Measurement of the Charge-Averaged Elastic Lepton-Proton Scattering Cross Section by the OLYMPUS Experiment.

We report the first measurement of the average of the electron-proton and positron-proton elastic scattering cross sections. This lepton charge-averaged cross section is insensitive to the leading effects of hard two-photon exchange, giving more robust access to the proton's electromagnetic form factors. The cross section was extracted from data taken by the OLYMPUS experiment at DESY, in which alternating stored electron and positron beams were scattered from a windowless gaseous hydrogen target. Elastic scattering events were identified from the coincident detection of the scattered lepton and recoil proton in a large-acceptance toroidal spectrometer. The luminosity was determined from the rates of Møller, Bhabha, and elastic scattering in forward electromagnetic calorimeters. The data provide some selectivity between existing form factor global fits and will provide valuable constraints to future fits.

Study of Two-Photon Exchange via the Beam Transverse Single Spin Asymmetry in Electron-Proton Elastic Scattering at Forward Angles over a Wide Energy Range.

We report on a new measurement of the beam transverse single spin asymmetry in electron-proton elastic scattering, A_{⊥}^{ep}, at five beam energies from 315.1 to 1508.4 MeV and at a scattering angle of 30°<θ<40°. The covered Q^{2} values are 0.032, 0.057, 0.082, 0.218, 0.613 (GeV/c)^{2}. The measurement clearly indicates significant inelastic contributions to the two-photon-exchange (TPE) amplitude in the low-Q^{2} kinematic region. No theoretical calculation is able to reproduce our result. Comparison with a calculation based on unitarity, which only takes into account elastic and πN inelastic intermediate states, suggests that there are other inelastic intermediate states such as ππN, KΛ, and ηN. Covering a wide energy range, our new high-precision data provide a benchmark to study those intermediate states.

First Measurement of the Q

We report on the first Q^{2}-dependent measurement of the beam-normal single spin asymmetry A_{n} in the elastic scattering of 570 MeV vertically polarized electrons off ^{12}C. We cover the Q^{2} range between 0.02 and 0.05 GeV^{2}/c^{2} and determine A_{n} at four different Q^{2} values. The experimental results are compared to a theoretical calculation that relates A_{n} to the imaginary part of the two-photon exchange amplitude. The result emphasizes that the Q^{2} behavior of A_{n} given by the ratio of the Compton to charge form factors cannot be treated independently of the target nucleus.

New Measurements of the Beam Normal Spin Asymmetries at Large Backward Angles with Hydrogen and Deuterium Targets.

New measurements of the beam normal single spin asymmetry in the electron elastic and quasielastic scattering on the proton and deuteron, respectively, at large backward angles and at ⟨Q^{2}⟩=0.22 (GeV/c)^{2} and ⟨Q^{2}⟩=0.35 ( GeV/c)^{2} are reported. The experimentally observed asymmetries are compared with the theoretical calculation of Pasquini and Vanderhaeghen [Phys. Rev. C 70, 045206 (2004).PRVCAN0556-281310.1103/PhysRevC.70.045206]. The agreement of the measurements with the theoretical calculations shows a dominance of the inelastic intermediate excited states of the nucleon, πN and the Δ resonance. The measurements explore a new, important parameter region of the exchanged virtual photon virtualities.

Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus.

Autoantibodies to nuclear structures are a hallmark of systemic lupus erythematosus (SLE), including autoantibodies to nuclear protein high mobility group box 1 (HMGB1). HMGB1 consists of three separate domains: box A, box B and an acidic tail. Recombinant box A acts as a competitive antagonist for HMGB1 and might be an interesting treatment option in SLE. However, antibodies to box A might interfere. Therefore, levels of anti-box A were examined in SLE patients in association with disease activity and clinical parameters. Serum anti-box A was measured in 86 SLE patients and 44 age- and sex-matched healthy controls (HC). Serum samples of 28 patients with primary Sjögren's syndrome and 32 patients with rheumatoid arthritis were included as disease controls. Anti-HMGB1 and anti-box B levels were also measured by enzyme-linked immunosorbent assay during quiescent disease [SLE Disease Activity Index (SLEDAI) ≤ 4, n = 47] and active disease (SLEDAI ≥ 5, n = 39). Anti-box A levels in active SLE patients were higher compared to quiescent patients, and were increased significantly compared to HC and disease controls. Anti-box A levels correlated positively with SLEDAI and anti-dsDNA levels and negatively with complement C3 levels. Increased levels of anti-box A antibodies were present in the majority of patients with nephritic (73%) and non-nephritic exacerbations (71%). Antibodies to the box A domain of HMGB1 might be an interesting new biomarker, as these had a high specificity for SLE and were associated with disease activity. Longitudinal studies should be performed to evaluate whether these antibodies perform better in predicting an exacerbation, especially non-nephritic exacerbations.

