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The knowledge of variables associated with quality of life in women with nonvertebral fractures is poor. The aim of this study was to examine the independent associations between sociodemographic and clinical factors, self-care, and quality of life in this specific population. We undertook a 3-year multicenter longitudinal study on a cohort of Italian postmenopausal osteoporotic women with three follow-ups at 1, 3, and 6 months. Nurses asked women to complete questionnaires on quality of life and self-care. The sample (n= 532) had a mean age of 74.78 years. The results showed that women taking more than two medications per day (p= .026) and those with nine or more years of education (p= .036) were more likely to exhibit better quality of life levels (p< .001) than their counterparts. Both self-care and quality of life scores improved over time in all participants. This study shows positive independent associations between quality of life and polypharmacy, education, and self-care behaviors, which were improved by educational interventions to attain a better quality of life in our participants.

We prove that if Kis a set of type (q-1,n)with n>q-1in PG(3, q), then n=2q-1.

Objective: To evaluate the features and prognosis of melanoma of glans penis and urethra, with the presentation of a significant case report.Materials and methods: A systematic literature review was performed using the MEDLINE (PubMed) and Cochrane Libraries databases to identify all cases of male mucosal melanoma reported.Results: Two hundred fifty-two patients with male mucosal primary melanoma were found. Glans penis and fossa navicularis as primary site includes the 81.6% of all lesions considered. Median Breslow’s depth is 2.1 mm, whereas nine in situ melanomas have been reported. At the diagnosis, the disease was at a non-localized stage in 21.4% for glans penis melanomas and 11.7% urethral lesions, respectively. The 2 and 5-year survival for glans melanoma is 62.5% and 38.4%; higher rates were observed in the 2012–2020 period (76% and 58.8%, respectively). Two-year survival for urethral melanomas is 66.7%, while 5-year survival is 12.5%. 22 patients survived over 5 years with a Breslow’s depth reported always < 3.3 mm.Conclusion: Melanoma of the glans penis and urethra is a rare neoplasm associated with a poor prognosis, however recent reports show higher survival rates. Surgery remains the mainstay for a localized disease. Taking into account the small number of cases reported, topical imiquimod seems to be a valid non-surgical alterative for melanoma in situ. The use of immunotherapy and targeted therapy should be considered only in an adjuvant setting according to the recommendations of cutaneous melanoma; however, additional clinical data on male mucosal melanoma are needed to draw definitive conclusions.

IMPORTANCE: Single-agent carboplatin is often proposed instead of a conventional carboplatin–paclitaxel doublet in vulnerable older patients with ovarian cancer. Such an approach could have a detrimental effect on outcomes for these patients. OBJECTIVE: To compare the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin–paclitaxel, or conventional every-3-weeks carboplatin–paclitaxel in vulnerable older patients with ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, 3-arm randomized clinical trial screened 447 women 70 years and older with newly diagnosed stage III/IV ovarian cancer by determining their Geriatric Vulnerability Score; 120 patients with a Geriatric Vulnerability Score of 3 or higher were stratified by country and surgical outcome. Enrollment took place at 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada from December 11, 2013, to April 26, 2017. Final analysis database lock April 2019. Data analysis was performed from February 1 to December 31, 2019. INTERVENTIONS: Patients were randomized to receive 6 cycles of (1) carboplatin, area under the curve (AUC) 5 mg/mL·min, plus paclitaxel, 175 mg/m2, every 3 weeks; (2) single-agent carboplatin, AUC 5 mg/mL·min or AUC 6 mg/mL·min, every 3 weeks; or (3) weekly carboplatin, AUC 2 mg/mL·min, plus paclitaxel, 60 mg/m2, on days 1, 8, and 15 every 4 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects–related treatment discontinuation, or death. RESULTS: A total of 120 women were randomized. The mean and median age was 80 (interquartile range, 76-83; range, 70-94) years; 43 (36%) had a Geriatric Vulnerability Score of 4 and 13 (11%) had a Geriatric Vulnerability Score of 5; 40 (33%) had stage IV disease. During its third meeting, the independent data monitoring committee’s recommendation led to the termination of the trial because single-agent carboplatin was associated with significantly worse survival. Six cycles were completed in 26 of 40 (65%), 19 of 40 (48%), and 24 of 40 (60%) patients in the every-3-weeks combination, single-agent carboplatin, and weekly combination groups, respectively. Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%]). Treatment-related deaths occurred in 4 patients (2 of 40 [5%] in each combination group). CONCLUSIONS AND RELEVANCE: This randomized clinical trial shows that compared with every-3-weeks or weekly carboplatin–paclitaxel regimens, single-agent carboplatin was less active with significantly worse survival outcomes in vulnerable older patients with ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02001272

The aim of this study was developing and testing a new tool for measuring quality of life (QoL) in patients with osteoporosis who had experienced nonvertebral fractures (NVFXs). Two main phases were carried out. First, the tool was developed based on expert opinion through three focus groups. Second, the tool was tested with exploratory factor analysis and confirmatory factor analysis in a sample of 458 postmenopausal women. The reliability of the developed Quality of Life Osteoporosis Scale—Nonvertebral Fractures (QoLOS-NVFX) was measured using Cronbach's α, maximal reliability (MR), composite reliability (CR), and average variance extracted (AVE). The QoLOS-NVFX resulted in a unidimensional scale with 23 items and showed good reliability, with a Cronbach's α of 0.94, an MR of 0.96, a CR of 0.96, and an AVE of 0.70. The QoLOS-NVFX shows good psychometric properties and can be used to assess the impact of NVFX on QoL in osteoporotic women. Furthermore, it can be easily used in clinical practice and research.

