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The global polarization of Λ hyperons along the total orbital angular momentum of a relativistic heavy-ion collision is presented based on the high statistics data samples collected in Au+Au collisions at sNN=2.4 GeV and Ag+Ag at 2.55 GeV with the High-Acceptance Di-Electron Spectrometer (HADES) at GSI, Darmstadt. This is the first measurement below the strangeness production threshold in nucleon-nucleon collisions. Results are reported as a function of the collision centrality as well as a function of the hyperon's transverse momentum (pT) and rapidity (yCM) for the range of centrality 0–40%. We observe a strong centrality dependence of the polarization with an increasing signal towards peripheral collisions. For mid-central (20 – 40%) collisions the polarization magnitudes are 〈PΛ〉(%)=6.8±1.3(stat.)±2.1(syst.) for Au+Au and 〈PΛ〉(%)=6.2±0.4(stat.)±0.6(syst.) for Ag+Ag, which are the largest values observed so far. This observation thus provides a continuation of the increasing trend previously observed by STAR and contrasts expectations from recent theoretical calculations predicting a maximum in the region of collision energies about 3 GeV. The observed polarization is of a similar magnitude as predicted by 3D-fluid-dynamics and the UrQMD plus thermal vorticity model and significantly above results from the AMPT model.

In this letter we report the first multi-differential measurement of correlated pion-proton pairs from 2 billion Au+Au collisions at sNN=2.42 GeV collected with HADES. In this energy regime the population of Δ(1232) resonances plays an important role in the way energy is distributed between intrinsic excitation energy and kinetic energy of the hadrons in the fireball. The triple differential d3N/dMπ±pdpTdy distributions of correlated π±p pairs have been determined by subtracting the πp combinatorial background using an iterative method. The invariant-mass distributions in the Δ(1232) mass region show strong deviations from a Breit-Wigner function with vacuum width and mass. The yield of correlated pion-proton pairs exhibits a complex isospin, rapidity and transverse-momentum dependence. In the invariant mass range 1.1

We investigate identical pion HBT intensity interferometry in central Au+Au collisions at 1.23A GeV. High-statistics π−π− and π+π+ data are measured with HADES at SIS18/GSI. The radius parameters, derived from the correlation function depending on relative momenta in the longitudinally comoving system and parametrized as three-dimensional Gaussian distribution, are studied as function of transverse momentum. A substantial charge-sign difference of the source radii is found, particularly pronounced at low transverse momentum. The extracted source parameters agree well with a smooth extrapolation of the center-of-mass energy dependence established at higher energies, extending the corresponding excitation functions down towards a very low energy.

We present first data on sub-threshold production of Ks0 mesons and Λ hyperons in Au+Au collisions at sNN=2.4 GeV. We observe an universal 〈Apart〉 scaling of hadrons containing strangeness, independent of their corresponding production thresholds. Comparing the yields, their 〈Apart〉 scaling, and the shapes of the rapidity and the pt spectra to state-of-the-art transport model (UrQMD, HSD, IQMD) predictions, we find that none of them can simultaneously describe these observables with reasonable χ2 values.

Background: Cytomegalovirus (CMV) is the most common viral infection among lung transplant recipients and is associated with chronic lung allograft dysfunction. There is a need for better therapeutics as well as biomarkers to enable effective stratification of CMV seropositive patient risk for developing CMV DNAemia to inform prophylaxis duration. Methods: CMV-specific immunoglobulin G (IgG) binding and functional responses were evaluated in a discovery cohort of longitudinal plasma samples from 51 CMV seropositive human lung transplant recipients, collected as part of the clinical trials in organ transplantation (CTOT)-20 and CTOT-22 consortium studies. Pre-transplant plasma from an additional 43 CMV seropositive lung transplant recipients was evaluated as a validation cohort. Results: In the discovery cohort with longitudinal samples, pre-transplant plasma IgG binding to CMV surface glycoproteins glycoprotein H (gH)/glycoprotein L (gL), gH/gL/glycoprotein O (gO), and pentameric complex, as well as neutralization of CMV in epithelial cells, is associated with increased risk of CMV DNAemia post-prophylaxis. However, these results were not confirmed by the validation cohort. Conclusions: While quantification of pre-transplant CMV-specific antibody responses showed association with DNAemia in the discovery cohort, additional clinical variables and/or known risk factors for CMV, such as patient CMV-specific T-cell responses, may need to be considered in combination with humoral immunity to effectively stratify risk of CMV DNAemia.

