Bayesian Estimation of Small Proportions Using Binomial Group Test

Group testing has long been considered as a safe and sensible relative to one-at-a-time testing in applications where the prevalence rate p is small. In this thesis, we applied Bayes approach to estimate p using Beta-type prior distribution. First, we showed two Bayes estimators of p from prior on p derived from two different loss functions. Second, we presented two more Bayes estimators of p from prior on π according to two loss functions. We also displayed credible and HPD interval for p. In addition, we did intensive numerical studies. All results showed that the Bayes estimator was preferred over the usual maximum likelihood estimator (MLE) for small p. We also presented the optimal β for different p, m, and k.

Evolution of specific antibodies and proviral DNA in milk of small ruminants infected by small ruminant lentivirus

The diagnosis of Small Ruminant Lentivirus (SRLV) is based on clinical signs, pathological lesions and laboratory testing. No standard reference test for the diagnosis of maedi visna has been validated up to the present, and it is puzzling that tests which detect antibodies against the virus and tests which detect the proviral genome may render opposite results. The aim of this study was to evaluate the presence in milk throughout a lactation period of specific antibodies by ELISA and of SRLV proviral DNA by a PCR of the highly conserved pol region. A six-month study was conducted with the milk of 28 ewes and 31 goats intensively reared. The percentage of animals with antibodies against SRLV increased throughout the study period. Seroprevalence in sheep was 28% at the beginning of the study and by the end it had increased up to 52.4%. In goats, initial seroprevalence of 5.6% increased to 16%. The percentage of PCR positive ewes was stable throughout the study period. Of the positive sheep, 21.4% were PCR-positive before antibodies could be detected and most of them became PCR-negative shortly after the first detection of antibodies. This might suggest that antibodies have a neutralizing effect. In addition, an equal percentage of sheep were always PCR-negative but either became ELISA-positive or was always ELISA-positive, which might support this hypothesis. On the other hand, the PCR results in goats did not follow any pattern and oscillated between 35.3% and 55.6% depending on the month. Most goats positive by PCR failed to develop antibodies in the 6 months tested. We may conclude that the infection and the antibody response to it follow a different trend in sheep and goats.

Multiresistance in Pasteurella multocida is mediated by coexistence of small plasmids

In most gram-negative bacteria, acquired multiresistance is conferred by large plasmids compiling numerous antimicrobial resistance genes. Here, we show an evolutionary alternative strategy used by Pasteurella multocida to become resistant to multiple clinically relevant antibiotics. Thirteen beta-lactam-resistant clinical isolates, concomitantly resistant to tetracyclines and/or streptomycin as well as to sulfonamides, were studied. Pulsed-field gel electrophoresis analysis revealed different profiles among the isolates, showing that clonal dissemination was not the sole event responsible for the spread of multiresistance. Each P. multocida strain carried two or three small plasmids between 4 and 6 kb in size. A direct association between resistance profile and plasmid content was found. Complete nucleotide sequencing of all plasmids revealed seven different replicons, six of them belonging to the ColE1 superfamily. All plasmids carried one, or a maximum of two, antimicrobial resistance determinants. Plasmids pB1000 and pB1002 bore bla(ROB-1), pB1001 carried tet(B), pB1003 and pB1005 carried sul2 and strA, pB1006 harbored tet(O), and p9956 bore the tet(H) gene. All plasmids except pB1002 and pB1006 were successfully transformed into Escherichia coli. pB1000, also involved in beta-lactam resistance in Haemophilus parasuis (A. San Millan et al., Antimicrob. Agents Chemother. 51:2260-2264, 2007), was mobilized in E. coli using the conjugation machinery of an IncP plasmid. Stability experiments proved that pB1000 was stable in P. multocida but highly unstable in E. coli. In conclusion, bla(ROB-1) is responsible for beta-lactam resistance in P. multocida in Spain. Coexistence and the spread of small plasmids are used by P. multocida to become multiresistant.

