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Computing for Optimized Biological Microscopy Data Processing and Analysis at The Rosalind Franklin Institute
- Luís M. A. Perdigão, Neville B.-y Yee, Elaine M. L. Ho, Avery H. Pennington, Oliver N.F. King, Michele C. Darrow, Mark Basham
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- Journal:
- Microscopy and Microanalysis / Volume 28 / Issue S1 / August 2022
- Published online by Cambridge University Press:
- 22 July 2022, pp. 1462-1464
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- August 2022
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
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- August 2022
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
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Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Treatment of refractory obsessive–compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study
- Jerome Sarris, Gerard J. Byrne, Georgina Oliver, Lachlan Cribb, Scott Blair-West, David Castle, Olivia M. Dean, David A. Camfield, Vlasios Brakoulias, Chad Bousman, Nathan Dowling, Carolyn Ee, Jenifer Murphy, Ranjit Menon, Michael Berk, Suneel Chamoli, Mark Boschen, Chee H. Ng
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- Journal:
- CNS Spectrums / Volume 27 / Issue 5 / October 2022
- Published online by Cambridge University Press:
- 21 June 2021, pp. 588-597
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Background
Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach.
ObjectiveTo assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium.
MethodsA 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks.
ResultsAn intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD.
ConclusionsWhile this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
Effects of maternal periconceptional undernutrition in sheep on offspring glucose–insulin axis function into adulthood
- Mark H. Oliver, Frank H. Bloomfield, Amita Bansal, Hui Hui Phua, Eric B. Thorstensen, Jane E. Harding, Anne L. Jaquiery
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- Journal:
- Journal of Developmental Origins of Health and Disease / Volume 12 / Issue 5 / October 2021
- Published online by Cambridge University Press:
- 20 November 2020, pp. 714-720
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Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.
Effects of preterm birth induced with or without exogenous glucocorticoids on the ovine glucose–insulin axis
- Amita Bansal, Jane M. Alsweiler, Mark H. Oliver, Anne Jaquiery, Hui Hui Phua, Mike Dragunow, Rob de Matteo, Jane E. Harding, Frank H. Bloomfield
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- Journal:
- Journal of Developmental Origins of Health and Disease / Volume 12 / Issue 1 / February 2021
- Published online by Cambridge University Press:
- 15 January 2020, pp. 58-70
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Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11–14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12–13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml−1·kg−1·min−1·ng−1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%–71% in NG-Prem vs. G-Prem and 42%–80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.
Neonatal milk supplementation in lambs has persistent effects on growth and metabolic function that differ by sex and gestational age
- Mary J. Berry, Anne L. Jaquiery, Mark H. Oliver, Jane E. Harding, Frank H. Bloomfield
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- Journal:
- British Journal of Nutrition / Volume 116 / Issue 11 / 14 December 2016
- Published online by Cambridge University Press:
- 15 December 2016, pp. 1912-1925
- Print publication:
- 14 December 2016
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The perinatal environment has a major influence on long-term health and disease risk. Preterm birth alters early-life environment and is associated with altered metabolic function in adulthood. Whether preterm birth per se or the early nutritional interventions used to support growth in preterm infants underpins this association is unknown. Lambs born preterm, following dexamethasone induction of labour, or spontaneously at term were randomised to receive nutrient supplementation, analogous to the milk fortifier used clinically or water as a control for the first 2 weeks after birth. Thereafter, nutrition was not different between groups. Growth was monitored, and the glucose–insulin axis function was assessed in juvenile (4 months) and adult life (14 months). Early nutrition influenced adult metabolic function and body composition to a greater extent than preterm birth. In supplemented females, arginine-stimulated insulin secretion was increased in preterm but reduced in term-born juveniles compared with controls (repeated-measures ANOVA P<0·01). In supplemented preterm males, adult weight, ponderal index (PI) and fasting insulin concentrations were elevated compared with preterm controls (weight, 75 (sem 3) v. 69 (sem 2) kg; PI, 48·0 (sem 2·1) v. 43·7 (sem 1·7) kg/m3; fasting insulin, 0·19 (sem 0·02) v. 0·10 (sem 0·02) ng/ml). Conversely, supplemented term-born males had reduced adult weight, PI and fasting insulin concentrations compared with term-born controls (weight, 64 (sem 2) v. 70 (sem 2) kg; PI, 44·4 (sem 1·8) v. 48·2 (sem 1·7) kg/m3; fasting insulin, 0·09 (sem 0·02) v. 0·14 (sem 0·02) ng/ml; all group×supplement interactions P<0·05). Adult metabolic health may reflect both gestational age at birth and early nutrition. Human studies are urgently needed to investigate the adult sex-specific health implications of neonatal nutritional strategies.
