The impact of early retirement reform on firms’ employment adjustment

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA – School of Business and Economics

C-reactive protein in early risk assessment in acute pancreatitis

ABSTRACT:C-reactive protein (CRP) has been widely used in the early risk assessment of patients with acute pancreatitis (AP), but unclear aspects about its prognostic accuracy in this setting persist. This project evaluated first CRP prognostic accuracy for severity, pancreatic necrosis (PNec), and in-hospital mortality (IM) in AP in terms of the best timing for CRP measurement and the optimal CRP cutoff points. Secondly it was evaluated the CRP measured at approximately 24 hours after hospital admission (CRP24) prognostic accuracy for IM in AP individually and in a combined model with a recent developed tool for the early risk assessment of patients with AP, the Bedside Index for Severity in AP (BISAP). Two single-centre retrospective cohort studies were held. The first study included 379 patients and the second study included 134 patients. Statistical methods such as the Hosmer-Lemeshow goodness-of-fit test, the area under the receiver-operating characteristic curve, the net reclassification improvement, and the integrated discrimination improvement were used. It was found that CRP measured at approximately 48 hours after hospital admission (CRP48) had a prognostic accuracy for severity, PNec, and IM in AP better than CRP measured at any other timing. It was observed that the optimal CRP48 cutoff points for severity, PNec, and IM in AP varied from 170mg/l to 190mg/l, values greater than the one most often recommended in the literature – 150mg/l. It was found that CRP24 had a good prognostic accuracy for IM in AP and that the cutoff point of 60mg/l had a negative predictive value of 100%. Finally it was observed that the prognostic accuracy of a combined model including BISAP and CRP24 for IM in AP could perform better than the BISAP alone model. These results might have a direct impact on the early risk assessment of patients with AP in the daily clinical practice.--------- RESUMO: A proteina c-reactiva (CRP) tem sido largamente usada na avaliação precoce do risco em doentes com pancreatite aguda (AP), mas aspectos duvidosos acerca do seu valor prognóstico neste contexto persistem. Este projecto avaliou primeiro o valor prognóstico da CRP para a gravidade, a necrose pancreática (PNec) e a mortalidade intra-hospitalar (IM) na AP em termos do melhor momento para efectuar a sua medição e dos seus pontos-de-corte óptimos. Em segundo lugar foi avaliado o valor prognóstico da proteína c-reactiva medida aproximadamente às 24 horas após a admissão hospitalar (CRP24) para a IM na AP isoladamente e num modelo combinado, que incluiu uma ferramenta de avaliação precoce do risco em doentes com AP recentemente desenvolvida, o Bedside Index for Severity in Acute Pancreatitis (BISAP). Dois estudos unicêntricos de coorte retrospectivo foram realizados. O primeiro estudo incluiu 379 doentes e o segundo estudo incluiu 134 doentes. Metodologias estatísticas como o teste de Hosmer-Lemeshow goodness-of-fit, a area under the receiver-operating characteristic curve, o net reclassification improvement e o integrated discrimination improvement foram usadas. Verificou-se que a CRP medida às 48 horas após a admissão hospitalar (CRP48) teve um valor prognóstico para a gravidade, a PNec e a IM na AP melhor do que a CRP medida em qualquer outro momento. Observou-se que os pontos de corte óptimos da CRP48 para a gravidade, a PNec e a IM na AP variaram entre 170mg/l e 190mg/l, valores acima do valor mais frequentemente recomendado na literatura – 150mg/l. Verificou-se que a CRP medida aproximadamente às 24 horas após a admissão hospitalar (CRP24) teve um bom valor prognóstico para a IM na AP e que o ponto de corte 60mg/l teve um valor preditivo negativo de 100%. Finalmente observou-se que o valor prognóstico de um modelo combinado incluindo o BISAP e a CRP24 para a IM na AP pode ter um desempenho melhor do que o do BISAP isoladamente. Estes resultados podem ter um impacto directo na avaliação precoce do risco em doentes com AP na prática clínica diária.

