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1.  A developmental model for alcohol use disorders in Swedish men 
Psychological medicine  2016;46(13):2759-2770.
Background
Alcohol use disorder (AUD) is a classic multifactorial syndrome and it is critical to understand the diversity of the relevant risk factors and how they inter-relate over development.
Method
We examined 21 risk factors for AUD in four developmental tiers reflecting (i) birth, (ii) childhood and early adolescence, (iii) late adolescence, and (iv) early adulthood in 47 414 Swedish men of whom 3907 (8.2%) were registered for AUD at or after age 25 with a mean length of follow-up of 33.9 (6.6) years. Structural equational model fitting was performed using Mplus.
Results
The best-fitting model provided a good fit to the data and explained 23.4% of the variance in AUD. The five strongest predictors were: externalizing behaviors, criminal behavior, father’s alcohol consumption, genetic risk, and low educational attainment. Two developmentally early familial/genetic risk factors had substantial direct paths to AUD: father’s alcohol consumption and genetic liability. Other broad developmental pathways to risk for AUD were evident: externalizing, psychosocial and internalizing. Overall, the externalizing pathway to AUD was the strongest. However, these pathways were substantially interwoven over time such that risk factors from one domain were commonly predicted by and/or predicted risk factors from the other broad domains of risk.
Conclusion
AUD in men is an etiologically complex syndrome influenced by familial-genetic, psychosocial, internalizing, and especially externalizing risk factors that act and interact over development and have complicated mediational pathways.
doi:10.1017/S0033291716001409
PMCID: PMC5030176  PMID: 27443147
Alcohol use disorder; development; environment; personality; path models
2.  A hairy fall: syncope resulting from topical application of minoxidil 
BMJ Case Reports  2015;2015:bcr2015210945.
We describe the case of a young man who developed syncope after using a high strength formulation of topical minoxidil as a hair growth restorer. Other potential cardiovascular and endocrine causes were excluded, and his symptoms resolved on discontinuation of the product. While syncope is a recognised side effect of using this powerful systemic antihypertensive agent, few cases are documented in the literature, which we illustrate in our discussion.
doi:10.1136/bcr-2015-210945
PMCID: PMC4567759  PMID: 26347235
3.  A novel sibling-based design to quantify genetic and shared environmental effects: application to drug abuse, alcohol use disorder and criminal behavior 
Psychological medicine  2016;46(8):1639-1650.
Background
Twin studies have been criticized for upwardly biased estimates that might contribute to the missing heritability problem.
Method
We identified, from the general Swedish population born 1960–1990, informative sibships containing a proband, one reared-together full- or half-sibling and a full-, step- or half-sibling with varying degrees of childhood cohabitation with the proband. Estimates of genetic, shared and individual specific environment for drug abuse (DA), alcohol use disorder (AUD) and criminal behavior (CB), assessed from medical, legal or pharmacy registries, were obtained using Mplus.
Results
Aggregate estimates of additive genetic effects for DA, AUD and CB obtained separately in males and females varied from 0.46 to 0.73 and agreed with those obtained from monozygotic and dizygotic twins from the same population. Of 54 heritability estimates from individual classes of informative sibling trios (3 syndromes × 9 classes of trios × 2 sexes), heritability estimates from the siblings were lower, tied and higher than those from obtained from twins in 26, one and 27 comparisons, respectively. By contrast, of 54 shared environmental estimates, 33 were lower than those found in twins, one tied and 20 were higher.
Conclusions
With adequate information, human populations can provide many methods for estimating genetic and shared environmental effects. For the three externalizing syndromes examined, concerns that heritability estimates from twin studies are upwardly biased or were not generalizable to more typical kinds of siblings were not supported. Overestimation of heritability from twin studies is not a likely explanation for the missing heritability problem.
doi:10.1017/S003329171500224X
PMCID: PMC4856545  PMID: 26996079
Alcoholism; crime; drug abuse; heritability; siblings
4.  Validity assessment of the PROMIS fatigue domain among people living with HIV 
Purpose
To evaluate psychometric characteristics and cross-sectional and longitudinal validity of the 7-item PROMIS® Fatigue Short Form and additional fatigue items among people living with HIV (PLWH) in a nationally distributed network of clinics collecting patient reported data at the time of routine clinical care.