Relevance of anatomy to medical education and clinical practice: perspectives of medical students, clinicians, and educators

Introduction: Against a backdrop of ever-changing diagnostic and treatment modalities, stakeholder perceptions (medical students, clinicians, anatomy educators) are crucial for the design of an anatomy curriculum which fulfils the criteria required for safe medical practice. This study compared perceptions of students, practising clinicians, and anatomy educators with respect to the relevance of anatomy education to medicine. Methods: A quantitative survey was administered to undergraduate entry (n = 352) and graduate entry students (n = 219) at two Irish medical schools, recently graduated Irish clinicians (n = 146), and anatomy educators based in Irish and British medical schools (n = 30). Areas addressed included the association of anatomy with medical education and clinical practice, mode of instruction, and curriculum duration. Results: Graduate-entry students were less likely to associate anatomy with the development of professionalism, teamwork skills, or improved awareness of ethics in medicine. Clinicians highlighted the challenge of tailoring anatomy education to increase student readiness to function effectively in a clinical role. Anatomy educators indicated dissatisfaction with the time available for anatomy within medical curricula, and were equivocal about whether curriculum content should be responsive to societal feedback. Conclusions: The group differences identified in the current study highlight areas and requirements which medical education curriculum developers should be sensitive to when designing anatomy courses.

Comparative fixed gear studies in the Cyclades (Aegean Sea): size selectivity of small-hook longlines and monofilament gill nets

Fishing trials with monofilament gill nets and longlines using small hooks were carried out at the same fishing grounds in Cyclades (Aegean Sea) over 1 year. Four sizes of MUSTAD brand, round bent, flatted sea hooks (Quality 2316 DT, numbers 15, 13, 12 and 11) and four mesh sizes of 22, 24, 26 and 28 turn nominal bar length monofilament gill nets were used. Significant differences in the catch size frequency distributions of the two gears were found for four out of five of the most important species caught by both the gears (Diplodus annularis, Diplodus vulgaris, Pagellus erythrinus, Scorpaena porcus and Serranus cabrilla), with longlines catching larger fish and a wider size range than gill nets. Whereas longline catch size frequency distributions for most species for the different hook sizes were generally highly overlapped, suggesting little or no differences in size selectivity, gill net catch size frequency distributions clearly showed size selection, with larger mesh sizes catching larger fish. A variety of models were fitted to the gill net data, with the lognormal providing the best fit in most cases. A maximum likelihood method was also used to estimate the parameters of the logistic model for the longline data. Because of the highly overlapped longline catch size frequency distributions parameters could only be estimated for two species. This study shows that the two static gears have different impacts in terms of size selection. This information will be useful for the more effective management of these small-scale, multi-species and multi-gear fisheries. (C) 2002 Elsevier Science B.V. All rights reserved.

Trophic signatures of small-scale fishing gears: implications for conservation and management

We quantified the ecosystem effects of small-scale gears operating in southern European waters (Portugal, Spain, Greece), based on a widely accepted ecosystem measure and indicator, the trophic level (TL). We used data from experimental fishing trials during 1997 to 2000. We studied a wide range of gear types and sizes: (1) gill nets of 8 mesh sizes, ranging from 44 to 80 mm; (2) trammel nets of 9 inner panel mesh sizes, ranging from 40 to 140 mm; and (3) longlines of 8 hook sizes, ranging from Nos. 15 (small) to 5 (large). We used the number of species caught per TL class for constructing trophic signatures (i.e. cumulative TL distributions), and estimated the TL at 25, 50 and 75% cumulative frequency (TL25, TL50, TL75) and the slopes using the logistic function. We also estimated the mean weighted TL of the catches (TLW). Our analyses showed that the TL characteristics of longlines varied much more than those of gill and trammel nets. The longlines of large hooks (Nos. 10, 9, 7, 5) were very TL selective, and their trophic signatures had very steep slopes, the highest mean TL50 values, very narrow mean TL25 to TL75 ranges and mean TLW > 4. In addition, the mean number of TL classes exploited was smaller and the mean TL50 and TLW were larger for the longlines of small hooks (Nos. 15, 13, 12, 11) in Greek than in Portuguese waters. Trammel and gill nets caught more TL classes, and the mean slopes of their trophic signatures were significantly smaller than those of longlines as a group. In addition, the mean number of TL classes exploited, the mean TL50 and the TLW of gill nets were significantly smaller than those of trammel nets. We attribute the differences between longlines of small hooks to bait type, and the differences between all gear types to their characteristic species and size-selectivity patterns. Finally, we showed how the slope and the TL50 Of the trophic signatures can be used to characterise different gears along the ecologically 'unsustainable-sustainable' continuum.