New roles of Rab GTPases on eye diseases: targeting VEGF secretion

RESUMO: A retina é composta, entre outras estruturas, pelo epitélio pigmentar da retina (EPR)e pela coróide. A região central da retina denomina-se mácula, e é a zona mais afetada na degenerescência macular relacionada com a idade, a forma mais comum de degenerescência da retina. Nesta doença, a secreção de fatores de crescimento pelo EPR é afetada, nomeadamente a do fator de crescimento vascular endotelial (VEGF), e pouco se sabe ainda sobre os mecanismos moleculares conducentes a esta condição. A família de proteínas Rab GTPases está envolvida nas vias intracelulares de sinalização e tráfego membranares, essenciais na transdução de sinais extracelulares em respostas biológicas. A sua crucial importância nestes mecanismos levou-nos a considerar o seu potencial envolvimento nas vias de secreção do VEGF, e a questionar-nos se teriam algum papel regulador sobre as mesmas. O principal objetivo deste trabalho é identificar Rab GTPases importantes para as vias de secreção e endocitose do VEGF no EPR. Essa identificação ajudará a esclarecer a patogénese da degenerescência macular da retina, e poderá servir para uma procura mais direcionada de novos agentes terapêuticos. A caracterização de dois modelos in vitro do EPR, células primárias isoladas de murganho e a linha celular B6-RPE07,levou-nos a concluir que são ambos semelhantes. Contudo, a linha celular foi escolhida como protótipo do EPR por permitir o acesso a um número ilimitado de células. No decurso deste trabalho, desenvolvemos e caracterizámos uma biblioteca de ferramentas moleculares que nos permitiram reduzir os níveis proteicos das proteínas Rab GTPases, com base na tecnologia de ácido ribonucleico (ARN) de interferência. O papel das proteínas Rab GTPases na secreção do VEGF no EPR foi estudado com base no silenciamento de apenas uma proteína, ou combinando várias, segundo a sua localização e funções intracelulares descritas. Este trabalho permitiu-nos concluir que as proteínas Rab GTPases são importantes intervenientes no processo de secreção de VEGF pelo EPR, e confirmar dados anteriores que relatam o envolvimento de algumas Rab GTPases endocíticas no processo. Propomos ainda um novo modelo para a interação destas proteínas no EPR, e sugerimos que a Rab10 e a Rab14 atuam negativamente sobre a Rab8, controlando o seu funcionamento. Os nossos resultados evidenciam a importância das proteínas Rab GTPases na secreção do VEGF pelas células do EPR, e servem de base a futuros estudos que melhor procurem compreender este mecanismo e de que modo a sua alteração se relaciona com a degenerescência da retina.--------ABSTRACT: Retinal pigment epithelium (RPE) and choroid are components of the mammalian retina, of which the central region is called macula. The most common form of retinaldegeneration, age-related macular degeneration (AMD), involves primarily deregulation of growth factors secretion by the RPE. Very little is known about the molecular mechanisms that lead to impairment of RPE’s homeostatic intracellular processes, namely the secretion of vascular endothelial growth factor (VEGF). Rab GTPases’ family regulates membrane targeting and traffic, being essential in the transduction of signal pathways. Given Rab proteins’ role in intracellular trafficking, we propose to identify key regulatory Rab proteins involved in either the secretory or the recycling pathways of VEGF in RPE. Understanding how Rab proteins’ function disruption could lead to retinal and choroidal pathology would ultimately contribute to find new therapeutic agents. Here, we characterized two mouse RPE in vitro cell models, primary cells and B6-RPE07 cell line, and concluded that both display important epithelial features as the RPE presents in vivo. Considering unlimited cell number and results reproducibility, we chose B6-RPE07 cells to further study Rab proteins’ function. To scrutinize the consequences of Rab proteins’ absence or diminished levels, we have developed novel molecular tools to achieve silencing of these key proteins using miRNA technology. We further addressed the effect of Rab proteins’ absence on VEGF secretion by performing an extensive screening where different Rab proteins were silenced, both individually and in multiple combinations considering their cellular/ compartment location. We conclude that Rab GTPases are important intervenients in VEGF secretion by RPE cells, confirming endocytic Rab proteins’ role in regulation of VEGF biology. We also propose a novel model for Rab proteins’ interaction in RPE. Our results suggest that Rab10 and Rab14 might influence Rab8 in a negative feedback mechanism, important for controlling VEGF secretion. Our achievements’ unravel Rab proteins’ role in VEGF secretion by RPE cells and are the basis for future studies to better understand RPE molecular secretory machinery.

