Copulatory behaviour and genital mechanics suggest sperm allocation by a non-intromittent sclerite in a pholcid spider.

The male genitalia of pholcid spiders, which is one of the most species-rich spider families, are characterized by a procursus, which is a morphologically diverse projection of the copulatory organ. It has been shown that the procursus interacts with the female genitalia during copulation. Here, we investigate the function of the procursus in Gertschiola neuquena, a species belonging to the early branched and understudied subfamily Ninetinae, using behavioural and morphological data. Although many aspects of the copulatory behaviour of G. neuquena follow the general pattern described for the family, males use only one pedipalp during each copulation. Based on our micro-CT analysis of cryofixed mating pairs using virgin females, we can show that the long and filiform procursus is inserted deeply into the unpaired convoluted female spermatheca, and the intromittent sclerite, the embolus, is rather short and stout only reaching the most distal part of the female sperm storage organ. Histological data revealed that sperm are present in the most proximal part of the spermatheca, suggesting that the procursus is used to allocate sperm deeply into the female sperm storage organ. This represents the first case of a replacement of the sperm allocation function of the intromittent sclerite in spiders.

Maternal care interacts with prenatal stress in altering sexual dimorphism in male rats.

The present study analyzes the interaction between prenatal stress and mother's behavior on brain, hormonal, and behavioral development of male offspring in rats. It extends to males our previous findings, in females, that maternal care can alter behavioral dimorphism that becomes evident in the neonates when they mature. Experiment 1 compares the maternal behavior of foster mothers toward cross-fostered pups versus mothers rearing their own litters. Experiment 2 ascertains the induced "maternal" behavior of the male pups, derived from Experiment 1 when they reached maturity. The most striking effect was that the males non-exposed to the stress as fetuses and raised by stressed foster mothers showed the highest levels of "maternal" behavior of all the groups (i.e., induction of maternal behavior and retrieving behavior), not differing from the control, unstressed, female groups. Furthermore, those males showed significantly fewer olfactory bulb mitral cells than the control males that were non-stressed as fetuses and raised by their own non-stressed mothers. They also presented the lowest levels of plasma testosterone of all the male groups. The present findings provide evidence that prenatal environmental stress can "demasculinize" the behavior, brain anatomy and hormone secretion in the male fetuses expressed when they reach maturity. Moreover, the nature of the maternal care received by neonates can affect the behavior and physiology that they express at maturity.

First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG.

BACKGROUND: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. PATIENTS AND METHODS: We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients). RESULTS: Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC. CONCLUSION: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.

Persistent effects of early augmented acoustic environment on the auditory brainstem.

Acoustic experiences significantly shape the functional organization of the auditory cortex during postnatal "critical periods." Here, we investigate the effects of a non-traumatic augmented acoustic environment (AAE) on the central nucleus of the inferior colliculus (ICC) and lower brainstem nuclei in rat during the critical period. Our results show that an AAE during P9-P28 had a persistent effect on the evoked auditory brainstem responses leading to a decreased latency and an increased amplitude of the response at and above the frequency of the stimulus used for the AAE. These findings are correlated with increased numbers of sites in the ICC that responded to the AAE frequency and show higher thresholds. There also were persistent effects in neurons with a best frequency higher than the AAE stimulus. These neurons showed decreased activity at low sound levels in the low frequency tail of the frequency response area. This was at, below and above the AAE stimulus frequency. Less often, increased activity at higher sound levels also was seen. Together, these findings suggest multifaceted interactions between activity-dependent plasticity, homeostasis, and development in the brainstem during the initial stages of hearing. A neonate exposed to an altered auditory environment may experience long-lasting change over the entire network of the auditory system.

Effects of undernourishment on the hypothalamic orexinergic system.

The present study examined the effects of a severely restricted diet during the pre- and postnatal periods with later nutritional rehabilitation on orexin hypothalamic neurons in male and female Wistar rats. Immunocytochemistry was used to reveal orexin-immunoreactive (orexin-ir) cells in the ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), lateral hypothalamic area (LH) and the perifornical nucleus (PF). Dietary restriction decreased the number of orexin-ir cells in the LH, whereas DMH or PF orexin-ir populations were not affected in either male or female rats. Nutritional rehabilitation resulted in a differential recovery that depended on the period during which rehabilitation occurred and on the sex of the animal. In summary, our study suggests that the hypothalamic nuclei implicated in eating behavior present a differential vulnerability to adverse environmental conditions during development. Specifically, among the studied nuclei only the LH orexin-ir cells were sensitive to severe food deprivation during development in male and female rats. These results suggest that starvation interferes with developmental events that occur during CNS sexual differentiation.

