Anomalous nucleation of crystals within amorphous germanium nanowires during thermal annealing.

In this work, germanium nanowires rendered fully amorphous via xenon ion irradiation have been annealed within a transmission electron microscope to induce crystallization. During annealing crystallites appeared in some nanowires whilst others remained fully amorphous. Remarkably, even when nucleation occurred, large sections of the nanowires remained amorphous even though the few crystallites embedded in the amorphous phase were formed at a minimum of 200 °C above the temperature for epitaxial growth and 100 °C above the temperature for random nucleation and growth in bulk germanium. Furthermore, the presence of crystallites was observed to depend on the diameter of the nanowire. Indeed, the formation of crystallites occurred at a higher annealing temperature in thin nanowires compared with thicker ones. Additionally, nanowires with a diameter above 55 nm were made entirely crystalline when the annealing was performed at the temperature normally required for crystallization in germanium (i.e. 500 °C). It is proposed that oxygen atoms hinder both the formation and the growth of crystallites. Furthermore, as crystallites must reach a minimum size to survive and grow within the amorphous nanowires, the instability of crystallites may also play a limited role for the thinnest nanowires.

Sonographic discrimination between benign and malignant adnexal masses in premenopause.

PURPOSE: The aim of this study was to assess the diagnostic value of sonographic pattern recognition by experts, a standardized morphological scoring system, the risk malignancy index (RMI) and CA 125 assay for the preoperative assessment of ovarian lesions in premenopausal patients. MATERIAL AND METHODS: Diagnostic work-up of 1320 patients who underwent surgical exploration due to an adnexal mass at a tertiary referral center were included. We assessed the discriminative value of pattern recognition, a sonographic morphological scoring system, RMI and CA 125 by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa for each diagnostic approach while using histopathology as the reference standard. RESULTS: Pattern recognition showed the highest discriminative power with an observed kappa of 0.53. Sensitivity and specificity yielded 0.76 and 0.97 respectively. Combining pattern recognition with CA 125 serum measurement in the context of a triage system diminished the diagnostic value (kappa: 0.24; sensitivity: 0.29 specificity: 0.97). For the RMI we observed a sensitivity of 0.54 and a specificity of 0.96 and estimated kappa value yielded 0.37. Omitting the CA 125 assay and using a morphological sonographic assessment system increased the kappa value to 0.45 with sensitivity and specificity observed at 0.61 and 0.97 respectively. CONCLUSION: Expert pattern recognition was found to be the method with the highest discriminative power in assessing an adnexal mass during premenopause. Additional assessment of serum CA 125 diminished the diagnostic accuracy. Standardized morphological sonographic assessment resulted in a moderate diagnostic accuracy. Supplementing the morphological sonographic assessment with CA 125 by using the RMI algorithm did not improve the diagnostic value.

Laparoscopic lymphocele fenestration in gynaecological cancer patients after retroperitoneal lymph node dissection as a first-line treatment option.

OBJECTIVE: To evaluate laparoscopic lymphocele fenestration (LLF) as a first-line treatment in gynaecological cancer patients with a history of retroperitoneal lymph node dissection (LND). DESIGN: Retrospective cohort study. SETTING: A tertiary referral centre. POPULATION: Patients who underwent LLF between January 2001 and December 2010 for a symptomatic lymphocele following retroperitoneal LND. METHODS: Surgical outcomes of 102 patients who underwent LLF at our hospital between January 2001 and December 2010 were analysed. Patients were identified using hospital database search software, and hand-written and electronic charts were reviewed. MAIN OUTCOME MEASURES: Outcomes included operating time, blood loss, conversion rate, intra- and postoperative complication rates, hospital stay and relapse rate. RESULTS: A total of 132 lymphoceles were fenestrated in 102 patients. The mean duration of surgery was 115.6 minutes and the average intraoperative blood loss per patient was 146 ml. The overall conversion rate to laparotomy was 7.8%. Intra- and postoperative complication rates were estimated at 9.8 and 5.9%, respectively. The rate of intraoperative and postoperative complications was significantly higher in patients after pelvic plus paraaortic LND (23.8%), compared with those after pelvic LND only (3.6%; P > 0.01). The mean follow-up time was 60.4 months and a total of seven symptomatic recurrences of lymphoceles were observed (a recurrence rate of 6.9%). CONCLUSIONS: For the treatment of symptomatic lymphoceles, LLF has previously been established as an efficient first-line treatment option in a post-transplant context. Our data suggest that these favourable results for LLF may be transferable to gynaecological cancer patients.

Assessment of Risk for Ventricular Tachycardia based on Extensive Electrophysiology Simulations.

Patients that have suffered a myocardial infarction are at high risk of developing ventricular tachycardia. Patient stratification is often determined by characterization of the underlying myocardial substrate by cardiac imaging methods. In this study, we show that computer modeling of cardiac electrophysiology based on personalized fast 3D simulations can help to assess patient risk to arrhythmia. We perform a large simulation study on 21 patient digital twins and reproduce successfully the clinical outcomes. In addition, we provide the sites which are prone to sustain ventricular tachycardias, i.e, onset sites around the scar region, and validate if they colocalize with exit sites from slow conduction channels.Clinical relevance- Fast electrophysiological simulations can provide advanced patient stratification indices and predict arrhythmic susceptibility to suffer from ventricular tachycardia in patients that have suffered a myocardial infarction.

[Investigation of epidemiology of neurotrauma in the Republic of Guinea].

The paper focuses on analysis of incidence of neurotrauma in economically underdeveloped country such as Republic of Guinea. It is found that leading etiology of central nervous system injuries are road accidents and indoor traumatism. Investigation of system of medical care revealed its poor condition and severe defects which prevent practical application of evidence-based recommendations for management of traumatic brain injury in underdeveloped countries including Republic of Guinea. Development of multiplanar strategy of control of neurotrauma is required which can be achieved only in case of massive governmental and international aid.

Prognostic role of platinum sensitivity in patients with brain metastases from ovarian cancer: results of a German multicenter study.

BACKGROUND: Ovarian cancer is the leading cause of death in women with gynecological malignancies. Brain metastases are considered an uncommon metastatic site. Only few data exist on prognostic factors for this patient collective. PATIENTS AND METHODS: A multicenter retrospective chart review was carried out including all patients with histologically confirmed ovarian cancer from six different German hospitals from 1981 to 2008. Overall, 4277 cases of patients with ovarian cancer were screened and patients with brain metastasis were identified and analyzed regarding various clinical variables and survival. RESULTS: A total of 74 women with brain metastases were identified, resulting in an incidence of 1.73%. In multivariate analysis, the following clinical parameters had a significant impact on overall survival: multiple lesions [hazard ratio (HR) 4.4, 95% confidence interval (CI) 2.0-9.7] and low grading (HR 3.1, 95% CI 1.7-5.8) were associated with a negative impact. Platinum sensitivity (HR 0.23, 95% CI 0.12-0.48) was significantly associated with a favorable outcome. Good performance status (60%-80% HR 0.48, 95% CI 0.23-0.99 and 90%-100% HR 0.21, 95% CI 0.08-0.53) also had a positive impact on overall survival. CONCLUSIONS: Platinum sensitivity is the most important prognostic factor in patients with ovarian cancer metastatic to the brain. This novel finding should be considered in the strategy of multimodal therapy for brain metastases in ovarian cancer.

A geographical approach to identify sleeping sickness risk factors in a mangrove ecosystem.

OBJECTIVES: To provide a better understanding of sleeping sickness transmission and spread in mangrove areas to optimize its control. METHODS: In the Forecariah mangrove area, Guinea, 19 sleeping sickness cases and 19 matched controls were followed up in their living areas (at home, in fields and at water points). All occupational sites and pathways were mapped and then placed in their environmental context. RESULTS: The sleeping sickness cases displayed a significantly broader and more diverse spatial occupation than the controls. They covered double the daily walking distances of controls and had on average two more occupational sites, most of which were located in mangrove forests. Activities with a higher transmission risk (rice culture, attendance of pirogue jetties) were identified as well as high-risk areas and pathways. CONCLUSIONS: An entomological control strategy targeting transmission risk areas is proposed. Its implementation in a control programme would reduce by 86% the efforts needed for a classical vector control programme throughout the area. Medical surveys set up at specific locations, such as pirogue jetties and high-risk paths, should also enable better targeting of the population at highest risk.

Sequential chemotherapy with carboplatin followed by weekly paclitaxel in advanced ovarian cancer: results of a multicenter phase II study of the northeastern German society of gynecological oncology.

BACKGROUND: For the adjuvant setting of advanced ovarian cancer (AOC) after primary radical surgery the combination of paclitaxel and platinum in a 3-week schedule has emerged as the current standard. In preclinical studies additional anti-angiogenic effects of low dose paclitaxel infusion were demonstrated. A sequential schedule of carboplatin and paclitaxel has the potential to improve the therapeutic index. METHODS: In this multicenter phase II trial four cycles of carboplatin at a dose of AUC 5 (d1/q21d) followed by 12 cycles of weekly paclitaxel at a dose of 80 mg/m(2) (d1/q7d) were applied after primary radical surgery. Eligible were all optimally or sub-optimally debulked patients with FIGO IA-IV ovarian cancer. All patients with hemoglobin levels <12 mg/dl received erythropoietin additionally. RESULTS: Between July 2003 and May 2005, 105 patients from 27 institutions were enrolled. The median age was 60 years (range: 23-80 years). A median number of 16 courses (range 1-16) were applied. The incidence of non-hematological toxicities was very low. Only 41% of patients experienced alopecia (grade 1-2). Neurotoxicity (grade 3-4) was not observed. Grade 3-4 hematological toxicity (43% of all patients) included thrombocytopenia (17%), anemia (3%), leucopenia (23%), and neutropenic fever (0%). Ninety-seven percent received erythropoietin. Thromboembolic events (4%) were not increased in patients who received erythropoietin. After a median time of 23 months (range: 1-42 months) 32 patients had died, and the median overall survival was not reached. The progression-free survival was 25.4 months (95% CI: 18.8-40+). CONCLUSION: These results suggest that this sequential regimen using weekly paclitaxel represents an efficacious and well-tolerated regimen. A randomized study comparing this new schedule with the conventional 3-week protocol is warranted.

Treatment of endometriosis of uterosacral ligament and rectum through the vagina: description of a modified technique.

BACKGROUND: Endometriosis is common in women of childbearing age, whereas involvement of the rectosigmoid requiring resection is rare. Laparoscopy has become a standard procedure in the management of endometriosis. The optimum way to diagnose endometriosis is by direct visualization of the implants. Usually for the removal of the specimen, an additional larger abdominal incision is needed. METHODS: Here we report on cases of four patients with a uterosacral ligament and rectal endometriosis who were successfully treated with combined laparovaginal resection, using a modification of an existing technique. They had been complaining of rectal bleeding and lower abdominal pain in relation to their menstrual cycle. The aim of this technique is to achieve a careful and margin-free resection of the area involved. This can be done without any large incisions of the abdominal wall. The hypogastric nerves remain preserved on both sides. RESULTS: The intra- and post-operative courses were uneventful. No blood transfusions were needed. Haemoglobin decrease was usually < or =1 mmol/l. The average tumour diameter was 3.5 cm. CONCLUSIONS: Our technique circumvents a larger abdominal incision. This combined laparoscopic-transvaginal approach, avoiding the extension of port-site incisions, represents a viable option for the treatment of bowel endometriosis.

Diffusion-weighted imaging (DWI) in MR mammography (MRM): clinical comparison of echo planar imaging (EPI) and half-Fourier single-shot turbo spin echo (HASTE) diffusion techniques.

Diffusion-weighted imaging (DWI) techniques have shown potential to differentiate between benign and malignant neoplasms. However, the diagnostic significance of using DWI under routine conditions remains unclear. This study investigated the use of echo planar imaging (EPI) and half-Fourier acquired single-shot turbo spin echo (HASTE)-DWI with respect to the three parameters: lesion visibility, apparent diffusion coefficient (ADC) measurements, and size estimation. Following MRM (1.5 T), EPI- and HASTE-DWI were applied in 65 patients. Lesion visibility on DWI was compared with lesion visibility on subtracted contrast-enhanced T1w images (CE-T1w). Statistical tests were applied to diameter, visibility, and ADC value measurements. Seventy-four lesions were identified. ADC value measurements did not differ significantly between the two DWI sequences. The sensitivity and specificity of routine diagnostics (97.4% and 85.7%) were superior to EPI-DWI (87.2% and 82.9%) and HASTE-DWI (76.9% and 88.6%). Selecting only nonmass lesions, DWI did not prove to be of diagnostic value. Lesion demarcation by DWI was significantly lower compared with that by CE-T1w, with EPI-DWI showing the better performance (p < 0.001). No significant differences were found for size measurements between CE-T1w and DWI. Although clearly inferior compared with CE-T1w imaging, both DWI techniques are applicable for lesion assessment and size measurements.

Sentinel lymph node biopsy in vulvar cancer: a pilot study.

BACKGROUND: The aim of the pilot study was to assess the feasibility, efficacy, and accuracy of the sentinel lymph node biopsy (SLNB) procedure in vulvar cancer. PATIENTS AND METHODS: From February 2003 to March 2007, 17 patients with vulvar cancer, clinical Stages I and II, underwent SLN (sentinel lymph node) detection, followed by a complete inguinal-femoral lymphadenectomy. Demographic, surgical, and pathologic data on all patients were reviewed. RESULTS: 17 patients underwent the SLNB procedure. Sixteen had vulvar carcinoma and one patient suffered from melanoma of the vulva. Midline localisation was done in 11 patients (64.7%). A total of 371 lymph nodes were resected. The median number of removed lymph nodes was 15 (range 2 to 81). Nineteen lymph nodes were positive with a maximum of six in one patient. Overall the detection rate for the sentinel lymph node was 88.2% (15 out of 17). One of the two patients with a non detectable sentinel node had positive lymph nodes. Eighty lymph nodes were detected as the sentinel node. The median number of sentinel nodes was five (range 0 to 11). Seventeen sentinel nodes were involved. The sentinel node was negative in nine patients; one of these had involved lymph nodes. CONCLUSIONS: SLNB is feasible and safe to perform in vulvar cancer. Further evaluation is needed until new guidelines allow the use in early-stage vulvar cancer.

[Gayet-Wernicke's encephalopathy. A study of 13 cases observed in a refugee population hospitalized at the Conakry Teaching Hospital]. / Encéphalopathie de Gayet-Wernicke. Etude de 13 observations dans une population de patients réfugiés hospitalisés pour affections neurologiques au CHU de Conakry.

The authors report 13 cases of Gayet-Wernicke's encephalopathy observed in 13 patients of a refugee population. 11 presented the classical triad: oculomotor signs, cerebral ataxia and state of confusion and in 2 patients, only 2 symptoms were noted. The etiological factors: chronic alcoholism, malnutrition, uncontrollable vomiting, HIV and tuberculosis were identified. The outcome was evaluated on the basis of the disappearance of symptoms after treatment with 500 mg of thiamine in 7 patients, 1 death and 5 patients progressed toward Korsakoff amnesic syndrome.

Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis.

The canonical Wnt signalling pathway plays a key role during embryogenesis and defects in this pathway have been implicated in the pathogenesis of various types of tumours, including breast cancer. The gene for secreted frizzled-related protein 1 (SFRP1) encodes a soluble Wnt antagonist and is located in a chromosomal region (8p22-p12) that is often deleted in breast cancer. In colon, lung, bladder and ovarian cancer SFRP1 expression is frequently inactivated by promoter methylation. We have previously shown that loss of SFRP1 protein expression is a common event in breast tumours that is associated with poor overall survival in patients with early breast cancer. To investigate the cause of SFRP1 loss in breast cancer, we performed mutation, methylation and expression analysis in human primary breast tumours and breast cell lines. No SFRP1 gene mutations were detected. However, promoter methylation of SFRP1 was frequently observed in both primary breast cancer (61%, n=130) and cell lines analysed by methylation-specific polymerase chain reaction (MSP). We found a tight correlation (P<0.001) between methylation and loss of SFRP1 expression in primary breast cancer tissue. SFRP1 expression was restored after treatment of tumour cell lines with the demethylating agent 5-aza-2'-deoxycytidine. Most interestingly, SFRP1 promoter methylation was an independent factor for adverse patient survival in Kaplan-Meier analysis. Our results indicate that promoter hypermethylation is the predominant mechanism of SFRP1 gene silencing in human breast cancer and that SFRP1 gene inactivation in breast cancer is associated with unfavourable prognosis.

Markov-modeling for the administration of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-line chemotherapy with epithelial ovarian carcinoma.

PURPOSE: So far there is no analysis available on the cost effectiveness of the paclitaxel/platinum-analogue combination versus carboplatin monotherapy with ovarian cancer. Up-to-now only a cost-utility analysis on ovarian carcinoma has been published (Ortega et al. in Gynecol Oncol 66(3):454-463, 1997), which in addition to the first-line chemotherapy included second-line chemotherapy with effectiveness and cost data in the analysis. Therefore, within the scope of our study the cost effectiveness of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-lie chemotherapy was to be determined with epithelial ovarian carcinoma. METHODS: For this purpose a decision-making Markov model was developed which represents the medical and economic consequences of the administration of paclitaxel and platinum derivatives in first-line chemotherapy and the administration of topotecan and liposomal doxorubicin in second-line chemotherapy in the treatment of epithelial ovarian carcinoma by means of data from the literature. Patients were treated either in the early (FIGO stage I-IIa) or advanced stage (FIGO stage IIb-IV). RESULTS: The therapeutic strategy caboplatin followed by topotecan costs 20,123.91 euros, the therapeutic strategy carboplatin followed by liposomal doxorubicin 22,336.57 euros, the therapeutic strategy carboplatin/pactlitaxel followed by liposomal topotecan 29,820.64 euros and the therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin 31,560.47 euros from the time of diagnosis until death or survival within 5 years. With lives saved, accordingly of 2.55, 2.70, 2.60 and 2.65 years' costs amounted to 7,891 euros, 8,270.35 euros, and 11,453.62 euros per year of life saved. CONCLUSIONS: Based on the threshold value of social willingness to pay 45,500 euros per year of life saved, the therapeutic strategy carboplatin followed by topotecan, the therapeutic strategy carboplatin followed by liposomal doxorubicin, the therapeutic strategy carboplatin/paclitaxel followed by topotcan and the therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin can be evaluated to be cost effective.

Cardiac function estimation from MRI using a heart model and data assimilation: advances and difficulties.

In this paper, we present a framework to estimate local ventricular myocardium contractility using clinical MRI, a heart model and data assimilation. First, we build a generic anatomical model of the ventricles including muscle fibre orientations and anatomical subdivisions. Then, this model is deformed to fit a clinical MRI, using a semi-automatic fuzzy segmentation, an affine registration method and a local deformable biomechanical model. An electromechanical model of the heart is then presented and simulated. Finally, a data assimilation procedure is described, and applied to this model. Data assimilation makes it possible to estimate local contractility from given displacements. Presented results on fitting to patient-specific anatomy and assimilation with simulated data are very promising. Current work on model calibration and estimation of patient parameters opens up possibilities to apply this framework in a clinical environment.

Simulation of cardiac pathologies using an electromechanical biventricular model and XMR interventional imaging.

Simulating cardiac electromechanical activity is of great interest for a better understanding of pathologies and for therapy planning. Design and validation of such models is difficult due to the lack of clinical data. XMR systems are a new type of interventional facility in which patients can be rapidly transferred between X-ray and MR systems. Our goal is to design and validate an electromechanical model of the myocardium using XMR imaging. The proposed model is computationally fast and uses clinically observable parameters. We present the integration of anatomy, electrophysiology, and motion from patient data. Pathologies are introduced in the model and simulations are compared to measured data. Initial qualitative comparison on the two clinical cases presented is encouraging. Once fully validated, these models will make it possible to simulate different interventional strategies.

Long-term risk of fibroid recurrence after laparoscopic myomectomy.

OBJECTIVE: The use of laparoscopic myomectomy as a surgical treatment for uterine leiomyoma is associated with low intraoperative morbidity and short hospitalization. Limited data about the long-term outcome of this surgical approach are available. The aims of this study were to estimate the risk of uterine fibroid recurrence after laparoscopic myomectomy and to identify factors contributing to the rate of fibroid relapse. STUDY DESIGN: Between 1996 and 2003, 331 patients underwent laparoscopic myomectomy to treat uterine leiomyoma in our hospital; 224 of these patients consented to participate in our 2009 follow-up survey. Clinical symptomatic uterine leiomyoma recurrence was defined as relapse. Recurrence rates at 24 and 60 months post-operatively were calculated for the study population. Fisher's exact tests were used to examine the impacts of factors previously linked to an increased risk of fibroid recurrence, including (1) patient age at the time of initial surgery, (2) pre-operative body mass index, (3) number and localization of uterine leiomyoma removed, and (4) pregnancy and (5) delivery after laparoscopic myomectomy on fibroid recurrence in our study cohort. RESULTS: We observed 75 recurrences in 224 patients. The cumulative risk of recurrence was 4.9% at 24 months and 21.4% at 60 months post-operatively. An age of 30-40 years and the presence of more than one fibroid at the time of initial laparoscopic myomectomy were identified as factors significantly increasing the risk of symptomatic recurrence after laparoscopic myomectomy (31.25% and 38.71%, respectively; both p<0.01). CONCLUSION: Patients with multiple uterine leiomyoma and those in the third decade of life should be counselled thoroughly about the risk of recurrence prior to laparoscopic myomectomy. The low observed recurrence rate in peri- and postmenopausal patients in our study may support the use of laparoscopic myomectomy as a uterus-preserving surgical alternative beyond the reproductive period.

Heterogeneity of circulating epithelial tumour cells from individual patients with respect to expression profiles and clonal growth (sphere formation) in breast cancer.

BACKGROUND: The detection of tumour cells circulating in the peripheral blood of patients with breast cancer is a sign that cells have been able to leave the primary tumour and survive in the circulation. However, in order to form metastases, they require additional properties such as the ability to adhere, self-renew, and grow. Here we present data that a variable fraction among the circulating tumour cells detected by the Maintrac(®) approach expresses mRNA of the stem cell gene NANOG and of the adhesion molecule vimentin and is capable of forming tumour spheres, a property ascribed to tumour-initiating cells (TICs). PATIENTS AND METHODS: Between ten and 50 circulating epithelial antigen-positive cells detected by the Maintrac approach were selected randomly from each of 20 patients with breast cancer before and after surgery and were isolated using automated capillary aspiration and deposited individually onto slides for expression profiling. In addition, the circulating tumour cells were cultured without isolation among the white blood cells from 39 patients with breast cancer in different stages of disease using culture methods favouring growth of epithelial cells. RESULTS: Although no epithelial cell adhesion molecule (EpCAM)-positive cells expressing stem cell genes or the adhesion molecule vimentin was detected before surgery, 10%-20% of the cells were found to be positive for mRNA of these genes after surgery. Tumour spheres from circulating cells of 39 patients with different stages of breast cancer were grown without previous isolation in a fraction increasing with the aggressivity of the tumour. SUMMARY: Here we show that among the peripherally circulating tumour cells, a variable fraction is able to express stem cell and adhesion properties and can be grown into tumour spheres, a property ascribed to cells capable of initiating tumours and metastases.

Understanding the mechanisms amenable to CRT response: from pre-operative multimodal image data to patient-specific computational models.

This manuscript describes our recent developments towards better understanding of the mechanisms amenable to cardiac resynchronization therapy response. We report the results from a full multimodal dataset corresponding to eight patients from the euHeart project. The datasets include echocardiography, MRI and electrophysiological studies. We investigate two aspects. The first one focuses on pre-operative multimodal image data. From 2D echocardiography and 3D tagged MRI images, we compute atlas based dyssynchrony indices. We complement these indices with presence and extent of scar tissue and correlate them with CRT response. The second one focuses on computational models. We use pre-operative imaging to generate a patient-specific computational model. We show results of a fully automatic personalized electromechanical simulation. By case-per-case discussion of the results, we highlight the potential and key issues of this multimodal pipeline for the understanding of the mechanisms of CRT response and a better patient selection.