Time-dependent Bias Research Articles

The disruption index is biased by citation inflation

Abstract A recent analysis of scientific publication and patent citation networks by Park et al. (Nature, 2023) suggests that publications and patents are becoming less disruptive over time. Here we show that the reported decrease in disruptiveness is an artifact of systematic shifts in the structure of citation networks unrelated to innovation system capacity. Instead, the decline is attributable to ‘citation inflation’, an unavoidable characteristic of real citation networks that manifests as a systematic time-dependent bias and renders cross-temporal analysis challenging. One driver of citation inflation is the ever-increasing lengths of reference lists over time, which in turn increases the density of links in citation networks, and causes the disruption index to converge to 0. The impact of this systematic bias further stymies efforts to correlate disruption to other measures that are also time-dependent, such as team size and citation counts. In order to demonstrate this fundamental measurement problem, we present three complementary lines of critique (deductive, empirical and computational modeling), and also make available an ensemble of synthetic citation networks that can be used to test alternative citation-based indices for systematic bias. Peer Review https://www.webofscience.com/api/gateway/wos/peer-review/10.1162/qss_a_00333

Tailored accelerometer calibration by POD for thermospheric density retrieval with GRACE and GRACE-FO

The density of the upper atmosphere can be determined by orbit and accelerometer data from low Earth orbit satellites as insitu measurements along the orbit. One main challenge therein is the estimation of physical accelerometer calibration parameters, meaning that these parameters should not absorb other effects and model deficiencies in the Precise Orbit Determination (POD) process. The accelerometers of all geodetic satellites like GRACE and GRACE-FO are affected by time dependent bias and scale factors. Therefore a calibration of the data is indispensable.A dynamic POD based physical accelerometer calibration is developed for the complete GRACE and GRACE-FO missions. We investigate different parametrization strategies and utilize different observation data, as the accurate inter-satellite ranging additionally to GPS orbit data. For the estimation parameters we distinguish between offset and scale, furthermore, cross-track and radial directions are significantly less sensitive than along-track and require a different evaluation. For the offset, constant and time dependent parameters are investigated. Furthermore, a continuous offset calibration over arc boundaries is implemented and tested. The sensitivity of the scale factor is lower, although, in contrast to the offset, it increases with higher total accelerations. This means that it needs to be estimated over longer time periods. We investigate periods between three hours and one month as well as results from Gravity Field Recovery (GFR). Monthly scale factors give valuable results, at least for x-axis and when the Solar activity is not very low. Nevertheless, we also estimate weighted constant scale factors from the monthly results and use these in a subsequent POD, giving more realistic offset results for most periods and cross-track and radial directions.From the used background models in the POD, Earth’s gravitational model has a noticeable influence on the estimated calibration parameters, especially the scale factors. We utilized several different models. Results with monthly ITSG solutions are distinctly better than the ones with the time dependent GOCO06s model.We show that the validation with usual metrics, like post-fit POD residuals, is not able to reflect the quality of the different estimated calibration parameters. For a quantitative validation we introduce an approach based on the modeled non-gravitational accelerations. Therefore, the uncertainty of the models is evaluated first. The influence of main error sources in the models is assessed and propagated to the results.We compare our scale parameters to available references and the complete calibration to TU Delft’s latest results. Finally we show the effect of different calibration options on the retrieved density.The estimated calibration parameters and non-gravitational accelerations for the whole GRACE and GRACE-FO missions are available on our data server www.zarm.uni-bremen.de/zarm_daten.

Simulation of the continuous time random walk using subordination schemes.

The continuous time random walk model has been widely applied in various fields, including physics, biology, chemistry, finance, social phenomena, etc. In this work, we present an algorithm that utilizes a subordinate formula to generate data of the continuous time random walk in the long time limit. The algorithm has been validated using commonly employed observables, such as typical fluctuations of the positional distribution, rare fluctuations, the mean and the variance of the position, and breakthrough curves with time-dependent bias, demonstrating a perfect match.

