Stitching techniques for measuring X-ray synchrotron mirror topography.

Optical metrology and polishing techniques are continuously evolving to satisfy the increasingly stringent specifications required for X-ray optical components for synchrotron and free-electron laser light source beamlines. For both spherical and aspherical geometries, the most demanding applications may have target residual figure errors close to 1 nm. To achieve such specifications and maintain them in the optomechanical mount, it is critical to develop methods capable of measuring the topography of the optical surface over the clear aperture of the mirror. The European Synchrotron Radiation Facility optical metrology laboratory has developed a stitching tool initially aimed at measuring long flat mirrors up to 1 m long with a Fizeau interferometer. The system is routinely used providing 2D maps of the optical surface. The instrument capabilities have been extended to characterize moderately curved optics using a transmission flat element, and results obtained on a high quality spherical mirror with 120 m of radius of curvature are presented. As a novel approach of stitching application, the technique has been used to improve the measurement accuracy of the Fizeau interferometer when measuring short plane mirrors. Acquisition of 2D topographies on a short plane mirror by micro-stitching interferometry is also presented and discussed.

Mathematical model for preoperative identification of obstructed nasal subsites.

The planning of experimental studies for evaluation of nasal airflow is particularly challenging given the difficulty in obtaining objective measurements in vivo. Although standard rhinomanometry and acoustic rhinometry are the most widely used diagnostic tools for evaluation of nasal airflow, they provide only a global measurement of nasal dynamics, without temporal or spatial details. Furthermore, the numerical simulation of nasal airflow as computational fluid dynamics technology is not validated. Unfortunately, to date, there are no available diagnostic tools to objectively evaluate the geometry of the nasal cavities and to measure nasal resistance and the degree of nasal obstruction, which is of utmost importance for surgical planning. To overcame these limitations, we developed a mathematical model based on Bernoulli's equation, which allows clinicians to obtain, with the use of a particular direct digital manometry, pressure measurements over time to identify which nasal subsite is obstructed. To the best of our knowledge, this is the first study to identify two limiting curves, one below and one above an average representative curve, describing the time dependence of the gauge pressure inside a single nostril. These upper and lower curves enclosed an area into which the airflow pattern of healthy individuals falls. In our opinion, this model may be useful to study each nasal subsite and to objectively evaluate the geometry and resistances of the nasal cavities, particularly in preoperative planning and follow-up.

Stitching methods at the European Synchrotron Radiation Facility (ESRF).

X-ray mirror quality has continuously improved over the past 20 years and manufacturers are now able to provide long mirrors with slope errors below 0.2 µrad. Nevertheless, these mirrors are mounted on holders or even mechanical benders to adjust their curvature and their intrinsic quality must be preserved from any parasitic deformation such as twist. The most direct method of detecting these deformations is to measure the 3D topography of the optical surface. At the ESRF metrology laboratory, three different stitching systems are under development based on Fizeau sub-aperture measurements. The first one consists of measuring long flat mirrors, the second based on the relative angle determinable stitching interferometry (RADSI) method developed at SPring-8 is aimed primarily at the measurement of short mirrors with strong curvature down to a few meters, and the last, also based on the RADSI method, is dedicated to characterize longer mirrors with intermediate curvature. For each method we will describe the measurement setup and discuss first results obtained. Micro-stitching interferometry is also currently used at the ESRF metrology laboratory. The technique is suitable for measuring deeply curved aspherical profiles and will be illustrated with results from a Kirkpatrick-Baez mirror system for nano-focusing.

Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment.

The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35-59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.

Differences among young adults, adults and elderly chronic myeloid leukemia patients.

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.

Phosphorylation of the human respiratory syncytial virus N protein provokes a decrease in viral RNA synthesis.

When HEp-2 cells are infected by human respiratory syncytial virus (HRSV) its N protein becomes phosphorylated at tyrosine (Y) Y38, in a strictly regulated way. To determine how this phosphorylation affects nucleocapsid (NC) template activity during viral RNA synthesis, N protein variants were analysed in which Y38 and nearby Y residues were substituted by phenylalanine (F; Y23F, Y38F and Y69F) or aspartic acid (D; Y23D and Y38D). While the capacity of these proteins to form the NC and to interact with the P protein was maintained, their NC template activity was altered affecting distinctly viral transcription and replication of HRSV based minigenomes. Thus, Y38 phosphorylation of the HRSV N protein modulates NC template activity probably by altering the interactions of the monomeric components of the NC.

