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Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35–82) for the EVA and 57.8 years (range 35.0–82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1–48) and 12.4 months (range 2.9–70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.

Background Rates of occupational injury among immigrant workers are widely believed to be underestimated. The goal of this study was to enhance understanding of the burden of occupational injury and the work organization factors underlying injury among immigrant Latino residential construction workers. Methods Prospective data were obtained from a community-based sample of Latino residential construction workers (N = 107) over a 3-month period. Results Twenty-eight participants were injured, resulting in an injury incidence rate of 55.0/100 FTE (95% CI = 41.4–71.6) during the 3-month observation period. The injury rate involving days away from work during the observation period was 3.9/100 FTE (CI = 0.2–7.2). Injuries were elevated among roofers relative to framers and general construction workers. Roofers had elevated exposure to a variety of deleterious work organization factors. Conclusions Although imprecise given the small sample, our results suggest a threefold to fourfold underestimate of the injury burden to immigrant Latino construction workers. Work organization may contribute to elevated rates of non-fatal occupational injury, particularly among roofers. Am. J. Ind. Med. 55:698–706, 2012. © 2012 Wiley Periodicals, Inc.

J Oral Pathol Med (2010) 40: 510–515 Objective: To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ). Methods: Test subjects were 30 Italian female patients with BRONJ (Group A). Control subjects were 30 female patients with a history of intravenous bisphosphonate use without any evidence of osteonecrosis (Group B) and 125 unrelated healthy volunteers (Group C). Three single-nucleotide polymorphisms were investigated: −634 G>C, occurring in 5′ untranslated region (UTR); +936 C>T, occurring in 3′ UTR; and −2578 C>A of the promoter region. Results: The frequency of the VEGF CAC (+936/−2578/−634) haplotype was increased in patients with BRONJ, compared with female disease-negative controls [odds ratio (OR) = 2.76, 95% CI = 1.09–4.94, P = 0.039; corrected P value: Pc = 0.117], and was also increased compared with female healthy controls (OR = 2.11, 95% CI = 1.14–3.89, P = 0.024; corrected P value: Pc = 0.072). The CC homozygotes of −634G>C of VEGF gene and AA homozygotes of −2578C>A have also been significantly correlated in female patients who developed BRONJ compared with healthy controls (OR = 2.04, 95% CI = 1.12–3.70, P = 0.008; corrected P value: Pc = 0.024). Conclusions: These results suggest a possible haplotype effect of VEGF polymorphisms expression in BRONJ Italian female patients. Studies with different and larger populations possibly using TagSNP to represent all haplotypes within the VEGF gene are needed to further delineate the genetic contribution of this gene to BRONJ.

This work studies the existence of positive prime periodic solutions of higher order for rational recursive equations of the form y n = A + y n − 1 y n − m , n = 0 , 1 , 2 , … , with y − m , y − m + 1 , … , y − 1 ∈ ( 0 , ∞ ) and m ∈ { 2 , 3 , 4 , … } . In particular, we show that for sufficiently small A > 0 , there exist periodic solutions with prime period 2 m + U m + 1 , for almost all m , where U m = max { i ∈ N : i ( i + 1 ) ≤ 2 ( m − 1 ) } .

BACKGROUND To assess the efficacy of primary single-agent epirubicin (120 mg/m(2) every 3 weeks for three cycles) in reducing tumor burden in operable breast cancer >or=2.5 cm in largest diameter at diagnosis and its effect on the rate of conservative surgery. PATIENTS AND METHODS A total of 319 eligible patients, who were all candidates for mastectomy, were enrolled on to a multicenter prospective non-randomized study. Tumor response was assessed clinically and pathologically. Relapse-free and overall survival were assessed on major prognostic variables. RESULTS After primary epirubicin, complete disappearance of invasive neoplastic cells accounted for only 2.6% of patients, but 40% of patients had their primary tumor downstaged to