The attributable mortality, length of stay, and health care costs of methicillin-resistant Staphylococcus aureus infections in Singapore

ObjectivesWe used a multi-state model, which mitigates time-dependent bias, to estimate the mortality, length of stay (LOS), and costs of methicillin-resistant Staphylococcus aureus (MRSA) infections in Singapore. MethodsWe conducted a retrospective study in a hospital in Singapore from 2018 to 2022. Patients with MRSA infections were matched 1:1:3 to patients with MRSA colonization and patients without MRSA by age, gender, specialty, and intensive care admission, respectively. A multi-state model was used to derive excess LOS and mortality hazard ratios. The attributable cost of infections was estimated in 2022 Singapore dollars (SGDs) from the health care perspective. ResultsWe matched 536 patients with MRSA infections to 536 patients with MRSA colonization, and to 1608 patients without MRSA. The excess LOS due to MRSA infection was 2.11 (95% confidence interval [CI] 2.05-2.17) days compared with MRSA colonization and 3.75 (95% CI 3.69-3.80) days compared with no MRSA, which translated to an excess cost of SGD $1825 and SGD $3238, respectively. Of the different MRSA infection types, pneumonia had the highest mortality risk (hazard ratio 4.13; 95% CI 2.28-7.50) compared with patients without MRSA. ConclusionsMRSA infections increased hospital LOS and health care costs in Singapore. Our estimates can inform future economic analyses of management strategies against MRSA.

Prevalence of hepatitis B virus infection among pregnant women in Africa: A systematic review and meta-analysis.

Africa exhibits a considerably high prevalence of the hepatitis B virus among pregnant women. Furthermore, there is a discernible lack of a well-established surveillance system to adequately monitor and comprehend the epidemiology of the hepatitis B virus, particularly among pregnant women. The eradication efforts of the virus in Africa have been impeded by the significant disease burden in the region, and there is a lack of evidence regarding the pooled prevalence of the hepatitis B virus in Africa. Consequently, this systematic review and meta-analysis aims to determine the prevalence of hepatitis B virus infection among pregnant women in Africa. We conducted a systematic literature search using reputable databases such as PubMed, Advanced Google Scholar, Scopus, and the Cochrane Library. The search spanned from July 2013 to July 2023 and included all relevant articles published within this period. To identify potentially eligible articles, we conducted a comprehensive manual review of the reference lists of the identified studies. Our review encompassed articles from the African Journal Online. The analysis focused on observational studies published in peer-reviewed journals that reported the prevalence of hepatitis B surface antigen-positive testing among pregnant women. We utilized the Newcastle-Ottawa critical appraisal checklist to assess the methodological quality of each paper. Finally, a meta-analysis was conducted using a random-effects model. Out of the 774 studies identified, 31 studies involving 33,967 pregnant women were selected for the meta-analysis. According to the random-effects model, the combined prevalence of hepatitis B virus among pregnant women was 6.77% [95% CI: 5.72, 7.83]. The I2 statistic was calculated to be 95.57% (p = 0.00), indicating significant heterogeneity among the studies. The high I2 value of 95.57% suggests a substantial degree of heterogeneity. A subgroup meta-analysis revealed that factors such as time-dependent bias, sample size dependence, or individual variation among study participants contributed to this heterogeneity (p-difference < 0.05). According to the findings of this study, the pooled prevalence of hepatitis B infection among pregnant women in Africa was found to be intermediate-high. It is recommended that policymakers implement hepatitis B virus immunization programs targeting pregnant women and their new-born babies at higher risk of exposure.

Vaping Transitions and Incident Depressive Symptoms among Young Adults: A Marginal Structural Model Analysis.

The extent to which vaping influences depression is unclear, but could be estimated through application of novel epidemiologic methods. Among a prospective cohort of young adults from California who screened negative for depression, we estimated repeated measures marginal structural models to examine the association of four vaping transitions from time T to T+1 (persistent use, discontinuation, initiation, persistent nonuse) with risk of clinically significant depressive symptoms at T+1, simultaneously across three ~1.5 year time-intervals between 2017-2021. Stabilized inverse probability of treatment and censoring weights adjusted for time-dependent confounders and selection bias. Among n=3,496 observations (1,806 participants, mean pooled baseline age=19.5), 8.1% reported persistent vaping from T to T+1, 6.2% reported discontinuation (i.e., use at T and no use at T+1), 6.5% initiated e-cigarettes (i.e., no use at T and use at T+1), and 79.2% reported persistent nonuse at both time-points. Compared to persistent vaping at two waves, persistent nonuse (RR=0.76, 95%CI:0.62-0.93) and discontinuation (RR=0.71, 95%CI:0.52-0.96) were associated with lower risk of depression. Associations were robust to sensitivity analyses, including restricting to tobacco naïve participants and varying temporal assumptions to reduce potential for reverse causation. Young adults who consistently avoid or discontinue vaping may be protected from depressive symptom occurrence.