Extension and patterning of the vertebrate body

Dissertation presented to obrain the Ph.D degree in Biology. Developmental Biology

Interaction of malaria parasites with host late endocytic and autophagic pathways is essential for Plasmodium liver stage development

RESUMO: A Malária é causada por parasitas do género Plasmodium, sendo a doença parasitária mais fatal para o ser humano. Apesar de, durante o século passado, o desenvolvimento económico e a implementação de diversas medidas de controlo, tenham permitido erradicar a doença em muitos países, a Malária continua a ser um problema de saúde grave, em particular nos países em desenvolvimento. A Malária é transmitida através da picada de uma fêmea de mosquito do género Anopheles. Durante a picada, os esporozoítos são injetados na pele do hospedeiro, seguindo-se a fase hepática e obrigatória do ciclo de vida. No fígado, os esporozoítos infetam os hepatócitos onde se replicam, dentro de um vacúolo parasitário (VP) e de uma forma imunitária silenciosa, em centenas de merozoitos. Estas novas formas do parasita são as responsáveis por infetar os eritrócitos, iniciando a fase sanguínea da doença, onde se os primeiros sintomas se manifestam, tais como a característica febre cíclica. A fase hepática da doença é a menos estudada e compreendida. Mais ainda, as interações entre o VP e os organelos da células hospedeira estão ainda pouco caracterizados. Assim, neste estudo, as interações entre os organelos endocíticos e autofágicos da célula hospedeira e o VP foram dissecados, observando-se que os anfisomas, que são organelos resultantes da intersecção do dois processos de tráfego intracelular, interagem com o parasita. Descobrimos que a autofagia tem também uma importante função imunitária durante a fase hepática inicial, ao passo, que durante o desenvolvimento do parasita, já numa fase mais tardia, o parasita depende da interação com os endossomas tardios e anfisomas para crescer. Vesiculas de BSA, EGF e LC3, foram, também, observadas dentro do VP, sugerindo que os parasitas são capazes de internalizar material endocítico e autofágico do hospedeiro. Mais ainda, mostramos que esta interação depende da cinase PIKfyve, responsável pela conversão do fosfoinositidio-3-fosfato no fosfoinositidio-3,5-bifosfato, uma vez que inibindo esta cinase o parasita não é capaz de crescer normalmente. Finalmente, mostramos que a proteína TRPML1, uma proteína efetora do fosfoinositidio-3,5-bifosfato, e envolvida no processo de fusão das membranas dos organelos endocíticos e autofágicos, também é necessária para o crescimento do parasita. Desta forma, o nosso estudo sugere que a membrana do VP funde com vesiculas endocíticas e autofágicas tardias, de uma forma dependente do fositidio-3,5-bifosfato e do seu effetor TRPML1, permitindo a troca de material com a célula hospedeira. Concluindo, os nossos resultados evidenciam que o processo autofágico que ocorre na célula hospedeira tem um papel duplo durante a fase hepática da malaria. Enquanto numa fase inicial os hepatócitos usam o processo autofágico como forma de defesa contra o parasita, já durante a fase de replicação o VP funde com vesiculas autofágicas e endocíticas de forma a obter os nutrientes necessários ao seu desenvolvimento.--------- ABSTRACT: Malaria, which is caused by parasites of the genus Plasmodium, is the most deadly parasitic infection in humans. Although economic development and the implementation of control measures during the last century have erradicated the disease from many areas of the world, it remains a serious human health issue, particularly in developing countries. Malaria is transmitted by female mosquitoes of the genus Anopheles. During the mosquito blood meal, Plasmodium spp. sporozoites are injected into the skin dermis of the vertebrate host, followed by an obligatory liver stage. Upon entering the liver, Plasmodium parasites infect hepatocytes and silently replicate inside a host cell-derived parasitophorous vacuole (PV) into thousands of merozoites. These new parasite forms can infect red blood cells initiating the the blood stage of the disease which shows the characteristic febrile malaria episodes. The liver stage is the least characterized step of the malaria infection. Moreover, the interactions between the Plasmodium spp. PV and the host cell trafficking pathways are poorly understood. We dissected the interaction between Plasmodium parasites and the host cell endocytic and autophagic pathways and we found that both pathways intersect and interconnect in the close vicinity of the parasite PV, where amphisomes are formed and accumulate. Interestingly, we observed a clearance function for autophagy in hepatocytes infected with Plasmodium berghei parasites at early infection times, whereas during late liver stage development late endosomes and amphisomes are required for parasite growth. Moreover, we found the presence of internalized BSA, EGF and LC3 inside parasite vacuoles, suggesting that the parasites uptake endocytic and autophagic cargo. Furthermore, we showed that the interaction between the PV and host traffic pathways is dependent on the kinase PIKfyve, which converts the phosphoinositide PI(3)P into PI(3,5)P2, since PIKfyve inhibition caused a reduction in parasite growth. Finally, we showed that the PI(3,5)P2 effector protein TRPML1, which is involved in late endocytic and autophagic membrane fusion, is also required for parasite development. Thus, our studies suggest that the parasite parasitophorous vacuole membrane (PVM) is able to fuse with late endocytic and autophagic vesicles in a PI(3,5)P2- and TRPML1-dependent manner, allowing the exchange of material between the host cell and the parasites, necessary for the rapid development of the latter that is seen during the liver stage of infection. In conclusion, we present evidence supporting a specific and essential dual role of host autophagy during the course of Plasmodium liver infection. Whereas in the initial hours of infection the host cell uses autophagy as a cell survival mechanism to fight the infection, during the replicative phase the PV fuses with host autophagic and endocytic vesicles to obtain nutrients required for parasite growth.

