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Purpose To describe multiple ocular (and non-ocular) manifestations of disease that can present in a person who injects drugs (PWID). We report a case of a patient consecutively presenting across multiple visits to an ambulatory eye care clinic as the initial point of contact for endogenous endophthalmitis, fungal keratitis, bacteremia, and psoas abscess with vertebral osteomyelitis within a matter of weeks. Observations A 51-year-old male with past medical history of alcohol use disorder and injection drug use was initially seen in an eye clinic three days after suffering vision loss in the left eye associated with floaters, photophobia, and eye pain. After initial workup and treatment for panuveitis, endogenous endophthalmitis was suspected. A pars plana vitrectomy was performed, and intravitreal medications were given. A pathogen was never isolated from vitreous samples. Two weeks later, the patient presented with complaints of pain, blurry vision, and foreign body sensation in his opposite (right) eye. Examination revealed a corneal ulcer later identified as a Paecliomyces fungal infection. Two weeks after this, he developed fever, chills, and right-sided flank pain radiating to his testicles. Following evaluation by the emergency department and subsequent hospitalization after bacteremia was noted, he was found to have a right-sided psoas abscess with lumbar vertebral osteomyelitis. Fluid was drained, cultured, and grew methicillin-sensitive Staphylococcus aureus (MSSA). At his last visit, his best-corrected visual acuity was 20/20 OS and 20/30 OD despite central corneal scarring. It was only after hospitalization that he affirmed recent injection drug use, despite being queried about it through the course of his infections. Conclusions and importance Injection drug use is an increasingly common concern for all healthcare providers as the opioid crisis in the United States remains widespread. This case highlights multiple potential infectious processes which may impact persons who inject drugs when seen by eye care providers. It also describes difficulties in caring for people who inject drugs who may not provide critical and timely information relating to their injection drug use and/or may delay care even when faced with potentially vision- and/or life-threatening conditions.

Background: Recent studies have demonstrated that women with early stage ER-positive (ER+) and HER2-negative (HER2-) breast cancer have a persistent risk of recurrence and cancer related death up to 20 years post diagnosis, highlighting the chronic nature of ER+ breast cancer and critical need to identify tumor characteristics that are more predictive of risk of recurrence than standard clinical covariates. However, progress in delineating the dynamics of breast cancer relapse and biomarkers of late recurrence has been hindered by the lack of large cohorts with long-term clinical follow-up and molecular information. Methods: We report the results of a cohort of 3,240 breast cancer patients from the United Kingdom and Canada with 20 years of follow-up (median 9.75 years), including 1,980 with accompanying molecular data from the primary breast tumor. Information for each patient on loco-regional recurrence (LR), distant recurrence (DR), and site(s) of metastases was collected. We developed a non-homogenous Markov chain model that accounted for different clinical endpoints and timescales, as well as competing risks of mortality and the distinct baseline hazards that characterize different molecular subgroups. This approach enabled robust analysis of the spatio-temporal dynamics of breast cancer recurrence across the clinical subgroups, PAM50 subgroups and the integrative clusters, while also enabling individual risk of relapse predictions. Results: We employed our multistate model to compute the probability of experiencing a LR or DR, as well as the baseline transition probabilities from surgery, LR or DR at various time intervals for average individuals in each of the clinical/molecular subgroups. These analyses reveal four late-recurring ER+ (predominantly HER2-) subgroups, together accounting for 26% of all ER+ tumors, with high (median 42-55%) risk of recurrence up to 20 years post-diagnosis. Each of these four subgroups maps to one of the Integrative Clusters, defined based on genomic copy number alterations and gene expression, and is enriched for a characteristic copy number amplification events: 11q13 (CCND1, RSF1), 8p12 (FGFR1, ZNF703), 17q23 (RPS6KB1) and 8q24 (MYC). These four molecular subgroups are superior in predicting late DR than standard clinical variables. Conclusions: A detailed understanding of the rates and routes of metastasis and their variability across the distinct molecular subtypes is essential for devising personalized approaches to breast cancer care. We describe a molecularly characterized breast cancer cohort with long-term clinical follow-up and a statistical modeling framework, enabling delineation of the dynamics of breast cancer recurrence at unprecedented resolution. These analyses reveal four late recurring ER+ subgroups and accompanying biomarkers that collectively define the quarter of ER+ cases at highest risk of recurrence. Our findings highlight opportunities for improved patient stratification and biomarker-driven clinical trials directed at the subset of breast cancer patients with persistent risk of recurrence. Citation Format: Curtis C, Rueda OM, Sammut S-J, Chin S-F, Caswell-Jin JL, Seoane JA, Callari M, Batra R, Pereira B, Bruna A, Ali HR, Provenzano E, Liu B, Parisien M, Gillett C, McKinney S, Green A, Murphy L, Purushotham A, Ellis I, Pharoah P, Rueda C, Aparicio S, Caldas C. Dynamics of breast cancer relapse reveal molecularly defined late recurring ER-positive subgroups: Results from the METABRIC study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-06.

Supplying high voltage radio frequency (RF) is a critical part of ion trapping system due to impedance mismatching between RF source and the ion trap. A helical resonator has been constructed in order to deliver narrow bandwidth and high voltage RF to the ion trap for stable confinement of ions. The performances of the helical resonator have been studied for different capacitive load of the ion trap. Both the resonant frequency and quality factor of the resonator show strong dependence on external capacitive loads.

The United States has experienced a dramatic rise in opioid and injection drug use over the past 2 decades. A public health emergency was declared in 2017 and subsequently, there have been several new reports on the rise of endogenous endophthalmitis specifically associated with injection drug use. The purpose of this review is to provide a current perspective of the ocular harms posed by injection drug use.The opioid epidemic has prompted several new studies from New England, one of the US regions most heavily affected, that examine the trends and characteristics of injection drug use-associated endogenous endophthalmitis. Patients may delay seeking care and may be infected with a variety of rare and atypical microbes, and as a result clinical appearance may vary widely. Injection drug use also leads to embolic phenomena such as talc retinopathy and septic emboli from endocarditis. HIV is highly associated with injection drug use and although HAART has drastically reduced the morbidity and mortality of HIV-associated infections, a variety of ocular disease may accompany an immunocompromised patient.Healthcare providers must remain vigilant in the recognition of injection drug use patients with vision loss and ocular inflammation to ensure prompt medical and/or surgical treatment.