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- By Linda S. Aglio, Cyrus Ahmadi Yazdi, Syed Irfan Qasim Ali, Caryn Barnet, Jessica Bauerle, Felicity Billings, Evan Blaney, Beverly Chang, Christopher Chen, Zinaida Chepurny, Hyung Sun Choi, Allison Clark, Lauren J. Cornella, Lisa Crossley, Michael D’Ambra, Galina Davidyuk, Whitney de Luna, Manisha S. Desai, Sukumar P. Desai, Kelly G. Elterman, Michaela K. Farber, Iuliu Fat, Jaida Fitzgerald, Devon Flaherty, John A. Fox, Gyorgy Frendl, Rejean Gareau, Joseph M. Garfield, Andrea Girnius, Laverne D. Gugino, J. Tasker Gundy, Carly C. Guthrie, Lisa M. Hammond, M. Tariq Hanifi, James Hardy, Philip M. Hartigan, Thomas Hickey, Richard Hsu, Mohab Ibrahim, David Janfaza, Yuka Kiyota, Suzanne Klainer, Benjamin Kloesel, Hanjo Ko, Bhavani Kodali, Vesela Kovacheva, J. Matthew Kynes, Robert W. Lekowski, Joyce Lo, Jeffrey Lu, Alvaro A. Macias, Zahra M. Malik, Erich N. Marks, Brendan McGinn, Jonathan R. Meserve, Annette Mizuguchi, Srdjan S. Nedeljkovic, Ju-Mei Ng, Michael Nguyen, Olutoyin Okanlawon, Jennifer Oliver, Krishna Parekh, Jessica Patterson, Christian Peccora, Pete Pelletier, Sujatha Pentakota, James H. Philip, Marc Philip T. Pimentel, Timothy D. Quinn, Elizabeth M. Rickerson, Susan L. Sager, Julia Serber, Shaheen Shaikh, Stanton Shernan, David Silver, Alissa Sodickson, Pingping Song, George P. Topulos, Agnieszka Trzcinka, Richard D. Urman, Rosemary Uzomba, Joshua Vacanti, Assia Valovska, Michael Vaninetti, Scott W. Vaughan, Kamen Vlassakov, Christopher Voscopoulos, Emily L. Wang, Laura Westfall, Zhiling Xiong, Stephanie Yacoubian, Dongdong Yao, Martin Zammert, Maksim Zayaruzny, Jose Luis Zeballos, Natthasorn Zinboonyahgoon, Jie Zhou
- Edited by Linda S. Aglio, Robert W. Lekowski, Richard D. Urman
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- Essential Clinical Anesthesia Review
- Published online:
- 05 February 2015
- Print publication:
- 08 January 2015, pp xi-xvi
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A study of National Health Service management of chronic osteoarthritis and low back pain
- Oliver R. Hart, Ruth M. Uden, James E. McMullan, Mark S. Ritchie, Timothy D. Williams, Blair H. Smith
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- Primary Health Care Research & Development / Volume 16 / Issue 2 / March 2015
- Published online by Cambridge University Press:
- 27 March 2014, pp. 157-166
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Aim
To describe treatment and referral patterns and National Health Service resource use in patients with chronic pain associated with low back pain or osteoarthritis, from a Primary Care perspective.