La biotecnología adquiere una relevancia creciente en la región originada por una doble vertiente: por un lado, desde su contribución al desarrollo económico-comercial de los países del MERCOSUR, tanto en materia de alimentos como en cuestiones energéticas, y por otro, a partir de los desafíos que representan las preocupaciones medioambientales ante la adopción de esta tecnología. En el marco de las condiciones estructurales recién descritas, esta contribución analizará intertemporalmente la construcción de la política biotecnológica del MERCOSUR y el valor de los principios de derecho internacional del medio ambiente como condicionantes de las aproximaciones comerciales que han caracterizado históricamente los procesos de integración en la región. Metodológicamente, este trabajo se dividirá en dos partes. En la primera, tras describir las condiciones estructurales del complejo productivo de los países del MERCOSUR y el perfil exterior de cada uno de ellos, se analizará el proceso de construcción de la política de biotecnología del MERCOSUR. En la segunda parte, desde una perspectiva jurídico-analítica, se abordará la influencia de los principios del derecho internacional del medio ambiente como vectores y modeladores de la política regional. En particular, se analizarán las dificultades estructurales que emergen de la disparidad de obligaciones internacionales asumidas por los Estados Miembros, en materia de biotecnología, y asimismo, los posibles mecanismos que faciliten la construcción de políticas regionales. En conclusión, este trabajo pretende, desde un abordaje multidisciplinar, presentar los problemas jurídico-políticos que emergen en materia de biotecnología en el MERCOSUR, así como proponer las potenciales soluciones que concilien los aspectos ambientales y comerciales que presenta la biotecnología.

A scenario is presented in which an engineer in the field finds that there is a problem with the system specifications and a symmetric finite impulse response (FIR) filter in the software does not do the job; it needs reduced passband ripple or, maybe, more stopband attenuation. We present a simple method for transforming an FIR filter into one with better passband and stopband characteristics, while maintaining phase linearity. While filter sharpening may not be used often, it does have its place in an engineer's toolbox. An optimal filter has a shorter impulse response than a sharpened filter with the same passband and stopband ripple, and thus is more computationally efficient. However, filter sharpening can be used whenever a given filter response cannot be modified, such as a software code that makes use of an unchangeable filter subroutine. The scenario described is hypothetical, but all practicing engineers have been in situations where a problem needs to be solved without the full arsenal of normal design tools. Filter sharpening could be used when improved filtering is needed, but insufficient ROM space is available to store more filter coefficients, or as a way to reduce ROM requirements. In addition, in some hardware applications using filter ASICs, it may be easier to add additional chips to a design than it is to design a new ASIC.

Normally, hydrophobic treatments and coatings are selectively chosen to repair or protect different substrates depending on the climatic conditions, colour, change of initial aspect of the substrate, etc. The combination of these two different treatments in the same repair work is not normally considered. Recent investigations in different dispersion and impregnations technologies used and a combination of both in different products have been determined to work in synergy to give better results and permit the specific design of the work in each case according to the needs of a particular building or structure. This synergy between impregnations/patinas gave an optimal result in some singular buildings in Madrid. The concept is a toolbox of waterproofing/repair solutions to specifically design the best system on site, after laboratory screening tests.

To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ).Test subjects were 30 Italian female patients with BRONJ (Group A). Control subjects were 30 female patients with a history of intravenous bisphosphonate use without any evidence of osteonecrosis (Group B) and 125 unrelated healthy volunteers (Group C). Three single-nucleotide polymorphisms were investigated: -634 GC, occurring in 5' untranslated region (UTR); +936 CT, occurring in 3' UTR; and -2578 CA of the promoter region.The frequency of the VEGF CAC (+936/-2578/-634) haplotype was increased in patients with BRONJ, compared with female disease-negative controls [odds ratio (OR) = 2.76, 95% CI = 1.09-4.94, P = 0.039; corrected P value: P(c) = 0.117], and was also increased compared with female healthy controls (OR = 2.11, 95% CI = 1.14-3.89, P = 0.024; corrected P value: P(c) = 0.072). The CC homozygotes of -634GC of VEGF gene and AA homozygotes of -2578CA have also been significantly correlated in female patients who developed BRONJ compared with healthy controls (OR = 2.04, 95% CI = 1.12-3.70, P = 0.008; corrected P value: P(c) = 0.024).These results suggest a possible haplotype effect of VEGF polymorphisms expression in BRONJ Italian female patients. Studies with different and larger populations possibly using TagSNP to represent all haplotypes within the VEGF gene are needed to further delineate the genetic contribution of this gene to BRONJ.

