Gas phase Elemental abundances in Molecular cloudS (GEMS) II. On the quest for the sulphur reservoir in molecular clouds: the H2S case.

CONTEXT: Sulphur is one of the most abundant elements in the Universe. Surprisingly, sulphuretted molecules are not as abundant as expected in the interstellar medium and the identity of the main sulphur reservoir is still an open question. AIMS: Our goal is to investigate the H2S chemistry in dark clouds, as this stable molecule is a potential sulphur reservoir. METHODS: Using millimeter observations of CS, SO, H2S, and their isotopologues, we determine the physical conditions and H2S abundances along the cores TMC 1-C, TMC 1-CP, and Barnard 1b. The gas-grain model Nautilus is used to model the sulphur chemistry and explore the impact of photo-desorption and chemical desorption on the H2S abundance. RESULTS: Our modeling shows that chemical desorption is the main source of gas-phase H2S in dark cores. The measured H2S abundance can only be fitted if we assume that the chemical desorption rate decreases by more than a factor of 10 when n H > 2 × 104. This change in the desorption rate is consistent with the formation of thick H2O and CO ice mantles on grain surfaces. The observed SO and H2S abundances are in good agreement with our predictions adopting an undepleted value of the sulphur abundance. However, the CS abundance is overestimated by a factor of 5 - 10. Along the three cores, atomic S is predicted to be the main sulphur reservoir. CONCLUSIONS: The gaseous H2S abundance is well reproduced, assuming undepleted sulphur abundance and chemical desorption as the main source of H2S. The behavior of the observed H2S abundance suggests a changing desorption efficiency, which would probe the snowline in these cold cores. Our model, however, highly overestimates the observed gas-phase CS abundance. Given the uncertainty in the sulphur chemistry, we can only conclude that our data are consistent with a cosmic elemental S abundance with an uncertainty of a factor of 10.

Gas phase Elemental abundances in Molecular cloudS (GEMS): I. The prototypical dark cloud TMC 1.

GEMS is an IRAM 30m Large Program whose aim is determining the elemental depletions and the ionization fraction in a set of prototypical star-forming regions. This paper presents the first results from the prototypical dark cloud TMC 1. Extensive millimeter observations have been carried out with the IRAM 30m telescope (3 mm and 2 mm) and the 40m Yebes telescope (1.3 cm and 7 mm) to determine the fractional abundances of CO, HCO+, HCN, CS, SO, HCS+, and N2H+ in three cuts which intersect the dense filament at the well-known positions TMC 1-CP, TMC 1-NH3, and TMC 1-C, covering a visual extinction range from A V ~ 3 to ~20 mag. Two phases with differentiated chemistry can be distinguished: i) the translucent envelope with molecular hydrogen densities of 1-5×103 cm-3; and ii) the dense phase, located at A V > 10 mag, with molecular hydrogen densities >104 cm-3. Observations and modeling show that the gas phase abundances of C and O progressively decrease along the C+/C/CO transition zone (A V ~ 3 mag) where C/H ~ 8×10-5 and C/O~0.8-1, until the beginning of the dense phase at A V ~ 10 mag. This is consistent with the grain temperatures being below the CO evaporation temperature in this region. In the case of sulfur, a strong depletion should occur before the translucent phase where we estimate a S/H ~ (0.4 - 2.2) ×10-6, an abundance ~7-40 times lower than the solar value. A second strong depletion must be present during the formation of the thick icy mantles to achieve the values of S/H measured in the dense cold cores (S/H ~8×10-8). Based on our chemical modeling, we constrain the value of ζ H2 to ~ (0.5 - 1.8) ×10-16 s-1 in the translucent cloud.

Evaluation of the methodological quality of studies of the performance of diagnostic tests for bovine tuberculosis using QUADAS.

There has been little assessment of the methodological quality of studies measuring the performance (sensitivity and/or specificity) of diagnostic tests for animal diseases. In a systematic review, 190 studies of tests for bovine tuberculosis (bTB) in cattle (published 1934-2009) were assessed by at least one of 18 reviewers using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist adapted for animal disease tests. VETQUADAS (VQ) included items measuring clarity in reporting (n = 3), internal validity (n = 9) and external validity (n = 2). A similar pattern for compliance was observed in studies of different diagnostic test types. Compliance significantly improved with year of publication for all items measuring clarity in reporting and external validity but only improved in four of the nine items measuring internal validity (p < 0.05). 107 references, of which 83 had performance data eligible for inclusion in a meta-analysis were reviewed by two reviewers. In these references, agreement between reviewers' responses was 71% for compliance, 32% for unsure and 29% for non-compliance. Mean compliance with reporting items was 2, 5.2 for internal validity and 1.5 for external validity. The index test result was described in sufficient detail in 80.1% of studies and was interpreted without knowledge of the reference standard test result in only 33.1%. Loss to follow-up was adequately explained in only 31.1% of studies. The prevalence of deficiencies observed may be due to inadequate reporting but may also reflect lack of attention to methodological issues that could bias the results of diagnostic test performance estimates. QUADAS was a useful tool for assessing and comparing the quality of studies measuring the performance of diagnostic tests but might be improved further by including explicit assessment of population sampling strategy.