BackgroundOsteoarthritis and low back pain are the two commonest debilitating causes of chronic pain, with high health and social costs, and particularly important in primary care. Understanding current practice and resource use in their management will inform health service and educational requirements and the design and optimisation of future care.
MethodMulti-centre, retrospective, descriptive study of adults (⩾18 years) with chronic pain arising from low back pain or osteoarthritis, identified through primary care records. Five general practices in Scotland, England (two), Northern Ireland and Wales. All patients with a diagnosis of low back pain or osteoarthritis made on or before 01/09/2006 who had received three or more prescriptions for pain medication were identified and a sub-sample randomly selected then consented to an in-depth review of their medical records (n=264). Data on management of chronic pain were collected retrospectively from patients’ records for three years from diagnosis (‘newly diagnosed’ patients) or for the most recent three years (‘established’ patients).
FindingsPatients received a wide variety of pain medications with no overall common prescribing pattern. GP visits represented the majority of the resource use and ‘newly diagnosed’ patients were significantly more likely to visit their GP for pain management than ‘established’ patients. Although ‘newly diagnosed’ patients had more referrals outside the GP practice, the number of visits to secondary care for pain management was similar for both groups.
ConclusionThis retrospective study confirmed the complexity of managing these causes of chronic pain and the associated high resource use. It provides an in-depth picture of prescribing and referral patterns and of resource use.
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- By John A. Bargh, Lisa Feldman Barrett, Veronica Benet-Martínez, Elliot T. Berkman, Jim Blascovich, Marilynn B. Brewer, Heining Cham, Tanya L. Chartrand, Robert B. Cialdini, William D. Crano, William A. Cunningham, Rick Dale, Jan De Houwer, Alice H. Eagly, J. Mark Eddy, Craig K. Enders, Leandre R. Fabrigar, Susan T. Fiske, Shelly L. Gable, Bertram Gawronski, Kevin J. Grimm, K. Paige Harden, Richard E. Heyman, Oliver P. John, Blair T. Johnson, Charles M. Judd, Deborah A. Kashy, David A. Kenny, Norbert L. Kerr, Nuri Kim, Jon A. Krosnick, Paul J. Lavrakas, Matthew D. Lieberman, Kristen A. Lindquist, Todd D. Little, Yu Liu, Michael F. Lorber, Michael R. Maniaci, Kerry L. Marsh, Gina L. Mazza, Gary H. McClelland, Dominique Muller, Elizabeth Levy Paluck, Karen S. Quigley, Harry T. Reis, Mijke Rhemtulla, Michael J. Richardson, Ronald D. Rogge, Alexander M. Schoemann, Eliot R. Smith, R. Scott Tindale, Eric Turkheimer, Penny S. Visser, Duane T. Wegener, Stephen G. West, Tessa V. West, Keith F. Widaman, Vincent Y. Yzerbyt
- Edited by Harry T. Reis, University of Rochester, New York, Charles M. Judd, University of Colorado Boulder
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- Book:
- Handbook of Research Methods in Social and Personality Psychology
- Published online:
- 05 June 2014
- Print publication:
- 24 February 2014, pp vii-viii
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- Edited by Simon N. M. Young, The University of Hong Kong, Yash Ghai, The University of Hong Kong
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- Hong Kong's Court of Final Appeal
- Published online:
- 05 December 2013
- Print publication:
- 12 December 2013, pp xi-xii
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- By C. Alan Anderson, Celso Arango, David B. Arciniegas, Igor Bombin, Robert W. Buchanan, C. Robert Cloninger, Joshua Cosman, C. Munro Cullum, Felipe DeBrigard, Steven L. Dubovsky, Robert Feinstein, Lynne Fenton, Christopher M. Filley, Laura A. Flashman, Morris Freedman, Oliver Freudenreich, Kimberly L. Frey, Lauren C. Frey, Kelly S. Giovanello, Deborah A. Hall, John Hart, Kenneth M. Heilman, Katherine L. Howard, Robin A. Hurley, Daniel I. Kaufer, Sita Kedia, James P. Kelly, B. K. Kleinschmidt-DeMasters, Benzi M. Kluger, David G. Lichter, Deborah M. Little, Deborah M. Lucas, Thomas W. McAllister, Mario F. Mendez, Doron Merims, Steven G. Ojemann, Fred Ovsiew, Brian D. Power, Bruce H. Price, Gila Z. Reckess, Martin L. Reite, Matthew Rizzo, Donald C. Rojas, Michael Henry Rosenbloom, Elliott D. Ross, Jeremy D. Schmahmann, Stuart A. Schneck, Jonathan M. Silver, Mark C. Spitz, Sergio E. Starkstein, Katherine H. Taber, Robert L. Trestman, Hal S. Wortzel
