Increased risk of chronic otitis media in chronic rhinosinusitis patients: a longitudinal follow-up study using a national health screening cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) and chronic otitis media (COM) share pathophysiological mechanisms such as bacterial infection, biofilm, and persistence of the obstruction state of ventilation routes. However, only a few studies have investigated the relationship between these two diseases nationwide and in the general population. The purpose of this study was to determine whether the incidence of COM in patients with CRS differed from that of a matched control from the national health screening cohort. METHODS: Data from the Korean Health Insurance Review and Assessment Service-National Patient Samples were collected from 2002 to 2015. Participants who were treated ≥ ≥ ≥2 times and underwent head and neck computed tomography evaluation were selected. A 1:4 matched CRS group (n=8,057) and a control group (n=32,228) were selected. The control group included participants who were never treated with the ICD-10 code J32 from 2002 to 2015. The CRS group included CRS patients with/without nasal polyps. RESULTS: The incidence of COM was significantly higher in the CRS group than in the control group. In a subgroup analysis, the incidence of COM in all age groups and in men and women was significantly higher in the CRS group than in the control group. More, CRS increased the risk of COM. CONCLUSIONS: A significant association was observed between CRS and COM. This indicates that CRS patients have a high risk of developing COM.

ALK-positive anaplastic large cell lymphoma with a monomorphic small-cell pattern masquerading as inflammatory gastric lesions.

INTRODUCTION: Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with a non-common pattern can be diagnostic challenging. Pathologists can be unavoidably and unintentionally blind to non-descript tumor cells in a lymphohistiocytic- (LH) or small-cell (SC)-pattern. We report a case of primary systemic ALK+ ALCL with a SC pattern that presented as secondary gastric lesions with a mixed LH and SC pattern that was masqueraded as inflammatory lesions. CASE REPORT: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered. DISCUSSION: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.

Base of tongue cancer-is it tongue cancer located at the base of the tongue, or is it a type of lingual tonsil cancer? The perspective from a genomic analysis.

The aim of this study was to determine whether base of tongue (BOT) cancer is tongue cancer located at the base of the tongue or lingual tonsil cancer originating from tonsil tissue. This was a retrospective study using data from The Cancer Genome Atlas (TCGA). The genomic patterns of three primary cancers (BOT, oral tongue, and tonsil) were compared to determine their similarities and differences. Gene expression data (n=193; 26 BOT, 125 oral tongue, and 42 tonsil cases), copy number alteration data (n=142; 19 BOT, 96 oral tongue, and 27 tonsil cases), and somatic mutation data (n=187; 25 BOT, 122 oral tongue, and 40 tonsil cases) were analyzed using the t-test, heatmap analysis, and OncoPrint, respectively. Clinical information for the three tumour groups was included in the analyses. When using multiplatform analysis, BOT cancer showed nearly the same genomic pattern as tonsil cancer, but not oral tongue cancer. The χ2 test and survival analysis revealed that BOT cancer had the same clinical and survival patterns as tonsil cancer. In conclusion, BOT cancer showed a genomic pattern similar to that of tonsil cancer, but different to that of oral tongue cancer. Further prospective studies are warranted before the results of this study can be applied in a clinical setting.

Characterization of the reference wave in a compact digital holographic camera.

A hologram is a recording of the interference between an unknown object wave and a coherent reference wave. Providing the object and reference waves are sufficiently separated in some region of space and the reference beam is known, a high-fidelity reconstruction of the object wave is possible. In traditional optical holography, high-quality reconstruction is achieved by careful reillumination of the holographic plate with the exact same reference wave that was used at the recording stage. To reconstruct high-quality digital holograms the exact parameters of the reference wave must be known mathematically. This paper discusses a technique that obtains the mathematical parameters that characterize a strongly divergent reference wave that originates from a fiber source in a new compact digital holographic camera. This is a lensless design that is similar in principle to a Fourier hologram, but because of the large numerical aperture, the usual paraxial approximations cannot be applied and the Fourier relationship is inexact. To characterize the reference wave, recordings of quasi-planar object waves are made at various angles of incidence using a Dammann grating. An optimization process is then used to find the reference wave that reconstructs a stigmatic image of the object wave regardless of the angle of incidence.