Uterine myomas during pregnancy: a longitudinal sonographic study.

OBJECTIVE: To evaluate volumetric changes of uterine myomas (fibroids) during pregnancy. METHODS: This was an observational, longitudinal and prospective study of 38 consecutive Caucasian women with singleton pregnancies and a total of 42 uterine myomas, enrolled from a cohort of 1492 women who took part in our first-trimester Down syndrome screening program. Myoma volume was evaluated by ultrasound at 11-14, 20-22 and 32-34 weeks of gestation. RESULTS: Mean myoma volume increased significantly throughout pregnancy. Taking a volumetric change of > 10% between gestational periods to be an increase in size, 71.4% of uterine myomas increased in size between the first and second gestational periods, while this percentage was slightly lower (66.6%) between the second and third periods. Logistic regression analysis revealed that greater maternal age was correlated with a reduction/no change in overall myoma size and multiparity was correlated with a decrease/no change between the first and second trimesters, while a higher prepregnancy maternal body mass index (BMI) was correlated with a volumetric increase between the first and second trimesters and a decrease/no change between the second and third trimesters. CONCLUSIONS: Fibroids enlarge during pregnancy regardless of their initial size or local factors, and maternal age, prepregnancy BMI and parity are apparently correlated with these changes.

Liposomal amphotericin B in the treatment of visceral leishmaniasis in immunocompromised patients.

Leishmaniasis is a zoonosis caused by a protozoan of the Leishmania genus. First-line treatment for all forms is currently represented by the use of antimony derivatives, although toxic effects and the number of resistant strains in both immunocompromised and immunocompetent patients is increasing. Liposomal amphotericin B (L-AMB) is less toxic, more effective, and better tolerated, especially in human immunodeficiency virus-negative immunocompromised patients. We present 2 cases of transplanted patients affected by visceral leishmaniasis treated successfully with L-AMB.

BU/melphalan and auto-SCT in AML patients in first CR: a 'Gruppo Italiano Trapianto di Midollo Osseo (GITMO)' retrospective study.

AML patients (total 129; median age =50 years; range 16-72) in first CR received BU and melphalan (BU/Mel) as conditioning regimen before auto-SCT. In all, 82 patients (63.6%) received PBSCs and 47 patients (36.4%) received BM cells. The distribution of cytogenetic categories was conventionally defined as favorable (15.5%), intermediate (60.1%) and unfavorable (24.3%). With a median follow-up of 31 months, the 8-year projected OS and disease-free survival (DFS) was 62 and 56% for the whole population, respectively. The relapse rate was 46% and the non-relapse mortality was 4.65%. Although PBSC transplantation led to a faster hematological recovery than BM transplantation, in univariate analysis the stem cell source, cytogenetics and different BU formulations did not significantly affect OS and DFS, whereas age and the number of post-remission chemotherapy cycles did have a significant effect on the clinical outcome. Multivariate analysis identified age <55 years as the only important independent predictor for OS and DFS. Our data suggest that BU/Mel, being associated with a low toxicity profile (mainly mucositis) and mortality, is an effective conditioning regimen even for high-risk AML patients in first CR undergoing auto-SCT.

Endovascular Treatment of Cerebral Arteriovenous Malformation Bleeding during Pregnancy. A Case Report.

Cerebral arteriovenous malformations (AVMs) represent congenital anomalies of blood vessels composed of a nidus of anomalous arterial and venous vessels without a capillary network. We describe a case of bleeding cerebral AVM in a pregnant women at the second quarter of gestation and diagnosed by digital subtraction angiography showing a large principal arterial nidus supply. The AVM was treated by endovascular embolization at the 27th week of gestation. The post-operative course was uneventful and a caesarean section was performed at the 37th week of gestation. The endovascular approach may represent a safe method in the treatment of this cerebral condition during pregnancy.

[Establishment of a quality indicator for pharmaceutical care]. / Establecimiento de un indicador de calidad de atención farmacéutica.

