Association of BRAFV600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers

Background: Studies have demonstrated an association of the BRAFV600E mutation and microRNA (miR) expression with aggressive clinicopathologic features in papillary thyroid cancer (PTC). Analysis of BRAFV600E mutations with miR expression data may improve perioperative decision making for patients with PTC, specifically in identifying patients harboring central lymph node metastases (CLNM). Methods: Between January 2012 and June 2013, 237 consecutive patients underwent total thyroidectomy and prophylactic central lymph node dissection (CLND) at four endocrine surgery centers. All tumors were tested for the presence of the BRAFV600E mutation and miR-21, miR-146b-3p, miR-146b-5p, miR-204, miR-221, miR-222, and miR-375 expression. Bivariate and multivariable analyses were performed to examine associations between molecular markers and aggressive clinicopathologic features of PTC. Results: Multivariable logistic regression analysis of all clinicopathologic features found miR-146b-3p and miR-146b-5p to be independent predictors of CLNM, while the presence of BRAFV600E almost reached significance. Multivariable logistic regression analysis limited to only predictors available preoperatively (molecular markers, age, sex, and tumor size) found miR-146b-3p, miR-146b-5p, miR-222, and BRAFV600E mutation to predict CLNM independently. While BRAFV600E was found to be associated with CLNM (48% mutated in node-positive cases vs. 28% mutated in node-negative cases), its positive and negative predictive values (48% and 72%, respectively) limit its clinical utility as a stand-alone marker. In the subgroup analysis focusing on only classical variant of PTC cases (CVPTC), undergoing prophylactic lymph node dissection, multivariable logistic regression analysis found only miR-146b-5p and miR-222 to be independent predictors of CLNM, while BRAFV600E was not significantly associated with CLNM. Conclusion: In the patients undergoing prophylactic CLNDs, miR-146b-3p, miR-146b-5p, and miR-222 were found to be predictive of CLNM preoperatively. However, there was significant overlap in expression of these miRs in the two outcome groups. The BRAFV600E mutation, while being a marker of CLNM when considering only preoperative variables among all histological subtypes, is likely not a useful stand-alone marker clinically because the difference between node-positive and node-negative cases was small. Furthermore, it lost significance when examining only CVPTC. Overall, our results speak to the concept and interpretation of statistical significance versus actual applicability of molecular markers, raising questions about their clinical usefulness as individual prognostic markers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140269/1/thy.2015.0378.pd

Impact of Intraoperative Parathyroid Hormone Monitoring on the Prediction of Multiglandular Parathyroid Disease

Optimal interpretation of the results of intraoperative parathyroid hormone (IOPTH) monitoring during neck exploration for primary hyperparathyroidism (pHPT) is still controversial. The reliability of the “50% rule” in multiglandular disease (MGD) is often disputed, mostly because of competing pathophysiologic paradigms. The aim of this study was to ascertain and corroborate the ability of IOPTH monitoring to detect MGD in a practice, combining conventional and alternative parathyroidectomy techniques. This is a retrospective single institution analysis of 69 consecutive patients undergoing cervical exploration for pHPT by various approaches. The IOPTH measurements were performed after induction of anesthesia but prior to skin incision and 10 minutes after excision of the first visualized enlarged parathyroid gland. In this series, 55 patients (80%) had single adenomas, and 14 patients (20%) had MGD. In 8 of the 14 patients with MGD, IOPTH levels were obtained sequentially after removal of every enlarged gland. Of these 8 patients, 6 (75%) had a false-positive decrease (decrease below 50% of baseline value in presence of another enlarged gland) failing to predict the presence of a second enlarged gland. In 2 cases IOPTH monitoring provided a true-negative result, correctly predicting MGD. If MGD is defined by gross morphologic criteria, IOPTH monitoring fails to predict the presence of MGD reliably. However, if MGD is defined by functional criteria, the course of these patients does not seem significantly affected. The importance of these findings must be further investigated, especially with regard to the outcome of minimally invasive parathyroid procedures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41301/1/268_2003_Article_7255.pd

