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In this paper, we propose a Jacobian smoothing inexact Newton-type algorithm for solving the nonlinear complementarity problem by reformulating it as a system of nonlinear equations. We show that the algorithm converges up to q-quadratically and present numerical experiments that show its good local performance. In order to compare in terms of time our algorithm with other known algorithms, we introduce a new normalized measurement that we call time index. [ABSTRACT FROM AUTHOR]

This work presents a comparative theoretical analysis of spatial modal evolution in micro/nano-optical fiber (MNF) tapers. The study proposes the use of the Spectral Parameter Power Series (SPPS) Method and compares its performance with results from the so-called Exact Modes Method (EMM) and the Finite Element Method (FEM) (the method employed by the COMSOL© software in which the computations were implemented). By using these techniques, the modal analysis and intensity evolution are discussed along different sections of the optical fiber taper. Furthermore, the data are compared considering experimental values from a real micro/nano-optical fiber taper sample. The SPPS method offers a competitive accuracy and versatility to deal with graded index profiles, its computational costs are low, and its implementation is relatively easy. The results from the SPPS method fit to those of the EM method, which sometimes involves intricated models, and those of the FEM, which may require more computational time. The SPPS method offers an average relative error of less than 5% with respect to the exact method with less computational cost compared to the FEM method for radii bigger than 2 μm at 1550 nm. [ABSTRACT FROM AUTHOR]

Organ preservation strategies, especially watch and wait, after neoadjuvant treatment in locally advanced rectal cancer, have become topics that generate significant interest, for both patients and clinicians. The obvious advantage of these strategies is the avoidance of surgery with its associated risks and functional consequences. Over time, it has become evident that these strategies offer acceptable safety in oncological terms and, in most patients, allows preservation of the rectum without harming patients in terms of distant metastasis or survival. However, there is a small group of patients in whom the tumor returns after an initially diagnosed clinical complete response; patients with local tumor regrowth. The main threat in these patients is not simply local disease, which can be successfully managed in most cases, but the possible effects it may have on distant metastases. The pathophysiology of the phenomenon of local tumor regrowth is not well known and, therefore, strategies to minimize possible impact on survival are not well defined. Our aim is to review key issues in this subgroup that pose a substantial threat to the safety and viability of organ-preserving and watch-and-wait strategies. We also explore possible pathophysiologic explanations and future directions and perspectives that may improve both local and systemic disease control. [ABSTRACT FROM AUTHOR]