OBJECTIVE: To establish a quality indicator for pharmaceutical care in an integral system for personalized medication dispensing (ISPMD) with electronic prescription. METHODS: Descriptive transversal study. PERIOD: 2007. On a daily basis, we revised the pharmaceutical treatment of patients admitted to hospital units with ISPMD. STUDY VARIABLES: a) suitability of pharmaceutical interventions: important or very important; b) acceptance of those interventions. The LASER method was used to identify patients with improvement opportunities. RESULTS: In absolute terms (mean +/- SD): important pharmaceutical interventions, 26.6 +/- 14.8; very important, 31.5 +/- 24.6; acceptance, 57.5 +/- 25.9. Percentages (95 % CI): pharmaceutical interventions: important, 33.7 (9.3-58.0); very important, 39.80 (17.7-62.2); acceptance, 72.6 (64.7-80.5). CONCLUSIONS: Implementation of the quality indicator for pharmaceutical care allowed us to evaluate the clinical significance and the acceptance rate of the pharmaceutical care being provided.

Establecimiento de un indicador de calidad de atención farmacéutica* / Establishment of a quality indicator for pharmaceutical care

Objetivo: Establecer un indicador de calidad de atención farmacéutica en un centro con sistema integral de dispensación individualizada de medicación (SIDIM) y prescripción electrónica. Métodos: Estudio descriptivo transversal. Periodo: año 2007. Se realizó una revisión diaria del tratamiento farmacoterapéutico de los pacientes ingresados en unidades de hospitalización con SIDIM. Variables de estudio: a) idoneidad de las intervenciones farmacéuticas: importantes, muy importantes, y b) aceptación de éstas. Para la identificación de pacientes con oportunidades de mejora en su farmacoterapia se empleó la metodología LASER®. Resultados: En términos absolutos (media ± desviación estándar): intervenciones farmacéuticas importantes, 26,6 ± 14,8; muy importantes, 31,5 ± 24,6; aceptación, 57,5 ± 25,9. En porcentaje (intervalo de confianza del 95 %): intervenciones farmacéuticas importantes, 33,7 (9,3-58,0); muy importantes, 39,80 (17,7-62,2); aceptación, 72,6 (64,7-80,5). Conclusiones: La implantación del indicador de calidad de atención farmacéutica ha permitido evaluar la significación clínica y el grado de aceptación de las intervenciones farmacéuticas realizadas (AU)

Objective: To establish a quality indicator for pharmaceutical care in an integral system for personalised medication dispensing (ISPMD) with electronic prescription. Methods: Descriptive transversal study. Period: 2007. On a daily basis, we revised the pharmaceutical treatment of patients admitted to hospital units with ISPMD. Study variables: a) suitability of pharmaceutical interventions: important or very important; b) acceptance of those interventions. The LASER® method was used to identify patients with improvement opportunities. Results: In absolute terms (mean ± SD): important pharmaceutical interventions, 26.6 ± 14.8; very important, 31.5 ± 24.6; acceptance, 57.5 ± 25.9. Percentages (95 % CI): pharmaceutical interventions: important, 33.7 (9.3-58.0); very important, 39.80 (17.7-62.2); acceptance, 72.6 (64.7-80.5). Conclusions: Implementation of the quality indicator for pharmaceutical care allowed us to evaluate the clinical significance and the acceptance rate of the pharmaceutical care being provided (AU)

Caesarean section on request: are there loco-regional factors influencing maternal choice? An Italian experience.

We aimed to evaluate regional differences in women's motivations and in obstetricians' attitudes re 'caesarean section on request' between obstetricians practicing in Southern and Northern Italy. An anonymous questionnaire was sent to 70 randomly selected specialists practicing in the Veneto region and Sicily. Demographic characteristics, percentage of caesarean section, increase of caesarean section on demand, maternal motivations and the role played by anxiety, relatives and instrumental examinations were analysed. Moreover, obstetricians' opinion and their behaviour in fulfilling, or not, the maternal request were evaluated. Among the emotional reasons, fear of pain was more frequently reported in Sicily (p = 0.045), and previous negative experiences and gestational anxiety in the Veneto region (p = 0.009; p = 0.001). As regards instrumental examinations influencing maternal request, a significant difference was found for ultrasonography (28% in Sicily vs 60% in Veneto, p = 0.002). The husband's role was more frequently reported in the Veneto region (p = 0.006). Obstetricians of both regions noticed a rising rate of caesarean section on maternal request. The reasons for this upward trend are complex, vary from one region to another and are influenced by local socio-cultural and healthcare background.