Ultrasonic wave propagation in cementitious materials: a multiphase approach of a self-consistent multiple scattering model.

This paper examines ultrasonic wave propagation through strongly heterogeneous materials such as cementitious materials, and deals meanly with the formulation of a multiphase approach of a self-consistent multiple scattering model, the so-called dynamic generalized self-consistent model (DGSCM) proposed by Yang [J. Appl. Mech. 70(2003) 575-582]. This extended model can describe the influence of the size and volume fraction of aggregates on cementitious materials, as well as the interaction, contribution, and influence of entrapped air voids together with the aggregates on frequency-dependent parameters such as the phase velocity and the attenuation coefficient. To show the performance of this approach, theoretical predictions were compared with experimental ultrasonic measurements over a wide frequency range from several mortar specimens with different features in their microstructure properties and concentrations of aggregates up to 60%. The multiphase approaches of both the DGSCM and the Waterman-Truell model (WT) were also compared. The obtained results of the multiphase DGSCM were found to be significantly better than those obtained from the N-phase WT model for ultrasonic measurements from cementitious materials at high aggregate concentrations. The feasibility of material characterization using the multiphase approach of DGSCM was also discussed.

On the measurement of frequency-dependent ultrasonic attenuation in strongly heterogeneous materials.

This paper deals with the measurement of frequency-dependent ultrasonic attenuation in strongly heterogeneous materials, such as cementitious materials. To improve the measurement of this parameter on this kind of materials, a linear swept-frequency signal is used to drive an emitter transducer to conduct a through-transmission inspection in immersion. To filter out undesirable frequency content, time-frequency filtering and detection process are performed. The use of this method has been compared with two excitation techniques, the broadband and the narrowband pulses. The results obtained using the swept-frequency excitation together with the time-frequency filtering, allows the determination of the attenuation curves with high accuracy over a wide frequency range without the need for complicated equipment, and improves the effective bandwidth by using a unique pair of transducers.

[<> (REgistro de TRAuma grave de la provincia de TOledo): general view and mortality]. / <> (REgistro de TRAuma grave de la provincia de TOledo): visión general y mortalidad.

OBJECTIVE: To analyze the management and progression of the critical trauma patient. DESIGN: A retrospective, descriptive analysis. SETTING: The ICU in the province of Toledo. PATIENTS: All patients with traumatic injury admitted during the 2001-2007 period (7 years). MAIN VARIABLES OF INTEREST: These include the variables at the scene of the accident, pre-hospitalization, during transportation, variables on admission and during development until discharge or death. RESULTS: A total of 1090 trauma patients admitted were included. Of these, 79.5% were male, with an average age of 36.5 years (16% ≥ 65 years). There was a progressive decrease of patients from 2001 (142 patients) to 2007 (133 patients), with 46.9% admissions between May and September. A total of 29.4% did not belong to the health area. The causes were car accident (43.3%), fall from a height/fall (20.8%), motorcycle accident (13.8%), pedestrian being run over (6.6%). There were 2172 injuries; 30.1% had 3 injuries and 8.4% ≥ 4. The most frequently occurring injury was a head injury (33.7%), followed by thoracic trauma (20.2%) and orthopedic trauma (15.6%). 36.4% required surgery on the first day. Average length of stay in the ICU was 10.4+/-13.2 days. Time on mechanical ventilation was 7.3+/-12 days (median 1 day). Fifteen percent died in the ICU. This remains within the multivariable ICU mortality prediction model, including the pre-hospitalization variables: age (OR 1.05; 95% CI: 1.03-1.06), mydriasis (OR 2.6; 95% CI: 1.3-5.3), motor component of the Glascow Coma Score (GCS) (OR 0.7; 95% CI: 0.6-0.8), pre-hospitalization shock (OR 3.2; 95% CI: 1.8-5.5) and Injury Severity Score (ISS) (OR 1.1; 95% CI: 1.05-1.1). CONCLUSIONS: The use of multicenter trauma registers gives an overall view of trauma management and helps improve the care.

Maternal care counteracts behavioral effects of prenatal environmental stress in female rats.