- Edited by David B. Arciniegas, C. Alan Anderson, Christopher M. Filley
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- Book:
- Behavioral Neurology & Neuropsychiatry
- Published online:
- 05 February 2013
- Print publication:
- 24 January 2013, pp vii-x
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- By Susan F. Beegel, Milton A. Cohen, Nancy R. Comley, Kirk Curnutt, Albert J. DeFazio, Suzanne del Gizzo, David M. Earle, Carl P. Eby, Robert E. Fleming, Stacey Guill, Peter L. Hays, Ryan Hediger, Gary Edward Holcomb, Jill Jividen, Hilary K. Justice, Verna Kale, Jeremy Kaye, J. Gerald Kennedy, Kelli A. Larson, Leonard J. Leff, Nghana tamu Lewis, Kevin Maier, Miriam B. Mandel, James H. Meredith, Peter Messent, Debra A. Moddelmog, Lisa Narbeshuber, Matthew Nickel, Charles M. Oliver, Mark P. Ott, James Plath, Russ Pottle, Ann Putnam, John Raeburn, Gail Sinclair, Sandra Spanier, Amy Strong, Thomas Strychacz, Frederic Svoboda, Robert W. Trogdon, Lisa Tyler, Alex Vernon, Emily O. Wittman, Susan Wrynn
- Edited by Debra A. Moddelmog, Ohio State University, Suzanne del Gizzo
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- Book:
- Ernest Hemingway in Context
- Published online:
- 18 December 2013
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- 17 December 2012, pp xi-xxii
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Effects of periconceptional undernutrition on maternal taurine concentrations in sheep
- Eric B. Thorstensen, José G. B. Derraik, Mark H. Oliver, Anne L. Jaquiery, Frank H. Bloomfield, Jane E. Harding
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- Journal:
- British Journal of Nutrition / Volume 107 / Issue 4 / 28 February 2012
- Published online by Cambridge University Press:
- 26 July 2011, pp. 466-472
- Print publication:
- 28 February 2012
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Taurine has an important role in numerous physiological processes, including many aspects of fetal development such as development of the pancreas and brain, and requirements increase during pregnancy. Periconceptional undernutrition has long-term effects on pancreas and brain function of the offspring, but the effects on maternal taurine economy are unknown. We, therefore, studied the effects of different periods of periconceptional undernutrition on maternal plasma and urine taurine concentrations before and during pregnancy. Four groups of singleton-bearing ewes were studied (n 10–11): controls fed ad libitum, and groups undernourished from 60 d before until mating (PreC), from 2 d before mating until 30 d after mating (PostC) or from 60 d before until 30 d after mating (Pre+PostC). In PreC ewes, plasma taurine concentrations remained at control levels for the first 30 d, and then decreased through the remainder of undernutrition, but recovered by 30 d after mating; urinary taurine excretion was low at mating, but recovered similarly. In PostC ewes, plasma taurine concentrations recovered after 2 weeks despite ongoing undernutrition; urinary taurine excretion had recovered by 30 d after mating. Pre+PostC ewes followed the same pattern as PreC for the first 60 d, but plasma taurine concentrations and urinary excretion recovered slowly, and did not reach the control levels until 97 d. These data suggest that different periods of mild periconceptional undernutrition in sheep have different but substantial effects on maternal taurine homoeostasis. These effects may be one mechanism by which maternal periconceptional undernutrition alters development of the offspring with implications for adult health.
