These particles are easily prepd. by spincoat impregnation from a RhCl3 soln. followed by H2 redn. XPS before and after redn. shows that rhodium is reduced to Rh0 and that all chlorine is removed. At. force microscope images the distribution of the particles, which are 3-4 nm in height. When the crystal is exposed to pressures up to 1 mbar of CO, a gas which is inert to the silica support, the stretch vibration of linearly adsorbed CO on the Rh nanoparticles is detected at 2023 cm-1, while no bridged CO or geminal dicarbonyl species can be distinguished. The min. detectable coverage is estd. .apprx.0.005 CO per nm2 substrate area or .apprx.5 * 10-4 ML. [on SciFinder (R)

Factors affecting health-related quality of life in Thai children with thalassemia

<p>Abstract</p> <p>Background</p> <p>Knowledge of the factors associated with health-related quality of life (HRQOL) among patients with thalassemia is essential in developing more suitable clinical, counseling, and social support programs to improve treatment outcomes of these patients. In light of the limited research in this area, this study aims to examine factors associated with HRQOL among children and adolescents with thalassemia in Thailand.</p> <p>Methods</p> <p>A cross-sectional survey was conducted in three selected hospitals in Thailand during June to November 2006. PedsQL™ 4.0 Generic Core Scale (Thai version) was used to assess HRQOL in 315 thalassemia patients between 5 and 18 years of age. Other related clinical characteristics of the patients were collected via medical record review.</p> <p>Results</p> <p>The mean (SD) of the total summary score was 76.67 (11.40), while the means (SD) for the Physical Health Summary score and Psychosocial Health Summary score were 78.24 (14.77) and 75.54 (12.76), respectively. The school functioning subscale scored the lowest, with a mean of 67.89 (SD = 15.92). The following factors significantly affected the HRQOL of the patients: age; age at onset of anemia and age at first transfusion; pre-transfusion hemoglobin (Hb) level; receiving a blood transfusion during the previous three months; and disease severity. In addition, iron chelation therapy had a significant negative effect on HRQOL in the school functioning subscale. In contrast, serum ferritin level, frequency of blood transfusions per year, and gender were not significantly related to HRQOL among these patients. The results from multivariate analysis also confirmed these findings.</p> <p>Conclusions</p> <p>To improve HRQOL of thalassemia patients, suitable programs aimed at providing psychosocial support and a link between the patient, school officials, the family and the physician are important, especially in terms of improving the school functioning score. The findings also confirmed the importance of maintaining a pre-transfusion Hb level of at least 9-10.5 g/dL. In addition, special care and attention should be given to patients with a severe condition, and those who are receiving subcutaneous iron chelation therapy.</p