Polarized light ions and spectator nucleon tagging at EIC

An Electron-Ion Collider (EIC) with suitable forward detection capabilities would enable a unique experimental program of deep-inelastic scattering (DIS) from polarized light nuclei (deuterium 2H, helium 3He) with spectator nucleon tagging. Such measurements promise significant advances in several key areas of nuclear physics and QCD: (a) neutron spin structure, by using polarized deuterium and eliminating nuclear effects through on-shell extrapolation in the spectator proton momentum; (b) quark/gluon structure of the bound nucleon at x > 0.1 and the dynamical mechanisms acting on it, by measuring the spectator momentum dependence of nuclear structure functions; (c) coherent effects in QCD, by exploring shadowing in tagged DIS on deuterium at x << 0.1. The JLab MEIC design (CM energy sqrt{s} = 15-50 GeV/nucleon, luminosity ~ 10^{34} cm^{-2} s^{-1}) provides polarized deuterium beams and excellent coverage and resolution for forward spectator tagging. We summarize the physics topics, the detector and beam requirements for spectator tagging, and on-going R&D efforts.Comment: 6 pages, 2 figures. Prepared for proceedings of DIS 2014, XXII. International Workshop on Deep-Inelastic Scattering and Related Subjects, University of Warsaw, Poland, April 28 - May 2, 201

Neutron spin structure with polarized deuterons and spectator proton tagging at EIC

The neutron's deep-inelastic structure functions provide essential information for the flavor separation of the nucleon parton densities, the nucleon spin decomposition, and precision studies of QCD phenomena in the flavor-singlet and nonsinglet sectors. Traditional inclusive measurements on nuclear targets are limited by dilution from scattering on protons, Fermi motion and binding effects, final-state interactions, and nuclear shadowing at x << 0.1. An Electron-Ion Collider (EIC) would enable next-generation measurements of neutron structure with polarized deuteron beams and detection of forward-moving spectator protons over a wide range of recoil momenta (0 < p_R < several 100 MeV in the nucleus rest frame). The free neutron structure functions could be obtained by extrapolating the measured recoil momentum distributions to the on-shell point. The method eliminates nuclear modifications and can be applied to polarized scattering, as well as to semi-inclusive and exclusive final states. We review the prospects for neutron structure measurements with spectator tagging at EIC, the status of R&D efforts, and the accelerator and detector requirements.Comment: 11 pages, 3 figures. To appear in proceedings of Tensor Polarized Solid Target Workshop, Jefferson Lab, March 10-12, 201

Diabetes in pregnancy and infant adiposity: systematic review and meta-analysis

Objective: Maternal glycaemia and anthropometry-derived newborn adiposity are strongly correlated. The children of mothers with diabetes are at greater risk of adverse metabolic health, and increased adiposity is a plausible mediator. We undertook a systematic review and meta-analysis to compare adiposity in infants of mothers with (IDM) and without diabetes (NIDM). Design: We identified observational studies reporting adiposity in IDM and NIDM. We searched references, traced forward citations and contacted authors for additional data. We considered all body composition techniques and compared fat mass, fat-free mass, body fat % and skinfold thickness. We used random effects meta-analyses and performed subgroup analyses by maternal diabetes type (type 1, type 2, gestational) and infant sex. We examined the influence of pre-pregnancy BMI and conducted sensitivity analyses. Results: We included data from 35 papers and over 24,000 infants. IDM have greater fat mass than NIDM (mean difference [95% CI]); 83g [49, 117]. Fat mass is greater in infants of mothers with gestational diabetes; 62g [29, 94] and type 1 diabetes; 268g [139, 397]. Insufficient studies reported data for type 2 diabetes separately. Compared with NIDM, fat mass was greater in IDM boys; 87g [30, 145], but not significantly different in IDM girls; 42g [- 33, 116]. There was no attenuation after adjustment for maternal BMI. Conclusions: IDM have significantly greater adiposity in comparison to NIDM. These findings are justification for studies to determine whether measures to reduce infant adiposity will improve later health

The acute management of trauma hemorrhage: a systematic review of randomized controlled trials.