Modern untargeted mass spectrometry (MS) analyses quickly detect and resolve thousands of molecular compounds. Although features are readily annotated with a molecular formula in high-resolution small-molecule MS applications, the large majority of them remains unidentified in terms of their full molecular structure. Collision-induced dissociation tandem mass spectrometry (CID-MS 2 ) provides a diagnostic molecular fingerprint to resolve the molecular structure through a library search. However, for de novo identifications, one must often rely on in silico generated MS 2 spectra as reference. The ability of different in silico algorithms to correctly predict MS 2 spectra and thus to retrieve correct molecular structures is a topic of lively debate, for instance in the CASMI contest. Underlying the predicted MS 2 spectra are the in silico generated product ion structures, which are normally not used in de novo identification, but which can serve to critically assess the fragmentation algorithms. Here we evaluate in silico generated MS n product ion structures by comparison with structures established experimentally by infrared ion spectroscopy (IRIS). For a set of three dozen product ion structures from five precursor molecules, we find that virtually all fragment ion structure annotations in three major in silico MS 2 libraries (HMDB, METLIN, mzCloud) are incorrect and caution the reader against their use for structure annotation of MS/MS ions., (© 2024. The Author(s).)

Background: Mastocytosis is characterized by an accumulation of clonal mast cells (MCs) in tissues such as the skin. Skin lesions in mastocytosis may be clinically subtle or heterogeneous, and giving the correct diagnosis can be difficult., Methods: This study compiles personal experiences together with relevant literature, discussing possible obstacles encountered in diagnosing skin involvement in mastocytosis and cutaneous mastocytosis (CM)., Results: The nomenclature of the term "CM" is ambiguous. The WHO classification defines CM as mastocytosis solely present in the skin. However, the term is also used as a morphological description, e.g., in maculopapular cutaneous mastocytosis (MPCM). This is often seen in systemic, as well as cutaneous, mastocytosis. Typical CM manifestations (MPCM), including mastocytoma or diffuse cutaneous mastocytosis (DCM), all share a positive Darier's sign, and can thus be clinically recognized. Nevertheless, distinguishing monomorphic versus polymorphic MPCM may be challenging, even for experienced dermatologists. Less typical clinical presentations, such as MPCM with telangiectatic erythemas (formerly called telangiectasia macularis eruptiva perstans), confluent, nodular or xanthelasmoid variants may require a skin biopsy for histopathological confirmation. Because MC numbers in CM have a large overlap to those in healthy and inflamed skin, detailed histopathological criteria to diagnose mastocytosis in MPCM are needed and have been proposed. D816V KIT mutational analysis in tissue is helpful for confirming the diagnosis. Biomarkers allow the prediction of the course of CM into regression or evolution of the disease. Further diagnostic measures should screen for concomitant diseases, such as malignant melanoma, and for systemic involvement., Conclusions: Whereas in typical cases the diagnosis of CM may be uncomplicated, less typical manifestations may require specific investigations for making the diagnosis and predicting its course.

Introduction: The correct moment for return to driving after total hip arthroplasty (THA) remains unclear. Until today no uniform recommendation exists on the ability to perform an emergency brake.The aim of this prospective study was to investigate the braking ability of patients before and after THA implantation based on brake reaction time in milliseconds (BRT) and braking force in N (BF)., Methods: In total, 25 patients (15 men, 10 women, mean age 51.3 ± 10.1 years) were treated with THA on the right side. Inclusion criteria consisted of a valid driving licence, frequent road participation and at least 2 years of driving experience. Exclusion criteria were underlying neurological disorders as well as severe complaints in the lumbar spine and the right knee joint. The brake ability was evaluated for emergency braking with a car simulator and a measuring sole. Measurements were performed preoperatively, 6 days, 2, 4 and 6 weeks after surgery., Results: Preoperatively, the mean BRT was 671.3 ± 123.5 ms and the BF 455.4 ± 185.0 N. Significant differences were observed at 6 days and 2 weeks after surgery, (BRT 836.4 ± 219.7 ms, respectively, BRT 735.0 ± 186.7 ms, and BF 302.6 ± 154.9 N, respectively, BF 375.5 ± 149.3 N, p  < 0.05). Only 4 weeks after, no significant differences were seen compared to pre-operative with a BRT of 647.0 ± 91.9ms ( p  = 0.354) and BF of 435.9 ± 177.4 ( p  = 0.843). Furthermore, the BRT improved significantly after 6 weeks (607.4 ± 87.6; p  = 0.005)., Conclusions: The braking force is significantly reduced, and the brake reaction time is prolonged directly after surgery for at least 2 weeks. After 4 weeks, no statistically significant differences were measured, although special care should still be taken during return to activity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 10 2.0 , influenza B virus at 10 2.2 , and SARS-CoV-2 at 10 0.3 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2.

Flow coefficients v&#95;{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s&#95;{NN}]=2.4  GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7  GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})&#95;{W}/(K^{-}/K^{+})&#95;{C} is found to be 0.319±0.009(stat)&#95;{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)&#95;{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)&#95;{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.