Plerixafor inhibits CXCR4, thus inducing the mobilization of hematopoietic stem/progenitor cells in lymphoma and multiple myeloma (MM) patients eligible for autologous stem cell transplantation (ASCT). However, the kinetics of plerixafor-induced mobilization of lymphocyte subsets is poorly known. Here, we evaluated the graft content, the engraftment, and the immunological reconstitution of MM patients receiving plerixafor. Thirty-seven patients undergoing one or tandem ASCT were enrolled. After mobilization with cyclophosphamide plus G-CSF, plerixafor was added at hematological recovery regardless of CD34+cell count. We evaluated the number of CD34+, CD34+/CD38−, CD3+, CD4+, CD8+, CD19+, CD56+/CD3−, CD4+/CD25+/FOXP3+, and CD138+/CD38+cells on each apheresis. Hematological and immunological recovery were determined at 30 days, 3, 6, 9, and 12 months after ASCT. Overall, 34/37 patients mobilized a median of 10.1 × 106CD34+cells/Kg (IQ 7.7–13.4). Patients with <20/µL CD34+cells at plerixafor administration (18/33) had a significantly higher CD34+cell fold increase, but not a higher absolute number, than 16/33 patients with ≥20/µL CD34+cells. A similar CD34+and immune graft composition was reported. A higher number of CD3+and CD8+cells/µL was observed at 3 months after first ASCT (p< 0.05) in the group with ≥20 CD34+cells/µL. Thus, in MM patients, the timing of plerixafor administration influences immunological recovery.

Herein, we report the synthesis and biological characterization of the new peptide ψRGDechi as the first step toward novel-targeted theranostics in melanoma. This pseudopeptide is designed from our previously reported RGDechi peptide, known to bind selectively αvβ3integrin, and differs for a modified amide bond at the main protease cleavage site. This chemical modification drastically reduces the enzymatic degradation in serum, compared to its parental peptide, resulting in an overall magnification of the biological activity on a highly expressing αvβ3human metastatic melanoma cell line. Selective inhibition of cell adhesion, wound healing, and invasion are demonstrated; near-infrared fluorescent ψRGDechi derivative is able to detect αvβ3integrin in human melanoma xenografts in a selective fashion. More, molecular docking studies confirm that ψRGDechi recognizes the receptor similarly to RGDechi. All these findings pave the way for the future employment of this novel peptide as promising targeting probe and therapeutic agent in melanoma disease.

Background:Acute myeloid leukemia (AML) poses significant challenges, especially in intermediate and high-risk cases due to modest rates of complete remission (CR) of 50-60% yelding a 2-year survival probability of about 30-40%. Preliminary results from the AML1718 part 1 trial have demonstrated remarkable improvements, with a composite complete remission (CCR) rate reaching an impressive 82%, and a 1-year survival probability of 72%. These findings represent a substantial advancement compared to historical data. Hereby, we present the comprehensive results of the AML1718 study, with a primary focus on the CCR as the primary endpoint.

In a randomized Phase III trial, CPX-351has shown to be more effective than conventional 3+7 chemotherapy as frontline treatment for secondary or therapy-related AML. However, longer time for haematologic recovery (HR) after induction cycle (IC) was observed among CPX-351 treated patients. Later real-world evidences confirmed this observation, noting in addition that the time to HR was quite variable among different patients, as some patients showed quick recovery whereas others showed very delayed HR. However, despite the high clinical relevance, no specific factors related to a longer time to HR have been identified in CPX-351 treated patients so far.The aim of this study was to identify patients-related factors related to delayed HR and the outcome of patients showing a late HR. Data from 130patientswith newly diagnosed AML who received 1 or 2 cycles of CPX-351 were retrospectively collected. All patients received the EMA-approved dosing and schedule of CPX-351. Median age was 66 years (32-78). MDS-related cytogenetic abnormalities(CA) were found in 68 patients (52%), whereas MDS-related genetic abnormalities in absence of CA were found in 30 patients (23%). 32 patients had t-AML (24%) and 61 (47%) had a previous diagnosis of MDS. The CR+CRi rate after induction cycle was 67%. 89/130 pts received a second course of CPX-351 after IC, with CR+CRi rate of 71% after the second induction course. Among 92 pts who achieved CR/Cri, 88 were evaluable for flow cytometry-based MRD and among them 62 (71%) had reached negativity. Forty-two patients underwent allogeneic stem cell transplantation (ASCT) in first CR (32%, 46% of responding patients), with a median time to transplant of 213 days (range 52-638). Nine more patients received ASCT in second CR. After a median follow-up of 23 months (IC 95% 14.4 - 36.7), the median OS was 21 months (95% CI 17.5-25.7). In responding patients, median time to neutrophils (PMN) >0.5×109/L and platelet (PLT)>20×109/L recovery was 32 (14-54) and 31 (10-94) days, respectively. Seven patients never achieved PMN or PLT recovery even if in CRi. A total of 23 patients (18%) showed a late HR, defined as a time to PMN >500 recovery > 35 days and/or PLT>20.000 > 40 days).

AbstractWe give a characterization of the parabolic quadric Q(4, q).

