Effect Of Treatment Research Articles

Effect of ultrasound-assisted L-lysine treatment on pork meat quality and myofibrillar protein properties during postmortem aging.

This paper aimed to investigate the effects of ultrasound-assisted L-lysine treatment on meat quality and myofibrillar proteins (MPs) properties of pork longissimus dorsi during postmortem aging. The results revealed that the L-lysine (Lys) and/or ultrasound treatment significantly increased (p < 0.05) the water-holding capacity and tenderness of the pork during postmortem aging, while the ultrasound-assisted Lys treatment had the lowest cooking loss, pressurization loss, Warner-Bratzler shear force, and hardness. In addition, L-lysine and/or ultrasound treatment increased (p < 0.05) pH value, T21, and myofibrillar fragmentation index, while the ultrasound-assisted Lys treatment had the highest value. Meanwhile, the protein solubility was increased with Lys and/or ultrasound treatment during postmortem aging, and ultrasound-assisted Lys treatment had the highest solubility, reaching 88.19%, 92.98%, and 91.73% at 0, 1, and 3 days, respectively. The result of protein conformational characteristics showed that Lys and/or ultrasound treatment caused the unfolding of the α-helix structure, resulting in the exposure of more hydrophobic amino acids and buried sulfhydryl groups, ultimately enhancing MPs solubility. In summary, ultrasound-assisted Lys treatment altered the structure of MPs, resulting in the enhancement of the water-holding capacity and tenderness of the pork. PRACTICAL APPLICATION: This study showed that ultrasound-assisted L-lysine (Lys) treatment could enhance the water-holding capacity and tenderness of pork during postmortem aging. The results might provide a reference for the application of ultrasound-assisted Lys treatment on the improvement of pork meat quality. To facilitate practical applications in production, the development of medium and large-sized ultrasound equipment for conducting small-scale and pilot experiments is crucial for future research.

Re-weighting the randomized controlled trial for generalization: finite-sample error and variable selection

Abstract Randomized controlled trials (RCTs) may suffer from limited scope. In particular, samples may be unrepresentative: some RCTs over- or under-sample individuals with certain characteristics compared to the target population, for which one wants conclusions on treatment effectiveness. Re-weighting trial individuals to match the target population can improve the treatment effect estimation. In this work, we establish the expressions of the bias and variance of such re-weighting procedures—also called inverse propensity of sampling weighting (IPSW)—in presence of categorical covariates for any sample size. Such results allow us to compare the theoretical performance of different versions of IPSW estimates. Besides, our results show how the performance (bias, variance, and quadratic risk) of IPSW estimates depends on the two sample sizes (RCT and target population). A by-product of our work is the proof of consistency of IPSW estimates. In addition, we analyse how including covariates that are not necessary for identifiability of the causal effect may impact the asymptotic variance. Including covariates that are shifted between the two samples but not treatment-effect modifiers increases the variance while non-shifted but treatment-effect modifiers do not. We illustrate all the takeaways in a didactic example, and on a semi-synthetic simulation inspired from critical care medicine.

Impact of taurolidine use during cardiac electronic implantable device implantation in heart failure patients

