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The purpose of writing this article was to describe RADEC learning model in building critical thinking skills. This study was conducted because of the need for a learning model that fits the Indonesian context to build critical thinking skills that can be used at elementary school level. This study used the literature review. This study produced one solution to be able to build critical thinking skills using RADEC learning model (read-answer-discuss-explain and create). The approach in learning done by the teacher plays a role in improving critical thinking skills. The teacher needs to use a learning model that can stimulate students’ critical thinking skills.

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References

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RESULTS

High and intermediate levels of IgG auto-Abs against IFN-α2 and/or IFN-ω in

20% of patients with critical COVID-19

Auto-Abs neutralizing IFN-α2 and/or IFN-ω (10 ng/ml) in almost 10% of the critical patients

Anti–type I IFN auto-Ab positive
(amount of type I IFN neutralized,
in plasma diluted 1:10)
Proportion of critical patients with
neutralizing auto-Abs
OR [95% CI]P value
Anti–IFN-α2 and anti–IFN-ω auto-Abs
(10 ng/ml)
5.6%67 [4–1109]7.8 × 10 −13
Anti–IFN-α2 and/or anti–IFN-ω auto-Abs
(10 ng/ml)
9.8%17 [7–45]<10 −13
Anti–IFN-α2 auto-Abs (10 ng/ml)9%45 [9–225]<10 −13
Anti–IFN-α2 auto-Abs only (10 ng/ml)3.4%21 [4–107]1.8 × 10 −09
Anti–IFN-ω auto-Abs (10 ng/ml)6.4%13 [4–38]1.4 × 10 −12
Anti–IFN-ω auto-Abs only (10 ng/ml)0.8%3 [0.9–10]0.057
Anti–IFN-α2 and anti–IFN-ω auto-Abs
(100 pg/ml)
7.1%54 [11–275]<10 −13
Anti–IFN-α2 and/or anti–IFN-ω auto-Abs
(100 pg/ml)
13.6%13 [8–21]<10 −13
Anti–IFN-α2 auto-Abs (100 pg/ml)10%23 [10–55]<10 −13
Anti–IFN-α2 auto-Abs only (100 pg/ml)2.9%10 [3–26]2.8 × 10 −09
Anti–IFN-ω auto-Abs (100 pg/ml)10.7%13 [7–23]<10 −13
Anti–IFN-ω auto-Abs only (100 pg/ml)3.6%6 [3–12]3.9 × 10 −10
Anti–IFN-β auto-Abs (10 ng/ml)1.3%8 [2–36]1.7 × 10 −3
Anti–IFN-β auto-Abs only (10 ng/ml)0.96%5 [1–25]0.043
Anti–IFN-β auto-Abs (10 ng/ml) and
anti–IFN-α2 and/or anti–IFN-ω auto-Abs
(100 pg/ml)
0.34%16 [0.5–497]0.018
Anti–IFN-β (10 ng/ml) and anti–IFN-α2
and anti–IFN-ω auto-Abs (100 pg/ml)
0.28%16 [0.5–502]0.019

Auto-Abs neutralizing IFN-α2 and/or IFN-ω (100 pg/ml) in at least 13.6% of critical patients and 6.8% of severe patients

Auto-Abs neutralize low concentrations of IFN-α2 protective against SARS-CoV-2

100 pg/ml) or 20 pM (

400 pg/ml) IFN-α2 on five samples from patients with life-threatening COVID-19 and two samples from uninfected elderly individuals with auto-Abs neutralizing IFN-α2 (100 pg/ml but not 10 ng/ml). As controls, we tested a commercial mAb against IFN-α2, a sample from a patient with auto-Abs neutralizing IFN-α2 (10 ng/ml), samples from three patients with life-threatening COVID-19, and three healthy controls without detectable auto-Abs against type I IFNs. We found that the 1:100 dilutions of plasma from four of the five patients with critical COVID-19 and one of the two elderly individuals with auto-Abs neutralizing IFN-α2 (100 pg/ml) were able to neutralize the protective effect of IFN-α2 (

400 pg/ml) against SARS-CoV-2, whereas samples from all these individuals fully or partially neutralized IFN-α2 (

100 pg/ml) (Fig. 2A). No such neutralizing effect was observed for any of the auto-Ab–negative controls. Overall, our findings indicate that auto-Abs against type I IFNs capable of neutralizing IFN (100 pg/ml) in 1% plasma can block the protective effect of IFN-α2 (

400 pg/ml) against SARS-CoV-2. These findings raise the possibility that even 100-fold lower levels of auto-Abs against type I IFNs, capable of neutralizing lower, physiological concentrations of IFN-α2 (10 pg/ml) may be present in an even larger proportion of patients. The testing of this hypothesis will require the development of new, more sensitive methods to screen for neutralization.

400 pg/ml) in the presence of 1:100 plasma from healthy controls without auto-Abs (N = 3, in blue), from patients with life-threatening COVID-19 but without auto-Abs against IFN-α2 (N = 3, in black), a commercial anti–IFN-α2 antibody (mAb; in red); from a patient with life-threatening COVID-19 and auto-Abs neutralizing IFN-α2 (10 ng/ml) in plasma 1:100 (COVID-19 AAB + ; N = 1, in orange), from patients with life-threatening COVID-19 and auto-Abs neutralizing IFN-α2 (100 pg/ml) in plasma 1:100 (N = 5, in gray); and from elderly individuals with auto-Abs neutralizing IFN-α2 (100 pg/ml) in plasma 1:100 (N = 2, in purple). Each dot represents a technical replicate. All experiments were done in triplicate. (B) ELISA for auto-Abs against the 13 IFN-α forms, IFN-ω, IFN-β, IFN-ε, and IFN-κ in patients with life-threatening COVID-19 and auto-Abs neutralizing IFN-α2 (100 pg/ml) (N = 6), patient with APS-1 with life-threatening COVID-19 and auto-Abs neutralizing IFN-α2 and IFN-ω (10 ng/ml) (N = 1), and healthy controls (N = 2). (C) RLA after stimulation with the all individual IFN-α at a concentration of 1 ng/ml, with 1:10 plasma from a healthy control (negative control), a patient with APS-1 (positive control), and patients with life-threatening COVID-19 and neutralizing IFN-α2 and/or IFN-ω or a mAb anti–IFN-α2. (D) Neutralization of IFN-β (10 ng/ml) in the presence of plasma 1:10 from patients with critical COVID-19 (N = 1773), severe COVID-19 (N = 187), or asymptomatic/mild controls (N = 1044).

Conclusion

The situation in Syria will continue to evolve with or without external military intervention, and those contemplating such action should be prepared to deal with the attendant uncertainties. The effects of sanctions, the regime’s cohesion, and the nature and resilience of the opposition are questions that can only be resolved over time. And inevitably, concerns will arise regarding precisely how, why, and under what conditions to support unarmed or armed opposition elements. Yet waiting for complete clarity before deciding to intervene can lead to paralysis.

Unquestionably, military intervention in Syria on any significant scale would be a complicated and arduous course of action with some risks. But not intervening in the face of the regime’s now fully revealed violent and repressive nature carries its own dangers and, likely, adverse consequences. Either way, the United States and its allies should begin discussing the issue publicly now — a vigorous debate would itself serve as an important signal to the regime.

Jeffrey White is a defense fellow at The Washington Institute, specializing in military and security affairs.

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