Neolithic transitions: can genetic data help us understand a major demographic event in human prehistory?

Dissertation presented to obtain the Ph.D degree in Biology

Bioengineering of Lactococcus lactis through modulation of its major glucose transporter

Dissertation to obtain the Master Degree in Biotechnology

Variation in Haemodynamic Monitoring for Major Surgery in European Nations: Secondary Analysis of the EuSOS Dataset

BACKGROUND: The use of cardiac output monitoring may improve patient outcomes after major surgery. However, little is known about the use of this technology across nations. METHODS: This is a secondary analysis of a previously published observational study. Patients aged 16 years and over undergoing major non-cardiac surgery in a 7-day period in April 2011 were included into this analysis. The objective is to describe prevalence and type of cardiac output monitoring used in major surgery in Europe. RESULTS: Included in the analysis were 12,170 patients from the surgical services of 426 hospitals in 28 European nations. One thousand four hundred and sixteen patients (11.6 %) were exposed to cardiac output monitoring, and 2343 patients (19.3 %) received a central venous catheter. Patients with higher American Society of Anesthesiologists (ASA) scores were more frequently exposed to cardiac output monitoring (ASA I and II, 643 patients [8.6 %]; ASA III-V, 768 patients [16.2 %]; p < 0.01) and central venous catheter (ASA I and II, 874 patients [11.8 %]; ASA III-V, 1463 patients [30.9 %]; p < 0.01). In elective surgery, 990 patients (10.8 %) were exposed to cardiac output monitoring, in urgent surgery 252 patients (11.7 %) and in emergency surgery 173 patients (19.8 %). A central venous catheter was used in 1514 patients (16.6 %) undergoing elective, in 480 patients (22.2 %) undergoing urgent and in 349 patients (39.9 %) undergoing emergency surgery. Nine hundred sixty patients (7.9 %) were monitored using arterial waveform analysis, 238 patients (2.0 %) using oesophageal Doppler ultrasound, 55 patients (0.5 %) using a pulmonary artery catheter and 44 patients (2.0 %) using other technologies. Across nations, cardiac output monitoring use varied from 0.0 % (0/249 patients) to 27.5 % (19/69 patients), whilst central venous catheter use varied from 5.6 % (7/125 patients) to 43.2 % (16/37 patients). CONCLUSIONS: One in ten patients undergoing major surgery is exposed to cardiac output monitoring whilst one in five receives a central venous catheter. The use of both technologies varies widely across Europe.

Mutations in the MECP2 Gene Are Not a Major Cause of Rett Syndrome-Like or Related Neurodevelopmental Phenotype in Male Patients

Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls, but mutations in the causative MECP2 gene have also been identified in boys with classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome-like phenotype; the patients had diverse clinical presentations that included perturbations of the autistic spectrum, microcephaly, mental retardation, manual stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2 gene, including the detection of large rearrangements, and we did not detect any pathogenic mutations in the MECP2 gene in these patients, in whom the genetic basis of disease remained unidentified. Thus, additional genes should be screened in this group of patients.

Perfil de internamentos por Depressão Major no SNS português nos anos de 2008 e 2013 : variação em período de crise económica

RESUMO - O início da crise económica global colocou Portugal num contexto de restrição orçamental que gerou repercussões em várias áreas, especificamente na saúde mental das pessoas, evidenciadas a partir de 2009. O objetivo deste trabalho foi analisar o impacto da crise económica no perfil de internamentos por Depressão Major na população em idade ativa nos hospitais do SNS em Portugal Continental. Tratou-se de um estudo epidemiológico, observacional, descritivo e transversal. Foi efetuada uma análise individual, concretizada através da análise dos episódios de internamento; e ecológica, ao nível de distritos; nos anos de 2008 e 2013. Foram analisados dados relativos aos episódios de internamento, à população em idade ativa e às camas de internamento de psiquiatria. Os resultados permitem afirmar que os distritos com menores índices de urbanização e de densidade populacional apresentaram taxas de internamento por Depressão Major, na população em idade ativa, mais elevadas, e os seus habitantes apresentaram um risco de internamento superior, em ambos os períodos. Observou-se um aumento da taxa de internamentos e do risco de internamento por Depressão Major, na maioria dos distritos, no período de crise económica. Adicionalmente, verificou-se que a taxa de internamentos foi influenciada positivamente pelo número de camas disponíveis e ocorreu um aumento do número de internamentos por Depressão Major por cama de internamento disponível, no período de crise económica. Este estudo, de carater exploratório e com limitações identificadas, permitiu observar a variação geográfica e temporal do internamento por Depressão Major fomentando a necessidade de investigação futura neste âmbito.