Abstract Background Cardiac Implantable Electronic Device (CIED) infections represent a critical health threat with potentially fatal consequences. The TauroPace™ is an innovative solution that contains taurolidine specifically formulated to eradicate environmental microbial contamination on the surface of CIEDs. To date, scarce data are available in literature about Taurolidine’s effect on preventing CIED infections. Aims To investigate the ability of the TauroPace™ to reduce major CIED infections through 12 months follow-up in fragile patients such as heart failure (HF) patients. Methods This prospective cohort study included patients with HF and an ejection fraction ≤ 35%, who were referred for de novo implantation, upgrading or battery replacement of Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy with defibrillator (CRT-D), to the EP labs of two tertiary care hospitals. Patients with previous CIED infections were excluded. During the procedures, the catheters were submerged in the TauroPace™ solution and the pocket was irrigated with taurolidine. Starting from the main risk factors for the development of CIED-related infections as identified in the literature (including individuals with heart failure, diabetes, chronic kidney disease, and those undergoing defibrillators implantation, especially upgrades or revisions procedure), we conducted a meta-analysis and meta-regression to evaluate the relationship between the treatment effect's magnitude and various predictors. To estimate the incidence of CIED infections in high-risk subgroups, we utilized the percentage of patients with diabetes, chronic renal failure, or those undergoing replacement, upgrade, or revision procedures, along with other risk factors for CIED infections, as continuous variables and we were able to modify our comparison parameters based on the real percentage of risk factors that we obtained. Results The study included 69 consecutive patients (53 male [76.8 %], 34 ischemic [49,3 %], median [IQR] age 68 [59-73] years, 19 diabetic [27.5 %] and 34 [49.2 %] with chronic renal failure), of whom 39 (56.5 %) received ICD and 30 (43.5 %) CRT-D, with 28 (40.6 %) replacement procedures, 2 (2.9 %) upgrades, and 39 (57%) de novo implantations. During the one-year follow-up period, 1 [1.45 (Standard Error, SE 0.014) %] patient undergoing a CRT replacement developed an infection. The available data from the literature estimate an incidence rate of 6% (SE 0.0106) when considering a selected patient population with a very high risk of infection similar to our population. This is significantly higher than our cohort (z-score -2.5447, p value = 0.011). Conclusions Taurolidine has yielded promising results, demonstrating a low incidence rate of infections within our cohort of high-risk patients, which is below that reported in the literature. Further data will be necessary to validate and confirm these initial findings.

Effect of TiO2-SiC and heat treatment on tribological characteristics of bimodal hybrid aluminium composites under dry sliding condition

Abstract The dry sliding wear behavior of bimodal TiO2np/SiCp/Al6082 composites was studied using a pin-on-disk tribometer. The investigation included both as-cast alloy and T6 heat-treated composites, with variations in applied load (40 N, 60 N, and 80 N) and sliding distance (600, 900, 1200, 1500, 1800, and 2100 m) at a constant sliding speed of 2 m/s. The microstructure of the composites and the worn surface were examined using a scanning electron microscope. A linear increase in wear rate was observed with sliding distance up to the transition limit. It was found that at 40 N, a shield began to develop between the disc and pin surface, reducing the coefficient of friction (COF), and friction and oxide were the primary processes of wear mechanisms. A larger load caused the protective layer to be destroyed; increasing COF, and adhesion and delamination were the two types of wear that were noticed. The wear resistance of alloys and bimodal composites were increased by heat treatment because it strengthened the matrix.

Hypotension with neurovascular changes and cognitive dysfunction: An epidemiological, pathobiological, and treatment review.

Hypotension is a leading cause of age-related cognitive impairment. The available literature evidences that vascular factors are associated with dementia and that hypotension alters cerebral perfusion flow and can aggravate the neurodegeneration of Alzheimer's disease (AD). Despite the discovery of biomarkers and the recent progress made in neurovascular biology, epidemiology, and brain imaging, some key issues remain largely unresolved: the potential mechanisms underlying the neural deterioration observed in AD, the effect of cerebrovascular alterations on cognitive deficits, and the positive effects of hypotension treatment on cognition. Therefore, further well-designed studies are needed to unravel the potential association between hypotension and cognitive dysfunction and reveal the potential benefits of hypotension treatment for AD patients. Here, we review the current epidemiological, pathobiological, and treatment-related literature on neurovascular changes and hypotension-related cognitive dysfunction and highlight the unsettled but imminent issues that warrant future research endeavors.

Effect of Different Surface Treatments on the Bonding Strength of Three Different Post Biomaterials to a Resin-Based Luting Agent

ABSTRACT Aim: The aim of this study was to evaluate how different post-surface treatments affect the ability of luting cement to bond three different dental post materials to a resinous surface. Materials and Methods: The study analyzed a total of 108 posts categorized into three main groups: stainless steel, cast, and fiber posts. Next, the core group was divided into four subgroups (n = 9) according to the type of surface treatment applied: no surface treatment (NS), silanization (SZ), sandblasting (SB), and sandblasting plus silanization (SBSZ). Results: Stainless steel posts exhibited the lowest bond strength, whereas fiber posts demonstrated the highest shear bond strength. When it comes to surface treatments, dental post-surfaces treated with sandblasting have been found to exhibit the highest bond strength, outperforming other methods. Conclusion: Comparing all methods of surface modification, sandblasting with 50 um Al2O3 particles demonstrated the strongest connection.

