Hypertensive Disorders during Pregnancy and Risk of Bronchopulmonary Dysplasia in Very Preterm Infants.

 It is not yet fully known whether hypertensive disorders (HTD) during pregnancy impose an increased risk of development of bronchopulmonary dysplasia (BPD) in preterm newborn infants. OBJECTIVE:  To test the hypothesis that preeclampsia and other HTD are associated with the development of BPD in preterm infants. MATERIALS AND METHODS:  Data on mothers and preterm infants with gestational age 24 to 30 weeks were prospectively analyzed in 11 Portuguese level III centers. Statistical analysis was performed using IBM SPSS statistics 23. RESULTS:  A total of 494 preterm infants from 410 mothers were enrolled, and 119 (28%) of the 425 babies, still alive at 36 weeks, developed BPD. The association between chronic arterial hypertension, chronic arterial hypertension with superimposed preeclampsia, and gestational hypertension in mothers and BPD in preterm infants was not significant (p = 0.115; p = 0.248; p = 0.060, respectively). The association between preeclampsia-eclampsia and BPD was significant (p = 0.007). The multivariate analysis revealed an association between preeclampsia-eclampsia and BPD (odds ratio [OR] = 4.6; 95% confidence interval [CI] 1.529-13.819; p = 0.007) and a protective effect for BPD when preeclampsia occurred superimposed on chronic arterial hypertension in mothers (OR = 0.077; 95%CI 0.009-0.632; p = 0.017). CONCLUSION:  The results of this study support the association of preeclampsia in mothers with BPD in preterm babies and suggest that chronic hypertension may be protective for preterm babies.info:eu-repo/semantics/publishedVersio

Thyroid Metastasis as the Initial Presentation of an Asymptomatic Clear Cell Renal Carcinoma

Introdução: A metastização para a glândula tiroideia de um carcinoma renal de células claras é rara e só diagnosticável após análise imunohistoquímica de uma amostra histológica. O objetivo deste artigo é reportar um caso de metastização tiroideia como primeira manifestação de um carcinoma renal de células claras. Caso Clínico: Doente do sexo masculino com um nódulo sólido no lobo esquerdo da tiróide, com 5,3 cm, suspeito de malignidade, submetido a tiroidectomia total com linfadenectomia do compartimento central. A análise histológica concluiu serem duas metástases de carcinoma renal de células claras. Após estudo dirigido ao rim, o doente foi submetido a nefrectomia radical quatro meses depois. Discussão: O interesse deste caso reside no facto de a metastização para a tiroide como primeira manifestação de carcinoma renal de células claras ser rara mas, se tratada precocemente, permite uma ‘dupla resseção cirúrgica’ que pode levar a sobrevidas aos cinco anos de 80%

The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression

© 2014 Elsevier Inc.Proper chromosome segregation during meiosis requires the assembly of the synaptonemal complex (SC) between homologous chromosomes. However, the SC structure itself is indifferent to homology, andpoorly understood mechanisms that depend on conserved HORMA-domain proteins prevent ectopic SC assembly. Although HORMA-domain proteins are thought to regulate SC assembly as intrinsic components of meiotic chromosomes, here we uncover a key role for nuclear soluble HORMA-domain protein HTP-1 in the quality control of SC assembly. We show that a mutant form of HTP-1 impaired in chromosome loading provides functionality of an HTP-1-dependent checkpoint that delays exit from homology search-competent stages until all homolog pairs are linked by the SC. Bypassing of this regulatory mechanism results in premature meiotic progression and licensing of homology-independent SC assembly. These findings identify nuclear soluble HTP-1 as a regulator of early meiotic progression, suggesting parallels with the mode of action of Mad2 in the spindle assembly checkpoint

The impact of population-level HbA1c screening on reducing diabetes diagnostic delay in middle-aged adults: a UK Biobank analysis