Hard Two-Photon Contribution to Elastic Lepton-Proton Scattering Determined by the OLYMPUS Experiment.

The OLYMPUS Collaboration reports on a precision measurement of the positron-proton to electron-proton elastic cross section ratio, R_{2γ}, a direct measure of the contribution of hard two-photon exchange to the elastic cross section. In the OLYMPUS measurement, 2.01 GeV electron and positron beams were directed through a hydrogen gas target internal to the DORIS storage ring at DESY. A toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight scintillators detected elastically scattered leptons in coincidence with recoiling protons over a scattering angle range of ≈20° to 80°. The relative luminosity between the two beam species was monitored using tracking telescopes of interleaved gas electron multiplier and multiwire proportional chamber detectors at 12°, as well as symmetric Møller or Bhabha calorimeters at 1.29°. A total integrated luminosity of 4.5 fb^{-1} was collected. In the extraction of R_{2γ}, radiative effects were taken into account using a Monte Carlo generator to simulate the convolutions of internal bremsstrahlung with experiment-specific conditions such as detector acceptance and reconstruction efficiency. The resulting values of R_{2γ}, presented here for a wide range of virtual photon polarization 0.456<ε<0.978, are smaller than some hadronic two-photon exchange calculations predict, but are in reasonable agreement with a subtracted dispersion model and a phenomenological fit to the form factor data.

Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands.

OBJECTIVES: To determine the prevalence of anticitrullinated protein antibodies (ACPAs) and their association with known rheumatoid arthritis (RA) risk factors in the general population. METHODS: Lifelines is a multidisciplinary prospective population-based cohort study in the Netherlands. Cross-sectional data from 40 136 participants were used. The detection of ACPA was performed by measuring anti-CCP2 on the Phadia-250 analyser with levels ≥6.2 U/mL considered positive. An extensive questionnaire was taken on demographic and clinical information, including smoking, periodontal health and early symptoms of musculoskeletal disorders. RA was defined by a combination of self-reported RA, medication use for the indication of rheumatism and visiting a medical specialist within the last year. RESULTS: Of the total 40 136 unselected individuals, 401 (1.0%) had ACPA level ≥6.2 U/mL. ACPA positivity was significantly associated with older age, female gender, smoking, joint complaints, RA and first degree relatives with rheumatism. Of the ACPA-positive participants, 22.4% had RA (15.2% had defined RA according to our criteria and 7.2% self-reported RA only). In participants without RA, 311 (0.8%) were ACPA-positive. In the non-RA group, older age, smoking and joint complaints remained significantly more frequently present in ACPA-positive compared with ACPA-negative participants. CONCLUSIONS: In this large population-based study, the prevalence of ACPA levels ≥6.2 U/mL was 1.0% for the total group and 0.8% when excluding patients with RA. Older age, smoking and joint complaints were more frequently present in ACPA-positive Lifelines participants. To our knowledge, this study is the largest study to date on ACPA positivity in the general, mostly Caucasian population.

Measurement of strange quark contributions to the vector form factors of the proton at Q2 = 0.22 (GeV / c)2.

A new measurement of the parity violating asymmetry in elastic electron scattering on hydrogen at backward angles and at a four momentum transfer of Q;{2} = 0.22 (Ge V / c);{2} is reported here. The measured asymmetry is A_{LR} = (-17.23 +/- 0.82_{stat} +/- 0.89_{syst}) x 10;{-6}. The standard model prediction assuming no strangeness is A_{0} = (-15.87 +/- 1.22) x 10;{-6}. In combination with previous results from measurements at forward angles, it is possible to disentangle for the first time the strange form factors at this momentum transfer, G_{E};{s} = 0.050 +/- 0.038 +/- 0.019 and G_{M};{s} = -0.14 +/- 0.11 +/- 0.11.

