Characterization of time-dependence for dissipative solitons stabilized by nonlinear gradient terms: Periodic and quasiperiodic vs chaotic behavior.

We investigate the properties of time-dependent dissipative solitons for a cubic complex Ginzburg-Landau equation stabilized by nonlinear gradient terms. The separation of initially nearby trajectories in the asymptotic limit is predominantly used to distinguish qualitatively between time-periodic behavior and chaotic localized states. These results are further corroborated by Fourier transforms and time series. Quasiperiodic behavior is obtained as well, but typically over a fairly narrow range of parameter values. For illustration, two examples of nonlinear gradient terms are examined: the Raman term and combinations of the Raman term with dispersion of the nonlinear gain. For small quintic perturbations, it turns out that the chaotic localized states are showing a transition to periodic states, stationary states, or collapse already for a small magnitude of the quintic perturbations. This result indicates that the basin of attraction for chaotic localized states is rather shallow.

Quartic solitons of a mode-locked laser distributed model.

Dissipative quartic solitons have gained interest in the field of mode-locked lasers for their energy-width scaling which allows the generation of ultrashort pulses with high energies. Pursuing the characterization of such pulses, here we found soliton solutions of a distributed model for mode-locked lasers in the presence of either positive or negative fourth-order dispersion (4OD). We studied the impact the laser parameters may have on the profiles, range of existence, and energy-width relation of the output pulses. The most energetic and narrowest solutions occur for negative 4OD, with the energy having an inverse cubic dependence with the width in most cases. Our simulations showed that the spectral filtering has the biggest contribution in the generation of short (widths as low as 39 fs) and very energetic (391 nJ) optical pulses.

Dissipative solitons stabilized by nonlinear gradient terms: Time-dependent behavior and generic properties.

We study the time-dependent behavior of dissipative solitons (DSs) stabilized by nonlinear gradient terms. Two cases are investigated: first, the case of the presence of a Raman term, and second, the simultaneous presence of two nonlinear gradient terms, the Raman term and the dispersion of nonlinear gain. As possible types of time-dependence, we find a number of different possibilities including periodic behavior, quasi-periodic behavior, and also chaos. These different types of time-dependence are found to form quite frequently from a window structure of alternating behavior, for example, of periodic and quasi-periodic behaviors. To analyze the time dependence, we exploit extensively time series and Fourier transforms. We discuss in detail quantitatively the question whether all the DSs found for the cubic complex Ginzburg-Landau equation with nonlinear gradient terms are generic, meaning whether they are stable against structural perturbations, for example, to the additions of a small quintic perturbation as it arises naturally in an envelope equation framework. Finally, we examine to what extent it is possible to have different types of DSs for fixed parameter values in the equation by just varying the initial conditions, for example, by using narrow and high vs broad and low amplitudes. These results indicate an overlapping multi-basin structure in parameter space.

Dissipative solitons for generalizations of the cubic complex Ginzburg-Landau equation.

We found stable soliton solutions for two generalizations of the cubic complex Ginzburg-Landau equation, namely, one that includes the term that, in optics, represents a delayed response of the nonlinear gain and the other including the self-steepening term, also in the optical context. These solutions do not require the presence of the delayed response of the nonlinear refractive index, such that, they exist regardless of the term previously considered essential for stabilization. The existence of these solitons was predicted by a perturbation approach, and then confirmed by solving the ordinary differential equations, resulting from a similarity reduction, and also by applying a linear stability analysis. We found that these solitons exist for a large region of the parameter space and possess very asymmetric amplitude profiles as well as a complicated chirp characteristic.

The cancer registry as an ally in monitoring treatment effectiveness.

