The u- and d-quark contributions to the elastic nucleon electromagnetic form factors have been determined by using experimental data on G(E)(n), G(M)(n), G(E)(p), and G(M)(p). Such a flavor ...separation of the form factors became possible up to negative four-momentum transfer squared Q(2) = 3.4 GeV(2) with recent data on G(E)(n) from Hall A at Jefferson Lab. For Q(2) above 1 GeV(2), for both the u and the d quark, the ratio of the Pauli and Dirac form factors, F(2)/F(1), was found to be almost constant in sharp contrast to the behavior of F(2)/F(1) for the proton as a whole. Also, again for Q(2)>1 GeV(2), both F(2)(d) and F(1)(d) are roughly proportional to 1/Q(4), whereas the dropoff of F(2)(u) and F(1)(u) is more gradual.
Symmetry permeates nature and is fundamental to all laws of physics. One example is parity (mirror) symmetry, which implies that flipping left and right does not change the laws of physics. Laws for ...electromagnetism, gravity and the subatomic strong force respect parity symmetry, but the subatomic weak force does not. Historically, parity violation in electron scattering has been important in establishing (and now testing) the standard model of particle physics. One particular set of quantities accessible through measurements of parity-violating electron scattering are the effective weak couplings C2q, sensitive to the quarks' chirality preference when participating in the weak force, which have been measured directly only once in the past 40 years. Here we report a measurement of the parity-violating asymmetry in electron-quark scattering, which yields a determination of 2C2u - C2d (where u and d denote up and down quarks, respectively) with a precision increased by a factor of five relative to the earlier result. These results provide evidence with greater than 95 per cent confidence that the C2q couplings are non-zero, as predicted by the electroweak theory. They lead to constraints on new parity-violating interactions beyond the standard model, particularly those due to quark chirality. Whereas contemporary particle physics research is focused on high-energy colliders such as the Large Hadron Collider, our results provide specific chirality information on electroweak theory that is difficult to obtain at high energies. Our measurement is relatively free of ambiguity in its interpretation, and opens the door to even more precise measurements in the future.
Cytokines play an important role in ischemic injury and repair. However, little is known about their prognostic value in cardiovascular disease. The aim of this study was to investigate the ...prognostic importance of chemokines CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC for the risk of future cardiovascular events in patients with acute coronary syndromes (ACS). Baseline levels of CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC were determined in ACS patients from the Bad Nauheim ACS II registry (n = 609). During the following 200 days, patients were monitored for the occurrence of fatal and non-fatal cardiovascular events. Patients with CCL3/MIP1α, CCL5/RANTES and CCL18/PARC concentrations in the highest tertile were associated with an increased risk of a fatal event during follow-up (HR: 2.19, 95%CI: 1.04-4.61 for CCL3/MIP1α, HR: 3.45, 95%CI: 1.54-7.72 for CCL5/RANTES and HR: 3.14, 95%CI: 1.33-7.46 for CCL18/PARC). This risk was highest for patients with all three biomarkers concentrations in the upper tertile (HR: 2.52, 95%CI: 1.11-5.65). Together with known risk predictors of cardiovascular events, CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC combined improved the c-statistics from 0.74 to 0.81 (p = 0.007). In conclusion, CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC are independently associated with the risk of short-term mortality in ACS patients. Combining all three biomarkers further increased their prognostic value.
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The standard of care for patients with Adrenal Insufficiency (AI) is suboptimal. Administration of hydrocortisone three times a day produces plasma cortisol fluctuations associated ...with negative health outcomes. Furthermore, there is a high inter-individual variability in cortisol need, necessitating a personalized approach. It is hypothesized that a personalized, sustained release formulation would enhance the pharmacotherapy by mimicking the physiological cortisol plasma concentration at a higher level. Therefore, a novel 24 h sustained release 3D printed (3DP) hydrocortisone formulation has been developed (M3DICORT) by coupling hot-melt extrusion with fused deposition modeling. A uniform drug distribution in the 3DP tablets is demonstrated by a content of 101.66 ± 1.60 % with an acceptance value of 4.01. Furthermore, tablets had a stable 24 h dissolution profile where the intra-batch standard deviation was ± 2.8 % and the inter-batch standard deviation was ± 6.8 %. Tablet height and hydrocortisone content were correlated (R2 = 0.996), providing a tool for easy dose personalization. Tablets maintained critical quality attributes, such as dissolution profile (f2 > 60) and content uniformity after process transfer from a single-screw extruder to a twin-screw extruder. Impurities were observed in the final product which should be mitigated before clinical assessment. To our knowledge, M3DICORT is the first 3DP hydrocortisone formulation specifically developed for AI.
