Transatlantic Brokers. A global history of Jean Monnet’s network 1914-1943

Jean Monnet, possibly the most important actor during the first post-war decades of European integration, is constantly described in the literature as part of a network that included several influential individuals in Europe and in the United States who, at different moments, held key positions. An important aspect in this regard is that some of Monnet’s transatlantic friends promoted European integration and contributed to a cross-fertilization process across the Atlantic. Considering that most of the authors either list a number of people as being part of this network, or focus on particular individuals’ relationship with Monnet, it is fair to ask to what extent his network helped him in pursuing his goals, if Monnet was simply accepted, and why, in already existing networks, if we can consider his as a transatlantic working group and if we can retrace in this story elements of continuity and long durée that can contribute to the historiography of early European Integration. Considering new trends and interpretations that highlight the role played by networks, examination of Monnet’s techniques and his reliance on his transatlantic connections reveal important findings about his relationship with policymakers, shading also a light on important features of XX century diplomatic and transatlantic history. This dissertation’s attempt, therefore, is to define these as elements of continuity throughout the formative years of one of founding fathers of the Integration process.

Unlocking ecological history using fish remains: Eco-evolutionary consequences of exploitation in the Atlantic bluefin tuna

During recent decades, the health of ocean ecosystems and fish populations has been threatened by overexploitation, pollution, and anthropogenic-driven climate change. Due to a lack of long-term data, we have a poor understanding of when intensive exploitation began and what impact anthropogenic activities have had on the ecology and evolution of fishes. Such information is crucial to recover degraded and depleted marine ecosystems and fish populations, maximise their productivity in-line with historical levels, and predict their future dynamics. In this thesis, I evaluate anthropogenic impacts on the iconic Atlantic bluefin tuna (Thunnus thynnus; BFT), one of the longest and recently most intensely exploited marine fishes, with a tremendous cultural and economic importance. Using a long-time series of archaeological and archived faunal remains (bones) dating back to approximately two millennia ago, I apply morphological, isotopic, and genomic techniques to perform the first studies on long-term BFT size and growth, diet and habitat use, and demography and adaptation, and produce the first genome-wide data on this species. My findings suggest that exploitation had impacted BFT foraging behaviour by the ~16th century when coastal ecosystem degradation induced a pelagic shift in diet and habitat use. I reveal that BFT biomass began to decline much earlier than hitherto documented, by the 19th century, consistent with intensive tuna trap catches during this period and catch-at-size increasing. I find that BFT juvenile growth had increased by the early 1900s (and more dramatically by the 21st century) which may reflect an evolutionary response to size selective harvest–which I find putative genomic signatures of. Further, I observed that BFT foraging behaviours have been modified following overexploitation during the 20th century, which previously included a isotopically distinct, Black Sea niche. Finally, I show that despite biomass declining from centuries ago, BFT has retained genomic diversity.

TiMMing: developing an innovative suite of bioinformatic tools to harmonize and track the origin of copy number alterations in the evolutive history of multiple myeloma

Multiple Myeloma (MM) is a hematologic cancer with heterogeneous and complex genomic landscape, where Copy Number Alterations (CNAs) play a key role in the disease's pathogenesis and prognosis. It is of biological and clinical interest to study the temporal occurrence of early alterations, as they play a disease "driver" function by deregulating key tumor pathways. This study presents an innovative bioinformatic tools suite created for harmonizing and tracing the origin of CNAs throughout the evolutionary history of MM. To this aim, large cohorts of newly-diagnosed MM (NDMM, N=1582) and Smoldering-MM (SMM, N=282) were aggregated. The tools developed in this study enable the harmonization of CNAs as obtained from different genomic platforms in such a way that a high statistical power can be obtained. By doing so, the high numerosity of those cohorts was harnessed for the identification of novel genes characterized as "driver" (NFKB2, NOTCH2, MAX, EVI5 and MYC-ME2-enhancer), and the generation of an innovative timing model, implemented with a statistical method to introduce confidence intervals in the CNAs-calls. By applying this model on both NDMM and SMM cohorts, it was possible to identify specific CNAs (1q(CKS1B)amp, 13q(RB1)del, 11q(CCND1)amp and 14q(MAX)del) and categorize them as "early"/ "driver" events. A high level of precision was guaranteed by the narrow confidence intervals in the timing estimates. These CNAs were proposed as critical MM alterations, which play a foundational role in the evolutionary history of both SMM and NDMM. Finally, a multivariate survival model was able to identify the independent genomic alterations with the greatest effect on patients’ survival, including RB1-del, CKS1B-amp, MYC-amp, NOTCH2-amp and TRAF3-del/mut. In conclusion, the alterations that were identified as both "early-drivers” and correlated with patients’ survival were proposed as biomarkers that, if included in wider survival models, could provide a better disease stratification and an improved prognosis definition.