Specificity of the comparative skin test for bovine tuberculosis in Great Britain.

A novel method for estimating specificity of the Single Intradermal Comparative Cervical Tuberculin (SICCT) test for bovine tuberculosis (bTB) using surveillance tests results is reported. The specificity of the SICCT test at three cut-offs was estimated from the dates, locations and skinfold measurements of all routine tests carried out in Officially TB Free (OTF) cattle herds in Great Britain (GB) between 2002 and 2008, according to their separation (by distance and time) from known infected (OTF-withdrawn) herds. The proportion of animals that tested positive was constant (P>0.20) when the distance between tested herds and nearest infected herd exceeded 8 km. For standard cut-off, calculated specificity was 99.98 per cent (95 per cent confidence interval ±0.004 per cent), equating to one false positive result per 5000 uninfected animals tested. For severe cut-off it was 99.91 per cent (±0.013 per cent) and for ultrasevere cut-off (selecting all reactors and inconclusive reactors) it was 99.87 per cent (±0.017 per cent). The estimated positive predictive value of the test averaged 91 per cent and varied by regional prevalence. This study provides further evidence of the high specificity of the SICCT test under GB conditions, suggests that over 90 per cent of cattle currently culled using this test in GB were infected, and endorses slaughter of at least these cattle for bTB control.

Reconstrucción de defectos amplios en tronco mediante colgajo de perforante en piedra clave / Reconstruction of large defects in trunk using the keystone perforator flap

El colgajo en piedra clave (Keystone Perforator Island Flap KPIF), es un colgajo local fasciocutáneo en isla que no requiere identificación de perforantes, descrito por Behan en 2003, que permite el cierre en un único acto quirúrgico tanto del defecto como de la zona dadora sin precisar, generalmente, autoinjerto cutáneo. Nuestro objetivo es el mostrar la utilidad de este colgajo para la cobertura de defectos amplios en tronco. De los más de 120 casos realizados en nuestro Servicio con esta técnica sin tener en cuenta la localización del problema entre abril de 2011 y abril de 2013, presentamos 5 casos que, tras resección quirúrgica por diferentes etiologías, fueron los que presentaron defectos de cobertura de mayor tamaño en tronco (entre 10 y 25 cm de diámetro máximo) que fueron solventados satisfactoriamente mediante el KPIF. En todos obtuvimos un cierre directo tanto de la zona del defecto como de la zona dadora, sin complicaciones durante el acto quirúrgico ni en el postoperatorio, con resultados estéticos óptimos, sin deformidades significativas ni alteraciones funcionales. Creemos que el KPIF es un colgajo óptimo para la cobertura de defectos amplios en el tronco ya que permite cubrir el defecto y hacer un cierre primario de la zona dadora generando poca morbilidad, con un buen resultado estético, con un corto tiempo quirúrgico y con un bajo coste (AU)

The Keystone Perforator Island Flap (KPIF) is a local fasciocutaneous islanded flap, first published in 2003 by Behan, that does not require identification of the underlying perforator vessels. It permits the closure in a single surgical procedure of both, the defect and the donor site, usually with no need of skin grafting. Our goal is to demonstrate the usefulness of the KPIF for the coverage of large defects of the trunk. Over 120 cases have been reconstructed at our Service using the KPIF from April 2011 to May 2013. We present a series of 5 patients who underwent reconstruction of large defects of the trunk (maximum diameter ranging from 10 to 25 cm) All the surgeries were performed successfully and both, the excision defect and the donor site, were directly closed. All the patients experienced an uneventful intra and postoperative period, and all were satisfied with the eventual aesthetic appearance, without significant deformities or functional impairments. We conclude that KPIF is an optimal flap for the coverage of large defects in the trunk. It allows performing a soft tissue defect reconstruction, while the donor site is closed by direct apposition, with minimal morbidity, good cosmesis, short operative time and at a relatively low economic cost (AU)

Bovine tuberculosis trends in the UK and the Republic of Ireland, 1995-2010.