The Galileo High Accuracy Service (HAS) is a new capability of the European Global Navigation Satellite System that is currently under development. The Galileo HAS will start providing satellite orbit and clock corrections (i.e. non-dispersive effects) and soon it will also correct dispersive effects such as inter-frequency biases and, in its full capability, ionospheric delay. We analyse here an ionospheric correction system based on the fast precise point positioning (Fast-PPP) and its potential application to the Galileo HAS. The aim of this contribution is to present some recent upgrades to the Fast-PPP model, with the emphasis on the model geometry and the data used. The results show the benefits of integer ambiguity resolution to obtain unambiguous carrier phase measurements as input to compute the Fast-PPP model. Seven permanent stations are used to assess the errors of the Fast-PPP ionospheric corrections, with baseline distances ranging from 100 to 1000 km from the reference receivers used to compute the Fast-PPP corrections. The 99% of the GPS and Galileo errors in well-sounded areas and in mid-latitude stations are below one total electron content unit. In addition, large errors are bounded by the error prediction of the Fast-PPP model, in the form of the variance of the estimation of the ionospheric corrections. Therefore, we conclude that Fast-PPP is able to provide ionospheric corrections with the required ionospheric accuracy, and realistic confidence bounds, for the Galileo HAS. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to assess differences in low back stabilization and underlying mechanisms between patients with low back pain (LBP) and healthy controls. It has been hypothesized that inadequate trunk stabilization could contribute to LBP through high tissue strains and/or impingement. Evidence to support this is inconsistent, and not all methods that have been used to study trunk stabilization are equally suitable. We have recently developed a method to assess intrinsic and reflexive contributions to trunk stabilization, which aims to circumvent the limitations of previous studies. Methods: Forty-nine participants suffering from chronic LBP and a control group of fifty healthy subjects participated in this study. Trunk stabilization was measured using force-controlled perturbations directly applied to the trunk. The actuator displacement and contact force between the actuator and subject were measured as well as electromyography (EMG) of the M. Longissimus. Underlying mechanisms were characterized using system identification. Results: LBP patients showed lower admittance, i.e., less displacement per unit of force applied, mainly due to higher position, velocity and acceleration feedback gains. Among patients, lower trunk admittance and higher reflex gains were associated with more negative pain-related cognitions. Conclusion: Trunk stabilization differs between LBP patients and controls, with the same perturbations causing less trunk movement in patients, due to stronger reflexes. We interpret these changes as reflecting protective behavior. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Background: An organ-preserving strategy may be a valid alternative in the treatment of selected patients with rectal cancer after neoadjuvant radiotherapy. Preoperative assessment of the risk for tumor recurrence is a key component of surgical planning. The aim of the present study was to increase the current knowledge on the risk factors for tumor recurrence. Methods: The present study included individual participant data of published studies on rectal cancer surgery. The literature was reviewed according to according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data checklist (PRISMA-IPD) guidelines. Series of patients, whose data were collected prospectively, having neoadjuvant radiotherapy followed by transanal local excision for rectal cancer were reviewed. Three independent series of univariate/multivariate binary logistic regression models were estimated for the risk of local, systemic and overall recurrence, respectively. Results: We identified 15 studies, and 7 centers provided individual data on 517 patients. The multivariate analysis showed higher local and overall recurrences for ypT3 stage (OR 4.79; 95% CI 2.25–10.16 and OR 6.43 95% CI 3.33–12.42), tumor size after radiotherapy > 10 mm (OR 5.86 95% CI 2.33–14.74 and OR 3.14 95% CI 1.68–5.87), and lack of combined chemotherapy (OR 3.68 95% CI 1.78–7.62 and OR 2.09 95% CI 1.10–3.97), while ypT3 was the only factor correlated with systemic recurrence (OR 5.93). The analysis of survival curves shows that the overall survival is associated with ypT and not with cT. Conclusions: Local excision should be offered with caution after neoadjuvant chemoradiotherapy to selected patients with rectal cancers, who achieved a good response to neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Osteosarcoma and atypical teratoid rhabdoid tumors are tumor entities with varying response to common standard therapy protocols. Histone acetylation affects chromatin structure and gene expression which are considered to influence radiation sensitivity. The aim of this study was to investigate the effect of the combination therapy with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and irradiation on atypical teratoid rhabdoid tumors and osteosarcoma compared to normal tissue cell lines.Methods: Clonogenic assay was used to determine cell survival. DNA double-strand breaks (DSB) were examined by pulsed-field electrophoresis (PFGE) as well as by γH2AX immunostaining involving flow cytometry, fluorescence microscopy, and immunoblot analysis.Results: SAHA lead to an increased radiosensitivity in tumor but not in normal tissue cell lines. γH2AX expression as an indicator for DSB was significantly increased when SAHA was applied 24 h before irradiation to the sarcoma cell cultures. In contrast, γH2AX expression in the normal tissue cell lines was significantly reduced when irradiation was combined with SAHA. Analysis of initial DNA fragmentation and fragment rejoining by PFGE, however, did not reveal differences in response to the SAHA pretreatment for either cell type.Conclusion: SAHA increases radiosensitivity in tumor but not normal tissue cell lines. The increased H2AX phosphorylation status of the SAHA-treated tumor cells post irradiation likely reflects its delayed dephosphorylation within the DNA damage signal decay rather than chromatin acetylation-dependent differences in the overall efficacy of DSB induction and rejoining. The results support the hypothesis that combining SAHA with irradiation may provide a promising strategy in the treatment of solid tumors. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia (PA) is a leading cause of neuronal damage in newborns, resulting in long-term neurological and cognitive deficits, in part due to impairment of mesostriatal and mesolimbic neurocircuitries. The insult can be as severe as to menace the integrity of the genome, triggering the overactivation of sentinel proteins, including poly (ADP-ribose) polymerase-1 (PARP-1). PARP-1 overactivation implies increased energy demands, worsening the metabolic failure and depleting further NAD availability. Using a global PA rat model, we report here evidence that hypoxia increases PARP-1 activity, triggering a signalling cascade leading to nuclear translocation of the NF-κB subunit p65, modulating the expression of IL-1β and TNF-α, pro-inflammatory molecules, increasing apoptotic-like cell death in mesencephalon of neonate rats, monitored with Western blots, qPCR, TUNEL and ELISA. PARP-1 activity increased immediately after PA, reaching a maximum 1-8 h after the insult, while activation of the NF-κB signalling pathway was observed 8 h after the insult, with a >twofold increase of p65 nuclear translocation. IL-1β and TNF-α mRNA levels were increased 24 h after the insult, together with a >twofold increase in apoptotic-like cell death. A single dose of the PARP-1 inhibitor nicotinamide (0.8 mmol/kg, i.p.), 1 h post delivery, prevented the effect of PA on PARP-1 activity, p65 translocation, pro-inflammatory cytokine expression and apoptotic-like cell death. The present study demonstrates that PA leads to PARP-1 overactivation, increasing the expression of pro-inflammatory cytokines and cell death in mesencephalon, effects prevented by systemic neonatal nicotinamide administration, supporting the idea that PARP-1 inhibition represents a therapeutic target against the effects of PA. [ABSTRACT FROM AUTHOR]

