Quality of life returns from basic research

<p>Abstract</p> <p>Background</p> <p>Assessing the consequences of research is an increasingly important task in research and innovation policy. This paper takes a broader view of those consequences than the conventional economic approach, placing researchers and their activities in the centre of the assessment process and examining results for professional practice and general education as well as contributions to knowledge.</p> <p>Methods</p> <p>The paper uses historical and documentary analysis to illustrate the approach, focusing on U.S. biomedicine over the past century. At aggregate level, the analysis attributes portions of the change in aggregate health indicators to research and research-based institutions, through several available types of logic: either through correlations between timing of institutional changes and changes in the indicators or through direct or indirect causal connections.</p> <p>Results</p> <p>The analysis shows that while biomedical research has certainly contributed to improved health in the United States, other factors have also contributed. In some ways the institutional structure of science-based medicine has worked against creating benefits for some groups in U.S. society.</p> <p>Conclusions</p> <p>The paper concludes with a call for more strategic attention to dimensions of impact other than knowledge outcomes and for participatory planning for research.</p

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

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

Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The yield of charged particles associated with high-$p_{\rm T}$ trigger particles ($8 < p_{\rm T} < 15$ GeV/$c$) is measured with the ALICE detector in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV relative to proton-proton collisions at the same energy. The conditional per-trigger yields are extracted from the narrow jet-like correlation peaks in azimuthal di-hadron correlations. In the 5% most central collisions, we observe that the yield of associated charged particles with transverse momenta $p_{\rm T}> 3$ GeV/$c$ on the away-side drops to about 60% of that observed in pp collisions, while on the near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/350

Post-Traumatic Stress in Head and Neck Cancer Survivors and their Partners

The publisher's agreement states that: Author(s) retain the right to make an AAM (Author's Accepted Manuscript )of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period. An acknowledgement in the following form should be included, together with a link to the published version on the publisher's website: “This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]”.The publisher's agreement states that: Author(s) retain the right to make an AAM (Author's Accepted Manuscript )of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period. An acknowledgement in the following form should be included, together with a link to the published version on the publisher's website: “This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]”.The publisher's agreement states that: Author(s) retain the right to make an AAM (Author's Accepted Manuscript )of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period. An acknowledgement in the following form should be included, together with a link to the published version on the publisher's website: “This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]”.The publisher's agreement states that: Author(s) retain the right to make an AAM (Author's Accepted Manuscript )of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period. An acknowledgement in the following form should be included, together with a link to the published version on the publisher's website: “This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]”.The publisher's agreement states that: Author(s) retain the right to make an AAM (Author's Accepted Manuscript )of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period. An acknowledgement in the following form should be included, together with a link to the published version on the publisher's website: “This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]”.The publisher's agreement states that: Author(s) retain the right to make an AAM (Author's Accepted Manuscript )of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period. An acknowledgement in the following form should be included, together with a link to the published version on the publisher's website: “This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]”.The publisher's agreement states that: Author(s) retain the right to make an AAM (Author's Accepted Manuscript )of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period. An acknowledgement in the following form should be included, together with a link to the published version on the publisher's website: “This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]”.The publisher's agreement states that: Author(s) retain the right to make an AAM (Author's Accepted Manuscript )of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period. An acknowledgement in the following form should be included, together with a link to the published version on the publisher's website: “This is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]”.Purpose: Head and neck cancer (HNC) diagnosis and treatment are distressing and have immediate detrimental impacts on functioning and quality of life (QoL). Nevertheless, little is known about long-term psychosocial effects. The aim of this study was to determine the prevalence and correlates of clinical post-traumatic stress disorder (PTSD) and subclinical post-traumatic stress symptoms (PTSS) in HNC patients surviving more than 2 years since treatment and in their partners. Methods: HNC survivors identified from the cancer registry of a London hospital and their partners completed measures of PTSS, depression and anxiety, fear of cancer recurrence, social support, appearance concerns and health-related QoL. Data regarding their clinical and demographic characteristics were also collected. Correlations, as well as linear and logistic regression coefficients, were calculated to estimate associations with PTSS scores. Results: In this analysis of 93 HNC survivors, at a mean of 6 years (SD = 4) after treatment, 33.4% reported PTSS and 11.8% met the criteria for post-traumatic stress disorder (PTSD). Fear of cancer recurrence was independently associated with PTSS (p  .05). Conclusions: This is the first examination of post-traumatic stress in survivors of HNC and shows that high levels of cancer-related PTSS exist for many years after diagnosis in both patients and their partners.Doctoral Scholarship from Saving Faces—The Facial Surgery Research Foundation

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Performance of the ALICE experiment at the CERN LHC

ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables

Elliptic flow of identified hadrons in Pb-Pb collisions at 1asNN = 2.76 TeV

The elliptic flow coefficient (v2) of identified particles in Pb-Pb collisions at 1asNN = 2.76 TeV was measured with the ALICE detector at the Large Hadron Collider (LHC). The results were obtained with the Scalar Product method, a two-particle corre- lation technique, using a pseudo-rapidity gap of | 06\u3b7| > 0.9 between the identified hadron under study and the reference particles. The v2 is reported for \u3c0\ub1, K\ub1, K0S, p+p, \u3c6, \u39b+\u39b, \u39e 12+\u39e+ and \u3a9 12+\u3a9+ in several collision centralities. In the low transverse momentum (pT) region, pT 3 GeV/c