A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients.

BACKGROUND: A prospective, single-arm, open-label, nonrandomized phase II combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus radioimmunotherapy trial was conducted to evaluate the efficacy and safety in untreated elderly diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS: From February 2005 to April 2006, in our institute we treated 20 eligible elderly (age > or =60 years) patients with previously untreated DLBCL using a novel regimen consisting of six cycles of CHOP chemotherapy followed 6-10 weeks later by (90)Y ibritumomab tiuxetan. RESULTS: The overall response rate to the entire treatment regimen was 100%, including 95% complete remission (CR) and 5% partial remission. Four (80%) of the five patients who achieved less than a CR with CHOP improved their remission status after radioimmunotherapy. With a median follow-up of 15 months, the 2-year progression-free survival was estimated to be 75%, with a 2-year overall survival of 95%. The (90)Y ibritumomab tiuxetan toxicity included grade > or =3 hematologic toxicity in 12 of 20 patients; the most common grade > or =3 toxic effects were neutropenia (12 patients) and thrombocytopenia (7 patients). Transfusions of red blood cells and/or platelets were given to one patient. CONCLUSION: This study has established the feasibility, tolerability, and efficacy of this regimen for elderly patients with DLBCL.

Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group.

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

Liposome-encapsulated doxorubicin citrate in previously treated recurrent/metastatic gynecological malignancies.

The aim of this study was to evaluate the safety and efficacy of liposome-encapsulated doxorubicin citrate (LEDC) in patients affected by recurrent/metastatic gynecological malignancies scheduled for palliative chemotherapy. Inclusion criteria were proven recurrent/advanced gynecological neoplasms, measurable/assessable disease, adequate organ function, left ventricular ejection fraction >50% as determined by echocardiography, informed consent. LEDC was administered intravenously over 1 h at the dose of either 75 mg/m(2) or 60 mg/m(2) (every 3 weeks until disease progression or toxicity prohibiting further therapy). From May 2003 to September 2005, 36 patients were enrolled. Primary disease was ovarian, endometrial, and cervical cancers in 15 (42%), 11 (30%), and 10 (28%) patients, respectively. LEDC was employed as third- or fourth-line chemotherapy in 25 (70%) and 11 (30%) patients, respectively. The median number of courses of LEDC received was 3 (range 2-9). Six patients (17%) achieved a partial response to treatment lasting 27 weeks and 10 patients (28%) experienced stable disease lasting 18 weeks. The predominant toxicity was hematological, especially neutropenia. Among patients receiving a dose of 75 mg/m(2), two (11%) suspended therapy for febrile neutropenia, and nine (50%) required a dose reduction of 25%. As a result, the next 18 patients were treated at a reduced dose (60 mg/m(2)) of LEDC. Severe neutropenia (G3-G4) was significantly less common in this group (61% versus 22%; P= 0.04). LEDC has shown antineoplastic activity in previously treated recurrent/metastatic gynecological cancer patients and the toxicity profile could be considered acceptable at a 60 mg/m(2) dosage.

Impact of surgery on the development of duodenal cancer in patients with familial adenomatous polyposis.

