A 16-parts-per-trillion measurement of the antiproton-to-proton charge-mass ratio.

The standard model of particle physics is both incredibly successful and glaringly incomplete. Among the questions left open is the striking imbalance of matter and antimatter in the observable universe1, which inspires experiments to compare the fundamental properties of matter/antimatter conjugates with high precision2-5. Our experiments deal with direct investigations of the fundamental properties of protons and antiprotons, performing spectroscopy in advanced cryogenic Penning trap systems6. For instance, we previously compared the proton/antiproton magnetic moments with 1.5 parts per billion fractional precision7,8, which improved upon previous best measurements9 by a factor of greater than 3,000. Here we report on a new comparison of the proton/antiproton charge-to-mass ratios with a fractional uncertainty of 16 parts per trillion. Our result is based on the combination of four independent long-term studies, recorded in a total time span of 1.5 years. We use different measurement methods and experimental set-ups incorporating different systematic effects. The final result, [Formula: see text], is consistent with the fundamental charge-parity-time reversal invariance, and improves the precision of our previous best measurement6 by a factor of 4.3. The measurement tests the standard model at an energy scale of 1.96 × 10-27 gigaelectronvolts (confidence level 0.68), and improves ten coefficients of the standard model extension10. Our cyclotron clock study also constrains hypothetical interactions mediating violations of the clock weak equivalence principle (WEPcc) for antimatter to less than 1.8 × 10-7, and enables the first differential test of the WEPcc using antiprotons11. From this interpretation we constrain the differential WEPcc-violating coefficient to less than 0.030.

Sympathetic cooling of a trapped proton mediated by an LC circuit.

Efficient cooling of trapped charged particles is essential to many fundamental physics experiments1,2, to high-precision metrology3,4 and to quantum technology5,6. Until now, sympathetic cooling has required close-range Coulomb interactions7,8, but there has been a sustained desire to bring laser-cooling techniques to particles in macroscopically separated traps5,9,10, extending quantum control techniques to previously inaccessible particles such as highly charged ions, molecular ions and antimatter. Here we demonstrate sympathetic cooling of a single proton using laser-cooled Be+ ions in spatially separated Penning traps. The traps are connected by a superconducting LC circuit that enables energy exchange over a distance of 9 cm. We also demonstrate the cooling of a resonant mode of a macroscopic LC circuit with laser-cooled ions and sympathetic cooling of an individually trapped proton, reaching temperatures far below the environmental temperature. Notably, as this technique uses only image-current interactions, it can be easily applied to an experiment with antiprotons1, facilitating improved precision in matter-antimatter comparisons11 and dark matter searches12,13.

Direct limits on the interaction of antiprotons with axion-like dark matter.

Astrophysical observations indicate that there is roughly five times more dark matter in the Universe than ordinary baryonic matter1, and an even larger amount of the Universe's energy content is attributed to dark energy2. However, the microscopic properties of these dark components remain unknown. Moreover, even ordinary matter-which accounts for five per cent of the energy density of the Universe-has yet to be understood, given that the standard model of particle physics lacks any consistent explanation for the predominance of matter over antimatter3. Here we present a direct search for interactions of antimatter with dark matter and place direct constraints on the interaction of ultralight axion-like particles (dark-matter candidates) with antiprotons. If antiprotons have a stronger coupling to these particles than protons do, such a matter-antimatter asymmetric coupling could provide a link between dark matter and the baryon asymmetry in the Universe. We analyse spin-flip resonance data in the frequency domain acquired with a single antiproton in a Penning trap4 to search for spin-precession effects from ultralight axions, which have a characteristic frequency governed by the mass of the underlying particle. Our analysis constrains the axion-antiproton interaction parameter to values greater than 0.1 to 0.6 gigaelectronvolts in the mass range from 2 × 10-23 to 4 × 10-17 electronvolts, improving the sensitivity by up to five orders of magnitude compared with astrophysical antiproton bounds. In addition, we derive limits on six combinations of previously unconstrained Lorentz- and CPT-violating terms of the non-minimal standard model extension5.

A parts-per-billion measurement of the antiproton magnetic moment.