OBJECTIVE: To evaluate if the cancer registry database can be used to monitor treatment effectiveness using nivolumab treatment of non-small cell lung cancer (NSCLC) as an example. METHOD: An observational inception cohort was used, where all registered cases of NSCLC with authorisation to initiate treatment with nivolumab were monitored retrospectively to evaluate disease characteristics and response to prior treatments. Current exposure to nivolumab was prospectively characterised and treatment outcomes classified based on the clinical information registered in the patient medical record. The main outcome measure used to assess treatment effectiveness was overall survival (OS). Secondary outcomes considered were progression free survival (PFS) as a measure of effectiveness and occurrence of Adverse Drug Reaction (ADRs) as a measure of safety. Data were analysed using SPSS, version 24. RESULTS: A total of 115 patients received treatment with nivolumab for NSCLC, between November 1st 2015 and July 31st 2016, and were registered in the database. The majority were non-squamous type (n=107). The median OS was 11.4 months {CI95%: 11.1-11.7}, with a 1-year survival of 44%, in line with clinical trial data. Median PFS was 5.4 months {CI95%: 2.8-7.9}. Treatment was discontinued in 82 cases, most frequently due to disease progression. There were 38 cases of ADRs documented in the patient medical chart, 21 of which led to treatment discontinuation. CONCLUSION: The analysed data suggest that the cancer registry is a powerful tool to monitor treatment effectiveness, although considerable investment is needed to improve the medical culture of recording treatment exposure, particularly documentation of ADRs.

High COX-2 expression is associated with increased angiogenesis, proliferation and tumoural inflammatory infiltrate in canine malignant mammary tumours: a multivariate survival study.

COX-2 expression affects mammary tumourigenesis by promoting angiogenesis and cell proliferation, encouraging metastatic spread and tumour-associated inflammation. Samples of canine mammary tumours (n = 109) were submitted to immunohistochemistry to detect COX-2, CD31, VEGF, Ki-67, CD3 and MAC387 expression. Concurrent high expression of COX-2/CD31, COX-2/VEGF, COX-2/Ki-67, COX-2/CD3 and COX-2/MAC was associated with elevated grade of malignancy, presence of intravascular emboli and presence of lymph node metastasis. Tumours with high COX-2 (P < 0.001) and tumours with concurrent expression of high COX-2 and high CD31 (P = 0.008); high VEGF (P < 0.001); high Ki-67 (P < 0.001); high CD3+ T-lymphocytes (P = 0.002) and elevated MAC387 macrophages (P = 0.024) were associated with shorter overall survival (OS) time. Interestingly the groups with high COX-2/CD31 and high COX-2/VEGF retained their significance after multivariate analysis arising as independent predictors of OS. Present data highlight the importance of COX-2 in canine mammary tumourigenesis.

Plain and oscillatory solitons of the cubic complex Ginzburg-Landau equation with nonlinear gradient terms.

In this work, we present parameter regions for the existence of stable plain solitons of the cubic complex Ginzburg-Landau equation (CGLE) with higher-order terms associated with a fourth-order expansion. Using a perturbation approach around the nonlinear Schrödinger equation soliton and a full numerical analysis that solves an ordinary differential equation for the soliton profiles and using the Evans method in the search for unstable eigenvalues, we have found that the minimum equation allowing these stable solitons is the cubic CGLE plus a term known in optics as Raman-delayed response, which is responsible for the redshift of the spectrum. The other favorable term for the occurrence of stable solitons is a term that represents the increase of nonlinear gain with higher frequencies. At the stability boundary, a bifurcation occurs giving rise to stable oscillatory solitons for higher values of the nonlinear gain. These oscillations can have very high amplitudes, with the pulse energy changing more than two orders of magnitude in a period, and they can even exhibit more complex dynamics such as period-doubling.

Ki-67 and PCNA Expression in Canine Mammary Tumors and Adjacent Nonneoplastic Mammary Glands: Prognostic Impact by a Multivariate Survival Analysis.

The assessment of tumor proliferation has been considered a determining prognostic factor in canine mammary tumors (CMTs). However, no studies have assessed the prognostic importance of proliferation in adjacent nonneoplastic mammary glands. We included 64 CMTs (21 benign and 43 malignant) and studied the proliferation index (PI) of Ki-67 and proliferating cell nuclear antigen (PCNA) together with several clinicopathological characteristics. A positive and statistically significant correlation between the PI of Ki-67 and PCNA in tumors and adjacent nonneoplastic mammary glands was observed in benign and malignant tumors. Tumor size, skin ulceration, histological type, mitotic index, nuclear grade, differentiation grade, histological grade of malignancy, lymph node metastasis, Ki-67, and PCNA expression in tumors and adjacent nonneoplastic mammary glands were statistically associated with overall survival by univariate analysis in malignant cases (n = 43). Histological grade of malignancy and high intratumoral PCNA retained their significance by multivariate analysis arising as independent predictors of overall survival. Interestingly, the PI of Ki-67 and PCNA of adjacent nontumoral mammary glands were associated with clinicopathological features of tumor aggressiveness and shorter overall survival, demonstrating the need to better explore this adjacent non-neoplastic tissue.

