Taiwan was a coronavirus disease 2019 (COVID-19) outlier, with an extraordinarily long transmission-free record: 253 days without locally transmitted infections while the rest of the world battled ...wave after wave of infection. The appearance of the alpha variant in May 2021, closely followed by the delta variant, disrupted this transmission-free streak. However, despite low vaccination coverage (<1%), outbreaks were well-controlled.
This study analyzed the time to border closure and conducted one-sample t test to compare between Taiwan and Non-Taiwan countries prior to vaccine introduction. The study also collected case data to observe the dynamics of omicron transmission. Time-varying reproduction number,Rt, was calculated and was used to reflect infection impact at specified time points and model trends of future incidence.
The study analyzed and compare the time to border closure in Taiwan and non-Taiwan countries. The mean times to any border closure from the first domestic case within each country were -21 and 5.98 days, respectively (P < .0001). The Taiwanese government invested in quick and effective contact tracing with a precise quarantine strategy in lieu of a strict lockdown. Residents followed recommendations based on self-discipline and unity. The self-discipline in action is evidenced in Google mobility reports. The central and local governments worked together to enact non-pharmaceutical interventions (NPIs), including universal masking, social distancing, limited unnecessary gatherings, systematic contact tracing, and enhanced quarantine measures. The people cooperated actively with pandemic-prevention regulations, including vaccination and preventive NPIs.
This article describes four key factors underlying Taiwan's success in controlling COVID-19 transmission: quick responses; effective control measures with new technologies and rolling knowledge updates; unity and cooperation among Taiwanese government agencies, private companies and organizations, and individual citizens; and Taiwanese self-discipline.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mathematical and statistical models are used to predict trends in epidemic spread and determine the effectiveness of control measures. Automatic regressive integrated moving average (ARIMA) models ...are used for time-series forecasting, but only few models of the 2019 coronavirus disease (COVID-19) pandemic have incorporated protective behaviors or vaccination, known to be effective for pandemic control.
To improve the accuracy of prediction, we applied newly developed ARIMA models with predictors (mask wearing, avoiding going out, and vaccination) to forecast weekly COVID-19 case growth rates in Canada, France, Italy, and Israel between January 2021 and March 2022. The open-source data was sourced from the YouGov survey and Our World in Data. Prediction performance was evaluated using the root mean square error (RMSE) and the corrected Akaike information criterion (AICc).
A model with mask wearing and vaccination variables performed best for the pandemic period in which the Alpha and Delta viral variants were predominant (before November 2021). A model using only past case growth rates as autoregressive predictors performed best for the Omicron period (after December 2021). The models suggested that protective behaviors and vaccination are associated with the reduction of COVID-19 case growth rates, with booster vaccine coverage playing a particularly vital role during the Omicron period. For example, each unit increase in mask wearing and avoiding going out significantly reduced the case growth rate during the Alpha/Delta period in Canada (-0.81 and -0.54, respectively; both p < 0.05). In the Omicron period, each unit increase in the number of booster doses resulted in a significant reduction of the case growth rate in Canada (-0.03), Israel (-0.12), Italy (-0.02), and France (-0.03); all p < 0.05.
The key findings of this study are incorporating behavior and vaccination as predictors led to accurate predictions and highlighted their significant role in controlling the pandemic. These models are easily interpretable and can be embedded in a "real-time" schedule with weekly data updates. They can support timely decision making about policies to control dynamically changing epidemics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This modeling study considers different screening strategies, contact tracing, and the severity of novel epidemic outbreaks for various population sizes, providing insight into multinational ...containment effectiveness of emerging infectious diseases, prior to vaccines development. During the period of the ancestral SARS-Cov-2 virus, contact tracing alone is insufficient to achieve outbreak control. Although universal testing is proposed in multiple nations, its effectiveness accompanied by other measures is rarely examined. Our research investigates the necessity of universal testing when contact tracing and symptomatic screening measures are implemented. We used a stochastic transmission model to simulate COVID-19 transmission, evaluating containment strategies via contact tracing, one-time high risk symptomatic testing, and universal testing. Despite universal testing having the potential to identify subclinical cases, which is crucial for non-pharmaceutical interventions, our model suggests that universal testing only reduces the total number of cases by 0.0009% for countries with low COVID-19 prevalence and 0.025% for countries with high COVID-19 prevalence when rigorous contact tracing and symptomatic screening are also implemented. These findings highlight the effectiveness of testing strategies and contact tracing in reducing COVID-19 cases by identifying subclinical cases.