There is extensive evidence in rats that prenatal environmental stress (PES) exposure and early postnatal altered maternal care, as a consequence of stress during gestation, can detrimentally affect the brain and behavioral development of the offspring. In order to separate the effect of PES on the fetuses from that on the behavior of the mother, in the present study, we used a cross-fostering procedure in which PES-fetuses were raised by non-stressed mothers and non PES-fetuses were raised by stressed mothers. In Experiment 1, non-stressed mothers showed significantly more maternal behavior than stressed mothers. In Experiment 2, when the female offspring from Experiment 1 reached maturity, they were tested for: (1) induced maternal behavior (MB), (2) plasma levels of corticosterone (Cpd B), progesterone (P), and estradiol (E(2)), (3) number of accessory olfactory bulb (AOB) mitral cells, and (4) c-fos expression measured in AOB and medial preoptic area (MPOA) neurons. We replicated our previous findings that the PES group reared by their own stressed mothers, when adult, attacked the young, expressed disorganized MB and showed altered Cpd B, P and E(2) levels, plus a male-like neuro-morphological pattern in the AOB, by comparison with the non-PES group, reared by their own non-stressed mothers. By contrast, when adult, the PES group reared by non-stressed mothers showed hormonal and morphological neuronal alterations, but they displayed appropriate (full) MB. The non-PES group raised by stressed mothers also showed altered hormone levels, but showed full MB and no morphological neuronal changes. Significant differences in the AOB and MPOA c-fos activity, related to whether or not MB was expressed, were found in the non-PES groups, but not in the PES group reared by non-stressed mothers. To our knowledge, this is the first study to document that adequate maternal care, early in development, can shape the subsequent expression of induced MB, overcoming neuro-morphological and hormonal alterations that are produced by prenatal environmental stress. We conclude that maternal care during early postnatal development can counteract detrimental effects of prenatal environmental stress, exerting long-lasting effects that modulate the behavioral phenotype of the offspring.

[Functional and activity-dependent plasticity mechanisms in the adult and developing auditory brain]. / Mecanismos de plasticidad (funcional y dependiente de actividad) en el cerebro auditivo adulto y en desarrollo.

INTRODUCTION AND DEVELOPMENT: Sensory systems show a topographic representation of the sensory epithelium in the central nervous system. In the auditory system this representation originates tonotopic maps. For the last four decades these changes in tonotopic maps have been widely studied either after peripheral mechanical lesions or by exposing animals to an augmented acoustic environment. These sensory manipulations induce plastic reorganizations in the tonotopic map of the auditory cortex. By contrast, acoustic trauma does not seem to induce functional plasticity at subcortical nuclei. Mechanisms that generate these changes differ in their molecular basis and temporal course and we can distinguish two different mechanisms: those involving an active reorganization process, and those that show a simple reflection of the loss of peripheral afferences. Only the former involve a genuine process of plastic reorganization. Neuronal plasticity is critical for the normal development and function of the adult auditory system, as well as for the rehabilitation needed after the implantation of auditory prostheses. However, development of plasticity can also generate abnormal sensation-like tinnitus. Recently, a new concept in neurobiology so-called 'neuronal stability' has emerged and its implications and conceptual basis could help to improve the treatments of hearing loss. CONCLUSION: A combination of neuronal plasticity and stability is suggested as a powerful and promising future strategy in the design of new treatments of hearing loss.

Sand/cement ratio evaluation on mortar using neural networks and ultrasonic transmission inspection.

The quality and degradation state of building materials can be determined by nondestructive testing (NDT). These materials are composed of a cementitious matrix and particles or fragments of aggregates. Sand/cement ratio (s/c) provides the final material quality; however, the sand content can mask the matrix properties in a nondestructive measurement. Therefore, s/c ratio estimation is needed in nondestructive characterization of cementitious materials. In this study, a methodology to classify the sand content in mortar is presented. The methodology is based on ultrasonic transmission inspection, data reduction, and features extraction by principal components analysis (PCA), and neural network classification. This evaluation is carried out with several mortar samples, which were made while taking into account different cement types and s/c ratios. The estimated s/c ratio is determined by ultrasonic spectral attenuation with three different broadband transducers (0.5, 1, and 2 MHz). Statistical PCA to reduce the dimension of the captured traces has been applied. Feed-forward neural networks (NNs) are trained using principal components (PCs) and their outputs are used to display the estimated s/c ratios in false color images, showing the s/c ratio distribution of the mortar samples.

Non-plastic reorganization of frequency coding in the inferior colliculus of the rat following noise-induced hearing loss.