Parent decisional regret regarding neonatal circumcision in an American outpatient pediatric urology clinic

Requests for circumcision revision are common in our American pediatric urology clinic. As parents are the surrogate decision maker for their child, there are several influences that can impact a parent's decision for or against circumcision. We sought to assess parents' regret regarding their child's circumcision status and to correlate regret to factors that might have affected the original decision. From March 2023 to January 2024, we surveyed parents who brought their male child to our office for any reason, independent of circumcision status. The questionnaire was two-fold: a validated Decisional Regret Scale (DRS) (0-100 where higher scores=higher regret) and our questions regarding their decision-making process and outcome. Regret scores served as a function of each of the independent decision making and outcome variables. Overall, decisional regret scores from both uncircumcised and circumcised parent groups were positively skewed with a median 0, mean 22, and ranged from 0 to 75. For those circumcised (n=91), the median regret score was 0 (IQR 0-25). For those uncircumcised (n=28), median regret score was 0 (IQR 0-24). Overall, 55% of both groups reported no regret (DRS=0), 24% had low-mild regret (DRS 5-25), and 21% yielded moderate-strong regret (DRS 30-100). Parents who felt they made an informed decision or were counseled by any physician had lower regret scores. Parents who presented for issues related to their child's uncircumcised or circumcised penis (DRS score 37.5 and 25 respectively) had higher regret scores. We found that a large portion of parents expressed no regret regarding their decision to have or not have their child circumcised (55%). There also was no difference in median regret scores between parent groups. However, a significant portion of parents did express moderate-strong regret (21%) and several influential factors were correlated with regret scores. These factors included informed decision making, physician counseling, appearance satisfaction, and problems related to their child's circumcised or uncircumcised penis. These factors are supported by other literature using the DRS and population studies. The limitations of our study included the limited recruitment of participants and potential time dependent bias of responses. One in five parents of both circumcised and uncircumcised boys expressed moderate to strong regret regarding their decision about neonatal circumcision in our pediatric urology clinic. Our data suggests that ensuring parents have sufficient counseling prior to a decision regarding neonatal circumcision is important.

Tuning the Josephson diode response with an ac current

Josephson diodes are superconducting elements that show an asymmetry in the critical current depending on the direction of the current. Here, we theoretically explore how an alternating current bias can tune the response of such a diode. We show that for slow driving there is always a regime where the system can only carry zero-voltage dc current in one direction, thus effectively behaving as an ideal Josephson diode. Under fast driving, the diode efficiency is also tunable, although the ideal regime cannot be reached in this case. We also investigate the residual dissipation due to the time-dependent current bias and show that it remains small. All our conclusions are solely based on the critical current asymmetry of the junction, and are thus compatible with any Josephson diode. Published by the American Physical Society 2024

Dealing with time-dependent exposures and confounding when defining and estimating attributable fractions-Revisiting estimands and estimators.

The population-attributable fraction (PAF) is commonly interpreted as the proportion of events that can be ascribed to a certain exposure in a certain population. Its estimation is sensitive to common forms of time-dependent bias in the face of a time-dependent exposure. Predominant estimation approaches based on multistate modeling fail to fully eliminate such bias and, as a result, do not permit a causal interpretation, even in the absence of confounding. While recently proposed multistate modeling approaches can successfully eliminate residual time-dependent bias, and moreover succeed to adjust for time-dependent confounding by means of inverse probability of censoring weighting, inadequate application, and misinterpretation prevails in the medical literature. In this paper, we therefore revisit recent work on previously proposed PAF estimands and estimators in settings with time-dependent exposures and competing events and extend this work in several ways. First, we critically revisit the interpretation and applied terminology of these estimands. Second, we further formalize the assumptions under which a causally interpretable PAF estimand can be identified and provide analogous weighting-based representations of the identifying functionals of other proposed estimands. This representation aims to enhance the applied statistician's understanding of different sources of bias that may arise when the aim is to obtain a valid estimate of a causally interpretable PAF. To illustrate and compare these representations, we present a real-life application to observational data from the Ghent University Hospital ICUs to estimate the fraction of ICU deaths attributable to hospital-acquired infections.

