For several engineering and seismological applications, site effects can be synthetically evaluated as a soil amplification factor of the reference ground motion on a rock outcrop leading to the peak ...ground acceleration and/or the response spectrum expected at a soil site, classified according to its equivalent shear wave velocity, VS,30. In this work, nonlinear stratigraphic amplification factors as specified by Eurocode 8 (EC-8) and National Technical Code (NTC) were assessed with reference to selected accelerometric records of the Italian seismic network and well-characterized recording stations classified according to VS,30. A first set of ‘empirical’ amplification factors has been identified, by selecting those stations on deformable soil for which records of the same events exist also at a nearby reference station located on outcropping rock (4 sites, 102 records). A second set of ‘semi-empirical’ data has been obtained by analysing the accelerograms recorded at stations where the geotechnical characterization was comprehensive and the reference motion could be back-figured by de-convolution to the bedrock (7 sites, 50 records). A third set of ‘analytical’ data was obtained from 1D numerical simulations of seismic site response performed on virtual stratigraphic profiles, consistent with the ground classification adopted by EC-8 and NTC, and subjected to 80 acceleration time histories of 22 Italian earthquakes, recorded at 19 stations of the Italian Network classified as rock sites. Empirical, semi-empirical and analytical data have been therefore integrated to express the stratigraphic amplification factor of peak ground acceleration and spectral intensity as a function of the corresponding reference ground motion value for each class of subsoil.
•Stratigraphic amplification factors by European and Italian codes were assessed.•Empirical data were obtained from pairs of nearby stations on soil and rock outcrop.•Semi-empirical data were obtained by bedrock de-convolution of the recorded motions.•Analytical data were obtained from numerical simulations of seismic response.•Nonlinear expressions of stratigraphic amplification factors were obtained.
To assess the seismic performance of slopes, the simplified displacement-based methods represent a good-working balance between simplicity and reliability. The so-called uncoupled methods permit to ...account for the effects of deformability and ductility by computing separately the dynamic site response and the sliding block displacements. In this paper the procedure proposed by Bray and Rathje (
1998
) was revised and adapted to Italian seismicity on a set of subsoil models, representative of the different soil classes specified by the Italian and European Codes. The relationship expressing the decrease of the equivalent acceleration with earthquake/soil frequency ratio was then obtained by means of dynamic 1D seismic response analyses. Statistical correlations between calculated Newmark displacements, significant ground motion parameters and the critical acceleration ratio were also derived. To estimate the reference ground motion parameters necessary for the full implementation of the proposed procedure, literature predictive equations, calibrated on strong motion records of international databases, were revised for the Italian seismicity. These ground motion prediction equations, together with simplified displacements relationships, allowed for developing an original quick procedure to evaluate the seismic slope performance by specifying the probability of exceedance of a threshold displacement, based only on few seismic input motion parameters.
Intratumoral transport and binding are important mechanisms that determine the efficacy of cancer drugs. Current drug screening methods rely heavily on monolayers of cancer cells, which overlook the ...contribution of tissue-level transport and binding. To quantify these factors, we developed a method that couples an
in vitro
, drug-delivery device containing a three-dimensional cell mass and a mathematical model of drug diffusion, binding to DNA, release from carriers, and clearance. Spheroids derived from LS174T human colon carcinoma cells were inserted into rectangular chambers to form rectangular cell masses (tissue) and subjected to continuous medium perfusion. To simulate drug delivery and clearance, the tissues were treated with doxorubicin followed by drug-free medium. To evaluate the effect of liposome encapsulation, tissues were treated with liposome-encapsulated doxorubicin (Doxil). Spatiotemporal dynamics of drug distribution and apoptosis was measured by fluorescence microscopy. The diffusivity and DNA binding constant of doxorubicin were determined by fitting experimental data to the mathematical model. Results show that an ideal combination of diffusivity, binding constant, clearance rate, and cytotoxicity contribute to the high therapeutic efficacy of doxorubicin. There was no detectable release of doxorubicin from Doxil in the tissues. The rate of doxorubicin release, evaluated by fitting experimental data to the mathematical model, was below therapeutically effective levels. These results show that despite enhanced systemic circulation obtained by liposome encapsulation, the therapeutic effect of Doxil is limited by slow intratumoral drug release. The experimental and computational methods developed here to calculate drug efficacy provide mechanisms to explain poor performance of drug candidates, and enable design of more successful cancer drugs.
A method for predicting the efficacy of cancer drugs by measuring their intratumoral diffusion and binding, using a microfluidic device that contains 3D tumor tissue.