PURPOSE: Precancerous duodenal lesions in patients with familial adenomatous polyposis can be detected with duodenoscopy and treatment may prevent the development of cancer. We proposed to determine the frequency, natural history, cumulative risk, and risk factors of the precancerous duodenal lesions in a series of patients diagnosed in northern Italy. METHODS: A prospective, endoscopic, follow-up protocol was performed in 50 patients examined by gastroduodenoscopy at two years of interval or less. The presence and severity of precancerous lesions of the duodenal mucosa were evaluated by Spigelman score. Twenty-five patients (50 percent) had proctocolectomy and ileoanal anastomosis, 15 (30 percent) had colectomy and ileorectal anastomosis, and 5 (10 percent) had proctocolectomy and definitive ileostomy from 0 to 3 years before the admission to the surveillance program. All patients showed more than a thousand adenomas in the colorectal mucosa. No patients with attenuated polyposis were found. RESULTS: At the first endoscopy, duodenal adenomas could be detected in 19 of 50 patients (38 percent), whereas at the end of the follow-up, 43 (86 percent) had duodenal lesions. The final mean Spigelman score increased during the follow-up period (P<0.001 respect to baseline values). No duodenal cancer could be detected. Eleven patients had or developed severe precancerous duodenal lesions (Stage IV) treated with endoscopic or surgical resection. The distribution of patients with Stage IV according to the surgery of the colon was: 2 of 25 treated with ileoanal anastomosis and 8 of 15 with ileorectal anastomosis (P=0.0024, Fisher's exact test). CONCLUSIONS: Patients with familial adenomatous polyposis are at risk of significant neoplasia. The natural history of precancerous lesions might be related to surgical treatment of colorectal neoplasms.

Adiponectin and insulin resistance in early- and late-onset pre-eclampsia.

OBJECTIVE: To evaluate the importance of adiponectin and insulin resistance in early- and late-onset pre-eclampsia. DESIGN: A nested case-control study in 72 pregnant women who participated in the first-trimester Down-syndrome-screening programme and who delivered at our hospital. SETTING: University Hospital, Department of Obstetrics and Gynecology. POPULATION: Pregnant women: 36 women with pre-eclampsia of which 20 late onset and 16 early onset were compared with 36 uncomplicated pregnancies who delivered at term. METHODS: In all the women, insulin resistance was calculated by the homeostasis model assessment ratio (HOMA-IR) and plasma adiponectin was determined using an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Insulin resistance and adiponectin concentration. RESULTS: First-trimester plasma adiponectin mean levels in the whole pre-eclampsia group were significantly lower than that in the control group (8.4 +/- 3.3 versus 14.8 +/- 4.6 microgram/ml; P < 0.001), whereas first-trimester mean HOMA-IR values were significantly higher in the pre-eclampsia group than that in the control group (2.0 +/- 1.1 versus 1.0 +/- 0.4; P= 0.01). Plasma adiponectin concentrations at delivery in the pre-eclampsia group were significantly higher than that in the control group (9.2 +/- 3.7 versus 7.8 +/- 2.6 microgram/ml; P= 0.04). First-trimester plasma adiponectin mean concentrations in the late-onset subgroup were significantly lower compared with the concentrations in early-onset subgroup (6.2 +/- 1.4 microgram/ml versus 11.1 +/- 3.2 microgram/ml; P < 0.001), and there was a significant difference in adiponectin plasma values only between women in the late-onset pre-eclampsia group versus those in the control group (P < 0.001). First-trimester mean HOMA-IR values were significantly higher in the late-onset subgroup compared with that of the early-onset subgroup (2.5 +/- 1.3 versus 1.3 +/- 0.3; P= 0.02), and there was a significant difference only between the control group versus the late-onset subgroup (P= 0.001). CONCLUSIONS: First-trimester adiponectin and HOMA-IR values seem to select two completely different populations: early- and late-onset pre-eclampsia, which might suggest a different pathogenesis.

Upper body venous thrombosis associated with ovarian stimulation: case report and review of the literature.

Thromboembolic events are a serious complication of assisted conception treatment. Thrombosis may be either arterial or venous but the latter is far more common. This phenomenon is more frequent in the lower limb, but several cases of upper extremity thrombosis have been described in the literature. Although the aetiology of these thromboembolic disorders is not fully understood, the mechanism is thought to be due to a hypercoagulable state associated with haemostasis and thrombophilia. Predisposing factors seem to be hyperoestrogenism, ovarian hyperstimulation syndrome, a hereditary hypercoagulable state and multifoetal pregnancy. We report a case of superior sagittal sinus thrombosis that developed in a patient following successful assisted conception in the absence of evident risk factors. In the current literature, the site of thrombosis, possible predisposing factors, oestrogen levels, number of foetuses, maternal and foetal outcomes, and management of thrombosis were analysed.