Time-dependent magnetotransport in a hybrid graphene/single magnetic molecule structure

Graphene is potentially attractive for spintronics due to its weak intrinsic spin–orbit effect leading to a long spin relaxation length. This study examines molecular couplings on a planar graphene sheet, where one molecule is attached to the graphene sheet connected to ferromagnetic leads. The effects of a strong magnetic field, gate voltage, and time-dependent bias voltage on spin and charge tunneling currents are investigated. It is indicated that the studied model system could be controlled by applying a gate voltage and a time-dependent bias voltage. Regarding the interaction between graphene, magnetic molecule, and magnetic field, it is observed that the mutual interaction coefficients between them have the most considerable effect on the transport current. Applying the magnetic field shows that the response time of the current is very short, and the current is not zero in the steady state. In this situation, the current passes through the system continuously.

The importance of avoiding time-dependent bias when testing the prognostic value of an intervening event — Two acute cellular rejection examples in intestinal transplantation

In testing the prognostic value of the occurrence of an intervening event (clinical event that occurs posttransplant), 3 proper statistical methodologies for testing its prognostic value exist (time-dependent covariate, landmark, and semi-Markov modeling methods). However, time-dependent bias has appeared in many clinical reports, whereby the intervening event is statistically treated as a baseline variable (as if it occurred at transplant). Using a single-center cohort of 445 intestinal transplant cases to test the prognostic value of first acute cellular rejection (ACR) and severe (grade of) ACR on the hazard rate of developing graft loss, we demonstrate how the inclusion of such time-dependent bias can lead to severe underestimation of the true hazard ratio (HR). The (statistically more powerful) time-dependent covariate method in Cox’s multivariable model yielded significantly unfavorable effects of first ACR (P < .0001; HR = 2.492) and severe ACR (P < .0001; HR = 4.531). In contrast, when using the time-dependent biased approach, multivariable analysis yielded an incorrect conclusion for the prognostic value of first ACR (P = .31, HR = 0.877, 35.2% of 2.492) and a much smaller estimated effect of severe ACR (P = .0008; HR = 1.589; 35.1% of 4.531). In conclusion, this study demonstrates the importance of avoiding time-dependent bias when testing the prognostic value of an intervening event.

RE: Time-dependent Bias Existing in Their Statistical Analysis Must Be Properly Controlled/Avoided Before Drawing Any Conclusions.

RE: Time-dependent Bias Existing in Their Statistical Analysis Must Be Properly Controlled/Avoided Before Drawing Any Conclusions.

Intravenous methylprednisolone pulse therapy and the risk of in-hospital mortality among acute COVID-19 patients: Nationwide clinical cohort study

