The primary fibrin polymerization pocket: Three-dimensional structure of a 30-kDa C-terminal γ chain fragment complexed with the peptide Gly-Pro-Arg-Pro

After vascular injury, a cascade of serine protease activations leads to the conversion of the soluble fibrinogen molecule into fibrin. The fibrin monomers then polymerize spontaneously and noncovalently to form a fibrin gel. The primary interaction of this polymerization reaction is between the newly exposed N-terminal Gly-Pro-Arg sequence of the α chain of one fibrin molecule and the C-terminal region of a γ chain of an adjacent fibrin(ogen) molecule. In this report, the polymerization pocket has been identified by determining the crystal structure of a 30-kDa C-terminal fragment of the fibrin(ogen) γ chain complexed with the peptide Gly-Pro-Arg-Pro. This peptide mimics the N terminus of the α chain of fibrin. The conformational change in the protein upon binding the peptide is subtle, with electrostatic interactions primarily mediating the association. This is consistent with biophysical experiments carried out over the last 50 years on this fundamental polymerization reaction.

Cost effectiveness of shortening screening interval or extending age range of NHS breast screening programme: computer simulation study

Objective: To compare the cost effectiveness of two possible modifications to the current UK screening programme: shortening the screening interval from three to two years and extending the age of invitation to a final screen from 64 to 69.

Lack of the DNA repair protein O6-methylguanine-DNA methyltransferase in histologically normal brain adjacent to primary human brain tumors.

Exposure to exogenous alkylating agents, particularly N-nitroso compounds, has been associated with increased incidence of primary human brain tumors, while intrinsic risk factors are currently unknown. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a major defense against the carcinogenicity of N-nitroso compounds and other alkylators. We report here that in 55% (64/117) of cases, histologically normal brain tissue adjacent to primary human brain tumors lacked detectable MGMT activity [methyl excision repair-defective (Mer-) status]. The incidence of Mer- status in normal brain tissue from brain tumor patients was age-dependent, increasing from 21% in children 0.25-19 years of age to 75% in adults over 50. In contrast, Mer- status was found in 12% (5/43) of normal brain specimens from patients operated for conditions other than primary brain tumors and was not age-dependent. The 4.6-fold elevation in incidence of Mer- status in brain tumor patients is highly significant (chi2 = 24; p < or = 0.001). MGMT activity was independent of age in the lymphocytes of brain tumor patients and was present in lymphocytes from six of nine tumor patients whose normal brain specimen was Mer-. DNA polymerase beta, apurinic/apyrimidinic endonuclease, and lactate dehydrogenase activities were present in all specimens tested, including Mer- specimens from brain tumor patients. Our data are consistent with a model of carcinogenesis in human brain in which epigenetically regulated lack of MGMT is a predisposing factor and alkylation-related mutagenesis is a driving force.

Integrating Evidence-Based Practice in the Training Programme Bachelor’s Degree in Nursing, University Jaume I

The Evidence-Based Practice (EBP) aims to combine a form methodological process of professional experience in health with the most current information on the clinical situation. The professional novice can make better decisions despite lacking sufficient years in clinical practice. We then train the student in correct habits within the methodological process by which you can strengthen both their knowledge and their attitude and ability, allowing secure customs, where all of your work is based on PBE.

Factors Associated with the Cessation of Intimate Partner Violence in Women Attending Primary Care in Spain

This study aimed to identify factors associated with the likelihood of IPV cessation among women attending Spanish primary healthcare. Of the 2465 women who reported lifetime IPV, 36.1 % stated that violence had ceased. Those women not currently abused had higher levels of education and social support, were workers or students, and had no dependent children. When IPV duration was less than 5 years, the likelihood of cessation was two times higher than when IPV continued beyond 5 years. For women who have experienced physical IPV, the probability of ending the violent relationship was 10 times higher than for those suffering from psychological IPV. The implications of the findings regarding clinical significance and future research are discussed.

