We present an update of the global fit of the Standard Model electroweak sector to latest experimental results. We include new kinematic top quark and
W
boson mass measurements from the LHC, a
sin
2
...θ
eff
ℓ
result from the Tevatron, and a new evaluation of the hadronic contribution to
α
(
M
Z
2
)
. We present tests of the internal consistency of the electroweak Standard Model and updated numerical predictions of key observables. The electroweak data combined with measurements of the Higgs boson coupling strengths and flavour physics observables are used to constrain parameters of two-Higgs-doublet models.
For a long time, global fits of the electroweak sector of the standard model (SM) have been used to exploit measurements of electroweak precision observables at lepton colliders (LEP, SLC), together ...with measurements at hadron colliders (Tevatron, LHC) and accurate theoretical predictions at multi-loop level, to constrain free parameters of the SM, such as the Higgs and top masses. Today, all fundamental SM parameters entering these fits are experimentally determined, including information on the Higgs couplings, and the global fits are used as powerful tools to assess the validity of the theory and to constrain scenarios for new physics. Future measurements at the Large Hadron Collider (LHC) and the International Linear Collider (ILC) promise to improve the experimental precision of key observables used in the fits. This paper presents updated electroweak fit results using the latest NNLO theoretical predictions and prospects for the LHC and ILC. The impact of experimental and theoretical uncertainties is analysed in detail. We compare constraints from the electroweak fit on the Higgs couplings with direct LHC measurements, and we examine present and future prospects of these constraints using a model with modified couplings of the Higgs boson to fermions and bosons.
In view of the discovery of a new boson by the ATLAS and CMS Collaborations at the LHC, we present an update of the global Standard Model (SM) fit to electroweak precision data. Assuming the new ...particle to be the SM Higgs boson, all fundamental parameters of the SM are known allowing, for the first time, to overconstrain the SM at the electroweak scale and assert its validity. Including the effects of radiative corrections and the experimental and theoretical uncertainties, the global fit exhibits a
p
-value of 0.07. The mass measurements by ATLAS and CMS agree within 1.3
σ
with the indirect determination
. Within the SM the
W
boson mass and the effective weak mixing angle can be accurately predicted to be
M
W
=80.359±0.011 GeV and
from the global fit. These results are compatible with, and exceed in precision, the direct measurements. For the indirect determination of the top quark mass we find
, in agreement with the kinematic and cross-section-based measurements.
Objective
Rapid administration of antiseizure medications is a critical concept in the treatment of status epilepticus. Although undiluted levetiracetam (LEV) doses of up to 2500 mg have been ...evaluated, minimal data exist to support the safety of loading doses up to 4500 mg. This study will evaluate intravenous (IV) push administration of undiluted LEV from 2500 to 4500 mg for safety outcomes as well as tolerability.
Methods
This is a retrospective, observational, cohort analysis of adult patients who received at least one loading dose of undiluted IV push LEV from October 15, 2019, to April 30, 2022, at a large academic medical center in Phoenix, Arizona. Relevant outcomes include the safety and tolerability of rapid administration of undiluted LEV at higher loading doses.
Results
We evaluated 518 loading doses in 518 unique patients included during the study period. LEV was a new medication for witnessed or suspected seizures in 80.3% of patients, with 31.2% having a documented history of epilepsy or seizure disorder. At the time of LEV administration, 52.9% of patients were on a general medicine floor, 34.3% were in the intensive care unit, and 12.7% were in the emergency department. The median loading dose of LEV was 3600 mg (3000–4000 mg), with 4000 mg being the most common loading dose given. Peripheral IV lines were documented as the only available line in 78.6% of patients for loading dose administration. No adverse events associated with LEV administration were documented.
Significance
Rapid IV administration of undiluted doses of LEV is both safe and tolerable in loading doses of 2500–4500 mg, allowing for rapid drug administration in the setting of status epilepticus.
Type 1 diabetes is an autoimmune disease characterized by progressive loss of pancreatic beta cells. Golimumab is a human monoclonal antibody specific for tumor necrosis factor
that has already been ...approved for the treatment of several autoimmune conditions in adults and children. Whether golimumab could preserve beta-cell function in youth with newly diagnosed overt (stage 3) type 1 diabetes is unknown.
In this phase 2, multicenter, placebo-controlled, double-blind, parallel-group trial, we randomly assigned, in a 2:1 ratio, children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes to receive subcutaneous golimumab or placebo for 52 weeks. The primary end point was endogenous insulin production, as assessed according to the area under the concentration-time curve for C-peptide level in response to a 4-hour mixed-meal tolerance test (4-hour C-peptide AUC) at week 52. Secondary and additional end points included insulin use, the glycated hemoglobin level, the number of hypoglycemic events, the ratio of fasting proinsulin to C-peptide over time, and response profile.