This paper presents the first results of a hybrid synthetic aperture interferometric radiometer-GPS reflectometer called Passive Advanced Unit-Synthetic Aperture (PAU-SA). These tests are focused in the PAU-SA's performance with preliminary results at baseline level in order to characterize the radiometer part. The tests performed are: characterization of the radiometer noise and its stability through "Allan's variance", radiometric sensitivity, calibration of the offset errors and baseline response to a point source at different angles and polarizations.

This paper describes some potential improvements that could be eventually implemented for future MIRAS (Microwave Imaging Radiometer by Aperture Synthesis) payloads of the follow-on missions of the ESA's SMOS (Soil Moisture and Ocean Salinity) mission. A ground-based instrument concept demonstrator has been designed and it is being implemented to validate these improvements. Both MIRAS and the (Synthetic Aperture Passive Advanced Unit, SA-PAU) are Y shaped arrays, but the receiver topology and the processing unit are significantly different. This paper identifies the elements in the MIRAS's design that could be improved and presents a new instrument (Synthetic Aperture PAU) that could be used to test some potential improvements for future SMOSops (SMOS operational system).

Background This multicenter phase II study evaluated feasibility, clinical efficacy, toxicity and pharmacokinetics of the combination of pegylated liposomal doxorubicin (PLD) and vinorelbine (VNR) in patients with platinum–paclitaxel pretreated recurrent ovarian cancer. Patients and methods All patients received prior treatment with platinum and paclitaxel. Thirty-two heavily pretreated (median number of chemotherapy regimens two, range one to six) ovarian cancer patients received treatment with PLD 30 mg/m2 and VNR 30 mg/m2 every three weeks for six cycles. Ten patients entered the pharmacokinetic study, five receiving the PLD–VNR and five the VNR–PLD sequence. Results In 30 patients evaluated for response and toxicity, the overall response rate was 37% and 10% of patients achieved stable disease. Median time to progression and overall survival were 5.5 months (range 1–10) and 9 months (range 2–16), respectively. Toxicity was generally mild and reversible. VNR AUCtot and plasma levels were considerably higher in the PLD–VNR sequence. Conclusions The PLD–VNR regimen exhibits significant activity in heavily pretreated patients, is well tolerated and is associated with encouraging survival. Preliminary pharmacokinetic results suggest the PLD–VNR sequence for further clinical applications. This regimen should be considered as a treatment option in patients with chemotherapy-resistant ovarian cancer.

Several studies indicate that the short arm of chromosome 17 is one of the most frequently altered regions in sporadic breast carcinomas (45–60%). In the present report the 17p13.3-ter locus in tumour DNA of breast cancer patients, along with their matching normal lymphocyte DNA, have been mapped with four markers (D17S5, D17S379, ABR and D17S34), spanning nearly 3 cM of the telomer. Sixty-five of 143 heterozygous tumours had lost at least one of the markers at the minimum region of loss (45%). High levels of loss of these distal markers on 17p13.3 are independent of TP53 mutations and are associated with tumour cell proliferation. A follow-up period of over 7 years demonstrates that loss of these markers correlates both with disease-free (P = 0.004) and overall survival (P = 0.007). In addition we show that for disease-free survival the prognostic power of this genetic alteration is second only to axillary lymph node involvement (3.1 vs 6.3 relative risk), and is a better predictor than the mutational status of TP53 (1.6 relative risk). Our results are further evidence of the presence, within the region, of at least a second tumour suppressor gene distal to TP53, that might be targeted by deletions. © 1999 Cancer Research Campaign