Reinvigorating the sustainable development research agenda: the role of the sustainable development goals (SDG)

© 2017 Informa UK Limited, trading as Taylor & Francis Group. The United Nations Sustainable Development Goals (UN SDGs) contain a set of 17 measures to foster sustainable development across many areas. It offers a good opportunity to reinvigorate sustainable development research for two main reasons. First, it comprises many areas of SD research, which have become mainstream thanks to the UN SDGs. Second, the fact that the UN and its member countries have committed to attaining SDGs by 2030 has added a sense of urgency to the need to perform quality research on SD on the one hand, and reiterates the need to use the results of this research on the other. Even though the basic concept of sustainability goes back many centuries, it has only recently appeared on the international political agenda. This is partly due to an awakening of the fact that the human ecological pressure on the planet is still much larger than what nature can renew or compensate for. Based on this state of affairs, this paper presents an outline of the process leading to the agreement on the UN SDGs, and looks at some of the ecological aspects as a result of continued pressure of human activities on natural resources. Furthermore, a set of research needs is proposed–also based holistically on updated research trends–discussing the degree of urgency of some measures and explaining why the UN SDGs need to be accorded greater priority in international sustainable development research efforts

Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model

<div><p>Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids and reduced macroscopic and microscopic lesions whereas intranasal vaccination with experimental M2e epitope-based subunit vaccines did not. The results further highlight the importance using IAV-S type specific vaccines in pigs.</p></div

Trends in Utilization of Adrenalectomy in the United States: Have Indications Changed?

Minimally invasive approaches have dramatically reduced morbidity associated with adrenalectomy. There has been concern that an increased frequency of adrenal imaging along with the advantages of less morbidity could influence the indications for adrenalectomy. We tested the hypothesis that adrenalectomy has become more common over time and that benign diseases have been increasingly represented among procedural indications. The Nationwide Inpatient Sample (NIS) database was utilized to determine the incidence of adrenalectomy and the associated surgical indications in the United States between 1988 and 2000. All discharged patients were identified whose primary ICD-9-CM procedure code was for adrenalectomy, regardless of the specific surgical approach (laparoscopic adrenalectomy was not reliably coded). This subset was then queried for associated ICD-9-CM diagnostic codes. Linear regression and t -tests were utilized to determine the significance of trends. The total number of adrenalectomies increased significantly, from 12.9 per 100,000 discharges in 1988 to 18.5 per 100,000 discharges in 2000 ( p = 0.000003). The total number of adrenalectomies with a primary ICD-9-CM code for malignant adrenal neoplasm did not increase significantly: from 1.2 per 100,000 discharges in 1988 to 1.6 per 100,000 discharges in 2000 ( p = 0.47). The total number of adrenalectomies with a primary ICD-9-CM diagnostic code for benign adrenal neoplasm increased significantly, from 2.8 per 100,000 discharges in 1988 to 4.8 per 100,000 discharges in 2000 ( p = 0.00002). The average percentage of adrenalectomies performed for malignant neoplasm was significantly higher during the period 1988–1993 when compared to 1994–2000 (11% vs. 9%; p = 0.002). The average percentage of adrenalectomies performed for benign neoplasm was significantly lower during 1988–1993 when compared to 1994–2000 (25% vs. 28%; p = 0.015). Adrenalectomy is being performed with increasing frequency. This is associated with an increase in the proportion of adrenalectomies performed for benign neoplasms. Assuming no significant change in disease prevalence during the study period, these data suggest that indications for adrenalectomy may have changed somewhat over that period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41300/1/268_2004_Article_7619.pd

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP)(1). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed(2-6). Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions(7), is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions(8,9), but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results(10,11), indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.Peer reviewe