Contributors
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- By Waiel Almoustadi, Brian J. Anderson, David B. Auyong, Michael Avidan, Michael J. Avram, Roland J. Bainton, Jeffrey R. Balser, Juliana Barr, W. Scott Beattie, Manfred Blobner, T. Andrew Bowdle, Walter A. Boyle, Eugene B. Campbell, Laura F. Cavallone, Mario Cibelli, C. Michael Crowder, Ola Dale, M. Frances Davies, Mark Dershwitz, George Despotis, Clifford S. Deutschman, Brian S. Donahue, Marcel E. Durieux, Thomas J. Ebert, Talmage D. Egan, Helge Eilers, E. Wesley Ely, Charles W. Emala, Alex S. Evers, Heidrun Fink, Pierre Foëx, Stuart A. Forman, Helen F. Galley, Josephine M. Garcia-Ferrer, Robert W. Gereau, Tony Gin, David Glick, B. Joseph Guglielmo, Dhanesh K. Gupta, Howard B. Gutstein, Robert G. Hahn, Greg B. Hammer, Brian P. Head, Helen Higham, Laureen Hill, Kirk Hogan, Charles W. Hogue, Christopher G. Hughes, Eric Jacobsohn, Roger A. Johns, Dean R. Jones, Max Kelz, Evan D. Kharasch, Ellen W. King, W. Andrew Kofke, Tom C. Krejcie, Richard M. Langford, H. T. Lee, Isobel Lever, Jerrold H. Levy, J. Lance Lichtor, Larry Lindenbaum, Hung Pin Liu, Geoff Lockwood, Alex Macario, Conan MacDougall, M. B. MacIver, Aman Mahajan, Nándor Marczin, J. A. Jeevendra Martyn, George A. Mashour, Mervyn Maze, Thomas McDowell, Stuart McGrane, Berend Mets, Patrick Meybohm, Charles F. Minto, Jonathan Moss, Mohamed Naguib, Istvan Nagy, Nick Oliver, Paul S. Pagel, Pratik P. Pandharipande, Piyush Patel, Andrew J. Patterson, Robert A. Pearce, Ronald G. Pearl, Misha Perouansky, Kristof Racz, Chinniampalayam Rajamohan, Nilesh Randive, Imre Redai, Stephen Robinson, Richard W. Rosenquist, Carl E. Rosow, Uwe Rudolph, Francis V. Salinas, Robert D. Sanders, Sunita Sastry, Michael Schäfer, Jens Scholz, Thomas W. Schnider, Mark A. Schumacher, John W. Sear, Frédérique S. Servin, Jeffrey H. Silverstein, Tom De Smet, Martin Smith, Joe Henry Steinbach, Markus Steinfath, David F. Stowe, Gary R. Strichartz, Michel M. R. F. Struys, Isao Tsuneyoshi, Robert A. Veselis, Arthur Wallace, Robert P. Walt, David C. Warltier, Nigel R. Webster, Jeanine Wiener-Kronish, Troy Wildes, Paul Wischmeyer, Ling-Gang Wu, Stephen Yang
- Edited by Alex S. Evers, Washington University School of Medicine, St Louis, Mervyn Maze, University of California, San Francisco, Evan D. Kharasch, Washington University School of Medicine, St Louis
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- Book:
- Anesthetic Pharmacology
- Published online:
- 11 April 2011
- Print publication:
- 10 March 2011, pp viii-xiv
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The science of EChO
