Heterogeneous integration is leading to unprecedented miniaturization of solder joints, often with thousands of joints within a single package. The thermomechanical behavior of such SAC solder joints ...is critically important to assembly performance and reliability, but can be difficult to predict due to the significant joint-to-joint variability caused by the stochastic variability of the arrangement of a few highly-anisotropic grains in each joint. This study relies on grain-scale testing to characterize the mechanical behavior of such oligocrystalline solder joints, while a grain-scale modeling approach has been developed to assess the effect of microstructure that lacks statistical homogeneity. The contribution of the grain boundaries is modeled with isotropic cohesive elements and identified by an inverse iterative method that extracts material properties by comparing simulation with experimental measurements. The properties are extracted from the results of one test and validated by verifying reasonable agreement with test results from a different specimen. Equivalent creep strain heterogeneity within the same specimen and between different specimens are compared to assess typical variability due to the variability of microstructure.
Objective To assess the effects of vitamin D supplementation during pregnancy on obstetric outcomes and birth variables. Design Systematic review and meta-analysis of randomized controlled trials ...(RCTs). Setting Not applicable. Patient(s) Pregnant women and neonates. Intervention(s) PubMed and 5 other research databases were searched through March 2014 for RCTs evaluating vitamin D supplementation ± calcium/vitamins/ferrous sulfate vs. a control (placebo or active) during pregnancy. Main Outcome Measure(s) Measures were: circulating 25-hydroxyvitamin D 25(OH)D levels, preeclampsia, gestational diabetes mellitus (GDM), small for gestational age (SGA), low birth weight, preterm birth, birth weight, birth length, cesarean section. Mantel-Haenszel fixed-effects models were used, owing to expected scarcity of outcomes. Effects were reported as relative risks and their 95% confidence intervals (CIs). Result(s) Thirteen RCTs (n = 2,299) were selected. Circulating 25(OH)D levels were significantly higher at term, compared with the control group (mean difference: 66.5 nmol/L, 95% CI 66.2–66.7). Birth weight and birth length were significantly greater for neonates in the vitamin D group; mean difference: 107.6 g (95% CI 59.9–155.3 g) and 0.3 cm (95% CI 0.10–0.41 cm), respectively. Incidence of preeclampsia, GDM, SGA, low birth weight, preterm birth, and cesarean section were not influenced by vitamin D supplementation. Across RCTs, the doses and types of vitamin D supplements, gestational age at first administration, and outcomes were heterogeneous. Conclusion(s) Vitamin D supplementation during pregnancy was associated with increased circulating 25(OH)D levels, birth weight, and birth length, and was not associated with other maternal and neonatal outcomes. Larger, better-designed RCTs evaluating clinically relevant outcomes are necessary to reach a definitive conclusion.
Systems of differential equations with polynomial right-hand sides are very common in applications. In particular, when restricted to the positive orthant, they appear naturally (according to the law ...of
mass-action kinetics
) in ecology, population dynamics, as models of biochemical interaction networks, and models of the spread of infectious diseases. Their mathematical analysis is very challenging in general; in particular, it is very difficult to answer questions about the long-term dynamics of the variables (species) in the model, such as questions about persistence and extinction. Even if we restrict our attention to mass-action systems, these questions still remain challenging. On the other hand, if a polynomial dynamical system has a
weakly reversible single linkage class
(
W
R
1
)
realization
, then its long-term dynamics is known to be remarkably robust: all the variables are persistent (i.e., no species goes extinct), irrespective of the values of the parameters in the model. Here we describe an algorithm for finding
W
R
1
realizations of polynomial dynamical systems, whenever such realizations exist.