Violence against young women attending primary care services in Spain: prevalence and health consequences

Background. There are a significant number of studies assessing the negative health consequences of violence against women. However, a limited number of studies analyse the health consequences of violence committed against young women by different types of aggressors. Objectives. The goal of this study is to assess the prevalence of interpersonal violence against young women in Spain and analyse its impact on the physical and mental health of the victims. Methods. A total of 1076 women aged 18–25 years attending Spanish primary care services were selected. We estimated the prevalence of interpersonal violence and compared the health data and demographic characteristics of abused and non-abused young women, multi-logistic regression models were fitted. The Wald test was used to assess whether there were differences in the negative health consequences of intimate partner (IPV) versus non-IPV. Results. As many as 27.6% young women reported a history of abuse, of whom 42.7% had been assaulted by their partner, 41.1% by someone other than their partner and 16.2% both by their partner and another person. The distribution of social and demographic characteristics was similar for IPV and non-IPV victims. Young abused women were three times more likely to suffer psychological distress and have somatic complaints, and they were four times more likely to use medication as compared to non-abused women. Conclusion. Our results suggest that all forms of violence compromise young women’s health seriously. Including patients’ history of abuse in their health record may help make more informed clinical decisions and provide a more integrated care.

Effectiveness of influenza vaccination programme in preventing hospital admissions, Valencia, 2014/15 early results

Preliminary results for the 2014/15 season indicate low to null effect of vaccination against influenza A(H3N2)-related disease. As of week 5 2015, there have been 1,136 hospital admissions, 210 were due to influenza and 98% of subtype A strains were H3. Adjusted influenza vaccine effectiveness was 33% (range: 6–53%) overall and 40% (range: 13% to 59%) in those 65 years and older. Vaccination reduced by 44% (28–68%) the probability of admission with influenza.

Using realist evaluation to assess primary healthcare teams’ responses to intimate partner violence in Spain

Objective: Few evaluations have assessed the factors triggering an adequate health care response to intimate partner violence. This article aimed to: 1) describe a realist evaluation carried out in Spain to ascertain why, how and under what circumstances primary health care teams respond to intimate partner violence, and 2) discuss the strengths and challenges of its application. Methods: We carried out a series of case studies in four steps. First, we developed an initial programme theory (PT1), based on interviews with managers. Second, we refined PT1 into PT2 by testing it in a primary healthcare team that was actively responding to violence. Third, we tested the refined PT2 by incorporating three other cases located in the same region. Qualitative and quantitative data were collected and thick descriptions were produced and analysed using a retroduction approach. Fourth, we analysed a total of 15 cases, and identified combinations of contextual factors and mechanisms that triggered an adequate response to violence by using qualitative comparative analysis. Results: There were several key mechanisms —the teams’ self-efficacy, perceived preparation, women-centred care—, and contextual factors —an enabling team environment and managerial style, the presence of motivated professionals, the use of the protocol and accumulated experience in primary health care—that should be considered to develop adequate primary health-care responses to violence. Conclusion: The full application of this realist evaluation was demanding, but also well suited to explore a complex intervention reflecting the situation in natural settings.

Effects of Dialogic Reading in the Improvement of Reading Comprehension in Students of Primary Education

Reading is an essential factor for success at school that requires certain skills and strategies of great complexity rarely taught in schools. Verbalization of comprehension strategies can be considered an effective measure in learning to read. The purpose of this study was to analyze the effect of a program of teaching reading strategies implemented through interactive dialogic reading groups in the learning of reading comprehension. A quasi-experimental comparison with pretest and posttest design between groups was used. A sample of 355 participants aged between 8 and 9 years aged was used. The results weigh the potential value of the program and support the development of teaching models that integrate dialogic reading practices as they facilitate learning of reading comprehension.

Fundamental rights in the EU: three years after Lisbon, the Luxembourg perspective. Research Paper in Law (Cooperative Research Paper) 02/2013

For more than 10 years after the signature of the Treaty of Rome in 1957, the question of the protection of human rights had never been in issue. The emphasis was on the creation and consolidation of the common market establishing the free movement of persons, of services, of goods and of capital. Neither the initial Treaties nor the jurisprudence of the Court made any reference to the protection of human rights in the process of the creation of the common market. It all started in 1969 in the Stauder case with this very short sentence: “Interpreted in this way the provision at issue contains nothing capable of prejudicing the fundamental human rights enshrined in the general principles of Community law and protected by the Court”. Forty years later, with the adoption of the Treaty of Lisbon, which came into force on 1 December 2009, fundamental rights are part of primary law. The achievement has been remarkable if we consider the very beginning of the process. It is not an exaggeration to say that the Court with its jurisprudence has been the driving force and the source of inspiration for this achievement.