The rates and routes of lethal systemic spread in breast cancer are poorly understood owing to a lack of molecularly characterized patient cohorts with long-term, detailed follow-up data. Long-term follow-up is especially important for those with oestrogen-receptor (ER)-positive breast cancers, which can recur up to two decades after initial diagnosis1–6. It is therefore essential to identify patients who have a high risk of late relapse7–9. Here we present a statistical framework that models distinct disease stages (locoregional recurrence, distant recurrence, breast-cancer-related death and death from other causes) and competing risks of mortality from breast cancer, while yielding individual risk-of-recurrence predictions. We apply this model to 3,240 patients with breast cancer, including 1,980 for whom molecular data are available, and delineate spatiotemporal patterns of relapse across different categories of molecular information (namely immunohistochemical subtypes; PAM50 subtypes, which are based on gene-expression patterns10,11; and integrative or IntClust subtypes, which are based on patterns of genomic copy-number alterations and gene expression12,13). We identify four late-recurring integrative subtypes, comprising about one quarter (26%) of tumours that are both positive for ER and negative for human epidermal growth factor receptor 2, each with characteristic tumour-driving alterations in genomic copy number and a high risk of recurrence (mean 47–62%) up to 20 years after diagnosis. We also define a subgroup of triple-negative breast cancers in which cancer rarely recurs after five years, and a separate subgroup in which patients remain at risk. Use of the integrative subtypes improves the prediction of late, distant relapse beyond what is possible with clinical covariates (nodal status, tumour size, tumour grade and immunohistochemical subtype). These findings highlight opportunities for improved patient stratification and biomarker-driven clinical trials. A statistical framework for breast-cancer recurrence uses long-term follow-up data and a knowledge of molecular subcategories to model distinct disease stages and to predict the risk of relapse.

The resonant frequency of a helical resonator, that efficiently delivers high voltage rf to an electrodynamic ion-trap, depends on capacitive and inductive loads. Estimation of these loads for the parts that are attached to the resonator are thus necessary for designing a resonator operating at a desired frequency. On the other hand, the trapped ion experiences a voltage induced by the capacitance resulting from the electrodes. This results to excess micromotion to the ion. Here, we estimate the capacitive and resistive loads arising from different parts of ourtrap.

We are developing a frequency standard based on the ultra-narrow electric octupole transition of the ytterbium-ion (171Yb+), which is in the optical wavelength region. In this article, we describe optimized design of our end-cap type Paul trap which will be used for trapping single ions for precision frequency metrology. Selection of the materials for fabricating different parts of the trap assembly is also described. Customized design of the ultra-high vacuum chamber, which houses the ion trap, oven producing ytterbium atomic beam, compensation electrodes and high numerical aperture fluorescence collection lens together with four pairs of optical viewports is lastly described.

This medical record review study compares the clinical characteristics of endogenous endophthalmitis in patients with and without injection drug use.

Fluorescein angiography (FA) is an indispensable imaging modality in the diagnosis and management of patients with intermediate, posterior, and panuveitis. The pattern and type of retinovascular and chorioretinal involvement may be useful diagnostically and in the assessment of structural abnormalities associated with visual loss. Moreover, FA may provide a sensitive index with respect to extent of active inflammation and influence the threshold for treatment as well as monitoring the response to therapy. Finally, FA in combination with multimodal imaging provides not only expanded diagnostic and management capabilities but also may shed new light on our basic understanding of posterior segment inflammatory diseases.

Summary Objectives To describe whether body mass index (BMI) is a clinically meaningful predictor of patient reported outcomes following primary total hip replacement (THR) surgery. Design Combined data from prospective cohort studies. We obtained information from four cohorts of patients receiving primary THR for osteoarthritis: Exeter Primary Outcomes Study (EPOS) ( n = 1431); EUROHIP ( n = 1327); Elective Orthopaedic Centre ( n = 2832); and St. Helier ( n = 787). The exposure of interest was pre-operative BMI. Confounding variables included: age, sex, SF-36 mental health, comorbidities, fixed flexion, analgesic use, college education, OA in other joints, expectation of less pain, radiographic K&L grade, ASA grade, years of hip pain. The primary outcome was the Oxford Hip Score (OHS). Regression models describe the association of BMI on outcome adjusting for all confounders. Results For a 5-unit increase in BMI, the attained 12-month OHS decreases by 0.78 points 95%CI (0.27–1.28), P -value 0.001. Compared to people of normal BMI (20–25), those in the obese class II (BMI 35–40) would have a 12-month OHS that is 2.34 points lower. Although statistically significant this effect is small and not clinically meaningful in contrast to the substantial change in OHS seen across all BMI groupings. In obese class II patients achieved a 22.2 point change in OHS following surgery. Conclusions Patients achieved substantial change in OHS after THR across all BMI categories, which greatly outweighs the small difference in attained post-operative score. The findings suggest BMI should not present a barrier to access THR in terms of PROMs.

Traditional literature emphasizes the role of foreign capital, especially foreign direct investment (FDI) in explaining the high growth rates that many emerging economies have enjoyed during 1990s and 2000s. The present paper accepts this conventional wisdom but argues that the FDI has also created problems of urban sprawl and congestion that would not be so intense if economic development had primarily come from domestic sources. This is because the FDI is typically concentrated in urban areas that abound in manufacturing and it neglects the rural areas where agriculture predominates. The paper suggests that a small tax on foreign capital tends to mitigate the side effects of foreign investment.