Complex-balanced mass-action systems are some of the most important types of mathematical models of reaction networks, due to their widespread use in applications, as well as their remarkable ...stability properties. We study the set of positive parameter values (i.e., reaction rate constants) of a reaction network
G
that, according to mass-action kinetics, generate dynamical systems that can be realized as complex-balanced systems, possibly by using a different graph
G
′
. This set of parameter values is called the
disguised toric locus
of
G
. The
R
-
disguised toric locus
of
G
is defined analogously, except that the parameter values are allowed to take on any real values. We prove that the disguised toric locus of
G
is path-connected, and the
R
-disguised toric locus of
G
is also path-connected. We also show that the closure of the disguised toric locus of a reaction network contains the union of the disguised toric loci of all its subnetworks.
The dynamics exhibited by reaction networks is often a manifestation of their steady states. We show that there exists endotactic and strongly endotactic dynamical systems that are not weakly ...reversible and possess a family of infinitely many positive steady states. In addition, we prove for some of these systems that there exist no weakly reversible mass-action systems that are dynamically equivalent to mass-action systems generated by these networks. This extends a result by Boros, Craciun and Yu
1
, who proved the existence of weakly reversible dynamical systems with infinitely many steady states.
Enzymes are central to both metabolism and information processing in cells. In both cases, an enzyme’s ability to accelerate a reaction without being consumed in the reaction is crucial. ...Nevertheless, enzymes are transiently sequestered when they bind to their substrates; this sequestration limits activity and potentially compromises information processing and signal transduction. In this article, we analyse the mechanism of enzyme–substrate catalysis from the perspective of minimizing the load on the enzymes through sequestration, while maintaining at least a minimum reaction flux. In particular, we ask: which binding free energies of the enzyme–substrate and enzyme–product reaction intermediates minimize the fraction of enzymes sequestered in complexes, while sustaining a certain minimal flux? Under reasonable biophysical assumptions, we find that the optimal design will saturate the bound on the minimal flux and reflects a basic trade-off in catalytic operation. If both binding free energies are too high, there is low sequestration, but the effective progress of the reaction is hampered. If both binding free energies are too low, there is high sequestration, and the reaction flux may also be suppressed in extreme cases. The optimal binding free energies are therefore neither too high nor too low, but in fact moderate. Moreover, the optimal difference in substrate and product binding free energies, which contributes to the thermodynamic driving force of the reaction, is in general strongly constrained by the intrinsic free-energy difference between products and reactants. Both the strategies of using a negative binding free-energy difference to drive the catalyst-bound reaction forward and of using a positive binding free-energy difference to enhance detachment of the product are limited in their efficacy.
Antibiotic exposure is the most important risk factor for Clostridium difficile infection (CDI). Most evaluations of antimicrobial risk factors have been conducted in healthcare settings. The ...objective of this meta-analysis was to evaluate the association between antibiotic exposure and community-associated CDI (CA-CDI) (i.e. symptom onset in the community with no healthcare facility admission within 12 weeks) and to determine the classes of antibiotics posing the greatest risk.
We searched four electronic databases for subject headings and text words related to CA-CDI and antibiotics. Studies that investigated the risk of CA-CDI associated with antibiotic usage were considered eligible. Data from the identified studies were combined using a random-effects model and ORs were calculated.
Of 910 citations identified, eight studies (n = 30 184 patients) met our inclusion criteria. Antibiotic exposure was associated with an increased risk of CA-CDI (OR 6.91, 95% CI 4.17-11.44, I(2) = 95%). The risk was greatest with clindamycin (OR 20.43, 95% CI 8.50-49.09) followed by fluoroquinolones (OR 5.65, 95% CI 4.38-7.28), cephalosporins (OR 4.47, 95% CI 1.60-12.50), penicillins (OR 3.25, 95% CI 1.89-5.57), macrolides (OR 2.55, 95% CI 1.91-3.39) and sulphonamides/trimethoprim (OR 1.84, 95% CI 1.48-2.29). Tetracyclines were not associated with an increased CDI risk (OR 0.91, 95% CI 0.57-1.45).
Antibiotic exposure was an important risk factor for CA-CDI, but the risk was different amongst different antibiotic classes. The risk was greatest with clindamycin followed by fluoroquinolones and cephalosporins, whereas tetracyclines were not associated with an increased risk.