Effects of aging heat treatment on the mechanical properties of NiTi triply periodic minimal surface

This study investigated the impact of aging heat treatment time on the mechanical properties of NiTi triply periodic minimal surface structures fabricated through laser powder bed fusion. X-ray diffraction analysis results indicate that with increasing aging time, the NiTi2 phase precipitates while the content of the B19&amp;rsquo; phase decreases. At 10 h of aging time, the Ni4Ti3 phase becomes evident in the sample. The differential scanning calorimeter results show that R phase transformation occurs, and the phase transformation temperature increases when the aging time reaches 6 h. Microhardness increases with aging time, peaking at 477.8 HV after 10 h. Compression experiment results reveal a maximum elastic modulus of 1262.82 MPa for the gyroid sheet-shaped structure achieved after 2 h. In addition, the superelasticity test indicates the highest recoverable strains at 2%, 4%, and 6% compressive strain for the gyroid rod-shaped structure after aging for 10 h. In cyclic compression experiments, the ratio of shape memory recovery increases from 40% at 0 h to 97% at 6 h. Fracture analysis results show that the transition in the fracture mechanism from brittle fracture to quasi-cleavage fracture occurs after aging heat treatment.

Effects of heat treatment on microstructure and mechanical properties of 17-4PH/IN625 bimetallic parts fabricated through extrusion-based sintering-assisted additive manufacturing

The mechanical properties of bimetallic composites are significantly influenced by their interfacial morphologies. This study delves into the impact of various heat treatment conditions on the microstructure and mechanical attributes of steel/nickel bimetallic (17-4PH/IN625) components produced through extrusion-based sintering-assisted additive manufacturing (ES-AM). The bimetallic composites were annealed at 1150&amp;deg;C for 1, 4, and 8 h, followed by an aging treatment at 482&amp;deg;C for samples annealed for 8 h. After annealing, microstructural heterogeneities, including variations in grain size and elemental distribution within the transition zone close to the interface, were observed. It was found that in the diffusion transition zone between the two alloy layers, the diffusion of iron (Fe) and nickel (Ni) elements increased with longer holding times, as corroborated by microhardness tests and quantified through theoretical parabolic diffusion law. The transition zone exhibited two distinct areas: an Fe-predominant zone and a Ni-predominant zone, with the latter containing oxides and molybdenum (Mo)- and niobium (Nb)-rich precipitates. No new phases emerged post-heat treatment; however, shifts in peak due to stress relaxation and the emergence of precipitates were identified through X-ray diffraction (XRD) observations. Microhardness within the transition zone increased following heat treatment, peaking at 186 HV1.0 after a 4-h annealing. The optimal heat treatment condition was identified as 1150&amp;deg;C for 4 h, which facilitated the development of uniform microstructures and improved bonding strength. This study demonstrates an enhanced interfacial bonding strength in 17-4PH and IN625 bimetallic parts manufactured through ES-AM, suggesting their wide-ranging potential applications in industry.

Preservation of ovarian function using human pluripotent stem cell-derived mesenchymal progenitor cells.

Ovarian reserve diminishes with age, and older women experience a corresponding shift in sex hormone levels. These changes contribute to an age-dependent decrease in fertility and a decline in overall health. Furthermore, while survival rates following cancer treatment have improved for young female patients, a reduction in ovarian function due to the side effects of such treatments can be difficult to avoid. To date, no effective therapy has been recommended to preserve ovarian health in these patients. Mesenchymal progenitor cells (MPCs) are considered a promising option for cell therapy aimed at maintaining fertility and fecundity. Although MPCs derived from human adult tissues are recognized for their various protective effects against ovarian senescence, they are limited in quantity. Consequently, human pluripotent stem cell-derived MPCs (hPSC-MPCs), which exhibit high proliferative capacity and retain genetic stability during growth, have been utilized to delay reproductive aging. This review highlights the impact of hPSC-MPCs on preserving the functionality of damaged ovaries in female mouse models subjected to chemotherapy and natural aging. It also proposes their potential as a valuable cell source for fertility preservation in women with a variety of diseases.