Selected demographic features and trends in bovine tuberculosis (BTB) from 1995 to 2010 are described for the countries of the UK and the Republic of Ireland, using standardised definitions and measures. All countries experienced a reduction in the number of cattle and herds and in the proportion of dairy herds, while average herd size increased. In general, the trends indicate a stable situation of very low BTB prevalence in Scotland and, over most of the period, a rising prevalence in England and Wales. The prevalence in the Republic of Ireland declined while Northern Ireland experienced both a rise and fall. Differences in demography, BTB programme structure and test results were noted, particularly between the island of Ireland and Great Britain. Further investigation of these differences may provide valuable insights into risk factors for BTB and optimisation of existing BTB programmes.

Event-based criteria in GT-STAF information indices: theory, exploratory diversity analysis and QSPR applications.

Versatile event-based approaches for the definition of novel information theory-based indices (IFIs) are presented. An event in this context is the criterion followed in the "discovery" of molecular substructures, which in turn serve as basis for the construction of the generalized incidence and relations frequency matrices, Q and F, respectively. From the resultant F, Shannon's, mutual, conditional and joint entropy-based IFIs are computed. In previous reports, an event named connected subgraphs was presented. The present study is an extension of this notion, in which we introduce other events, namely: terminal paths, vertex path incidence, quantum subgraphs, walks of length k, Sach's subgraphs, MACCs, E-state and substructure fingerprints and, finally, Ghose and Crippen atom-types for hydrophobicity and refractivity. Moreover, we define magnitude-based IFIs, introducing the use of the magnitude criterion in the definition of mutual, conditional and joint entropy-based IFIs. We also discuss the use of information-theoretic parameters as a measure of the dissimilarity of codified structural information of molecules. Finally, a comparison of the statistics for QSPR models obtained with the proposed IFIs and DRAGON's molecular descriptors for two physicochemical properties log P and log K of 34 derivatives of 2-furylethylenes demonstrates similar to better predictive ability than the latter.

Controlling tuberculosis in a llama (Lama glama) herd using clinical signs, tuberculin skin testing and serology.

An outbreak of tuberculosis (TB), caused by Mycobacterium bovis, was investigated in a small herd of llamas (Lama glama). Based on three ante-mortem diagnostic methods (clinical signs, tuberculin skin test reactions, and 'Rapid Test' serology), 12 llamas were selected for examination post-mortem. Grossly visible lesions suspicious of TB were observed in eight animals, four of which had exhibited clinical signs, one was a skin test 'reactor', and three had been seropositive. M. bovis was isolated from seven of these eight animals. Clinical signs combined with serology were found to be useful in identifying infected animals, but tuberculin skin testing had limited negative predictive value as four llamas that were subsequently confirmed as infected were not detected using this assay.

On the contribution of molecular topology to drug design and discovery.

The role of molecular topology (MT) in the design and selection of new drugs is discussed. After an overview of the different in silico molecular design current technologies, the QSAR analysis is dealt in detail with particular emphasis in the use of topological indices as molecular descriptors. The results of the application of MT in drug design and discovery are described and finally a possible explanation is given about some of the key reasons explaining it's the extraordinary performance.

Assessment of antemortem tests used in the control of an outbreak of tuberculosis in llamas (Lama glama).

An outbreak of tuberculosis (TB) caused by Mycobacterium bovis in a llama herd is described. Over a 25-month period, a total of 70 llamas were selected for postmortem examination using four distinct criteria: clinical suspicion of disease (15 animals), positive tuberculin skin test result (three animals), antibody positive using a novel serological test (Rapid Test, 54 animals) and elective cull (five animals). Some animals qualified on more than one criterion. Gross lesions of TB were detected in 15 animals, with lung and lymph node lesions consistently observed. Samples were collected from 14 of 15 animals with visible lesions as well as those with no visible lesions, for histopathology and mycobacterial culture. All 14 llamas with visible lesions had caseonecrotic granulomatous lesions associated with acid-fast bacteria and variable mineralisation, and M bovis was isolated from 13. There were no histopathological lesions of TB in llamas with no grossly visible lesions, and M bovis was not isolated from any of these. The predictive value of suspicious gross lesions at postmortem examination was therefore high in the herd. Molecular typing results indicated that the outbreak was caused by a single strain likely to have originated from a local reservoir, probably cattle or wildlife. Antemortem indicators of infection assisted control of the outbreak, but no single test accurately identified all TB cases. Visible lesions were detected in nine of 15 llamas with clinical suspicion of disease, in two of three that had positive tuberculin skin test results and in 10 of 54 that were antibody positive; there was none (zero out of five) in llamas that were electively culled.