Objectives: High levels of religious involvement have been associated with positive mental health outcomes in older adults. This study investigated whether the effects of religion on healthy aging could generalize to older LGBTQ adults., Methods: This study examined religious affiliation in childhood versus at present, as well as the relationships of outness to religious community and religious engagement with depression and loneliness in 102 lesbian, gay, and bisexual cisgender, transgender, and questioning adults (LGBTQ) over the age of 55. As part of a larger study, participants completed several questions and measures including: one outness to religious community item, 4 religious engagement questions, the Center for Epidemiological Studies Depression Scale, and the 8-item UCLA Loneliness Scale., Results: Many older LGBTQ adults reported changes in religious affiliation from childhood to adulthood. Greater levels of outness to religious communities and lower religious engagement were related to lower levels of depression and loneliness., Conclusions: Findings suggest that outness to religious communities may be beneficial to the mental health of older LGBTQ adults. Higher levels of distress may lead to higher levels of religious engagement., Clinical Implications: Religion, especially those that are supportive of sexual minorities, may help to improve the well-being of older LGBTQ adults.

This article presents the evidence base for 'operator models' - that is, how to deliver a sustainable service through the interaction of the 'client', 'revenue collector' and 'operator' functions - for municipal solid waste management in emerging and developing countries. The companion article addresses a selection of locally appropriate operator models. The evidence shows that no 'standard' operator model is effective in all developing countries and circumstances. Each city uses a mix of different operator models; 134 cases showed on average 2.5 models per city, each applying to different elements of municipal solid waste management - that is, street sweeping, primary collection, secondary collection, transfer, recycling, resource recovery and disposal or a combination. Operator models were analysed in detail for 28 case studies; the article summarises evidence across all elements and in more detail for waste collection. Operators fall into three main groups: The public sector, formal private sector, and micro-service providers including micro-, community-based and informal enterprises. Micro-service providers emerge as a common group; they are effective in expanding primary collection service coverage into poor- or peri-urban neighbourhoods and in delivering recycling. Both public and private sector operators can deliver effective services in the appropriate situation; what matters more is a strong client organisation responsible for municipal solid waste management within the municipality, with stable political and financial backing and capacity to manage service delivery. Revenue collection is also integral to operator models: Generally the municipality pays the operator from direct charges and/or indirect taxes, rather than the operator collecting fees directly from the service user.

Unlabelled: Current standard practice for radioembolization treatment planning makes use of nuclear medicine imaging (NMI) of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) arterial distributions for the assessment of lung shunting and extrahepatic uptake. Our aim was to retrospectively compare NMI with mapping angiography in the detection and localization of extrahepatic (99m)Tc-MAA and to evaluate the typical and atypical findings of NMI in association with catheter placement., Methods: One hundred seventy-four patients underwent diagnostic angiography in preparation for radioembolization. (99m)Tc-MAA was administered to the liver via a microcatheter positioned in the desired hepatic artery. Planar scintigraphy imaging followed by SPECT/CT imaging was obtained within 2 h. All images were reviewed for hepatic and extrahepatic (99m)Tc-MAA deposition and compared with the mapping angiogram., Results: Intrahepatic lobe shunting was present on NMI in only 2.9% of the cases but was present in 62.5% of the patients with portal vein thrombosis. Extrahepatic distributions included lungs (100%), the gallbladder (49%) if present, and locations involving hepaticoenteric arterial anatomy recognized on angiograms (16%). Free pertechnetate was identified on 38% of the nuclear medicine images. Three percent of nuclear medicine images showed alternative findings such as a thyroid nodule or metallic artifact., Conclusion: Patients being considered for radioembolization should undergo both angiography and scintigraphy for the assessment of hepaticoenteric arterial anatomy, hepatopulmonary shunting, and appropriate dosimetry considerations. Knowledge of the expected distribution of (99m)Tc-MAA with normal variants and potential nontarget delivery to adjacent structures is critical in improving clinical outcomes., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Preclinical studies suggest that bortezomib, through inhibition of nuclear factor-κB (NF-κB) activation, may enhance the effects of radioimmunotherapy. This phase I trial was designed to determine the maximum tolerated dose (MTD) of weekly bortezomib induction combined with Y-90-ibritumomab tiuxetan followed at the time of count recovery by weekly bortezomib consolidation in patients with relapsed/refractory follicular or transformed non-Hodgkin lymphoma. Grade 3 or 4 toxicities were observed in eight of nine treated patients, and all but one of these toxicities were hematologic. One patient had grade 3 cardiotoxicity. A dose limiting toxicity (DLT) of grade 4 thrombocytopenia was observed in two of three patients treated with bortezomib at 1.6 mg/m(2), resulting in a MTD of 1.3 mg/m(2). The overall response rate was 89% (two complete response [CR], six partial response [PR], one stable disease [SD]), with a median progression-free survival of 6.5 months (range: 3-22.5+ months). A phase II trial at the MTD is under way to better define the toxicity and effectiveness of this regimen.