Effect of Heat Treatment on Structure of Carbon Shell-Encapsulated Pt Nanoparticles for Fuel Cells

Polymer electrolyte membrane fuel cells (PEMFCs) have attracted much attention as highly efficient, eco-friendly energy conversion devices. However, carbon-supported Pt (Pt/C) catalysts for PEMFCs still have several problems, such as low long-term stability, to be widely commercialized in fuel cell applications. To address the stability issues of Pt/C such as the dissolution, detachment, and agglomeration of Pt nanoparticles under harsh operating conditions, we design an interesting fabrication process to produce a highly active and durable Pt catalyst by introducing a robust carbon shell on the Pt surface. Furthermore, this approach provides insights into how to regulate the carbon shell layer for fuel cell applications. Through the application of an appropriate amount of H2 gas during heat treatment, the carbon shell pores, which are integral to the structure, can be systematically modulated to facilitate oxygen adsorption for the oxygen reduction reaction. Simultaneously, the carbon shell functions as a protective barrier, preventing catalyst degradation. In this regard, we investigate an in-depth analysis of the effects of critical parameters including H2 content and the flow rate of H2/N2 mixed gas during heat treatment to prepare better catalysts.

Exploring side effects of corticosteroids in myasthenia gravis: Unveiling alternatives for safer treatment

Myasthenia Gravis (MG) is a chronic organ-specific autoimmune disease that weakens voluntary muscles by affecting neuromuscular junctions. The formation of antibodies against acetylcholine receptors is the most prevalent cause. The incidence and prevalence rates of (MG) are increasing exponentially (1). In addition to symptomatic medication, corticosteroids continue to be the first-line treatment for MG due to their affordability, ease of access, and efficacy (2). Although corticosteroids are frequently prescribed, they are not without drawbacks. Long-term corticosteroid use can result in various side effects, including osteoporosis, weight gain, acne, elevated blood pressure, mood fluctuations, and a cushingoid appearance. It has also been linked to rare complications such as gastric and esophageal irritation, compressive fractures, and aseptic femoral head fracture (3). Given the hazards associated with long-term corticosteroid use in treating MG, researchers and healthcare professionals should investigate alternative MG treatments. By doing so, new and safer treatment options can be identified, which could contribute to improved treatment and substantially enhance the quality of life for MG-affected populations. Numerous nonsteroidal medications, including mycophenolate mofetil, methotrexate, and azathioprine, have demonstrated success in clinical trials for kidney transplantation, rheumatoid arthritis, and myasthenia gravis, respectively. To confirm the efficacy of these pharmaceuticals in the treatment of MG, urgent research and trials based on in vitro and animal models are required. Based on well-designed clinical trials, these also require human testing (4). The tapering of prednisone is an alternative option. Prednisone tapering is still a problem in the therapeutic management of patients with generalized MG because, although it is a useful treatment, it has a number of adverse effects that make it necessary to find the lowest possible effective dose as quickly as feasible. Rituximab and azathioprine enable quick tapering. It is necessary to evaluate and contrast the corticosteroid-sparing effect of novel treatments with that of azathioprine and rituximab. Given their impact on MG status, it's possible that these novel therapies will make it possible to drastically cut back on corticosteroids or possibly stop taking them entirely(5) The abnormal immune responses in MG can be managed and resolved with the new drugs that specifically target them. These agents include chimeric antigen receptor T [CART-T] cell therapy, autologous stem cell transplantation, B cell depleting agents (anti-CD 19 and 20, and B cell activating factor [BAFF] inhibitors), proteosome inhibitors, terminal complement C5 inhibitors, Fc receptor inhibitors, T cells, and cytokine-based therapies (subcutaneous immunoglobulin [SCIG]). ---Continue