Environmental influence on commercial fishery landings of small pelagic fish in Portugal

Small pelagic fishes are particularly abundant in areas with high environmental variability (zones of coastal upwelling and areas of tidal mixing and river discharge), and because of this, their abundance suffers large inter-annual and inter-decadal fluctuations. In Portugal, the most important species in terms of landings are European sardine, Atlantic horse mackerel and Atlantic chub mackerel. Small pelagic fish landings account for 62.8 % of the total fish biomass and represent 32.7 % of the economical value of all catches. We have investigated trends in landings of these small pelagic fishes and detected the effects of environmental factors in this fishery. In order to explain the variability of landings of small pelagic fishes, we have used official landings (1965-2012) for trawling and purse seine fisheries and applied generalized linear models, using the North Atlantic Oscillation index (NAO) (annual and winter NAO index), sea surface temperature (SST), wind data (strength and North-South and East-West wind components) and rainfall, as explanatory variables. Regression analysis was used to describe the relationship between landings and SST. The models explained between 50.16 and 51.07 % of the variability of the LPUE, with the most important factors being winter NAO index, SST and wind strength. The LPUE of European sardine and Atlantic horse mackerel was negatively correlated with SST, and LPUE of Atlantic chub mackerel was positively correlated with SST. The use of landings of three important species of small pelagic fishes allowed the detection of variations in landings associated with changes in sea water temperature and NAO index.

Comparison of small remotely operated vehicles and diver-operated video of circalittoral benthos

Underwater video transect methods using small remotely operated vehicles (ROVs) and diveroperated video (DOV) are commonly used in benthic biodiversity assessments. Constraints posed by deeper waters have made surveys of the circalittoral zone ([30 m depth), a particularly challenging problem. Here we compare benthic diversity metrics and cluster analyses obtained with ROV and DOV between 45 and 65 m depth off southwest Iberia, across local (tens to hundreds of meters) and regional scales (tens of kilometers). Results showed no difference between methods in terms of the benthic species richness, taxonomic distinctness, and beta diversity, but only minor differences in the spatial structure depicted at the regional level. At the local scale, DOV performed better at discriminating patterns likely because of the divers visual acuity. We found that small ROV and DOV are reliable and comparable methods for the study of circalittoral benthic assemblages and can be used in a complimentary way to detect the greatest amount of variation in benthic ecosystems. Our study facilitates the understanding of capabilities and limitations of two underwater video methods and provides important insight into choice of the most appropriate technique.

Controlled surface nanotopography and oxygen plasma treatment of PEEK to improve cellular response

Poly(aryl-ether-ether-ketone) (PEEK) is a semi crystalline polymer which exhibits properties that make it an attractive choice for use as an implant material. It displays natural radiolucency, and MRI compatibility, as well as good chemical and sterilization resistance, both of which make it of particular interest in orthopaedic implants. However, PEEK has demonstrated poor cellular adhesion both in vitro and in vivo. This is problematic as implant surfaces that do not develop a layer of adhesive cells are at risk of undergoing fibrous encapsulation, which in turn leads to lack of a strong interface between the implant device and the patient tissue, which can in turn lead to failure of the implant and revision surgery . As incorporating nanotopography into a polymer surface has been demonstrated to be able to direct the differentiation behaviour of stem cells, a possible solution to PEEKs underlying issues with poor cellular response would be to incorporate specific nanoscale topography into the material surface through injection moulding, and then analysing if this is a viable method for addressing PEEKs issues with cellular response. In addition to nanoscale topography, the experimental PEEK surfaces were treated with oxygen plasma to address the underlying cytophobicity of the material. As this type of treatment has been documented to be capable of etching the PEEK surface, experiments were carried out to quantify the effect of this treatment, both on the ability of cells to adhere to the PEEK surface, as well as the effect it has upon the nanotopography present at the PEEK surface. The results demonstrated that there were a range of plasma treatments which would significantly improve the ability of cells to adhere to the PEEK surface without causing unacceptable damage to the nanotopography. Three different types of cells with osteogenic capacity were tested with the PEEK surfaces to gauge the ability of the topography to alter their behaviour: SAOS-2, osteoprogenitors and 271+ MSCs. Due to PEEKs material properties (it is non transparent, exhibits birefringence and is strongly autofluorescent) a number of histological techniques were used to investigate a number of different stages that take place in osteogenesis. The different cell types did display slightly different responses to the topographies. The SAOS-2 cells cultured on surfaces that had been plasma treated for 2 minutes at 200W had statistically significantly higher levels of von Kossa staining on the NSQ surface compared to the planar surface, and the same experiment employing alizarin red staining, showed a statistically significantly lower level of staining on the SQ surface compared to the planar surface. Using primary osteoprogenitor cells designed to look into if whether or not the presence of nanotopography effected the osteogenic response of these cells, we saw a lack of statistically significant difference produced by the surfaces investigated. By utilising HRP based immunostaining, we were able to investigate, in a quantitative fashion, the production of the two osteogenic markers osteopontin and osteocalcin by cells. When stained for osteocalcin, the SQ nanotopography had total percentage of the surface with stained material, average area and average perimeter all statistically significantly lower than the planar surface. For the cells that were stained for osteopontin, the SQ nanotopgraphy had a total percentage of the surface with stained material, average area and average perimeter all highly statistically significantly lower than those of the planar surface. Additionally, for this marker the NSQ nanotopography had average areas and average perimeters that were highly significantly higher than those of the planar surface. There were no significant differences for any of the values investigated for the 271+ MSC’s When plasma treatment was varied, the SAOS-2 cells demonstrated an overall trend i.e. increasing the energy of plasma treatment in turn leads to an increase in the overall percentage of staining. A similar experiment employing stem cells isolated from human bone marrow instead of SAOS-2 cells showed that for polycarbonate surfaces , used as a control, mineralization is statistically significantly higher on the NSQ nanopattern compared to the planar surface, whereas on the PEEK surfaces we observe the opposite trend i.e. the NSQ nanotopography having a statistically significantly lower amount of mineralization compared to the planar surface at the 200W 2min and 30W 1min plasma treatments. The standout trend from the PEEK results in this experiment was that the statistically significant differences on the PEEK substrates were clustered around the lower energy plasma treatments, which could suggest that the plasma treatment disrupted a function of the nanotopograhy which is why, as the energy increases, there are less statistically significant differences between the NSQ nanotopography and the Planar surface This thesis documents the response of a number of different types of cells to specific nanoscale topographies incorporated into the PEEK surface which had been treated with oxygen plasma. It outlines the development of a number of histological methods which measure different aspects of osteogenesis, and were selected to both work with PEEK, and produce quantitative results through the use of Cell Profiler. The methods that have been employed in this body of work would be of interest to other researchers working with this material, as well as those working with similarly autofluorescent materials.