Objective Quantitative sensory testing (QST) and questionnaire-based assessments have been used to demonstrate features of neuropathic pain in subjects with musculoskeletal pain. However, their direct relationship has not been investigated in the community. The purpose of this study was to conduct an observational study to describe the characteristics of joint pain and to examine the relationship between QST measures and the PainDETECT Questionnaire (PD-Q). Methods Warm detection, heat pain, and mechanical pain thresholds as well as mechanical pain sensitivity over the sternum were determined and the PD-Q scores were calculated in a cross-sectional study of 462 participants in the Chingford Study. Comparisons were made between subjects with and those without joint pain. Logistic regression modeling was used to describe the association between neuropathic pain features, as determined by the PD-Q score, and each of the QST measures individually, adjusting for age, body mass index, and use of pain-modifying medications. Results A total of 66.2% of the subjects reported recent joint pain, with a median average pain severity of 5 of 10. There was increased sensitivity to painful stimuli in the group with pain as compared to the pain-free group, and this persisted after stratification by pain-modifying medication use. While only 6.7% of subjects had possible neuropathic pain features and 1.9% likely neuropathic pain features according to the standard PD-Q thresholds, features of neuropathic pain were common and were present in >50% of those reporting pain of at least moderate severity. Heat pain thresholds and mechanical pain sensitivity were significantly associated with features of neuropathic pain identified using the PD-Q, with an odds ratio (OR) of 0.88 (95% confidence interval [95% CI] 0.79–0.97; P = 0.011) and an OR of 1.24 (95% CI 1.04–1.48; P = 0.018), respectively. Conclusion QST measures and the PD-Q identified features of neuropathic pain in subjects in this community-based study, with significant overlap between the findings of the two techniques.

Objective:Genetic factors and abnormalities of joint morphology are important in the aetiology of hip osteoarthritis (OA). The extent to which genetic influences are manifest through joint morphology has undergone limited investigation. Using a cohort with an hereditary predisposition to end-stage hip OA and a control group with no inherited risk, we aimed to identify associations with abnormal joint morphology and clinical features.Design:One hundred and twenty-three individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) (termed ‘sibkids’) were compared with 80 spouse controls. Morphology was assessed using standardised radiographs and cam, dysplasia, and pincer deformities defined. Regression modelling described the association of cohort with abnormal joint morphology, adjusting for confounders [age, gender, body mass index (BMI), OA, and osteophyte].Results:Sibkids had an odds ratio of 2.1 [95%confidence interval (CI) 1.3–3.5] for cam deformity. There were no differences in the prevalence of dysplasia or pincer deformities. In both groups, hips with cam deformities or dysplasia were more likely to have clinical features than normal hips [odds ratio (OR) 4.46 (1.8–11.3), and 4.40 (1.4–14.3) respectively]. Pincer deformity was associated with positive signs in the sibkids but not in the controls (OR 3.0; 1.1–8.2).Discussion:After adjustment for confounders that cause secondary morphological change, individuals with an hereditary predisposition to end-stage hip OA had a higher prevalence of morphological abnormalities associated with hip OA. Sibkids were more likely to demonstrate clinical features in the presence of pincer deformity, suggesting that the genes are acting not only through abnormal morphology but also through other factors that influence the prevalence of pain.

At 8 and 16 weeks post DMM surgery, there was more effector microglia expression in the DH, particularly at the L4 level of the spinal cord (Fig 1). Conclusions: The temporal correlation of fractalkine release with microglial activation suggests that fractalkine may contribute to microglial activation in the DH of the spinal cord. Microglial activation in the DH has been reported in murine mono-iodoacetate (MIA) arthritis as well as nerve injurymodels. Results from this study will help elucidate how pain signals propagate from the peripheral to the central nervous system in osteoarthritis.

Summary Objective Genetic factors are important in the aetiology of hip osteoarthritis (OA), but studies are limited by cross-sectional design and poor association with clinically important disease. Identifying cohorts with progressive OA will facilitate development of OA biomarkers. Using a middle-aged cohort with genetic predisposition to hip OA and a control group, we compared the prevalence of clinical and radiographic hip OA and incidence of progression over 5 years. Design 123 individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) (‘sibkids') were compared with 80 (mean age 54 years) controls. The prevalence of radiographic OA [scored according to Kellgren & Lawrence (K&L)], clinical features, and incidence of clinical progression over a 5-year period were compared. A multivariate logistic regression model was used to adjust for confounders. Results Sibkids had odds ratios (ORs) of 2.7 [95% confidence interval (CI) 1.1–6.3, P = 0.02] for hip OA (K&L grade ≥2), 3.4 (1.4–8.4, P = 0.008) for clinical signs, and 2.1 (0.8–5.8, P = 0.14) for signs and symptoms. Over 5 years, sibkids had ORs of 4.7 (1.7–13.2, P = 0.003) for the development of signs, and 3.2 (1.0–10.3, P = 0.047) for the development of signs and symptoms. Discussion Compared to a control group and after adjustment for confounders, individuals with genetic predisposition to end-stage hip OA have higher prevalence of OA, clinical features, and progression. In addition to structural degeneration, the inherited risk may include predisposition to pain. Genetically-loaded cohorts are useful to develop hip OA biomarkers, as they develop progressive disease at a young age.

The purpose of this paper is to incorporate the currently mushrooming phenomenon of outsourcing into the standard two-sector, two-factor Heckscher–Ohlin model of international trade. We first show how outsourcing modifies a firm's production function, and then demonstrate that outsourcing generally raises the return to capital and lowers the real wage, although the nation's GDP rises in proportion to the value-added in the outsourcing industry. Furthermore, the output of the outsourcing sector may actually fall even though its unit cost goes down; the output of the other sector then rises. By contrast, employment in the outsourcing sector may actually rise.

Outsourcing has become an increasingly contentious subject ever since N. Gregory Mankiw remarked in 2004 that outsourcing is just another way of doing international trade, and must be beneficial to the nation, including the workers. We construct a simple two-sector specific-factor model and explore the validity of Mankiw's remarks. We find his ideas are valid when the country does not produce any outsourced factor's work at home in that both the laborers and the nation benefit. But when some outsourced factor cum intermediate good is also produced at home, the nation still benefits but the workers may suffer.