NOD2 polymorphisms predict severe acute graft-versus-host and treatment-related mortality in T-cell-depleted haematopoietic stem cell transplantation.

Single nucleotide polymorphisms (SNPs) in the NOD2 gene have significant impact on both treatment-related mortality (TRM) and acute GVHD (aGVHD) in haematopoietic stem cell transplantation (HSCT). The effect of these polymorphisms when using T-cell-depleted grafts has been poorly studied. We retrospectively analysed NOD2 polymorphisms in a cohort of 85 patients and donors who received an HLA-identical sibling partially T-cell-depleted HSCT (0.5 x 10(6) CD3+ T cells per kg) following idarubicin-containing conditioning regimens. NOD2 polymorphisms were present in 14 of 85 (16.5%) of patients and 18 of 85 (21%) of donors. The risk of severe aGVHD (grade III-IV) and the 1-year TRM was significantly higher in the presence of NOD2 polymorphisms (hazard ratio (HR) 6.0, P=0.02 for severe aGVHD and HR 3.3, P=0.02 for TRM, respectively) and was most prominent in cases where patient and donor both had a polymorphism (HR 10.5, P=0.002 and HR 3.9, P=0.002). There was also a trend towards increased risk of bacteraemia due to coagulase-negative staphylococci in patients with an NOD2 polymorphism. We conclude that NOD2 polymorphism screening should be used to optimize donor selection and antimicrobial prophylaxis to reduce the occurrence of aGVHD and TRM following allogeneic HSCT.

Dynamics in chimerism of T cells and dendritic cells in relapsed CML patients and the influence on the induction of alloreactivity following donor lymphocyte infusion.

Donor lymphocyte infusion (DLI) after allogeneic SCT induces complete remissions in approximately 80% of patients with relapsed CML in chronic phase, but some patients do not respond to DLI. We studied absolute numbers of dendritic cell (DC) subsets and chimerism in T cells and two subsets of blood DCs (myeloid DCs (MDCs) and plasmacytoid DCs (PDCs)) in relation to DLI-induced alloreactivity. Based on T cell and DC chimerism, we identified three groups. Four patients were completely donor chimeric in T cells and DC subsets. These patients had an early stage of relapse, and three of the four patients attained complete molecular remission (CMolR) without significant GVHD. Six patients were completely donor in T cells and mixed chimeric in DC subsets. All patients entered CMolR, but this was associated with GVHD in four and cytopenia in three patients. Five patients had mixed chimerism in T cells and complete recipient chimerism in MDC; only two patients entered CMolR. Our data suggest that the combination of donor T cells and mixed chimerism in DC subsets induces a potent graft-versus-leukemia (GVL) effect in association with GVHD. DLI in patients with an early relapse and donor chimerism in both T cells and DC subsets results in GVL reactivity without GVHD.

HIV/AIDS and disability: differences in HIV/AIDS knowledge between deaf and hearing people in Nigeria.

PURPOSE: Studies both in North America and Europe have found that deaf individuals lack access to AIDS information, due to problems in communication, low literacy and tightly woven social networks within the deaf community. However few comparable studies are available from countries in the Developing World. The present study was undertaken in Nigeria where there is an estimated adult HIV prevalence rate of 5.4%. We sought to compare HIV knowledge among deaf and hearing individuals in order to identify how effectively deaf members of the community are being reached by HIV/AIDS messages. METHODS: A survey comparing knowledge about HIV/AIDS among deaf and hard of hearing adolescents (n = 50) and young adults (n = 50) was undertaken. RESULTS: Significant differences (p < 0.05) in levels of understanding about certain aspects of how AIDS is spread were identified as well as differences in available resources for access to accurate information among deaf members of the population. CONCLUSION: These findings from Nigeria speak strongly to the need for the development of interventions that include people with disabilities in public health and HIV/AIDS strategies and that address their specific vulnerabilities. Evaluating the adaptation of education material and the inclusion of the deaf population in HIV awareness programmes is an urgent 'next step.'