Role of Notch signaling on the differentiation of early lymphoid progenitors cells: a view throughout the development of the embryonic chicken thymus and spleen

Dissertação para a obtenção do grau de Mestre em Genética Molecular e Biomedicina

Exposição a ozono em cabinas de avião

RESUMO - O ozono é o principal componente da poluição fotoquímica do ar. Como agente irritante do aparelho respiratório, os seus efeitos sobre a saúde caracterizam-se, essencialmente, por tosse, dispneia, desconforto torácico e alterações da função pulmonar, encontrando-se também associadas à exposição ambiental a O3 tanto uma maior frequência e gravidade de crises de asma como a ocorrência de quadros clínicos de irritação conjuntival. É sobretudo a partir dos anos 50, com a descoberta de concentrações elevadas de ozono em ambientes de trabalho respeitantes à actividade de soldadura «a arco», que aquele gás passa a ser encarado como factor profissional de risco. No início dos anos 60 surgem os primeiros estudos de exposição a O3 em cabinas de avião, suscitados pela ocorrência, em tripulantes e passageiros, de queixas clínicas de irritação do tracto respiratório. Esta sintomatologia era, até então, atribuída à acção de outros factores, designadamente o sistema de ventilação e o baixo teor de humidade do ar. Posteriormente, alguns estudos revelaram que, em voos comerciais subsónicos, os teores elevados de O3 observados no interior das cabinas poderiam ser provocados pela sua insuficiente destruição nos sistemas de entrada de ar.O presente estudo, efectuado em voos de longo curso realizados em aeronaves Airbus A340-300 numa única rota comercial, teve por objectivo avaliar a exposição a ozono no ar interior em cabina de avião. Os teores médios de concentração de ozono observados foram inferiores aos valores susceptíveis de provocarem efeitos adversos sobre o aparelho respiratório. Como valor máximo instantâneo, foi atingida a concentração de 152 ppb. Adicionalmente, foi constatada a influência das estações do ano nos teores de O3. O conjunto dos resultados obtidos permite concluir que as concentrações de ozono no ar interior nas cabinas de avião estudadas são inferiores às correspondentes concentrações máximas admissíveis, tendo, em todos os voos, sido observado o cumprimento da norma da FAA respeitante à protecção da exposição ao ozono em cabinas de aeronaves de aviação comercial.