We are developing the first optical frequency standard in India with single ytterbium ion (171Yb+), which is confined and laser cooled in an ion trap. This precision clock experiment needs to be automated for running it reliably and continuously over few days. For this we are developing a computer control systems. Some of its supporting hardware modules have already been designed and tested. In this article we describe scheme of our automation and control system.

This paper presents a framework which simplifies the task of developing, deploying, and managing complex, integrated, and standards-compliant eGovernance solutions. The framework enables development, configuration, integration, and management of solutions at a higher semantic level. It also provides commonly used services such as access to citizen and property records, access control and authentication services, public key infrastructure, and support for digital signatures. The ability to manage solutions at a higher semantic level enables administrators who are not proficient in programming to customize solutions in order to address specific needs of the different national, state, and local governments. This includes the ability to customize interfaces for multiple local languages used in government transactions and to customize workflows to conform to the organizational structure and policies to manage access to and retention of government records.

Breast cancer is the most common cancer among women showing high clinical and molecular heterogeneity. Current clinical management causes patients overtreatment with implications on both patients’ quality of life and healthcare costs. Moreover, intrinsic or acquired tumor resistance to treatment leads to incurable metastatic progression in a significant proportion of patients. Consequently, there is an urgent need for better predictive biomarkers and a better understanding of the mechanisms driving response to treatment. As part of the METABRIC initiative, we fully molecularly characterized 2000 breast primary tumors, measuring gene expression, copy number aberration, somatic mutations and methylation. In addition, a biobank of breast cancer patient-derived tumor xenograft (PDTX) models (n=92) has been generated in our lab and a comprehensive molecular characterization was also obtained. We recently demonstrated that breast cancer PDTXs maintain originating cancers intra-tumor heterogeneity, hence representing a more relevant preclinical model than cell lines. An ex-vivo drug screening was performed in these models generating response data (IC50 and AUC) for 100 different drugs, including "best in class" PI3K, PARP and CDK4/6 inhibitors, novel biological and chemical inhibitors of HER2, ER, IGF1R and HER3, as well as standard of care agents. Here we derived signatures of pathway activation/disruption by integrating different data types in the METABRIC cohort. Their association with previous breast cancer classifications, as well as their prognostic significance was studied. The predictive power of these signatures was investigated in the PDTX cohort to identify novel pharmacogenomics associations. They were tested independently as well as in combination, to derive molecular predictors of response to treatment. We found known and novel associations between genomic/transcriptomic features and drug response. For example, our results confirmed the known association between estrogen receptor-related genes and response to tamoxifen treatment. We also identified markers of response to inhibitors of the PI3K/AKT/mTOR pathway. Selected findings were validated in clinical cohorts as well as in independent PDTX models. In conclusion, by integrating molecular data from large cohorts of clinical samples and PDTX we have generated a computational framework for the systematic identification of pharmacogenomics associations in breast cancer and to generate hypothesis for rational drug-drug combinations. Citation Format: Maurizio Callari, Rajbir N. Batra, Ankita Sati Batra, Wendy Greenwood, Suet-Feung Chin, Alejandra Bruna, Oscar M. Rueda, Carlos Caldas. Integrative analysis of molecular and drug response data from clinical samples and PDTXs to identify pharmacogenomic associations in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2991. doi:10.1158/1538-7445.AM2017-2991