Who is doing better? Exploring the effect of COVID-19 on students’ academic performance across the test score distribution

ABSTRACT Previous studies have found a negative effect on average student performance on standardised tests following the Covid-19 crisis. However, the effects might differ depending on the student’s position in the achievement distribution. Understanding distributional effects allows us to determine how to better direct resources to students most affected. Using a quantile treatment effects model, we estimate the effects of Covid-19 on academic performance of students in the Colombian standardised high school exit examination. Our estimates show a U-shaped pattern: the negative effect is smaller for students located at the tails of the test score distribution.

Short cell-penetration peptide conjugated bioreducible polymer enhances gene editing of CRISPR system

CRISPR-based gene therapy offers precise targeting and specific editing of disease-related gene sequences, potentially yielding long-lasting treatment effects. However, efficient delivery remains a significant challenge for its widespread application. In this study, we design a novel short peptide-conjugated bioreducible polymer named TSPscp as a safe and effective delivery vector for the CRISPR system. Our results show that TSPscp markedly boosts transcriptional activation and genome editing activities of multiple CRISPR systems as confirmed by decomposition-seq and Deep-seq, which is resulted from its capability in facilitating delivery of plasmid DNA by promoting cellular uptake and lysosomal escape. Additionally, TSPscp further enhances genome editing of CRISPR by delivery of minicircle DNA, a condensed form of regular plasmid DNA. More importantly, TSPscp significantly improves delivery and genome editing of CRISPR system in vivo. In summary, our study highlights TSPscp as a promising delivery tool for CRISPR applications in vivo.Graphical

Investigation on the efficiency of lentinan for injection combining cisplatin on treating malignant pleural effusion based on systematic review and meta-analysis.

Malignant pleural effusion (MPE) is a frequently observed complication in advanced malignant tumors. Clinical studies have shown that lentinan for injection (LNT) is beneficial for improving patients' quality of life and prolonging their survival. The purpose of this meta-analysis is to evaluate the efficacy and safety of LNT combining cisplatin in the treatment of MPE. Randomized controlled trials (RCTs) of LNT combining cisplatin in the treatment of MPE were searched in 6 literature databases from the establishment time of each database by 2 researchers. According to the inclusion criteria, 2 researchers independently screened studies, assessed the risk of bias and conducted subgroup analyses for different outcome indicators according to the specific characteristics of the included literature. Analyzing the data by Revman software, and evaluating the stability of the results by Stata software. A total of 52 RCTs were included. The results showed that combined use of LNT and cisplatin could improve the treatment effect, and the difference between groups was statistically significant (RR = 1.40, 95%CI: 1.33 ~ 1.46, P < .001). And the combined use of LNT could increase the quality of life (RR = 1.45, 95%CI: 1.35 ~ 1.56, P < .001). The using of LNT could significantly decrease the incidence of gastrointestinal reactions (RR = 0.86, 95%CI: 0.78 ~ 0.94, P < .001). Sensitivity analysis results showed that there were no qualitative changes in the indicator, and suggested the possibility of publication bias. Available evidence suggested the combined use of LNT and cisplatin showed better efficacy in treating MPE without increasing ADR incidence than using cisplatin alone. LNT is an ideal treatment for MPE, which has high clinical application value.

A Comprehensive Approach to PROMs in Elective Orthopedic Surgery: Comparing Effect Sizes across Patient Subgroups