Methods
Cross-sectional and longitudinal fatigue data were collected from September 2012 through April 2013 across clinics participating in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). We analyzed data regarding psychometric characteristics including simulated computerized adaptive testing and differential item functioning, and regarding associations with clinical characteristics.
Results
We analyzed data from 1597 PLWH. Fatigue was common in this cohort. Scores from the PROMIS® Fatigue Short Form and from the item bank had acceptable psychometric characteristics and strong evidence for validity, but neither performed better than shorter instruments already integrated in CNICS.
Conclusions
The PROMIS® Fatigue Item Bank is a valid approach to measuring fatigue in clinical care settings among PLWH, but in our analyses did not perform better than instruments associated with less respondent burden.
Electronic supplementary material
The online version of this article (doi:10.1186/s12981-017-0146-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12981-017-0146-y
PMCID: PMC5387298
Fatigue; HIV; PROMIS; Validity; Psychometrics; Measurement; Patient burden
5.  A prospective longitudinal model predicting early adult alcohol problems: evidence for a robust externalizing pathway 
Psychological medicine  2015;46(5):957-968.
Background
Risk factors for alcohol problems (AP) include biological and environmental factors that are relevant across development. The pathways through which these factors are related, and how they lead to AP, are optimally considered in the context of a comprehensive developmental model.
Method
Using data from a prospectively assessed, population-based UK cohort, we constructed a structural equation model that integrated risk factors reflecting individual, family and peer/community-level constructs across childhood, adolescence and young adulthood. These variables were used to predict AP at the age of 20 years.
Results
The final model explained over 30% of the variance in liability to age 20 years AP. Most prominent in the model was an externalizing pathway to AP, with conduct problems, sensation seeking, AP at age 17.5 years and illicit substance use acting as robust predictors. In conjunction with these individual-level risk factors, familial AP, peer relationships and low parental monitoring also predicted AP. Internalizing problems were less consistently associated with AP. Some risk factors previously identified were not associated with AP in the context of this comprehensive model.
Conclusions
The etiology of young adult AP is complex, influenced by risk factors that manifest across development. The most prominent pathway to AP is via externalizing and related behaviors. These findings underscore the importance of jointly assessing both biologically influenced and environmental risk factors for AP in a developmental context.
doi:10.1017/S0033291715002457
PMCID: PMC4801516  PMID: 26670459
Alcohol problems; Avon Longitudinal Study of Parents and Children; development; externalizing pathways
6.  Genetic effects influencing risk for major depressive disorder in China and Europe 
Bigdeli, T B | Ripke, S | Peterson, R E | Trzaskowski, M | Bacanu, S-A | Abdellaoui, A | Andlauer, T F M | Beekman, A T F | Berger, K | Blackwood, D H R | Boomsma, D I | Breen, G | Buttenschøn, H N | Byrne, E M | Cichon, S | Clarke, T-K | Couvy-Duchesne, B | Craddock, N | de Geus, E J C | Degenhardt, F | Dunn, E C | Edwards, A C | Fanous, A H | Forstner, A J | Frank, J | Gill, M | Gordon, S D | Grabe, H J | Hamilton, S P | Hardiman, O | Hayward, C | Heath, A C | Henders, A K | Herms, S | Hickie, I B | Hoffmann, P | Homuth, G | Hottenga, J-J | Ising, M | Jansen, R | Kloiber, S | Knowles, J A | Lang, M | Li, Q S | Lucae, S | MacIntyre, D J | Madden, P A F | Martin, N G | McGrath, P J | McGuffin, P | McIntosh, A M | Medland, S E | Mehta, D | Middeldorp, C M | Milaneschi, Y | Montgomery, G W | Mors, O | Müller-Myhsok, B | Nauck, M | Nyholt, D R | Nöthen, M M | Owen, M J | Penninx, B W J H | Pergadia, M L | Perlis, R H | Peyrot, W J | Porteous, D J | Potash, J B | Rice, J P | Rietschel, M | Riley, B P | Rivera, M | Schoevers, R | Schulze, T G | Shi, J | Shyn, S I | Smit, J H | Smoller, J W | Streit, F | Strohmaier, J | Teumer, A | Treutlein, J | Van der Auwera, S | van Grootheest, G | van Hemert, A M | Völzke, H | Webb, B T | Weissman, M M | Wellmann, J | Willemsen, G | Witt, S H | Levinson, D F | Lewis, C M | Wray, N R | Flint, J | Sullivan, P F | Kendler, K S
Translational Psychiatry  2017;7(3):e1074-.
Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
doi:10.1038/tp.2016.292
PMCID: PMC5404611  PMID: 28350396
7.  A loss of host-derived MMP-7 promotes myeloma growth and osteolytic bone disease in vivo 
Molecular Cancer  2017;16:49.
Matrix metalloproteinases (MMPs) play a critical role in cancer pathogenesis, including tumor growth and osteolysis within the bone marrow microenvironment. However, the anti-tumor effects of MMPs are poorly understood, yet have significant implications for the therapeutic potential of targeting MMPs. Host derived MMP-7 has previously been shown to support the growth of bone metastatic breast and prostate cancer. In contrast and underscoring the complexity of MMP biology, here we identified a tumor-suppressive role for host MMP-7 in the progression of multiple myeloma in vivo. An increase in tumor burden and osteolytic bone disease was observed in myeloma-bearing MMP-7 deficient mice, as compared to wild-type controls. We observed that systemic MMP-7 activity was reduced in tumor-bearing mice and, in patients with multiple myeloma this reduced activity was concomitant with increased levels of the endogenous MMP inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1). Our studies have identified an unexpected tumour-suppressive role for host-derived MMP-7 in myeloma bone disease in vivo, and highlight the importance of elucidating the effect of individual MMPs in a disease-specific context.
doi:10.1186/s12943-017-0616-9
PMCID: PMC5330156  PMID: 28241871
Multiple myeloma; Bone; MMP-7; Osteoclast; Microenvironment; Bone disease; Mouse model
8.  Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer 
British Journal of Cancer  2016;116(2):227-236.
Background:
Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression.
Methods:
Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis.
Results:
ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival.
Conclusions:
Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.
doi:10.1038/bjc.2016.402
PMCID: PMC5243990  PMID: 28006818
prostate cancer; metastasis; alkaline phosphatase; bone; EMT; MET
9.  Role of polysaccharides in food, digestion, and health 
ABSTRACT
Polysaccharides derived from plant foods are major components of the human diet, with limited contributions of related components from fungal and algal sources. In particular, starch and other storage carbohydrates are the major sources of energy in all diets, while cell wall polysaccharides are the major components of dietary fiber. We review the role of these components in the human diet, including their structure and distribution, their modification during food processing and effects on functional properties, their behavior in the gastrointestinal tract, and their contribution to healthy diets.
doi:10.1080/10408398.2014.939263
PMCID: PMC5152545  PMID: 25921546
Starch; nonstarch polysaccharides; dietary fiber; food processing; health benefits
10.  The stratigraphy and evolution of lower Mount Sharp from spectral, morphological, and thermophysical orbital data sets 
Abstract
We have developed a refined geologic map and stratigraphy for lower Mount Sharp using coordinated analyses of new spectral, thermophysical, and morphologic orbital data products. The Mount Sharp group consists of seven relatively planar units delineated by differences in texture, mineralogy, and thermophysical properties. These units are (1–3) three spatially adjacent units in the Murray formation which contain a variety of secondary phases and are distinguishable by thermal inertia and albedo differences, (4) a phyllosilicate‐bearing unit, (5) a hematite‐capped ridge unit, (6) a unit associated with material having a strongly sloped spectral signature at visible near‐infrared wavelengths, and (7) a layered sulfate unit. The Siccar Point group consists of the Stimson formation and two additional units that unconformably overlie the Mount Sharp group. All Siccar Point group units are distinguished by higher thermal inertia values and record a period of substantial deposition and exhumation that followed the deposition and exhumation of the Mount Sharp group. Several spatially extensive silica deposits associated with veins and fractures show that late‐stage silica enrichment within lower Mount Sharp was pervasive. At least two laterally extensive hematitic deposits are present at different stratigraphic intervals, and both are geometrically conformable with lower Mount Sharp strata. The occurrence of hematite at multiple stratigraphic horizons suggests redox interfaces were widespread in space and/or in time, and future measurements by the Mars Science Laboratory Curiosity rover will provide further insights into the depositional settings of these and other mineral phases.