It is well established that restricted mechanical lesions of the cochlea result in reorganization of the tonotopic map in the auditory thalamus and cortex, but it is unclear whether acoustic trauma produces similar effects at earlier stages of the auditory pathways. To test whether the tonotopic map is reorganized after acoustic trauma at the midbrain level, i.e. the inferior colliculus (IC), we exposed rats to an acoustic trauma and let them survive for at least 5 weeks to ensure that we produced a permanent threshold shift. Experiments were carried out in urethane-anesthetized animals 35-296 days after the traumatic exposure. The acoustic lesions were assessed by measuring the compound action potential. We mapped the frequency organization of the IC using multiunit recordings. In addition, we recorded frequency response areas (FRAs) when a single unit was isolated (N=142). The results show that acoustic trauma produces a persistent reorganization of the tonotopic map and that the normal stepwise representation of sound frequency in the IC is profoundly disrupted. Although the reorganization in the IC is similar to that previously described in the cortex and thalamus in that the affected area appears to be invaded by the adjacent normal frequencies, changes in thresholds and FRAs in these regions are different from those in the forebrain. We conclude that most of the changes can be explained by the residual-response hypothesis [Irvine DR, Rajan R, Smith S (2003) Effects of restricted cochlear lesions in adult cats on the frequency organization of the inferior colliculus. J Comp Neurol 467:354-374]. Plastic reorganization of frequency response areas and tonotopic organization does not seem to occur at the midbrain level following acoustic trauma in adult animals in a manner similar to that previously shown in the auditory cortex. Maintaining the stability of the neuronal circuitry for frequency coding in the IC may be important for the treatment of noise-induced hearing loss.

Time-varying prediction filter for structural noise reduction in ultrasonic NDE.

Predominant physical phenomenon in highly scattering materials is the attenuation due to dispersion. Therefore, received echo has high frequencies more severely attenuated than low frequencies and the structural noise can be modeled as a non-stationary random process. Most of the proposed techniques for enhancing the flaw visibility do not exploit the frequency dependency of the incoming flaw signal, assuming homogeneous behaviour of the insonified material. In this work, a new technique based on exploiting the non-stationary nature of the incoming UT signal is presented. Proposed technique is based on the prediction error obtained with a linear and time-varying parametric model of the noise. By this method, when the analyzed UT echo has only structural noise, the prediction error is low, however, if it contains a flaw, high prediction error occurs because a flaw is a non-predictable alteration of the material structure. Experiments with stainless steel show that this method has an excellent performance on SNR enhancement.

A multicenter phase II study of the cryptophycin analog LY355703 in patients with platinum-resistant ovarian cancer.

LY355703 is a synthetic product structurally related to the cryptophycin family isolated from the blue-green algae, which exerts a potent destabilization of microtubules during mitosis. This study was performed to determine the activity of LY355703 in patients with platinum-resistant advanced ovarian cancer and to characterize its toxicity profile. Twenty-six patients were enrolled in this study. Resistant disease was defined as a platinum-free interval of <6 months from primary treatment or rechallenge. LY355703 (1.5 mg/m(2)) was administered intravenously on days 1 and 8, every 3 weeks, infused over 2 h. From 24 patients evaluable for response, three partial responses (12.5%) and seven disease stabilizations were registered (29.2%), for an overall clinical benefit of 41.7%. Fourteen patients (58.3%) experienced a progression of the disease during treatment. Among the 25 patients evaluable for toxicity, two episodes of grade 3 anemia (8%); one, grade 3 thrombocytopenia (4%); one, grade 4 elevation of creatinine (4%); and one, grade 3 hyperbilirubinemia (4%) were reported. LY355703 has a modest activity in patients with platinum-resistant advanced ovarian cancer. Nevertheless, the considerable rate of disease stabilization in the absence of serious adverse events in this poor-prognosis study population suggests that this novel cryptophycin may deserve further investigation in this setting.

[Anaemia predicts mortality in heart failure]. / La anemia es un factor pronóstico de mortalidad en la insuficiencia cardiaca.

