Advances in research on the impacts of anti-submarine sonar on beaked whales.

Mass stranding events (MSEs) of beaked whales (BWs) were extremely rare prior to the 1960s but increased markedly after the development of naval mid-frequency active sonar (MFAS). The temporal and spatial associations between atypical BW MSEs and naval exercises were first observed in the Canary Islands, Spain, in the mid-1980s. Further research on BWs stranded in association with naval exercises demonstrated pathological findings consistent with decompression sickness (DCS). A 2004 ban on MFASs around the Canary Islands successfully prevented additional BW MSEs in the region, but atypical MSEs have continued in other places of the world, especially in the Mediterranean Sea, with examined individuals showing DCS. A workshop held in Fuerteventura, Canary Islands, in September 2017 reviewed current knowledge on BW atypical MSEs associated with MFAS. Our review suggests that the effects of MFAS on BWs vary among individuals or populations, and predisposing factors may contribute to individual outcomes. Spatial management specific to BW habitat, such as the MFAS ban in the Canary Islands, has proven to be an effective mitigation tool and mitigation measures should be established in other areas taking into consideration known population-level information.

Requirement for urgent tracheal intubation after traumatic injury: a retrospective analysis of 11,010 patients in the Trauma Audit Research Network database.

Advanced airway management is a treatment priority in trauma care. It is likely that a proportion of patients who receive urgent airway management on arrival in the emergency department represent an unmet demand for airway intervention in the pre-hospital phase. This study aimed to investigate emergency airway practice in major trauma patients and establish any unmet demand in this patient group. A retrospective review of the Trauma Audit and Research Network database was performed to identify airway intervention(s) performed for patients admitted to major trauma centres in England from 01 April 2012 to 27 June 2016. In total, 11,010 patients had airway interventions: 4375 patients (43%) had their tracheas intubated in the pre-hospital setting compared with 5889 patients (57%) in the emergency department. Of the patients whose tracheas were intubated in the emergency department, this was done within 30 min of hospital arrival in 3264 patients (75%). Excluding tracheal intubation, 1593 patients had a pre-hospital airway intervention of which 881 (55%) subsequently had their trachea intubated in the emergency department; tracheal intubation was done within 30 min of arrival in the majority of these cases (805 patients (91%)). Over 70% of emergency department tracheal intubations in patients with traumatic injuries were performed within 30 min of hospital arrival; this suggests there may be an unmet demand in pre-hospital advanced airway management for trauma patients in England.

Cardiotrophin 1 protects beta cells from apoptosis and prevents streptozotocin-induced diabetes in a mouse model.

AIMS/HYPOTHESIS: Cardiotrophin 1 (CT-1) is a recently described cytokine originally isolated from the heart where it has been shown to play an important role in apoptotic protection of cardiomyocytes and heart hypertrophy. Its beneficial properties have also been described in other organs such as liver and neuromuscular tissue. In the present study, we investigated whether CT-1 can confer protection against pro-apoptotic stimuli in pancreatic beta cells, and its role in insulin secretion and diabetes development. METHODS: The effects of CT-1 on apoptosis and function were studied using MIN6B1 cells and freshly isolated murine pancreatic islets. The impact on the development of diabetes was evaluated in Ct1-null (Ct1 (-/-)) mice (the gene Ct1 is also known as Ctf1) using two streptozotocin (STZ)-induced models of diabetes. RESULTS: CT-1 has a protective effect in MIN6B1 cells and murine islets under the pro-apoptotic stimulus of serum deprivation, which correlates with the expression of B cell lymphoma-extra large, or following exposure to a mixture of cytokines. In addition, CT-1 enhances glucose-stimulated insulin secretion in MIN6B1 cells and this was repressed by inhibitors of phospholipase C. Furthermore, Ct1 (-/-) mice were more prone to develop diabetes, and their glucose tolerance test showed impaired plasma glucose clearance which correlated with decreased pancreatic insulin secretion. CONCLUSIONS/INTERPRETATION: The results obtained from both in vitro and in vivo experiments show that CT-1 improves beta cell function and survival, and protects mice against STZ-induced diabetes.

Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2.

