Abstract
Background
The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to ...evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock.
Methods
We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).
Results
Five studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio OR = 0.45; 95% CI, 0.34 to 0.61;
P
< 0.00001;
χ
2
= 3.74;
I
2
= 0%). Secondary outcomes demonstrated that the time to achieved target MAP of the early group was shorter than that of the late group (mean difference = − 1.39; 95% CI, − 1.81 to − 0.96;
P
< 0.00001;
χ
2
= 1.03;
I
2
= 0%). The volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = − 0.50; 95% CI, − 0.68 to − 0.32;
P
< 0.00001;
χ
2
= 33.76;
I
2
= 94%). There was no statistically significant difference in the ICU length of stay between the two groups (mean difference = − 0.11; 95% CI, − 1.27 to 1.05;
P
= 0.86;
χ
2
= 0.85;
I
2
= 0%).
Conclusions
Early initiation of norepinephrine in patients with septic shock was associated with decreased short-term mortality, shorter time to achieved target MAP, and less volume of intravenous fluids within 6 h. There was no significant difference in ICU length of stay between early and late groups. Further large-scale RCTs are still required to confirm these results.
As protective coatings or transition layers, pure Zn coatings were deposited on AZ31b substrate by cold spraying. Processing parameters and mechanical properties were evaluated by scanning electron ...microscopy, microhardness, and adhesion strength test. The corrosion properties and protective mechanism of the coatings were investigated by potentiodynamic polarization testing and electrochemical impedance spectroscopy (EIS) measurements. The results indicated that the dense, low-porosity Zn coatings were successfully deposited on AZ31b magnesium with good mechanical properties. The cold sprayed pure Zn coatings exhibited higher corrosion resistance than that of the substrate, and the open circuit potential and corrosion potential of cold sprayed Zn coatings were close to those of bulk Zn. A change involving the diffusion of reactants and production of corrosion products in EIS equivalent circuit was observed during immersion for 10 d. The corrosion behavior was related to the unique morphology of cold sprayed Zn coating, and a “corrosion tunnel” was observed in the cross-section of the coatings after immersion, corresponding to the evolutionary mechanism of the particle–particle interface microstructure.
•The pure Zn coatings can be sprayed on magnesium with good mechanical properties.•The corrosion resistance of cold sprayed Zn coating is much higher than that of magnesium substrate.•The EIS pattern of cold sprayed Zn coatings can change due to diffusion.•The corrosion mechanisms of pure Zn coatings are related to the effect of impact-induced melting.
Using nanotechnology for improving the immunotherapy efficiency represents a major research interest in recent years. However, there are paradoxes and obstacles in using a single nanoparticle to ...fulfill all the requirements in the complicated immune activation processes. Herein, a supramolecular assembled programmable immune activation nanomedicine (PIAN) for sequentially finishing multiple steps after intravenous injection and eliciting robust antitumor immunity in situ is reported. The programmable nanomedicine is constructed by supramolecular assembly via host–guest interactions between poly‐(N‐2‐hydroxyethyl)‐aspartamide‐Pt(IV)/β‐cyclodextrin (PPCD), CpG/polyamidoamine‐thioketal‐adamantane (CpG/PAMAM‐TK‐Ad), and methoxy poly(ethylene glycol)‐thioketal‐adamantane (mPEG‐TK‐Ad). After intravenous injection and accumulation at the tumor site, the high level of reactive oxygen species in the tumor microenvironment promotes PIAN dissociation and the release of PPCD (mediating tumor cell killing and antigen release) and CpG/PAMAM (mediating antigen capturing and transferring to the tumor‐draining lymph nodes). This results in antigen‐presenting cell activation, antigen presentation, and robust antitumor immune responses. In combination with anti‐PD‐L1 antibody, the PIAN cures 40% of mice in a colorectal cancer model. This PIAN provides a new framework for designing programmable nanomedicine as in situ cancer vaccine for cancer immunotherapy.
A novel strategy to use programmable nanomedicine for cancer immunotherapy is presented. A programmable immune activation nanomedicine (PIAN) is constructed through supramolecular modular assembly, which automatically transforms after intravenous injection and finishes sequential multiple steps for eliciting robust immune responses in vivo.
The effect of alternative spontaneous breathing trial (SBT) techniques on extubation success and other clinically important outcomes is uncertain. A systematic review and meta-analysis was performed ...to clarify the preferable SBT (T-piece or pressure support ventilation PSV).