Hyperactivation of the Hedgehog (Hh) pathway, which controls refueling of multiple myeloma (MM) clones, might be critical to disease recurrence. Although several studies suggest the Hh pathway is activated in CD138- immature cells, differentiated CD138+ plasma cells might also be able to self-renew by producing themselves the Hh ligands. We studied the gene expression profiles of 126 newly diagnosed MM patients analyzed in both the CD138+ plasma cell fraction and CD138-CD19+ B-cell compartment. Results demonstrated that an Hh-gene signaturewas able to cluster patients in two subgroups characterized by the opposite Hh pathway expression in mature plasma cells and their precursors. Strikingly, patients characterized by Hh hyperactivation in plasma cells, but not in their B cells, displayed high genomic instability and an unfavorable outcome in terms of shorter progression-free survival (hazard ratio: 1.92; 95% confidence interval: 1.19–3.07) and overall survival (hazard ratio: 2.61; 95% confidence interval: 1.26–5.38). These results suggest that the mechanisms triggered by the Hh pathway ultimately led to identify a more indolent vs a more aggressive biological and clinical subtype of MM. Therefore, patient stratification according to their molecular background might help the fine-tuning of future clinical and therapeutic studies.

Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide 18F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58–5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM.

The aim of this paper is to describe a scientific methodology (i.e., the combination of different well-established modeling techniques) and its application to a real case scenario of contaminated dust emissions in high winds. This scenario addresses potential air pollution problems at the water treatment plant (WTP) at Qarmat-Ali, Basra, Iraq, during 2003. Workplace practices at the WTP before 2003 resulted in sodium dichromate contamination in the area. Looting at the site in early 2003 also contributed to this contamination. Individuals who were assigned to provide security at the site in 2003 have claimed adverse health effects caused by exposure to dust containing hexavalent chromium [Cr(VI)]. This report presents our modeling study with respect to these claims in relation to (1) amount of Cr(VI) present in the soil, (2) wind erosion episodes, and (3) possible long-term (e.g., annual average) Cr(VI) concentrations inhaled by different people while at the site. Our modeling approach included (1) the analysis of Cr(VI) soil measurements to assess the degree of contamination in different areas of the plant at different times; (2) the use of DUSTRAN model equations to calculate the emission rate of particulate matter (PM) less than 10 µm in diameter (PM10) during high-wind episodes; (3) the use of the U.S. Environmental Protection Agency (EPA) AERMOD modeling system to estimate Cr(VI) concentrations at the site; and (4) the calculation of modeling results in the form of both contour lines of average Cr(VI) concentrations at the site, and specific concentration values for selected individuals, based upon their recollection of their visits to the site.Implications: The assessment of individual exposure to contaminated dust during high-wind episodes requires a combination of modeling tools and the calculation of concentration impacts at precise locations and times. We have combined several state-of-the art simulation algorithms to provide a credible methodology for assessing individual exposure. The methodology has been applied to an actual case where exposure was claimed by individuals.

The role of high-dose therapy and autologous stem-cell transplantation (ASCT) in the treatment of multiple myeloma (MM) has continued to evolve in recent years. The novel agents thalidomide, bortezomib, and lenalidomide have been successfully incorporated into induction therapy in preparation for ASCT and are currently being investigated also as post-ASCT consolidation and maintenance therapy. Consolidation treatment is generally short term and aims to increase the frequency and depth of response obtained with the previous treatment phases, including novel agent-based induction therapy and ASCT. This review will focus on recent trials of novel agents as post-ASCT consolidation therapy, offering an overview of pros and cons of this new treatment strategy in the ASCT sequence for MM patients.

Human papillomavirus type 16 (HPV16) and other oncogenic viruses have been reported to deregulate immunity by suppressing the function of the double-stranded DNA innate sensor TLR9. However, the mechanisms leading to these events remain to be elucidated. We show that infection of human epithelial cells with HPV16 promotes the formation of an inhibitory transcriptional complex containing NF-κBp50–p65 and ERα induced by the E7 oncoprotein. The E7-mediated transcriptional complex also recruited the histone demethylase JARID1B and histone deacetylase HDAC1. The entire complex bound to a specific region on the TLR9 promoter, which resulted in decreased methylation and acetylation of histones upstream of the TLR9 transcriptional start site. The involvement of NF-κB and ERα in the TLR9 down-regulation by HPV16 E7 was fully confirmed in cervical tissues from human patients. Importantly, we present evidence that the HPV16-induced TLR9 down-regulation affects the interferon response which negatively regulates viral infection. Our studies highlight a novel HPV16-mediated mechanism that combines epigenetic and transcriptional events to suppress a key innate immune sensor.

We prospectively analyzed the prognostic relevance of positron emission tomography–computed tomography (PET/CT) at diagnosis, after thalidomide-dexamethasone (TD) induction therapy and double autotransplantation (ASCT) in 192 newly diagnosed multiple myeloma (MM) patients. Presence at baseline of at least 3 focal lesions (FLs; 44% of cases), a standardized uptake value (SUV) > 4.2 (46%), and extramedullary disease (EMD; 6%) adversely affected 4-year estimates of progression-free survival (PFS; ≥ 3 FLs: 50%; SUV > 4.2: 43%; presence of EMD: 28%). SUV > 4.2 and EMD were also correlated with shorter overall survival (OS; 4-year rates: 77% and 66%, respectively). Persistence of SUV > 4.2 after TD induction was an early predictor for shorter PFS. Three months after ASCT, PET/CT was negative in 65% of patients whose 4-year rates of PFS and OS were superior to those of PET-positive patients (PFS: 66% and OS: 89%). In a multivariate analysis, both EMD and SUV > 4.2 at baseline and persistence of fluorodeoxyglucose (FDG) uptake after ASCT were independent variables adversely affecting PFS. PET/CT involvement at diagnosis, after novel agent-based induction and subsequent ASCT is a reliable predictor of prognosis in MM patients. This study is registered at www.clinicaltrials.govas NTC01341262.