Transimpedance amplifier for early detection of breast cancer

Breast cancer is the most common type of cancer worldwide. The effectiveness of its treatment depends on early stage detection, as well as on the accuracy of its diagnosis. Recently, diagnosis techniques have been submitted to relevant breakthroughs with the upcoming of Magnetic Resonance Imaging, Ultrasound Sonograms and Positron Emission Tomography (PET) scans, among others. The work presented here is focused on studying the application of a PET system to a Positron Emission Mammography (PEM) system. A PET/PEM system works under the principle that a scintillating crystal will detect a gamma-ray pulse, originated at the cancerous cells, converting it into a correspondent visible light pulse. The latter must then be converted into an electrical current pulse by means of a Photo- -Sensitive Device (PSD). After the PSD there must be a Transimpedance Amplifier (TIA) in order to convert the current pulse into a suitable output voltage, in a time period lower than 40 ns. In this Thesis, the PSD considered is a Silicon Photo-Multiplier (SiPM). The usage of this recently developed type of PSD is impracticable with the conventional TIA topologies, as it will be proven. Therefore, the usage of the Regulated Common-Gate (RCG) topology will be studied in the design of the amplifier. There will be also presented two RCG variations, comprising a noise response improvement and differential operation of the circuit. The mentioned topology will also be tested in a Radio-Frequency front-end, showing the versatility of the RCG. A study comprising a low-voltage self-biasing feedback TIA will also be shown. The proposed circuits will be simulated with standard CMOS technology (UMC 130 nm), using a 1.2 V power supply. A power consumption of 0.34 mW with a signal-to-noise ratio of 43 dB was achieved.

A description of the Australian early psychosis intervention model and a proposal to establish a Pilot Early Intervention Program in Santa Cruz de la Sierra, Bolívia

RESUMO: Em 2011, a Associação Psiquiátrica Mundial lançou um programa de bolsas de investigação para psiquiatras em início de carreira a partir de países de renda baixa ou média-baixa, no âmbito deste programa, o autor foi selecionado para uma bolsa de pesquisa no Centre for Youth Mental Health/Orygen Youth Health Research Centre da Universidade de Melbourne. Orygen, é a principal organização de pesquisa e tradução do conhecimento do mundo com foco em problemas de saúde mental em pessoas jovens. O estágio foi baseado em Prevenção e Intervenção Precoce Psychosis Centre (EPPIC), que faz parte do Orygen. EPPIC fornece programa de tratamento abrangente e integrada, baseada na comunidade para o primeiro episódio de psicose. Esta dissertação descreve o modelo EPPIC, e seus componentes essenciais e fatores que são necessários para uma implementação de serviço direito. Além disso, uma proposta de criação de um programa-piloto de intervenção psicose precoce é discutido. Este programa inclui um programa de extensão inovadora que combina princípios comerciais sólidos, com metas sociais, a fim de combater especificamente a maior barreira para o tratamento da psicose precoce na Bolívia: o estigma da doença mental. Ao utilizar uma equipe de tratamento móvel, multidisciplinar, que enfatiza os papéis dos gerentes do caso treinados focada em fornecer indivíduo intensiva e apoio familiar no lar, este programa irá prestar cuidados culturalmente apropriados que irá alavancar contribuições de um suprimento limitado de psiquiatras e mudar longe da dependência um sistema médico fragmentado. ---------------------------- ABSTRACT: In 2011, the World Psychiatric Association launched a programme of research fellowships for early-career psychiatrists from low- or lower-middle income countries, within this programme, the author was selected to a research fellowship at the Centre for Youth Mental Health/Orygen Youth Health Research Centre at University of Melbourne. Orygen, is the world’s leading research and knowledge translation organization focusing on mental ill-health in young people. The traineeship was based on Early Psychosis Prevention and Intervention Centre (EPPIC), which is part of Orygen. EPPIC provides comprehensive, integrated, community-based treatment program for first-episode psychosis. This dissertation describes the EPPIC model, and its core components and factors which are necessary to a right service implementation. Additionally, a proposal to establish a pilot early psychosis intervention programme is discussed. This programme includes an innovative outreach programme that combines sound business principals with social goals in order to specifically target the largest barrier to early psychosis treatment in Bolivia: the stigma of mental illness. By utilizing a mobile, multidisciplinary treatment team that emphasizes the roles of trained case managers focused on providing intensive individual and family support in the home, this programme will provide culturally appropriate care that will leverage contributions from a limited supply of psychiatrists and shift dependence away from a fragmented medical system.