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S209 Purpose: Non-steroidal anti-inflammatory agents (NSAIDs) are commonly used to manage symptoms in patients with knee osteoarthritis (OA). While randomized controlled trials have demonstrated efficacy, real world effectiveness of these agents in long term studies is lacking. This study sought to estimate the effectiveness of NSAIDs on symptom management over 4 years among persons with radiographically confirmed OA. Marginal structural models, which take into consideration the likely dual role of indices of disease severity as confounders and intermediary variables, were compared to standard repeated-measure analyses. Methods: We identified NSAID naive participants with radiographic knee OA in the Osteoarthritis Initiative. Participants were evaluated over 4 years. NSAID users included those reporting any use of prescription medication use (i.e., either regular use or as-needed use) at each assessment. Outcome measures included WOMAC Pain, Stiffness and Physical Function. Beta coefficients derived from marginal structural models and generalized estimating equation models represented the average change in outcomemeasures attributed to long term NSAID use. Minimally important clinical differences were a priori set as at least 1.2 for pain, 0.5 for stiffness, and 4.1 for function. Results: Persons with radiographically confirmed OA with long term reports of prescription NSAIDS use experienced improvements in WOMAC Pain: -0.99 (95% Confidence Interval (CI): -2.38 to 0.4); WOMAC Stiffness: -0.64 (95% CI: -1.52 to 0.24); and WOMAC Function: -5.29 (95% CI: -9.7 to -0.89). In contrast, the analysis with generalized estimating equations yields an estimate of -0.03, -0.08 and 0.07 for difference in Pain, Stiffness and Function, respectively. Conclusions: When evaluated using marginal structural models, long term use of NSAIDs showed a modest trend towards relieving symptoms and a clinically significant improvement in function in patients with radiographically confirmed OA, whereas a standard regression models didn’t show such benefits. Studies on the treatment of OA using non-experimental data should consider using marginal structural models when evaluating the overall treatment effect from a timevarying treatment. 366 PATIENT REPORTED OUTCOMES FOLLOWING PRIMARY HIP REPLACEMENT SURGERY: DEVELOPMENT AND INTERNAL VALIDATION OF A PROGNOSTIC TOOL A. Judge yz, R.N. Batra y, D. Murray y, P.A. Dieppe x, M.T. Sanchez-Santos y, G. Thomas y, D. Beard y, M.K. Javaid yz, K. Dreinh€ ofer k{, K. Peter-G€ unther#, C. Cooper yz, N.K. Arden yz. yNIHR Musculoskeletal BioMed. Res. Unit, Univ. of Oxford, Oxford, United Kingdom; zMRC Lifecourse Epidemiology Unit, Univ. of Southampton, Southampton, United Kingdom; x Peninsula Coll. of Med. and Dentistry, Univ. of Plymouth, Plymouth, United Kingdom; k Inst. for Muskuloskeletal Rehabilitation, Charit e Univ.smedizin Berlin, Berlin, Germany; {Dept. of Orthopaedics, Traumatology and Sports Med., Med. Park Berlin Humboldtm€ uhle, Berlin, Germany; Dept. of Orthopaedic Surgery, Univ. Hosp. Carl Gustav Carus, Med. Faculty of the Technical Univ. of Dresden, Dresden, Germany Purpose: Although Total Hip Replacement (THR) is a successful surgical intervention, there are a minority of patients who do not achieve clinically meaningful improvement or whose symptoms get worse following surgery. The aim of this study was to develop a clinical risk prediction tool to predict patient reported outcomes following primary hip replacement surgery. Methods: We obtained data on two prospective cohorts of patients receiving primary THR for osteoarthritis: Exeter Primary Outcomes Study (n 1⁄4 1247); EUROHIP (n 1⁄4 845). The primary outcome was the Oxford Hip Score (OHS). Combining data from two large prospective cohort studies allowed us to take account of a wide and comprehensive range of both traditional and novel risk factors, including patient, radiographic and surgical predictors. Linear regression modelling was used to identify predictors of outcome. For internal validationwe used a combination of multiple imputation and bootstrapping with backward selection. Performance of the predictive model was assessed in terms of calibration and discrimination. Results: Of the radiographic variables pattern of OA was an important determinant of outcome. Those with superomedial, medial or concentric disease had worse outcomes than patients with a superolateral pattern of OA or no reduction in joint space. Arthritis in other joints, and previous surgery on other joints, were associated with worse outcomes. For surgical variables, a posterior surgical approach, and larger femoral component offset had better outcomes. For patient factors, worse preoperative pain/function, increasing age when over age 75, increasing BMI, lower levels of educational attainment and those with worse preoperative SF36 mental health scores, also had worse outcomes. These factors were operationalized into a clinical risk prediction tool. Calibration of the predicted 12-month post-operative OHS, and absolute change in OHS was good. The model showed good discriminatory ability with a bias corrected R-squared of 23.1%. We tested the ability of the model to identify patients with the worst possible outcomes following THR (defined as a change in OHS < 5-points of whom 89 (4.25%) patients met this criterion). Performance of the tool to identify patients with the worst outcomes was good (C-statistic 0.77 95%CI (0.72 to 0.82)). Conclusions: We have developed a clinical risk prediction tool that would provide information on the likely outcomes of hip replacement surgery. Following hip replacement the majority of patients do very well, and only a minority will not achieve clinically meaningful symptomatic change in OHS. The clinical tool performed well in terms of its calibration and discriminatory ability, and identification of those patients with the worst possible outcomes was good. The tool provides individualised risk prediction and allows patients to understand their expected outcomes of surgery – it has the potential to guide patientclinician decision-making. It will now undergo external validation in a new prospective cohort of patients. 367 COURSE OF PHYSICAL FUNCTIONING AND PAIN IN OSTEOARTHRITIS OF THE KNEE OR HIP: A SYSTEMATIC REVIEW M. de Rooij y, M. van der Leeden yz, A. H€ akkinen#x, W.F. Lems ky, L.D. Roorda y, C. Veenhof{, H.C. de Vet #, J. Dekker yy. yAmsterdam Rehabilitation Res. Ctr. j Reade, Amsterdam, Netherlands; zVU Univ. Med. Ctr., Dept. of Rehabilitation Med., Amsterdam, Netherlands; xDept. of Hlth. Sci., Univ. of Jyv€ askyl€ a and Jyv€ askyl€ a Central Hosp., Jyv€ askyl€ a, Finland; kVU Univ. Med. Ctr., Dept. of Rheumatology, Amsterdam, Netherlands; {Netherlands Inst. for Hlth. Services Res., Utrecht, Netherlands; VU Univ. Med. Ctr. EMGO Inst. for Hlth. and Care Res., Dept. of Epidemiology and Biostatistics, Amsterdam, Netherlands; yyVU Univ. Med. Ctr., Dept. of Psychiatry, Dept. of Rehabilitation Med., EMGO Inst., Amsterdam, Netherlands Purpose: (1) The aim of the study was to systematically summarize the literature from March 2005 to January 2013 on the course of physical functioning and pain in patients with OA of the knee or hip and (2) to provide an overview of prognostic factors of physical functioning and future pain for these patients. Methods: A search was conducted in PubMed, CINAHL, Embase and Psych-INFO in January 2013. Eligible studies were prospective cohort studies (minimum follow up was 6 months) that included participants with knee or hip OA diagnosed with radiographically and/or

In this paper we present a model that highlights the relationship between international trade and environmental pollution. It includes a small open economy that produces a domestic composite good and imports another composite good and energy products. The pollution is created by local production, global production and transportation. Given this model we demonstrate that free trade within the current political and economic context may produce a suboptimal level of welfare. The rationale is based upon the argument that transportation is energy-intensive and that, therefore, trade itself is a source of pollution. Consequently, under certain global conditions the introduction of an energy tariff in a small open economy raises social welfare and is superior to free trade. A consumption tariff adopted by a single nation will not have similar consequences because it has no impact upon local usage. However, when a consumption tariff is globally adopted there is the opportunity for a net benefit. Finally, we argue that a global tariff that raises both the price of energy and the price of the imported composite good may generate the greatest increase in welfare by reducing both energy-intensive production and energy-intensive trade.