Electroconvulsive therapy (ECT) in patients with major depression is associated with volume changes and markers of neuroplasticity in the hippocampus, in particular in the dentate gyrus. It is ...unclear if these changes are associated with cognitive side effects.
We investigated whether changes in cognitive functioning after ECT were associated with hippocampal structural changes. It was hypothesized that 1) volume increase of hippocampal subfields and 2) changes in perfusion and diffusion of the hippocampus correlated with cognitive decline.
Using ultra high field (7 T) MRI, intravoxel incoherent motion and volumetric data were acquired and neurocognitive functioning was assessed before and after ECT in 23 patients with major depression. Repeated measures correlation analysis was used to examine the relation between cognitive functioning and structural characteristics of the hippocampus.
Left hippocampal volume, left and right dentate gyrus and right CA1 volume increase correlated with decreases in verbal memory functioning. In addition, a decrease of mean diffusivity in the left hippocampus correlated with a decrease in letter fluency.
Due to methodological restrictions direct study of neuroplasticity is not possible. MRI is used as an indirect measure.
As both volume increase in the hippocampus and MD decrease can be interpreted as indirect markers for neuroplasticity that co-occur with a decrease in cognitive functioning, our results may indicate that neuroplastic processes are affecting cognitive processes after ECT.
•ECT-induced volume change of the hippocampus relate to cognitive decline.•Diffusivity changes in the hippocampus correlate with cognitive changes after ECT.•This study indicates that neuroplasticity after ECT underlies structural changes.
Cisplatin (cDDP) has regained interest for metastatic breast cancer (MBC) patients, given the platinum sensitivity in subtypes and better manageable toxicity. Here, the primary aim was to determine ...whether molecular characteristics of circulating tumor cells (CTCs) could identify patients responding to cDDP and to describe the outcomes to cDDP monotherapy in a large group of MBC patients pretreated with anthracycline- and taxane-based treatments.
Based on cell line data, a CTC-cDDP-sensitivity profile was generated. Applying an A'Herns single-stage phase II design, further investigation was considered worthwhile if 5/10 patients with a favorable profile responded to cDDP. Patients received 70mg/m
cDDP every three weeks, CTCs were enumerated and the CTC-cDDP-sensitivity profile was determined. In total, 65 heavily pretreated MBC patients (77% received ≥2 lines of previous chemotherapy for MBC) were eligible for the per-protocol analysis. Primary endpoint was response rate, secondary endpoints included best observed response, progression-free survival (PFS) and overall survival (OS).
The best observed response during cDDP therapy was a partial response in 7% and stable disease in 56% of the patients. None of the patients with a favorable CTC-cDDP-sensitivity profile had a response. The median baseline CTC count was 8 (range 0-3254). Patients with <5 CTCs had a better PFS and OS than patients with ≥5 CTCs (median PFS 4.5 months (95%CI 2.38-6.62)
. 2.1 months (95%CI 1.34-2.80)(
=0.009) and median OS 13.1 months (95%CI 9.89-16.33)
. 5.6 months (95%CI 3.60-7.64)(
=0.003). No other factors than CTC count were associated with outcome to cDDP therapy, including triple-negative breast cancer versus ER-positive tumors.
The CTC-cDDP-sensitivity profile was unable to select patients responding to cDDP monotherapy. In an unselected group of heavily pretreated MBC patients, cDDP yields outcomes comparable to other chemotherapeutic regimens for heavily pretreated MBC patients. CTC count was the only factor associated with outcome in these patients.
(https://www.trialregister.nl/trial/3885, identifier NTR4046).
We summarize the major aspects of the remarkable, fairly long lasting period (
∼
2005
to
∼
2010
) of low solar activity, that we will call
the Transition
. It is the transitional stage between the ...Grand Maximum of the 20th century and a forthcoming (most probably Regular) episode of solar activity. The various kinds of activity in the functioning of the equatorial components of the solar dynamo before and during the Transition are summarized. While the behavior of unipolar magnetic regions and their rest-latitudes already gave very early indications – mid 20th century – of the forthcoming Transition, more such indications became available around 1995 and the main part of it occurred between 2005 and 2010. Some of the inferences are discussed. We submit the hypothesis that the solar tachocline undergoes pulsations and we present some helioseismic evidences. In that scenario we find that its equatorial part has moved downward over a fairly small semi-amplitude (
∼
0.03
solar radii) during the time of the Transition. There are several indications, apart from this ‘pulsation’, that the tachocline may even be pulsating with still smaller amplitudes in more modes. We speculate about the physical mechanism(s).