Background:Abiraterone is a CYP17A1 inhibitor that improves survival in castration-resistant prostate cancer (CRPC). Abiraterone is licensed in combination with prednisone 5 mg twice daily to prevent a syndrome of secondary mineralocorticoid excess. We hypothesised that a 'steroid switch' from prednisone to dexamethasone would induce secondary responses in patients progressing on abiraterone and prednisone 5 mg b.i.d.Methods:We performed a 'steroid switch' in patients with CRPC at PSA progression on abiraterone and prednisolone. Patients were monitored for secondary declines in PSA, radiological tumour regression and toxicity.Results:A retrospective analysis of 30 CRPC patients who underwent a steroid switch from prednisolone to dexamethasone while on abiraterone was performed. A total of six patients (20%) had a ⩾50% PSA decline that was confirmed by a second PSA level at least 3 weeks later. In all, 11 patients (39.2%) had a confirmed ⩾30% PSA decline. Median time to PSA progression on abiraterone and dexamethasone was 11.7 weeks (95% CI: 8.6-14.8 weeks) in the whole cohort and 27.6 weeks (95% CI: 14.5-40.7 weeks) in patients who achieved a confirmed 50% PSA decline. Nine patients had RECIST evaluable disease: two of these patients had RECIST partial response, six patients had stable disease and one patient had progressive disease at the first imaging assessment. Treatment was well tolerated, with no grade 3 and grade 4 adverse events. One patient had to be reverted to prednisolone because of grade 2 hypotension.Conclusions:Durable PSA responses occur in up to 40% of patients following a 'steroid switch' for PSA progression on abiraterone and prednisone. Studies are ongoing to elucidate the mechanisms underlying this response. [ABSTRACT FROM AUTHOR]

Patients "capable" of dealing with extra costs associated with the experimental prophylactic HIPEC arm are more likely to have been "better" candidates (clinically, nutritionally, etc.) than patients in whom such financial burden was significant, and therefore declined such treatment alternative. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy has become a valid alternative for the treatment of peritoneal carcinomatosis in selected patients with colorectal cancer. [Extracted from the article]

The healthcare sector is an important contributor to mercury (Hg) pollution because of the potential presence of mercury in thermometers, blood pressure cuffs, amalgams, etc. There are also other potential sources of mercury in this sector which are used frequently and in high volumes where the presence of the metal is not obvious and which might be collectively contributing to pollution. For instance, some chemicals used for the clinical diagnosis of illness may contain mercury. The goal of this study was to investigate potential sources of mercury pollution, which originate from clinical laboratory discharges, using an exploratory approach. The focus was on the residue generated during automatic analysis of patients' bodily fluids at a medical center in Hermosillo, Sonora, Mexico. This study shows an overview of what might be happening in the region or the country related to non-obvious sources of mercury in the healthcare sector. The results showed measurable levels of mercury in the residues coming from urine sediment analysis. These amounts do not exceed the maximum allowed by Mexican environmental regulations; nevertheless, the frequency and cumulative volume of residues generated, combined with the potential for persistence and the bioaccumulation of mercury in the environment, warrant attention. The work carried out in this study is being taken as a model for future studies for pollution prevention in the healthcare sector with the goal of measuring mercury emissions to the environment from clinical laboratory wastewater, including identifying sources which-while not obvious- could be important given the frequency and volume of their use in the clinical diagnosis. [ABSTRACT FROM AUTHOR]

Background: Molecular imaging using positron emission tomography/computerized tomography (PET/CT) may add relevant incremental diagnostic information to standard structural cross-sectional imaging. Such information may allow identification of patients with rectal cancer that are more likely to develop complete tumor regression after neoadjuvant chemoradiation therapy (CRT). The objective of this report was to identify PET/CT features that are associated with a complete response after CRT. Methods: 99 cT2-4N0-2M0 distal rectal cancer patients (≤7 cm from anal verge) were included in this prospective single center trial (NCT 00254683). Patients underwent baseline PET/CT followed by 54 Gy and 5-fluorouracil-based neoadjuvant CRT. After completion of therapy, patients underwent 6- and 12-week PET/CT. Clinical assessment of tumor response was performed at 12 weeks and was blinded to radiological information. Patients were treated according to clinical assessment. Results: There were seven patients with a complete pathological response (pCR) and 16 with a complete clinical response (cCR) (23 complete responders). Comparison of pCR exclusively and non-pCR revealed that only baseline primary tumor standard uptake value (SUV) was a significant predictor of response. Comparison of complete responders (pCR or cCR) and non-complete responders showed that depth of rectal wall uptake at baseline PET/CT ( p = 0.002) and variation between baseline and 12-week maximum standard uptake value (SUVmax) of primary tumor ( p = 0.001) were independent predictors for complete response at multivariate analysis. A decrease >67 % between baseline and 6-week or 76 % between baseline and 12-week SUVmax were associated with complete response (pCR or cCR; p = 0.02 and p < 0.001, respectively). Conclusions: Positron emission tomography/computerized tomography at baseline, 6 and 12 weeks, may provide information regarding patients with a higher likelihood of developing complete tumor regression following neoadjuvant CRT. [ABSTRACT FROM AUTHOR]