High temporal resolution insights into early life histories: integrating histomorphometric, trace element and isotopic analyses of dental hard tissues in archaeological populations from Italy

Teeth, with their high mineralisation, incremental growth, and lack of remodelling, serve as biological archives that document an individual's development. This project aims to utilise the potential of teeth in bioarchaeological studies to achieve three primary objectives: 1) to investigate the application of histological and histochemical methods in reconstructing developmental bio-chronologies and early life histories; 2) to refine the temporal precision of isotopic analysis of dentine collagen by developing a novel protocol that integrates micro-sampling techniques with high-resolution histomorphometrics; and 3) to synthesise data from enamel and dentine for a comprehensive understanding of early life development and dietary transitions. This study adopts an integrated multidisciplinary bioarchaeological approach, conducting histomorphometric analysis on enamel and dentine across deciduous and permanent dentitions. It applies high-temporal resolution trace element analysis to enamel using LA-ICPMS and δ13C and δ15N isotope analyses through sequential micro-sampling to dentine of permanent teeth. Samples were selected from diverse archaeological contexts across the Italian peninsula, covering the Upper Palaeolithic, Copper Age, and Early Medieval periods, providing insight into diachronic variations in infant development and life history. Findings highlight the efficacy of histological and histochemical techniques in accurately determining growth rates, physiological stress, dietary shifts (particularly timing of weaning), and age at death in infant remains. The consistency and comparison between enamel and dentine underscores the enhanced insight obtained from integrating information from both tissues. Importantly, the newly proposed protocol significantly improves the temporal accuracy of dentine collagen analysis, facilitating precise chronological placement of the results over broad developmental associations. This study reaffirms the significance of teeth as valuable bioarchaeological instruments. By introducing and testing multidisciplinary methods, it provides deeper insights into early life history and cultural practices across diverse chronological contexts, highlighting the importance of advanced methodologies in extracting detailed, accurate, and nuanced information from past populations.

Fractalkine (cx3cl1) Is Involved In The Early Activation Of Hypothalamic Inflammation In Experimental Obesity.

Hypothalamic inflammation is a common feature of experimental obesity. Dietary fats are important triggers of this process, inducing the activation of toll-like receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells, which are the cellular components of the innate immune system in the brain, are expected to play a role in the early activation of diet-induced hypothalamic inflammation. Here, we use bone marrow transplants to generate mice chimeras that express a functional TLR4 in the entire body except in bone marrow-derived cells or only in bone marrow-derived cells. We show that a functional TLR4 in bone marrow-derived cells is required for the complete expression of the diet-induced obese phenotype and for the perpetuation of inflammation in the hypothalamus. In an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly induced in the neurons of the hypothalamus after the introduction of a high-fat diet. The inhibition of hypothalamic fractalkine reduces diet-induced hypothalamic inflammation and the recruitment of bone marrow-derived monocytic cells to the hypothalamus; in addition, this inhibition reduces obesity and protects against diet-induced glucose intolerance. Thus, fractalkine is an important player in the early induction of diet-induced hypothalamic inflammation, and its inhibition impairs the induction of the obese and glucose intolerance phenotypes.

Neonatal Outcomes Of Late Preterm And Early Term Birth.

To compare neonatal deaths and complications in infants born at 34-36 weeks and six days (late preterm: LPT) with those born at term (37-41 weeks and six days); to compare deaths of early term (37-38 weeks) versus late term (39-41 weeks and six days) infants; to search for any temporal trend in LPT rate. A retrospective cohort study of live births was conducted in the Campinas State University, Brazil, from January 2004 to December 2010. Multiple pregnancies, malformations and congenital diseases were excluded. Control for confounders was performed. The level of significance was set at p<0.05. After exclusions, there were 17,988 births (1653 late preterm and 16,345 term infants). A higher mortality in LPT versus term was observed, with an adjusted odds ratio (OR) of 5.29 (p<0.0001). Most complications were significantly associated with LPT births. There was a significant increase in LPT rate throughout the study period, but no significant trend in the rate of medically indicated deliveries. A higher mortality was observed in early term versus late term infants, with adjusted OR: 2.43 (p=0.038). LPT and early term infants have a significantly higher risk of death.