The Civil Society Forum of the Eastern Partnership four years on: Progress, challenges and prospects. CEPS Special Report, January 2014

Established in 2009, during the Eastern Partnership Summit in Prague, the Eastern Partnership Civil Society Forum supports the development of civil society organisations from the EU-28 and the six Partnership countries, namely Armenia, Azerbaijan, Belarus, Georgia, Moldova and Ukraine. After four years of operation, the Secretariat of the Forum’s Steering Committee commissioned CEPS to conduct a comprehensive evaluation of its programme. This report singles out the institutionalisation and socialisation inculcated among its members as the Forum’s greatest accomplishment. In contrast to its internal developments, it argues that the external policy successes of the Forum remain modest. This report is the first attempt to conduct an in-depth assessment of the Forum's Annual Assembly, the Steering Committee and its Secretariat, the Working Groups and National Platforms. Ten actionable recommendations are put forward aimed at improving the Civil Society Forum’s standing and performance.

The European Central Bank’s quantitative easing programme: limits and risks. Bruegel Policy Contribution Issue 2016/04, February 2016

The European Central Bank (ECB) has made a number of significant changes to the original guidelines of its quantitative easing (QE) programme since the programme started in January 2015. These changes are welcome because the original guidelines would have rapidly constrained the programme’s implementation. The changes announced expand the universe of purchasable assets and give some flexibility to the ECB in the execution of its programme. However, this might not be enough to sustain QE throughout 2017, or if the ECB wishes to increase the monthly amount of purchases in order to provide the necessary monetary stimulus to the euro area to bring inflation back to 2 percent. To increase the programme’s flexibility, the ECB could further alter the composition of its purchases. The extension of the QE programme also raises some legitimate questions about its potential adverse consequences. However, the benefits of this policy still outweigh its possible negative implications for financial stability or for inequality. The fear that the ECB’s credibility will be undermined because of its QE programme also seems to be largely unfounded. On the contrary, the primary risk to the ECB’s credibility is the risk of not reaching its 2 percent inflation target, which could lead to expectations becoming disanchored.

Establishment of a confluent monolayer model with human primary trophoblast cells: novel insights into placental glucose transport

STUDY HYPOTHESIS Using optimized conditions, primary trophoblast cells isolated from human term placenta can develop a confluent monolayer in vitro, which morphologically and functionally resembles the microvilli structure found in vivo. STUDY FINDING We report the successful establishment of a confluent human primary trophoblast monolayer using pre-coated polycarbonate inserts, where the integrity and functionality was validated by cell morphology, biophysical features, cellular marker expression and secretion, and asymmetric glucose transport. WHAT IS KNOWN ALREADY Human trophoblast cells form the initial barrier between maternal and fetal blood to regulate materno-fetal exchange processes. Although the method for isolating pure human cytotrophoblast cells was developed almost 30 years ago, a functional in vitro model with primary trophoblasts forming a confluent monolayer is still lacking. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Human term cytotrophoblasts were isolated by enzymatic digestion and density gradient separation. The purity of the primary cells was evaluated by flow cytometry using the trophoblast-specific marker cytokeratin 7, and vimentin as an indicator for potentially contaminating cells. We screened different coating matrices for high cell viability to optimize the growth conditions for primary trophoblasts on polycarbonate inserts. During culture, cell confluency and polarity were monitored daily by determining transepithelial electrical resistance (TEER) and permeability properties of florescent dyes. The time course of syncytia-related gene expression and hCG secretion during syncytialization were assessed by quantitative RT-PCR and enzyme-linked immunosorbent assay, respectively. The morphology of cultured trophoblasts after 5 days was determined by light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Membrane makers were visualized using confocal microscopy. Additionally, glucose transport studies were performed on the polarized trophoblasts in the same system. MAIN RESULTS AND THE ROLE OF CHANCE During 5-day culture, the highly pure trophoblasts were cultured on inserts coated with reconstituted basement membrane matrix . They exhibited a confluent polarized monolayer, with a modest TEER and a size-dependent apparent permeability coefficient (Papp) to fluorescently labeled compounds (MW ∼400-70 000 Da). The syncytialization progress was characterized by gradually increasing mRNA levels of fusogen genes and elevating hCG secretion. SEM analyses confirmed a confluent trophoblast layer with numerous microvilli, and TEM revealed a monolayer with tight junctions. Immunocytochemistry on the confluent trophoblasts showed positivity for the cell-cell adhesion molecule E-cadherin, the tight junction protein 1 (ZO-1) and the membrane proteins ATP-binding cassette transporter A1 (ABCA1) and glucose transporter 1 (GLUT1). Applying this model to study the bidirectional transport of a non-metabolizable glucose derivative indicated a carrier-mediated placental glucose transport mechanism with asymmetric kinetics. LIMITATIONS, REASONS FOR CAUTION The current study is only focused on primary trophoblast cells isolated from healthy placentas delivered at term. It remains to be evaluated whether this system can be extended to pathological trophoblasts isolated from diverse gestational diseases. WIDER IMPLICATIONS OF THE FINDINGS These findings confirmed the physiological properties of the newly developed human trophoblast barrier, which can be applied to study the exchange of endobiotics and xenobiotics between the maternal and fetal compartment, as well as intracellular metabolism, paracellular contributions and regulatory mechanisms influencing the vectorial transport of molecules. LARGE-SCALE DATA Not applicable. STUDY FUNDING AND COMPETING INTERESTS This study was supported by the Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Switzerland, and the Swiss National Science Foundation (grant no. 310030_149958, C.A.). All authors declare that their participation in the study did not involve factual or potential conflicts of interests.