Unlabelled: Radioembolization with 90Y microspheres represents a novel transarterial radiation treatment for liver tumors. The purpose of this pilot study was to evaluate the findings of postimplantation PET/CT of 90Y glass microspheres., Methods: Three patients with hepatocellular carcinoma and 2 patients with liver metastases (1 neuroendocrine, 1 colorectal) underwent PET/CT after radioembolization. Four patients underwent imaging at 1 mo to assess response and confirm PET/CT findings; 1 patient underwent PET/CT at 4 d after 90Y implantation. Patients were followed for adverse events., Results: Standard PET/CT enabled the localization of 90Y glass microspheres for all patients. None of the patients experienced adverse events related to nontarget deposition., Conclusion: Standard PET/CT may be used to assess the localization of 90Y glass microspheres. This approach provides a simple, rapid, and universally applicable method of confirming microsphere deposition. With further validation, this technique may potentially become the standard of care for confirming microsphere distribution.

Purpose: This study prospectively evaluated the use of lymphangiogram, computed tomography/magnetic resonance imaging, and positron emission tomography (PET) imaging of lymph node metastasis in patients receiving definitive chemoradiotherapy for cervical cancer., Materials and Methods: Twenty patients underwent lymphangiogram, computed tomography/magnetic resonance imaging, and PET. There was no histologic verification of metastasis. Four lymph node regions, including the internal, external, and common iliacs, and para-aortic, were scored as positive or negative for metastasis. Agreement between imaging was analyzed using multirater kappa and disease-free survival utilizing Kaplan Meier survival curves and log-rank test., Results: Agreement between imaging was most consistent in the common iliacs (P < 0.001) and least in the para-aortic region (P = 0.41). Disease-free survival (DFS) at one year was statistically associated with positive PET imaging (25%) versus negative PET imaging (86%) (P = 0.033) in the common iliac lymph node region. No other single lymph node region in any modality was statistically associated with DFS. One-year DFS in patients with any positive areas on PET imaging was 50% compared with 90% in patients with negative PET imaging (P = 0.02). Seven patients were noted to have no metastasis in any region by all 3 of the imaging modalities; the 1-year DFS in these 7 patients was 100% compared with 59% in the 13 patients with any positive nodal area (P = 0.05)., Conclusions: Positive lymphadenopathy on PET imaging was associated with reduced DFS.

Purpose: Therapeutic strategies to enhance the efficacy of radioimmunotherapy have not been explored. Motexafin gadolinium is a novel anticancer agent that targets redox-dependent pathways and enhances sensitivity of tumor cells to ionizing radiation., Experimental Design: We did preclinical studies examining motexafin gadolinium combined with rituximab and/or radiation in lymphoma cells. We subsequently completed a phase I clinical trial combining escalating doses of motexafin gadolinium concurrently with standard [(90)Y]ibritumomab tiuxetan for patients with relapsed/refractory non-Hodgkin's lymphoma., Results: In HF1 lymphoma cells, motexafin gadolinium and rituximab resulted in synergistic cytotoxicity (combination index, 0.757) through a mitochondrial-mediated caspase-dependent pathway, whereas cell death in Ramos and SUDHL4 cells was additive. Motexafin gadolinium/rituximab combined with radiation (1-3 Gy) resulted in additive apoptosis. Twenty-eight of 30 patients were evaluable on the phase I clinical trial. Median age was 65 years (47-87 years), and histologies were marginal-zone (n = 1), mantle-cell (n = 3), diffuse large cell (n = 6), and follicular lymphoma (n = 18). Of all patients, 86% were rituximab refractory. Therapy was well tolerated, and no dose-limiting toxicity was seen. Overall response rate was 57% [complete remission (CR), 43%], with median time-to-treatment failure of 10 months (1-48+ months) and median duration-of-response of 17 months. Of note, all responses were documented at 4 weeks. Furthermore, in rituximab-refractory follicular lymphoma (n = 14), overall response rate was 86% (CR, 64%), with a median time-to-treatment failure of 14 months (2-48+ months)., Conclusions: This represents the first report of a novel agent to be combined safely concurrently with radioimmunotherapy. Furthermore, tumor responses with [(90)Y]ibritumomab tiuxetan/motexafin gadolinium were prompt with a high rate of CRs, especially in rituximab-refractory follicular lymphoma.

Purpose: To correlate changes in 2-deoxy-2-[18F]fluoro-d-glucose (18-FDG) positron emission tomography (PET) (18-FDG-PET) uptake with response and disease-free survival with combined modality neoadjuvant therapy in patients with locally advanced rectal cancer., Methods and Materials: Charts were reviewed for consecutive patients with ultrasound-staged T3x to T4Nx or TxN1 rectal adenocarcinoma who underwent preoperative chemoradiation therapy at Fox Chase Cancer Center (FCCC) or Robert H. Lurie Comprehensive Cancer Center of Northwestern University with 18-FDG-PET scanning before and after combined-modality neoadjuvant chemoradiation therapy . The maximum standardized uptake value (SUV) was measured from the tumor before and 3 to 4 weeks after completion of chemoradiation therapy preoperatively. Logistic regression was used to analyze the association of pretreatment SUV, posttreatment SUV, and % SUV decrease on pathologic complete response (pCR), and a Cox model was fitted to analyze disease-free survival., Results: A total of 53 patients (FCCC, n = 41, RLCCC, n = 12) underwent pre- and postchemoradiation PET scanning between September 2000 and June 2006. The pCR rate was 31%. Univariate analysis revealed that % SUV decrease showed a marginally trend in predicting pCR (p = 0.08). In the multivariable analysis, posttreatment SUV was shown a predictor of pCR (p = 0.07), but the test results did not reach statistical significance. None of the investigated variables were predictive of disease-free survival., Conclusions: A trend was observed for % SUV decrease and posttreatment SUV predicting pCR in patients with rectal cancer treated with preoperative chemoradiation therapy. Further prospective study with a larger sample size is warranted to better characterize the role of 18-FDG-PET for response prediction in patients with rectal cancer.