The patent expiry as a major inflection point in a branded Rx drug's life and strategies to counter generic competition - exemplified at Pfizer's blockbuster drug Lipitor in the USA

A large number of expensive, but highly profitable branded prescription drugs will go off-patent in the USA between 2011 and 2015. Their revenues are crucial to fund the immense costs associated with the development of an innovative drug. The rising cost pressure on pharmaceutical stakeholders has increased the demand for more affordable medications, as provided by the branded drug's generic counterpart. Yet, research based incumbents are moving beyond the traditional late lifecycle strategies and deploy more aggressive tactics in order to protect their brands, as seen with Pfizer's Lipitor!. It is doubtful, whether these efforts will help the blockbuster business model to resist current market conditions.

Factors associated with a diagnosis of major depression among HIV-infected elderly patients

Introduction Acquired immunodeficiency syndrome (AIDS) is being increasingly reported among the elderly and major depression (MD) may be associated with suboptimal adherence to treatment. Methods Cross-sectional study on factors associated with MD among 72 HIV-infected elderly individuals. Results Twenty (27.7%) patients were found to have MD. The female gender (odds ratio [OR] = 10.65; p = 0.00586), a low CD4 count during the study (OR = 1.005247; p = 0.01539), and current smoking status (OR = 12.89; p = 0.01693) were independently associated with MD. Conclusions Our data underscore the need to attentively search and treat MD among HIV-infected elderly patients.

The existence of only one haplotype of Leishmania major in the main and potential reservoir hosts of zoonotic cutaneous leishmaniasis using different molecular markers in a focal area in Iran

IntroductionLeishmania major is the causative agent of zoonotic cutaneous leishmaniasis (ZCL), and great gerbils are the main reservoir hosts in Iran. Abarkouh in central Iran is an emerging focal point for which the reservoir hosts of ZCL are unclear. This research project was designed to detect any Leishmania parasites in different wild rodent species.MethodsAll rodents captured in 2011 and 2012 from Abarkouh district were identified based on morphological characteristics and by amplification of the rodent cytochrome b (Cyt b) gene. To detect Leishmania infection in rodents, deoxyribonucleic acid (DNA) of each ear was extracted. Internal transcribed spacer-ribosomal deoxyribonucleic acid (ITS-rDNA), microsatellites, kinetoplast deoxyribonucleic acid (kDNA) and cytochrome b genes of Leishmania parasites were amplified by polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) and sequencing were employed to confirm the Leishmania identification.ResultsOf 68 captured rodents in the region, 55 Rhombomys opimus were identified and nine Leishmaniainfections (9/55) were found. In addition, eight Meriones libycus and two Tatera indicawere sampled, and one of each was confirmed to be infected. Two Meriones persicus and one Mus musculuswere sampled with no infection.ConclusionsThe results showed that all 11 unambiguously positive Leishmania infections were Leishmania major. Only one haplotype of L. major(GenBank access No. EF413075) was found and at least three rodents R. opimus, M. libycus and T. indica—appear to be the main and potential reservoir hosts in this ZCL focus. The reservoir hosts are variable and versatile in small ZCL focal locations.

Insider threats: the major challenge to security risk management

Security risk management is by definition, a subjective and complex exercise and it takes time to perform properly. Human resources are fundamental assets for any organization, and as any other asset, they have inherent vulnerabilities that need to be handled, i.e. managed and assessed. However, the nature that characterize the human behavior and the organizational environment where they develop their work turn these task extremely difficult, hard to accomplish and prone to errors. Assuming security as a cost, organizations are usually focused on the efficiency of the security mechanisms implemented that enable them to protect against external attacks, disregarding the insider risks, which are much more difficult to assess. All these demands an interdisciplinary approach in order to combine technical solutions with psychology approaches in order to understand the organizational staff and detect any changes in their behaviors and characteristics. This paper intends to discuss some methodological challenges to evaluate the insider threats and its impacts, and integrate them in a security risk framework, that was defined according to the security standard ISO/IEC_JTC1, to support the security risk management process.

Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review

Objectives: The therapeutic effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BMs) as an outcome. Therefore, our aim was to review noninvasive brain stimulation trials in depression using BMs. Methods: The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and transcranial direct current stimulation as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. Results: Of 1234 potential articles, 52 articles were included. Only studies using TMS were found. Biological markers included immune and endocrine serum markers, neuroimaging techniques, and electrophysiological outcomes. In 12 articles (21.4%), end point BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. Biological marker outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. Conclusions: Functional magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, cortical excitability, and brain-derived neurotrophic factor consistently showed positive results. Brain-derived neurotrophic factor was the best predictor of patients’ likeliness to respond. These initial results are promising; however, all studies investigating BMs are small, used heterogeneous samples, and did not take into account confounders such as age, sex, or family history. Based on our findings, we recommend further studies to validate BMs in noninvasive brain stimulation trials in MDD.

On the length of bank-firm relationships: an empirical application to a major French bank

NIPE - WP 01/ 2016

60,000 years of interactions between Central and Eastern Africa documented by major African mitochondrial haplogroup L2

Mitochondrial DNA (mtDNA) haplogroup L2 originated in Western Africa but is nowadays spread across the entire continent. L2 movements were previously postulated to be related to the Bantu expansion, but L2 expansions eastwards probably occurred much earlier. By reconstructing the phylogeny of L2 (44 new complete sequences) we provide insights on the complex net of within-African migrations in the last 60 thousand years (ka). Results show that lineages in Southern Africa cluster with Western/Central African lineages at a recent time scale, whereas, eastern lineages seem to be substantially more ancient. Three moments of expansion from a Central African source are associated to L2: (1) one migration at 70-50 ka into Eastern or Southern Africa, (2) postglacial movements (15-10 ka) into Eastern Africa; and (3) the southward Bantu Expansion in the last 5 ka. The complementary population and L0a phylogeography analyses indicate no strong evidence of mtDNA gene flow between eastern and southern populations during the later movement, suggesting low admixture between Eastern African populations and the Bantu migrants. This implies that, at least in the early stages, the Bantu expansion was mainly a demic diffusion with little incorporation of local populations.

Long-term prognosis of geriatric major depression in relation to cognition and white matter integrity: follow up of two cases

INTRODUCTION: The geriatric depression (GD) represents one of the most frequent psychiatric disorders in outpatient services specialized in old-age treatment. OBJECTIVE: The course of two illustrative cases of GD is discussed, highlighting its clinical picture after antidepressant treatment and underlining variables related to disease prognosis, treatment effectiveness and conversion to major cognitive disorders such as vascular dementia (VD). METHODS: The cognitive performance, depressive symptoms, autonomy and brain structural measurements as white matter hyperintensities (WMH) and hippocampal size, and microstructural integrity of WM with diffusion tensor imaging were followed during four years. RESULTS: Case 1, with a severe degree of WMH, was associated with worsening cognition and increasing functional disability. Case 2, with mild WMH, an improvement of cognitive functioning could be seen. CONCLUSIONS: The existence of different subtypes of GD, as presented in this report, points a pathophysiological heterogeneity of GD, and suggests a possible continuum vascular depression (VaDp) and vascular cognitive impairment (VCI).

Assessing cardiorespiratory capacity in older adults with major depression and Alzheimer disease

ABSTRACT Objective To assess cardiorespiratory capacity through subjective and objective tests in older adults diagnosed with major depression (MDD), Alzheimer disease (AD) and healthy older adults. Methods Fifty seven subjects (72 ± 7.9 years) were divided into three groups: MDD (n = 20), AD (n = 17) and Healthy (n = 20). The subjects answered Hamilton Scale (HAM-D), Mini-Mental State Examination (MMSE), Veterans Specific Activity Questionnaire (VSAQ) and 2-minute Step test. Results MDD and AD showed lower scores than healthy group for Nomogram VSAQ (p < 0.001) and 2-minute Step (p = 0.009; p = 0.008, respectively). Adjusted for age and educational level, no differences among groups were observed for Step (MDD, p = 0.097; AD, p = 0.102). AD group did not present differences to healthy group for Step, when adjusting for MMSE (p = 0.261). Conclusions Despite the lower cardiorespiratory fitness of elderly patients with DM and DA have been found in both evaluations, the results should be viewed with caution, since the tests showed low correlation and different risk classifications of functional loss. In addition, age, level educational and cognitive performance are variables that can influence the performance objective evaluation.

Differential predictors of acute post-surgical pain intensity after abdominal hysterectomy and major joint arthroplasty

Author's personal copy