BackgroundSteroids are widely used to modulate the inflammatory reactions associated with coronavirus disease 2019 (COVID-19); however, the optimal upper limit dose of steroid use for acute COVID-19 care remains unclear and currently available data may suffer from a time-dependent bias of no effectiveness or reversed causation given the desperate situation of treatment during this pandemic. Accordingly, the aim of this study was to elucidate the impact of intravenous pulse therapy with methylprednisolone (500 mg or greater per day) on the risk of in-hospital mortality among patients with COVID-19 by controlling for time-dependent bias.MethodsWe performed a prospective cohort study with 67,348 hospitalised acute COVID-19 patients at 438 hospitals during 2020–2021 in Japan. The impact of intravenous methylprednisolone pulse therapy on the risk of in-hospital mortality was examined based on hazard ratios (HRs) and 95% confidence intervals (95% CIs), with stratification according to the status of invasive mechanical ventilation (iMV). Time-dependent bias was controlled for in a marginal structural model analysis, with reference to patients without methylprednisolone therapy.ResultsDuring the study period, 2400 patients died. In-hospital mortality rates of iMV-free patients without or with methylprednisolone pulse therapy were 2.3% and 19.5%, and the corresponding values for iMV-receiving patients were 24.7% and 28.6%, respectively. The marginal structural model analysis showed that intravenous pulse therapy with methylprednisolone was associated with a lower risk of in-hospital mortality among patients receiving-iMV (HR 0.59; 95% CI 0.52–0.68). In contrast, pulse therapy with methylprednisolone increased the risk of in-hospital mortality among iMV-free patients (HR 3.38; 95% CI 3.02–3.79). The benefits of pulse therapy for iMV-receiving patients were greater than in those treated with intermediate/higher doses (40–250 mg intravenously) of methylprednisolone (HR 0.80; 95% CI 0.71–0.89).ConclusionThe results of our study suggest that intravenous methylprednisolone showed dose–response efficiencies, and pulse therapy may benefit critically ill patients with acute COVID-19, such as those requiring iMV.

Genetically-encoded BRET probes enlight ligand bias-induced variable ion selectivity in TRPV1 and P2X5/7.

Whether ion channels experience ligand-dependent dynamic ion selectivity remains of critical importance since this could support ion channel functional bias. Tracking selective ion permeability through ion channels remains, however, challenging even with patch-clamp electrophysiology. In this study, we have developed highly-sensitive Bioluminescence Resonance Energy Transfer (BRET) probes providing dynamic measurements of Ca2+ and K+ concentrations and ionic strength in the nanoenvironment of TRPV1 and P2X channels pore in real-time and in live cells during drug challenges. Our results indicate that AMG517, BCTC, and AMG21629, three well-known TRPV1 inhibitors, more potently inhibit the CAPS-induced Ca2+ influx than the CAPS-induced K+ efflux through TRPV1. Even more strikingly, we found that AMG517, when injected alone, is a partial agonist of the K+ efflux through TRPV1 and triggers TRPV1-dependent cell membrane hyperpolarization. In a further effort to exemplify ligand bias in other families of cationic channels, using the same BRET-based strategy, we also detected concentration- and time-dependent ligand biases in P2X7 and P2X5 cationic selectivity when activated by Bz-ATP. These new custom-engineered BRET-based probes now open up avenues for adding value to ion-channel drug discovery platforms by taking ligand bias into account.

Remote Actuation of Silicon Nitride Nanomechanical Resonators Using On-Chip Substrate Capacitors

Mechanical actuation of high mechanical quality (Q) factor silicon nitride (SiN) resonators often imposes a tradeoff between integration and performance. Fully integrated electrical actuation is possible, but typically require modification of the resonators to include electrodes that can increase material damping and reduce Q-factors. Conversely, remote actuation using piezo ceramics or optical forces is bulky and typically suitable only in laboratory settings. Here we demonstrate an actuation method that does not require modifications to the resonators and that is monolithically integrated on the same chip. We show that time dependent biasing of metal-dielectric-semiconductor (MDS) capacitors on the same substrate as the resonators creates acoustic waves that can propagate towards the resonator and enable actuation without resonator modification. For a 2 V actuation signal, Ni-pSi capacitors are found to achieve 10 nm actuation amplitude in square ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$1.7\times1.7$ </tex-math></inline-formula> mm) low-stress (~100 MPa) SiN membrane resonators. In this case, electrical power dissipation in the chip is on the order of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$0.1 ~\mu \text{W}$ </tex-math></inline-formula> , and spurious heating is less than 1 mK. Both these values could be further reduced by doping the substrate to minimize resistive dissipation. First-principle models describing actuation in the charge accumulation (Ni-pSi) and charge depletion (Al-pSi) regimes are also developed. These models predict more efficient actuation using charge accumulation than charge depletion, which is confirmed experimentally. The developed actuation method is remarkably simple. In the case of Ni-pSi, it only requires attachment of wires to the chip with vacuum-compatible nickel paste, with no extra photolithography step. All the chips presented in this work are fabricated in-house, and a detailed fabrication procedure is provided. [2022-0107]