Existence and stability of solutions of the cubic complex Ginzburg-Landau equation with delayed Raman scattering.

We found two stationary solutions of the cubic complex Ginzburg-Landau equation (CGLE) with an additional term modeling the delayed Raman scattering. Both solutions propagate with nonzero velocity. The solution that has lower peak amplitude is the continuation of the chirped soliton of the cubic CGLE and is unstable in all the parameter space of existence. The other solution is stable for values of nonlinear gain below a certain threshold. The solutions were found using a shooting method to integrate the ordinary differential equation that results from the evolution equation through a change of variables, and their stability was studied using the Evans function method. Additional integration of the evolution equation revealed the basis of attraction of the stable solutions. Furthermore, we have investigated the existence and stability of the high amplitude branch of solutions in the presence of other higher order terms originating from complex Raman, self-steepening, and imaginary group velocity.

Tumour-associated macrophages are associated with vascular endothelial growth factor expression in canine mammary tumours.

Tumour-associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin-fixed paraffin-embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease.

Concurrent expression of cyclo-oxygenase-2 and epidermal growth factor receptor in canine malignant mammary tumours.

Canine mammary tumours (CMTs) are reported to express cyclo-oxygenase (COX)-2 and epidermal growth factor receptor (EGFR); however, no studies have evaluated concurrent expression of these proteins. In this study, 43 malignant CMTs were evaluated immunohistochemically for concurrent expression of COX-2 and EGFR and expression was correlated with malignancy. High COX-2 expression was associated with tumour size (P = 0.033), mitotic index (P = 0.040), nuclear grade (P = 0.021), histological grade of malignancy (P = 0.020) and lymph node metastasis (P = 0.029). High EGFR immunoreactivity was associated with tumour size (P = 0.001), necrosis (P = 0.001), mitotic index (P = 0.022), histological grade of malignancy (P = 0.041) and lymph node metastasis (P = 0.005). Simultaneous high-expression of COX-2 and EGFR was associated with high-nuclear grade (P = 0.049), high-histological grade of malignancy (P = 0.031) and the presence of lymph node metastasis (P = 0.025). A positive correlation between COX-2 and EGFR expression (r = 0.474; P = 0.001) was also observed. These results suggest that combined use of selective inhibitors of COX-2 and EGFR may be a useful approach to the treatment of malignant CMTs.

Propagation of Airy-related beams.

New types of finite energy Airy beams are proposed. We consider two different types of beams, namely, beams that are obtained as blocked and exponentially attenuated versions of Airy functions Ai and Bi, and beams of finite width but having the Airy functions typical phase. All of them show very interesting properties, such as parabolic trajectories for longer propagation distances, profile evolution exhibiting less diffraction, or better definiteness of the main peak, when compared with other finite energy Airy beams studied before.

Soliton self-frequency shift: Self-similar solutions and their stability.

Ultrashort pulse propagation in fibers is affected by intrapulse Raman scattering (IRS) which causes both a linear frequency downshift and a quadratic displacement of the peak pulse, as functions of the propagation distance. This effect has been known and treated by perturbation methods applied to the nonlinear Schrödinger equation since the period of intense research on soliton propagation. Here, we find solutions of the model equation using an accelerating self-similarity variable and study their stability. These solutions have Airy function asymptotics which give them infinite energy. For small IRS, the algebraically decaying tail is negligible and these solutions are a very good approximation of the profiles observed in the full equation simulations. For strong IRS (but beyond the regime in which the evolution equation is valid for silica fibers), the self-similar pulses have noticeable left tails exhibiting Airy oscillations. Whenever their truncated forms are used as initial conditions of the full equation, they experience amplitude decay and show left tails that are consistent with radiation escaping from the central pulse. These observations are interpreted as being the effects of a continuum constitution of the infinite left tail.