A total of 84 participants underwent randomization - 56 were assigned to the golimumab group and 28 to the placebo group. The mean (±SD) 4-hour C-peptide AUC at week 52 differed significantly between the golimumab group and the placebo group (0.64±0.42 pmol per milliliter vs. 0.43±0.39 pmol per milliliter, P<0.001). A treat-to-target approach led to good glycemic control in both groups, and there was no significant difference between the groups in glycated hemoglobin level. Insulin use was lower with golimumab than with placebo. A partial-remission response (defined as an insulin dose-adjusted glycated hemoglobin level score calculated as the glycated hemoglobin level plus 4 times the insulin dose of ≤9) was observed in 43% of participants in the golimumab group and in 7% of those in the placebo group (difference, 36 percentage points; 95% CI, 22 to 55). The mean number of hypoglycemic events did not differ between the trial groups. Hypoglycemic events that were recorded as adverse events at the discretion of investigators were reported in 13 participants (23%) in the golimumab group and in 2 (7%) of those in the placebo group. Antibodies to golimumab were detected in 30 participants who received the drug; 29 had antibody titers lower than 1:1000, of whom 12 had positive results for neutralizing antibodies.
Among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo. (Funded by Janssen Research and Development; T1GER ClinicalTrials.gov number, NCT02846545.).
Environmentally induced or epigenetic-related beta-cell dysfunction and insulin resistance play a critical role in the progression to diabetes. We developed a mathematical modeling framework capable ...of studying the progression to diabetes incorporating various diabetogenic factors. Considering the heightened risk of beta-cell defects induced by obesity, we focused on the obesity-diabetes model to further investigate the influence of obesity on beta-cell function and glucose regulation. The model characterizes individualized glucose and insulin dynamics over the span of a lifetime. We then fit the model to the longitudinal data of the Pima Indian population, which captures both the fluctuations and long-term trends of glucose levels. As predicted, controlling or eradicating the obesity-related factor can alleviate, postpone, or even reverse diabetes. Furthermore, our results reveal that distinct abnormalities of beta-cell function and levels of insulin resistance among individuals contribute to different risks of diabetes. This study may encourage precise interventions to prevent diabetes and facilitate individualized patient treatment.
We present an update of the Standard Model fit to electroweak precision data. We include newest experimental results on the top-quark mass, the
W
mass and width, and the Higgs-boson mass bounds from ...LEP, Tevatron and the LHC. We also include a new determination of the electromagnetic coupling strength at the
Z
pole. We find for the Higgs-boson mass
and
when not including and including the direct Higgs searches, respectively. From the latter fit we indirectly determine the
W
mass to be
. We exploit the data to determine experimental constraints on the oblique vacuum polarisation parameters, and confront these with predictions from the Standard Model (SM) and selected SM extensions. By fitting the oblique parameters to the electroweak data we derive allowed regions in the BSM parameter spaces. We revisit and consistently update these constraints for a fourth fermion generation, two Higgs doublet, inert Higgs and littlest Higgs models, models with large, universal or warped extra dimensions and technicolour. In most of the models studied a heavy Higgs boson can be made compatible with the electroweak precision data.
Despite substantial evidence of the benefit of frequent self-monitoring of blood glucose (SMBG) in type 1 diabetes, certain insurers limit the number of test strips that they will provide. The large ...database of the T1D Exchange clinic registry provided an opportunity to evaluate the relationship between the number of SMBG measurements per day and HbA1c levels across a wide age range of children and adults.
The analysis included 20,555 participants in the T1D Exchange clinic registry with type 1 diabetes ≥1 year and not using a continuous glucose monitor (11,641 younger than age 18 years and 8,914 18 years old or older). General linear models were used to assess the association between the number of SMBG measurements and HbA1c levels after adjusting for potential confounding variables.
A higher number of SMBG measurements per day were associated with non-Hispanic white race, insurance coverage, higher household income, and use of an insulin pump for insulin delivery (P < 0.001 for each factor). After adjusting for these factors, a higher number of SMBG measurements per day was strongly associated with a lower HbA1c level (adjusted P < 0.001), with the association being present in all age-groups and in both insulin pump and injection users.
There is a strong association between higher SMBG frequency and lower HbA1c levels. It is important for insurers to consider that reducing restrictions on the number of test strips provided per month may lead to improved glycemic control for some patients with type 1 diabetes.
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