OBJECTIVES: To identify patient characteristics and surgical factors associated with patient-reported outcomes over 5 years following primary total hip replacement (THR). DESIGN: Prospective cohort study. SETTING: Seven hospitals across England and Scotland. PARTICIPANTS: 1431 primary hip replacements for osteoarthritis. MAIN OUTCOME MEASURES: The Oxford Hip Score (OHS) was collected preoperatively and each year up to 5 years postoperatively. Repeated measures such as linear regression modelling are used to identify patient and surgical predictors of outcome and describe trends over time. RESULTS: The majority of patients demonstrated substantial improvement in pain/function in the first year after surgery-between 1 and 5 years follow-up, there was neither further improvement nor decline. The strongest determinant of attained postoperative OHS was the preoperative OHS-those with worse preoperative pain/function had worse postoperative pain/function. Other predictors with small but significant effects included: femoral component offset-women with an offset of 44 or more had better outcomes; age-compared to those aged 50-60, younger (age 60) had worse outcome, increasing body mass index (BMI), more coexisting diseases and worse Short Form 36 mental health (MH) was related to worse postoperative pain/function. Assessment of change in OHS between preoperative and postoperative assessments revealed that patients achieved substantial and clinically relevant symptomatic improvement (change), regardless of variation in these patient and surgical factors. CONCLUSIONS: Patients received substantial benefit from surgery, regardless of their preoperative assessments and surgical characteristics (baseline pain/function, age, BMI, comorbidities, MH and femoral component offset). Further research is needed to identify other factors that can improve our ability to identify patients at risk of poor outcomes from THR surgery.

To create a prognostic tool to quantify the 5-year cardiovascular (CV) risk in patients with newly diagnosed Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) without premorbid CV disease. We reviewed CV outcomes during the long-term followup of patients in the first 4 European Vasculitis Study Group (EUVAS) trials of WG and MPA. CV events were defined as CV death, stroke, myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention. Logistic regression was performed to create a model to predict the absolute risk of a CV event. The model was tested using the Wegener's Granulomatosis Etanercept Trial (WGET) cohort. Seventy-four (13.8%) of 535 patients with 5 years of followup from the EUVAS trials had at least 1 CV event: 33 (11.7%) of 281 WG versus 41 (16.1%) of 254 MPA. The independent determinants of CV outcomes were older age (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.11-1.90), diastolic hypertension (OR 1.97, 95% CI 0.98-3.95), and positive proteinase 3 (PR3) antineutrophil cytoplasmic antibody (ANCA) status (OR 0.39, 95% CI 0.20-0.74). The model was validated using the WGET cohort (area under the receiver operating characteristic curve of 0.80). Within 5 years of diagnosis of WG or MPA, 14% of patients will have a CV event. We have constructed and validated a tool to quantify the risk of a CV event based on age, diastolic hypertension, and PR3 ANCA status in patients without prior CV disease. In patients with vasculitis, PR3 ANCA is associated with a reduced CV risk compared to myeloperoxidase ANCA or negative ANCA status. Copyright © 2011 by the American College of Rheumatology.

OBJECTIVE: Assessment of disease activity in vasculitis can be achieved using the BVAS, a clinical checklist of relevant symptoms, signs and features of active disease. The aim of this study was to revalidate the BVAS version 3 (BVAS v. 3) in a cohort of patients with systemic vasculitis. METHODS: A total of 238 patients with vasculitis from seven countries in Europe were evaluated at a single time point. Spearman's correlation coefficients were calculated between BVAS v. 3 scores, vasculitis activity index (VAI), physician's global assessment (PGA), the physician's treatment decision, CRP and the vasculitis damage index (VDI) to demonstrate that the BVAS v. 3 measures disease activity. RESULTS: WG (63%), Churg-Strauss syndrome (9%) and microscopic polyangiitis (9%) were the most common diagnoses. The BVAS v. 3 showed convergent validity with the VAI [ρ = 0.82 (95% CI 0.77, 0.85)], PGA [ρ = 0.85 (95% CI 0.81, 0.88)] and the physician's treatment decision [ρ = 0.54 (95% CI 0.44, 0.62)]. There was little or no correlation between BVAS v. 3 and the CRP level [ρ = 0.18 (95% CI 0.05, 0.30)] or with the VDI [ρ = -0.10 (95% CI 0.22, 0.03)]. The inter-observer reliability was very high with an intra-class correlation coefficient (ICC) of 0.996 (95% CI 0.990, 0.998) for the total BVAS v. 3 score. CONCLUSION: The BVAS v. 3 has been evaluated in a large cohort of patients with vasculitis and the important properties of the tool revalidated. This study increases the utility of the BVAS v. 3 in different populations of patients with systemic vasculitis.

ObjectiveTo determine whether neuromyelitis optica (NMO) immunoglobulin (IgG) antibody status in NMO/Devic’s disease patients followed prospectively is persistent or can change relative to the clinical status and/or response to therapy.DesignA cross-sectional group of patients with NMO, relapsing extensive longitudinal transverse myelitis (RLETM) or optico-spinal multiple sclerosis (OSMS) were evaluated for the presence of NMO IgG antibodies. Repeated evaluation was made in all NMO/RLETM patients and in a subgroup of OSMS patients.SettingBaird Multiple Sclerosis Center, Buffalo, New York, an academic multiple sclerosis center.ResultsOut of a consecutive cohort of 38 patients evaluated for the presence of NMO IgG, 12 had NMO and 26 had OSMS. Five of the 12 NMO/RLETM patients were NMO IgG positive at the time of their initial evaluation. Four of these patients were repeatedly tested for NMO IgG: two of these became negative and two remained positive. One patient who was initially negative became positive during an acute event and again became negative during the stable disease phase following treatment. A positive test result was associated with active disease, whereas a negative NMO IgG result was consistently found in stable, long-term treated patients. None of the OSMS patients were positive for NMO IgG even during acute attacks.ConclusionsNMO IgG antibodies are associated with active NMO/RLETM. A well-controlled stable disease usually under effective immunosuppressive therapy can transform the NMO IgG to a negative status. Repeated NMO IgG testing should be considered as a useful biological marker for monitoring NMO/RLETM disease and or response to therapy.