Drift distances, times and primary grain sources of the Arctic Ocean, Exp302 (ACEX)

Knowledge of the long-term history of the perennial ice is an important issue that has eluded study because the Cenozoic core material needed has been unavailable until the recent Arctic Coring Expedition (ACEX). Detrital Fe oxide mineral grains analyzed by microprobe from the last 14 Ma (164 m) of the ACEX composite core on the Lomonosov Ridge were matched to circum-Arctic sources with the same mineral and 12-element composition. These precise source determinations and estimates of drift rates were used to determine that these sand grains could not be rafted to the ACEX core site in less than a year. Thus the perennial ice cover has existed since 14 Ma except for the unlikely rapid return to seasonal ice between the average sampling interval of about 0.17 Ma. Both North America and Russia contributed significant Fe grains to the ACEX core during the last 14 Ma.

AMS C-14 ages of coretops collected on RRS Charles Darwin cruise CD159, July 2004, N. Atlantic, for the NERC RAPID programme

Material and data were collected at 41 sites in the subpolar North Atlantic Ocean between Scotland and Newfoundland, during the RRS CharlesDarwin CD159 cruise in July 2004 (McCave, 2005). Sites were selected to reflect the major inputs of water that becomes the North Atlantic Deep Water (NADW); the Iceland-Scotland Overflow Water (ISOW), the Denmark Strait Overflow Water (DSOW) and the Labrador Sea Water (LSW). Areas cored were the south Iceland Rise, SE Greenland slope/rise and Eirik Drift, and the Labrador margin. A total of 29 box cores, 19 piston cores, 6 kasten cores, 9 short gravity cores and 20 CTD casts as well as 28 surface water samples were collected during the cruise. Here we present sediment core-top sample ages. The cores were sampled at 1 or 0.5 cm intervals and we used the top 1 or 2 cm, depending on availability of foraminifera in the samples. Sediment samples were disaggregated on an end-over-end wheel, wet sieved at >63 um, and dry sieved to 63-150 and >150 um. Accelerator Mass Spectrometer (AMS) radiocarbon dating was done for each core top based on between 900-1600 monospecific planktonic foraminifera (Globigerina bulloides or Neogloboquadrina pachyderma (sinistral)). All dates were of modern or late Holocene age except site RAPID-08-5B (9806 ± 38 uncorrected 14C years BP) and site RAPID-14-10B (11543 ± 40 uncorrected 14C years BP). The >150 um fraction was split until approximately 300 foraminifera remained and counted for number of lithic grains, benthic foraminifera, planktonic foraminifera and foraminifera fragments. In all but the shallowest sample (Greenland rise, 761m water depth) benthic foraminifera constituted less than 2% of the total >150 um fraction of the sample.