The CD19 protein forms a complex with CD21, CD81, and CD225 in the membrane of mature B cells. Together with the B-cell antigen receptor, this complex signals the B cell to decrease its threshold for ...activation by the antigen.
We evaluated four patients from two unrelated families who had increased susceptibility to infection, hypogammaglobulinemia, and normal numbers of mature B cells in blood. We found a mutation in the CD19 gene in all four patients. The CD19 gene in the patients and their first-degree relatives was sequenced, and flow-cytometric immunophenotyping of B cells, immunohistochemical staining of lymphoid tissues, and DNA and messenger RNA analysis were performed. B-cell responses on the triggering of the B-cell receptor were investigated by in vitro stimulation; the antibody response after vaccination with rabies vaccine was also studied.
All four patients had homozygous mutations in the CD19 gene. Levels of CD19 were undetectable in one patient and substantially decreased in the other three. Levels of CD21 were decreased, whereas levels of CD81 and CD225 were normal, in all four patients. The composition of the precursor B-cell compartment in bone marrow and the total numbers of B cells in blood were normal. However, the numbers of CD27+ memory B cells and CD5+ B cells were decreased. Secondary follicles in lymphoid tissues were small to normal in size and had a normal cellular composition. The few B cells that showed molecular signs of switching from one immunoglobulin class to another contained V(H)-C(alpha) and V(H)-C(gamma) transcripts with somatic mutations. The response of the patients' B cells to in vitro stimulation through the B-cell receptor was impaired, and in all four patients, the antibody response to rabies vaccination was poor.
Mutation of the CD19 gene causes a type of hypogammaglobulinemia in which the response of mature B cells to antigenic stimulation is defective.
The T2K experiment presents new measurements of neutrino oscillation parameters using
19.7
(
16.3
)
×
10
20
protons on target (POT) in (anti-)neutrino mode at the far detector (FD). Compared to the ...previous analysis, an additional
4.7
×
10
20
POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on
sin
2
θ
13
and the impact of priors on the
δ
CP
measurement. Both analyses prefer the normal mass ordering and upper octant of
sin
2
θ
23
with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on
sin
2
θ
13
from reactors,
sin
2
θ
23
=
0
.
561
-
0.032
+
0.021
using Feldman–Cousins corrected intervals, and
Δ
m
32
2
=
2
.
494
-
0.058
+
0.041
×
10
-
3
eV
2
using constant
Δ
χ
2
intervals. The CP-violating phase is constrained to
δ
CP
=
-
1
.
97
-
0.70
+
0.97
using Feldman–Cousins corrected intervals, and
δ
CP
=
0
,
π
is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than
2
σ
credible level using a flat prior in
δ
CP
,
and just below
2
σ
using a flat prior in
sin
δ
CP
.
When the external constraint on
sin
2
θ
13
is removed,
sin
2
θ
13
=
28
.
0
-
6.5
+
2.8
×
10
-
3
,
in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.
Abstract The T2K experiment presents new measurements of neutrino oscillation parameters using $$19.7(16.3)\times 10^{20}$$ 19.7 ( 16.3 ) × 10 20 protons on target (POT) in (anti-)neutrino mode at ...the far detector (FD). Compared to the previous analysis, an additional $$4.7\times 10^{20}$$ 4.7 × 10 20 POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on $$\sin ^2\theta _{13}$$ sin 2 θ 13 and the impact of priors on the $$\delta _{\textrm{CP}}$$ δ CP measurement. Both analyses prefer the normal mass ordering and upper octant of $$\sin ^2\theta _{23}$$ sin 2 θ 23 with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on $$\sin ^2\theta _{13}$$ sin 2 θ 13 from reactors, $$\sin ^2\theta _{23}=0.561^{+0.021}_{-0.032}$$ sin 2 θ 23 = 0 . 561 - 0.032 + 0.021 using Feldman–Cousins corrected intervals, and $$\varDelta {}m^2_{32}=2.494_{-0.058}^{+0.041}\times 10^{-3}~\text {eV}^2$$ Δ m 32 2 = 2 . 494 - 0.058 + 0.041 × 10 - 3 eV 2 using constant $$\varDelta \chi ^{2}$$ Δ χ 2 intervals. The CP-violating phase is constrained to $$\delta _{\textrm{CP}}=-1.97_{-0.70}^{+0.97}$$ δ CP = - 1 . 97 - 0.70 + 0.97 using Feldman–Cousins corrected intervals, and $$\delta _{\textrm{CP}}=0,\pi $$ δ CP = 0 , π is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than $$2\sigma $$ 2 σ credible level using a flat prior in $$\delta _{\textrm{CP}},$$ δ CP , and just below $$2\sigma $$ 2 σ using a flat prior in $$\sin \delta _{\textrm{CP}}.$$ sin δ CP . When the external constraint on $$\sin ^2\theta _{13}$$ sin 2 θ 13 is removed, $$\sin ^2\theta _{13}=28.0^{+2.8}_{-6.5}\times 10^{-3},$$ sin 2 θ 13 = 28 . 0 - 6.5 + 2.8 × 10 - 3 , in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.
To describe adaptations in the provision of rehabilitation services proposed by scientific and professional rehabilitation organizations to avoid interruptions to patients rehabilitation process and ...delays in starting rehabilitation in patients with COVID-19.
A narrative review approach was used to identify the recommendations of scientific and professional organizations in the area of rehabilitation. A systematic search was performed in the main data-bases in 78 international and regional web portals of rehabilitation organizations. A total of 21 publications from these organizations were identified and selected.