Self-bending of dark and gray photorefractive solitons.

We investigate the effects of diffusion on the evolution of steady-state dark and gray spatial solitons in biased photorefractive media. Numerical integration of the nonlinear propagation equation shows that the soliton beams experience a modification of their initial trajectory, as well as a variation of their minimum intensity. This process is further studied using perturbation analysis, which predicts that the center of the optical beam moves along a parabolic trajectory and, moreover, that its minimum intensity varies linearly with the propagation distance, either increasing or decreasing depending on the sign of the initial transverse velocity. Relevant examples are provided.

Observation of locked optical kink-antikink spatial shock waves.

We report the first experimental observation of optical spatial shock-wave pairs. The shock waves consist of two coupled kink and antikink beams that remain locked to each other throughout propagation in a nonlinear diffusion-driven photorefractive crystal. These coupled shock-wave pairs move undistorted at angles that fall outside their original angular sector of propagation.

Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy.

PURPOSE: Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first-line drug in the treatment of epilepsy. We evaluated the efficacy of CLB as add-on therapy in patients with refractory partial epilepsy. METHODS: This was an open, retrospective study, conducted at the epilepsy clinic of our university hospital. All patients had chronic epilepsy and were being evaluated for epilepsy surgery. CLB was introduced as add-on therapy (starting with 10 mg/ day) in patients with previous failure of at least two AEDs. Information was obtained from clinical notes and follow-up visits. RESULTS: We evaluated 97 patients, 37 men and 60 women. Ages ranged from 15 to 70 years (mean, 35.8 years). Etiology of epilepsy was hippocampal atrophy in 67 (69%), cortical dysgenesis in nine (9.3%), and other etiologies in nine (9.3%). In 12 (12.3%) patients, the etiology of epilepsy was not identified despite clinical and neurologic investigation. Patients used CLB for a period ranging from 1 month to 7 years and 9 months (mean, 16.7 months) with doses ranging from 10 to 60 mg/day (mean, 29.7 mg/day). Seven (7.2%) patients were seizure free, 48 (49.4%) had > or =50% of improvement in seizure control, 39 (40.2%) had <50% of improvement in seizure control, and in three (3.1%), no data were available. CONCLUSIONS: We conclude that CLB may have efficacy equivalent to that of the new AEDs when used as add-on therapy in patients with refractory epilepsy. CLB should be considered an economic alternative in the treatment of patients with refractory epilepsy.

[Familial partial epilepsies]. / Epilepsias parciais familiares.

OBJECTIVE: To investigate the clinical and genetic characteristics of familial partial epilepsies. METHOD: Family history of seizures was questioned in all patients followed in our epilepsy clinics, from October 1997 to December 1998. Those with positive family history were further investigated and detailed pedigrees were obtained. All possibly affected individuals available underwent clinical evaluation. Seizures and epilepsy syndromes were classified according to the ILAE recommendations. Whenever possible, EEG and MRI were performed. RESULTS: Positive family history was identified in 32 unrelated patients. A total of 213 possibly affected individuals were identified, 161 of whom have been evaluated. The number of affected subjects per family ranged from two to 23. Temporal lobe epilepsy (TLE) was identified in 22 families (68%), frontal lobe epilepsy in one family (3%), partial epilepsy with centrotemporal spikes in five families (15%), and other benign partial epilepsies of childhood in four families (12%). Most of the affected individuals in the TLE families (69%) had clinical and/or EEG characteristics of typical TLE. However, the severity of epilepsy was variable, with 76% of patients with spontaneous seizure remission or good control with medication and 24% with refractory seizures, including 7 patients that underwent surgical treatment. In the other 10 families, we identified 39 possibly affected subjects, 23 of whom were evaluated. All had good seizure control (with or without medication) except for one patient with frontal lobe epilepsy. Pedigree analysis suggested autosomal dominant inheritance with incomplete penetrance in all families. CONCLUSION: Family history of seizures is frequent among patients with partial epilepsies. The majority of our families had TLE and its expression was not different from that observed in sporadic cases. The identification of genes involved in partial epilepsies may be usefull in classification of syndromes, to stablish prognosis and optimal treatment.