Introduction Sleep disorders is a common complaint in patients with multiple sclerosis (MS). These include insomnia, nocturnal movement disorders, sleep-disordered breathing, narcolepsy, excessive ...daytime sleepiness (EDS), fatigue and REM dysregulation. However, it would seem necessary a different evaluation of the pharmacological treatment in patients with MS and EDS. Materials and methods A 76-year-old female with MS (detected 32 years ago) showed from 18 years clinical features of chronic indistinguishable insomnia, EDS, fatigue, social and quality of life impairment and severe limitations in walking and home mobility. The sleep was less than 6 h and the patient snored mildly. She did not present other diseases: BMI was 19.2 kg/m2 , neck circumference was 34 cm, and was also screened for depression (neg). Nocturnal polysomnography revealed: TIB 549 min, TST 281 min, Sleep Efficiency 52.9%, WASO 138 min, StageN1 2.3%, StageN2 13.3%, StageN3 38.4%, Stage R 0.7%, Wake/Mov 45.3%. AHI was 4.3/h, ODI 2.1/h, RDI 10.2/h; PLM av 4.3/h; av O2 sat. 92%; Nadir O2 sat. 83%; ESS 23. Neuroimaging study (brain MRI) confirmed morphological evidences of MS in the corona radiata, centro semiovale, in the bilateral cerebellar hemisphere and a nuanced alteration of signal level at the midbrain, which extends caudally in the pons and in the reticular formation, in relation to the degenerative phenomena and neuronal deafferentation. The patient had been taking, for many years, benzodiazepines, non-benzodiazepine hypnotics, amitriptyline, mirtazapine, promazine, gabapentin, without any clinical effect. So, we started the administration of the following drugs: quetiapine 25 mg, trazodone 50 mg, escitalopram 20 mg; there was no need to add melatonin receptor agonist. Results At the control, the patient showed a significant improvement in sleep efficiency and decrease of EDS; a second nocturnal polysomnography demonstrate: TIB 420 min, TST 416 min, Sleep Efficiency 99%, WASO 2 min, Stage N1 10.3%, StageN2 45.4%, Stage N3 32.2%, Stage R 11.2%, Wake/Mov 0.9%. AHI was 2.3/h, ODI 1.6/h, RDI 3.2/h; PLM av 0.6/h; av O2 sat. 93%; Nadir O2 sat. 86%; ESS 9. Conclusion There are no specific guidelines for treatment of insomnia in MS patients; however, the CNS lesions, such as brainstem lesion and/or damage to the medullary reticular formation, are assumed to play a main role for the effectiveness or ineffectiveness of drug therapies. Finally, our data suggest to investigate the potentially reversible sleep disorders in MS patients. Acknowledgement Stefano Bastianello, MD Neuroradiologist.
STUDY QUESTION
What is the risk of complications after uterine leiomyoma embolization and what are the factors associated with complications?
SUMMARY ANSWER
The cumulative risk of complications after ...embolization is relatively low even in the long term, but submucosal leiomyoma location may increase the risk.
WHAT IS KNOWN ALREADY
A broad spectrum of complications after leiomyoma embolization have been described with widely varying rates. There is uncertainty over the actual risk of complications and the factors associated with this risk.
STUDY DESIGN, SIZE, DURATION
This was a prospective cohort study of 288 consecutive women undergoing leiomyoma embolization in the general gynaecology clinic of a university teaching hospital between January 2001 and December 2010.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Complications occurring after embolization were categorized as major or minor according to the severity of their impact on health, the level of care required and the outcome. Cumulative complication rates were estimated by survival analysis and log-rank tests according to baseline variables. Multivariable Cox proportional hazards analysis was performed to adjust for confounders.
MAIN RESULTS AND THE ROLE OF CHANCE
There were 48 patients who experienced a complication at a median of 5 months (95% confidence interval, 4.1–11.4) after embolization. Complications were minor in 38 patients and major in 10 patients. The cumulative overall complication rate was 13% (95% CI, 9.0–17.0) at 6 months, 16% (95% CI, 11.0–20.0) at 1 year, 17% (95% CI, 12.0–22.0) at 3 years and 18% (95% CI, 12.9–22.8) at 5 years. The most frequent complication (19/48, 39.6%) was leiomyoma expulsion, which occurred spontaneously in 13 (68.4%) of these cases and required assistance in 6 (31.6%) cases. Eight (2.8%) patients underwent re-intervention, including six hysteroscopic myomectomies, one laparoscopic myomectomy and one hysteroscopic adhesiolysis, as a result of a complication. Submucosal leiomyoma location was the only baseline variable associated with an increased risk for complications Hazard ratio (HR), 2.28, 95% CI, 1.24–4.18, P = 0.008.