We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) from inception to the 31st of July 2019. We included RCTs involving adult patients (> 18 years) who underwent at least two different SBT methods. All authors reported our primary outcome of successful extubation rate and clearly compared PS versus T-piece with clinically relevant secondary outcomes (rate of reintubation, ICU and hospital length of stay, and ICU and hospital mortality). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).
Ten RCTs including 3165 patients were included. The results of this meta-analysis showed that there was no significant difference in the successful extubation rate between the T-piece group and PS group (odds ratio OR = 0.91; 95% CI, 0.78-1.07; P = 0.27; I
= 79%). In addition, compared with the PS group, the T-piece group showed no significant difference in the rate of reintubation (odds ratio OR = 0.99; 95% CI, 0.78-1.26; P = 0.95; I
= 5%), ICU mortality (odds ratio OR = 1.22; 95% CI, 0.83-1.80; P = 0.30; I
= 0%), hospital mortality (odds ratio OR = 1.36; 95% CI, 0.99-1.87; P = 0.06; I
= 19%), ICU length of stay (mean difference = - 0.10; 95% CI, - 0.59 to 0.39; P = 0.69; I
= 13%), and hospital length of stay (mean difference = - 0.82;95% CI, - 2.2 to 0.55; P = 0.24; I
= 0%).
T-piece and PSV as SBTs are considered to have comparable predictive power of successful extubation in critically ill patients. The analysis of secondary outcomes also shows no significant difference in the rate of reintubation, ICU and hospital length of stay, and ICU and hospital mortality between the two groups. Further randomized controlled studies of SBTs are still required.
Organic field‐effect transistors and near‐infrared (NIR) organic phototransistors (OPTs) have attracted world's attention in many fields in the past decades. In general, the sensitivity, ...distinguishing the signal from noise, is the key parameter to evaluate the performance of NIR OPTs, which is decided by responsivity and dark current. 2D single crystal films of organic semiconductors (2DCOS) are promising functional materials due to their long‐range order in spite of only few molecular layers. Herein, for the first time, air‐stable 2DCOS of n‐type organic semiconductors (a furan‐thiophene quinoidal compound, TFT‐CN) with strong absorbance around 830 nm, by the facile drop‐casting method on the surface of water are successfully prepared. Almost millimeter‐sized TFT‐CN 2DCOS are obtained and their thickness is below 5 nm. A competitive field‐effect electron mobility (1.36 cm2 V−1 s−1) and high on/off ratio (up to 108) are obtained in air. Impressively, the ultrasensitive NIR phototransistors operating at the off‐state exhibit a very low dark current of ≈0.3 pA and an ultrahigh detectivity (D*) exceeding 6 × 1014 Jones because the devices can operate in full depletion at the off‐state, superior to the majority of the reported organic‐based NIR phototransistors.
High‐performance organic field‐effect transistors and near‐infrared phototransistors with n‐type two‐dimensional organic single crystals are successfully fabricated. A field‐effect electron mobility (1.36 cm2 V−1 s−1) and high on/off ratio (108) are obtained. Impressively, the ultrasensitive near‐infrared phototransistors exhibit an ultrahigh detectivity exceeding 6 × 1014 Jones, superior to the majority of the reported organic‐based near‐infrared phototransistors.
Mortality and other clinical outcomes between culture-negative and culture-positive septic patients have been documented inconsistently and are very controversial. A systematic review and ...meta-analysis was performed to compare the clinical outcomes of culture-negative and culture-positive sepsis or septic shock.
We searched the PubMed, Cochrane and Embase databases for studies from inception to the 1st of January 2021. We included studies involving patients with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality and clearly compared culture-negative versus culture-positive patients with clinically relevant secondary outcomes (ICU length of stay, hospital length of stay, mechanical ventilation requirements, mechanical ventilation duration and renal replacement requirements). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).