s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S152 study ,using the cell culturing technology, was to observe what different results would come out from the MTTassay of the ATDC5 cell proliferation, whick had been cultured with different concentration E2. Methods: The 17-bestradiol we use was ordered from Sigma co. and the ATDC5 cell line was form the Riken cell bank. We culture the ATDC5 24 hours in the media with different concentration 17-bestradiol, then we test the OD value of the different cells in MTT assay to assume the proliferation of the ATDC5. Results: After culturing 24 hours in the media with different concentration 17-bestradiol, the proliferation of the ATDC5 in different concentration 17-bestradiol were different significantly, the higher of the concentration, the higher of the proliferation, as follows: beside the 10-11M against 0 M, the 10-10,10-9,10-8 and 10-7 M have significant difference in stimulating the proliferation of ATDC5 against 0 M. between the different concentration groups, only 10-8 M has significant difference against 10-11,10-10 M. Conclusions: First, 17-bestradiol has stimulation on the proliferation of ATDC5. Second, 10-8 M concentration of 17-bestradiol has the strongest stimulating effect than the other concentration of 17-bestradiol. Clinical Aspects / Outcomes 302 PRE-OPERATIVE BMI AS A PREDICTOR OF PATIENT REPORTED OUTCOMES OF PRIMARY HIP REPLACEMENT SURGERY: A COMBINED ANALYSIS OF 4 PROSPECTIVE COHORT STUDIES R.N. Batra , A. Judge , M.K. Javaid , G.E. Thomas , D. Beard , D. Murray , P. Dieppe , K. Drienhoefer , K. Peter-Geunther , R. Field , C. Cooper , N.K. Arden . NIHR BioMed. Res. Unit, Univ. of Oxford, Oxford, United Kingdom; MRC Lifecourse Epidemiology Unit, Univ. of Southampton, Southampton, United Kingdom; 3 Peninsula Coll. of Med. and Dentistry, Plymouth, United Kingdom; Charite Univ.smedizin Berlin, Dept. of Orthop., Traumatology and Sports Med., Berlin, Germany; Univ. Hosp. Carl Gustav Carus, Technical Univ. of Dresden, Dresden, Germany; 6 Elective Orthop. Ctr., Epsom, United Kingdom Purpose: Total hip replacement (THR) is a successful surgical intervention, providing relief from pain, increasingmobility and improving quality of life for majority of patients. Within the literature some, but not all studies, have found that obesity is associated with worse patient reported outcomes (PROMs) of THR, and there is increasing concern that obesity may be used as a barrier to accessing surgery. Methods: We obtained information from 4 prospective cohort studies of patients receiving primary THR for osteoarthritis (OA): Exeter Primary Outcomes Study (EPOS) (n1⁄41589); EUROHIP (n1⁄4908); South West London Elective Orthopaedic Centre (SWLEOC) (n1⁄41523); and St. Helier (n1⁄4799). The primary outcome was the 12 month Oxford Hip Score (OHS) which is used to assess pain and function.For the EUROHIP study, we imputed the OHS from WOMAC scores using truncated regression. Confounding variables included: age, sex, SF-36 mental health, comorbidities, fixed flexion, analgesic use, college education, OA in other joints, expectation of less pain, radiographic KL only age and sex were available in all 4 cohorts. Linear regression (ANCOVA) is used to describe the association of BMI on the 12 month OHS, adjusting for the pre-operative OHS. Multiple imputation methods were used to handle missing data. In order to combine data across the 4 studies we used two methodological approaches: a) Meta-Analysis For each study, separate models are built to describe the association of BMI on outcome. Models are adjusted only for age and sex in order to construct related hypotheses in each study. Fixed effects metaanalysis is used to combine the results; b) Combining studies Data from all 4 studies are combined using multiple imputation methods to impute data on missing confounders, allowing the association of BMI on outcome to be adjusted for all potential confounders. Results: a) Meta-Analysis Adjusting for age and sex, for a 5 unit increase in BMI, the 12 month OHS decreases by 0.81 95%CI (0.55 1.08) units (Figure 1); Ă b) Combining Studies Adjusting for age and sex alone, for a 5 unit increase in BMI, the 12 month OHS decreases by 0.72 (0.46 0.99) units. Adjusting for all potential confounders, the effect is attenuated to 0.51 (0.09 0.92). Hence, for each 5 unit increase in BMI, the difference in post-op OHS becomes larger and more important. For example, compared to people with a normal BMI (20 25), those in the morbidly obese group (BMI 35 40) would have a post-op OHS that is 1.53 units lower. However, there is a substantial improvement in OHS after THR across all BMI groups, which greatly outweighs any difference in post-op score (Figure 2).

Purpose: Establishing a population-based estimate for the lifetime risk of total hip and knee replacement (THR/TKR) is an important epidemiological development which will assist health service planners in assessing the future burden of lower limb arthroplasty. Methods:We used data from the U.K. General Practice Research Database (GPRD) which contains all the computerised records of 6.25m patients, and is representative of the population of the U.K. We collected data on all THRs and TKRs performed between 1991 and 2006, a total of over 27,000 THRs and 24,000 TKRs. We calculated incidence rates for THR/TKR under a Poisson model and combined these rates with mortality rates from the U.K Office for National Statistics (ONS) using a life-table framework. These estimates were then aggregated to produce a simple lifetime risk of THR and TKR by gender for age 50 and above. We also calculated the temporal trend in lifetime risk at age 50 by single calendar year from 1991 to 2006. Results: We estimated that at age 50 the mortality-adjusted lifetime risk of THR was 7.80% for females and 5.05% for males (TKR: 6.66% and 5.04% respectively). The risks of THR for females aged 50 was 54% greater for than for males (32% greater for TKR). The risk percentage decreases with increasing age for both THR and TKR in males and females. At age 80 the gender gap in risk of THR remains in favour of females (53% higher) but in TKR it is two-thirds of that at age 50 (females 21% higher). Between 1991 and 2006, the lifetime risk of THR rose from 3.89% to 10.41% for females and for males from 3.43% to 6.34%. Over the same period, for TKR the risk for females increased from 2.78% to 10.02% and for males from 1.57% to 7.39%.