This is the final version. Available on open access from Springer via the DOI in this recordData availability: UK Biobank data are available through a procedure described at http://www.ukbiobank.ac.uk/using-the-resource/Aims/hypothesis Screening programmes can detect cases of undiagnosed diabetes earlier than symptomatic or incidental diagnosis. However, the improvement in time to diagnosis achieved by screening programmes compared with routine clinical care is unclear. We aimed to use the UK Biobank population-based study to provide the first population-based estimate of the reduction in time to diabetes diagnosis that could be achieved by HbA1c-based screening in middle-aged adults. Methods We studied UK Biobank participants aged 40–70 years with HbA1c measured at enrolment (but not fed back to participants/clinicians) and linked primary and secondary healthcare data (n=179,923) and identified those with a pre-existing diabetes diagnosis (n=13,077, 7.3%). Among the remaining participants (n=166,846) without a diabetes diagnosis, we used an elevated enrolment HbA1c level (≥48 mmol/mol [≥6.5%]) to identify those with undiagnosed diabetes. For this group, we used Kaplan–Meier analysis to assess the time between enrolment HbA1c measurement and subsequent clinical diabetes diagnosis up to 10 years, and Cox regression to identify clinical factors associated with delayed diabetes diagnosis. Results In total, 1.0% (1703/166,846) of participants without a diabetes diagnosis had undiagnosed diabetes based on calibrated HbA1c levels at UK Biobank enrolment, with a median HbA1c level of 51.3 mmol/mol (IQR 49.1–57.2) (6.8% [6.6–7.4]). These participants represented an additional 13.0% of diabetes cases in the study population relative to the 13,077 participants with a diabetes diagnosis. The median time to clinical diagnosis for those with undiagnosed diabetes was 2.2 years, with a median HbA1c at clinical diagnosis of 58.2 mmol/mol (IQR 51.0–80.0) (7.5% [6.8–9.5]). Female participants with lower HbA1c and BMI measurements at enrolment experienced the longest delay to clinical diagnosis. Conclusions/interpretation Our population-based study shows that HbA1c screening in adults aged 40–70 years can reduce the time to diabetes diagnosis by a median of 2.2 years compared with routine clinical care. The findings support the use of HbA1c screening to reduce the time for which individuals are living with undiagnosed diabetes.Research EnglandNational Institute for Health Research (NIHR)Wellcome Trus

The trend is our friend: Risk parity, momentum and trend following in global asset allocation

We examine applying a trend following methodology to global asset allocation between equities, bonds, commodities and real estate. This strategy offers substantial improvement in risk-adjusted performance compared to buy-and-hold portfolios and a superior method of asset allocation than risk parity. We believe the discipline of trend following overcomes many of the behavioural biases investors succumb to, such as regret and herding, and offers a solution to the inappropriate sequence of returns which can be problematic for decumulation portfolios. The other side of behavioural biases is that they may be exploited by investors: an example is momentum investing where herding leads to continuation of returns and has been identified across many assets. Momentum and trend following differ as the former is a relative concept and the latter absolute. Combining both can achieve the higher return levels associated with momentum portfolios with much reduced volatility and drawdowns due to trend following. Measures based on utility of a representative investor reinforce the superiority of combining trend following with momentum strategies. These techniques help address the sequencing of returns issue which can be a serious issue for financial planning

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

Cetuximab plus platinum-based chemotherapy in head and neck Squamous Cell Carcinoma: a retrospective study in a single Comprehensive European Cancer Institution

Background: The use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort. Patients and Methods: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. Results: The median patient age was 53 (37-78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316) and PFS of 8 months (CI 95%, 6.051-9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%). Conclusions: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.info:eu-repo/semantics/publishedVersio

Interpreting Meta-Analyses of Genome-Wide Association Studies

Meta-analysis is an increasingly popular tool for combining multiple genome-wide association studies in a single analysis to identify associations with small effect sizes. The effect sizes between studies in a meta-analysis may differ and these differences, or heterogeneity, can be caused by many factors. If heterogeneity is observed in the results of a meta-analysis, interpreting the cause of heterogeneity is important because the correct interpretation can lead to a better understanding of the disease and a more effective design of a replication study. However, interpreting heterogeneous results is difficult. The standard approach of examining the association p-values of the studies does not effectively predict if the effect exists in each study. In this paper, we propose a framework facilitating the interpretation of the results of a meta-analysis. Our framework is based on a new statistic representing the posterior probability that the effect exists in each study, which is estimated utilizing cross-study information. Simulations and application to the real data show that our framework can effectively segregate the studies predicted to have an effect, the studies predicted to not have an effect, and the ambiguous studies that are underpowered. In addition to helping interpretation, the new framework also allows us to develop a new association testing procedure taking into account the existence of effect