Neural prostheses translate neural activity from the brain into control signals for guiding prosthetic devices, such as computer cursors and robotic limbs, and thus offer individuals with ...disabilities greater interaction with the world. However, relatively low performance remains a critical barrier to successful clinical translation; current neural prostheses are considerably slower, with less accurate control, than the native arm. Here we present a new control algorithm, the recalibrated feedback intention-trained Kalman filter (ReFIT-KF) that incorporates assumptions about the nature of closed-loop neural prosthetic control. When tested in rhesus monkeys implanted with motor cortical electrode arrays, the ReFIT-KF algorithm outperformed existing neural prosthetic algorithms in all measured domains and halved target acquisition time. This control algorithm permits sustained, uninterrupted use for hours and generalizes to more challenging tasks without retraining. Using this algorithm, we demonstrate repeatable high performance for years after implantation in two monkeys, thereby increasing the clinical viability of neural prostheses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Somatic gain-of-function mutations in isocitrate dehydrogenases (
) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite (
)-2-hydroxyglutarate ...(2HG). 2HG competitively inhibits α-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the TET family, causing epigenetic dysregulation and a block in cellular differentiation.
studies have provided proof of concept for mutant IDH inhibition as a therapeutic approach. We report the discovery and characterization of AG-221, an orally available, selective, potent inhibitor of the mutant IDH2 enzyme. AG-221 suppressed 2HG production and induced cellular differentiation in primary human
mutation-positive acute myeloid leukemia (AML) cells
and in xenograft mouse models. AG-221 also provided a statistically significant survival benefit in an aggressive IDH2
-mutant AML xenograft mouse model. These findings supported initiation of the ongoing clinical trials of AG-221 in patients with
mutation-positive advanced hematologic malignancies.
Mutations in
are identified in approximately 20% of patients with AML and contribute to leukemia via a block in hematopoietic cell differentiation. We have shown that the targeted inhibitor AG-221 suppresses the mutant IDH2 enzyme in multiple preclinical models and induces differentiation of malignant blasts, supporting its clinical development.
.
We investigate the unintended benefits of mandatory dividend payout regulations for Chinese listed firms seeking refinancing to enhance their investment efficiency, even though the initial intention ...of these regulations is to protect powerless external minority shareholders. We find that, while these regulations mitigate the overinvestment of all listed firms, this effect is more pronounced among refinancing firms than among non‐refinancing firms. We further find evidence partially showing that the mitigating effect of these regulations on overinvestment is driven mainly by state‐owned enterprises (SOEs). These findings suggest dividend payout regulations are used to partially ameliorate Chinese listed firms’ investment inefficiency, particularly those of SOEs.
Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown ...that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event.
To objectively ascertain whether alcohol consumption heightens risk for an AF ...episode.
A prospective, case-crossover analysis.
Ambulatory persons in their natural environments.
Consenting patients with paroxysmal AF.
Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events.
Of 100 participants (mean age, 64 years SD, 15; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio OR, 2.02 95% CI, 1.38 to 3.17) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 CI, 1.63 to 7.89) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 CI, 1.04 to 1.83 per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 CI, 1.06 to 1.22 per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours.
Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population.
Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur.
National Institute on Alcohol Abuse and Alcoholism.
Previously, we demonstrated capture and concentration of
Salmonella enterica
subspecies
enterica
ser. Typhimurium using magnetic ionic liquids (MILs), followed by rapid isothermal detection of ...captured cells via recombinase polymerase amplification (RPA). Here, we report work intended to explore the broader potential of MILs as novel pre-analytical capture reagents in food safety and related applications. Specifically, we evaluated the capacity of the (P
66614
+
Ni(hfacac)
3
−
) (“Ni(II)”) MIL to bind a wider range of human pathogens using a panel of
Salmonella
and
Escherichia coli
O157:H7 isolates, including a “deep rough” strain of
S
. Minnesota. We extended this exploration further to include other members of the family
Enterobacteriaceae
of food safety and clinical or agricultural significance. Both the Ni(II) MIL and the (P
66614
+
Dy(hfacac)
4
−
) (“Dy(III)”) MIL were evaluated for their effects on cell viability and structure-function relationships behind observed antimicrobial activities of the Dy(III) MIL were determined. Next, we used flow imaging microscopy (FIM) of Ni(II) MIL dispersions made in model liquid media to examine the impact of increasing ionic complexity on MIL droplet properties as a first step towards understanding the impact of suspension medium properties on MIL dispersion behavior. Finally, we used FIM to examine interactions between the Ni(II) MIL and
Serratia marcescens
, providing insights into how the MIL may act to capture and concentrate Gram-negative bacteria in aqueous samples, including food suspensions. Together, our results provide further characterization of bacteria-MIL interactions and support the broader utility of the Ni(II) MIL as a cell-friendly capture reagent for sample preparation prior to cultural or molecular analyses.
Graphical abstract
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