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The ISSG-AO Complication Intervention Score, but Not Major/Minor Designation, is Correlated With Length of Stay Following Adult Spinal Deformity Surgery.
No full textStudy designRetrospective review.ObjectivesThe International Spine Study Group-AO (ISSG-AO) Adult Spinal Deformity (ASD) Complication Classification System was developed to improve classification, reporting, and study of complications among patients undergoing ASD surgery. The ISSG-AO system classifies interventions to address complications by level of invasiveness: grade zero (none); grade 1, mild (e.g., medication change); grade 2, moderate (e.g., ICU admission); grade 3, severe (e.g., reoperation related to surgery of interest). To evaluate the efficacy of the ISSG-AO ASD Complication Classification System, we aimed to compare correlations between postoperative length of stay (LOS) and complication severity as classified by the ISSG-AO ASD and traditional major/minor complication classification systems.MethodsPatients age ≥18 in a multicenter ASD database who sustained in-hospital complications were identified. Complications were classified with the major/minor and ISSG-AO systems and correlated with LOS using an ensemble-based machine learning algorithm (conditional random forest) and a generalized linear mixed model.Results490 patients at 19 sites were included. 64.9% of complications were major, and 35.1% were minor. By ISSG-AO classification, 20.4%, 66.1%, 6.7%, and 6.7% were grades 0-3, respectively. ISSG-AO complication grading demonstrated significant correlation with LOS, whereas major/minor complication classification demonstrated inverse correlation with LOS. In conditional random forest analysis, ISSG-AO classification had the greatest relative importance when assessing correlations across multiple variables with LOS.ConclusionsThe ISSG-AO system may help identify specific complications associated with prolonged LOS. Targeted interventions to avoid or reduce these complications may improve ASD surgical quality and resource utilization
Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.
No full textBackgroundThe kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer's disease and related dementias (ADRD).ObjectiveThe objective of this study was to determine the associations of plasma KP metabolites (kynurenine [KYN], kynurenic acid [KA], and tryptophan [TRP]) with a panel of plasma ADRD biomarkers (Aβ42/ β40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and cognitive performance in a subset of older adults drawn from the Duke Physical Performance Across the LifeSpan (PALS) study.MethodsThe Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. We used multivariate multiple regression to evaluate associations of the KYN/TRP and KA/KYN ratios with MoCA score and plasma ADRD biomarkers at baseline and over two years (n = 301; Age = 74.8±8.7).ResultsOver two years, an increasing KYN/TRP ratio was associated with increasing plasma concentrations of plasma p-Tau181 (β= 6.151; 95% CI [0.29, 12.01]; p = 0.040), GFAP (β= 11.12; 95% CI [1.73, 20.51]; p = 0.020), and NfL (β= 11.13; 95% CI [2.745, 19.52]; p = 0.009), but not MoCA score or the Aβ42/Aβ40 ratio. There were no significant associations of KA/KYN with MoCA score or plasma ADRD biomarkers.ConclusionOur findings provide evidence that greater concentrations of KP metabolites are associated longitudinally over two years with greater biomarker evidence of neurofibrillary tau pathology (pTau-181), neuroinflammation (GFAP), and neurodegeneration (NfL), suggesting that dysregulated KP metabolism may play a role in ADRD pathogenesis
Mapping Ecosystem Services for the Southeast United States: Conservation Priorities for Recreational Birding
No full textThis methods brief focuses on recreational birding, which is a popular activity in the United States. This analysis maps the location of recreational birding activity in the southeastern U.S. Regional priorities for conservation of birding areas are identified based on the total amount of birding activity and the proportion of birding activity that takes place on unprotected land. Spatial datasets for these priority areas and associated metrics are available on ScienceBase
Essays on International Tax and Firm Behavior
No full textThis dissertation examines unique tax incentives faced by multinational corporations (MNCs). Although nearly all businesses engage in profit-maximizing behavior, many do not have the ability to set up numerous subsidiaries in multiple jurisdictions. MNCs, on the other hand, often operate in a global context. The largest MNCs have hundreds of related subsidiaries that are distributed worldwide. Firms can utilize this geographic dispersion to take advantage of heterogeneity in tax laws across the jurisdictions in which they operate to minimize their tax burden. In the following chapters, I examine (1) common mechanisms used by some of the largest MNCs that facilitate the movement of income from high-tax jurisdictions to low-tax jurisdictions, (2) the extent to which researchers can trust different sources of data to measure the foreign activity of MNCs, and (3) how regulatory uncertainty concerning tax regimes can distort various aspects of firm behavior and financial reporting.The second chapter studies the adoption and use of specific forms of tax planning by US multinational corporations (MNCs). Along with my coauthors, I use IRS data to identify hybrid tax planning affiliates (HTPs) that allow MNCs to avoid corporate income taxes by targeting mismatches between US and Irish, Dutch, and Luxembourg tax law. By 2016, we find that more than 35\% of the foreign profits of US MNCs were linked to these HTPs. Difference-in-difference models reveal that, after adoption, corporations intensify