Detection of purkinje images for automatic positioning of fixation target and interferometric measurements of anterior eye chamber

In cataract surgery, the eye’s natural lens is removed because it has gone opaque and doesn’t allow clear vision any longer. To maintain the eye’s optical power, a new artificial lens must be inserted. Called Intraocular Lens (IOL), it needs to be modelled in order to have the correct refractive power to substitute the natural lens. Calculating the refractive power of this substitution lens requires precise anterior eye chamber measurements. An interferometry equipment, the AC Master from Zeiss Meditec, AG, was in use for half a year to perform these measurements. A Low Coherence Interferometry (LCI) measurement beam is aligned with the eye’s optical axis, for precise measurements of anterior eye chamber distances. The eye follows a fixation target in order to make the visual axis align with the optical axis. Performance problems occurred, however, at this step. Therefore, there was a necessity to develop a new procedure that ensures better alignment between the eye’s visual and optical axes, allowing a more user friendly and versatile procedure, and eventually automatizing the whole process. With this instrument, the alignment between the eye’s optical and visual axes is detected when Purkinje reflections I and III are overlapped, as the eye follows a fixation target. In this project, image analysis is used to detect these Purkinje reflections’ positions, eventually automatically detecting when they overlap. Automatic detection of the third Purkinje reflection of an eye following a fixation target is possible with some restrictions. Each pair of detected third Purkinje reflections is used in automatically calculating an acceptable starting position for the fixation target, required for precise measurements of anterior eye chamber distances.

Do hospitals react to random demand pressure by early discharges?

This project tries to assess whether hospitals react to random demand pressure by discharging patients earlier than expected. As a matter of fact, combining an unpredictable demand for medical services with limited and, to some extent, fixed medical resources, generates strong incentives to discharge patients earlier than expected when demand is high − increasing the risk of readmission and decreasing the benefit from treatment. This work was conducted as a way to determine whether those incentives actually affect discharging decisions. Analysis of Portuguese hospitals data shows that hospital utilization levels at the time of admission, prior to the admission and post admission do have a negative impact over the length of stay in hospital, although this impact is quantitatively irrelevant. More than that, larger utilization levels have a positive impact over the probability of being discharged at certain days of the week, indicating that an early discharges problem may exist.

Improving the early diagnostic of prostate cancer by multiple biomarker detection with new biosensing devices

Prostate cancer (PCa) is the most common form of cancer in men, in Europe (World Health Organization data). The most recent statistics, in Portuguese territory, confirm this scenario, which states that about 50% of Portuguese men may suffer from prostate cancer and 15% of these will die from this condition. Its early detection is therefore fundamental. This is currently being done by Prostate Specific Antigen (PSA) screening in urine but false positive and negative results are quite often obtained and many patients are sent to unnecessary biopsy procedures. This early detection protocol may be improved, by the development of point-of-care cancer detection devices, not only to PSA but also to other biomarkers recently identified. Thus, the present work aims to screen several biomarkers in cultured human prostate cell lines, serum and urine samples, developing low cost sensors based on new synthetic biomaterials. Biomarkers considered in this study are the following: prostate specific antigen (PSA), annexin A3 (ANXA3), microseminoprotein-beta (MSMB) and sarcosine (SAR). The biomarker recognition may occurs by means of molecularly imprinted polymers (MIP), which are a kind of plastic antibodies, and enzymatic approaches. The growth of a rigid polymer, chemically stable, using the biomarker as a template allows the synthesis of the plastic antibody. MIPs show high sensitivity/selectivity and present much longer stability and much lower price than natural antibodies. This nanostructured material was prepared on a carbon solid. The interaction between the biomarker and the sensing-material produces electrical signals generating quantitative or semi-quantitative data. These devices allow inexpensive and portable detection in point-of-care testing.