Key Points
We have developed a stratigraphy for lower Mount Sharp using analyses of new spectral, thermophysical, and morphologic orbital data productsSiccar Point group records a period of deposition and exhumation that followed the deposition and exhumation of the Mount Sharp groupLate state silica enrichment and redox interfaces within lower Mount Sharp were pervasive and widespread in space and/or in time
doi:10.1002/2016JE005095
PMCID: PMC5101845  PMID: 27867788
Mount Sharp; remote sensing; orbital mapping; spectroscopy; stratigraphy
11.  SNP-based heritability estimates of the personality dimensions and polygenic prediction of both neuroticism and major depression: findings from CONVERGE 
Translational Psychiatry  2016;6(10):e926-.
Biometrical genetic studies suggest that the personality dimensions, including neuroticism, are moderately heritable (~0.4 to 0.6). Quantitative analyses that aggregate the effects of many common variants have recently further informed genetic research on European samples. However, there has been limited research to date on non-European populations. This study examined the personality dimensions in a large sample of Han Chinese descent (N=10 064) from the China, Oxford, and VCU Experimental Research on Genetic Epidemiology study, aimed at identifying genetic risk factors for recurrent major depression among a rigorously ascertained cohort. Heritability of neuroticism as measured by the Eysenck Personality Questionnaire (EPQ) was estimated to be low but statistically significant at 10% (s.e.=0.03, P=0.0001). In addition to EPQ, neuroticism based on a three-factor model, data for the Big Five (BF) personality dimensions (neuroticism, openness, conscientiousness, extraversion and agreeableness) measured by the Big Five Inventory were available for controls (n=5596). Heritability estimates of the BF were not statistically significant despite high power (>0.85) to detect heritabilities of 0.10. Polygenic risk scores constructed by best linear unbiased prediction weights applied to split-half samples failed to significantly predict any of the personality traits, but polygenic risk for neuroticism, calculated with LDpred and based on predictive variants previously identified from European populations (N=171 911), significantly predicted major depressive disorder case–control status (P=0.0004) after false discovery rate correction. The scores also significantly predicted EPQ neuroticism (P=6.3 × 10−6). Factor analytic results of the measures indicated that any differences in heritabilities across samples may be due to genetic variation or variation in haplotype structure between samples, rather than measurement non-invariance. Findings demonstrate that neuroticism can be significantly predicted across ancestry, and highlight the importance of studying polygenic contributions to personality in non-European populations.
doi:10.1038/tp.2016.177
PMCID: PMC5290344  PMID: 27779626
12.  Randomised clinical study: inulin short‐chain fatty acid esters for targeted delivery of short‐chain fatty acids to the human colon 
Summary
Background
Short‐chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well‐controlled trials are limited in humans.
Aims
To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake.
Methods
Inulin SCFA esters were developed and tested as site‐specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0–61 wt% (IPE‐0–IPE‐61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE‐27 or IPE‐54 (10 g/day all treatments). Propionate release was determined using 13C‐labelled IPE variants.
Results
In vitro, IPE‐27–IPE‐54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05). In vivo, IPE‐27 led to greater 13C recovery in breath CO 2 than IPE‐54 (64.9 vs. 24.9%, P = 0.001). IPE‐27 also led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE‐54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE‐54 was not significantly different from inulin control.
Conclusions
IPE‐27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short‐chain fatty acid esters provide a novel tool for probing the diet–gut microbiome–host metabolism axis in humans.