Outbreak of Burkholderia cepacia pseudobacteraemia caused by intrinsically contaminated commercial 0.5% chlorhexidine solution in neonatal intensive care units.

BACKGROUND: Burkholderia cepacia is intrinsically resistant to certain antiseptics. The authors noted a sudden increase in the frequency of isolation of B. cepacia from blood cultures in a neonatal intensive care unit (NICU) of a university-affiliated hospital. AIM: To identify the source and intervene in the ongoing infections. METHODS: The cases were defined as patients with positive blood cultures for B. cepacia in an NICU between November 2014 and January 2015. Medical records were reviewed and NICU healthcare workers were interviewed. Samples of suspected antiseptics, blood culture bottles, cotton balls, gauze and a needle used in the NICU were analysed microbiologically. FINDINGS: During the outbreak period, B. cepacia was identified in 25 blood cultures obtained from 21 patients. The clinical features of the patients were suggestive of pseudobacteraemia. Regarding environmental samples, B. cepacia was cultured from 0.5% chlorhexidine gluconate (CHG) solution products that had been used as a skin antiseptic during blood drawing in the NICU. The clinical B. cepacia isolate and two strains obtained from 0.5% CHG exhibited identical pulsed-field gel electrophoresis patterns. After the CHG products were withdrawn, the outbreak was resolved. CONCLUSIONS: The pseudobacteraemia cases were caused by contaminated 0.5% CHG produced by a single manufacturer. Stricter government regulation is needed to prevent contamination of disinfectants during manufacturing. In addition, microbial contamination of antiseptics and disinfectants should be suspected when a B. cepacia outbreak occurs in hospitalized patients.

The Effect of Intraoperative Nefopam Administration on Acute Postoperative Pain and Chronic Discomfort After Robotic or Endoscopic Assisted Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Acute postoperative pain and chronic discomfort are reported after robotic or endoscopic thyroidectomy. The purpose of this prospective, randomized, and double-blinded clinical trial was to investigate whether intraoperative infusion of nefopam decreases acute postoperative pain and chronic discomfort following either a robotic or endoscopic thyroidectomy via the bilateral axillo-breast approach (BABA). METHODS: Patients were randomized into two groups: The control group (n = 29) or the nefopam group (n = 29). Patients in each group were infused with the same volume of saline or nefopam (0.2 mg/kg bolus, 120 µg/kg/h continuous infusion) during surgery. Acute postoperative pain, the need for rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Chronic pain and discomfort was recorded at 3 months after surgery. RESULTS: Patients in the nefopam group reported lower pain scores in the neck, as well as the axilla and anterior chest areas at 1, 6, 24, and 48 h postoperatively, when compared with the control group (P < 0.05 at each time points). Rescue analgesics were required less in the nefopam group than in the control group (1.4 [1] vs. 2.3 [1.5]; P = 0.001). The degree of chronic pain and discomfort were relatively lower in the nefopam group (P < 0.05). CONCLUSION: We report that intravenous nefopam infusion during surgery decreased acute postoperative pain and the need for rescue analgesics, as well as chronic discomfort, following BABA robotic or endoscopic thyroidectomy without adverse events.

Normal 'heart' in Parkinson's disease: is this a distinct clinical phenotype?

BACKGROUND AND PURPOSE: Reduction of metaiodobenzylguanidine (MIBG) uptake has been observed in almost all patients with Parkinson's disease (PD), associated with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG uptake have been reported to have milder disease and preserved cognition compared with those with lower MIBG. The aim of this study was to investigate whether non-motor manifestations of PD differ between patients with normal and abnormal myocardial MIBG uptake. METHODS: Among 160 de-novo cases of PD, 44 had normal MIBG uptake. Twelve candidate non-motor features were evaluated using questionnaires and laboratory tests. RESULTS: Patients with decreased MIBG uptake had more constipation, RBD, cognitive impairment, hyposmia and orthostatic hypotension than did those with normal MIBG uptake. On linear regression analysis, orthostatic hypotension, olfactory function and probable RBD were significantly associated with MIBG uptake in PD. The principal component analysis showed that the group with normal MIBG was not associated with non-motor impairments. CONCLUSIONS: These results suggest that patients with PD with normal MIBG scans have a relatively low disease burden compared with those with abnormal MIBG. Fewer synuclein pathologies in the myocardia and sympathetic ganglia in PD with preserved MIBG uptake might be associated with lower threshold patterns of Braak synuclein pathology for non-motor manifestations compared with PD with decreased MIBG.