Precise comparisons of the fundamental properties of matter-antimatter conjugates provide sensitive tests of charge-parity-time (CPT) invariance, which is an important symmetry that rests on basic assumptions of the standard model of particle physics. Experiments on mesons, leptons and baryons have compared different properties of matter-antimatter conjugates with fractional uncertainties at the parts-per-billion level or better. One specific quantity, however, has so far only been known to a fractional uncertainty at the parts-per-million level: the magnetic moment of the antiproton, . The extraordinary difficulty in measuring with high precision is caused by its intrinsic smallness; for example, it is 660 times smaller than the magnetic moment of the positron. Here we report a high-precision measurement of in units of the nuclear magneton µN with a fractional precision of 1.5 parts per billion (68% confidence level). We use a two-particle spectroscopy method in an advanced cryogenic multi-Penning trap system. Our result = -2.7928473441(42)µN (where the number in parentheses represents the 68% confidence interval on the last digits of the value) improves the precision of the previous best measurement by a factor of approximately 350. The measured value is consistent with the proton magnetic moment, µp = 2.792847350(9)µN, and is in agreement with CPT invariance. Consequently, this measurement constrains the magnitude of certain CPT-violating effects to below 1.8 × 10-24 gigaelectronvolts, and a possible splitting of the proton-antiproton magnetic moments by CPT-odd dimension-five interactions to below 6 × 10-12 Bohr magnetons.

Laminectomy plus Fusion versus Laminectomy Alone for Lumbar Spondylolisthesis.

BACKGROUND: The comparative effectiveness of performing instrumented (rigid pedicle screws affixed to titanium alloy rods) lumbar spinal fusion in addition to decompressive laminectomy in patients with symptomatic lumbar grade I degenerative spondylolisthesis with spinal stenosis is unknown. METHODS: In this randomized, controlled trial, we assigned patients, 50 to 80 years of age, who had stable degenerative spondylolisthesis (degree of spondylolisthesis, 3 to 14 mm) and symptomatic lumbar spinal stenosis to undergo either decompressive laminectomy alone (decompression-alone group) or laminectomy with posterolateral instrumented fusion (fusion group). The primary outcome measure was the change in the physical-component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; range, 0 to 100, with higher scores indicating better quality of life) 2 years after surgery. The secondary outcome measure was the score on the Oswestry Disability Index (range, 0 to 100, with higher scores indicating more disability related to back pain). Patients were followed for 4 years. RESULTS: A total of 66 patients (mean age, 67 years; 80% women) underwent randomization. The rate of follow-up was 89% at 1 year, 86% at 2 years, and 68% at 4 years. The fusion group had a greater increase in SF-36 physical-component summary scores at 2 years after surgery than did the decompression-alone group (15.2 vs. 9.5, for a difference of 5.7; 95% confidence interval, 0.1 to 11.3; P=0.046). The increases in the SF-36 physical-component summary scores in the fusion group remained greater than those in the decompression-alone group at 3 years and at 4 years (P=0.02 for both years). With respect to reductions in disability related to back pain, the changes in the Oswestry Disability Index scores at 2 years after surgery did not differ significantly between the study groups (-17.9 in the decompression-alone group and -26.3 in the fusion group, P=0.06). More blood loss and longer hospital stays occurred in the fusion group than in the decompression-alone group (P<0.001 for both comparisons). The cumulative rate of reoperation was 14% in the fusion group and 34% in the decompression-alone group (P=0.05). CONCLUSIONS: Among patients with degenerative grade I spondylolisthesis, the addition of lumbar spinal fusion to laminectomy was associated with slightly greater but clinically meaningful improvement in overall physical health-related quality of life than laminectomy alone. (Funded by the Jean and David Wallace Foundation and others; SLIP ClinicalTrials.gov number, NCT00109213.).

Measurement of Ultralow Heating Rates of a Single Antiproton in a Cryogenic Penning Trap.

We report on the first detailed study of motional heating in a cryogenic Penning trap using a single antiproton. Employing the continuous Stern-Gerlach effect we observe cyclotron quantum transition rates of 6(1) quanta/h and an electric-field noise spectral density below 7.5(3.4)×10^{-20} V^{2} m^{-2} Hz^{-1}, which corresponds to a scaled noise spectral density below 8.8(4.0)×10^{-12} V^{2} m^{-2}, results which are more than 2 orders of magnitude smaller than those reported by other ion-trap experiments.

Barriers and facilitators to adoption, implementation and sustainment of obesity prevention interventions in schoolchildren- a DEDIPAC case study.