OBJECTIVES:Extracorporeal cardiopulmonary resuscitation has shown survival benefit in select patients with refractory cardiac arrest but there is insufficient data on the frequency of different types ...of brain injury. We aimed to systematically review the prevalence, predictors of and survival from neurologic complications in patients who have undergone extracorporeal cardiopulmonary resuscitation.
DATA SOURCES:MEDLINE (PubMed) and six other databases (EMBASE, Cochrane Library, CINAHL Plus, Web of Science, and Scopus) from inception to August 2019.
STUDY SELECTION:Randomized controlled trials and observational studies in patients greater than 18 years old.
DATA EXTRACTION:Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for randomized controlled trials, the Newcastle-Ottawa Scale for cohort and case-control studies, and the Murad tool for case series. Random-effects meta-analyses were used to pool data.
DATA SYNTHESIS:The 78 studies included in our analysis encompassed 50,049 patients, of which 6,261 (12.5%) received extracorporeal cardiopulmonary resuscitation. Among extracorporeal cardiopulmonary resuscitation patients, the median age was 56 years (interquartile range, 52–59 yr), 3,933 were male (63%), 3,019 had out-of-hospital cardiac arrest (48%), and 2,289 had initial shockable heart rhythm (37%). The most common etiology of cardiac arrest was acute coronary syndrome (n = 1,657, 50% of reported). The median extracorporeal cardiopulmonary resuscitation duration was 3.2 days (interquartile range, 2.1–4.9 d). Overall, 27% (95% CI, 0.17–0.39%) had at least one neurologic complication, 23% (95% CI, 0.14–0.32%) hypoxic-ischemic brain injury, 6% (95% CI, 0.02–0.11%) ischemic stroke, 6% (95% CI, 0.01–0.16%) seizures, and 4% (95% CI, 0.01–0.1%) intracerebral hemorrhage. Seventeen percent (95% CI, 0.12–0.23%) developed brain death. The overall survival rate after extracorporeal cardiopulmonary resuscitation was 29% (95% CI, 0.26–0.33%) and good neurologic outcome was achieved in 24% (95% CI, 0.21–0.28%).
CONCLUSIONS:One in four patients developed acute brain injury after extracorporeal cardiopulmonary resuscitation and the most common type was hypoxic-ischemic brain injury. One in four extracorporeal cardiopulmonary resuscitation patients achieved good neurologic outcome. Further research on assessing predictors of extracorporeal cardiopulmonary resuscitation-associated brain injury is necessary.
An estimated 20-30% of patients with primary Clostridium difficile infection (CDI) develop recurrent CDI (rCDI) within 2 weeks of completion of therapy. While the actual mechanism of recurrence ...remains unknown, a variety of risk factors have been suggested and studied. The aim of this systematic review and meta-analysis was to evaluate current evidence on the risk factors for rCDI.
We searched MEDLINE and 5 other databases for subject headings and text related to rCDI. All studies investigating risk factors of rCDI in a multivariate model were eligible. Information on study design, patient population, and assessed risk factors were collected. Data were combined using a random-effects model and pooled relative risk ratios (RRs) were calculated.
A total of 33 studies (n=18,530) met the inclusion criteria. The most frequent independent risk factors associated with rCDI were age≥65 years (risk ratio RR, 1.63; 95% confidence interval CI, 1.24-2.14; P=.0005), additional antibiotics during follow-up (RR, 1.76; 95% CI, 1.52-2.05; P<.00001), use of proton-pump inhibitors (PPIs) (RR, 1.58; 95% CI, 1.13-2.21; P=.008), and renal insufficiency (RR, 1.59; 95% CI, 1.14-2.23; P=.007). The risk was also greater in patients previously on fluoroquinolones (RR, 1.42; 95% CI, 1.28-1.57; P<.00001).
Multiple risk factors are associated with the development of rCDI. Identification of modifiable risk factors and judicious use of antibiotics and PPI can play an important role in the prevention of rCDI.
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