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There is increasing interest in understanding how trait networks can be manipulated to improve the performance of crop species. Working towards this goal, we have identified key traits linking the acquisition of water, the transport of water to the sites of evaporation and photosynthesis, stomatal conductance, and growth across eight maize hybrid lines grown under well-watered and water-limiting conditions in Northern Colorado. Under well-watered conditions, hybrids with higher end-of-season growth and grain yield exhibited higher leaf-specific conductance, lower operating water potentials, higher rates of midday stomatal conductance, higher rates of net CO2 assimilation, and greater leaf osmotic adjustment. This trait network was similar under water-limited conditions with the notable exception that linkages between water transport, midday stomatal conductance, and growth were even stronger than under fully watered conditions. The maintenance of high leaf-specific conductance throughout the day was achieved via higher maximal conductance rates rather than lower susceptibility to conductance loss. Our results suggest that efforts to improve maize performance in well-watered and water-limiting conditions would benefit from considering the physiological trait networks governing water and carbon flux rather than focusing on single traits independently of one another.

There is increasing interest in understanding how trait networks can be manipulated to improve the performance of crop species. Working towards this goal, we have identified key traits linking the acquisition of water, the transport of water to the sites of evaporation and photosynthesis, stomatal conductance, and growth across eight maize hybrid lines grown under well-watered and water-limiting conditions in Northern Colorado. Under well-watered conditions, well-performing hybrids exhibited high leaf-specific conductance, low operating water potentials, high rates of midday stomatal conductance, high rates of net CO2 assimilation, greater leaf osmotic adjustment, and higher end-of-season growth and grain yield. This trait network was similar under water-limited conditions with the notable exception that linkages between water transport, midday stomatal conductance, and growth were even stronger than under fully-watered conditions. The results of this experiment suggest that similar trait networks might confer improved performance under contrasting climate and soil conditions, and that efforts to improve the performance of crop species could possibly benefit by considering the water transport pathway within leaves, as well as within the whole-xylem, in addition to root-level and leaf-level traits.

Objective.Previous studies combining biologic disease-modifying antirheumatic drugs (bDMARD) to treat rheumatoid arthritis (RA) have shown an increased risk of infection. However, the risk of infection with concurrent use of denosumab, a biologic agent for the treatment of osteoporosis, and a bDMARD remains unclear. Here, we evaluated the incidence of serious and opportunistic infections in patients treated concurrently with denosumab and a bDMARD and patients treated with a bDMARD alone.Methods.A chart review of patients with RA from 2 Canadian rheumatology practices between July 1, 2010, and July 31, 2014, identified 2 groups of patients: those taking denosumab and a bDMARD concurrently (concurrent group) and those taking only a bDMARD (biologic-alone group). Patients were followed from the time of initiation of denosumab, or a matched index date for the biologic-alone group, to the end of the study or loss to followup. Instances of serious or opportunistic infections were recorded.Results.A total of 308 patients (n = 102 for the concurrent group and n = 206 for the biologic-alone group) were evaluated. Within the concurrent group, 3 serious infection events occurred. Within the biologic-alone group, 4 serious infection events and 1 opportunistic infection event occurred. In both groups, all patients with serious or opportunistic infection recovered, and there were no instances of death during the study period.Conclusion.This study demonstrated a low occurrence of serious and opportunistic infections in patients with RA taking bDMARD, including patients with concurrent denosumab use.

Although denosumab (Prolia) has been shown to be a safe and efficacious therapy for osteoporotic patients in numerous clinical trials, few studies have determined its effectiveness in real world clinical practice. A retrospective review of patients prescribed Prolia assessing the impact that noncompliance from the regular dosing regimen of six months for denosumab has on bone mineral density (BMD) was performed. 924 patient records were reviewed between August 2012 and September 2013 with 436 patients meeting the eligibility criteria. Patients were divided into three groups: subsequent injection of denosumab (1) less than five months, (2) between five and seven months, and (3) more than seven months after their initial subcutaneous injection. A multivariable regression analysis was conducted comparing the differences among the three prespecified groups in BMD change (g/cm2) after one year of denosumab therapy at both the lumbar spine (LS) and femoral neck (FN). The differences in LS and FN BMD have shown that the relationship between the timing of drug administration in these three groups and change in BMD over 1 year was not clinically or statistically significant (p>0.05). A follow-up study with a larger sample size and longer follow-up duration is required to further characterize this relationship.