Search for a common baryon source in high-multiplicity pp collisions at the LHC

We report on the measurement of the size of the particle-emitting source from two-baryon correlations with ALICE in high-multiplicity pp collisions at s=13 TeV. The source radius is studied with low relative momentum p–p, p‾–p‾, p–Λ, and p‾–Λ‾ pairs as a function of the pair transverse mass mT considering for the first time in a quantitative way the effect of strong resonance decays. After correcting for this effect, the radii extracted for pairs of different particle species agree. This indicates that protons, antiprotons, Λ s, and Λ‾ s originate from the same source. Within the measured mT range (1.1–2.2) GeV/c2the invariant radius of this common source varies between 1.3 and 0.85 fm. These results provide a precise reference for studies of the strong hadron–hadron interactions and for the investigation of collective properties in small colliding systems. © 2020 CERN for the benefit of the ALICE CollaborationPeer reviewe

Long- and short-range correlations and their event-scale dependence in high-multiplicity pp collisions at 1as = 13 TeV

Two-particle angular correlations are measured in high-multiplicity proton-proton collisions at s = 13 TeV by the ALICE Collaboration. The yields of particle pairs at short-( 06\u3b7 3c 0) and long-range (1.6 < | 06\u3b7| < 1.8) in pseudorapidity are extracted on the near-side ( 06\u3c6 3c 0). They are reported as a function of transverse momentum (pT) in the range 1 < pT< 4 GeV/c. Furthermore, the event-scale dependence is studied for the first time by requiring the presence of high-pT leading particles or jets for varying pT thresholds. The results demonstrate that the long-range \u201cridge\u201d yield, possibly related to the collective behavior of the system, is present in events with high-pT processes as well. The magnitudes of the short- and long-range yields are found to grow with the event scale. The results are compared to EPOS LHC and PYTHIA 8 calculations, with and without string-shoving interactions. It is found that while both models describe the qualitative trends in the data, calculations from EPOS LHC show a better quantitative agreement for the pT dependency, while overestimating the event-scale dependency. [Figure not available: see fulltext.

Inclusive J/ψ production at forward and backward rapidity in p-Pb collisions at √sNN=8.16 TeV

Inclusive J/psi production is studied in p-Pb interactions at a centre-of-mass energy per nucleon-nucleon collision sqrt(s_NN) = 8.16TeV, using the ALICE detector at the CERN LHC. The J/psi meson is reconstructed, via its decay to a muon pair, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and -4.46 < ycms < -2.96, where positive and negative ycms refer to the p-going and Pb-going direction, respectively. The transverse momentum coverage is pT < 20 GeV/c. In this paper, ycms- and pT-differential cross sections for inclusive J/psi production are presented, and the corresponding nuclear modification factors RpPb are shown. Forward results show a suppression of the J/psi yield with respect to pp collisions, concentrated in the region pT < 5 GeV/c. At backward rapidity no significant suppression is observed. The results are compared to previous measurements by ALICE in p-Pb collisions at sqrt(s_NN) = 5.02TeV and to theoretical calculations. Finally, the ratios RFB between forward- and backward-ycms RpPb values are shown and discussed

Global baryon number conservation encoded in net-proton fluctuations measured in Pb–Pb collisions at √sNN = 2.76 TeV

Experimental results are presented on event-by-event net-proton fluctuation measurements in Pb–Pb collisions at √SNN=2.76 TeV, recorded by the ALICE detector at the CERN LHC. These measurements have as their ultimate goal an experimental test of Lattice QCD (LQCD) predictions on second and higher order cumulants of net-baryon distributions to search for critical behavior near the QCD phase boundary. Before confronting them with LQCD predictions, account has to be taken of correlations stemming from baryon number conservation as well as fluctuations of participating nucleons. Both effects influence the experimental measurements and are usually not considered in theoretical calculations. For the first time, it is shown that event-by-event baryon number conservation leads to subtle long-range correlations arising from very early interactions in the collisions.publishedVersio