behavior commonly linked to profit shifting, significantly increasing related-party loans, book values of foreign intangible assets, and profits held abroad relative to control MNCs. These changes coincide with stark reductions in foreign effective tax rates. MNCs that adopt HTPs also experience large increases in foreign tangible assets and in domestic R\&D, payroll, and investment relative to other types of multinationals. To separate selection and treatment effects, we develop and estimate a model that rationalizes the selection of MNCs into HTPs and the changes that we observe in their reported economic activity.The third chapter examines whether data that is commonly used to study MNCs can be trusted by researchers. Recent literature has noted the potential for significant measurement error, unique to MNCs, in tax and accounting data. I examine a key source of measurement error that can affect administrative tax data --- aggregation error. I link data from tax filings and public disclosures to quantify the extent to which commonly-used aggregation techniques may result in double counting of foreign earnings. A comparison of book and tax data reveals that aggregation error has been increasing over time. The matched sample also reveals large inconsistencies in the reporting of corporate income tax across firms' books and tax filings, particularly in extractive and financial industries. I introduce a simple correction for aggregation error and examine the extent to which it harmonizes measurement of foreign income and tax rates across firms' books and tax filings. Applying this correction yields a 30% reduction in the magnitude of foreign earnings as measured in tax data in 2016 and significantly reduces book-tax differences. Furthermore, this correction breaks the systematic relationship between book-tax differences and the size of multinationals' foreign affiliate networks. Unadjusted book-tax differences are increasing over time. After applying the correction, this is no longer true. Finally, I replicate estimates from prior literature that do not correct for aggregation error and discuss robustness.The fourth chapter examines how MNCs reacted to a regulatory loophole that emerged after the implementation of transfer pricing regulations passed in 1995. This loophole allowed US-based MNCs to shift labor costs from low-tax foreign affiliates to US parent companies by utilizing stock-based compensation. A 2005 tax court ruling created regulatory uncertainty around enforcement of the loophole, increasing the market value of firms that were in a position to take advantage of it. This period of regulatory uncertainty extended for over a decade. During this period, exposed firms increased their overall usage of stock-based compensation and its relative intensity as a share of their total labor costs. Exposed firms also increased their overall R&D activity and claimed domestic tax credits for larger portions of their overall R&D expense.</p
Inference for Dynamic Treatment Regimes using Overlap Sampling Splitting
No full textDynamic treatment regime is a sequence of decision rules mapping patient informa- tion at a specific time to a recommended treatment, with the goal of maximizing long-term clinical outcome. However, the inference for the estimator of optimal regime is challenging due to the nonregularity resulting from the maximize operator. In this paper, we review methods for estimating optimal regimes and discuss the problem of nonregularity. We propose a novel approach based on sample splitting to construct valid confidence sets for both the optimal regime and the maximized value function. Additionally, we conduct a hypothesis test to compare the optimal regime to the treatment regime used in usual clinical practice. We evaluate the proposed approach using simulated data from the Sequential Multiple Assignment Randomized Trials (SMART) design and assess the coverage of the confidence sets and the power of the hypothesis test.</p
Macular Vascular Microcirculation in Eyes With Open-angle Glaucoma Using Different Visual Field Severity Classification Systems.
No full textPrecisWe found significant differences in macular vascular microcirculation between normal and glaucomatous eyes using optical coherence tomography angiography (OCTA). Macular vascular microcirculation changes also showed significant correlations with visual field (VF) severity classification systems.PurposeTo correlate VF severity defined by different classification systems and macular vascular microcirculation in eyes with glaucoma using OCTA.Patients and methodsTwenty normal and 58 open-angle glaucoma (OAG) eyes were scanned using a swept-source OCTA (Plex Elite 9000) and macular vascular microcirculation was measured by calculating the overall blood flux index (BFI) and vessel area density (VAD) over the entire 6×6 mm area excluding the big retinal vessels. Glaucomatous eyes were staged into severity groups based on 4 VF severity classifications: Hodapp-Parrish-Anderson scale, Glaucoma Severity Staging system, ICD-10 glaucoma staging definitions, and VF mean deviation. Central 10-degree VF mean sensitivity (CMS) was calculated based on 24-2 VF. One-way analysis of variance was used to analyze the differences and correlation between macular vascular microcirculation and other clinical parameters.ResultsGlaucomatous eyes had significantly lower ganglion cell and inner plexiform layer BFI and VAD (PConclusionMacular vascular microcirculation metrics detected by OCTA correlate with disease severity in glaucomatous eyes. VF CMS, calculated from only 12 tested central 10-degree points, correlated best with macular OCTA
Treatment of gastrointestinal tumor (GIST) of the rectum requiring abdominoperineal resection following neoadjuvant imatinib: a cost-effectiveness analysis.
No full textBackgroundNeoadjuvant imatinib for gastrointestinal stromal tumors (GIST) of the rectum can reduce, but may not eliminate, risk of surgical morbidity from permanent bowel diversion. We sought to evaluate the cost-effectiveness of alternative strategies in rectal GIST patients requiring abdominoperineal resection following neoadjuvant imatinib.MethodsWe developed a Markov model using a healthcare payers' perspective to estimate costs in 2017 Singapore dollars (SGD) and quality adjusted life years (QALYs) for upfront abdominoperineal resection (UAPR) versus continued imatinib until progression (CIUP) following 1 year of neoadjuvant imatinib. Transition probabilities and utilities were obtained from published data, and costs were estimated using data from the National Cancer Centre Singapore. Deterministic and probabilistic sensitivity analyses were conducted to probe model uncertainty. Incremental cost-effectiveness ratio below SGD 50,000 per QALY gained was considered cost-effective.ResultsIn the base case, UAPR dominates CIUP being both more effective (8.66 QALYS vs 5.43 QALYs) and less expensive (SGD 312,627 vs SGD 339,011). These estimates were most sensitive to 2 variables, utility of abdominoperineal resection and annual recurrence probability post-abdominoperineal resection. However, simultaneously varying the values of these variables to maximally favor CIUP did not render it the more cost effective strategy at willingness to pay (WTP) of SGD 50,000. In probabilistic sensitivity analysis, UAPR had probability of being cost-effective compared with CIUP greater than 95%, reaching 100% at WTP SGD 10,000.ConclusionUAPR is more effective and less costly than CIUP for patients with rectal GIST requiring abdominoperineal resection following neoadjuvant imatinib, and is the strategy of choice in this setting
Completion of two-parameter period maps by nilpotent orbits
No full textWe show that every two-parameter period map admits a Kato--Nakayama--Usui
completion to a morphism of log manifolds
Effects of acute estradiol and progesterone on perimenstrual exacerbation of suicidal ideation and related symptoms: a crossover randomized controlled trial.
No full textFemale suicide attempts peak peri-menstrually-around the onset of menses-when the ovarian steroids estradiol (E2) and progesterone (P4) fall rapidly. Given preclinical evidence that withdrawal from either E2 or P4 can provoke behaviors consistent with elevated suicide risk, we hypothesized that withdrawal from one or both of these steroids contributes to perimenstrual exacerbation of suicidal ideation (SI) and related symptoms. In a randomized, controlled, double-blind crossover experiment (NCT03720847), a transdiagnostic sample of naturally cycling, medically healthy psychiatric outpatients reporting past-month SI completed two conditions during two different 14-day experimental intervals (days 7-20 where the luteinizing hormone surge = day 0), separated by a monthlong washout cycle. In the E2 and P4 (EP) condition, participants received transdermal E2 (0.1 mg/day) plus oral micronized P4 (200 mg/day as 100 mg twice daily) to buffer perimenstrual steroid withdrawal. A matched placebo (PBO) condition allowed natural perimenstrual steroid withdrawal. Participants reported daily SI and planning (primary outcomes) and indices of depression (low mood, hopelessness), threat sensitivity (anxiety, perceived stress), executive functioning (difficulty concentrating, impulsivity), and social cognitive bias (rejection sensitivity, perceived burdensomeness). In baseline cycles, no participant met prospective criteria for DSM-5 premenstrual dysphoric disorder, but 59% met all criteria except full follicular symptom remission, and 93% showed the highest SI in the perimenstrual phase. Of 29 randomized, 28 were analyzed (14 EP-PBO, 14 PBO-EP). Experimental administration of E2 and P4 (relative to PBO) reduced perimenstrual exacerbation of SI, suicide planning, depression, hopelessness, perceived stress, rejection sensitivity, and perceived burdensomeness, particularly in the perimenstrual (natural E2 and P4 withdrawal) days. Further, delayed withdrawal from experimental E2 and P4 (but not PBO) recapitulated SI, hopelessness, and rejection sensitivity. Acute perimenstrual withdrawal from ovarian steroids may play a causal role in perimenstrual worsening of depression and SI