Background: There is limited knowledge regarding the comparative patient-reported outcomes (PROMs) and effect sizes (ESs) across orthopedic elective surgery. Methods: All patient data between January 2020 and December 2022 were collected, and treatment outcomes assessed as a PROM difference between baseline and one-year follow-up. The cohort was divided into subgroups (hand, elbow, shoulder, spine, hip, knee, and foot/ankle). The PROM ESs were calculated for each patient separately, and patients with ES &gt; 0.5 were considered responders. Results: In total, 7695 patients were operated on. The mean ES across all patient groups was 1.81 (SD 1.41), and the largest ES was observed in shoulder patients and the smallest in hand patients. Overall, shoulder, hip, and knee patients had a larger ES compared to hand, spine, and foot/ankle patients (p &lt; 0.0001). The proportion of positive responders ranged between 91–94% in the knee, shoulder, and hip, and 69–70% in the hand, spine, and foot/ankle subgroups. Conclusions: The ESs are generally high throughout elective orthopedic surgery. However, based on our institutional observations, shoulder, hip, and knee patients experience larger treatment effects compared to hand, spine, and foot/ankle patients, among whom there are also more non-responders. The expected treatment outcomes should be clearly communicated to patients when considering elective surgery. Because of the study limitations, the results should be approached with some caution.

P.039 Informing treatment advancement and innovation in a tertiary care neurocritical care (NCC)) program

Background: Children with neurological injuries/insults carry the highest risk of death and disability in Pediatric and Neonatal ICUs. These patients comprise 25-30% of admissions and have a myriad of diagnoses. Longitudinal outcome data is required to inform treatment effects and innovation strategies. NCC at the Alberta Children’s Hospital (ACH) participates in acute, subacute, and long-term/outpatient management with an aim to use comprehensive clinical data to improve outcomes. Methods: A prospective, longitudinal, population-based observational cohort study of NCC patients from local NICUs, PICU, and a NCC follow-up program, with comprehensive data from clinical records, development scores and QoL assessments. Results: Since 2019, 929 patients have been enrolled including: 407 neonates, 167 infants, 106 preschool-age and 100 school-age children, and 152 adolescents. The most common reasons for NCC consult were paroxysmal events (36%), encephalopathy (27%) and neonatal HIE (20%). Conclusions: Our database encapsulates the diverse nature of NCC patients and has enabled cohort-specific studies (e.g., neonatal HIE and ECLS outcomes). Program evolution will further facilitate higher powered research studies through large enrollment, comprehensive data capture (with a provincial EHR), and longitudinal outcomes. Engagement with staff and families will also inform treatment and afford evidence-based counseling to families.

Digital Revolution and Job Quality of Lower Class Workers: Quasi‐experimental Evidence from the Broadband China Program

AbstractThis study examines the impact of the digital revolution on the job quality of workers with a specific focus on those at the lowest end of the spectrum in China's domestic labor market. Leveraging exogenous timing variations that result from the implementation of the Broadband China Program across different cities, it provides quasi‐experimental evidence concerning the effects of the digital revolution on the job quality of lower class workers, particularly rural‐urban migrant workers. Using data from China Migrants Dynamic Survey, this study reveals that migrants’ comprehensive job quality index increased by 0.0138 (5.33 percent), and its component indices experienced positive effects after the Broadband China Program was implemented. This study also investigates heterogeneous policy treatment effects among workers with diverse demographic and occupational characteristics. Underlying mechanisms are considered, including positive macroeconomic shocks, increased social interactions, and Internet use. In particular, migrants’ attitudes toward local settlement became more positive, suggesting that the positive effects of the digital revolution on livelihood lasted for some time. Taking China as an example, this study contributes valuable empirical evidence of how the digital revolution can affect lower class workers’ employment or living conditions in a developing country. Related policy implications are also considered.

A nonparametric proportional risk model to assess a treatment effect in time-to-event data.

Time-to-event analysis often relies on prior parametric assumptions, or, if a semiparametric approach is chosen, Cox's model. This is inherently tied to the assumption of proportional hazards, with the analysis potentially invalidated if this assumption is not fulfilled. In addition, most interpretations focus on the hazard ratio, that is often misinterpreted as the relative risk (RR), the ratio of the cumulative distribution functions. In this paper, we introduce an alternative to current methodology for assessing a treatment effect in a two-group situation, not relying on the proportional hazards assumption but assuming proportional risks. Precisely, we propose a new nonparametric model to directly estimate the RR of two groups to experience an event under the assumption that the risk ratio is constant over time. In addition to this relative measure, our model allows for calculating the number needed to treat as an absolute measure, providing the possibility of an easy and holistic interpretation of the data. We demonstrate the validity of the approach by means of a simulation study and present an application to data from a large randomized controlled trial investigating the effect of dapagliflozin on all-causemortality.