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We determined in cultured kidney epithelial cells (LLC-PK) the effects of high glucose, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) on mRNA and protein expression of the renal glucose transporters SGLT1 and SGLT2. Cultured monolayers were incubated with similar concentrations of IL-6 and TNF-α to those produced by LLC-PK in the presence of 20 mM glucose. Confluent monolayers with either 5 (controls, C) or 20 mM glucose (high glucose, HG) were incubated in the presence of 5 mM glucose, 20 mM glucose, 10 pg/ml IL-6, or TNF-α alone or in combination. Separate groups with IL-6 and TNF-α were incubated with antibodies to their respective receptors. HG induced an increased SGLT1 mRNA at 48 h ( p < 0.05 vs. C) and protein expression in 120 h ( p < 0.05 vs. C). HG also induced an increased SGLT2 mRNA at 72 and 96 h ( P < 0.05 vs. C) and SGLT2 protein expression at 120 h ( p < 0.05 vs. C). In C, 10 pg/ml IL-6 or TNF-α did not modify SGLT1 mRNA (n.s vs. in the absence of cytokines). In contrast, cytokines induced an increased expression of SGLT1 protein at 120 h ( p < 0.05 vs. in the absence of cytokines), and SGLT2 mRNA and protein were increased at 96 and 120 h, respectively ( p < 0.05 vs. in absence of cytokines). No changes were observed when cells were incubated with cytokines and HG (n.s vs. C). In conclusion, this study showed that SGLT2 increased in the presence of IL-6 and TNF-α, indicating an autocrine modulation of the expression of this transporter by cytokines. [ABSTRACT FROM AUTHOR]

Collagen-hydroxyapatite (HA) scaffolds for the non-viral delivery of a plasmid encoding the osteoinductive protein bone morphogenetic protein (BMP)-7 were developed. The collagen-HA was obtained by the combination of calcium phosphate cement in a collagen template. The effect on cell behavior of increasing amounts of HA in the scaffolds was evaluated. Collagen-HA scaffolds containing 13, 23 or 83 wt% HA were prepared. Cell proliferation was reduced in the 83% HA scaffold after 1 day compared to 13 and 23% HA, but by 14 days the number of cells in 83% HA considerably increased. Alkaline phosphatase (ALP) activity was 8 times higher for the 83% HA scaffolds. BMP-7 plasmid was incorporated into the 83% HA scaffold. The transfection was low, although significant levels of BMP7 were expressed, associated with an increase in cell proliferation. [ABSTRACT FROM AUTHOR]

It is shown in this letter that in the framework of an inhomogeneous geometry and a massive non-self-interacting scalar field with spherical symmetry, one needs a homogeneous patch bigger than a dizain of horizons in order to start inflation. The results are completely independent of initial conditions on the spatial distribution of the scalar field. The initial condition on the metric parameters are also justified. This is a generalization of the results obtained by E. Calzetta and M. Sakellariadou [1]: Phys. Rev. D 45, 2802 (1992), showing that their conclusions are rather robust. [ABSTRACT FROM AUTHOR]

Background: Management of rectal cancer has become increasingly complex and a multidisciplinary approach is considered of key importance for improving outcomes. A national survey among specialists involved in this multidisciplinary setting was performed. Methods: A web-based survey containing 11 questions regarding rectal cancer management was sent to surgeons and medical oncologists registered by their corresponding societies as members. Statistical analysis was performed using the chi-square and Fisher's exact tests for all categorical variables according to response to individual questions. Multivariate analysis was performed using Cox's logistic regression. Results: Overall, 418 email recipients responded the survey. Local staging was performed without either magnetic resonance imaging or endorectal ultrasound by 64% of responders. Seventy-two percent considered that final management decision should be made after neoadjuvant chemoradiation therapy. Additionally, 46% considered that an alternative procedure (local excision or observation) was appropriate in a patient with a complete clinical response. Colorectal surgeons were more frequently in favor of longer intervals after completion of chemoradiation therapy ( P = 0.001) and of alternative management procedures after a complete clinical response ( P = 0.02). After multivariate analysis, the choice of a watch and wait approach after a complete clinical response following neoadjuvant chemoradiation therapy was significantly more frequent among surgeons (OR 3.5, 95% CI 1.8-7.1). Conclusions: Surgeons seem to be more in favor of tailoring management of rectal cancer according to tumor response after neoadjuvant chemoradiation therapy, with longer intervals after chemoradiation therapy, decisions about treatment strategy being made after chemoradiation therapy instead of before, and the use of alternative surgical procedures after a complete clinical response following neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Over the 10 years following the planting of Eucalyptus globulus on an area of 320 ha in 1998, air temperature was measured in the middle of a power line corridor and compared with temperatures recorded at meteorological stations located 11.2 and 35.7 km away. At these reference stations, the annual means of both daily minimum and daily maximum temperature remained approximately constant. In the power line corridor, annual mean daily minimum temperature also remained approximately constant, but annual mean daily maximum temperature fell by about 3.6°C; in particular, between years 4 and 7 the cooling rate was on average about 0.7°C per year. The resulting sigmoid time course of annual mean daily temperature range may partly reflect the evolution of evapotranspiration from the plantation, but seems to be mainly attributable to the shading of the power line corridor by the growing trees, being closely correlated with solar irradiance at the center of the corridor as estimated from tree growth data using sun charts and standard formulae for clear-sky solar irradiance. [ABSTRACT FROM AUTHOR]