Application of molecular topology to the prediction of mosquito repellents of a group of terpenoid compounds.

A topological-mathematical model based on multilinear regression analysis has been built to search new terpenoid actives as mosquito repellents. The structural depiction was performed using topological indices, and a four-variable model for the prediction of corrected repellent ratio (r (2) = 0.9672, Q (2) = 0.9435) was selected. The model was checked by cross-validation, internal validation, and randomization test. The results confirm its capability to predict the property analyzed. After carrying out a virtual screening upon such a model, new structures with potential repellent activity against mosquitoes are proposed.

Outbreak of tuberculosis caused by Mycobacterium bovis in golden Guernsey goats in Great Britain.

An outbreak of caprine tuberculosis caused by Mycobacterium bovis was disclosed in June 2008, affecting goats of the golden Guernsey breed kept on 10 separate smallholdings in south-west Wales and the west of England. Following the initial diagnosis at postmortem examination, 30 goats that reacted positively to the single intradermal comparative cervical tuberculin (SICCT) test, together with five in-contact animals, were euthanased and subjected to postmortem examination and mycobacterial culture. Spoligotyping and variable number tandem repeat analysis of isolates showed that they were all of the same genotype, endemic to south-west Wales. Retrospective movement tracings identified a goat herd in south-west Wales, by then completely dispersed, as the probable common source of infection. There was a perfect correlation between the SICCT test and culture results in all slaughtered goats. Grossly visible tubercular lesions were observed at postmortem examination in all but one reactor.

Tratamiento de la enfermedad de Cushing con ketoconazol / Treatment of Cushing's disease with ketoconazole

La enfermedad de Cushing (EC), debida fundamentalmente a un microadenoma hipofisario, es un cuadro clínico poco frecuente en la edad pediátrica y se asocia a una significativa morbilidad. La principal indicación terapéutica es la cirugía transesfenoidal, aunque se reserva el ketoconazol como alternativa terapéutica temporal durante el período de espera previo, a fin de controlar el hipercortisolismo. A continuación se presenta el caso de una niña de 13 años y 8 meses con EC. Sus manifestaciones clínicas eran obesidad, disminución de la velocidad del crecimiento, fenotipo cushingoide, cefaleas e hipertensión arterial. Las determinaciones hormonales pusieron de manifiesto valores elevados de cortisol libre urinario y de corticotropina (ACTH). El ritmo de cortisol y de ACTH así como el test corto y largo de dexametasona confirmaron un hipercortisolismo dependiente de ACTH. La resonancia magnética craneal con gadolinio mostró la presencia de microadenoma en hemiadenohipófisis derecha. El diagnóstico se confirmó tras realizar un cateterismo selectivo de senos petrosos inferiores con estímulo de corticoliberina. En espera de cirugía transesfenoidal, el tratamiento con ketoconazol (200mg/24h) durante 6 meses controló el cuadro de hipercortisolismo. Tras la adenomectomía transesfenoidal, recibió tratamiento sustitutivo con hidrocortisona durante un mes. En la actualidad, la niña lleva 2 años y medio en remisión clínica y hormonal sin cumplir los criterios iniciales posquirúrgicos de curación (AU)

Cushing’s disease (CD), which is caused fundamentally by a pituitary microadenoma, is a rare endocrine disease in the paediatric age and which is associated with significant morbidity. The current treatment of choice for CD is trans-sphenoidal selective adenomectomy resulting in long-term remission rates. Pharmacological management of CD is directed at decreasing adrenal steroid secretion. Ketoconazole inhibits adrenal enzyme activity and decreases cortisol secretion. Our patient is a girl of 13 years and eight months of age with CD. The clinical manifestations were obesity, decrease in growth rate, Cushingoid phenotype, headache and arterial hypertension. The hormone determinations showed elevated values of UFC and ACTH. The circadian rhythm cortisol and ACTH and the short and long dexamethasone tests of provide definitive diagnosis of CD. The cranial MRI with gadolinium suggests the presence of microadenoma in the right pituitary lobe. The diagnosis is confirmed after performing a selective catheterisation of the inferior petrosal sinuses with CRH stimulus. While waiting for trans-sphenoidal surgery, the treatment with ketoconazole (200mg/24h) controlled the hypercortisolism. After the surgical procedure, the patient received replacement therapy with hydrocortisone for 1 month. At the present time, the patient, without fulfilling the post surgery cure criteria, has been 2 and a half years in clinical and hormonal remission (AU)

[Treatment of Cushing's disease with ketoconazole]. / Tratamiento de la enfermedad de Cushing con ketoconazol.