Clínica e cirurgia de animais de companhia

Este relatório foi elaborado no âmbito do estágio curricular do Mestrado Integrado em Medicina Veterinária. Encontra-se dividido em duas partes. Na primeira parte é feita uma análise da casuística seguida durante o estágio. A segunda parte é constituída por uma monografia de revisão bibliográfica sobre o tema ”Tromboembolismo Arterial Felino”(TAF), bem como a descrição e discussão de dois casos clínicos acompanhados durante o estágio. O TAF é caracterizado pela embolização de um trombo numa artéria da circulação sistémica, sendo a localização mais frequente a trifurcação ilíaca da artéria aorta. Na maioria dos casos, o trombo tem origem no átrio esquerdo, como resultado de cardiomiopatia. Apesar do diagnóstico ser facilmente obtido através de sinais clínicos, o tratamento e a prevenção desta afeção representam um desafio para o médico veterinário, já que a taxa de reincidência de tromboembolismo e mortalidade são elevadas, projectando um prognóstico reservado; Clinic and Surgery of Small Animals Abstract: This report was done within the scope of the internship integrated master’s degree in Veterinay Medicine. It is divided in two parts. In the first part, an analisys of the casuistic followed during the internship is done. The second part is composed by a literature review about the theme ”Feline Arterial Thromboembolism”(FAT), as well as the description and discussion of two clinical cases followed during the internship. FAT is characterized by the embolization of a thrombus in a artery of systemic circulation, being its location more frequently in iliac trifurcation of aorta artery. On most of the cases the thrombus has its origins on the left atrium, as a result of cardiomyopathy. Besides the diagnosis being easily obtained through clinical signs, the treatment and prevention of this disease represents a challenge to the veterinarian clinician, due to the FAT recurrance rate and high mortality, projecting a pour/reserved prognosis.

Long term performance evaluation of small-diameter vascular grafts based on polyvinyl alcohol hydrogel and dextran and MSCs-based therapies using the ovine pre-clinical animal model.

The functional and structural performance of a 5 cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic / diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.

Effects of small scale non-mechanised forest management and high impact and mechanised forest management on the forest dynamics and growth of the residual trees.

This study was perfonned in PSPs located at the CPAr-ACRE EMORAPA expcrirnental area and at the PC Peixoto management areas. AI CPA F-ACR E the managed area was meehanically exploited in 1992 and at PC Peixoto animal traction was used to extract the planks.