BACKGROUND: The aim of the study was to explore the implementation of school based diet and physical activity interventions with respect to the barriers and facilitators to adoption, implementation and sustainability; supportive actions required for implementation and recommendations to overcome identified barriers. Two interventions rolled out nationally in Ireland were chosen; Food Dudes, a programme to encourage primary school children to consume more fruit and vegetables and Green Schools Travel (GST), an active travel to school programme in primary and secondary schools. Trained school coordinators (teachers) cascade the programmes to other teaching staff. METHODS: Multiple case study design using qualitative semi-structured interviews with key stakeholders: primary and secondary school teachers, school coordinators, project coordinators/managers, funders and intermediaries. Fifteen interviews were conducted. Data were coded using a common categorization matrix. Thematic analysis was undertaken using the Adoption, Implementation and Maintenance elements of the RE-AIM implementation framework. RESULTS: Good working relationships within and across government departments, intermediaries and schools were critical for intervention adoption, successful implementation and sustainability. Organisational and leadership ability of coordinators were essential. Provision of participation incentives acted as motivators to engage children's interest. A deep understanding of the lives of the target children was an important contextual factor. The importance of adaptation without compromising core components in enhancing intervention sustainability emerged. Successful implementation was hindered by: funding insecurity, school timetable constraints, broad rather than specific intervention core components, and lack of agreement on conduct of programme evaluation. Supportive actions for maintenance included ongoing political support, secure funding and pre-existing healthy lifestyle policies. CONCLUSIONS: Successful implementation and scale up of public health anti-obesity interventions in schools is dependent on good contextual fit, engagement and leadership at multiple levels and secure funding. Recommendations to overcome barriers include: capacity to deliver within an already overcrowded curriculum and clear specification of intervention components within a conceptual framework to facilitate evaluation. Our findings are generalisable across different contexts and are highly relevant to those involved in the development or adaptation, organisation or execution of national public health interventions: policy makers, guidelines developers, and staff involved in local organisation and delivery.

Single crystal Er3+ : YAG fibers with tailored refractive index profiles.

Erbium-doped yttrium aluminum garnet (Er3+:YAG) rods were inserted inside undoped tubes and grown into single-crystal fibers of a diameter of 300 µm using the laser-heated pedestal growth technique. Growth at various rates resulted in radially graded distributions of Er3+ dopant ions, as observed using laser-induced fluorescence imaging. Profiles of the refractive index were measured using cross-sectional reflectometry in a microscope. Dopant distributions and the corresponding index profiles were compared with thermal diffusion theory to determine the inter-diffusion coefficient of Y3+ and Er3+ ions at 2000°C, yielding an estimated value of D=(9.10±0.8)×10-11 m2/s. This work constitutes a step toward controlled growth of fibers with high thermal conductivities, low Brillouin gain, and waveguiding properties required for high-power optical amplifier and laser applications.

Implementing Population Medicine in a Pain Management Practice.

PURPOSE: To document and improve the quality of our chronic pain management using population management methods. METHODS: An analytic registry was developed, and all new patients were enrolled for 12 months. Patient demographics, standardized pain and function measures, and treatments were recorded. Usual care was provided. The registry was used to organize care and analyze management and outcomes. RESULTS: Of 454 total patients, only 154 (34%) completed a 6-month cycle of care. High no-show rates were documented for follow-up appointments for several reasons. The majority of 6-month completers showed improved pain levels. DISCUSSION: This quality improvement project identified assessment and care gaps and led to improvements. An ongoing need to improve measures of pain and function was documented.

Increased Patient Enrollment to a Randomized Surgical Trial Through Equipoise Polling of an Expert Surgeon Panel.

OBJECTIVE: To determine whether patients who learned the views of an expert surgeons' panel's assessment of equipoise between 2 alternative operative treatments had increased likelihood of consenting to randomization. BACKGROUND: Difficulty obtaining patient consent to randomization is an important barrier to conducting surgical randomized clinical trials, the gold standard for generating clinical evidence. METHODS: Observational study of the rate of patient acceptance of randomization within a 5-center randomized clinical trial comparing lumbar spinal decompression versus lumbar spinal decompression plus instrumented fusion for patients with symptomatic grade I degenerative lumbar spondylolisthesis with spinal stenosis. Eligible patients were enrolled in the trial and then asked to accept randomization. A panel of 10 expert spine surgeons was formed to review clinical information and images for individual patients to provide an assessment of suitability for randomization. The expert panel vote was disclosed to the patient by the patient's surgeon before the patient decided whether to accept randomization or not. RESULTS: Randomization acceptance among eligible patients without expert panel review was 40% (19/48) compared with 81% (47/58) among patients undergoing expert panel review (P < 0.001). Among expert-reviewed patients, randomization acceptance was 95% when all experts or all except 1 voted for randomization, 75% when 2 experts voted against randomization, and 20% with 3 or 4 votes against (P < 0.001 for trend). CONCLUSIONS: Patients provided with an expert panel's assessment of their own suitability for randomization were twice as likely to agree to randomization compared with patients receiving only their own surgeon's recommendation.