Cushing's disease (CD), which is caused fundamentally by a pituitary microadenoma, is a rare endocrine disease in the paediatric age and which is associated with significant morbidity. The current treatment of choice for CD is trans-sphenoidal selective adenomectomy resulting in long-term remission rates. Pharmacological management of CD is directed at decreasing adrenal steroid secretion. Ketoconazole inhibits adrenal enzyme activity and decreases cortisol secretion. Our patient is a girl of 13 years and eight months of age with CD. The clinical manifestations were obesity, decrease in growth rate, Cushingoid phenotype, headache and arterial hypertension. The hormone determinations showed elevated values of UFC and ACTH. The circadian rhythm cortisol and ACTH and the short and long dexamethasone tests of provide definitive diagnosis of CD. The cranial MRI with gadolinium suggests the presence of microadenoma in the right pituitary lobe. The diagnosis is confirmed after performing a selective catheterisation of the inferior petrosal sinuses with CRH stimulus. While waiting for trans-sphenoidal surgery, the treatment with ketoconazole (200mg/24h) controlled the hypercortisolism. After the surgical procedure, the patient received replacement therapy with hydrocortisone for 1 month. At the present time, the patient, without fulfilling the post surgery cure criteria, has been 2 and a half years in clinical and hormonal remission.

Human and canine pulmonary Mycobacterium bovis infection in the same household: re-emergence of an old zoonotic threat?

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a serious animal health problem in the UK, despite longstanding statutory surveillance and control measures. Endemic infection in the Eurasian badger population is thought to complicate bTB eradication efforts. Sporadic cases of M bovis infection have also been reported in domestic animals other than cattle. Human M bovis infection is extremely rare in the native UK population in the absence of unpasteurised milk consumption or residence abroad. Here, pulmonary TB infection in a UK born female and her pet dog is described, caused by an identical strain of M bovis. Latent TB infection was also identified in a household contact. The potential routes of infection and implications of this case are discussed.

Effect of an ibuprofen-releasing foam dressing on wound pain: a real-life RCT.

OBJECTIVE: To compare an ibuprofen-releasing foam dressing (Biatain Ibu, ColoplastA/S) with local best practice in the treatment of painful exuding wounds. METHOD: In this large-scale randomised comparative study, 853 patients were randomised to either ibuprofen-releasing foam (test) dressing (n=467) or local best practice (n=386). Primary endpoint was wound pain relief from day 1-7, assessed by the patients twice daily using a five-point verbal rating scale. Secondary endpoints were reduction in pain intensity from day 0-7 (assessed using an 11-point numeric box scale), quality of life (assessed using the WHO-5 well-being index and effect on health-related activities of daily living) and the incidence of adverse events. RESULTS: After seven days significantly more patients in the experimental group experienced relief from temporary and persistent pain and a reduction in pain intensity,when compared with patients in the local best practice group (p<0.0001). They also experienced a greater improvement in quality of life. The number of adverse events in both groups was low. CONCLUSION: The test dressing provided an appropriate wound healing environment, relieved temporary and persistent wound pain, and decreased pain intensity. It was also associated with an improvement in quality of life.

Aplicación de la Topología Molecular en la búsqueda de nuevos agentes activos frente a Leishmania / Application of the Molecular Topology in the search of new agents actives against Leishmania

Se ha desarrollado un modelo topológico-matemático encaminado a buscarnuevos compuestos derivados del 3,5 dinitrobenceno sulfonamida y/o benzamidaactivos frente a Leishmania. Utilizando el análisis lineal discriminante y el análisisde regresión multilineal se ha obtenido un modelo capaz de identificar la actividaddel 90% de los compuestos estudiados. Tras realizar un barrido virtual se proponennuevas estructuras potencialmente activas frente a L donovani

A topological-mathematical model has been arranged to search for newderivatives of 3,5-dinitrobenzene sulphonamide and/or benzamide, active againstL. donovani. By using linear discriminant analysis as well as multilinear regression,a model capable to identify the activity of 90% of the analyzed compounds hasbeen achieved. After carrying out a virtual screening based upon such a model, newstructures potentially active against the parasite are proposed