Background: Leptin and interleukin-1 (IL-1) upregulate vascular endothelial growth factor (VEGF), promote angiogenesis and are related to worse prognosis of breast cancer. However, it is unknown whether leptin regulates IL-1, and whether these effects are related to leptin-induction of VEGF/VEGFR2 in breast cancer.Methods: Several genetic and pharmacological approaches were used to determine the mechanisms involved in leptin regulation of IL-1 system (IL-1α, IL-1β, IL-1Ra and IL-1R tI) and the impact of IL-1 signalling on leptin-induced VEGF/VEGFR2 expression in mouse mammary cancer 4T1 cells (a model that resembles invasive and highly metastatic human breast cancer).Results: Leptin increased protein and mRNA levels of all components of the IL-1 system. IL-1 upregulation involved leptin activation of JAK2/STAT3, MAPK/ERK 1/2, PI-3K/AKT1, PKC, p38 and JNK. Leptin-induced phosphorylation of mTOR/4E-BP1 increased IL-1β and IL-1Ra expression, but downregulated IL-1α. Leptin upregulation of IL-1α promoter was linked to SP1 and NF-κB transcription factors. In addition, leptin receptor (Ob-Rb) was upregulated by leptin. Interestingly, leptin upregulation of VEGF/VEGFR2 was partially mediated by IL-1/IL-1R tI signalling.Conclusions: We show for the first time that leptin induces several signalling pathways to upregulate the translational and transcriptional expression of IL-1 system in breast cancer cells. Moreover, leptin upregulation of VEGF/VEGFR2 was impaired by IL-1 signalling blockade. These data suggest that leptin pro-angiogenic signature in breast cancer is linked to, or regulated, in part by IL-1 signalling. [ABSTRACT FROM AUTHOR]

Anti-idiotypic monoclonal antibodies (mAb) have been evaluated for actively induced immunotherapy with encouraging results. However, rational combination of cancer vaccines with chemotherapy may improve the therapeutic efficacy of these two approaches used separately. The main objective of this study was to evaluate the antitumor effect of the co-administration of 1E10 (Racotumomab), a monoclonal anti-idiotype tumor vaccine against an IgM mAb, named P3 that reacts specifically with NeuGc-containing gangliosides and low-dose Cyclophosphamide in a mammary carcinoma model. F3II tumor-bearing mice were immunized subcutaneously with 100 μg of 1E10 mAb in Alum or with 150 mg/m2 of Cyclophosphamide intravenously 7 days after the tumor inoculation. While a limited antitumor effect was induced by a single 1E10 mAb immunization; its co-administration with low-dose Cyclophosphamide reduced significantly the F3II mammary carcinoma growth. That response was comparable with the co-administration of the standard high-dose chemotherapy for breast cancer based on 60 mg/m2 of Doxorubicin and 600 mg/m2 of Cyclophosphamide, without toxicity signs. Combinatorial chemo-immunotherapy promoted the CD8+ lymphocytes tumor infiltration and enhanced tumor apoptosis. Furthermore, 1E10 mAb immunization potentiated the antiangiogenic effect of low-dose Cyclophosphamide. Additionally, splenic myeloid cells Gr1+/CD11b+ associated with a suppressor phenotype were significantly reduced in F3II tumor-bearing mice immunized with 1E10 mAb alone or in combination with low-dose Cyclophosphamide. This data may provide a rational for chemo-immunotherapy combinations with potential medical implications in breast cancer. [ABSTRACT FROM AUTHOR]

Objectives: To look for predictors in the clinical records of orders for "limitation of life sustaining treatment" (LLST) or "do not attempt resuscitation" (DNAR) in hospitalized elders and to assess the relationship between the presence of these orders and the quality of end-of-life (EOL) care. Design: Retrospective clinical record review. Setting: Inpatients of an inner city elderly acute care unit (EACU) in Spain. Participants: Of 103 hospitalized patients who died in the EACU during one year, 90 dying an expected death either from acute or chronic disease were included. Measurements: Demographic, functional, cognitive, clinical, and end-of-life (EOL) parameters. The influence of identifying closeness to death and the number of LLST suborders on the quality of EOL-management were considered simultaneously using structural equation modelling with LISREL 8.30 software. Results: LLST and specific DNAR orders were registered in 91.1% and 83.3% of patients, respectively. Failure of acute treatment, discussions with the patient/family, recognizing the presence of common EOL symptoms, and prescribing specific symptomatic treatment were recorded in 88.9%, 93.3%, 94.4%, and 86.7% of patients, respectively. LLST-orders were more likely to be documented if there was severe functional impairment prior to admission (p<0.001), advanced organ disease criteria were met (p=0.006), or closeness to death was acknowledged in writing (p<0.001). The quality of the EOL-management was better in patients for whom there were LLST-orders (p =0.01) and written acknowledgement of closeness to death (p<0.001). Conclusions: LLST-orders were more likely to be written in an EACU for patients with previous severe impairment, co-morbidity, or advanced disease. Written acknowledgement of closeness to death and LLST-orders were predictors of better EOL-management. [ABSTRACT FROM AUTHOR]