Cyclosporin A (CsA) is an immunosuppressive drug that inhibits the activity of transcription factors of the nuclear factor of activated T cells (NFAT) family, interfering with the induction of cytokines and other inducible genes required for the immune response. Here we show that CsA inhibits migration of primary endothelial cells and angiogenesis induced by vascular endothelial growth factor (VEGF); this effect appears to be mediated through the inhibition of cyclooxygenase (Cox)-2, the transcription of which is activated by VEGF in primary endothelial cells. Consistent with this, we show that the induction of Cox-2 gene expression by VEGF requires NFAT activation. Most important, the CsA-mediated inhibition of angiogenesis both in vitro and in vivo was comparable to the Cox-2 inhibitor NS-398, and reversed by prostaglandin E(2). Furthermore, the in vivo corneal angiogenesis induced by VEGF, but not by basic fibroblast growth factor, was selectively inhibited in mice treated with CsA systemically. These findings involve NFAT in the regulation of Cox-2 in endothelial cells, point to a role for this transcription factor in angiogenesis, and may provide a novel mechanism underlying the beneficial effects of CsA in angiogenesis-related diseases such as rheumatoid arthritis and psoriasis.

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells.

Cyclooxygenase-2 (Cox-2), the gastrin-release peptide (GRP) and its cognate receptor (GRP-R) are overexpressed in a significant percentage of colorectal carcinomas and are associated with cell growth, invasiveness and tumor progression. However, a molecular link between all of them in adenocarcinomas has not been established. Here, we show that bombesin (BBS), a GRP homolog, stimulates the expression of Cox-2 mRNA and protein in human colon adenocarcinoma Caco-2 cells, resulting in enhanced release of prostaglandin E(2). These effects were markedly inhibited by the specific BBS antagonist RC-3940-II. BBS promotes the activation of the nuclear factor of activated T cells (NFAT) through a Ca(2+)/calcineurin (Cn)-linked pathway. Upon BBS stimulation, the NFATc1 isoform translocates into the nucleus with a concomitant increase in NFATc1 binding to two specific recognition sites in the promoter region of the Cox-2 gene. Furthermore, inhibition of Cn activity by the immunosuppressive drug cyclosporin A impaired NFAT activation and diminished Cox-2 expression in BBS-stimulated cells. Interestingly, BBS pretreatment strongly enhances the invasive capacity of carcinoma cells, effect which was inhibited by a Cox-2-specific inhibitor. These findings provide the first evidence for the involvement of the Ca(2+)/Cn/NFAT pathway in BBS-mediated induction of genes involved in colon carcinoma invasiveness such as Cox-2.

Calibration of a portable HPGe detector using MCNP code for the determination of 137Cs in soils.

In situ gamma spectrometry provides a fast method to determine (137)Cs inventories in soils. To improve the accuracy of the estimates, one can use not only the information on the photopeak count rates but also on the peak to forward-scatter ratios. Before applying this procedure to field measurements, a calibration including several experimental simulations must be carried out in the laboratory. In this paper it is shown that Monte Carlo methods are a valuable tool to minimize the number of experimental measurements needed for the calibration.

Effect of marine ambient in the production of pollutants from the pyrolysis and combustion of a mixture of plastic materials.

A mixture of polyethylene (PE), polyethylene-terephtalate (PET), polypropylene (PP) and Nylon was submerged in marine water during 12 moths. The chlorine content of these plastics was measured through the passing time. Thermobalance was used to look for differences in the thermal decomposition of the plastics during in that time interval. Degradation of PET, PP and Nylon produced changes in the weight loss curve, but behaviour of PE is confusing. Pyrolysis and combustion at 850 °C was finally performed to get knowledge of the possible differences in the emission of main gases, volatiles and semivolatiles including polycyclic aromatic hydrocarbons (PAHs), polychlorinated benzenes (ClBzs), polychlorinated phenols (ClPhs), polybrominated phenols (BrPhs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Results show that the emission of chlorinated species is somewhat not affected by the chlorine content of the plastics mix. The production of PCBs and PCDD/Fs was very low, under 4 pg WHO-TEQ/g.

Improved outcomes for hepatic trauma in England and Wales over a decade of trauma and hepatobiliary surgery centralisation.