Evidence for strange-quark contributions to the nucleon's form factors at Q2=0.108 (GeV/c)2.

We report on a measurement of the parity violating asymmetry in the elastic scattering of polarized electrons off unpolarized protons with the A4 apparatus at MAMI in Mainz at a four momentum transfer value of Q(2)=0.108 (GeV/c)(2) and at a forward electron scattering angle of 30 degrees p)=[-1.36+/-0.29(stat)+/-0.13(syst)]x10(-6). The expectation from the standard model assuming no strangeness contribution to the vector current is A(0)=(-2.06+/-0.14)x10(-6). We have improved the statistical accuracy by a factor of 3 as compared to our previous measurements at a higher Q2. We have extracted the strangeness contribution to the electromagnetic form factors from our data to be G(s)(E)+0.106G(s)(M)=0.071+/-0.036 at Q(2)=0.108 (GeV/c)(2). We again find the value for G(s)(E)+0.106G(s)(M) to be positive, this time at an improved significance level of two sigma.

Measurement of the transverse beam spin asymmetry in elastic electron-proton scattering and the inelastic contribution to the imaginary part of the two-photon exchange amplitude.

We report on a measurement of the asymmetry in the scattering of transversely polarized electrons off unpolarized protons, A( perpendicular), at two Q2 values of 0.106 and 0.230 (GeV/c)(2) and a scattering angle of 30 degrees

Measurement of strange-quark contributions to the nucleon's form factors at Q(2) = 0.230 (GeV/c)(2).

We report on a measurement of the parity-violating asymmetry in the scattering of longitudinally polarized electrons on unpolarized protons at a Q2 of 0.230 (GeV/c)(2) and a scattering angle of theta (e) = 30 degrees - 40 degrees. Using a large acceptance fast PbF2 calorimeter with a solid angle of delta omega = 0.62 sr, the A4 experiment is the first parity violation experiment to count individual scattering events. The measured asymmetry is A(phys)=(-5.44+/-0.54(stat)+/-0.26(sys))x10(-6). The standard model expectation assuming no strangeness contributions to the vector form factors is A(0) = (-6.30+/-0.43) x 10(-6). The difference is a direct measurement of the strangeness contribution to the vector form factors of the proton. The extracted value is G(s)(E) + 0.225G(s)(M) = 0.039+/-0.034 or F(s)(1) + 0.130F(s)(2) = 0.032+/-0.028.

Quantification of donor and recipient hemopoietic cells by real-time PCR of single nucleotide polymorphisms.

Analysis of changes in recipient and donor hemopoietic cell origin is extremely useful to monitor the effect of stem cell transplantation (SCT) and sequential adoptive immunotherapy by donor lymphocyte infusions (DLI). We developed a sensitive and accurate method to quantify the percentage of recipient and donor cells by real-time PCR using single nucleotide polymorphisms (SNPs) as markers. Allele-specific PCR of seven SNPs resulted in specific markers for donor or recipient in 97% of HLA-identical sibling pairs. Both, recipient- and donor-derived hemopoietic cells can be simultaneously analyzed in 67% sibling pairs. We expect this can be increased to approximately 99% by developing three additional SNP-PCR. Serial dilution of SNP-positive DNA into either SNP-negative DNA or water revealed a detection limit of 0.1-0.01% depending on the amount of input DNA and start C(t) of the used SNP-PCR. Application of our real-time SNP-PCR method for a CML patient treated by allogeneic SCT and DLI demonstrated its feasibility to follow donor T-cell chimerism and early detection of residual and recurrent autologous hemopoiesis in response to treatment. This detailed monitoring of the genetic origin of hemopoietic cells, in particular immune effector cells and target cells after SCT and DLI, may substantially contribute to understanding of the mechanisms that play a role in the success of treatment.

Children's judgements about intentionally and unintentionally broken promises.