1) To assess, with a peripheral magnetic resonance imaging system (pMRI), the prevalence of bony and soft tissue abnormalities in the knee joints of normal subjects, osteoarthritis (OA) patients, and individuals who have suffered an anterior cruciate ligament (ACL) rupture; and 2) to compare the prevalence among groups.Magnetic resonance (MR) images of 28 healthy, 32 OA, and 26 ACL damaged knees were acquired with a 1.0-T pMRI system. Two radiologists graded the presence and severity of 9 MR image features: cartilage degeneration, osteophytes, subchondral cyst, bone marrow edema, meniscal abnormality, ligament integrity, loose bodies, popliteal cysts, and joint effusion.Ten of 28 healthy (35.7%), 24 of 26 ACL (92.3%), and all OA knees (100%) showed prevalent cartilage defects; 5 healthy (17.9%), 20 ACL (76.9%), and all OA knees (100%) had osteophytes; and 9 normal (32.1%), 21 ACL (80.8%), and 29 OA knees (90.6%) had meniscal abnormalities. One-half of the knees in the OA group (16 of 32, 50%) had subchondral cysts, and almost one-half had bone marrow edema (15 of 32, 46.9%). These features were not common in the ACL group (7.7%, and 11.5%, respectively) and were not observed in healthy knees. The OA group had the most severe cartilage defects, osteophytes, bone marrow edema, subchondral cysts, and meniscal abnormalities; the ACL group showed more severe cartilage defects, osteophytes, and meniscal abnormalities than did normal subjects.The results suggest that knees that have sustained ACL damage have OA-like reatures; most subjects (19 of 26, 73.1%) could be identified as in the early stage of OA. The prominent abnormalities present in ACL-damaged knees are cartilage defects, osteophytes, and meniscal abnormalities.

Background Fracture represents the single most important clinical event in patients with osteoporosis, yet remains under-predicted. As few premonitory symptoms for fracture exist, it is of critical importance that physicians effectively and efficiently identify individuals at increased fracture risk. Methods Of 3426 postmenopausal women in CANDOO, 40, 158, 99, and 64 women developed a new hip, vertebral, wrist or rib fracture, respectively. Seven easily measured risk factors predictive of fracture in research trials were examined in clinical practice including: age (, 65–69, 70–74, 75–79, 80+ years), rising from a chair with arms (yes, no), weight (< 57, ≥ 57kg), maternal history of hip facture (yes, no), prior fracture after age 50 (yes, no), hip T-score (>-1, -1 to >-2.5, ≤-2.5), and current smoking status (yes, no). Multivariable logistic regression analysis was conducted. Results The inability to rise from a chair without the use of arms (3.58; 95% CI: 1.17, 10.93) was the most significant risk factor for new hip fracture. Notable risk factors for predicting new vertebral fractures were: low body weight (1.57; 95% CI: 1.04, 2.37), current smoking (1.95; 95% CI: 1.20, 3.18) and age between 75–79 years (1.96; 95% CI: 1.10, 3.51). New wrist fractures were significantly identified by low body weight (1.71, 95% CI: 1.01, 2.90) and prior fracture after 50 years (1.96; 95% CI: 1.19, 3.22). Predictors of new rib fractures include a maternal history of a hip facture (2.89; 95% CI: 1.04, 8.08) and a prior fracture after 50 years (2.16; 95% CI: 1.20, 3.87). Conclusion This study has shown that there exists a variety of predictors of future fracture, besides BMD, that can be easily assessed by a physician. The significance of each variable depends on the site of incident fracture. Of greatest interest is that an inability to rise from a chair is perhaps the most readily identifiable significant risk factor for hip fracture and can be easily incorporated into routine clinical practice.