High-quality cell block preparation from scraping of conventional cytology slide: a technical report on a modified cytoscrape cell block technique.

BACKGROUND: Immunocytochemistry (ICC) on formalin-fixed paraffin embedded cell blocks is an ancillary tool commonly recruited for differential diagnoses of fine needle aspiration cytology (FNAC) samples. However, the quality of conventional cell blocks in terms of adequate cellularity and evenness of distribution of cytologic material is not always satisfactory for ICC. We introduce a modified agarose-based cytoscrape cell block (CCB) technique that can be effectively used for the preparation of cell blocks from scrapings of conventional FNAC slides. METHODS: A decoverslipped FNAC slide was mounted with a small amount of water. The cytological material was scraped off the slide into a tissue mold by scraping with a cell scraper. The cytoscrape material was pelleted by centrifugation and pre-embedded in ultra-low gelling temperature agarose and then re-embedded in conventional agarose. The final agarose gel disk was processed and embedded in paraffin. RESULTS: The quality of the ICC on the CCB sections was identical to that of the immunohistochemical stains on histological sections. By scrapping and harvesting the entirety of the cytological material off the cytology slide into a compact agarose cell button, we could avoid the risk of losing diagnostic material during the CCB preparation. CONCLUSION: This modified CCB technique enables concentration and focusing of minute material while maintaining the entire amount of the cytoscrape material on the viewing spot of the CCB sections. We believe this technique can be effectively used to improve the level of confidence in diagnosis of FNAC especially when the FNAC slides are the only sample available.

Role of fibroblast-derived factors in the pathogenesis of melasma.

BACKGROUND: The hyperactive melanocytes present in melasma skin are confined to the epidermis, but epidermal ablation to treat melasma pigmentation may lead to disease recurrence and aggravation. Melanocyte function is regulated by interactions between melanocytes and neighbouring cells such as keratinocytes and fibroblasts. Because melasma skin usually shows dermal changes after exposure to sunlight, we hypothesized that sun-damaged fibroblasts might play a crucial role in the pathogenesis of melasma. AIM: In this study, the melanogenic role of primary cultured fibroblasts from human melasma skin was investigated. METHODS: We explored whether primary cultured fibroblasts from melasma tissue have a melanogenic function on cultured human epidermal melanocytes and artificial skin. The cytokine profile derived from fibroblasts and their effect on the pigmented epidermal equivalents were investigated. RESULTS: Fibroblasts from the melasma lesion and perilesional skin increased melanogenesis in cultured human epidermal melanocytes and in artificial skin. Fibroblasts from the melasma lesion and perilesional skin secreted more nerve growth factor (NGF)-ß than those in normal buttock skin, and also increased melanogenesis and the expression level of NGF-ß in cultured human epidermal melanocytes and artificial skin. CONCLUSIONS: These results suggest that fibroblasts may play a role in melanogenesis and the pathogenesis of melasma.

Clinical and angiographic features and stroke types in adult moyamoya disease.