Purpose: To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 ((90)Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation., Patients and Methods: Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized (90)Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of (90)Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation., Results: Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively., Conclusion: Dose-escalated (90)Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.

Objective: To examine the relationship of baseline homocysteine levels with bone mineral density (BMD) and incidence of fractures over 2 years in women with and without systemic lupus erythematosus (SLE)., Methods: Women with SLE (n = 100) and without SLE (n = 100) were matched according to age (+/- 5 yrs), race, and menopausal status. Data were collected from 1997 to 2004, including hip, lumbar spine (L-spine), and distal forearm BMD, serum homocysteine levels, and a self-administered questionnaire on osteoporosis risk factors, medications and symptomatic fractures at baseline and 2-year followup. Analyses were performed to compare homocysteine levels, BMD, and incident fractures and to evaluate the relationship of homocysteine with BMD and incident fractures in both groups., Results: Mean homocysteine +/- SD was higher (p < 0.001) in women with SLE (9.88 +/- 3.8 micromol/l) than in women without SLE (7.98 +/- 2.6 micromol/l). Women with SLE had significantly lower L-spine BMD Z-scores, while hip BMD Z-scores and distal forearm BMD T-scores were nonsignificantly lower than in women without SLE. No significant correlations were observed between homocysteine and BMD in either group. Thirteen women with SLE experienced new fractures, while 4 women without SLE had new fractures over 2 years (p = 0.035); however, there was no association between homocysteine levels and incident fractures in either group., Conclusion: Women with SLE had significantly greater baseline homocysteine, lower L-spine BMD, and more new fractures over 2 years, compared with women without SLE. Homocysteine levels were not significantly associated with BMD and did not predict new fractures in women with or without SLE over 2 years.

Somatostatin receptors have been identified in many tissues throughout the human body. Alterations in the expression of somatostatin receptors have been reported in many disease states including both tumorous and nontumorous conditions. Somatostatin receptor scintigraphy utilizing OctreoScan (Mallinckrodt Medical, Inc., St. Louis, MO), a radiolabled form of octreotide, has been reported to be a highly sensitive imaging technique for identifying pathology, such as neuroendocrine tumors, that are somatostatin receptor dense. Unfortunately, many conditions cause an increase in the quantity of somatostatin receptors and therefore may cause false positive Octreoscans. In this report, we discuss the alterations in somatostatin receptors that occur with Crohn's disease and describe a case of an OctreoScan-positive inflammatory mass mimicking a carcinoid tumor.

Objective: To determine the frequency of fractures and associated factors in women with systemic lupus erythematosus (SLE)., Methods: Women with SLE (n = 304) completed this cross-sectional study conducted from 1996 to 2002. Self-reported fractures occurring after the diagnosis of SLE were evaluated. Hip and/or lumbar spine bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry, and the results were expressed as BMD Z-scores. Multiple logistic regression analyses were performed to identify factors associated with fractures., Results: Of the 304 women with SLE, 12.5% experienced fractures. Those with fractures had significantly lower BMD Z-scores at the hip (Fracture group -0.55 vs No Fracture group -0.14, group difference 0.41; 95% CI 0.04 to 0.78), but not at the lumbar spine (Fracture group -0.25 vs No Fracture group -0.18, group difference 0.07; 95% CI -0.43 to 0.57). Among women with fractures, 60.5% and 63.2% had normal BMD Z-scores (BMD Z-score > -1.0) at the hip and lumbar spine, respectively, and 50.0% had normal BMD Z-scores at both anatomical sites. In multiple logistic regression analysis, each year of disease duration (adjusted OR 1.11; 95% CI 1.05 to 1.17) and use of osteoporosis medications (adjusted OR 4.75; 95% CI 1.62 to 13.94) were significantly associated with fractures., Conclusion: . Longer duration of SLE and use of osteoporosis medications were significantly associated with fractures. Although women with fractures had significantly lower BMD Z-scores at the hip, an unexpectedly high proportion of women with SLE having normal BMD Z-score experienced fractures following SLE diagnosis.

Objective: To determine the association between race/ethnicity and bone mineral density (BMD) in women with systemic lupus erythematosus (SLE)., Methods: Women with SLE (n = 298), including 77 African Americans and 221 whites, completed this cross-sectional study conducted from 1996 to 2002. Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. Study participants completed a self-administered questionnaire and a physician completed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). BMD results were expressed as Z scores. Analyses were performed to identify factors, including race/ethnicity, associated with low BMD defined as a Z score -1.0 or less at the hip or lumbar spine., Results: African Americans compared with whites were younger at study visit (mean +/- SD 39.7 +/- 8.4 years versus 42.9 +/- 11.6 years) and had higher SDI (mean +/- SD 1.8 +/- 2.0 versus 1.0 +/- 1.6), but similar proportions of women were postmenopausal (31.2% versus 38.0%). African Americans had significantly lower mean BMD Z scores at the hip (-0.49 versus -0.07; group difference -0.41; 95% confidence interval [95% CI] -0.70, -0.13) and at the lumbar spine (-1.03 versus 0.10; group difference -1.13; 95% CI -1.48, -0.78) compared with whites. African American race/ethnicity was strongly associated with low BMD at the lumbar spine (adjusted odds ratio 4.42; 95% CI 2.19, 8.91) but not at the hip, adjusting for factors associated with low BMD., Conclusion: African American women compared with white women with SLE had lower BMD at the hip and lumbar spine. African American race/ethnicity was associated with low BMD at the lumbar spine controlling for relevant clinical covariates.

Background: [18F]Fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan is widely used for the staging evaluation of nonsmall cell lung cancer, however, its use in small cell lung cancer (SCLC) remains investigational., Patient and Methods: We designed a prospective study to evaluate the role of PET in SCLC. Patients with SCLC underwent PET scanning as well as conventional imaging before and after treatment., Results: A total of 39 PET scan examinations were performed in 21 patients with SCLC; 18 studies were performed before first-line chemotherapy and 21 studies were done during or after treatment. PET findings were compared with findings on CT scans of the chest or abdomen and bone scan. Discordant findings were detected in 14 out of 383 comparisons (4%) for 10 anatomic sites. In the thorax and the abdomen, PET agreed with CT scan in 92% to 100% of examinations assessing potential disease sites, including the contralateral chest, liver, and adrenals. PET agreed with bone scan in detecting bony lesions in 27 out of 32 imaging studies (84%): in 4 out of 5 discordant cases, PET findings were true and in 1 case indeterminate. Staging at baseline (limited, n = 6; extensive, n = 12) was identical when PET and sum of other staging procedures were compared. Response assessment was concordant between PET and CT scans in 8 of 9 patients who had evaluation before and after first-line chemotherapy., Conclusions: PET is potentially useful for the initial staging and monitoring of patients with SCLC and it may be superior to bone scan in detecting bone metastasis. The cost effectiveness of PET scan in SCLC remains to be determined.

The results and complications using the dorsal 2.4 mm 2.7 mm (AO/ASIF) pi-plate for the treatment of distal radius fractures were evaluated in a prospective study of 42 patients followed up clinically and radiologically and seven patients followed up with telephone call and radiological follow-up for an average time of 12.1 (range 4-32) months in a group of 50 patients with intraarticular distal radial fractures treated consecutively using this method. Twelve complications occurred in 10 patients including two extensor tendon ruptures, two transient cases of CRPS Type 1 (Reflex Sympathetic Dystrophy, Algodystrophy), two instances of screw loosening, three cases of posttraumatic carpal tunnel syndrome and three permanent sensory irritations on the dorsum of the hands. Using the AO score, there were 37 successful and 12 tolerable results, with no unsatisfactory outcomes. Using the NYOWR scale, there were 17 very good and 25 good results, with no satisfactory or poor outcomes. These results suggest that this osteosynthesis provides adequate fixation of comminuted distal intraarticular radius fractures with a reasonable incidence of complications.

Objectives: To evaluate the relationship between disease damage and bone mineral density (BMD) in women with systemic lupus erythematosus (SLE)., Methods: A cross-sectional study was conducted among 307 women with SLE. Patients attended a single clinic visit that included an interview, physical examination, laboratory testing and BMD measurements (hip and/or lumbar spine). Women were stratified by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology cumulative disease damage index (SDI) > or =1 (Damage) vs SDI=0 (No Damage), and prior use of corticosteroids (CS), yielding four groups: (1) Damage/CS(+) (n=138), (2) Damage/CS(-) (n=23), (3) no Damage/CS(-) (n=100), and (4) no Damage/CS(-) (n=46)., Results: Mean age at SLE diagnosis was 32.7 +/- 11.8 yr, 24.4% were African American, 65.0% were premenopausal, and mean SDI +/- S.D. was 1.3 +/- 1.8. In the unadjusted and adjusted models controlling for significant univariate risk factors for osteoporosis, the reference group (Group 1) had significantly lower mean BMD T-scores at the hip and lumbar spine than groups having no disease damage (Groups 3 and 4) independent of CS use status. Similar hip and lumbar spine mean BMD T-scores were observed in women with disease damage with and without CS exposure (Groups 1 and 2)., Conclusions: Women with SLE having disease damage and no CS use had BMD T-scores at the hip and lumbar spine similar to those of women with disease damage and prior CS use. These findings suggest an association between disease damage and lower BMD T-scores in women with SLE.

This report presents updated time-to-event variables from a multicenter phase II trial of reduced-dose 90Y ibritumomab tiuxetan in patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL) and mild thrombocytopenia (platelet counts of 100 to 149 x 10(9) platelets/L). Patients received a single course of ibritumomab tiuxetan radioimmunotherapy, with 90Y ibritumomab tiuxetan administered at 0.3 mCi/kg (compared to a standard dose of 0.4 mCi/kg). In 30 patients, the overall response rate was 83%, with complete responses (confirmed [CR] and unconfirmed [CRu]) of 47%. Median follow-up time is currently 36.5 months (range: 7.5-54.9+ months). Median duration of response was 11.5 months (range: 1.0-53.9 months), median time to progression was 9.4 months (range: 1.7-54.8+ months), and median time to next lymphoma therapy was 14.6 months (range: 2.3-54.9 months). Median overall survival time has not yet been reached. Long-term responses, defined as time to progression of 12 months or greater, have been seen in 14 of 30 patients (47%) overall, and 12 of 14 CR/CRu patients (86%). Toxicities were primarily hematologic and reversible. No additional long-term adverse events have been observed in the follow-up period, and treatment did not preclude subsequent lymphoma therapies., (Copyright Mary Ann Liebert, Inc.)

Paragangliomas are indolent tumors that arise from the chief cells of the paraganglia in the head and neck, mediastinum, and retroperitoneal regions. Less than 10% of paragangliomas metastasize. Paragangliomas are known to regress slowly and usually partially after radiation therapy, which has been attributed to the development of fibrosis within the abundant vascular elements of the tumor. Positron emission tomography (PET) scanning was used to monitor a 33-year-old woman with recurrent paraganglioma of the carotid body with lung and bone metastases before and after chemotherapy with cyclophosphamide, doxorubicin (Adriamycin), and dacarbazine. The patient derived clinical benefit from chemotherapy, with marked improvement of her systemic and respiratory symptoms, improvement of cancer-related anemia, and normalization of chromogranin A levels. A response was demonstrated on PET scan with decreased [18F] fluoro-2-deoxy-d-glucose uptake after chemotherapy, but no significant changes were detected on serial computed tomography (CT) scans. The patient has remained free of disease progression 24 months after chemotherapy completion. It is suggested that metabolic imaging with PET scans is superior to anatomical imaging with CT scans for the monitoring of patients with paragangliomas.

Unlabelled: Ibritumomab tiuxetan is an anti-CD20 murine IgG1 kappa monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates (111)In for imaging or dosimetry and (90)Y for radioimmunotherapy (RIT). Dosimetry and pharmacokinetic data from 4 clinical trials of (90)Y-ibritumomab tiuxetan RIT for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) were combined and assessed for correlations with toxicity data., Methods: Data from 179 patients were available for analysis. Common eligibility criteria included <25% bone marrow involvement by NHL, no prior myeloablative therapy, and no prior RIT. The baseline platelet count was required to be > or = 100,000 cells/mm(3) for the reduced (90)Y-ibritumomab tiuxetan administered dose (7.4-11 MBq/kg [0.2-0.3 mCi/kg]) or > or = 150,000 cells/mm(3) for the standard (90)Y-ibritumomab tiuxetan administered dose (15 MBq/kg [0.4 mCi/kg]). Patients were given a tracer administered dose of 185 MBq (5 mCi) (111)In-ibritumomab tiuxetan on day 0, evaluated with dosimetry, and then a therapeutic administered dose of 7.4-15 MBq/kg (0.2-0.4 mCi/kg) (90)Y-ibritumomab tiuxetan on day 7. Both ibritumomab tiuxetan administered doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve ibritumomab tiuxetan biodistribution. Residence times for (90)Y in blood and major organs were estimated from (111)In biodistribution, and the MIRDOSE3 computer software program was used, with modifications to account for patient-specific organ masses, to calculate radiation absorbed doses to organs and red marrow., Results: Median radiation absorbed doses for (90)Y were 7.42 Gy to spleen, 4.50 Gy to liver, 2.11 Gy to lung, 0.23 Gy to kidney, 0.62 Gy (blood-derived method) and 0.97 Gy (sacral image-derived method) to red marrow, and 0.57 Gy to total body. The median effective blood half-life was 27 h, and the area under the curve (AUC) was 25 h. No patient failed to meet protocol-defined dosimetry safety criteria and all patients were eligible for treatment. Observed toxicity was primarily hematologic, transient, and reversible. Hematologic toxicity did not correlate with estimates of red marrow radiation absorbed dose, total-body radiation absorbed dose, blood effective half-life, or blood AUC., Conclusion: Relapsed or refractory NHL in patients with adequate bone marrow reserve and <25% bone marrow involvement by NHL can be treated safely with (90)Y-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity.

Mildly thrombocytopenic patients with relapsed or refractory low-grade non-Hodgkin lymphoma (NHL) have an increased risk of chemotherapy-induced myelosuppression following treatment. The safety and efficacy of radioimmunotherapy with a reduced dose of (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]; maximum 32 mCi [1.2 GBq]) was evaluated in 30 patients with mild thrombocytopenia (100-149 x 10(9) platelets/L) who had advanced, relapsed or refractory, low-grade, follicular, or transformed B-cell NHL. The ibritumomab tiuxetan regimen included an infusion of rituximab (250 mg/m(2)) and injection of (111)In ibritumomab tiuxetan (5 mCi [185 MBq]) for dosimetry evaluation, followed 1 week later with rituximab (250 mg/m(2)) and (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]). Patients (median age, 61 years; 90% stage III/IV at study entry; 83% follicular lymphoma; and 67% with bone marrow involvement) had a median of 2 prior therapy regimens (range, 1-9). Estimated radiation-absorbed doses were well below the study-defined maximum allowable for all 30 patients. With the use of the International Workshop criteria for NHL response assessment, the overall response rate was 83% (37% complete response, 6.7% complete response unconfirmed, and 40% partial response). Kaplan-Meier estimated median time to progression (TTP) was 9.4 months (range, 1.7-24.6). In responders, Kaplan-Meier estimated median TTP was 12.6 months (range, 4.9-24.6), with 35% of data censored. Toxicity was primarily hematologic, transient, and reversible. The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 33%, 13%, and 3%, respectively. Reduced-dose ibritumomab tiuxetan is safe and well tolerated and has significant clinical activity in this patient population.

Rain data are collected all over the world because water is of paramount importance to all human life. WMO has provided standards for collection and standardized data processing of daily rainfall measurements. Currently no such standards are available for gauges with a resolution suitable for urban hydrology, where the resolution in time must not exceed a few minutes. The Group on Urban Rainfall under the International Water Association has made a comparison of national standards by means of a survey of 77 questions sent to 44 countries. The paper discusses the first results of the answers of the survey. Currently tipping bucket gauges are the dominating method of obtaining high resolution rain data, but the numbers of weighing gauges and radar measurements are rapidly growing. It is necessary to try to increase the awareness of documentation of current standards and to agree on standards for measurements and data processing on an international level in the future.

Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received (111)In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8 ) on day 0 followed by a therapeutic dose of 90Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of (111)In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T(1/2), blood AUC, plasma T(1/2), and plasma AUC. It is concluded that 90Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T(1/2), reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population.

Purpose: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy., Patients and Methods: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20(+) B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass > or = 5 cm., Results: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/microL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (> or = 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody)., Conclusion: These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.

Approximately 55,400 new cases of non-Hodgkin's lymphoma (NHL) are diagnosed each year, with the overall prevalence of the disease now estimated to be 243,000. Until recently, treatment alternatives for advanced disease included chemotherapy with or without external beam radiation. Based on the results of several clinical trials, the chimeric monoclonal antibody Rituximab has now been approved by the United States Food and Drug Administration as a treatment for patients with relapsed or refractory, low-grade or follicular, B-cell NHL. Several other monoclonal antibodies in conjugated and unconjugated forms have been evaluated in the treatment of NHL. Ibritumomab, the murine counterpart to Rituximab, radiolabeled with 90Y (Zevalin), is presently being evaluated in clinical trials. The success of radioimmunotherapy is dependent upon the appropriate choice of antibody, isotope, and chelator-linker. The Ibritumomab antibody targets the CD20 antigen. The antibody is covalently bound to the chelator-linker tiuxetan (MX-DTPA), which tightly chelates the isotope 90Y. To date, two Phase I/II Zevalin clinical trials have been completed in patients with low-grade, intermediate-grade, and mantle cell NHL. The overall response rate was 64% in the first trial and 67% in the later trial. Phase II and III trials are ongoing.

Fluorescence microscopy was used to examine Papanicolaou-stained smears of sputum and other secretions from the respiratory tract. Under these conditions Charcot-Leyden crystals (CLC) appear as bright yellow-green fluorescing needles. The study was performed to determine the value of this approach for the diagnosis of allergic lung diseases. The time taken to detect the crystals was recorded and the sensitivity of fluorescence microscopy for the detection of CLC was compared with light microscopy of the same samples. The data show that fluorescence microscopy is superior to light microscopy for the detection of CLC. The characteristic needle-shaped crystal can be recognized easily and fragments of crystals could be easily identified. In doubtful cases of allergic lung diseases, fluorescence microscopy may be used to supplement light microscopy for the detection of Charcot-Leyden crystals.