doi:10.1111/apt.13749
PMCID: PMC5026196  PMID: 27464984
13.  A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis 
Rivas, Manuel A. | Graham, Daniel | Sulem, Patrick | Stevens, Christine | Desch, A. Nicole | Goyette, Philippe | Gudbjartsson, Daniel | Jonsdottir, Ingileif | Thorsteinsdottir, Unnur | Degenhardt, Frauke | Mucha, Sören | Kurki, Mitja I. | Li, Dalin | D'Amato, Mauro | Annese, Vito | Vermeire, Severine | Weersma, Rinse K. | Halfvarson, Jonas | Paavola-Sakki, Paulina | Lappalainen, Maarit | Lek, Monkol | Cummings, Beryl | Tukiainen, Taru | Haritunians, Talin | Halme, Leena | Koskinen, Lotta L. E. | Ananthakrishnan, Ashwin N. | Luo, Yang | Heap, Graham A. | Visschedijk, Marijn C. | MacArthur, Daniel G. | Neale, Benjamin M. | Ahmad, Tariq | Anderson, Carl A. | Brant, Steven R. | Duerr, Richard H. | Silverberg, Mark S. | Cho, Judy H | Palotie, Aarno | Saavalainen, Päivi | Kontula, Kimmo | Färkkilä, Martti | McGovern, Dermot P. B. | Franke, Andre | Stefansson, Kari | Rioux, John D. | Xavier, Ramnik J. | Daly, Mark J. | Barrett, J. | de Lane, K. | Edwards, C. | Hart, A. | Hawkey, C. | Jostins, L. | Kennedy, N. | Lamb, C. | Lee, J. | Lees, C. | Mansfield, J. | Mathew, C. | Mowatt, C. | Newman, B. | Nimmo, E. | Parkes, M. | Pollard, M. | Prescott, N. | Randall, J. | Rice, D. | Satsangi, J. | Simmons, A. | Tremelling, M. | Uhlig, H. | Wilson, D. | Abraham, C. | Achkar, J. P. | Bitton, A. | Boucher, G. | Croitoru, K. | Fleshner, P. | Glas, J. | Kugathasan, S. | Limbergen, J. V. | Milgrom, R. | Proctor, D. | Regueiro, M. | Schumm, P. L. | Sharma, Y. | Stempak, J. M. | Targan, S. R. | Wang, M. H.
Nature Communications  2016;7:12342.
Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10−7, odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
While hundreds of loci are linked with inflammatory bowel diseases (IBDs), the functional consequences of the associated variants remain unclear. Here, the authors screened in ulcerative colitis (UC) patients' genomes for protein-truncating variants near IBD loci, and identify a protein truncating variant in RNF186 to be protective against UC.
doi:10.1038/ncomms12342
PMCID: PMC4980482  PMID: 27503255
14.  Life expextancy of parents with Hereditary Haemorrhagic Telangiectasia 
Background
Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disease associated with epistaxis, arteriovenous malformations and telangiectasias. Disease complications may result in premature death.
Method
We investigated life-expectancies of parents of HHT patients compared with their non-HHT partners using self- or telephone-administered questionnaires sent to their children. Patients were extracted from the databases of 2 participating HHT Centres: the Toronto HHT Database (Toronto, Canada) and the St. Antonius Hospital HHT Database (Nieuwegein, The Netherlands).
Results
Two hundred twenty five/407 (55 %) of respondents were included creating HHT- (n = 225) and control groups (n = 225) of equal size. Two hundred thirteen/225 (95 %) of the HHT group had not been screened for organ involvement of the disease prior to death. The life expectancy in parents with HHT was slightly lower compared to parents without (median age at death 73.3 years in patients versus 76.6 years in controls, p0.018). Parents with ACVRL 1 mutations had normal life expectancies, whereas parents with Endoglin mutations died 7.1 years earlier than controls (p = 0.024). Women with Endoglin mutations lived a median of 9.3 years shorter than those without (p = 0.04). Seven/123 (5 %) of deaths were HHT related with a median age at death of 61.5 years (IQ range 54.4–67.7 years).
Conclusion
Our study showed that the life expectancy of largely unscreened HHT patients was lower than people without HHT. Female patients with Endoglin mutations were most strikingly at risk of premature death from complications. These results emphasize the importance of referring patients with HHT for screening of organ involvement and timely intervention to prevent complications.
doi:10.1186/s13023-016-0427-x
PMCID: PMC4841052  PMID: 27102204
Hereditary Haemorrhagic Telangiectasia; Genetics; Mortality; Pulmonary medicine; Vascular disease
16.  Novel therapeutic targets in myeloma bone disease 
British Journal of Pharmacology  2014;171(16):3765-3776.