Investigation of hollow cylindrical metal terahertz waveguides suitable for cryogenic environments.

The field of terahertz (THz) waveguides continues to grow rapidly, with many being tailored to suit the specific demands of a particular final application. Here, we explore waveguides capable of enabling efficient and accurate power delivery within cryogenic environments (< 4 K). The performance of extruded hollow cylindrical metal waveguides made of un-annealed and annealed copper, as well as stainless steel, have been investigated for bore diameters between 1.75 - 4.6 mm, and at frequencies of 2.0, 2.85 and 3.4 THz, provided by a suitable selection of THz quantum cascade lasers. The annealed copper resulted in the lowest transmission losses, < 3 dB/m for a 4.6 mm diameter waveguide, along with 90° bending losses as low as ~2 dB for a bend radius of 15.9 mm. The observed trends in losses were subsequently analyzed and related to measured inner surface roughness parameters. These results provide a foundation for the development of a wide array of demanding low-temperature THz applications, and enabling the study of fundamental physics.

Growth hormone secretion decreases with age in paediatric Prader-Willi syndrome.

OBJECTIVE: Growth hormone deficiency is a common feature of Prader-Willi syndrome; however, biochemical deficiency is not uniformly demonstrated. Criteria for GH treatment in paediatric PWS vary with some countries requiring documentation of biochemical GH deficiency. Data regarding the significance of age in the interpretation of GH stimulation test results, particularly in infants, are lacking. We aimed to assess age-related trends in the prevalence of biochemical GH deficiency in infants and children with PWS. DESIGN: A retrospective chart review was conducted. Data from children with Prader-Willi syndrome that had GH stimulation tests performed at the Hospital for Sick Children in Toronto between the years 2000 and 2012 were collected. PATIENT: Charts of 47 children 0·4-15·5 years of age with PWS that had GH stimulation tests were reviewed. MEASUREMENTS: Biochemical GH status in relation to age and body mass index. RESULTS: Thirty-two of 47 patients (68%) were biochemically GH deficient. GH deficiency was significantly associated with older age (r = 0·45, P = 0·02) and higher body-mass-index z-score (r = 0·45, P = 0·02). Biochemical GH deficiency was less prevalent up to 18 months of age (3/11 27%) compared with older children (29/36 [81%]; P = 0·001). A higher prevalence of GH deficiency was also detected in obese patients (14/16 [88%]) compared with nonobese patients (18/31 [58%]; P = 0·04). CONCLUSIONS: The utility of performing GH stimulation tests as an indication of GH status under 18 months of age in Prader-Willi syndrome is questionable. If performed, results should be carefully interpreted in the context of age.

Efficient coupling of double-metal terahertz quantum cascade lasers to flexible dielectric-lined hollow metallic waveguides.

The growth in terahertz frequency applications utilising the quantum cascade laser is hampered by a lack of targeted power delivery solutions over large distances (>100 mm). Here we demonstrate the efficient coupling of double-metal quantum cascade lasers into flexible polystyrene lined hollow metallic waveguides via the use of a hollow copper waveguide integrated into the laser mounting block. Our approach exhibits low divergence, Gaussian-like emission, which is robust to misalignment error, at distances > 550 mm, with a coupling efficiency from the hollow copper waveguide into the flexible waveguide > 90%. We also demonstrate the ability to nitrogen purge the flexible waveguide, increasing the power transmission by up to 20% at 2.85 THz, which paves the way for future fibre based terahertz sensing and spectroscopy applications.

Building-related health symptoms and classroom indoor air quality: a survey of school teachers in New York State.