We prospectively analyzed the prognostic relevance of positron emission tomography–computed tomography (PET/CT) at diagnosis, after thalidomide-dexamethasone (TD) induction therapy and double autotransplantation (ASCT) in 192 newly diagnosed multiple myeloma (MM) patients. Presence at baseline of at least 3 focal lesions (FLs; 44% of cases), a standardized uptake value (SUV) > 4.2 (46%), and extramedullary disease (EMD; 6%) adversely affected 4-year estimates of progression-free survival (PFS; ≥ 3 FLs: 50%; SUV > 4.2: 43%; presence of EMD: 28%). SUV > 4.2 and EMD were also correlated with shorter overall survival (OS; 4-year rates: 77% and 66%, respectively). Persistence of SUV > 4.2 after TD induction was an early predictor for shorter PFS. Three months after ASCT, PET/CT was negative in 65% of patients whose 4-year rates of PFS and OS were superior to those of PET-positive patients (PFS: 66% and OS: 89%). In a multivariate analysis, both EMD and SUV > 4.2 at baseline and persistence of fluorodeoxyglucose (FDG) uptake after ASCT were independent variables adversely affecting PFS. PET/CT involvement at diagnosis, after novel agent-based induction and subsequent ASCT is a reliable predictor of prognosis in MM patients. This study is registered at www.clinicaltrials.gov as NTC01341262.

AbstractIn this paper we prove that, in PG(3, q), qodd, a (q2+ q+1)-set of type ((n− 1)q+ 1, nq+ 1, (n+ 1)q+ 1)2, 1 ≤ n ≤ q, and type (a, b, c, d)1, with , such that any external line is contained in exactly one ((n− 1)q+ 1)-secant plane is a parabolic quadric.

Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma.

AbstractThere are several kinds of burst errors for which error detecting and error correcting codes have been constructed. In this paper, we consider a new kind of burst error which will be termed as ‘m-repeated burst error of length b(fixed)’. The paper presents lower bounds on the number of parity-check digits required for a linear code that is capable of detecting errors which are m-repeated burst errors of length b(fixed). Further, codes capable of detecting and simultaneously correcting such errors have also been studied.

There are several kinds of burst errors for which error detecting and error correcting codes have been constructed. In this paper, we consider a new kind of burst error which will be termed as ‘m-repeated burst error of length b(fixed)’. The paper presents lower bounds on the number of parity-check digits required for a linear code that is capable of detecting errors which are m-repeated burst errors of length b(fixed). Further, codes capable of detecting and simultaneously correcting such errors have also been studied.

Among RGD-dependent integrins, the αvβ3 receptor has recently received increasing attention as a therapeutic target because of its critical role in tumor-induced angiogenesis and metastasis formation. Here, we describe a new peptide antagonist of αvβ3 receptor, designed on the basis of the crystal structure of integrin αvβ3 in complex with c(RGDf[NMe]V) and the NMR structure of echistatin. Cell adhesion assays have demonstrated that the peptide is a potent and selective antagonist of the αvβ3 receptor.

AbstractA systematic investigation of solid and gaseous atmospheric emissions from some coke-oven batteries of one of Europe’s largest integrated steel factory (Taranto, Italy) has been carried out. In air monitoring samples, polycyclic aromatic hydrocarbons (PAHs) were consistently detected at concentrations largely exceeding threshold limit values. By means of PAHs speciation profile and benzo (a)pyrene (BaP) equivalent dispersion modeling from diffuse sources, the study indicated that serious health risks exist not only in working areas, but also in a densely populated residential district near the factory.

In order to reduce sea turtle by-catches on surface drifting long-lines during professional swordfish (Xiphias gladius) fishing, the relevance of olfactory stimuli in eliciting predation by loggerhead sea turtles (Caretta caretta) was investigated. Choice experiments were run in captivity. Squid-shaped plastic lures having or lacking scomber odour were presented to 27 specimens (22 immatures and 5 adults). The turtles' behavioural responses highlighted the importance of chemical clues in eliciting approaching and biting behaviours. This study was carried out within the framework of the EU-Life Project 'Urgent conservation measures for C. caretta in the Pelagie islands' (LIFE 99 NAT/IT/006271).

No Abstract

AbstractIn this note we prove that a (q2+ q+ 1)-set of PG (5, q) of type (1, m, n)4satisfying two suitable conditions is a quadric Veronesean.

AbstractIn the unique Steiner system S(5, 6, 12) the blocks, which do not contain a fixed point x , give us the blocks of a 4-(11, 6, 3) design, called the external contraction of S(5, 6, 12) at x . We prove that two distinct contractions are isomorphic and that each 4-(11, 6, 3) design can be embedded in S(5, 6, 12) . Moreover, the blocking sets of the 4-(11, 6, 3) design are completely characterized.