PublishedResearch Support, Non-U.S. Gov'tReviewINTRODUCTION: Worldwide, trauma is a leading cause of death and disability. Haemorrhage is responsible for up to 40% of trauma deaths. Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy. We undertook a systematic review of randomized controlled trials (RCT) which evaluated trauma patients with hemorrhagic shock within the first 24 hours of injury and appraised how the interventions affected three outcomes: bleeding and/or transfusion requirements; correction of trauma induced coagulopathy and mortality. METHODS: Comprehensive searches were performed of MEDLINE, EMBASE, CENTRAL (The Cochrane Library Issue 7, 2010), Current Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) and the National Health Service Blood and Transplant Systematic Review Initiative (NHSBT SRI) RCT Handsearch Database. RESULTS: A total of 35 RCTs were identified which evaluated a wide range of clinical interventions in trauma hemorrhage. Many of the included studies were of low methodological quality and participant numbers were small. Bleeding outcomes were reported in 32 studies; 7 reported significantly reduced transfusion use following a variety of clinical interventions, but this was not accompanied by improved survival. Minimal information was found on traumatic coagulopathy across the identified RCTs. Overall survival was improved in only three RCTs: two small studies and a large study evaluating the use of tranexamic acid. CONCLUSIONS: Despite 35 RCTs there has been little improvement in outcomes over the last few decades. No clear correlation has been demonstrated between transfusion requirements and mortality. The global trauma community should consider a coordinated and strategic approach to conduct well designed studies with pragmatic endpoints.This research project was funded by the National Institute for Health Research Programme Grant for Applied Research (RP-PG-0407-10036)

Kuiper Binary Object Formation

It has been observed that binary Kuiper Belt Objects (KBOs) exist contrary to theoretical expectations. Their creation presents problems to most current models. However, the inclusion of a third body (for example, one of the outer planets) may provide the conditions necessary for the formation of these objects. The presence of a third massive body not only helps to clear the primordial Kuiper Belt but can also result in long lived binary Kuiper belt objects. The gravitational interaction between the KBOs and the third body causes one of four effects; scattering into the Oort cloud, collisions with the growing protoplanets, formation of binary pairs, or creation of a single Kuiper belt object. Additionally, the initial location of the progenitors of the Kuiper belt objects also has a significant effect on binary formation

A comparison of human brain dissection by drill versus saw on nucleic acid quality

This study examined the effect of two dissection techniques on the quality of human brain specimens. Frozen cerebellar samples were obtained from postmortem brains of 10 subjects free from neurological and psychiatric disease. These tissues were tested for RNA and DNA concentration and quality after being dissected with either an electric dental drill or a small handsaw. RNA and DNA were extracted separately from each sample, and the concentrations and quality of each were measured. We found that dissection technique does not significantly affect RNA or DNA quality/yield. RNA and DNA yields, as well as RNA integrity showed no significant differences between the two dissection techniques. Therefore, these results support the use of a high-speed hand-held electric dental drill as an efficient and anatomically precise means of human brain dissection without compromising tissue quality. Published by Elsevier B.V

Systematic review of the psychological consequences of false-positive screening mammograms