BACKGROUND AND PURPOSE: This study was conducted to elucidate the association between clinical and angiographic characteristics and stroke types in adult Moyamoya disease that has been rarely evaluated. MATERIALS AND METHODS: We analyzed the clinical and radiologic data obtained from a retrospective adult Moyamoya disease cohort with acute strokes, which were classified into 7 categories: large-artery infarct, hemodynamic infarct, perforator infarct, deep intracerebral hemorrhage, lobar intracerebral hemorrhage, intraventricular hemorrhage, and SAH. With conventional angiography, which was performed in the hemispheres with acute strokes, the Suzuki angiographic stage, intracranial aneurysm, major artery occlusion, and collateral vessel development were confirmed within 1 month of stroke onset. RESULTS: This study included 79 patients with acute ischemic stroke and 96 patients with acute hemorrhagic stroke. The angiographic stage had a strong tendency to be more advanced in the hemorrhagic than the ischemic patients (P = .061). Intracranial aneurysms were more frequently found in the hemorrhagic than ischemic or control hemispheres (P = .002). Occlusions of the anterior cerebral artery and development of fetal-type posterior cerebral artery were more frequently observed in the hemorrhagic than the ischemic (P = .001 and .01, respectively) or control hemispheres (P = .011 and .013, respectively). MCA occlusion (P = .039) and collateral flow development, including the ethmoidal Moyamoya vessels (P = .036) and transdural anastomosis of the external carotid artery (P = .022), occurred more often in the hemorrhagic than the ischemic hemispheres. Anterior cerebral artery occlusion occurred more frequently in patients with deep intracerebral hemorrhage or intraventricular hemorrhage than with lobar intracerebral hemorrhage (P = .009). CONCLUSIONS: In adult Moyamoya disease, major artery occlusion and collateral compensation occurred more often in the hemorrhagic than in the ischemic hemispheres. Thus, anterior cerebral artery occlusion with or without MCA occlusion and intracranial aneurysms may be the main contributing factors to hemorrhagic stroke in adult patients with Moyamoya disease.

The correlation between expression of synuclein-gamma, glucose transporter-1, and survival outcomes in endometrioid endometrial carcinoma.

PURPOSE: To evaluate the correlation between immunohistochemical expression of synuclein-gamma, glucose transporter-1, and survival outcomes in endometrioid endometrial carcinoma. MATERIALS AND METHODS: A tissue microarray was constructed using formalinfixed, paraffin-embedded tissue that included 23 early and 18 advanced cases. The intensity and area of the immunohistochemical reactions were evaluated using the semi-quantitative scoring system. RESULTS: Synuclein-y expression was higher in the advanced stage, although it was not statistically significant (p = 0.51). Glucose transporter-1 was overexpressed in the advanced stage (p = 0.01). Synuclein-gamma (score = 0 vs > 0) and glucose transporter-1 (score < or = 7 vs > 7) did not show any differences in overall survival (p = 0.54, p = 0.48) and disease-free survival (p = 0.61, p = 0.14). CONCLUSION: In this study the expression of synuclein-y and glucose transporter-1 were not considered to be a prognostic factor and were not related with survival outcomes in endometrioid endometrial carcinoma.

Regional cerebellar volume reflects static balance in elite female short-track speed skaters.

The cerebellum plays a critical role in balance control. Particularly, elite short-track speed skaters require fine postural control to keep a postural balance during high velocity movement across smooth ice. We investigated whether skating proficiency and gender have an effect on the volume of cerebellar subregions and static balance, using 3-dimensional magnetic resonance imaging volumetry. In addition, we further analyzed which subregions of the cerebellum correlates with the balance. The volumes of cerebellar subregions and static balance index were compared among 12 male and 11 female elite short-track speed skaters, and 11 male and 14 female healthy matched subjects. We found significant main effects of skating proficiency and gender on the volume of vermian lobule VI-VII (declive, folium, and tuber), short-track speed skaters having greater volume than control and women revealing greater volume than men. Especially, in female athletic group, the volume of vermian lobule VI-VII significantly correlates with left static balance. In addition, men showed larger skating proficiency-related differences than women in the performance of static balance. The correlation between the volume of this region and static balance in female short-track speed skaters suggests that this region would plays a critical role in balance.

Kimura disease: CT and MR imaging findings.