The early metallurgy in Southwestern Iberia: metals from the Chalcolithic Settlement of São Pedro (Redondo)

Archaeological excavations carried out in the archaeological site of São Pedro (Southern Portugal) revealed a Chalcolithic settlement occupied in different moments of the 3rd millennium BC. The material culture recovered includes different types of materials, such as ceramics, lithics and metals. The later comprises about 30 artefacts with different typologies such as tools (e.g. awls, chisels and a saw) and weapons (e.g. daggers and arrowheads) mostly belonging to the 2nd and 3rd quarter of the 3rd millennium BC. In the present work the collection of chalcolithic metallic artefacts recovered in São Pedro was characterized. Analytical studies involved micro energy dispersive X-ray fluorescence spectrometry (micro-EDXRF) to determine elemental composition, together with optical microscopy and Vickers microhardness testing for microstructural characterisation and hardness determination. Main results show copper with variable amounts of arsenic and very low content of other impurities, such as iron. Moreover, nearly half of the collection is composed by arsenical copper alloys (As > 2 wt.%) and an association was found between arsenic content and typology since the weapons group (mostly daggers) present higher values than tools (mostly awls). These results suggest some criteria in the selection of arsenic-rich copper ores or smelting products. Furthermore, after casting an artefact would have been hammered, annealed and sometimes, finished with a hammering operation. Additionally, microstructural variations in this collection reveal somewhat different operational conditions during casting, annealing and forging, as expected in such a primitive metallurgy. Moreover the operational sequence seems to be used to achieve the required shape to the object, rather than to intentionally make the alloy harder. Overall, this study suggests that Chalcolithic metallurgists might have a poor control of the addition of arsenic and/or were unable to use this element to increase the hardness of tools and weapons. Finally, the compositions, manufacturing processes and hardness were compared to those from neighbouring regions and different chronological periods.

On the function of the floccular complex of the vertebrate cerebellum: implications in paleoneuroanatomy

The cerebellum floccular complex lobes (FCLs) are housed in the FCL fossa of the periotic complex. There is experimental evidence indicating that the FCLs integrate visual and vestibular information, responsible for the vestibulo-ocular reflex, vestibulo-collic reflex, smooth pursuit and gaze holding. Thus, the behavior of extinct animals has been correlated with FCLs dimension in multiple paleoneuroanatomy studies. Here I analyzed braincase endocasts of a representative sample of Mammalia (48 species) and Aves (59 species) rendered using tomography and image segmentation and tested statistical correlations between the floccular complex volume, ecological and behavioral traits to assess various previously formulated paleobiological speculations. My results demonstrate: 1) there is no significant correlation between relative FCL volume and body mass; 2) there is no significant correlation between relative FCL and optic lobes size in birds; 3) average relative FCL size is larger in diurnal than in nocturnal birds but there is no statistically significant difference in mammals; 4) feeding strategies are related with different FCL size patterns in birds, but not in mammals; 5) locomotion type is not related with relative FCL size in mammals; 6) agility is not significantly correlated with FCL size in mammals. I conclude that, despite the apparent relation between FCL size and ecology in birds, the cerebellum of tetrapods is a highly plastic structure and may be adapted to control different functions across different taxonomic levels. For example, the european mole (Talpa europaea) which is fossorial and practically blind, has a FCL fossae relative size larger than those of bats, which are highly maneuverable. Therefore, variation in FCL size may be better explained by a combination of multiple factors with relation to anatomical and phylogenetic evolutionary constraints.

Proboscideans and other vertebrates from Anchrif, Morocco

The paleontological richness of Morocco has been scientifically known since at least the early 20th century. The region of the Middle Atlas, more specifically the Boulemane area, has been however only sparsely studied since the 60’s when it supplied various vertebrate fossils from the Middle Jurassic.In the beginning of the 2000’s some fossil bones were discovered in a new fossil-site near the village of Taghrout, in the Boulemane area and in September 2013 a Moroccan-Portuguese expedition made excavations in the site with the help locals from the village of Taghrout. The site is Pleistocene in age and is located on a rare bone bearing small high-altitude sedimentary basin, non-charted in previous geological maps. The excavations yielded new bone material from large mammals. The most common findings are elephants ascribed to the genus Elephas, but artiodactyls, turtles, and in-situ hominid Acheulean tools were also collected. During the excavation campaign the Jurassic sites were revisited and new dinosaur trails and possible crocodilomorph bones were discovered. Surface collection of in a cave near Taghrout with Holocene mammal material, including the genera Canis, Capra, Bos, Panthera and Hystrix was also conducted and its fossils elements identified.