2023. Excess Cost of Healthcare-Associated Infections in the Central Texas Veterans Health Care System

Abstract Background Many studies reporting the excess cost of healthcare-associated infections (HAIs) have used data from positive cultures found in electronic medical records. These data are often limited in a number of ways including whether the positive culture truly represents an actual infection and not just colonization, when the onset of the infection occurred, and whether the infection was device related. Our objective was to generate estimates of the excess cost of HAIs in one facility, the Central Texas Veterans Health Care System (CTVHCS), using highly reliable information extracted from chart review regarding the infection. Methods Our study included data from all inpatient admissions between 1/1/2014 and 12/31/2019 at CTVHCS. HAIs were identified via chart review and were classified based on the infecting organism, specimen location, and whether the infection was device related using 2017 National Health and Safety Network definitions. To minimize time-dependent bias in our estimates of the excess cost of HAIs, we matched each patient with an HAI on day t of their inpatient stay to up to 4 patients who had not had an HAI up until day t of their inpatient stay. We used multivariable generalized estimating equations models to compare the inpatient costs prior to discharge between patients with and without HAIs. Finally, we used multivariable 2-part models to estimate the impact of HAIs on post-discharge readmission costs. Results Our analysis cohort consisted of 425 patients with HAIs who were matched to 1,645 patients without HAIs. HAIs were associated with $29,412 (95% CI:$18,064-$40,759) excess pre-discharge costs, 46.3% increase in the odds of a post-discharge readmission, and $16,049 excess post-discharge costs (see Table 1). The excess pre-discharge costs for central line, catheter-associated urinary tract, and surgical site infections (SSIs) were $96,655 (95% CI:$61,557-$131,754), $34,026 (95% CI:$9,562-$58,491), and $20,014 (95% CI:$5,324-$34,703), respectively. As seen in Table 2, the excess readmission cost for SSIs was $28,222 (95% CI:$9,523-$46,920). Table 1Multivariable regression model results - excess pre-discharge costs associated with healthcare-associated infectionsTable 2Multivariable regression model results - excess post-discharge costs associated with healthcare-associated infections Conclusion We found that HAIs significantly increased both pre- and post-discharge inpatient costs. These costs could potentially be saved if interventions to prevent HAIs could be successfully implemented. Disclosures Piyali Chatterjee, PhD, AHRQ Grant # 1R03HS027667-01: Grant/Research Support|AHRQ Grant # 1R03HS027667-01: Central Texas Veterans Health Care System Chetan Jinadatha, MD, MPH, AHRQ R01 Grant-5R01HS025598: Grant/Research Support|EOS Surfaces: Copper Coupons and materials for testing.

Genetically-encoded BRET probes shed light on ligand bias–induced variable ion selectivity in TRPV1 and P2X5/7

Whether ion channels experience ligand-dependent dynamic ion selectivity remains of critical importance since this could support ion channel functional bias. Tracking selective ion permeability through ion channels, however, remains challenging even with patch-clamp electrophysiology. In this study, we have developed highly sensitive bioluminescence resonance energy transfer (BRET) probes providing dynamic measurements of Ca2+ and K+ concentrations and ionic strength in the nanoenvironment of Transient Receptor Potential Vanilloid-1 Channel (TRPV1) and P2X channel pores in real time and in live cells during drug challenges. Our results indicate that AMG517, BCTC, and AMG21629, three well-known TRPV1 inhibitors, more potently inhibit the capsaicin (CAPS)-induced Ca2+ influx than the CAPS-induced K+ efflux through TRPV1. Even more strikingly, we found that AMG517, when injected alone, is a partial agonist of the K+ efflux through TRPV1 and triggers TRPV1-dependent cell membrane hyperpolarization. In a further effort to exemplify ligand bias in other families of cationic channels, using the same BRET-based strategy, we also detected concentration- and time-dependent ligand biases in P2X7 and P2X5 cationic selectivity when activated by benzoyl-adenosine triphosphate (Bz-ATP). These custom-engineered BRET-based probes now open up avenues for adding value to ion-channel drug discovery platforms by taking ligand bias into account.

