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Background: The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long‐term outcome of kidney transplantation. The CYP3A single‐nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. Methods: A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12 months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. Results: The group with high IPV had a significantly higher rate of de novo donor‐specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p =.003). The high IPV group also had a higher incidence of T‐cell‐mediated rejection (TCMR; p <.001). The high IPV had no significant influence on Epstein–Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p =.003). Overall, the graft survival rate was inferior in the high IPV group (p <.001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR‐free survival rate (p <.001). Conclusion: The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac. [ABSTRACT FROM AUTHOR]

This article examines how multiple ownership changes unfold in international equity joint venture (IEJV) evolution and how such repeated changes impact short-term performance and long-term survival. By theorizing a new [...]

Subsidiaries' decision to expand or contract during an economic crisis is analyzed in relation to across-country operational flexibility and within-country growth. Results show that economic crises may be damaging to subsidiaries that have greater within-country orientations. Subsidiary expansion or contraction is also not solely determined by network characteristics.

Background and Objectives: The COVID-19 pandemic has brought serious changes in healthcare systems worldwide, some of which have affected patients who need emergency surgery. Acute appendicitis is the most common surgical disease requiring emergency surgery. This study was performed to determine how the COVID-19 pandemic has changed the treatment of patients with acute appendicitis in South Korea. Materials and Methods: We retrospectively reviewed a medical database that included patients who underwent surgery for acute appendicitis in our hospital from January 2019 to May 2021. We classified the patients into two groups according to whether they were treated before or after the COVID pandemic and 10 March 2020 was used as the cutoff date, which is when the World Health Organization declared the COVID pandemic. Results: A total of 444 patients were included in the "Pre-COVID-19" group and 393 patients were included in the "COVID-19" group. In the "COVID-19" group, the proportion of patients with severe morbidity was significantly lower. The time that the patients spent in the emergency room before surgery was significantly longer in the "COVID-19" group (519.11 ± 486.57 min vs. 705.27 ± 512.59 min; p-value < 0.001). There was no difference observed in the severity of appendicitis or in the extent of surgery between the two groups. Conclusions: During the COVID-19 pandemic, a statistically significant time delay (186.16 min) was needed to confirm COVID-19 infection status. However, there was no clinical difference in the severity of appendicitis or in the extent of surgery. To ensure the safety of patients and medical staff, a COVID-19 PCR test should be performed. [ABSTRACT FROM AUTHOR]

A total of 361 patients with acute or recent HIV-1 infection are prospectively studied over a decade (1995-2004) with respect to HIV-1 genotypes and longitudinal T-cell subsets and HIV-1 RNA levels to describe the changing pattern of transmitted drug-resistant HIV-1 in a well-defined cohort in New York City. Data provided have important implications for selection of empiric first- line regimens for treatment of acutely infected antiretroviral- naive individuals and reinforce the need or baseline resistance testing in acute and early HIV- 1 infection.

This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6–25.5%] and 16.0% [11.5–23.5%], respectively, P =.602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = − 0.067, P =.527; dosing adherence, ρ = − 0.098, P =.352; timing adherence, ρ = − 0.113, P =.284). Similarly, adherence measured by self-report did not significantly affect the IPV (P =.452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV. [ABSTRACT FROM AUTHOR]

With small kidneys, EBKTs could provide sufficient renal mass but could lead to inefficient use of resources, while SKTs could result in insufficient function due to small renal mass. We aimed to compare the outcomes of EBKT and SKT from small donors weighing ≤15 kg to pediatric recipients. We retrospectively reviewed all pediatric patients who met the inclusion criteria between January 1, 1984, and April 30, 2019, at a single institution. Of a total of 23 patients, 12 received EBKT and 11 received SKT. The median age of donors, weight of donors, and weight of recipients were comparable between the two groups. The median age of recipients and median weight of allografts were greater in the EBKT group than in the SKT group. The median follow‐up was 53.9 months. There was no significant difference in eGFR, protein creatinine ratios at 1‐year follow‐up, and overall graft survival. The size of the kidney increased by approximately 13%‐43% in the EBKT group and 40%‐60% in the SKT group. This study demonstrated that kidneys from small donors weighing 5‐15 kg could be split in pediatric recipients without compromising the outcome. [ABSTRACT FROM AUTHOR]