Objective: To determine appropriate terminology for addressing women in pregnancy. Design: 100 women (aged 15–50) were asked to fill in a questionnaire using one of the six choices provided for addressing women in pregnancy. Setting: Antenatal clinic of a teaching hospital. Results: Preferences vary according to context but simple terms like mother-to-be and pregnant women were more popular than client, consumer and maternant. Conclusion: No single terminology for addressing women in pregnancy wins all round approval but simple softer terms like Mother-to-be please a vast majority.

In this paper we provide a synthesis between the neoclassical and the Heckscher-Ohlin models of international trade by developing the properties of a two-sector, three-factor model. The neoclassical model, where one or more factors are specific to one or both industries, and the Heckscher-Ohlin model, where two (or all factors) are nonspecific, then can be analyzed as special cases of our model. The theorems by Rybczynski, Stolper and Samuelson, Jones and Chipman, among others, are reexamined in terms of our generalized model.

In this paper, we introduce diminishing returns to scale in Brecher's model of international trade with unemployment and then investigate some issues embodied in the theory of international trade. Our principal results are that tariffs need not improve a country's terms of trade and that capital accumulation also need not result in a predictable change in the terms of trade.

This paper extends the Harris-Todaro model with intersectoral capital mobility to include sector specific imported technologies. Technologies are assumed to be embodied in imported capital goods. The small economy in the South, for which the model is defined, can import any amount of these technologies from the North at given royalty rates. We find that if the North agrees to reduce the royalty rate on the industrial technology, both the level and the rate of urban unemployment would rise and the income distribution change against the wage earners, whereas such a reduction for the agricultural technology would have just the opposite effects. A decrease in either royalty rate would increase the national income in the South, although the magnitude of the increase in income would be larger with reduced royalty rate for agricultural rather than industrial technology. The policy implication is that the South should emphasize the import of agricultural technology over the industrial technology.

The purpose of this paper is to examine the implications of uncertainty for resource allocation, real income, and income distribution in terms of a simple two-sector general equilibrium model of a small country where uncertainty is introduced by assuming that production in one sector occurs in a stochastic environment. Assuming decreasing risk aversion, we show that an increase in uncertainty causes the movement of the resources away from the uncertain sector, a decline in expected real income, and a shift in the distribution of income against the factor employed intensively by the uncertain sector.

Summary Objective Femoroacetabular Impingement (FAI) and Acetabular Dysplasia are common deformities, which have been implicated as a major cause of hip osteoarthritis (OA). We examined whether these subtle deformities of the hip are associated with the development of radiographic OA and total hip replacement (THR) in women. Design A population-based, longitudinal cohort of 1003 women underwent pelvis radiographs at years 2 and 20. Alpha Angle, Triangular Index Height, Lateral Centre Edge (LCE) angle and Extrusion Index were measured. An alpha angle of greater than 65° was defined as Cam-type FAI. Radiographic OA and the presence of a THR were then determined at 20 years. Results Cam-type FAI was significantly associated with the development of radiographic OA. Each degree increase in alpha angle above 65° was associated with an increase in risk of 5% (Odds Ratio (OR) 1.05 [95% confidence interval (CI) 1.01–1.09]) for radiographic OA and 4% (OR 1.04 [95% CI 1.00–1.08]) for THR. For Acetabular Dysplasia, each degree reduction in LCE angle below 28° was associated with an increase in risk of 13.0% (OR 0.87 [95% CI 0.78–0.96]) for radiographic OA and 18% (OR 0.82 [95% CI 0.75–0.89]) for THR. Conclusions This study demonstrates that Cam-type FAI and mild Acetabular Dysplasia are predictive of subsequent OA and THR in a large female population cohort. These are independent of age, BMI and joint space and significantly improve current predictive models of hip OA development.

One of the most fundamental issues in international trade theory concerns the determination of a country’s pattern of trade. The problem is to determine what goods a country will export or import. Stated differently, is it possible to prognosticate a country’s configuration of importables or exportables just by examining the characteristics of its closed economy? The answer to this question defines not only a country’s trade pattern but also the basis for the very presence of international trade. In other words, the explanation for the trade pattern is also, in general, an explanation for why a country trades at all.

Recent years have witnessed a steadily growing application of the standard two-factor, two-good model to the solution of questions that arise in a growing economy, questions that were first raised in a seminal contribution by Oniki and Uzawa [5]. Although some insights as to what happens in the economy under conditions of growing factor supplies and technology were gained in Chapter 6, the nature of our analysis there was essentially comparative statics, for we were concerned primarily with the implications of exogenous and once-for-all growth in factor supplies. In the present chapter, however, our concern will be the development of a dynamic model where labour grows exogenously at a certain given rate, but where capital grows endogenously as a result of the savings habits of the factor owners. Oniki and Uzawa and, following them, otherst have used a technique which, for want of a better substitute, I call the ‘production function’ technique. The mathematical calculations under this technique are quite lengthy and oppressive, and a superficial glance is sufficient to discourage the student from getting seriously involved with the problem. Fortunately, the technique suggested by the activity-analysis approach used in the past chapters cuts down the length of the derivations and makes the issues susceptible to better comprehension.

Every country produces goods which cannot be traded at all either because of the nature of the goods, like houses, services, etc., or because of political barriers preventing, for example, the export of certain strategic military equipment, or because of artificial trade barriers like prohibitive tariffs. In all the preceding chapters we ignored the presence of such products, much at the expense of economic reality. The objective of this chapter is to examine how and to what extent the results derived from the two-traded-goods model are modified when a non-traded final good is incorporated into the framework.

In the last chapter we studied how changes in the commodity-price ratio occur under the thrust of variations in the factor-price ratio, the overall capital/labour ratio and the relative rate of technical advance in the two industries. Any theory attempting to explain the basis of international trade must always commence with the theory of resource allocation and production in a closed economy. This task having been accomplished in the previous chapters, we are now in a position to pinpoint the factors that determine a country’s pattern of trade. The issue is what goods a country will export and import. Stated differently, is it possible to predict a country’s configuration of exports and imports just by examining the characteristics of a closed economy? Seeking a clear-cut answer to this query constitutes the subject-matter of this chapter.