Multiple myeloma is a neoplastic disorder of plasma cells characterized by clonal proliferation within the bone marrow. One of the major clinical features of multiple myeloma is the destructive osteolytic bone disease that occurs in the majority of patients. Myeloma bone disease is associated with increased osteoclast activity and suppression of osteoblastogenesis. Bisphosphonates have been the mainstay of treatment for many years; however, their use is limited by their inability to repair existing bone loss. Therefore, research into novel approaches for the treatment of myeloma bone disease is of the utmost importance. This review will discuss the current advances in our understanding of osteoclast stimulation and osteoblast suppression mechanisms in myeloma bone disease and the treatments that are under development to target this destructive and debilitating feature of myeloma.
doi:10.1111/bph.12742
PMCID: PMC4128042  PMID: 24750110
17.  Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior 
Translational Psychiatry  2015;5(4):e558-.
Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case–control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human brain. AAB was measured using a count of the number of Antisocial Personality Disorder criteria endorsed under criterion A from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants were genotyped on the Illumina Human 1M BeadChip. In total, all single-nucleotide polymorphisms (SNPs) accounted for 25% of the variance in AAB, although this estimate was not significant (P=0.09). Enrichment tests indicated that more significantly associated genes were over-represented in seven gene sets, and most were immune related. Our most highly associated SNP (rs4728702, P=5.77 × 10−7) was located in the protein-coding adenosine triphosphate-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1). In a gene-based test, ABCB1 was genome-wide significant (q=0.03). Expression analyses indicated that ABCB1 was robustly expressed in the brain. ABCB1 has been implicated in substance use, and in post hoc tests we found that variation in ABCB1 was associated with DSM-IV alcohol and cocaine dependence criterion counts. These results suggest that ABCB1 may confer risk across externalizing behaviors, and are consistent with previous suggestions that immune pathways are associated with externalizing behaviors. The results should be tempered by the fact that we did not replicate the associations for ABCB1 or the gene sets in a less-affected independent sample.
doi:10.1038/tp.2015.36
PMCID: PMC4462601  PMID: 25918995
18.  Jet energy measurement and its systematic uncertainty in proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=7$$\end{document}s=7 TeV with the ATLAS detector 
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The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton–proton collision data with a centre-of-mass energy of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=7$$\end{document}s=7 TeV corresponding to an integrated luminosity of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.7$$\end{document}4.7\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\,\,\text{ fb }^{-1}$$\end{document}fb-1. Jets are reconstructed from energy deposits forming topological clusters of calorimeter cells using the anti-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$k_{t}$$\end{document}kt algorithm with distance parameters \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$R=0.4$$\end{document}R=0.4 or \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$R=0.6$$\end{document}R=0.6, and are calibrated using MC simulations. A residual JES correction is applied to account for differences between data and MC simulations. This correction and its systematic uncertainty are estimated using a combination of in situ techniques exploiting the transverse momentum balance between a jet and a reference object such as a photon or a \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$Z$$\end{document}Z boson, for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${20} \le p_{\mathrm {T}}^\mathrm {jet}<{1000}\, ~\mathrm{GeV }$$\end{document}20≤pTjet<1000GeV and pseudorapidities \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$|\eta |<{4.5}$$\end{document}|η|<4.5. The effect of multiple proton–proton interactions is corrected for, and an uncertainty is evaluated using in situ techniques. The smallest JES uncertainty of less than 1 % is found in the central calorimeter region (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$|\eta |<{1.2}$$\end{document}|η|<1.2) for jets with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${55} \le p_{\mathrm {T}}^\mathrm {jet}<{500}\, ~\mathrm{GeV }$$\end{document}55≤pTjet<500GeV. For central jets at lower \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{\mathrm {T}}$$\end{document}pT, the uncertainty is about 3 %. A consistent JES estimate is found using measurements of the calorimeter response of single hadrons in proton–proton collisions and test-beam data, which also provide the estimate for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{\mathrm {T}}^\mathrm {jet}> 1$$\end{document}pTjet>1 TeV. The calibration of forward jets is derived from dijet \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{\mathrm {T}}$$\end{document}pT balance measurements. The resulting uncertainty reaches its largest value of 6 % for low-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{\mathrm {T}}$$\end{document}pT jets at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$|\eta |=4.5$$\end{document}|η|=4.5. Additional JES uncertainties due to specific event topologies, such as close-by jets or selections of event samples with an enhanced content of jets originating from light quarks or gluons, are also discussed. The magnitude of these uncertainties depends on the event sample used in a given physics analysis, but typically amounts to 0.5–3 %.
doi:10.1140/epjc/s10052-014-3190-y
PMCID: PMC4684939  PMID: 26709345
19.  Global assessment of the status of coral reef herbivorous fishes: evidence for fishing effects 
On coral reefs, herbivorous fishes consume benthic primary producers and regulate competition between fleshy algae and reef-building corals. Many of these species are also important fishery targets, yet little is known about their global status. Using a large-scale synthesis of peer-reviewed and unpublished data, we examine variability in abundance and biomass of herbivorous reef fishes and explore evidence for fishing impacts globally and within regions. We show that biomass is more than twice as high in locations not accessible to fisheries relative to fisheries-accessible locations. Although there are large biogeographic differences in total biomass, the effects of fishing are consistent in nearly all regions. We also show that exposure to fishing alters the structure of the herbivore community by disproportionately reducing biomass of large-bodied functional groups (scraper/excavators, browsers, grazer/detritivores), while increasing biomass and abundance of territorial algal-farming damselfishes (Pomacentridae). The browser functional group that consumes macroalgae and can help to prevent coral–macroalgal phase shifts appears to be most susceptible to fishing. This fishing down the herbivore guild probably alters the effectiveness of these fishes in regulating algal abundance on reefs. Finally, data from remote and unfished locations provide important baselines for setting management and conservation targets for this important group of fishes.
doi:10.1098/rspb.2013.1835
PMCID: PMC3843826  PMID: 24258715
fishing; reef-fish; phase shift; resilience; herbivory; macroalgae and turf algae
20.  Muon reconstruction efficiency and momentum resolution of the ATLAS experiment in proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=7$$\end{document}s=7 TeV in 2010 
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This paper presents a study of the performance of the muon reconstruction in the analysis of proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=7$$\end{document}s=7 TeV at the LHC, recorded by the ATLAS detector in 2010. This performance is described in terms of reconstruction and isolation efficiencies and momentum resolutions for different classes of reconstructed muons. The results are obtained from an analysis of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$J/\psi $$\end{document}J/ψ meson and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$Z$$\end{document}Z boson decays to dimuons, reconstructed from a data sample corresponding to an integrated luminosity of 40 pb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1. The measured performance is compared to Monte Carlo predictions and deviations from the predicted performance are discussed.
doi:10.1140/epjc/s10052-014-3034-9
PMCID: PMC4371051  PMID: 25814911
21.  The differential production cross section of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi $$\end{document}ϕ(1020) meson in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}$$\end{document}s = 7 TeV \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$pp$$\end{document}pp collisions measured with the ATLAS detector 
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A measurement is presented of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi \times \mathcal {BR}(\phi \rightarrow K^{+}K^{-})$$\end{document}ϕ×BR(ϕ→K+K-) production cross section at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}$$\end{document}s = 7 TeV using \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$pp$$\end{document}pp collision data corresponding to an integrated luminosity of 383 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm {\upmu b^{-1}}$$\end{document}μb-1, collected with the ATLAS experiment at the LHC. Selection of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi $$\end{document}ϕ(1020) mesons is based on the identification of charged kaons by their energy loss in the pixel detector. The differential cross section is measured as a function of the transverse momentum, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{\mathrm {T,\phi }}$$\end{document}pT,ϕ, and rapidity, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$y_{\phi }$$\end{document}yϕ, of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi $$\end{document}ϕ(1020) meson in the fiducial region 500 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$$$\end{document}pT,K> 230 MeV and kaon momentum \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{K}<$$\end{document}pK< 800 MeV. The integrated \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi (1020)$$\end{document}ϕ(1020)-meson production cross section in this fiducial range is measured to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\phi } \times \mathcal {BR}(\phi \rightarrow K^{+}K^{-}) $$\end{document}σϕ×BR(ϕ→K+K-) = 570 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pm $$\end{document}± 8 (stat) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pm $$\end{document}± 66 (syst) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pm $$\end{document}± 20 (lumi) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm {\upmu b}$$\end{document}μb.
doi:10.1140/epjc/s10052-014-2895-2
PMCID: PMC4371126  PMID: 25814898
22.  The costs of late detection of developmental dysplasia of the hip 
Purpose
Debate currently exists regarding the economic viability for screening for developmental dysplasia of the hip in infants.