BACKGROUND: Over the last decade trauma services have undergone a reconfiguration in England and Wales. The objective is to describe the epidemiology, management and outcomes for liver trauma over this period and examine factors predicting survival. METHODS: Patients sustaining hepatic trauma were identified using the Trauma Audit and Research Network database. Demographics, management and outcomes were assessed between January 2005 and December 2014 and analysed over five, 2-year study periods. Independent predictor variables for the outcome of liver trauma were analysed using multiple logistic regression. RESULTS: 4368 Patients sustained hepatic trauma (with known outcome) between January 2005 and December 2014. Median age was 34 years (interquartile range 23-49). 81% were due to blunt and 19% to penetrating trauma. Road traffic collisions were the main mechanism of injury (58.2%). 241 patients (5.5%) underwent liver-specific surgery. The overall 30-day mortality rate was 16.4%. Improvements were seen in early consultant input, frequency and timing of computed tomography (CT) scanning, use of tranexamic acid and 30-day mortality over the five time periods. Being treated in a unit with an on-site HPB service increased the odds of survival (odds ratio 3.5, 95% confidence intervals 2.7-4.5). CONCLUSIONS: Our study has shown that being treated in a unit with an on-site HPB service increased the odds of survival. Further evaluation of the benefits of trauma and HPB surgery centralisation is warranted.

Maxillofacial injuries in patients with major trauma.

Major trauma is an important cause of mortality and morbidity worldwide. Mortality is high with rates over 10% commonly reported. We studied the epidemiology and aetiology of maxillofacial injuries in patients who presented with major trauma as recorded nationally by retrospectively analysing the database of the Trauma Audit Research Network from 2001 to 2015. All patients who had major trauma with associated maxillofacial injuries were included in the analysis. Of 104645 patients recorded as having had major trauma during the study period, 22148 (21.2%) had an associated maxillofacial injury. Most of them were male (74.2%), and the type of injury was usually blunt (97.5%). Road traffic collisions were the most common mechanism (44.1%), followed by falls of less than 2m (21.6%). An associated serious head injury was more common in those who had a facial injury (81% compared with 60.6%, p<0.0001). Nearly all the facial injuries (94%) were minor, or moderately severe. Maxillofacial injuries commonly present with major trauma but are rarely severe. A maxillofacial injury may indicate an increased likelihood of an associated head injury.

Neonatal hypothyroidism affects the timely expression of myelin-associated glycoprotein in the rat brain.

Congenital hypothyroidism strongly affects myelination. To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the steady state levels of myelin-associated glycoprotein (MAG) and its mRNA in rat brain during the first postnatal month. As studied by immunoblot analysis of several brain regions, MAG increased from days 10-15 onwards, reaching constant levels by days 20-25. Hypothyroid samples showed a delay in the accumulation of MAG that was more severe in rostral regions, such as cortex and hippocampus. The effect of hypothyroidism on the accumulation of the protein correlated with mRNA levels. MAG mRNA started to accumulate in the cerebrum of normal animals by postnatal day 7, reaching maximal levels by day 20. Hypothyroid rats showed a delay of several days in the onset of mRNA expression, increasing thereafter at the same rate as in normal animals, and eventually reaching similar values. When individual brain regions were analyzed, we found strong regional differences in the effect of hypothyroidism. The cerebral cortex was most affected, with messenger levels lower than in normal animals at all ages. In more caudal regions differences between control and hypothyroid rats were evident only at the earlier stages of myelination, with spontaneous recovery at later ages. By run on analysis, we found no differences in transcriptional activities of the MAG gene in normal, hypothyroid, or T4-treated rats. Therefore, the effects of hypothyroidism on MAG mRNA and protein levels were most likely caused by decreased mRNA stability. We propose that thyroid hormone contributes to enhanced myelin gene expression by affecting the stability of newly transcribed mRNA in the early phases of myelination.

Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA.