Background Biological drugs have dramatically improved the prognosis of rheumatoid arthritis (RA), especially in those with early disease. These patientsare often in younger age with fewer co-morbidities. Recent Canadian data suggests the highest incidence and prevalence of RA is in the 55-85 year old age group, often with associated co-morbidities, poly-pharmacy, and often longstanding disease. Objectives The objective of this real world retrospective effectiveness study was to evaluate effectiveness, safety and durability of etanercept initiated in patients over the age of 65 (inclusive). Methods This study is a retrospective analysis of all elderly RA patients, started on etanercept for at least 3 months, between Jan 2004 and Dec 2011 at a single center in Hamilton, Canada. Information was collected on demographic variables, previous and ongoing DMARDs/steroids, swollen joint counts (SJC), tender joint counts (TJC), etanercept treatment details, reason for treatment discontinuation and any reported adverse event. Efficacy was evaluated by the change in swollen and tender joint counts over a period of time after etanercept treatment. Treatment effectiveness assessed by calculating the overall drug-survival. Results A total of 72 patients from the study period of January 2004 to December 2011 were included in the analysis. A total of 71% of the patients were female, with a mean age of 73.0±5.35 years, and 73.3% were rheumatoid factor positive. 42.6% of patients had a disease duration less than 10 years. The median drug survival was 42 months, with 60% and 50% patients respectively were still on etanercept in the age group of 65-75 and more than 75 years at the end of the study period. Significant improvement in the mean SJC ( p-value p-value Conclusions As the demographics of RA changes, knowledge about RA care in the elderly population will be crucial. In this real world effectiveness study assessing RA patients over age 65, our results suggest that etanercept was an effective therapy despite the advanced age, and often long disease duration. There were also no unexpected safety concerns. Disclosure of Interest A. Lau Grant/research support: Amgen, Roche, Speakers bureau: Amgen, Roche, A. Shah: None declared, M. Deamude: None declared, C. Mech: None declared, R. Bensen: None declared, W. Bensen: None declared DOI 10.1136/annrheumdis-2014-eular.6068

Background Prolia® (denosumab) has shown to be a safe and efficacious therapy for osteoporotic patients in numerous clinical trials. However, few studies have been performed to determine its effectiveness in real world clinical practice. Currently, best practice guidelines state that Prolia® should be administered every six months. This study explores whether deviation from this recommended subcutaneous injection course would have an impact on patient9s bone mineral density (BMD). Objectives The objective of this study is to assess if a delay in administration of Prolia will have a negative impact on the patient9s BMD measured at the lumbar spine and femoral neck, measured 12 months after initiation of Prolia therapy Methods A retrospective cohort study was conducted from August 2012 to August 2013 for all osteoporotic patients who received a minimum of two subcutaneous injections of Prolia® since May 2010. Patients who have only received their first subcutaneous injection and patients without a corresponding BMD score were excluded from the study. Data obtained included age, sex, injection history (number of days between subsequent injections), and BMD of the femoral neck and lumbar spine. Patients were classified into 3 categories: 1) subsequent injection less than five months, 2) between five to seven months, 3) more than seven months after their initial subcutaneous injection. Changes in BMD from a one-year follow-up were obtained and compared. Results Of the study population (n=212), the baseline characteristics were: mean (SD) age 68.78±11.56 years, 91.9% female, 8.1% male. After one year of treatment, BMD scores increased in all three groups for both lumbar spine (37.79%, 15.16%, 18.09%) and femoral neck (8.77%, 5.55%, 8.77%) for patients receiving a subsequent injection less than five months, between five to seven months and more than seven months after their initial injection, respectively. The relationship between drug administration and change in BMD was found to be not statistically significant (p>0.05). Conclusions This study suggest that the efficacy of Prolia® (denosumab), as assessed by BMD measurements at the lumbar spine and femoral neck is not affected by a delay in timing of the subsequent injection. Current best practice is to administer the drug every six months, and although we will continue to strive for this, the preliminary data that we present suggests that there is some flexibility in this timing, especially if a subsequent injection needs to be delayed. A follow-up study with a larger sample size will allow for a more indepth characterization of this relationship. Disclosure of Interest M. Wong-Pack: None declared, A. Kalani: None declared, J. Hordyk: None declared, G. Ioannidis: None declared, R. Bensen: None declared, W. Bensen: None declared, J. Adachi Grant/research support: Amgen, Speakers bureau: Amgen, Astra Zenica, Eli Lilly, GSK, Merck, Novartis, Nycomed, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Wyeth, BMS, A. Lau Grant/research support: Amgen, Roche, Speakers bureau: Amgen, Roche DOI 10.1136/annrheumdis-2014-eular.4744