Computational study on the asymmetric aminocatalysed Michael addition reaction of cyclohexanone to trans–β–nitrostyrene

Asymmetric organocatalysed reactions are one of the most fascinating synthetic strategies which one can adopt in order to induct a desired chirality into a reaction product. From all the possible practical applications of small organic molecules in catalytic reaction, amine–based catalysis has attracted a lot of attention during the past two decades. The high interest in asymmetric aminocatalytic pathways is to account to the huge variety of carbonyl compounds that can be functionalized by many different reactions of their corresponding chiral–enamine or –iminium ion as activated nucleophile and electrophile, respectively. Starting from the employment of L–Proline, many useful substrates have been proposed in order to further enhance the catalytic performances of these reaction in terms of enantiomeric excess values, yield, conversion of the substrate and turnover number. In particular, in the last decade the use of chiral and quasi–enantiomeric primary amine species has got a lot of attention in the field. Contemporaneously, many studies have been carried out in order to highlight the mechanism through which these kinds of substrates induct chirality into the desired products. In this scenario, computational chemistry has played a crucial role due to the possibility of simulating and studying any kind of reaction and the transition state structures involved. In the present work the transition state geometries of primary amine–catalysed Michael addition reaction of cyclohexanone to trans–β–nitrostyrene with different organic acid cocatalysts has been studied through different computational techniques such as density functional theory based quantum mechanics calculation and force–field directed molecular simulations.

Preclinical evaluation of a MYCN-specific inhibitor for the treatment of small cell lung cancer

Small cell lung cancer (SCLC) is the most aggressive form of lung cancer, characterized by rapid growth, early metastasis and acquired drug resistance. SCLC is usually sensitive to initial treatment, however, most patients relapse within few months; thus more effective therapies are urgently needed. Key genetic alterations very frequently observed in SCLC include loss of TP53 and RB1 and mutations in the MYC family genes (MYC, MYCL or MYCN). One of them is amplified and overexpressed in a mutually exclusive manner and represents the most prominent activating oncogene alteration in this malignancy. In particular, MYCN amplification is associated with tumor progression, treatment failure and poor prognosis. Given the role of MYCN in SCLC and its restricted expression profile, MYCN represents a promising therapeutic target; although it is considered undruggable by traditional approaches. An innovative approach to target the oncogene concerns specific MYCN expression inhibition, acting directly at the level of DNA, through an antigene peptide nucleic acid (agPNA) oligonucleotide, called BGA002. This thesis focused on the study of BGA002, as a possible targeted therapeutic strategy for the treatment of MYCN-related SCLC. In this context, BGA002 proved to be a specific and highly effective inhibitor. Furthermore, MYCN silencing induced alterations in many downstream pathways and led to apoptosis, in concomitance with autophagy reactivation. Moreover, systemic administration of BGA002 was effective in vivo as well, significantly increasing survival in MNA mouse models, even in the scenario of multidrug-resistance. In addition, BGA002 treatment successfully reduced N-Myc protein expression and, more importantly, caused a massive diminishment in tumor vascularization in the multidrug-resistant model. Overall, these results proved that MYCN inhibition by BGA002 may represent a new promising precision medicine approach, to treat MYCN-related SCLC.

Acoustic backscatter of small pelagic fish species in the Adriatic Sea

The aim of the present study is to apply a broad range of techniques to increase the knowledge of acoustic properties of Sprattus sprattus, Scomber colias and Trachurus mediterraneus in the Adriatic Sea. A novel study using tethered live fish but not involving hooks and anesthetic was tested on T. mediterraneus and S. colias through several ex situ experiments using a split-beam scientific echosounder operating at 38, 120, and 200 kHz. The mean TS was estimated for 29 live specimens, resulting in a conversion factor b20 value of -71.4 dB re 1 m2 and -71.6 dB re 1 m2 respectively which is ~3 dB lower than the current one in use in the Mediterranean Sea. Successively, two monospecific trawl hauls were analyzed through the application of in situ approach for the computation of TS values of S. sprattus which led to six b20 values for sprat (range, -68.8 dB re 1 m2 to -65.6 dB re 1 m2), all higher than the current known value of -71.7 dB re 1 m2. The high difference up to 4.2 dB compared to the current value translates in a significant decrease of absolute sprat biomass along the time series un to 20%. Finally, 149 specimens of the three species were collected for backscattering model application(i.e. Kirchhoff-ray mode model (KRM) and Finite Element Method (FEM)) from digital images of the fish body and swimbladder obtained from Computer Tomography (CT) and X-Ray scans. The values resulting from the application of KRM and FEM are in agreement with empirical results. In general terms the present work proposes the acoustic backscatter characterization of S. colias, S. sprattus and T. mediterraneus in the Mediterranean Sea.