Background In recent years, there has been a rapid and constant increase in the costs of cancer treatment but, with limited health care resources, it is essential to consider the economic implications of different health interventions. Purpose To evaluate the economic impact of the different prescribing models for trastuzumab on overall costs for breast cancer treatments in the Piemonte Region. Materials and Methods We systematically reviewed the MEDLINE-indexed, English-language literature to identify published, peer-reviewed economic analyses of trastuzumab in HER2± treatment of breast cancer. We rated study quality as per the Drummond criteria. Direct medical and unit costs were calculated from the perspective of a Regional health care system. We derived patient data by consulting a Regional administrative database and screening by File F File C and SDO for each patient treated in 2010. To obtain valid data, it is necessary to combine the data from this study into a single model, with an epidemiological measure from the Piemonte Cancer Registry. It is recommended to use an empirical Bayesian analysis to conduct this study because there is no single estimator for the parameters. Results The search strategy identified 948 articles, of which 340 were citations. From the 608 remaining, 23 articles were considered suitable for full review based on the inclusion criteria. Of these, 15 considered adjuvant trastuzumab treatment only, seven examined metastatic breast cancer treatment and one considered treatment with trastuzumab beyond progression. The analysis of the accuracy of information provided by the information systems showed us that there was only 40% correspondence with the administrative database within Molinette Hospital. Conclusions Preliminary results confirm the difficulty of obtaining accurate data from the administrative systems. We hope to obtain precise data on trastuzumab prescribing, and thus offer complementary information to cost-effectiveness analysis before the launching of a generic drug. No conflict of interest.

1132 Background: Taxanes are the cornerstone of first-line treatment in advanced breast cancer, which can be used as monotherapy or in combination with other agents. This study was designed to eval...

SummaryTwelve FIGO stage III-IV ovarian cancer patients progressing or relapsing after primary cisplatin-containing combination chemotherapy were treated with ifosfamide and etoposide. Only patients with clinically evaluable disease entered the trial. The 12 patients received a median number of 3 courses (range 1-6). No complete or partial response and two disease stabilizations were observed. Ten patients progressed on therapy. The combination of ifosfamide and etoposide does not appear to be an effective salvage treatment for advanced ovarian cancer.

In 26 seizure-prone gerbils, with chronically implanted electrodes, the electro-clinical relationship of seizures was studied. The results are based on 70 EEG recordings of fully developed seizures resulting from: (1) moving the animal from its home cage to the testing area, i.e., the naturally occurring environmentally precipitated seizures (EPS); (2) electrically induced by stimulation of cortical electrodes (ICS); and (3) electrically induced by stimulation of hippocampal electrodes (IHS). The EPS were categorized into 4 electro-clinical phases: myoclonic, clonic-tonic, tonic, and clonic movements; usually preceded by an incipient period and followed by a post-seizure period. Usually the EPS were preceded by focal single spiking in the posterior part of the hemisphere, during which the animal's behavior was normal. This spiking turned to generalized epileptic discharges (incipient period without epileptic behavior) which were followed by the 4 phases of generalized myoclonic and clonic-tonic seizures. Post-seizure coma-like behavior was associated with EEG depression. The ICS were very similar to the EPS, but of course lacking the incipient phase. In contrast to the EPS and ICS, the IHS were very different both in terms of EEG and clinical manifestations. Moreover, the post-seizure depression was absent or negligible. We conluded that in the EPS in gerbils, the cortex is of primary importance as to the site of origin of the seizure, while the hippocampal involvement is secondary to it.

Forty-two evaluable patients with advanced non-small cell lung cancer were treated with teniposide at doses ranging from 120 to 180 mg/m2 on Days 1, 3, and 5 every 3 weeks. Thirty-four patients had received no prior chemotherapy. Seven partial responses (16.6%) were obtained (21% in chemotherapy-unexposed patients). Marrow toxicity was the main side effect: life-threatening thrombocytopenia occurred in 9% of patients, and 54.5% experienced severe leukopenia. Teniposide, at the doses and schedule employed, has moderate activity in non-small cell lung cancer.