Astington (1988) found that seven- to nine-year-olds often fail to distinguish between promises and predictions when judging the utterances of characters in simple stories. Instead, these children attend only to the outcome of the story (i.e. whether the promised event occurred) when deciding whether a promise has been made and, to a lesser extent, when deciding whether the speaker is responsible for the outcome. The purpose of the present study was to examine whether seven- to nine-year-olds (a) vary their judgements of responsibility according to the reason that the promised action was not completed, and (b) recognize that an unfulfilled promise is a promise regardless of whether the speaker's failure is unavoidable or intentional. Seven-year-olds, nine-year-olds, and adults were asked to make promise and responsibility judgements for two story types: stories in which the promiser intentionally failed to fulfill his or her promise and stories in which an unforeseen event prevented the promiser from fulfilling the promise. Participants at all ages assigned responsibility correctly across both story types. In making promise judgements, however, the seven-year-olds' decisions about promises reflected a misguided attention to the outcome of a promise or the obstacle to its fulfillment. The nine-year-olds recognized that an unfulfilled promise is a promise but only when there was a clear reason for the speaker's failure to fulfill his or her obligation. We suggest that children consider only sincere promises to be instances of promising and make inferences about speaker sincerity by looking to external factors in the communicative context.

Prediction of functional and psychological status after percutaneous transluminal coronary angioplasty.

OBJECTIVE: To examine symptom, functional status, and psychological status profiles after percutaneous transluminal coronary angioplasty (PTCA) and determine indicators of outcome. DESIGN: Descriptive and correlational with repeated measures. SETTING: Hospital or home (2.1 days before PTCA) and home (3.9 and 10.2 months after discharge). MEASURES: Self-administered questionnaires (developed for study) for functional status (personal and instrumental activities of daily living), and cardiac symptoms (chest pain and shortness of breath at rest and on exertion). General Health Questionnaire(16) for psychological status. PATIENTS: One hundred thirty with PTCA (mean age 57 years, 84% male, 15% with prior PTCA). RESULTS: Chest pain and shortness of breath at rest and on exertion decreased and functional and psychological status improved 3.9 months after PTCA, with measures maintained at 10.2 months. At 3.9 months after PTCA, poorer psychological status was predicted by having had a longer duration of coronary artery disease before PTCA. Post-PTCA indicators of poor psychological status were continued chest pain and shortness of breath on exertion and not working. The presence of post-PTCA chest pain on exertion and not working were also correlated with reduced functional status. CONCLUSIONS: Although pre-PTCA variables such as duration of coronary artery disease can predict post-PTCA outcome, the use of variables measured after PTCA may also provide clinicians with accurate estimates of functional and psychological status after PTCA.

How to detect effects: statistical power and evidence-based practice in occupational therapy research.

The findings from 30 research investigations examining the effectiveness of occupational therapy interventions were reviewed and analyzed. The statistical conclusion validity was determined by computing post hoc power coefficients for the statistical hypothesis tests included in the examined studies. Data analysis revealed the median power values to detect small, medium, and large effect sizes were .09, .33, and .66, respectively. These results suggest a high probability of Type II errors in the sample of occupational therapy intervention research examined. In practical terms, this means the intervention produced a potentially useful treatment effect, but the effect was not detected as significant. Examples are provided that illustrate how low statistical power contributes to increases in Type II errors and inhibits the development of consensus through replication in the research literature. The presence of low-power studies with high rates of false negative findings prevents the establishment of guidelines for evidence-based practice and impedes the scientific progress of rehabilitation professions such as occupational therapy.

A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia.

Human minor histocompatibility antigens (mHags) play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). As most mHags are not leukemia specific but are also expressed by normal tissues, antileukemia reactivity is often associated with life-threatening graft-versus-host disease (GVHD). Here, we describe a novel mHag, HB-1, that elicits donor-derived CTL reactivity in a B cell acute lymphoblastic leukemia (B-ALL) patient treated by HLA-matched BMT. We identified the gene encoding the antigenic peptide recognized by HB-1-specific CTLs. Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus-transformed B cells. The HB-1 gene-encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene generates a single amino acid exchange from His to Tyr at position 8 within this peptide. This amino acid substitution is critical for recognition by HB-1-specific CTLs. The restricted expression of the polymorphic HB-1 Ag by B-ALL cells and the ability to generate HB-1-specific CTLs in vitro using peptide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD.