bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Bilateral Investment Treaties on FDI Inflows Into India: Some Empirical Results
Authors: Singh Jaivir , Shreeti Vatsala , Urdhwareshe Parnil 
Published: August 2021

After a run of adverse investor-state dispute settlements, India has recently denounced all its erstwhile investment treaties. New investment treaties need to be negotiated on the basis of a new Model Treaty that privilege state rights over investor rights. We study the impact of bilateral investment treaties on foreign direct investment (FDI) inflows into India before the denunciation with the intent of inferring the consequences of changing the system. Our work captures the effects of international investment agreements on FDI inflows specifically into India. We construct an empirical model drawing on the Gravity Model, and estimate parameters using generalised method of moments. The results show that while the individual signing of bilateral investment treaties does not influence the inflow of FDI, the effect of the cumulative bilateral investment treaties signed is statistically very significant—suggesting that the spill over effect of signing a series of bilateral investment treaties are important, signalling a regime of overall protection to investors. The importance of institutional variables in influencing FDI tells us that overall participation in a system governed by international investor agreements influenced the inflow of FDI positively and therefore recent policy changes should be viewed with caution. JEL Codes: F21, F23, F550, F63, K33, O19, C22, C29
Measuring and modeling moisture environment in underground metro stations during commissioning stage: A case study
Authors: Yu Yanzhe , You Shijun , Zhang Huan , Ye Tianzhen , Wang Yaran , Tang Chao , Wei Shen 
Published: August 2021

Due to the humid underground environment, underground metro stations often have internal condensation issues, especially during the commissioning and initial operation phases, and these issues will have a negative impact on the equipment operation and building life. This study aims to solve the issue by 1) identifying common areas with condensation risks based on on-site measurements and numerical simulation methods, and 2) proposing effective dehumidification solutions for the moisture control of stations. By on-site investigating the characteristics of the station’s moisture environment and numerical assessing the effects of two different dehumidification strategies, it has been found that 1) for Tianjin, during most times in summer, the air temperature of the station in the commissioning phase was maintained relatively stable, but with significantly changing humidity; 2) the relative humidity on the platforms was higher than 80% for almost 30% of the testing time, and the surface of the upper structure of platform doors having a high risk of condensation; 3) the dehumidification effect of industrial dehumidifiers was found to be better than that of increasing exhaust air volume. The authors hope that the research could aid the decision on dehumidification strategies and provide guidance for further moisture control in underground stations. Practical Application This article analyzed the moisture environment of the underground metro stations in the commissioning phase and conducted a numerical approach to assess the condensation risk. Potential dehumidification solutions including increasing the exhaust air volume and using industrial dehumidifiers have been proposed, and their effects have been investigated and compared. The authors hope that this research can aid the decision on dehumidification strategies for facilities maintenance and provide a guidance to further moisture control in underground stations.
Improving the Estimation of Subgroup Effects for Clinical Trial Participants with Multimorbidity by Incorporating Drug Class-Level Information in Bayesian Hierarchical Models: A Simulation Study
Authors: Hannigan Laurie J. , Phillippo David M. , Hanlon Peter , Moss Laura , Butterly Elaine W. , Hawkins Neil , Dias Sofia , Welton Nicky J. , McAllister David A. 
Published: August 2021

Background There is limited guidance for using common drug therapies in the context of multimorbidity. In part, this is because their effectiveness for patients with specific comorbidities cannot easily be established using subgroup analyses in clinical trials. Here, we use simulations to explore the feasibility and implications of concurrently estimating effects of related drug treatments in patients with multimorbidity by partially pooling subgroup efficacy estimates across trials. Methods We performed simulations based on the characteristics of 161 real clinical trials of noninsulin glucose-lowering drugs for diabetes, estimating subgroup effects for patients with a hypothetical comorbidity across related trials in different scenarios using Bayesian hierarchical generalized linear models. We structured models according to an established ontology—the World Health Organization Anatomic Chemical Therapeutic Classifications—allowing us to nest all trials within drugs and all drugs within anatomic chemical therapeutic classes, with effects partially pooled at each level of the hierarchy. In a range of scenarios, we compared the performance of this model to random effects meta-analyses of all drugs individually. Results Hierarchical, ontology-based Bayesian models were unbiased and accurately recovered simulated comorbidity-drug interactions. Compared with single-drug meta-analyses, they offered a relative increase in precision of up to 250% in some scenarios because of information sharing across the hierarchy. Because of the relative precision of the approaches, a large proportion of small subgroup effects was detectable only using the hierarchical model. Conclusions By assuming that similar drugs may have similar subgroup effects, Bayesian hierarchical models based on structures defined by existing ontologies can be used to improve the precision of treatment efficacy estimates in patients with multimorbidity, with potential implications for clinical decision making.
Comparison of different en bloc holmium laser enucleation of the prostate techniques to reduce the rate of postoperative transient urinary incontinence
Authors: Lin Chun-Hsuan , Wu Wen-Jeng , Li Ching-Chia , Ke Hung-Lung , Jhan Jhen-Hao , Wen Sheng-Chen 
Published: August 2021

Objective To investigate postoperative risk factors for transient urinary incontinence (TUI) after different en bloc holmium laser enucleation of the prostate (HoLEP) techniques. Methods We retrospectively analyzed 169 consecutive patients who underwent HoLEP using the original en bloc technique (n = 41), en bloc with early mucosal strip detachment technique (n = 72), and three horseshoe-shaped incisions technique (n = 56) to treat bladder outlet obstruction from January 2017 to October 2019. Preoperative variables and surgical quality indexes were compared between the groups. TUI was defined as any hygienic or social problem caused by involuntary loss of urine at 2 weeks postoperatively. The postvoid residual urine volume, maximum urinary flow rate, and International Prostate Symptom Score (IPSS) were assessed. Results Among all three techniques, the three horseshoe-shaped incisions technique was significantly associated with the lowest incidence of TUI and the lowest IPSS. Although not statistically significant, the three horseshoe-shaped incisions group also showed a trend toward a faster enucleation time. No life-threatening intraoperative complications occurred in any group. Conclusion Use of three horseshoe-shaped incisions in en bloc HoLEP prevented urethral sphincter damage with a low rate of postoperative TUI. Further long-term, multicenter comparative assessment is required. Research Registry number: 6848
Measuring headache day severity using multiple features in daily diary designs
Authors: McGinley James S , Houts Carrie R , Wirth RJ , Lipton Richard B 
Published: August 2021

Objective Though migraine is thought of as a symptom complex, symptoms are typically assessed one at a time. For use in clinical research, we developed a composite measure of headache day severity by combining eight well-known symptoms captured in daily diaries. Subjects and Methods Data came from adults with a self-reported diagnosis of migraine (n  =  4380) who provided daily diary information assessed using a novel digital platform. Nine observed features theoretically linked to headache day severity were analyzed using latent variable modeling to create a psychometrically robust headache day severity score. Logistic regression was used to assess the cross-sectional relationships of headache day severity scores against an array of clinically-relevant outcomes. Results Participants were largely females (90%), approaching middle age (mean age of 37.3) and living in the United States (49%) or United Kingdom (23%). Findings supported a single latent headache day severity construct based on eight observed headache features. Headache day severity scores were associated with an increased odds of physician visits (Odds ratio[95% CI]: 1.71[1.32–2.21]), emergency department visits (4.12[2.23-7.60]), missed school/work (2.90[2.56–3.29]), missed household work (3.37[3.06–3.72]), and missed other activities (3.29[2.97–3.64]) (p < .0001 for all). Conclusions Modern measurement techniques support a single headache day severity construct that reflects migraine is a symptom complex. The headache day severity scores were associated with external validators and initial visualizations showed how headache day severity scores can be applied broadly in clinical practice and research.
Valproic Acid in the Management of Delirium
Authors: Cuartas Carlos Fernandez , Davis Mellar 
Published: August 2021

Context: Antipsychotics and benzodiazepines do not improve delirium. Valproic acid (VPA) has been used recently to treat agitation in delirium. Objectives: To review the evidence for VPA in the management of Delirium. Methods: Systematic review. English language, age 19 and above, from 1946 to January 12, 2021. Mesh Terms: “Valproic acid”, “valproate”, “sodium valproate”, “delirium”, “acute mania with delirium” in PubMed and Ovid. Exclusion: Studies of VPA used for diagnoses other than delirium. Results: 21 abstracts were identified and 10 studies were included in the review (252 patients): One prospective open label study (n: 7), 2 case series (n: 22), 4 retrospective studies (n: 219) and 3 case reports (n: 4). No randomized controlled trial (RCT) evaluates the effect of VPA in delirium. 237/250 (94.8%) patients were in the ICU. Mean age was 59.7 (27-87). 153/204 (74%) were male. The mean starting dose was 733 mg/day in 148 patients and the mean dose at follow up was 1061 mg/day in 205 patients. CAM ICU was used to diagnose delirium in 6 reviews. Delirium improved in case series in 19/22 patients. Delirium improved in retrospective studies at day 3 compared to day 1. VPA levels were not consistently reported. Hyperammonemia (12-19%) and thrombocytopenia (9-13%) were the most common side effects. No deaths were attributed to VPA. Conclusion: VPA is being used more frequently for delirium. The evidence is limited to retrospective studies and case series. There is a need for RCT to evaluate the effect of VPA in delirium compared to other alternatives and placebo.
Surgical 5-year Outcomes of Extra-Anatomical Bypass for Middle Aortic Syndrome: A Case Series
Authors: Yamamoto Taira , Endo Daisuke , Shimada Akie , Yamaoka Hironobu , Ooishi Atsumi , Dohi Shizuyuki , Matsushita Satoshi , Asai Tohru , Amano Atsushi 
Published: August 2021

Background Middle aortic syndrome is a rare disease. Several surgical treatments are available; however, the optimal treatment strategy and long-term outcomes remain unelucidated. We herein report the 5-year outcomes of six patients treated with extra-anatomical bypass surgery for middle aortic syndrome. Case presentations Between 2013 and 2016, six patients underwent extra-anatomical bypass for middle aortic syndrome at our institute: three had Takayasu’s arteritis, one had vessel vasculitis, and two had middle aortic hypoplastic syndrome of unknown origin. The patients included five women and one man, with a mean age of 59.7 years. Four patients had uncontrolled hypertension and were receiving antihypertensive medications. The mean ankle–brachial pressure index was .61. The three patients with Takayasu’s arteritis were hospitalized for congestive heart failure. These patients underwent bypass surgery from the descending aorta to the infrarenal abdominal aorta, and one also underwent concomitant heart surgery. The patient with microscopic polyangiitis underwent Y-grafting with an aortic aneurysmectomy. Subsequently, bypass surgery was performed from the descending aorta to the graft via the diaphragm. The two patients with unknown causes underwent bypass surgery from the proximal descending aorta to the distal descending thoracic aorta. There were no early or late deaths at the 5-year follow-up. We did not observe any changes in anastomotic site stenosis or new aneurysmal changes during the follow-up period. The number of antihypertensive medications was reduced in all cases, and critical symptoms, including headache, severe abdominal pain, claudication, and heart failure, improved in all patients. The ankle–brachial pressure index increased to 1.11 and did not change for five years. Renal function remained stable, and the brain natriuretic peptide level decreased from 302.8 to 74.5 pg/mL at follow-up. Conclusion Extra-anatomical bypass for middle aortic syndrome is safe and effective, and can help prevent renal failure, and relieve critical ischemic symptoms.
Joint testing of overall and simple effects for the two-by-two factorial trial design
Authors: Leifer Eric S , Troendle James F , Kolecki Alexis , Follmann Dean A 
Published: August 2021

Background/aims: The two-by-two factorial design randomizes participants to receive treatment A alone, treatment B alone, both treatments A and B( AB), or neither treatment ( C). When the combined effect of A and B is less than the sum of the A and B effects, called a subadditive interaction, there can be low power to detect the A effect using an overall test, that is, factorial analysis, which compares the A and AB groups to the C and B groups. Such an interaction may have occurred in the Action to Control Cardiovascular Risk in Diabetes blood pressure trial (ACCORD BP) which simultaneously randomized participants to receive intensive or standard blood pressure, control and intensive or standard glycemic control. For the primary outcome of major cardiovascular event, the overall test for efficacy of intensive blood pressure control was nonsignificant. In such an instance, simple effect tests of A versus C and B versus C may be useful since they are not affected by a subadditive interaction, but they can have lower power since they use half the participants of the overall trial. We investigate multiple testing procedures which exploit the overall tests’ sample size advantage and the simple tests’ robustness to a potential interaction. Methods: In the time-to-event setting, we use the stratified and ordinary logrank statistics’ asymptotic means to calculate the power of the overall and simple tests under various scenarios. We consider the A and B research questions to be unrelated and allocate 0.05 significance level to each. For each question, we investigate three multiple testing procedures which allocate the type 1 error in different proportions for the overall and simple effects as well as the AB effect. The Equal Allocation 3 procedure allocates equal type 1 error to each of the three effects, the Proportional Allocation 2 procedure allocates 2/3 of the type 1 error to the overall A (respectively, B) effect and the remaining type 1 error to the AB effect, and the Equal Allocation 2 procedure allocates equal amounts to the simple A (respectively, B) and AB effects. These procedures are applied to ACCORD BP. Results: Across various scenarios, Equal Allocation 3 had robust power for detecting a true effect. For ACCORD BP, all three procedures would have detected a benefit of intensive glycemia control. Conclusions: When there is no interaction, Equal Allocation 3 has less power than a factorial analysis. However, Equal Allocation 3 often has greater power when there is an interaction. The R package factorial2x2 can be used to explore the power gain or loss for different scenarios.
Cost-effective clinical trial design: Application of a Bayesian sequential model to the ProFHER pragmatic trial
Authors: Forster Martin , Brealey Stephen , Chick Stephen , Keding Ada , Corbacho Belen , Alban Andres , Pertile Paolo , Rangan Amar 
Published: August 2021

Background/Aims: There is growing interest in the use of adaptive designs to improve the efficiency of clinical trials. We apply a Bayesian decision-theoretic model of a sequential experiment using cost and outcome data from the ProFHER pragmatic trial. We assess the model’s potential for delivering value-based research. Methods: Using parameter values estimated from the ProFHER pragmatic trial, including the costs of carrying out the trial, we establish when the trial could have stopped, had the model’s value-based stopping rule been used. We use a bootstrap analysis and simulation study to assess a range of operating characteristics, which we compare with a fixed sample size design which does not allow for early stopping. Results: We estimate that application of the model could have stopped the ProFHER trial early, reducing the sample size by about 14%, saving about 5% of the research budget and resulting in a technology recommendation which was the same as that of the trial. The bootstrap analysis suggests that the expected sample size would have been 38% lower, saving around 13% of the research budget, with a probability of 0.92 of making the same technology recommendation decision. It also shows a large degree of variability in the trial’s sample size. Conclusions: Benefits to trial cost stewardship may be achieved by monitoring trial data as they accumulate and using a stopping rule which balances the benefit of obtaining more information through continued recruitment with the cost of obtaining that information. We present recommendations for further research investigating the application of value-based sequential designs.
Does Diabetes Alter CSF Total Protein Levels? A Retrospective Cohort Study
Authors: Breiner Ari , Bourque* Pierre R. , Warman-Chardon Jodi , Brooks John , McCudden Christopher R. 
Published: August 2021

Background and Purpose: Elevation of total protein level in cerebrospinal fluid (CSF-TP) in diabetic patients is often disregarded by clinicians. However, existing studies on the topic have significant limitations, and therefore we aimed to explore the relationship between diabetes and CSF-TP in a large database of CSF samples. Methods: Retrospective review of all diagnostic lumbar punctures at the Ottawa Hospital between 1996-2016. Patients were excluded if they had elevated CSF cell counts, or a condition known to elevate CSF-TP. Multivariate linear regression modeling considered the effects of age, sex, and diabetes. Results: Among 6124 patients (746 with diabetes, 5378 without), mean CSF-TP did not differ significantly between groups (0.39 and 0.35 mmol/L, p = 0.2). When controlled for age and sex, there was no significant effect of diabetes on CSF-TP and no significant correlation between mean serum glucose and CSF-TP (R2 = 0.12). Conclusions: CSF-TP did not differ significantly between diabetic and non-diabetic groups, once the influence of age and sex was controlled. Elevated CSF-TP should be regarded as pathologic, even in the setting of diabetes.
Persistent lymphopenia after diagnosis of COVID-19 predicts acute respiratory distress syndrome: A retrospective cohort study
Authors: Zou Zhi-ye , Ren Di , Chen Rong-ling , Yu Bao-jun , Liu Yan , Huang Jia-jia , Yang Zhen-jia , Zhou Zhi-peng , Feng Yong-wen , Wu Ming 
Published: August 2021

Background Lymphopenia is a marker of immunosuppression after severe coronavirus disease-2019 (COVID-19) which is characterized by acute respiratory distress syndrome (ARDS). This study aimed to evaluate the relationships between persistent lymphopenia and ARDS. Methods A retrospective cohort study of 125 patients with COVID-19 admitted to government-designated treatment center between 14 January 2020, and 20 March 2020 was conducted. We recorded all complete blood cell counts during the day 0th, 3rd, and 7th following the diagnosis of COVID-19. Patients were grouped based on the depression of the lymphocyte cell count, their return, or their failure to normal. The primary outcome was the occurrence of ARDS, and secondary outcomes included developing vital organ dysfunction and hospital lengths of stay. Results 17.6% (22/125) patients developed ARDS. The lymphocyte counts with ARDS and non-ARDS were 0.94 × 109/L, 1.20 × 109/L at admission, respectively ( p = 0.02). On the 3rd and 7th day, the median of lymphocyte count in ARDS was significantly lower than that of non-ARDS. Multivariable logistic regression, which was adjusting for potentially confounding factors (including age, comorbidities, and APACHE II score), showed that persistent lymphopenia within the 7th day was independently associated with ARDS (OR, 3.94 [95% CI, 1.26–12.33, p = 0.018). Further, patients with persistent lymphopenia had longer hospital lengths of stay ( p < 0.001). Conclusion The results showed persistent lymphopenia predicted ARDS after COVID-19. Further studies are needed to investigate whether immunostimulation of lymphocytes within 1 week can reduce ARDS occurrence in patients with COVID-19.