The effect of cardiac resynchronisation therapy upgrade from right ventricular pacing on symptoms and functional clinical outcomes, results from the BUDAPEST-CRT Upgrade trial

Abstract Background Based on the results of the BUDAPEST-CRT Upgrade trial, in patients with intermittent or permanent right ventricular (RV) pacing and reduced left ventricular ejection fraction (HFrEF) upgrade to cardiac resynchronization therapy (CRT) reduces morbidity and mortality. Purpose Whether the substantial treatment effect of the CRT upgrade could also be detected in a better functional and exercise capacity is scarcely investigated. We examined the changes of the prespecified tertiary endpoints such as symptoms, quality of life (QoL), exercise capacity and natriuretic peptide measurement from baseline to 12 months. Methods In the BUDAPEST CRT Upgrade trial 360 HFrEF patients with a priorly implanted PM or ICD and &amp;gt;20% of RV pacing burden were randomly assigned to CRT-D upgrade (n=215) or ICD (n=145) in a 3:2 ratio. The prespecified tertiary endpoints were changes in quality of life measured by EQ-5D-3L, New York Heart Association (NYHA) functional class, 6-minute walk test (6-MWT), and NT-proBNP. When data of trial patients were unavailable due to death at 12 months, imputed values were used as 0 (6MWT) and 0 score (EQ-5D-3L) or a 5th grade (NYHA class). Responders were defined as &amp;gt;15% change of left ventricular end-systolic volume at 12 months. Results From baseline to 12 months, NYHA functional class improved in the CRT-D upgrade arm compared with the ICD only group [adjusted odds ratio (OR) 0.50; 95% CI 0.32-0.80; P=0.003]. According to the adjusted model there was a statistically significant decrease in the NT-proBNP [adjusted difference -1257 pg/mL; 95% CI -2287 – (-228); P=0.017]. In responders, the changes in NT-proBNP levels were significantly greater than in non-responders [adjusted difference -1635 pg/mL; 95% CI -2811 - (-459); P=0.007]. The progression of worsening of QoL attributed to ageing was moderated only by CRT-D upgrade [EQ-5D-3L difference by age -0.01; 95% CI -0.02 - (-0.003); P=0.004; interaction P=0.003]. 6MWT did not improve significantly in either group. Conclusions Patients receiving CRT upgrade showed a substantial improvement in symptoms and a significant decrease in natriuretic peptide levels, as compared to ICD alone, which was more pronounced in responders. Moreover, CRT-D upgrade could moderate the progression of worsening of quality of life attributed to ageing in this vulnerable, older patient population.

Pigeonhole Design: Balancing Sequential Experiments from an Online Matching Perspective

Practitioners and academics have long appreciated the benefits of covariate balancing when they conduct randomized experiments. For web-facing firms running online A/B tests, however, it still remains challenging in balancing covariate information when experimental subjects arrive sequentially. In this paper, we study an online experimental design problem, which we refer to as the online blocking problem. In this problem, experimental subjects with heterogeneous covariate information arrive sequentially and must be immediately assigned into either the control or the treated group. The objective is to minimize the total discrepancy, which is defined as the minimum weight perfect matching between the two groups. To solve this problem, we propose a randomized design of experiment, which we refer to as the pigeonhole design. The pigeonhole design first partitions the covariate space into smaller spaces, which we refer to as pigeonholes, and then, when the experimental subjects arrive at each pigeonhole, balances the number of control and treated subjects for each pigeonhole. We analyze the theoretical performance of the pigeonhole design and show its effectiveness by comparing against two well-known benchmark designs: the matched-pair design and the completely randomized design. We identify scenarios when the pigeonhole design demonstrates more benefits over the benchmark design. To conclude, we conduct extensive simulations using Yahoo! data to show a 10.2% reduction in variance if we use the pigeonhole design to estimate the average treatment effect. This paper was accepted by George Shanthikumar, data science. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.02184 .