The mammalian brain is considered to be poorly responsive to thyroid hormone after the so called "critical periods" of brain development, which occur in the rat before postnatal days 15-20. In a previous work (Muñoz, A., A. Rodriguez-Peña, A. Perez-Castillo, B. Ferreiro, J.G. Sutcliffe, and J. Bernal. 1991. Mol. Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose expression is influenced by early neonatal hypothyroidism and thyroid hormone treatment. In the present work we show that adult-onset hypothyroidism leads to a reversible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and killed three months later showed a decreased RC3 mRNA concentration in the cerebral cortex and striatum. The same effect was observed in animals made hypothyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression was normal when hypothyroid animals were treated with T4 five days before being killed. In contrast, the mRNA encoding myelin proteolipid protein showed no changes in either experimental situation. RC3 mRNA levels were not affected by food restriction demonstrating that the effect of hypothyroidism was not related to the lack of weight gain. The control of RC3 mRNA is so far the only molecular event known to be regulated by thyroid hormone once the critical periods of brain development are over and could represent a molecular correlate for the age-independent, reversible alterations induced by hypothyroidism in the adult brain.

Artificial neural networks technology for neutron spectrometry and dosimetry.

Artificial Neural Network Technology has been applied to unfold neutron spectra and to calculate 13 dosimetric quantities using seven count rates from a Bonner Sphere Spectrometer with a (6)LiI(Eu). Two different networks, one for spectrometry and another for dosimetry, were designed. To train and test both networks, 177 neutron spectra from the IAEA compilation were utilised. Spectra were re-binned into 31 energy groups, and the dosimetric quantities were calculated using the MCNP code and the fluence-to-dose conversion coefficients from ICRP 74. Neutron spectra and UTA4 response matrix were used to calculate the expected count rates in the Bonner spectrometer. Spectra and H(10) of (239)PuBe and (241)AmBe were experimentally obtained and compared with those determined with the artificial neural networks.

Pollutant content in marine debris and characterization by thermal decomposition.

Marine debris (MDs) produces a wide variety of negative environmental, economic, safety, health and cultural impacts. Most marine litter has a very low decomposition rate (plastics), leading to a gradual accumulation in the coastal and marine environment. Characterization of the MDs has been done in terms of their pollutant content: PAHs, ClBzs, ClPhs, BrPhs, PCDD/Fs and PCBs. The results show that MDs is not a very contaminated waste. Also, thermal decomposition of MDs materials has been studied in a thermobalance at different atmospheres and heating rates. Below 400-500K, the atmosphere does not affect the thermal degradation of the mentioned waste. However, at temperatures between 500 and 800K the presence of oxygen accelerates the decomposition. Also, a kinetic model is proposed for the combustion of the MDs, and the decomposition is compared with that of their main constituents, i.e., polyethylene (PE), polystyrene (PS), polypropylene (PP), nylon and polyethylene-terephthalate (PET).

Human vascular smooth muscle cells but not endothelial cells express prostaglandin E synthase.

In a previous work, we postulated that endothelial cells possess only the following 2 enzymes involved in prostanoid synthesis: cyclooxygenase and prostacyclin synthase. The present work focused on investigating the expression of prostaglandin (PG) E synthase (PGES) in vascular cells. After incubation of vascular smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) with [(14)C]arachidonic acid, the profile of prostanoid synthesis was assessed by HPLC. Untransformed PGH(2) released by the cells was evaluated as the difference in the formation of PGF(2alpha) in the incubations performed in the presence and in the absence of SnCl(2). Resting SMCs and SMCs stimulated with phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha formed PGE(2) and PGI(2) (evaluated as 6-oxo-PGF(1alpha)), and in the presence of SnCl(2) only a small amount of PGE(2) was deviated toward PGF(2alpha). In contrast, resting and stimulated HUVECs produced PGI(2), PGE(2), PGF(2alpha), and PGD(2), and SnCl(2) completely diverted PGE(2) and PGD(2) toward PGF(2alpha). Reverse transcriptase-polymerase chain reaction analysis shows that mRNA encoding for PGES was not present in HUVECs and in endothelial cells from saphenous vein. Nevertheless, PGES was expressed in SMCs and induced by IL-1beta and TNF-alpha, and by PMA and LPS, although to a lesser extent. Whereas SMC stimulation led to an increase in the synthesis of PGE(2) and PGI(2) but not of untransformed PGH(2), stimulation of endothelial cells resulted in an enhanced release of the vasoconstricting prostanoid PGH(2).

Radon measurements with a PIN photodiode.