New tuberculosis treatments are needed to address drug resistance, lengthy treatment duration and adverse reactions of available agents. GSK3036656 (ganfeborole) is a first-in-class benzoxaborole ...inhibiting the Mycobacterium tuberculosis leucyl-tRNA synthetase. Here, in this phase 2a, single-center, open-label, randomized trial, we assessed early bactericidal activity (primary objective) and safety and pharmacokinetics (secondary objectives) of ganfeborole in participants with untreated, rifampicin-susceptible pulmonary tuberculosis. Overall, 75 males were treated with ganfeborole (1/5/15/30 mg) or standard of care (Rifafour e-275 or generic alternative) once daily for 14 days. We observed numerical reductions in daily sputum-derived colony-forming units from baseline in participants receiving 5, 15 and 30 mg once daily but not those receiving 1 mg ganfeborole. Adverse event rates were comparable across groups; all events were grade 1 or 2. In a participant subset, post hoc exploratory computational analysis of
F-fluorodeoxyglucose positron emission tomography/computed tomography findings showed measurable treatment responses across several lesion types in those receiving ganfeborole 30 mg at day 14. Analysis of whole-blood transcriptional treatment response to ganfeborole 30 mg at day 14 revealed a strong association with neutrophil-dominated transcriptional modules. The demonstrated bactericidal activity and acceptable safety profile suggest that ganfeborole is a potential candidate for combination treatment of pulmonary tuberculosis.ClinicalTrials.gov identifier: NCT03557281 .
We report on measurements of the neutron spin asymmetries A{sub 1,2}{sup n} and polarized structure functions g{sub 1,2}{sup n} at three kinematics in the deep inelastic region, with x=0.33, 0.47, ...and 0.60 and Q{sup 2}=2.7, 3.5, and 4.8 (GeV/c){sup 2}, respectively. These measurements were performed using a 5.7 GeV longitudinally polarized electron beam and a polarized {sup 3}He target. The results for A{sub 1}{sup n} and g{sub 1}{sup n} at x=0.33 are consistent with previous world data and, at the two higher-x points, have improved the precision of the world data by about an order of magnitude. The new A{sub 1}{sup n} data show a zero crossing around x=0.47 and the value at x=0.60 is significantly positive. These results agree with a next-to-leading-order QCD analysis of previous world data. The trend of data at high x agrees with constituent quark model predictions but disagrees with that from leading-order perturbative QCD (PQCD) assuming hadron helicity conservation. Results for A{sub 2}{sup n} and g{sub 2}{sup n} have a precision comparable to the best world data in this kinematic region. Combined with previous world data, the moment d{sub 2}{sup n} was evaluated and the new result has improved the precision of this quantity by about a factor of 2. When combined with the world proton data, polarized quark distribution functions were extracted from the new g{sub 1}{sup n}/F{sub 1}{sup n} values based on the quark-parton model. While results for {delta}u/u agree well with predictions from various models, results for {delta}d/d disagree with the leading-order PQCD prediction when hadron helicity conservation is imposed.
Background. In June 2000 a new ERA–EDTA Registry Office was opened in Amsterdam. This Registry will only collect core data on renal replacement therapy (RRT) through national and regional registries. ...This paper reports the technical and epidemiological results of a pilot study combining the data from six registries. Methods. Data from the national renal registries of Austria, Finland, French‐Belgium, The Netherlands, Norway, and Scotland were combined. Patients starting RRT between 1980 and 1999 (n=57371) were included in the analyses. Cox proportional hazards regression was used to predict survival. Results. The use of different coding systems for ESRD treatment by the registries made it difficult to merge the data. Incidence and prevalence of RRT showed a continuous increase with a marked variation in rates between countries. The 2‐, 5‐ and 10‐year patient survival was 67, 35 and 11% in dialysis patients and 90, 81 and 64% after a first renal allograft. Multivariate analysis showed a slightly better survival on dialysis in the 1990–1994 (RR 0.94, 95% CI 0.90–0.98) and the 1995–1999 cohort (RR 0.88, 95% CI 0.84–0.92) compared to the 1980–1984 cohort. In contrast, there was a much greater improvement in transplant‐patient survival, resulting in a 56% reduction in the risk of death within the 1995–1999 cohort (RR 0.44, 95% CI 0.39–0.50) compared to the 1980–1984 cohort. Conclusions. This study provides support for the feasibility of a ‘new style’ ERA–EDTA registry and the collection of data is now being extended to other countries. The improvement in patient survival over the last two decades has been much greater in transplant recipients than in dialysis patients.
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