Anti-idiotype monoclonal antibody (mAb) 1E10 was generated by immunizing BALB/c mice with an Ab1 mAb which recognizes NeuGc-containing gangliosides, sulfatides and some tumor antigens. 1E10 mAb induces therapeutic effects in a primary breast carcinoma and a melanoma model. However, the tumor immunity mechanisms have not been elucidated. Here we show that aluminum hydroxide-precipitated 1E10 mAb immunization induced anti-metastatic effect in the 3LL-D122 Lewis Lung carcinoma, a poorly immunogenic and highly metastatic model in C57BL/6 mice. The therapeutic effect was associated to the increment of T cells infiltrating metastases, the reduction of new blood vessels formation and the increase of apoptotic tumor cells in lung nodules. Interestingly, active immunization does not induce measurable antibodies to the 1E10 mAb, the NeuGc-GM3 or tumor cells, which may suggest a different mechanism which has to be elucidated. These findings may support the relevance of this target for cancer biotherapy. [ABSTRACT FROM AUTHOR]

As epidermal growth factor receptor (EGFR) has been reported to be a radiation response modulator, HER inhibitors are regarded to act as potential radiosensitisers. Our study examined the role of nimotuzumab and cetuximab both, the two monoclonal antibodies (mAbs) to EGFR, as radiosensitisers in a murine glioma model in vivo. Co-administration of both the antibodies with radiation increased the radiosensitivity of U87MG, resulting in a significant delay of subcutaneous (s.c.) tumour growth. Furthermore, the addition of antibodies to the radiation decreased brain tumour sizes and is inhibited by 40-80% the increased tumour cell invasion provoked by radiotherapy, although promoted tumour cell apoptosis. Whereas nimotuzumab led to a reduction in the size of tumour blood vessels and proliferating cells in s.c. tumours, cetuximab had no significant antiangiogenic nor antiproliferative activity. In contrast, cetuximab induced a more marked inhibition of EGFR downstream signalling compared with nimotuzumab. Moreover, both antibodies reduced the total number of radioresistant CD133+ cancer stem cells (CSCs). These results were encouraging, and showed the superiority of combined treatment of mAbs to EGFR and radiation over each single therapy against glioblastoma multiforme (GBM), confirming the role of these drugs as radiosensitisers in human GBM. In addition, we first showed the ability of mAb specifics against EGFR to target radioresistant glioma CSC, supporting the potential use in patients. [ABSTRACT FROM AUTHOR]

Standardization of total mesorectal excision (TME) had a great impact on decreasing local recurrence rates for the treatment of rectal cancer. However, exact numbers and distribution of lymph nodes (LN) along the mesorectum remains controversial with some studies suggesting that few LNs are present in the distal third of the mesorectum. Eighteen fresh cadavers without a history of rectal cancer were studied. The rectum was removed by TME and then was divided into right lateral, posterior and left lateral sides, which were further subdivided into 3 levels (upper, middle and lower). A pathologist determined the number and sizes of the LNs in each of the nine areas, b linded to their anatomical origin. Overall, the mesorectum had a mean of 5.7 LNs (SD=3.7) and on average each LN had a maximum diameter of 3.0 mm (SD=2.7). There was no association between the mean number or size of LNs with gender, BMI, or age. There was a significantly higher prevalence of LNs in the posterior location (2.8 per mesorectum) than in the two lateral locations (0.8 and 1.2 per mesorectum; p=0.02). The distribution of LNs in the three levels of the rectum was not significant. The distribution of LNs reinforces the fact that TME should always include the distal third of the mesorectum. Care must be taken to not violate the posterior aspect of the mesorectum. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on Clostridium difficile published in the previous issue.

The measurements of radioactivity in drinking water enable us to determine the exposure of the population to radiation through their usual consumption of water. An intensive study of the water supply in the city of Malaga has been carried out to determine both the gross alpha-and gross beta-activity concentrations. Gamma spectrometry was used in order to detect certain types of radionuclides. Results indicated that 95% of the water tested contained a gross alpha-radioactivity of less than 0.1 Bq/1, and 100% gross beta-activity of less than 1 Bq/1 — the activity limit recommended by the Spanish Regulatory Organization. Several factors were found to have an influence on radioactivity levels, such as total hardness, potassium and pH. [ABSTRACT FROM AUTHOR]

The Helmholtz equation describing the propagation of acoustic and electromagnetic waves in a nonhomogeneous media slowly varying in the horizontal direction is considered. The contribution of the discrete and continuous spectra of the transversal Sturm-Liouville problem to the asymptotics is studied. A uniform asymptotics for the Green function in neighborhoods of thresholds is obtained. [ABSTRACT FROM AUTHOR]

A letter to the editor about flame retardancy using an oligomric organophosphorus compound is presented.

The article outlines an investigation on two promising non-reactive 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO)-based flame retardants selected to modify an epoxy matrix for a woven carbon fiber-reinforced composite for high-performance applications. The effectiveness of either DOP-Ethyl or DOP-Cyanur compounds at phosphorus contents of 2 wt% is reported.