Newborn Hearing Screening And Early Diagnostic In The Nicu.

The aim was to describe the outcome of neonatal hearing screening (NHS) and audiological diagnosis in neonates in the NICU. The sample was divided into Group I: neonates who underwent NHS in one step and Group II: neonates who underwent a test and retest NHS. NHS procedure was automated auditory brainstem response. NHS was performed in 82.1% of surviving neonates. For GI, referral rate was 18.6% and false-positive was 62.2% (normal hearing in the diagnostic stage). In GII, with retest, referral rate dropped to 4.1% and false-positive to 12.5%. Sensorineural hearing loss was found in 13.2% of infants and conductive in 26.4% of cases. There was one case of auditory neuropathy spectrum (1.9%). Dropout rate in whole process was 21.7% for GI and 24.03% for GII. We concluded that it was not possible to perform universal NHS in the studied sample or, in many cases, to apply it within the first month of life. Retest reduced failure and false-positive rate and did not increase evasion, indicating that it is a recommendable step in NHS programs in the NICU. The incidence of hearing loss was 2.9%, considering sensorineural hearing loss (0.91%), conductive (1.83%) and auditory neuropathy spectrum (0.19%).

Hypothermia And Early Neonatal Mortality In Preterm Infants.

To evaluate intervention practices associated with hypothermia at both 5 minutes after birth and at neonatal intensive care unit (NICU) admission and to determine whether hypothermia at NICU admission is associated with early neonatal death in preterm infants. This prospective cohort included 1764 inborn neonates of 22-33 weeks without malformations admitted to 9 university NICUs from August 2010 through April 2012. All centers followed neonatal International Liaison Committee on Resuscitation recommendations for the stabilization and resuscitation in the delivery room (DR). Variables associated with hypothermia (axillary temperature <36.0 °C) 5 minutes after birth and at NICU admission, as well as those associated with early death, were analyzed by logistic regression. Hypothermia 5 minutes after birth and at NICU admission was noted in 44% and 51%, respectively, with 6% of early neonatal deaths. Adjusted for confounding variables, practices associated with hypothermia at 5 minutes after birth were DR temperature <25 °C (OR 2.13, 95% CI 1.67-2.28), maternal temperature at delivery <36.0 °C (OR 1.93, 95% CI 1.49-2.51), and use of plastic bag/wrap (OR 0.53, 95% CI 0.40-0.70). The variables associated with hypothermia at NICU admission were DR temperature <25 °C (OR 1.44, 95% CI 1.10-1.88), respiratory support with cold air in the DR (OR 1.40, 95% CI 1.03-1.88) and during transport to NICU (OR 1.51, 95% CI 1.08-2.13), and cap use (OR 0.55, 95% CI 0.39-0.78). Hypothermia at NICU admission increased the chance of early neonatal death by 1.64-fold (95% CI 1.03-2.61). Simple interventions, such as maintaining DR temperature >25 °C, reducing maternal hypothermia prior to delivery, providing plastic bags/wraps and caps for the newly born infants, and using warm resuscitation gases, may decrease hypothermia at NICU admission and improve early neonatal survival.

[how The Gynecologist Can Guide Women With A Family History Of Cancer?].

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[the Modified Us7 Score In The Assessment Of Synovitis In Early Rheumatoid Arthritis].

To evaluate the modified US7 score (MUS7 score SYN) in the assessment of patients with early rheumatoid arthritis (ERA). In addition, dorsal and palmar recesses of the wrists as well as of small joints of the hands and feet were examined for the presence of synovitis by means of a global assessment of joints. The study sample comprised 32 patients treated for arthritis, with an average disease duration of 13 months. An ultrasound machine with high frequency transducer was used. Hands were also X-rayed and analysed by Larsen score. Out of the 832 examined joints, synovitis was detected in 173 (20,79%), tenosynovitis in 22 (4,91%), and erosions in 3 (1,56%). Synovitis was predominantly detected in the dorsal recess (73,38%) of MCP and PIP joints, when compared with palmar recess (26%). The presence of synovitis in the joints evaluated correlated with clinical (HAQ-DI, DAS28), laboratory (ACPA, RF, CRP), and ultrasound results (r = 0,37 to r = 0,42; p = 0,04 to p = 0,003). We found correlation of the MUS7 score SYN of the gray scale US or of the power Doppler US with DAS28 (PCR) values (r = 0,38; p = 0,0332), and with CRP results (r = 0,39; p = 0,0280), respectively. The dorsal recess, the wrist, and small joints can be considered as important sites to detect synovitis by the MUS7 score SYN in patients with ERA.