19F magnetic resonance (MR) based detection coupled with well‐designed inorganic systems shows promise in biological investigations. Two proof‐of‐concept inorganic probes that exploit a novel mechanism for 19F MR sensing based on converting from low‐spin (S=0) to high‐spin (S=1) Ni2+ are reported. Activation of diamagnetic NiL1 and NiL2 by light or β‐galactosidase, respectively, converts them into paramagnetic NiL0, which displays a single 19F NMR peak shifted by >35 ppm with accelerated relaxation rates. This spin‐state switch is effective for sensing light or enzyme expression in live cells using 19F MR spectroscopy and imaging that differentiate signals based on chemical shift and relaxation times. This general inorganic scaffold has potential for developing agents that can sense analytes ranging from ions to enzymes, opening up diverse possibilities for 19F MR based biosensing. [ABSTRACT FROM AUTHOR]

Fine‐needle aspiration (FNA) for serial hepatic sampling may be an efficient and less invasive alternative to core needle biopsy (CNB), the current standard for liver tissue sampling. In this randomized, open‐label trial in 31 participants with hepatitis C virus genotype 1 infection (NCT01678131/Merck protocol PN048), we evaluated the feasibility of using FNA to obtain human liver tissue samples appropriate for measuring hepatic pharmacokinetics (PK), using vaniprevir as a tool compound. The primary end point was successful retrieval of liver tissue specimens with measurable vaniprevir concentrations at two of three specified FNA time points. Twenty‐nine patients met the primary end point and, therefore, were included in the PK analyses. Hepatic vaniprevir concentrations obtained with FNA were consistent with known vaniprevir PK properties. The shape of liver FNA and CNB concentration‐time profiles were comparable. In conclusion, FNA may be effective for serial tissue sampling to assess hepatic drug exposure in patients with liver disease. [ABSTRACT FROM AUTHOR]

The article identifies three institutional forms adopted by foreign subsidiaries in post-crisis environments: majority joint-ventures, wholly-owned subsidiaries, or trading operations. It is therefore posited that foreign subsidiaries with these capabilities are better situated to survive crises than others; the 1997 financial crisis in Asia is used as an illustration.

There is much debate over when conduct qualifies as protected free speech. While the First Amendment extends past the. spoken or written word to certain expressive acts, such as flag burning, there is no clear way to determine when conduct is sufficiently expressive to deserve protection. The Supreme Court, has inconsistently applied two expressive conduct tests, which has further led to conflicting decisions among lower courts. As the. Court prepares to hear an expressive conduct case involving the baking of a cake, it should establish a consistent standard to better protect free speech by applying both tests. [ABSTRACT FROM AUTHOR]

To evaluate imaging and histopathologic differences between screen-detected benign and malignant upgraded lesions initially assessed as BI- RADS 3 at diagnostic evaluation. An IRB approved retrospective review of the mammography data base from January 1, 2004 to December 31, 2008 identified 1,188 (1.07%) of 110,776 screening examinations assessed as BI- RADS 3 following diagnostic evaluation at our academic center (staffed by breast specialists) or our outpatient center (staffed by general radiologists), 1,017 with at least 24 months follow-up or biopsy. Sixty (5.9%) BI- RADS 3 lesions were upgraded to BI- RADS 4 or 5 during imaging surveillance (study population). Prospective reports, patient demographics, and clinical outcomes were abstracted from the longitudinal medical record. Mean patient age was 54.1 years (range 35-85). Lesions consisted of 7 masses, 12 focal asymmetries and 41 calcifications. Fifteen (25%) of 60 lesions upgraded from initial BI- RADS 3 assessment were malignant (1.47% of total; 15/1,017 BI- RADS 3 studies). Malignancy rates by upgraded lesion type showed no significant difference: Thirty-three (73.3%) of 45 benign upgraded lesions were calcifications compared to 8 (53.3%) of 15 malignant upgraded lesions (p = 0.202). Twelve (26.7%) of 45 benign upgraded lesions were masses or focal asymmetries, compared to 7 (46.7%) of 15 upgraded malignant lesions (p = 0.202). Six (85.7%) of 7 malignant upgraded masses/focal asymmetries had no US correlate at initial BI- RADS 3 assessment compared to 7 (58.3%) of 12 benign upgraded masses/focal asymmetries (p = 0.33). Breast-imaging specialists interpreted 21 studies, 3 (14.3%) malignant; general radiologists interpreted 39 studies, 12 (30.8%) malignant (p = 0.218). There was no significant difference in malignancy rate among different types of upgraded mammographic lesions, nor depending on subspecialty interpretation versus nonsubspecialist interpretation. Although calcifications made up a majority of upgraded lesions, most were benign, suggesting that decreased surveillance of calcifications may be appropriate. [ABSTRACT FROM AUTHOR]