The structure-property-relationships, thermal stability and flame retardancy of a DGEBA-DDS system containing various organo-phosphorus compounds as flame retardants is investigated. Three non-reactive (DOP-ethyl, DOP-ethylhexyl and DOP-cyanur) and one reactive (DOP-glycidyl) phosphorous compounds are added separately to the epoxy resin and the mixtures are cured with 4,4′-DDS in a substoichiometric ratio. The addition of such DOPO-compounds leads to improved flame retardancy at low phosphorus contents of about 2 wt.% (about 20 wt.% of additive) without significantly affecting other important properties such as fracture toughness ( K lc) and glass transition temperature ( T g) of the matrix. Neither the type nor the amount of additive affects the fracture toughness of cured epoxies up to additive concentrations of between 18 and 24 wt.%. Furthermore, the loss in glass transition temperature of the cured resin can be correlated with the amount and chemical reactivity of the organo-phosphorus additive. The reactive DOP-glycidyl and the non-reactive DOP-cyanur additive are observed to maintain the highest glass transition temperature of the epoxy system mainly due to a higher extent of the cross-linking reaction. The results presented in this study highlight the potential of optimising the flame retardancy and the resulting physical and mechanical properties of epoxy systems for liquid composite moulding applications by varying the chemical structure of the organo-phosphorus compounds. [ABSTRACT FROM AUTHOR]

Background. Vestibular nerve section is considered to be the most effective surgical procedure to control intractable symptoms secondary to Menière’s disease (MD). This study was developed to analyze the adequacy of retrosigmoid vestibular neurectomy in terms of vertigo control, hearing preservation and clinical complications of this procedure.Methods. A retrospective review was carried out on 14 patients affected by definite unilateral MD who underwent vestibular neurectomy via the retrosigmoid approach.Findings. One patient was lost from follow-up; another one had only a short postoperative observation. At follow-up performed on 12 cases, no patients reported any crisis of acute vertigo. Four patients were free from any vestibular symptoms, while 8 reported some slight gait disturbances. Hearing function was preserved in 10 patients and improved in 2. 1 year postoperative vestibular function was absent at the side operated on and unchanged on the other side in all the cases.Conclusions. Vestibular neurectomy via the retrosigmoid approach can be considered a safe and effective procedure in relieving medically refractory vertigo in Menière’s disease, while preserving hearing. [ABSTRACT FROM AUTHOR]

An experimental method to obtain multiple-walled nanotubes of BN using low energy is presented. The method is based on the use of mechanical alloying techniques with elemental boron powders and nitrogen gas mixed in an autoclave at room temperature. The chemical and structural characteristics of the multiple-walled nanotubes were obtained using different techniques, such as X-ray diffraction, transmission electron microscopy, EELS microanalysis, high-resolution electron microscopy images and theoretical simulations based on the multisliced approach of the electron diffraction theory. This investigation clearly illustrates the production of multiple-wall BN nanotubes at room temperature. These results open up a new kind of synthesis method with low expense and important perspectives for use in large-quantity production. [ABSTRACT FROM AUTHOR]

The effect of different types of thermal treatment, designed to increase the product’s shelf-life, on the volatile composition of “Campo Real” unfermented table olives, has been studied by headspace solid-phase microextraction (HS-SPME) and GC-MS analysis. Different SPME fibres were evaluated to determine their selectivity for a mixture of the main components of the different spices used in “Campo Real” olive dressing. Of the different fibres investigated, the polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibre was selected for analysis of the olive brines, which contained nine main aroma components. The types of thermal treatment were sterilisation (121 °C, 15 min) and four pasteurisation conditions (60 °C or 80 °C each for 5 or 9 min). Pasteurisation did not lead to significant changes in the amounts of these nine volatile compounds; the 2-butanol signal was reduced by treatment at 80 °C. On the other hand, sterilisation of the brine resulted in an decrease in the signals from these compounds and the appearance of a new, high signal for benzaldehyde; the origin of this has not yet been determined. Results suggest that the selected pasteurisation conditions do not significantly modify the typical, and valued, aroma characteristics of “Campo Real”. [ABSTRACT FROM AUTHOR]