Infections are the most common cause of death in tumor patients. The risk of infection is progressively increased in relation to the severity of neutropenia. It is therefore essential to start empirical antibiotic therapy in these patients at the first sign of infection. Forty-three neutropenic tumor patients were entered into the above study when it was assumed that they had bacterial infections (temperature above 38.5 degrees C and/or signs and symptoms of infection). Patients with greater than 1000 neutrophils/mm3 were given piperacillin alone while those with more severe neutropenia (less than 1000/mm3) were given a combination of piperacillin plus amikacin. Of the 43 patients who had entered the study, 41 could be evaluated whereas the remaining two were considered dropouts either because of non-compliance with the study protocol or because the infection was found to be non-bacterial. In both groups of patients (greater than 1000 and less than 1000 neutrophils/mm3) infection resolved completely in a large percentage of cases (92% and 82%, respectively). The efficacy of piperacillin was therefore reconfirmed for the management of infection in oncologic patients with neutropenia, and proved to be an effective therapeutic resource in patients with both slight and severe neutropenia.

A synergistic effect between alpha-Interferon and Bleomycin has been recently shown in in vitro and in vivo experimental systems. Although active, Bleomycin and other antineoplastic drugs give low response rates in non-small cell lung cancer, but, like the other antineoplastic agents, responses are short-lived. We treated 13 patients with advanced non-small cell lung cancer with the combination Bleomycin 15 mg/m2 i.v. at hour 0 and alpha-Interferon 9 X 10(6) U i.m. given at hours 6, 30 and 54. Major side effects were pyrexia, astenia and anorexia; only one case of moderate leukopenia was observed. No major responses were obtained and stable disease lasted a median of 5 months. Further study of this combination is not warranted in patients with pretreated non-small cell lung cancer.

Myelotoxicity is one of the most important side effects of antineoplastic drugs. Even in using the same dosages, the gravity of this toxicity varies greatly among different patients. With the aim of evaluating if an in vitro test may predict such an effect we have measured in bone marrow samples taken from 15 patients undergoing chemotherapy for small-cell lung cancer the in vitro uptake of 3H-thymidine in the presence or absence of the cytostatic drugs used for the clinical treatment of these patients. We did not find a clear correlation between the in vitro results and the myelotoxicity observed during the clinical course.

One hundred sixty-five patients with surgically treated thymoma were followed over 28 years; 73% had myasthenia gravis at presentation. Invasiveness was based on macroscopic findings at operation. Postsurgical radiotherapy or chemotherapy were not routinely used. Overall survival was 84%, 79%, and 65% at 3, 5, and 10 years, respectively. Patients with invasive thymoma survived for a shorter period than patients with noninvasive tumors (67% versus 85% at 5 years); when radical excision was possible, no difference was detectable between the two groups. Patients with subtotally resected or only biopsied invasive thymomas survived 59% and 42% at 5 years, respectively. Lymphoepithelial cases had the worst prognosis of the histologic types considered. Myasthenia gravis did not adversely affect survival. Surgery is the basic treatment of thymomas. Macroscopic invasiveness and degree of excision judged by the surgeon have prognostic value and are reliable criteria of malignancy. Radiotherapy and chemotherapy may be effective, but their use should be limited to controlled trials.

Invasive thymomas are rare neoplasms arising from the epithelial cells of the thymus. In this paper, we report five cases of invasive thymoma treated with cisplatin either alone or combined with etoposide. Two partial responses (lasting 1 and 27+ months from the start of chemotherapy), two minor responses (lasting 1.5 and 13+ months from the start of chemotherapy), and one mixed response were observed. Further studies with cisplatin-containing regimens are warranted in the treatment of this rare tumor.