LIMITATIONS, REASONS FOR CAUTION
Our population did not include women of African descent, who have been reported to be at higher risk of post-procedural complications compared with Causcasian women. If such women were involved in the study, higher morbidity rates might have been observed.
WIDER IMPLICATIONS OF THE FINDINGS
Women with submucosal leiomyomas at the time of embolization are more likely to have post-procedural complications. This is important new information for counselling patients contemplating this therapeutic approach.
STUDY FUNDING/COMPETING INTEREST(S)
The authors have no competing interests to declare. The study was not supported by any external grant.
BACKGROUND
Unilocular-solid ovarian cysts are a rare but challenging pathology in young women, with a desire to spare their fertility. In these cases, the risks of borderline and invasive disease are ...around 10 and 20%, respectively. No ultrasound rule has yet demonstrated the ability to discriminate with high accuracy, a borderline tumor from a benign tumor or ‘invasive tumor’. The aim of this study was to assess the predictive performance of different ultrasound parameters in differentiating benign and borderline tumors versus invasive malignant tumors in premenopausal patients with unilocular-solid ovarian masses.
METHODS
Women aged ≤50 years with unilocular-solid adnexal masses with a maximum diameter ≤10 cm, undergoing surgery in our department within 3 months from ultrasound examination, were included in this retrospective study. A standardized ultrasound examination technique and predefined definitions of ultrasound characteristics were used. The results of ultrasound examination using gray scale and color Doppler were compared with the histological examination of the respective surgical specimens.
RESULTS
The study included 51 patients. On histological examination, 36 (70%) lesions were classified as benign, 10 (20%) as borderline ovarian tumors and 5 (10%) as invasively malignant tumors. In receiver-operating characteristic curve analysis, the best cut-off for the largest solid component with regard to discriminating non-invasive (benign or borderline) from invasive tumors was 14 mm. A largest solid component >14 mm, the presence of papillation blood flow and the combination of the two parameters provided a sensitivity of 100% and a specificity of 63, 63 and 80%, respectively.
CONCLUSIONS
Transvaginal ultrasound examination seems to be able to discriminate between invasive and non-invasive tumors in the premenopausal patients with unilocular-solid adnexal masses. Because of the retrospective nature of the study, further prospective clinical trials are needed to confirm the accuracy of the selected sonographic parameters in discriminating the invasive and non-invasive adnexal tumors.
Non-surgical management of uterine fibroids Tropeano, Giovanna; Amoroso, Sonia; Scambia, Giovanni
Human reproduction update,
05/2008, Letnik:
14, Številka:
3
Journal Article
Recenzirano
Odprti dostop
BACKGROUND: Efforts to develop alternatives to surgery for management of symptomatic uterine fibroids have provided new techniques and new medications. This review summarizes the existing literature ...on uterine artery embolization (UAE) and investigational studies on four newer approaches. METHODS: PubMed, Cochrane and Embase were searched up to December 2007. Studies reporting side-effects and complications and presenting numerical data on at least one outcome measure were included. RESULTS: Case studies report 50–60% reduction in fibroid size and 85–95% relief of symptoms following UAE. The largest of these studies reported an in-hospital complication rate of 2.7% (90 of 3041 patients) and a post-discharge complication rate of 26% (710 of 2729 patients). Eight studies compared UAE with conventional surgery. Best evidence suggested that UAE offered shorter hospital stays (1–2 days UAE versus 5–5.8 days surgery, 3 randomized controlled trials (RCTs)) and recovery times (9.5–28 days UAE versus 36.2–63 days surgery, 3 RCTs) and similar major complication rates (2–15% UAE versus 2.7–20% surgery, 3 RCTs). Four studies analysing cost-effectiveness found UAE more cost-effective than surgery. There is insufficient evidence regarding fertility and pregnancy outcome after UAE. Five feasibility studies after transvaginal temporary uterine artery occlusion in 75 women showed a 40–50% reduction in fibroid volume and two early studies using magnetic resonance guided–focused ultrasound showed symptom relief at 6 months in 71% of 109 women. Two small RCTs assessing mifepristone and asoprisnil showed promising results. CONCLUSIONS: Good quality evidence supports the safety and effectiveness of UAE for women with symptomatic fibroids. The current available data are insufficient to routinely offer UAE to women who wish to preserve or enhance their fertility. Newer treatments are still investigational.
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