Zinc phthalocyanine (ZnPc) is a promising candidate for solar-cell applications, because it is easily synthesized and is non-toxic to the environment. Recently, phthalo-cyanine (Pc) was considered by many researchers as the active part in all-organic solar cells, i.e. plastic solar cells. It is a self-assembling liquid crystal developed from a common deep-blue-green pigment. It exhibits a characteristic structural self-organization, which is reflected in an efficient energy migration in the form of extinction transport. In this paper we have report structural, surface morphological, optical and thermal properties of flash-evaporated zinc phthalocyanine thin films. The samples were prepared by using a vacuum coating unit on well-cleaned glass substrates under a pressure of 7 × 10[SUP-6] Torr. A constant rate of evaporation (1 Å/s) was maintained throughout the evaporation of the ZnPc thin films. A rotary drive was employed to obtain uniform thickness during the evaporation. Thicknesses of the films were monitored by a quartz-crystal thickness monitor and were cross verified by the multiple-beam interferometry technique. The X-ray-diffraction pattern reveals the crystalline nature of the films deposited at higher substrate temperatures. Scanning electron microscope and scanning probe microscope nanoscope studies were carried out to determine the surface uniformity and homogeneity of the films for interfacing and application purposes. All the films were found to possess small crystallites less than 100 nm in size. The optical transmittance measurements were carried out using a spectrophotometer in the visible region (400-800 nm) and the films were found to be absorbing in nature. The band gap of the ZnPc thin films is 1.97 eV and the optical transition was found to be direct and allowed. The absorption coefficient, extinction coefficient and refractive index of the ZnPc films were evaluated and the results are discussed. Differential scanning... [ABSTRACT FROM AUTHOR]

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10[SUP5] polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma. [ABSTRACT FROM AUTHOR]

Molecular Dynamics simulations and high resolution electron microscope observations were used to determine the mechanism of nanocluster coalescence in detail. In the simulations, the tight-binding second momentum approximation potential was used to describe the interatomic interactions. The calculations not only reproduced the experimentally observed translation and reorientation during the coalescing process, but also made it possible to determine the time scale of each step in the process and to observe details of the process that could not be obtained from the experiment. For high temperature coalescence, a new mechanism differing from classical theory is proposed. [ABSTRACT FROM AUTHOR]

The temporal evolution of chymotrypsin activity during early ontogeny of laboratory reared red drum larvae was accomplished using a combination of biochemical assays and electrophoretic methods (substrate SDS-PAGE). Optimal functional conditions for chymotrypsin were also determined. Chymotrypsin activity was first detected prior to the onset of exogenous feeding. Total chymotrypsin activity increased with age and standard length. Specific activity was greatest on day 10 post-hatch. Maximal chymotrypsin activity was observed at 50 °C, pH 7.8, and Ca2+ concentration of 25 mM. Using substrate gel electrophoresis and specific inhibitors the molecular weight of red drum chymotrypsin was estimated to be 26–27 kD. Our results indicate that the digestive system of red drum larvae is capable of alkaline proteolysis before first feeding and suggest that chymotrypsin may have potential as an indicator of nutritional condition. [ABSTRACT FROM AUTHOR]

In a previous study we have demonstrated the existence of pulvinar (puv) cells which were optimally activated when a monkey executed reaching movements with his limbs (Acuña et al 1983). We now describe further observations in four Macaca nemestrina monkeys trained to perform goal directed reaching movements aimed at four different positions in space. Extracellular unit activity in the lateralis posterior (lp) and puv nuclei, together with electrooculograms were recorded during the execution of the task. Seven hundred and sixty neurons were studied in the lp-puv complex. One hundred and twenty three cells (16%) showed changes in activity related to the reaching movements. Reaching related cells fell into two categories: goal direction sensitive (28/123 = 23%) and pandirectional (95/123 = 77%). Goal direction sensitive cells showed different responses depending on the direction of the goal relative to the starting point of the movement. The responses of the pandirectional cells were independent of goal direction. The activity of the remaining cells (637/760) could not be correlated with reaching movements. In a smaller number of area 5a (PE) cells (n = 109) studied in one monkey, 82 (75%) were classified as reaching related cells. Of these, 76% (62/82) were goal direction sensitive and 24% (20/82) pandirectional. The lp-puv cells were more dependent on the intentionality of movement than area 5a cells, and not reliably activated by passive manipulation of the limb. After injection of HRP-WGA in area 5a, where the reaching cells were recorded, labeled cells and terminals were located in the lp-puv zones where reaching cells were also found. The data shown here suggest that the lp-puv reaching related cells are both anatomically and functionally linked to cortical zones concerned with information regarding directional movement. Cortical areas might be involved in encoding the direction of movement, whereas the lp-puv might participate by redirecting attention during aimed movements. [ABSTRACT FROM AUTHOR]

The damping behavior of graphite particulate-reinforced 6061A1 alloy metal matrix composites (MMCs) processed by spray atomization and codeposition is studied. Four spray deposition experiments are made, yielding materials with graphite volume fractions of 0, 0.05, 0.07, and 0.10. A dynamic mechanical thermal analyzer is used to measure the damping capacity and elastic modulus at 0.1, 1, and 10 Hz over the temperature range of 30 °C to 250 °C. The damping capacity of the materials is shown to increase with increasing volume fraction of graphite. Hot extrusion of the spray-deposited MMCs is shown to further increase the damping capacity. The elastic moduli of the spray-deposited MMCs are reduced with the addition of graphite but are improved by hot extrusion. At low temperatures (below 150 °C), the high damping capacity of the MMCs is attributed primarily to thermal expansion mismatch-induced dislocations and the high intrinsic damping of graphite. At high temperatures (above approximately 200 °C), the damping capacity is attributed to Al/graphite interface viscosity, preferred orientation of the graphite, and the presence of dislocations. [ABSTRACT FROM AUTHOR]