Background: In the UK, women aged 50-73 years are invited for screening by mammography every 3 years. In 2009-10, more than 2.24 million women in this age group in England were invited to take part in the programme, of whom 73% attended a screening clinic. Of these, 64,104 women were recalled for assessment. Of those recalled, 81% did not have breast cancer; these women are described as having a false-positive mammogram. Objective: The aim of this systematic review was to identify the psychological impact on women of false positive screening mammograms and any evidence for the effectiveness of interventions designed to reduce this impact. We were also looking for evidence of effects in subgroups of women. Data sources: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Health Management Information Consortium, Cochrane Central Register for Controlled Trials, Cochrane Database of Systematic Reviews, Centre for Reviews and Dissemination (CRD) Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment (HTA), Cochrane Methodology, Web of Science, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index-Science, Conference Proceeding Citation Index-Social Science and Humanities, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Sociological Abstracts, the International Bibliography of the Social Sciences, the British Library's Electronic Table of Contents and others. Initial searches were carried out between 8 October 2010 and 25 January 2011. Update searches were carried out on 26 October 2011 and 23 March 2012. Review methods: Based on the inclusion criteria, titles and abstracts were screened independently by two reviewers. Retrieved papers were reviewed and selected using the same independent process. Data were extracted by one reviewer and checked by another. Each included study was assessed for risk of bias. Results: Eleven studies were found from 4423 titles and abstracts. Studies that used disease-specific measures found a negative psychological impact lasting up to 3 years. Distress increased with the level of invasiveness of the assessment procedure. Studies using instruments designed to detect clinical levels of morbidity did not find this effect. Women with false-positive mammograms were less likely to return for the next round of screening [relative risk (RR) 0.97; 95% confidence interval (CI) 0.96 to 0.98] than those with normal mammograms, were more likely to have interval cancer [odds ratio (OR) 3.19 (95% CI 2.34 to 4.35)] and were more likely to have cancer detected at the next screening round [OR 2.15 (95% CI 1.55 to 2.98)]. Limitations: This study was limited to UK research and by the robustness of the included studies, which frequently failed to report quality indicators, for example failure to consider the risk of bias or confounding, or failure to report participants' demographic characteristics. Conclusions: We conclude that the experience of having a false-positive screening mammogram can cause breast cancer-specific psychological distress that may endure for up to 3 years, and reduce the likelihood that women will return for their next round of mammography screening. These results should be treated cautiously owing to inherent weakness of observational designs and weaknesses in reporting. Future research should include a qualitative interview study and observational studies that compare generic and disease-specific measures, collect demographic data and include women from different social and ethnic groups

Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib.

BackgroundEarly detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.MethodsA nested case-control analysis of paired plasma samples at baseline and at 3 months was performed in 249 participants assigned to torcetrapib plus atorvastatin and 223 participants assigned to atorvastatin only. Within each treatment arm, cases with events were matched to controls 1:1. Main outcomes were a survey of 1129 proteins for discovery of biological pathways altered by torcetrapib and a 9-protein risk score validated to predict myocardial infarction, stroke, heart failure, or death.ResultsPlasma concentrations of 200 proteins changed significantly with torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in endocrine systems, including in aldosterone function and glycemic control. At baseline, 9-protein risk scores were similar in the 2 treatment arms and higher in participants with subsequent events. At 3 months, the absolute 9-protein derived risk increased in the torcetrapib plus atorvastatin arm compared with the atorvastatin-only arm by 1.08% (P=0.0004). Thirty-seven proteins changed in the direction of increased risk of 49 proteins previously associated with cardiovascular and mortality risk.ConclusionsHeretofore unknown effects of torcetrapib were revealed in immune and inflammatory functions. A protein-based risk score predicted harm from torcetrapib within just 3 months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00134264

Trajectories of quality of life, life satisfaction, and psychological adjustment after prostate cancer

Background: To describe trajectories of health-related quality of life (QoL), life satisfaction, and psychological adjustment for men with prostate cancer over the medium to long term and identify predictors of poorer outcomes using growth mixture models. Methods: One-thousand sixty-four (82.4% response) men diagnosed with prostate cancer were recruited close to diagnosis and assessed over a 72-month (6-year) period with self-report assessment of health-related QoL, life satisfaction, cancer-related distress, and prostate specific antigen anxiety. Urinary, bowel, and sexual function were also assessed using validated questionnaires. Results: Poorer physical QOL was predicted by older age, lower education, lower income, comorbidities, and receiving hormone therapy. Lower life satisfaction was related to younger age, lower income, not being partnered, and comorbidities. Poorer psychological trajectories were predicted by younger age, lower income, comorbidities, and receiving radical prostatectomy or brachytherapy. Better urinary, bowel, and sexual function were related to better global outcomes over time. Anxiety about prostate specific antigen testing was rare. Conclusions: Distinct trajectories exist for medium- to long-term QoL, life satisfaction, and psychological adjustment after prostate cancer; with age and socioeconomic deprivation playing a differential role in men\u27s survivorship profile and the impact of functional status on outcomes increasing over time. These results reinforce the need for an appraisal of men\u27s life course in addition to treatment side effects when planning survivorship care after cancer