Sexual behaviour and infection rates for HIV, blood-borne and sexually transmitted infections among patients attending drug treatment centres in Rio de Janeiro, Brazil.

A survey was carried out in 2 drug use treatment centres (TCs) in Rio de Janeiro, Brazil, to assess risk behaviours, HIV infection and other sexually transmitted infections/blood-borne infections (STIs/BBIs). Two hundred and twenty-five drug users (195 males and 30 females) were interviewed and clinically examined, and their blood and urine were tested for STIs/BBIs. Prevalences (%) for these infections were as follows--HIV: 0.9, hepatitis B virus (HBV): 14.7, hepatitis C virus (HCV): 5.8, syphilis: 5.3, gonorrhoea/chlamydia (CT/NG): 4.7. In bivariate analyses CT/NG infection was associated with younger age (P=0.003); current genitourinary symptoms (odds ratio [OR]=6.2) and a mainly illegal source of income (OR=9.1). Hepatitis C infection was associated with a history of ever having injected any drug (OR=19.6), and with each one of the injected drugs. After multiple logistic regression, lower educational level (adjusted odds ratio [AOR]=3.70) and 'ever having injected drugs' (AOR=3.69) remained as independent risk factors for hepatitis B infection. In conclusion, TCs must implement programmes directed towards the prevention of STIs/BBIs.

HIV-1 diversity in Brazil: genetic, biologic, and immunologic characterization of HIV-1 strains in three potential HIV vaccine evaluation sites. Brazilian Network for HIV Isolation and Characterization.

The Brazilian Network for HIV Isolation and Characterization was established for the surveillance of HIV variability in Brazil. Here, we report characterization of HIV strains and virus-specific immune responses from 35 clinical samples collected from three potential HIV vaccine sites. Three genetic subtypes of HIV-1 were identified by heteroduplex mobility assay (HMA) B (in 82.9% of the samples), F (14.3%), and C (2.9%). Phylogenetic analysis based on the C2V3/env DNA sequence from all 25 specimens examined was 100% concordant with HMA results. Four variants of subtype B with different tetrapeptides at the tip of the V3 loop were found: the GPGR motif (North American), GWGR motif (Brazilian B"), and two minor variants, GFGR and GPGS, as previously detected. No significant association was found between HIV-1 subtypes and the mode of transmission or biologic properties of HIV-1 isolates (derived from 88.6% of the specimens). Only 5 of 16 isolates studied were neutralized by the autologous sera. Consistent with previous results, no relation between viral subtype and peptide enzyme-linked immunosorbent assay (ELISA) seroreactivity or neutralization was evident. This study also demonstrated the effectiveness of the collaborative approach followed by Brazilian scientists when addressing a complex subject such as HIV variability.

Surrogate markers of disease progression in HIV-infected children in Rio de Janeiro, Brazil.

In order to test the predictive value of immune complex-dissociated p24 antigenaemia (ICD-p24Ag), beta 2 microglobulin (beta 2-M), and neopterin as markers of disease progression, 53 HIV-1 infected children (mean age 68 months) and nine HIV-negative controls (mean age 65 months) were studied prospectively for 9 months. Five were classified in category E (CDC-1994) and seroreverted during the study, 14 in category A, nine in category B, and 25 in category C (CDC-1994). Blood samples were taken at medium intervals of 61 days and tested for ICD-p24Ag, beta 2 microglobulin, and neopterin. The results were correlated with clinical outcome and CD4-lymphocyte counts. All three groups (A, B, C) of symptomatic children had similar positivity in an ICD-p24Ag test (48.1, 58.8, and 51.0 per cent, respectively), and all in group E had negative p24 antigenaemia. beta 2 microglobulin and neopterin tests showed no correlation with clinical stages of HIV-1 infection. There was no significant correlation between these three tests with age-matched CD4 lymphocyte counts (p > 0.05). In contrast, the CD4 lymphocyte count correlated well with disease stages. These data suggest that the markers evaluated in the present study do not correlate well with clinical findings or with CD4 lymphocyte counts. Of all the markers tested, CD4 count was the best to predict prognosis of HIV disease in this cohort.