Silicon photodiodes are well suited to detect alphas coming from different sources as neutron reactions or radon daughters. In this work a radon in air detecting device, using an 18x18 mm silicon PIN photodiode is studied. The ionized airborne decay products formed during radon diffusion were focused by an accelerating high voltage to the PIN surface. Several conducting rings were disposed inside a cylindrical PVC vessel in such a way that they reproduced the electric field created by a punctual charge located behind PIN position. Alpha spectra coming from the neutral and ionized species deposited on the PIN surface, dominated by 218Po and 214Po progeny peaks, were recorded for varying conditions. Those include radon concentration from a Pylon source, high voltage (thousands of volts) and PIN inverse bias voltage. Different parameters such as temperature and humidity were also registered during data acquisition. The increase in the particle collection efficiency with respect to zero electric field was compared with the corresponding to a parallel plates configuration. A discussion is made in terms of the most appropriate voltages for different radon concentrations.

Mechanisms involved in the hemodynamic alterations in congestive heart failure as a basis for a rational pharmacological treatment.

Congestive heart failure is a complex syndrome and one of the major cardiological problems of our time. It is characterized by an important neurohumoral activation to compensate for the reduction of cardiac output and blood pressure, that worsens the prognosis with time. The aim of the treatment is focused on how to improve the quality of life and how to prolong survival. Usually, treatment, either symptomatic or directed to control the neuroendocrine compensatory changes, is necessary. The drugs currently used are angiotensin-converting enzyme inhibitors, diuretics, digoxin, and beta-adrenoceptor agonists. In addition, new drugs, such as angiotensin II receptor antagonists, beta-adrenoceptor antagonists, ibopamine, Ca(2+) antagonists, neutral endopeptidase inhibitors, vasopressin antagonists, Ca(2+)-sensitizers with cyclic AMP-dependent or -independent mechanisms, and endothelin antagonists, are also being used.

Monte Carlo simulation estimates of neutron doses to critical organs of a patient undergoing 18 MV x-ray LINAC-based radiotherapy.

Absorbed photoneutron dose to patients undergoing 18 MV x-ray therapy was studied using Monte Carlo simulations based on the MCNPX code. Two separate transport simulations were conducted, one for the photoneutron contribution and another for neutron capture gamma rays. The phantom model used was of a female patient receiving a four-field pelvic box treatment. Photoneutron doses were determinate to be higher for organs and tissues located inside the treatment field, especially those closest to the patient's skin. The maximum organ equivalent dose per x-ray treatment dose achieved within each treatment port was 719 microSv/Gy to the rectum (180 degrees field), 190 microSv/Gy to the intestine wall (0 degrees field), 51 microSv/Gy to the colon wall (90 degrees field), and 45 microSv/Gy to the skin (270 degrees field). The maximum neutron equivalent dose per x-ray treatment dose received by organs outside the treatment field was 65 microSv/Gy to the skin in the antero-posterior field. A mean value of 5 +/- 2 microSv/Gy was obtained for organs distant from the treatment field. Distant organ neutron equivalent doses are all of the same order of magnitude and constitute a good estimate of deep organ neutron equivalent doses. Using the risk assessment method of the ICRP-60 report, the greatest likelihood of fatal secondary cancer for a 70 Gy dose is estimated to be 0.02% for the pelvic postero-anterior field, the rectum being the organ representing the maximum contribution of 0.011%.

Study of the neutron field in the vicinity of an unshielded PET cyclotron.

The neutron field in the proximity of an unshielded PET cyclotron was investigated during 18F radioisotope production with an 18 MeV proton beam. Thermoluminescent detector (TLD) models TLD600 and TLD700 as well as Bonner moderating spheres were irradiated at different positions inside the vault room where the cyclotron is located to determine the thermal neutron flux, neutron spectrum and dose equivalent. Furthermore, from a combination of measurements and Monte Carlo simulations the neutron source intensity at the target was estimated. The resulting intensity is in good agreement with the IAEA recommendations. Neutron doses derived from the measured spectra were found to vary between 7 and 320 mSv per 1 microA h of proton-integrated current. Finally, gamma doses were determined from TLD700 readings and amounted to around 10% of the neutron doses.