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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.

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.

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.

Match-fixing is increasingly perceived by both national and European policy makers and independent observers as a major threat to the integrity of sports, and in particular football. A series of recent scandals in different European countries seems to corroborate the perception of football’s growing vulnerability to manipulations, suggesting that such vulnerability may be related to football’s popularity, the huge related financial interests and the rapid growth of online betting. Nonetheless, the empirical research on match-fixing in football has so far been very limited. Against this background, we present in this paper the results of survey amongst 595 referees belonging to the Royal Belgian Football Association about their attitudes towards the incidence, disclosure and combatting, and reporting of match-fixing, as well as their personal experiences with match-fixing. The main findings can be summarized as follows: (1) approximately 44% of the referees believes that at least one in ten Belgian football games is fixed; (2) 41% of the referees considers the likelihood of match-fixing in football being disclosed (very) low; (3) only 11% of the referees is aware of at least one protected reporting system for match-fixing; (4) 23.5% of the referees has already witnessed or suspected match-fixing in football; and (5) only 12% of the referees who witnessed or suspected match-fixing reported the only/last case of match-fixing they witnessed or suspected. Although our referee’s perceptions might not correspond to reality, our findings suggest the need to introduce adequate protected reporting systems, conduct awareness campaigns and intensify law enforcement agencies’ and sports bodies’ cooperation and data sharing.

Objective:We investigated the quality of life (QoL) of patients hospitalized with C. difficile infection (CDI).Design:Prospective survey study.Setting:US tertiary-care referral center, acute-care setting.Participants:Adults hospitalized with a diagnosis of CDI, defined as ≥3 episodes of unformed stool in 24 hours and a positive laboratory test for C. difficile.Methods:We surveyed patients from July 2019 to March 2020 using the disease-specific Cdiff32 questionnaire and the generic PROMIS GH survey. We compared differences in Cdiff32 scores among demographic and clinical subgroups (including CDI severity, CDI recurrence, and various comorbidities) using 2-sample t tests. We compared PROMIS GH scores to the general population T score of 50 using 1-sample t tests. We performed multivariable linear regression to identify predictors of Cdiff32 scores.Results:In total, 100 inpatients (mean age, 58.6 ±17.1 years; 53.0% male; 87.0% white) diagnosed with CDI completed QoL surveys. PROMIS GH physical health summary scores (T = 37.3; P < .001) and mental health summary scores (T = 43.4; P < .001) were significantly lower than those of the general population. In bivariate analysis, recurrent CDI, severe CDI, and number of stools were associated with lower Cdiff32 scores. In multivariable linear regression, recurrent CDI, severe CDI, and each additional stool in the previous 24 hours were associated with significantly decreased Cdiff32 scores.Conclusions:Patients hospitalized with CDI reported low scores on the Cdiff32 and PROMIS GH, demonstrating a negative impact of CDI on QoL in multiple health domains. The Cdiff32 questionnaire is particularly sensitive to QoL changes in patients with recurrent or severe disease.

INTRODUCTION:The use of proton-pump inhibitors (PPIs) has been associated with various adverse effects including increased risk of major adverse cardiovascular events, community acquired clostridium difficile infection, chronic kidney disease and dementia. Some studies over the past decade have suggested an association between PPIs use and ischemic stroke.METHODS:We pooled the data after comprehensive literature search from the PubMed, Embase, Cochrane Library and Scopus databases using ‘proton pump inhibitors’ AND ‘stroke’ as the keywords. RevMan was used for the entry and analysis of data. A random effects model was created given the significant heterogeneity of the included studies and a funnel plot was made to assess the publication bias. Our primary objective was to study whether all-comers patients on PPIs are at an increased risk of stroke. Sub-group analysis was also done to investigate the association between patients on dual anti-platelet therapy [DAPT] (aspirin and clopidogrel) with or without PPIs and stroke.RESULTS:After searching 774 titles, 25 titles were selected to be included in the systematic review and 15 articles for the meta-analysis. Our pooled analysis of 155,406 patients (46,652 patients on PPI and 101,892 patients without PPI found a positive association between the use of PPI and stroke (odds ratio = 1.28, 95% confidence interval = 1.12, 1.48, P = 0.001) [Figure 1]. Given the significant heterogeneity of the studies (I2= 60%) a sub-group analysis was done which also suggested an increased risk of stroke associated with PPI use among patients on dual antiplatelet therapy (OR: 1.43, 95% CI: 1.26, 1.66, p< 0.001, I2= 11%) [Figure 2]. Analysis of the included randomized controlled trials revealed an OR: 1.47, 95% CI: 0.66, 3.25 but the results were not statistically significant (p< 0.81) [Figure 3].CONCLUSION:In a pooled analysis of over 155,000 patients we found a positive association between the use of PPIs and stroke. Our results are limited by significant heterogeneity and retrospective study design of the observational studies. Rigorous clinical trials are needed to establish the safety of PPIs in relation to stroke, especially among patients on DAPT. Until definitive data emerges, patients on DAPT are probably best served by being off PPIs or being on alternative acid suppression regimen, unless there is a compelling indication for PPI use.

To identify risk factors for asymptomatic Clostridioides difficile colonization among hospitalized adults utilizing a meta-analysis, which may enable early identification of colonized patients at risk of spreading C. difficile. Meta-analysis and systematic review. We systematically searched MEDLINE, Scopus, Web of Science, and EMBASE from January 1, 1975, to February 15, 2020, for articles related to C. difficile colonization among hospitalized adults. Studies with multivariable analyses evaluating risk factors for asymptomatic colonization were eligible. Among 5,506 studies identified in the search, 19 studies met the inclusion criteria. Included studies reported 20,334 adult patients of whom 1,588 were asymptomatically colonized with C. difficile. Factors associated with an increased risk of colonization were hospitalization in the previous 6 months (OR, 2.18; 95% CI, 1.86-2.56; P < .001), use of gastric acid suppression therapy within the previous 8 weeks (OR, 1.42; 95% CI, 1.17-1.73; P < .001), tube feeding (OR, 2.02; 95% CI, 1.06-3.85; P = .03), and corticosteroid use in the previous 8 weeks (OR, 1.58; 95% CI, 1.14-2.17; P = .006). Receipt of antibiotics in the previous 3 months (OR, 1.37; 95% CI, 0.94-2.01; P = .10) was not associated with statistically significant effects on risk of colonization. C. difficile colonization was significantly associated with previous hospitalization, gastric acid suppression, tube feeding, and corticosteroid use. Recognition of these risk factors may assist in identifying asymptomatic carriers of C. difficile and taking appropriate measures to reduce transmission.

We consider the challenge of operating a reliable bit that can be rapidly erased. We find that both erasing and reliability times are non-monotonic in the underlying friction, leading to a trade-off between erasing speed and bit reliability. Fast erasure is possible at the expense of low reliability at moderate friction, and high reliability comes at the expense of slow erasure in the underdamped and overdamped limits. Within a given class of bit parameters and control strategies, we define ‘optimal’ designs of bits that meet the desired reliability and erasing time requirements with the lowest operational work cost. We find that optimal designs always saturate the bound on the erasing time requirement, but can exceed the required reliability time if critically damped. The non-trivial geometry of the reliability and erasing time scales allows us to exclude large regions of parameter space as suboptimal. We find that optimal designs are either critically damped or close to critical damping under the erasing procedure.