Childhood Maltreatment and BMI Trajectories to Mid-Adult Life: Follow-Up to Age 50y in a British Birth Cohort.

Childhood maltreatment including abuse and neglect has been associated with adult obesity, but evidence on life-course development of obesity or BMI gain is unclear. We aim to establish whether childhood maltreatments are related to obesity or BMI at different life-stages 7y-50y and to identify possible explanations for associations

KRAS early testing. Consensus initiative and cost-effectiveness evaluation for metastatic colorectal patients in an italian setting

KRAS testing is relevant for the choice of the most appropriate first-line therapy of metastatic colorectal cancer (CRC). Strategies for preventing unequal access to the test should be implemented, but their relevance in the practice is related to economic sustainability. The study adopted the Delphi technique to reach a consensus on several topics. Issues related to execution of KRAS testing were identified by an expert's board and proposed to 108 Italian oncologists and pathologists through two subsequent questionnaires. The emerging proposal was evaluated by decision analyses models employed by technology assessment agencies in order to assess cost-effectiveness. Alternative therapeutic strategies included most commonly used chemotherapy regimens alone or in combination with cetuximab or bevacizumab. The survey indicated that time interval for obtaining KRAS test should not exceed 15 days, 10 days being an optimal interval. To assure the access to proper treatment, a useful strategy should be to anticipate the test after radical resection in patients at high risk of relapse. Early KRAS testing in high risk CRC patients generates incremental cost-effectiveness ratios between 6,000 and 13,000 Euro per quality adjusted life year (QALY) gained. In extensive sensitivity analyses ICER's were always below 15,000 Euro per QALY gained, far within the threshold of 60,000 Euro/QALY gained accepted by regulatory institutions in Italy. In metastatic CRC a time interval higher than 15 days for result of KRAS testing limits access to therapeutic choices. Anticipating KRAS testing before the onset of metastatic disease in patients at high risk does not affect the sustainability and cost-effectiveness profile of cetuximab in first-line mCRC. Early KRAS testing may prevent this inequality in high-risk patients, whether they develop metastases, and is a cost-effective strategy. Based on these results, present joined recommendations of Italian societies of Oncology and Pathology should be updated including early KRAS testing

O crescimento recente do agronegócio brasileiro.

Carta da Agricultur

Detection of a variable ultra-fast outflow in the Narrow Line Seyfert 1 galaxy PG 1448+273

Relativistically blueshifted absorption features of highly ionised ions, the so-called ultra-fast outflows (UFOs), have been detected in the X-ray spectra of a number of accreting supermassive black holes. If these features truly originate from accretion disc winds accelerated to more than 10 per cent of the speed of light, their energy budget is very significant and they can contribute to or even drive galaxy-scale feedback from active galactic nuclei (AGN). However, the UFO spectral features are often weak due to high ionisation of the outflowing material, and the inference of the wind physical properties can be complicated by other spectral features in AGN such as relativistic reflection. Here we study a highly accreting Narrow Line Seyfert 1 galaxy PG 1448+273. We apply an automated, systematic routine for detecting outflows in accreting systems and achieve an unambiguous detection of a UFO in this AGN. The UFO absorption is observed in both soft and hard X-ray bands with the XMM-Newton observatory. The velocity of the outflow is (26900 +- 600) km/s (~0.09c), with an ionisation parameter of log ({\xi} / erg cm s^-1)=4.03_{-0.08}^{+0.10} and a column density above 10^23 cm^-2. At the same time, we detect weak warm absorption features in the spectrum of the object. Our systematic outflow search suggests the presence of further multi-phase wind structure, but we cannot claim a significant detection considering the present data quality. The UFO is not detected in a second, shorter observation with XMM-Newton, indicating variability in time, observed also in other similar AGN.Comment: Accepted for publication in MNRAS. 14 pages, 11 figures, 1 tabl

A 'p-n' diode with hole and electron-doped lanthanum manganite

The hole-doped manganite La0.7Ca0.3MnO3 and the electron-doped manganite La0.7Ce0.3MnO3 undergo an insulator to metal transition at around 250 K, above which both behave as a polaronic semiconductor. We have successfully fabricated an epitaxial trilayer (La0.7Ca0.3MnO3/SrTiO3/La0.7Ce0.3MnO3), where SrTiO3 is an insulator. At room temperature, i.e. in the semiconducting regime, it exhibits asymmetric current-voltage (I-V) characteristics akin to a p-n diode. The observed asymmetry in the I-V characteristics disappears at low temperatures where both the manganite layers are metallic. To the best of our knowledge, this is the first report of such a p-n diode, using the polaronic semiconducting regime of doped manganites.Comment: PostScript text and 2 figures, to be published in Appl. Phys. Lett

Attachment, Physiological and Familial Vulnerability in Childhood Obesity: an Interactive Multisystem Approach

The aims of the present study were to test the association between insecure attachment and basal cortisol and catecholamines levels in a sample of obese children. The role of familial vulnerability and gender was also investigated. Methods: Cortisol and catecholamines levels of 8- to 13-year olds obese children were measured. Self-report questionnaires were used to assess attachment pattern and current anxiety and depression, and parent-report questionnaires were used to assess attachment, current anxiety and depression and familial vulnerability. Linear regression analyses were performed for individuals that scored low versus high on parental internalizing problems, and for boys and girls, separately. Results: In the group with high parental internalizing problems, insecure attachment was significantly associated with reduced basal levels of cortisol, in boys (p=0.007, b= -0.861, R2= 73.0%). In the group with low parental internalizing problems, the association between insecure attachment and cortisol was not significant in either boys or girls, and it was negative in boys (p=0.075, b= -0.606, R2= 36.7%) and positive in girls (p=0.677, b= 0.176, R2= 3.1%) . Conclusions: Apparently, physiological risk factors for psicopathology in obesity are more evident in individuals with a high familial vulnerability. In addition, patterns of physiological risk for psicopathology in obesity are different in boys and girls. Therefore, it is important to take into account familial vulnerability and gender when investigating physiological risk factors for psycopathology in obesity. Insecure attachment in childhood may be a risk factor for obesity. Interventions to increase children's attachment security should examine the effects on children's weight

The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness

Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-029780; POCI-01-0145-FEDER-007274; POCI-01-0145-FEDER-029780) and National Funds through the Foundation for Science and Technology (FCT), under the projects: PTDC/BBB-EBI/0567/2014 (to C.A.R.), PTDC/MED-QUI/29780/2017 (to CG), and UID/BIM/04293 supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). F.P. was funded by FCT cofinanced by Fundo Social Europeu-FSE with a grant with reference: SFRH/BPD/115730/2016