Methods
A prospective study of infant hip dysplasia over the period of 1998–2008 (36,960 live births) was performed to determine treatment complexity and associated costs of disease detection and hospital treatment, related to the age at presentation and treatment modality. The involved screening programme utilised universal clinical screening of all infants and selective ultrasound screening of at-risk infants.
Results
One hundred and seventy-nine infants (4.8/1,000) presented with hip dysplasia. Thirty-four infants presented late (> 3 months of age) and required closed or open reduction. One hundred and forty-five infants presented at < 3 months of age, 14 of whom failed early Pavlik harness treatment. A detailed cost analysis revealed: 131 early presenters with successful management in a Pavlik harness at a cost of £601/child; 34 late presenters who required surgery (36 hips, 19 closed/17 open reductions, one revision procedure) at a cost of £4,352/child; and 14 early presenters with failed management in a Pavlik harness requiring more protracted surgery (18 hips, four closed/14 open reductions, seven revision procedures) at a cost of £7,052/child.
Conclusions
Late detection causes increased treatment complexity and a sevenfold increase in the short-term costs of treatment, compared to early detection and successful management in a Pavlik harness.
Discussion
Improved strategies are needed for the 10 % of early presenting infants who fail Pavlik harness treatment and require the most complex and costly interventions.
doi:10.1007/s11832-014-0599-7
PMCID: PMC4128950  PMID: 24973899
Developmental hip dysplasia; Screening; Economics; Ultrasound
23.  Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminating calves 
Glucagon-like peptide-2 (GLP-2) increases small intestinal mass and blood flow in ruminant calves, but its impact on nutrient metabolism across the portal-drained viscera (PDV) and liver is unknown. Eight Holstein calves with catheters in the carotid artery, mesenteric vein, portal vein and hepatic vein were paired by age and randomly assigned to control (0.5% bovine serum albumin in saline; n =4) or GLP-2 (100 μg/kg BW per day bovine GLP-2 in bovine serum albumin; n =4). Treatments were administered subcutaneously every 12 h for 10 days. Blood flow was measured on days 0 and 10 and included 3 periods: baseline (saline infusion), treatment (infusion of bovine serum albumin or 3.76 μg/kg BW per h GLP-2) and recovery (saline infusion). Arterial concentrations and net PDV, hepatic and total splanchnic fluxes of glucose, lactate, glutamate, glutamine, β-hydroxybutyrate and urea-N were measured on days 0 and 10. Arterial concentrations and net fluxes of all amino acids and glucose metabolism using continuous intravenous infusion of [U13-C]glucose were measured on day 10 only. A 1-h infusion of GLP-2 increased blood flow in the portal and hepatic veins when administered to calves not previously exposed to exogenous GLP-2, but after a 10-day administration of GLP-2 the blood flow response to the 1-h GLP-2 infusion was substantially attenuated. The 1-h GLP-2 infusion also did not appreciably alter nutrient fluxes on either day 0 or 10. In contrast, long-term GLP-2 administration reduced arterial concentrations and net PDV flux of many essential and non-essential amino acids. Despite the significant alterations in amino acid metabolism, glucose irreversible loss and utilization by PDV and non-PDV tissues were not affected by GLP-2. Fluxes of amino acids across the PDV were generally reduced by GLP-2, potentially by increased small intestinal epithelial growth and thus energy and amino acid requirements of this tissue. Increased PDV extraction of glutamine and alterations in PDV metabolism of arginine, ornithine and citrulline support the concept that GLP-2 influences intestine-specific amino acid metabolism. Alterations in amino acid metabolism but unchanged glucose metabolism suggests that the growth effects induced by GLP-2 in ruminants increase reliance on amino acids preferentially over glucose. Thus, GLP-2 increases PDV utilization of amino acids, but not glucose, concurrent with stimulated growth of the small intestinal epithelium in post-absorptive ruminant calves.
doi:10.1017/S175173111200095X
PMCID: PMC3973745  PMID: 23031436
blood flow; glucose; amino acid; flux; ruminant
24.  Measurement of jet shapes in top-quark pair events at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\sqrt{s} = 7 \ \mbox{TeV}$\end{document} using the ATLAS detector 
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