UNLABELLED: Most previous research on indoor environments and health has studied school children or occupants in non-school settings. This investigation assessed building-related health symptoms and classroom characteristics via telephone survey of New York State school teachers. Participants were asked about 14 building-related symptoms and 23 classroom characteristics potentially related to poor indoor air quality (IAQ). Poisson regression analysis was used to assess the relationship between these symptoms and each classroom characteristic, controlling for potential confounders. About 500 teachers completed the survey. The most frequently reported classroom characteristics included open shelving (70.7%), food eaten in class (65.5%), dust (59.1%), and carpeting (46.9%). The most commonly reported symptoms included sinus problems (16.8%), headache (15.0%), allergies/congestion (14.8%), and throat irritation (14.6%). Experiencing one or more symptoms was associated most strongly with reported dust (relative risk (RR) = 3.67; 95% confidence interval (CI): 2.62-5.13), dust reservoirs (RR = 2.13; 95% CI: 1.72-2.65), paint odors (RR = 1.73; 95% CI: 1.40-2.13), mold (RR = 1.71; 95% CI: 1.39-2.11), and moldy odors (RR = 1.65 95% CI: 1.30-2.10). Stronger associations were found with increasing numbers of reported IAQ-related classroom characteristics. Similar results were found with having any building-related allergic/respiratory symptom. This research adds to the body of evidence underscoring the importance to occupant health of school IAQ. PRACTICAL IMPLICATIONS: Teachers play an important role in educating children, and teacher well-being is important to this role. Health symptoms among New York teachers while at work are common and appear to be associated with numerous characteristics related to poor classroom IAQ. Improving school Indoor Air Quality may reduce sickness and absenteeism and improve teacher performance.

The rheumatoid arthritis treat-to-target trial: a cluster randomized trial within the Corrona rheumatology network.

BACKGROUND: The treat-to-target (T2T) approach to the care of patients with rheumatoid arthritis involves using validated metrics to measure disease activity, frequent follow-up visits for patients with moderate to high disease activity, and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores. The study described is a newly launched cluster-randomized behavioral intervention to assess the feasibility and effectiveness of the T2T approach in US rheumatology practices. It is designed to identify patient and provider barriers to implementing T2T management. This initial paper focuses on the novel study design and methods created to provide these insights. METHODS/DESIGN: This trial cluster-randomizes rheumatology practices from the existing Corrona network of private and academic sites rather than patients within sites or individual investigators to provide either T2T or usual care (UC) for qualified patients who meet the 2010 revised American College of Rheumatology criteria for the diagnosis of rheumatoid arthritis and have moderate to high disease activity. Specific medication choices are left to the investigator and patient, rather than being specified in the protocol. Enrollment is expected to be completed by the end of 2013, with 30 practices randomized and enrolling a minimum of 530 patients. During the 12-month follow-up, visits are mandated as frequently as monthly in patients with active disease in the T2T group and every 3 months for the UC group. Safety data are collected at each visit. The coprimary endpoints include a comparison of the proportion of patients achieving low disease activity in the T2T and UC groups and assessment of the feasibility of implementing T2T in rheumatology practices, specifically assessment of the rates of treatment acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity in the 2 groups. DISCUSSION: This cluster-randomized behavioral intervention study will provide valuable insights on the outcomes and feasibility of employing a T2T treatment approach in clinical practice in the United States. TRIAL REGISTRATION: NCT01407419.

Pre-diabetes in adults 45 years and over in Ireland: the Survey of Lifestyle, Attitudes and Nutrition in Ireland 2007.

OBJECTIVES: Pre-diabetes is an important indicator of future diabetes burden and many countries are reporting prevalence estimates of pre-diabetes. To date in Ireland, estimates of the prevalence of pre-diabetes were unavailable. Our objectives were to estimate the prevalence of pre-diabetes in a nationally representative sample of Irish adults and to explore determinants of pre-diabetes. METHODS: The Survey of Lifestyle Attitudes and Nutrition 2007 was a cross-sectional survey on health and lifestyle in a nationally representative sample of Irish adults. Analysis was performed on a subsample of 1132 participants ≥ 45 years who provided blood samples. Determination of pre-diabetes was based on American Diabetes Association HbA1c cut points of 39-46 mmol/mol (5.7-6.4%). To explore determinants, we modelled pre-diabetes prevalence as a function of a set of health system and socio-demographic variables using logistic regression. RESULTS: The overall weighted prevalence estimate of pre-diabetes in participants ≥ 45 years was 19.8% (95% CI 16.4-23.9). There was no significant difference between age or gender-specific prevalence rates. Obesity was significantly associated with pre-diabetes on univariate and multivariate analysis. Population attributable fraction estimates for excess BMI, physical inactivity and poor diet as causes of pre-diabetes were 31.3% (95% CI -3.9 to 54.5), 10.0% (95% CI -2.7 to 21.3) and 6.1% (95% CI -4.9 to 15.9), respectively. CONCLUSIONS: The high levels of pre-diabetes detected in this study are worrying. Population level interventions to address diet and lifestyle factors are needed urgently to prevent progression to diabetes in high-risk individuals.