Seven studies including 22,655 patients were included. The primary outcome of this meta-analysis showed that there was no statistically significant difference in the all-cause mortality between two groups (OR = 0.95; 95% CI, 0.88 to 1.01; P = 0.12; Chi-
= 30.71; I
= 80%). Secondary outcomes demonstrated that there was no statistically significant difference in the ICU length of stay (MD = - 0.19;95% CI, - 0.42 to 0.04; P = 0.10;Chi-
= 5.73; I
= 48%), mechanical ventilation requirements (OR = 1.02; 95% CI, 0.94 to 1.11; P = 0.61; Chi
= 6.32; I
= 53%) and renal replacement requirements (OR = 0.82; 95% CI, 0.67 to 1.01; P = 0.06; Chi-
= 1.21; I
= 0%) between two groups. The hospital length of stay of culture-positive group was longer than that of the culture-negative group (MD = - 3.48;95% CI, - 4.34 to - 2.63; P < 0.00001;Chi-
= 1.03; I
= 0%). The mechanical ventilation duration of culture-positive group was longer than that of the culture-negative group (MD = - 0.64;95% CI, - 0.88 to - 0.4; P < 0.00001;Chi-
= 4.86; I
= 38%).
Culture positivity or negativity was not associated with mortality of sepsis or septic shock patients. Furthermore, culture-positive septic patients had similar ICU length of stay, mechanical ventilation requirements and renal replacement requirements as those culture-negative patients. The hospital length of stay and mechanical ventilation duration of culture-positive septic patients were both longer than that of the culture-negative patients. Further large-scale studies are still required to confirm these results.
This letter considers a single hop wireless multicast network. We first introduce a new two-level queuing system consisting of a main queue and a virtual queue, where each packet in the virtual queue ...is associated with a user index set. Then, we propose a network coding based packet scheduling method to maximize the system input rate under the queue stability constraint. Our analytical and simulation results demonstrate the effectiveness of the proposed solution.
Semiconducting polymers with high mobility and mechanical robust properties are strongly dependent on their molecular weight. However, the relationship between molecular weights and solution chain ...entanglements, film microstructures, charge carrier mobility, and mechanical properties for donor–acceptor conjugated polymers remains less understood. Herein, P(NDI2OD-T2) with a weight-average molecular weight (M w) from 34.0 to 280 kDa was investigated as a model system. The polymer chain exhibited three regions in chloroform solutions: fewer entanglements (34.0–77.7 kDa), enhanced entanglements (170 kDa), and severe entanglements (280 kDa). This chain solution behavior resulted in three distinct film microstructures: (1) 34.0–77.7 kDa, liquid-crystalline-like morphologies with highly ordered chain arrangements and large crystallite lengths (l c) yet relatively low tie-chain densities that increased with M w; (2) 170 kDa, small fibril morphology with less ordered chain arrangements and a decreased l c of only 5.6 nm yet a high tie-chain density; and (3) 280 kDa, a seemingly amorphous film with vast well-connected local aggregates embedded in an entangled network. The structural change in films significantly affected the electrical and mechanical performances. The electron mobility increased continuously with M w, correlating well with the tie-chain density. By contrast, the crack-onset strain was less than 3% at 34.0–77.7 kDa and then jumped to 36.4 ± 0.9 and 60.4 ± 2.1% for 170 and 280 kDa, showing a close correlation with the solution entanglement density, which could be inherited into films. This study contributes to structural development of rigid chains with M w and demonstrates that the microstructure containing vast well-connected local aggregates and adequate entanglements is promising toward mechanically robust semiconducting films.
A queue stability analysis in a wireless multicast network with packet erasure channels is studied in this letter. In particular, a new queuing model consisting of several sub-queues is introduced, ...where each packet in a sub-queue is associated with an index set indicating its intended users. Our objective is to maximize the input rate under the queue stability constraints. We formulate it as a linear programming problem and propose a network coding-based packet scheduling scheme that finds the optimal solution. Finally, the simulation results corroborate our method.
Pathological conditions may result in certain genes having expression variance that differs markedly from that of the control. Finding such genes from gene expression data can provide invaluable ...candidates for therapeutic intervention. Under the dominant paradigm for modeling RNA-Seq gene counts using the negative binomial model, tests of differential variability are challenging to develop, owing to dependence of the variance on the mean.
Here, we describe clrDV, a statistical method for detecting genes that show differential variability between two populations. We present the skew-normal distribution for modeling gene-wise null distribution of centered log-ratio transformation of compositional RNA-seq data.
Simulation results show that clrDV has false discovery rate and probability of Type II error that are on par with or superior to existing methodologies. In addition, its run time is faster than its closest competitors, and remains relatively constant for increasing sample size per group. Analysis of a large neurodegenerative disease RNA-Seq dataset using clrDV successfully recovers multiple gene candidates that have been reported to be associated with Alzheimer's disease.
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