Excess length of stay and readmission following hospital-acquired bacteraemia: a population-based cohort study applying a multi-state model approach

ObjectivesPopulation-based estimates of excess length of stay after hospital-acquired bacteraemia (HAB) are few and prone to time-dependent bias. We investigated the excess length of stay and readmission after HAB. MethodsThis population-based cohort study included the North Denmark Region adult population hospitalized for ≥48 hours, from 2006 to 2018. Using a multi-state model with 45 days of follow-up, we estimated adjusted hazard ratios (aHRs) for end of stay and discharge alive. The excess length of stay was defined as the difference in residual length of stay between infected and uninfected patients, estimated using a non-parametric approach with HAB as time-dependent exposure. Confounder effects were estimated using pseudo-value regression. Readmission after HAB was investigated using the Cox regression. ResultsWe identified 3457 episodes of HAB in 484 291 admissions in 205 962 unique patients. Following HAB, excess length of stay was 6.6 days (95% CI, 6.2–7.1 days) compared with patients at risk. HAB was associated with decreased probability of end of hospital stay (aHR, 0.60; 95% CI, 0.57–0.62) driven by the decreased hazard for discharge alive; the aHRs ranged from 0.30 (95% CI, 0.23–0.40) for bacteraemia stemming from ‘heart and vascular’ source to 0.72 (95% CI, 0.69–0.82) for the ‘urinary tract’. Despite increased post-discharge mortality (aHR, 2.76; 95% CI, 2.38–3.21), HAB was associated with readmission (aHR, 1.42; 95% CI, 1.31–1.53). ConclusionHAB was associated with considerably excess length of hospital stay compared with hospitalized patients without bacteraemia. Among patients discharged alive, HAB was associated with increased readmission rates.

Utilizing Nonequilibrium Isotope Enrichments to Dramatically Increase Turnover Measurement Ranges in Single Biopsy Samples from Humans.

The synthesis of new proteins and the degradation of old proteins in vivo can be quantified in serial samples using metabolic isotope labeling to measure turnover. Because serial biopsies in humans are impractical, we set out to develop a method to calculate the turnover rates of proteins from single human biopsies. This method involved a new metabolic labeling approach and adjustments to the calculations used in previous work to calculate protein turnover. We demonstrate that using a nonequilibrium isotope enrichment strategy avoids the time dependent bias caused by variable lag in label delivery to different tissues observed in traditional metabolic labeling methods. Turnover rates are consistent for the same subject in biopsies from different labeling periods, and turnover rates calculated in this study are consistent with previously reported values. We also demonstrate that by measuring protein turnover we can determine where proteins are synthesized. In human subjects a significant difference in turnover rates differentiated proteins synthesized in the salivary glands versus those imported from the serum. We also provide a data analysis tool, DeuteRater-H, to calculate protein turnover using this nonequilibrium metabolic 2H2O method.

Satellite Clock Batch Estimation Accuracy Analysis and Its Impacts on PPP

The ultra-rapid satellite clock product based on the satellite clock batch estimation is commonly used for high-precision and reliable precise point positioning (PPP) services. In order to clarify the effect of different ranging errors on the satellite clock batch estimation accuracy, the source of the satellite clock bias induced by the batch observation model is classified into the initial clock bias (ICB) and time-dependent bias (TDB). In addition to the effect of the ICB and TDB, the analytic relationship between the observation redundancy and the satellite clock batch estimation accuracy are derived and verified. The suitable number of stations is suggested to be 40 for the satellite clock batch estimation to achieve the counterbalance between the efficiency and saturable accuracy. For the PPP based on the batch-estimated satellite clock, the impacts of the ICB and TDB on PPP are clarified. The satellite clock batch estimation and PPP experiments are carried out to investigate the impacts of the ICB and TDB on the satellite clock batch estimation accuracy and the PPP performance. The ICB causes a significant bias for the batch-estimated satellite clock. The TDB is impacted by the assimilation ability of the batch-estimated satellite clock to the satellite orbit error. The convergence time and the positioning accuracy after the convergence of PPP are primarily affected by the ICB and TDB, respectively.