The effectiveness of workplace dietary modification interventions: a systematic review.

OBJECTIVE: To evaluate the effectiveness of workplace dietary modification interventions alone or in combination with nutrition education on employees' dietary behaviour, health status, self-efficacy, perceived health, determinants of food choice, nutrition knowledge, co-worker support, job satisfaction, economic cost and food-purchasing patterns. METHOD: Data sources included PubMed, Medline, Embase, Psych Info., Web of Knowledge and Cochrane Library (November 2011). This review was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were randomised controlled trials and controlled studies. Interventions were implemented for at least three months. Cochrane Collaboration's risk of bias tool measured potential biases. Heterogeneity precluded meta-analysis. Results were presented in a narrative summary. RESULTS: Six studies conducted in Brazil, the USA, Netherlands and Belgium met the inclusion criteria. Four studies reported small increases in fruit and vegetable consumption (≤half serving/day). These studies involved workplace dietary modifications and three incorporated nutrition education. Other outcomes reported included health status, co-worker support, job satisfaction, perceived health, self-efficacy and food-purchasing patterns. All studies had methodological limitations that weakened confidence in the results. CONCLUSION: Limited evidence suggests that workplace dietary modification interventions alone and in combination with nutrition education increase fruit and vegetable intakes. These interventions should be developed with recommended guidelines, workplace characteristics, long-term follow-up and objective outcomes for diet, health and cost.

Prescribing practices in a US cohort of rheumatoid arthritis patients before and after publication of the American College of Rheumatology treatment recommendations.

OBJECTIVE: To examine prescribing practices in the use of biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs) to treat patients with rheumatoid arthritis (RA), before and after publication of the American College of Rheumatology (ACR) treatment recommendations. METHODS: Biologics-naive RA patients under the care of a rheumatologist in the US were identified from the Consortium of Rheumatology Researchers of North America registry. Patients were included if their visits occurred prior to and/or at least 6 months after publication of the ACR treatment recommendations (time periods of February 2002-June 2008 versus December 2008-December 2009). The population was divided into 2 mutually exclusive cohorts: 1) methotrexate (MTX) monotherapy users, and 2) multiple nonbiologic DMARD users. Initiation or dose escalation of biologic and nonbiologic DMARDs in response to active disease was assessed cross-sectionally and longitudinally in comparison to the ACR recommendations. The impact of the publication of the ACR recommendations on treatment practices was assessed using logistic regression, stratified by disease activity and adjusted for clustering of physicians and geographic region. RESULTS: After 1 visit, 24-37% of patients receiving MTX monotherapy who had moderate disease activity and a poor prognosis or high disease activity received care consistent with the ACR recommendations; after 2 visits, 34-56% of the MTX monotherapy group received care consistent with the recommendations. In the patients receiving multiple nonbiologic DMARDs, 31-47% of those with moderate or high disease activity received care consistent with the recommendations after 1 visit, and 43-51% received such care after 2 visits. Publication of the recommendations did not significantly change treatment patterns for those with active disease. CONCLUSION: Substantial numbers of RA patients with active disease did not receive care consistent with the current ACR treatment recommendations. Innovative approaches to improve care are necessary.

Formation of de novo centromeres and construction of first-generation human artificial microchromosomes.

We have combined long synthetic arrays of alpha satellite DNA with telomeric DNA and genomic DNA to generate artificial chromosomes in human HT1080 cells. The resulting linear microchromosomes contain exogenous alpha satellite DNA, are mitotically and cytogenetically stable in the absence of selection for up to six months in culture, bind centromere proteins specific for active centromeres, and are estimated to be 6-10 megabases in size, approximately one-fifth to one-tenth the size of endogenous human chromosomes. We conclude that this strategy results in the formation of de novo centromere activity and that the microchromosomes so generated contain all of the sequence elements required for stable mitotic chromosome segregation and maintenance. This first-generation system for the construction of human artificial chromosomes should be suitable for dissecting the sequence requirements of human centromeres, as well as developing constructs useful for therapeutic applications.