Facial Changes After Early Treatment Of Unilateral Coronal Synostosis Question The Necessity Of Primary Nasal Osteotomy.

The premature fusion of unilateral coronal suture can cause a significant asymmetry of the craniofacial skeleton, with an oblique deviation of the cranial base that negatively impacts soft tissue facial symmetry. The purpose of this study was to assess facial symmetry obtained in patients with unilateral coronal synostosis (UCS) surgically treated by 2 different techniques. We hypothesized that nasal deviation should not be addressed in a primary surgical correction of UCS. Consecutive UCS patients were enrolled in a prospective study and randomly divided into 2 groups. In group 1, the patients underwent total frontal reconstruction and transferring of onlay bone grafts to the recessive superior orbital rim (n = 7), and in group 2, the patients underwent total frontal reconstruction and unilateral fronto-orbital advancement (n = 5). Computerized photogrammetric analysis measured vertical and horizontal axis of the nose and the orbital globe in the preoperative and postoperative periods. Intragroup and intergroup comparisons were performed. Intragroup preoperative and postoperative comparisons showed a significant (all P < 0.05) reduction of the nasal axis and the orbital-globe axis in the postoperative period in the 2 groups. Intergroup comparisons showed no significant difference (all P > 0.05). Facial symmetry was achieved in the patients with UCS who underwent surgery regardless of surgical approach evaluated here. Our data showed a significant improvement in nasal and orbital-globe deviation, leading us to question the necessity of primary nasal correction in these patients.

Prospects For Early Investigational Therapies For Sickle Cell Disease.

Sickle cell disease (SCD) is a genetic disorder characterized by the production of abnormal hemoglobin that polymerizes at low oxygen concentrations, causing the erythrocyte to adopt a sickle-shaped morphology. SCD pathophysiology is extremely complex and can lead to numerous clinical complications, including painful vaso-occlusive crises (VOC), end-organ damage, and a shortened lifespan. An impressive number of investigational drugs are currently in early stages of clinical development with prospects for use either as chronic therapies to reduce VOC frequency and end-organ damage in SCD or for use at the time of VOC onset. Many of these agents have been developed using a pathophysiological-based approach to SCD, targeting one or more of the mechanisms that contribute to the disease process. It is plausible that a multi-drug approach to treating the disease will evolve in the coming years, whereby hydroxyurea (HU) (the only drug currently FDA-approved for SCD) is used in combination with drugs that amplify nitric oxide signaling and/or counteract hemolytic effects, platelet activation and inflammation.

Spontaneous puberty in girls with early diagnosis of Turner syndrome

OBJECTIVE: To verify if the frequency of spontaneous pubertal development among girls with Turner syndrome (TS) diagnosed in infancy and childhood is greater than that of patients diagnosed later. SUBJECTS AND METHODS: Thirty three girls aged < 10 years at the time of diagnosis were evaluated regarding pubertal development. The frequency of spontaneous puberty was compared with that of girls aged > 13 years diagnosed at the same service. RESULTS: Sixteen of 32 informative patients had signs of spontaneous puberty, a frequency greater than that of patients diagnosed later. In six patients, there was no progression of puberty; menarche occurred in six, and one became pregnant, but the fetus was a stillborn. Spontaneous puberty was absent in all cases with 45,X karyotype. CONCLUSIONS: The greater prevalence of spontaneous puberty in girls whose diagnosis was not based on pubertal delay suggests that, among those diagnosed later, there is a bias towards patients with hypogonadism. Arq Bras Endocrinol Metab. 2012;56(9):653-7

As artes marciais chinesas para pessoas com deficiência : contextos, dilemas e possibilidades = Chinese martial arts for people with disabilities : contexts, dilemmas and possibilities

Universidade Estadual de Campinas . Faculdade de Educação Física

Escala de autoaceitação para pessoas com cegueira congênita ou precoce : desenvolvimento e investigação psicométrica = Self-acceptance acale for people with congenital or early blindness : development and psychometric analysis

Universidade Estadual de Campinas . Faculdade de Educação Física