BACKGROUND: Anaemia frequently coexists with heart failure. Few studies have examined the impact of anaemia on mortality in this population. OBJECTIVE: To assess the prevalence of anaemia in patients with heart failure in an Internal Medicine Unit and its potential effects on mortality. MATERIAL AND METHODS: We evaluated the electronic medical records of 272 patients with heart failure that fulfilled the criteria admitted to the Internal Medicine Unit of Fundación Hospital Alcorcón (Madrid, Spain)between July and December 2003. Uni and multivariate logistic regression analysis for predictors of mortality. RESULTS: Most patients were women (71%), mean age was 82.1+/-9 years, 106 (39.9%) had anaemia (serum haemoglobin levels<12 g/dL), 69 (25%) had renal failure (serum creatinine levels>1.5 mg/dL and 154 patients (57%) had atrial fibrillation. There were 41 deaths (15%). The frequency of anaemia was higher and the haemoglobin levels were lower in the patients who died (65% vs 36%, and 11.2+/-2.4 g/dL vs 12.6+/-2.1g/dL, p<0.001 for both). Increased serum creatinine was also associated with mortality (1.8+/-0.8 vs 1.3+/-0.8 mg/dL p<0.001). Age, gender, atrial fibrillation or the aetiology of heart failure were not associated with mortality in univariate analysis. In contrast, by multivariate logistic regression analysis, haemoglobin (odds ratio [OR] 0, 78 per g/dL, 95%confidence interval [CI] 0.66- 0.923 p<0.01), New York Heart Association functional classification (OR 2.2, 95% Cl 1.2-3.9 p<0.01), and serum creatinine (OR 1.5 per mg/dL, 95% CI 0.98-2.31 p=0.06) were independent predictors of mortality. CONCLUSIONS: Anaemia is a frequent problem among patients with heart failure and it is a significant independent risk factor for death.

Progress in the clinical development of new marine-derived anticancer compounds.

Naturally derived anticancer agents continue to be instrumental in the systemic therapeutic intervention against solid tumors and hematological malignancies. Such compounds now have a relevant role in contemporary models of combination with targeted agents, thus providing a rationale to consider nature as a valid tool to discover new innovative anticancer agents. The marine ecosystem has increasingly been the focus of interest for new discoveries in the field that are expected to be of significant therapeutic impact in cancer patients. A critical review of the integrated data generated in our marine-derived anticancer program seems to confirm such expentancies. ET-743 (Yondelis) represents the first new agent developed against advanced pretreated soft tissue sarcoma in the past 25 years, and also harbors activity in women bearing pretreated ovarian cancer and a solid potential in combination therapy. The lack of cumulative toxicities makes this compound suitable for long-lasting therapies, reversible transaminitis being the most prevalent toxicity. Aplidin has shown a positive therapeutic index in phase I trials and phase II studies are ongoing. In contrast to the lack of bone marrow toxicity, a set of translational results anticipates a potential in leukemia. Kahalalide F has also successfully completed the phase I program in solid tumors with evidence of activity in resistant tumors and phase II studies are under way. Finally, the mechanistic data generated in parallel with the clinical program confirms the potential of the marine ecosystem in the discovery of new agents acting against new cellular targets of relevance in cancer cell biology.

Speckle reduction by energy time-frequency filtering.

Structural noise is a very important limitation to the visibility of flaw echoes in ultrasonic testing and evaluation of highly scattering materials. In order to enhance the signal-to-noise ratio, different algorithms have been developed. One of these techniques is based on filtering the spectrum low band of the received echo to obtain a significant improvement of the defect visibility. Based on this idea, in this work a new time-frequency technique is presented. In this method, block-processing autoregressive techniques are used to estimate the instantaneous center frequency of the traveling wave. From this information, a time-frequency filter is designed tuned at half the estimated instantaneous center frequency. Experimental results and the comparison with the non-time-frequency filtering technique are also included, showing that the proposed method has an excellent performance on SNR enhancement.

Application of vernier thinning techniques to segmented annular arrays.

Due to the aperture periodicity, the inter-element spacing of two-dimensional squared arrays is maintained near lambda/2 in order to avoid grating lobes. This condition gives rise to severe problems derived from the huge number of array elements and from their little size that causes the signal to noise ratio to bring down. Vernier techniques have been proposed to lower the number of active elements, but the drastic reduction of the ultrasonic energy is still a great problem for the image contrast. In this work, vernier techniques for segmented annular (SA) arrays are theoretically studied. SA arrays produce lower grating lobes than squared arrays and, therefore, allow the element size to be increased beyond the lambda/2 constraint. Using larger elements, SA arrays have advantage to squared arrays because they have larger active area and smaller thinning order for the same complexity (number of channels) of the image system. Theoretical results of the vernier techniques applied to SA arrays in both radial and tangential directions are presented and compared with the equivalent squared array.