- Giovanna Tinetti, James Y-K. Cho, Caitlin A. Griffith, Olivier Grasset, Lee Grenfell, Tristan Guillot, Tommi T. Koskinen, Julianne I. Moses, David Pinfield, Jonathan Tennyson, Marcell Tessenyi, Robin Wordsworth, Alan Aylward, Roy van Boekel, Angioletta Coradini, Therese Encrenaz, Ignas Snellen, Maria R. Zapatero-Osorio, Jeroen Bouwman, Vincent Coudé du Foresto, Mercedes Lopez-Morales, Ingo Mueller-Wodarg, Enric Pallé, Franck Selsis, Alessandro Sozzetti, Jean-Philippe Beaulieu, Thomas Henning, Michael Meyer, Giuseppina Micela, Ignasi Ribas, Daphne Stam, Mark Swain, Oliver Krause, Marc Ollivier, Emanuele Pace, Bruce Swinyard, Peter A.R. Ade, Nick Achilleos, Alberto Adriani, Craig B. Agnor, Cristina Afonso, Carlos Allende Prieto, Gaspar Bakos, Robert J. Barber, Michael Barlow, Peter Bernath, Bruno Bézard, Pascal Bordé, Linda R. Brown, Arnaud Cassan, Céline Cavarroc, Angela Ciaravella, Charles Cockell, Athéna Coustenis, Camilla Danielski, Leen Decin, Remco De Kok, Olivier Demangeon, Pieter Deroo, Peter Doel, Pierre Drossart, Leigh N. Fletcher, Matteo Focardi, Francois Forget, Steve Fossey, Pascal Fouqué, James Frith, Marina Galand, Patrick Gaulme, Jonay I. González Hernández, Davide Grassi, Matt J. Griffin, Ulrich Grözinger, Manuel Guedel, Pactrick Guio, Olivier Hainaut, Robert Hargreaves, Peter H. Hauschildt, Kevin Heng, David Heyrovsky, Ricardo Hueso, Pat Irwin, Lisa Kaltenegger, Patrick Kervella, David Kipping, Geza Kovacs, Antonino La Barbera, Helmut Lammer, Emmanuel Lellouch, Giuseppe Leto, Mercedes Lopez Morales, Miguel A. Lopez Valverde, Manuel Lopez-Puertas, Christophe Lovi, Antonio Maggio, Jean-Pierre Maillard, Jesus Maldonado Prado, Jean-Baptiste Marquette, Francisco J. Martin-Torres, Pierre Maxted, Steve Miller, Sergio Molinari, David Montes, Amaya Moro-Martin, Olivier Mousis, Napoléon Nguyen Tuong, Richard Nelson, Glenn S. Orton, Eric Pantin, Enzo Pascale, Stefano Pezzuto, Ennio Poretti, Raman Prinja, Loredana Prisinzano, Jean-Michel Réess, Ansgar Reiners, Benjamin Samuel, Jorge Sanz Forcada, Dimitar Sasselov, Giorgio Savini, Bruno Sicardy, Alan Smith, Lars Stixrude, Giovanni Strazzulla, Gautam Vasisht, Sandrine Vinatier, Serena Viti, Ingo Waldmann, Glenn J. White, Thomas Widemann, Roger Yelle, Yuk Yung, Sergey Yurchenko
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- Journal:
- Proceedings of the International Astronomical Union / Volume 6 / Issue S276 / October 2010
- Published online by Cambridge University Press:
- 10 November 2011, pp. 359-370
- Print publication:
- October 2010
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The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are?
In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life.
The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole.
EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates.
Contributors
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- By Farook Al-Azzawi, Wita Angrianni, Sanjay Asthana, Stephan Bandelow, Kathryn J. Bryan, Cynthia M. Carlsson, Jenna C. Carroll, Gemma Casadesus, Monique M. Cherrier, Laura H. Coker, María M. Corrada, Vita Priantina Dewi, Roberta Diaz Brinton, Mark A. Espeland, Mirjam I. Geerlings, Robert B. Gibbs, Carey E. Gleason, Victor W. Henderson, Patricia E. Hogan, Eef Hogervorst, Claudia H. Kawas, Anna Khaylis, Philip Kreager, Linda Kushandy, Donald Lehmann, Jin Li, Mary E. McAsey, Pauline M. Maki, Ralph N. Martins, Scott D. Moffat, Majon Muller, Theresia Ninuk, Annlia Paganini-Hill, George Perry, Christian J. Pike, Bevin N. Powers, Tri Budi W. Rahardjo, Natalie L. Rasgon, Susan M. Resnick, Emily R. Rosario, Sabarinah, Tony Sadjimim, Barbara B. Sherwin, Sally A. Shumaker, Mark A. Smith, Robert G. Struble, Chris Talbot, Wulf H. Utian, Giuseppe Verdile, Robert B. Wallace, Whitney Wharton, Katherine E. Williams, Oliver T. Wolf, Tonita E. Wroolie, Amina Yesufu, Yudarini, Liqin Zhao
- Edited by Eef Hogervorst, Loughborough University, Victor W. Henderson, Stanford University, California, Robert B. Gibbs, University of Pittsburgh, Roberta Diaz Brinton, University of Southern California
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- Book:
- Hormones, Cognition and Dementia
- Published online:
- 06 July 2010
- Print publication:
- 24 September 2009, pp vii-x
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Intramammary infections in heifers during early lactation following intramammary infusion of pirlimycin hydrochloride or penicillin-novobiocin at the first milking after parturition
- Stephen P Oliver, Susan I Headrick, Barbara E Gillespie, Mark J Lewis, David L Johnson, Kenneth C Lamar, Hugh Moorehead, Henry H Dowlen, John W Hallberg
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- Journal:
- Journal of Dairy Research / Volume 74 / Issue 2 / May 2007
- Published online by Cambridge University Press:
- 17 January 2007, pp. 211-217
- Print publication:
- May 2007
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A study was conducted to determine whether intramammary antibiotic treatment of heifer mammary glands following the first milking after calving was effective for reducing the percentage of mammary quarters infected during early lactation. Jersey and Holstein heifers from two research herds were assigned to one of three treatment groups: (1) no intramammary infusion following the first milking after parturition, (2) intramammary infusion of all quarters with pirlimycin hydrochloride following the first milking after parturition and (3) intramammary infusion of all quarters with novobiocin sodium plus penicillin G procaine following the first milking after parturition. Almost 93% of Jersey heifers (40/43) and 73·1% of quarters (125/171) were infected at the first milking. Almost 77% of quarters (33/43) were cured following treatment with pirlimycin, 61·8% (21/34) were cured following treatment with penicillin-novobiocin and 39·6% (19/48) of infections were eliminated spontaneously in the untreated control group. Significantly fewer infections were observed in pirlimycin or penicillin-novobiocin treated mammary glands of Jersey heifers during early lactation than in untreated control mammary glands. Almost 89% of Holstein heifers (32/36) and 52·8% of quarters (76/144) were infected at the first milking. About 57% (12/21) of quarters were cured following treatment with pirlimycin, 41·4% (12/29) were cured following treatment with penicillin-novobiocin and 23·1% (6/26) of infections were eliminated spontaneously in the untreated negative control group. Significantly fewer infections were observed in pirlimycin treated mammary glands of Holstein heifers during early lactation than in untreated control mammary glands. However, no significant differences were observed following penicillin-novobiocin treatment of Holstein heifers after the first milking of lactation compared with untreated control quarters. Coagulase-negative staphylococci, Streptococcus uberis and Streptococcus dysgalactiae subsp dysgalactiae were isolated most frequently in heifers from both herds.