The results are presented in 4 categories: adequacy of inpatient services, including acute care services and intensive care unit for patients with and without COVID-19; adequacy of outpatient services, including home-based rehabilitation and tele-rehabilitation; recommendations to prevent the spread of COVID-19; and regulatory standards and positions during the COVID-19 pandemic expressed by organizations for protecting the rights of health workers and patients.
Health systems around the world are rapidly learning from actions aimed at the reorganization of rehabilitation services for patients who are in the process of recovery from acute or chronic conditions, and the rapid response to the rehabilitation of survivors of COVID-19, as well as from efforts in the prevention of contagion of those providing the services.
The use of brief screening tools to identify inactive patients is essential to improve the efficiency of primary care-based physical activity (PA) programs. However, the current employment of short ...PA questionnaires within the Spanish primary care pathway is unclear. This study evaluated the validity of the Spanish version of a Brief Physical Activity Assessment Tool (SBPAAT).
A validation study was carried out within the EVIDENT project. A convenience sample of patients (n = 1,184; age 58.9±13.7 years; 60.5% female) completed the SBPAAT and the 7-day Physical Activity Recall (7DPAR) and, in addition, wore an accelerometer (ActiGraph GT3X) for seven consecutive days. Validity was evaluated by measuring agreement, Kappa correlation coefficients, sensitivity and specificity in achieving current PA recommendations with the 7DPAR. Pearson correlation coefficients with the number of daily minutes engaged in moderate and vigorous intensity PA according to the accelerometer were also assessed. Comparison with accelerometer counts, daily minutes engaged in sedentary, light, moderate, and vigorous intensity PA, total daily kilocalories, and total PA and leisure time expenditure (METs-hour-week) between the sufficiently and insufficiently active groups identified by SBPAAT were reported.
The SBPAAT identified 41.3% sufficiently active (n = 489) and 58.7% insufficiently active (n = 695) patients; it showed moderate validity (k = 0.454, 95% CI: 0.402-0.505) and a specificity and sensitivity of 74.3% and 74.6%, respectively. Validity was fair for identifying daily minutes engaged in moderate (r = 0.215, 95% CI:0.156 to 0.272) and vigorous PA (r = 0.282, 95% CI:0.165 to 0.391). Insufficiently active patients according to the SBPAAT significantly reported fewer counts/minute (-22%), fewer minutes/day of moderate (-11.38) and vigorous PA (-2.69), spent fewer total kilocalories/day (-753), and reported a lower energy cost (METs-hour-week) of physical activities globally (-26.82) and during leisure time (-19.62).
The SBPAAT is a valid tool to identify Spanish-speaking patients who are insufficiently active to achieve health benefits.
Effects of canola oil spraying on feed intake, ruminal volatile fatty acids (VFA) concentrations and methane (CH4) emissions were investigated in cattle grazing a temperate pasture. Sixty 1-yr-old ...crossbred steers were allocated into two groups (n=30/group), balanced for body weight (293.8±14.0kg). Following acclimatisation the groups were randomly assigned to one of the two grazing treatments: daily grazing pasture strips (0.1ha) sprayed daily with canola oil (Oil-spray, 12L/strip) and no oil sprayed (Control). The experimental phase involved two periods (Period 1 and 2), for which a paddock of perennial ryegrass (Lolium perenne) was subdivided by electric fences into 0.1ha strips. Period 1 lasted 5 days, whereas Period 2 lasted 12 days. Treatments were applied only in Period 2. Methane emissions were measured using the SF6 tracer technique over 3 days in Period 1 (baseline emissions) and over 4 days in Period 2. Individual animals' feed dry matter intake (DMI) were estimated only in Period 2 using TiO2 as faecal output marker and in vitro digestibility of forage dry matter (IVDMD). Concentrations of VFA in rumen fluid were determined in samples collected at the end of the study by stomach-tubing. Baseline CH4 emissions did not differ between the cattle groups. In Period 2, the herbage eaten by cattle on Oil-spray treatment had higher fat content than on Control (8.9 vs. 3.9% of DM), with no apparent difference in other chemical entities. Cattle grazed on Oil-spray pasture had higher (P=0.02) DMI than those on Control pasture (8.29 vs. 7.51kg/d). Methane emissions from cattle on Oil-spray treatment were lower (P<0.01) than those on Control pasture both on gross (138.6 vs. 156.1g/d) and per unit of feed intake (17.2 vs. 20.9g/kg DMI) basis. Oil spraying of pasture resulted in lower (P<0.001) acetate/propionate ratio in rumen fluid compared to Control pasture (4.2 vs. 5.1). It is concluded that enhanced dietary lipids contents is an effective means of reducing CH4 emissions from grazed pasture. Longer term evaluation of oil supplementation effects on CH4 emission and feeding value of grazed herbages may aid in defining forage breeding avenues targeting lipid content of forage species.
•Oil-spraying of pasture effectively increased the lipids intake by grazing cattle.•Oil-spraying resulted in enhanced feed intake and decreased methane emission.•Oil-spraying resulted in lowered acetate/propionate ratio in rumen fluid.•Forages high in lipids may have environmental and productivity benefits.
This paper reports the first measurement of muon neutrino charged-current interactions without pions in the final state using multiple detectors with correlated energy spectra at T2K. The data was ...collected on hydrocarbon targets using the off-axis T2K near detector (ND280) and the on-axis T2K near detector (INGRID) with neutrino energy spectra peaked at 0.6 GeV and 1.1 GeV respectively. The correlated neutrino flux presents an opportunity to reduce the impact of the flux uncertainty and to study the energy dependence of neutrino interactions. The extracted double-differential cross sections are compared to several Monte Carlo neutrino-nucleus interaction event generators showing the agreement between both detectors individually and with the correlated result.
To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA).
An ...observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin IVIG) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG).
Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88).
From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD.
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