ABSTRACTPrimary human embryo lung fibroblasts and adult diploid fibroblasts infected by the human cytomegalovirus (HCMV) display ß-galactosidase (ß-Gal) activity at neutral pH (senescence-associated ß-Gal [SA-ß-Gal] activity) and overexpression of the plasminogen activator inhibitor type 1 (PAI-1) gene, two widely recognized markers of the process designated premature cell senescence. This activity is higher when cells are serum starved for 48 h before infection, a process that speeds and facilitates HCMV infection but that is insufficient by itself to induce senescence. Fibroblasts infected by HCMV do not incorporate bromodeoxyuridine, a prerequisite for the formal definition of senescence. At the molecular level, cells infected by HCMV, beside the accumulation of large amounts of the cell cycle regulators p53 and pRb, the latter in its hyperphosphorylated form, display a strong induction of the cyclin-dependent kinase inhibitor (cdki) p16INK4a, a direct effector of the senescence phenotype in fibroblasts, and a decrease of the cdki p21CIP1/WAF. Finally, a replicative senescence state in the early phases of infection significantly increased the number of cells permissive to virus infection and enhanced HCMV replication. HCMV infection assays carried out in the presence of phosphonoformic acid, which inhibits the virus DNA polymerase and the expression of downstream genes, indicated that immediate-early and/or early (a) genes are sufficient for the induction of SA-ß-Gal activity. When baculovirus vectors expressing HCMV IE1-72 or IE2-86 proteins were inoculated into fibroblasts, the increase of p16INK4a(observed predominantly with IE2-86) was similar to that observed with the whole virus, as was the induction of SA-ß-Gal activity, suggesting that the viral IE2 gene leads infected cells into senescence. Altogether our results demonstrate for the first time that HCMV, after arresting the cell cycle and inhibiting apoptosis, triggers the cellular senescence program, probably through the p16INK4aand p53 pathways.

Purpose: To evaluate feasibility, safety, and effectiveness of endovascular abdominal aortic aneurysm (AAA) repair in patients whose fitness for surgery is questionable.Methods: Between April 1997 and December 2001, 389 consecutive patients underwent endovascular AAA repair. Of these, 51 (13.1%) were ASA grade IV. The perioperative and late outcomes of this group were compared to the remaining 338 patients with ASA grades 0.05). Actuarial survival at 30 months was 62.9% in ASA IV group and 88.0% in ASA

We have used yeast two-hybrid screening to isolate cDNA-encoding proteins interacting with the protein encoded by the interferon (IFN)-inducible gene Ifi204. Four independent overlapping clones were isolated from an NIH3T3 cDNA library. The largest clone encoded a protein (1203 amino acids in length) sharing 94% identity with the C-terminal portion of the human translocated promoter region (Tpr) protein. Northern blot analysis revealed a 7.5-kilobase mRNA present in both mouse and human cell lines. In addition, in vivo interaction was demonstrated by coimmunoprecipitation experiments. Anti-Tpr polyclonal monospecific antibodies (Ab) used for immunofluorescence staining labeled the nuclear envelope (NE) in a punctate pattern characteristic of nucleoporins and also yielded staining throughout the nuclear interior. The intranuclear Tpr occurred in apparently discrete foci. When superimposed on optical sections obtained with anti-p204 Abs, these colocalized, with the sole exception of the nucleolar compartment stained by the anti-p204 Abs only. Although the specific function of Tpr is not defined, it appears to mediate p204 translocation from the cytoplasmic to the nuclear compartment following IFN treatment.

Objective:to determine whether the presence of an iliac aneurysm compromises outcome of endovascular exclusion of AAA and to ascertain the fate of the iliac aneurysmal sac.

AbstractIn this paper we prove that a Rédei blocking set with two Rédei lines defines a quasigroup. In the first case by using quasigroups we determine the maximum number of non-isomorphic Rédei blocking sets with two Rédei lines.

Objective: to determine whether eversion carotid endarterectomy (CEA) was safe and more effective than conventional CEA. Methods: controlled trials comparing eversion vs conventional technique for CEA were identified from the Cochrane Stroke Review Group database plus additional hand searching. Researchers were contacted to identify additional published and unpublished studies. Randomised and pseudorandomised trials comparing eversion to conventional techniques in patients undergoing CEA were examined. Outcomes included stroke and death, carotid restenosis/occlusion, and local complications. Results: five trials were included comprising 2465 patients and 2590 arteries. There were no significant differences in the rate of perioperative stroke or death (1.7% vs 2.6%, odds ratio [OR] 0.44, 95% confidence interval [CI] 0.10–1.82) and stroke during follow-up (1.4% vs 1.7%; OR: 0.84; 95% CI: 0.43–1.64) between eversion and conventional CEA techniques. Eversion CEA was associated with a significantly lower rate of restenosis >50% during follow-up (2.5% vs 5.2%, OR: 0.48, 95% CI: 0.32–0.72). There were no statistically significant differences in local complications between the eversion and conventional group. When eversion procedures were compared with patch procedures only, non-significant differences were found in primary outcomes. Conclusions: eversion CEA may be associated with low risk of arterial occlusion and restenosis. However, numbers are too small to definitively assess the benefits and disadvantages of eversion CEA. Reduced restenosis rates did not appear to be associated with clinical benefit in terms of reduced stroke risk, either perioperatively or later. Until further evidence is available, the choice of the CEA technique should be based on the experience and familiarity of the individual surgeon.

Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging. In particular, cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with ¹¹¹In or ^99mTc for the purpose of developing radiopharmaceuticals for in vivo CCK-B receptor imaging. Labeling of CCK8 with ¹¹¹In was achieved at the N-terminus of the peptide by adding, in solid phase, a glutamate coupled diethylenetriaminepentaacetic acid (DTPA) moiety through a glycine linker, yielding DTPA–Glu–G–CCK8. For labeling with ^99mTc, the CCK8 peptide was modified at its N-terminus by introducing, in the following order—cysteine, glycine, and a diphenylphosphinopropionyl moiety—giving a 10-residue peptide derivative, Phos–GC–CCK8. A cell culture model was developed for the purpose of evaluating the binding properties of these two ligands. The human epidermoid carcinoma cell line, A431, was transfected with a plasmid containing the full coding sequence of the human CCK-BR under a strong viral promoter, obtaining a number of receptors in the range of 2–5 × 10⁶ per cell. Control cells were transfected with vector alone. An animal tumor model utilizing these two cell lines was developed to evaluate the specificity of interaction with the CCK-BR and biodistribution properties of the compounds. CCK-BR positive and control cells were subcutaneously injected in opposite flanks of CD1 female nude mice in order to obtain xenografts differing only in their ability to express CCK-B receptors. High performance liquid chromatography (HPLC) and other chromatographic methods were utilized to assess stability of the radiolabeled compounds after injection. Both ¹¹¹In–DTPA–Glu–G–CCK8 and ^99mTc–Phos–GC–CCK8 showed similar binding affinities for cultured CCK-BR expressing cells, with dissociation constants in the range of 20–40 nM. With the two xenograft approach, we were able to demonstrate specific interaction with the receptor of both CCK analogs in our animal model. The data obtained shows rapid specific localization of both compounds on the CCK-BR overexpressing xenografts. Both tracers show rapid plasma clearance of unbound peptide. Clearance of ¹¹¹In–DTPA–Glu–G–CCK8 appears to be preferentially through the kidneys, whereas ^99mTc–Phos–GC–CCK8 clearance occurs both through kidneys and the hepatobiliary system. Both our labeling approaches appear adequate for clinical use of peptide based radiopharmaceuticals, although ^99mTc–Phos–GC–CCK8 shows elevated accumulation in the gastrointestinal tract, which causes high background activity. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 66: 370–380, 2002

AbstractLower and upper bounds are given for the number of parity-check digits required for a linear code that locates a single sub-block containing errors which are in the form of high-density CT bursts.

Abstract:: The connection between the out of equilibrium linear response function and static properties established by Franz, Mezard, Parisi and Peliti for slowly relaxing systems is analyzed in the context of phase ordering processes. Separating the response in the bulk of domains from interface response, we find that in order for the connection to hold the interface contribution must be asymptotically negligible. How fast this happens depends on the competition between interface curvature and the perturbing external field in driving domain growth. This competition depends on space dimensionality and there exists a critical value d c = 3 below which the interface response becomes increasingly important eventually invalidating the connection between statics and dynamics as the limit d = 1 is reached. This mechanism is analyzed numerically for the Ising model with d ranging from 1 to 4 and analytically for a continuous spin model with arbitrary dimensionality.

An adjoint optimization method, based on the solution of an inverse flow problem, is proposed. Given a certain performance functional, it is necessary to find its extremum with respect to a flow variable distribution on the domain boundary, for example, pressure. The adjoint formulation delivers the functional gradient with respect to such a flow variable distribution, and a descent method can be used for optimization. The flow constraints are easily imposed in the parameterization of the distributed control, and therefore those problems with several strict constraints on the flow solution can be solved very efficiently. Conversely, the geometric constraints are imposed either by additional partial differential equations, or by penalization. By adequately constraining the geometric solution, the classical limitations of the inverse problem design can be overcome. Several examples pertaining to internal flows are given.

AbstractIn this paper we introduce the notion of (t, λ)-configuration and investigate its relation with partial geometries and t-designs. In particular the parameters of symmetric configurations obtained by 2-designs are analyzed. Using the characters of a c-set in a design we construct a wide variety of embedded (t, λ)-configurations.

The resolution of racemic α‐, β‐, and γ‐hydroxy‐ω‐alkenylphosphonates was achieved by enzymatic hydrolysis of the corresponding acetates. The optically active alcohols were transformed into β‐hydroxyaldehydes and allowed to react with dihydroxyacetone phosphate (DHAP) viaenzymatic aldol addition catalyzed by rabbit muscle fructose 1,6‐bisphosphate aldolase (FruArab). After enzymatic dephosphorylation, a set of novel sugar phosphonates was obtained.

Objectives to evaluate the role of endovascular repair (ER) of abdominal aortic aneurysm (AAA) repair in American Society for Anaesthesiology [ASA] class IV patients. Patients and Methodsbetween April 1997 and March 2000, 266 consecutive patients underwent ER for AAA. There were 26 patients (10%) with ASA grade IV. The remaining 240 patients, ASA grade between I and III (ASA

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med1998; 25: 714–720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlationr=0.69,P<0.0001) and in vivo score (Spearman rank correlation coefficientr=0.60,P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.

An analysis was carried out of some Ziegler–Natta catalysts precursors by small- and wide-angle X-ray scattering in order to get information on the crystallites dimensions, structural disorder and surface areas. The results were correlated with catalytic activities in polymerization of propylene. It was shown that the structural variations, which mainly influence the catalytic activity, are associated with the rotational disorder of the Cl–Mg–Cl triple layers and that the crystallites dimensions and surface areas play a determinant role in the same activity.

To identify predictive factors for postoperative success and potential predictors for satisfactory outcome of endovascular grafting for abdominal aortic aneurysm (AAA), we collected data from our prospective database, which includes a series of consecutive patients undergoing endovascular repair at the Vascular Surgery Unit, Policlinico Monteluce, Perugia, Italy. From April 1997 to July 1998, 202 patients were referred to our Unit for elective AAA repair; 94 patients (47%) were selected for endografting. Placement of the graft using endovascular technique without conversion to open laparotomy, in addition to no mortality, major morbidity, or endoleak at 30-day follow-up, was defined as postoperative success. The influence of anatomical features on postoperative results was analyzed by univariate and multivariate analysis. Our experience shows that endoluminal repair of AAA is safe and effective in the short term and male patients with small aneurysms are optimal candidates for successful repair.

Objective: to validate the role of duplex scan in endoleak detection in postoperative surveillance of endoluminal abdominal aneurysm repair (EAAR). Patients and methods between April 1997 and March 1999, 103 patients were eligible for duplex and computed tomography (CT) scan after EAAR. Mean follow-up was 8 months (range 1–24 months). The study protocol comprised concurrent examination with colour-duplex and CT scan at 1, 6, and 12 months after EAAR, for a total of 198 concurrent examinations. All duplex scan examinations were performed by two vascular surgeons with the same machine (ATL HDI 3000). Interobserver agreement in endoleak detection (κ=1) and in type of endoleak (κ=0.7) was evaluated in 50 random duplex examinations. Endoleak detection was examined comparatively in duplex and CT scan, the latter being the gold standard. Sensitivity and specificity tests together with negative- and positive-predictive values (NPV and PPV) were calculated. Results duplex scan was not feasible in one patient. On CT scan the endoleak rate was 4% at one month, 3% at 6 months, and 4% at one year. Overall, CT scan detected 12 endoleaks. With respect to endoleak detection, duplex scan revealed a great ability in ruling out false-negative results (sensitivity 91.7%, NPV 99.4%), but overestimated the presence of endoleak (specificity 98.4%, PPV 78.6%). Regarding type of endoleak, the ability of duplex scan to identify the source of endoleak was low (sensitivity 66.7%). Conclusions duplex scan, if validated, appears to be a reliable means for excluding the presence of endoleak after EAAR. Copyright 2000 Harcourt Publishers Ltd

Objective: The durability of carotid endarterectomy (CEA) may be affected by carotid restenosis. The data from randomized trials show that the highest incidence of restenosis after CEA occurs from 12 to 18 months after surgery. The optimal CEA technique to reduce perioperative complications and restenosis rates is still undefined. This study examines the long-term clinical outcome and incidence of recurrent stenosis in patients who undergo eversion CEA. Previously published perioperative results of this study did not show statistically significant differences in study endpoints between the eversion and standard techniques. Methods: From October 1994 to March 1997, 1353 patients with surgical indications for carotid stenosis were randomly assigned to undergo eversion (n = 678) or standard CEA (n = 675; primary closure, 419; patch, 256). Withdrawal from the assigned treatment occurred in 1.6% of the patients (in 13 assigned to eversion CEA, and in nine assigned to standard CEA). The clinical and duplex scan follow-up examination was 99% complete, and the mean follow-up interval was 33 months (range, 12 to 55 months). The primary outcomes were perioperative and late major stroke and death, carotid restenosis (stenosis >= 50% of the lumen diameter detected at duplex scanning), and carotid occlusion. The primary evaluation of study outcomes was conducted on the basis of an intention-to-treat analysis. Results: Restenosis was found at duplex scanning in 56 patients (19 in the eversion group, and 37 in the standard group). Within the standard group, the restenosis rates were 7.9% in the primary closure population and 1.5% in the patched population. Of the patients with restenosis, 36% underwent cerebral angiography that confirmed restenosis in all cases. The cumulative restenosis risk at 4 years was significantly lower in the group that underwent treatment with eversion CEA as compared with the standard group (3.6% vs 9.2%; P = .01), with an absolute risk reduction of 5.6% and a relative risk reduction of 62%. Eighteen patients would have had to undergo treatment with eversion CEA to prevent one restenosis during the 4-year period. The incidence rate of ipsilateral stroke was 3.3% in the eversion population and 2.2% in the standard group. There were no significant differences in the cumulative risks of ipsilateral stroke (3.9% for eversion, and 2.2% for standard; P = .2) and death (13.1% for eversion, and 12.7% for standard; P = .7)) in the two groups. Of the 18 variables that were examined for their influence on restenosis, eversion CEA (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.6; P = .0004) and patch CEA (hazard ratio, 0.2; 95% confidence interval, 0.07 to 0.6; P = .002) were negative independent predictors of restenosis with multivariate Cox proportional hazards regression analysis. Conclusion: The EVEREST (EVERsion carotid Endarterectomy versus Standard Trial) showed that eversion CEA is safe, effective, and durable. No statistically significant differences were found in late outcome between the eversion and standard techniques at the available follow-up examination. (J Vasc Surg 2000;31:19-30.)

The shape optimization problem governed by the Euler equations is posed in a fixed reference plane. The boundary control is exerted by a parametric mapping from the physical plane to the reference fixed plane. The adjoint equations are derived in such fixed plane. By using this approach remeshing is unnecessary; furthermore, as in many practical applications the parametric mapping can be easily differentiated, the computation of mesh sensitivities is avoided.

In recent years, water level in rigid foam formulations has been increased to such a point that the use of only the water/isocyanate reaction to provide all of the blowing has become a reality, at least for certain applications. Nevertheless, two limiting factors penalize the use of only CO2blown foams: a too high λ aged value and a poor dimensional stability.The objective of this research work was to record the variations with time of some parameters that affect dimensional stability of only CO2blown foams, in order to establish eventual correlation between them and foam behavior.

Purpose:Preoperative cerebral imaging has been considered not to be cost-effective in carotid endarterectomy (CEA) for asymptomatic carotid stenosis. Yet, silent brain infarction (SBI) has been associated with the embolization potential of a severe carotid stenosis. Thus the presence of SBI may represent an additional indication for CEA in asymptomatic patients. We examined the predictive value of preoperatively detected silent cerebral lesions on early and late outcomes in patients undergoing CEA for asymptomatic carotid stenosis. Methods:Preoperative cerebral tomographic (CT) scans performed on 301 asymptomatic patients undergoing 346 CEAs from 1986 to 1995 were reviewed by a single neuroradiologist blinded to patients' records. Mean follow-up was 67.3 months (range, 24-130 months). The degree of internal carotid lumen reduction was measured bilaterally in all patients (602 carotid arteries); carotid stenosis of 60% or more was found in 399 carotid arteries. Results:Of the 103 (34%) CT scans positive for cerebral lesions, 58% were lacunar. No significant association was observed between the side of the cerebral lesion on CT scan and the severity of the corresponding carotid stenosis; 38 silent lesions were detected in the 203 hemispheres ipsilateral to carotid stenoses that were less than 60% versus 95 SBIs in the 399 hemispheres ipsilateral to carotid stenoses that were 60% or more (19% vs 24%; P= .2). There were no significant differences in the perioperative stroke/death rate in patients with or without cerebral CT lesions (2% vs 1%; odds ratio, 1.94; P= .6). Mortality rate during follow-up was 22% in patients with preoperative SBI and 15% in patients without SBI (P= .1). However, actuarial survival at 10 years was shorter (P= .02) in patients with SBI. Late stroke occurred in 11% of patients with preoperative SBI and in 3% of patients without preoperative SBI (P= .006). Cox regression analysis showed that both preoperative lacunar and nonlacunar infarctions were independent predictors of late stroke (hazard ratio, 3.6; P= .04; and hazard ratio, 7.1; P= .001; respectively). Conclusion:In our experience, preoperative SBI did not occur more frequently in the hemisphere ipsilateral to asymptomatic severe carotid stenosis. Although our study lacks a medically treated control group, our data show that SBI is predictive of poor neurologic outcome in asymptomatic patients undergoing CEA. We conclude that CT before CEA, selectively applied, provides information on long-term neurologic prognosis and that a less aggressive attitude towards CEA in asymptomatic patients with SBI may be justified. (J Vasc Surg 1999;29:995-1005.)

Purpose: The low invasiveness of endoluminal abdominal aneurysm repair (EAAR) appears optimal for the use of epidural anesthesia (EA). However, reported series on EAAR show that general anesthesia (GA) is generally preferred. To evaluate the feasibility and problems encountered with EA for EAAR, patients undergoing EAAR with EA and patients undergoing EAAR with GA were examined. Methods: From April 1997 through October 1998, EAAR was performed on 119 patients at the Unit of Vascular Surgery at Policlinico Monteluce in Perugia, Italy. Four patients (3%) required conversion to open repair and were excluded from the analysis because they were not suitable candidates for evaluating the feasibility of EA. The study cohort thus comprised 115 patients undergoing abdominal aortic aneurysm (AAA) repair with the AneuRx Medtronic stent graft. The incidence of risk factors and anatomical features of the aneurysm were compared in patients selected for EA or GA on the basis of intention-to-treat analysis. Intraoperative and perioperative data were compared and analyzed on the basis of intention-to-treat and on-treatment analysis. Results: Sixty-one patients (54%) underwent the surgical procedure with EA (group A), and 54 (46%) underwent the surgical procedure with GA (group B). Conversion from EA to GA was required in four patients (3 of 61 patients, 5%). There were no statistically significant differences between the two study groups in demographics, clinical characteristics, and American Society of Anesthesiology classification (ASA). There was no perioperative mortality. Major morbidity occurred in 3% of patients (group B). According to intention-to-treat analysis, no significant differences were observed between the two groups in mean operating time, fluoro time, blood loss, amount of contrast media used, mean units of transfused blood, need of intensive care unit, mean postoperative hospital stay, and postoperative endoleak. Conversely, significant differences were found by means of on-treatment analysis in the need of intensive care unit (0 vs 5 patients; P = .02), and length of hospitalization (2.5 vs 3.2 days; P = .04). Multivariate logistic regression analysis showed that GA and ASA 4 were positive independent predictors of prolonged (more than 2 days) postoperative hospitalization (hazard ratio, 2.5; 95% CI, 1.1 to 5.8; P = .03, and hazard ratio, 5.1; 95% CI, 1.5 to 17.9; P = .007, respectively). Conclusion: EA for EAAR is feasible in a high percentage of patients in whom it is attempted, and it ensures a technical outcome comparable with that of patients undergoing EAAR with GA. Successful completion of EAAR with EA is associated with a short period of hospitalization. (J Vasc Surg 1999;30:651-7.)