BACKGROUND AND PURPOSE: KD is a rare chronic inflammatory disorder of unknown etiology. The purpose of this study was to evaluate the CT and MR imaging findings of KD in the head and neck. MATERIALS AND METHODS: We retrospectively reviewed the CT (n = 21) and MR (n = 9) images obtained in 28 patients (24 males and 4 females; mean age, 32 years; age range, 10-62 years) with histologically proved KD in the head and neck. RESULTS: In these 28 patients, CT and MR images demonstrated a total of 52 non-nodal lesions, 1-8 cm in greatest diameter, in the head and neck. The lesions were unilateral in 11 patients and bilateral in 17 patients. Eleven patients had a solitary lesion, and 17 patients had 2-4 lesions. The parotid and/or periparotid area was the most frequent location, with 36 lesions in 23 patients. The margin of the lesions was well-defined in 1 and ill-defined in 51 cases. Compared with the adjacent muscle, the MR signal intensity of all lesions was iso- to slightly hyperintense on T1-weighted images and hyperintense on T2-weighted images. Most of the lesions demonstrated mild or moderate enhancement on postcontrast CT scans and moderate or marked enhancement on postcontrast MR images. MR images also showed tubular signal-intensity voids in 7 of 13 lesions. Associated lymphadenopathy was demonstrated in 23 patients, usually bilaterally. CONCLUSIONS: Multiple ill-defined enhancing masses within and around the parotid gland with associated regional lymphadenopathy are characteristic CT and MR imaging findings of KD in the head and neck.

Hematological Responses, Survival, and Respiratory Exchange in the Olive Flounder, Paralichthys olivaceus, during Starvation.

A 12-wk experiment was conducted to examine the hematological changes, survival, and respiratory exchange in the olive flounder, Paralichthys olivaceus, during starvation. The growth, survival and respiratory exchange rates of the starved group were lower than those of the fed group during the experiment. Blood analysis, including hematocrit, hemoglobin, red blood cells, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscular volume, did not differ significantly (p>0.05) between the fed and starved groups at the end of the experiment. There were no significant differences in plasma cortisol, glucose, Na(+), Cl(-), K(+), or aspartate aminotransferase between the fed and starved groups (p>0.05). Alanine aminotransferase levels were higher in the starved group than in the fed group, whereas plasma osmolality was lower in the starved group than in the fed group. It was shown that starved fish had various problems after four weeks, which did not occur in the fed group. Long-term starvation is infrequent in aquaculture farms. However, starvation studies of this kind are very useful for a basic understanding of how physiological changes affect fish health, life expectancy, and growth.

A case of ovarian endometrioid adenocarcinoma with yolk sac tumor in a 35-year-old woman.

Ovarian yolk sac tumor (YST) is a malignant ovarian neoplasm differentiated from primordial germ cells that occur in young age, while endometrioid carcinoma (ECA) is a müllerian epithelial tumor that usually occurs in older patients. The coexistence of an ovarian ECA and YST component is very rare. Only 12 cases have been reported until now according to a Medline search of the English literatures. We present a case of a simultaneous ECA and a YST component in a 35-year-old woman. Exploratory laparotomy was performed. The parts of both ovaries that showed an endometrioid-like glandular pattern were positive for cytokeratin 7 and negative for AFP, but the YST component was negative for cytokeratin 7 and positive for AFP. After completion of four courses of BEP chemotherapy, two courses of taxane and carboplatin chemotherapy were added. The patient failed to respond and succumbed to the disease after 12 months of follow-up.

Fitz-Hugh-Curtis Syndrome: single centre experiences.

This study was conducted to report 10 cases of Fitz-Hugh-Curtis Syndrome (FHCS) diagnosed with CT and 101 cases of FHCS-like lesion that suggested perihepatitis during laparoscopic surgery. We reviewed retrospectively the images of 3,674 laparoscopies for obstetrical and gynaecological diseases and analysed 10 cases of FHCS diagnosed by clinical patterns and CT. All the 10 cases showed liver capsular enhancement on CT. Among the 3,674 laparoscopies, we found 101 cases (2.7%) with FHCS like lesion. Among them, 23 cases were during laparoscopic procedure for endometriosis, 16 for gynaecological malignant tumours, 16 for benign adnexal diseases excluding endometriosis, 13 for uterine leiomyoma, 7 for pelvic inflammatory disease, 2 had peritoneal tuberculosis and 21 for other gynaecological diseases. Further consideration should be given for the causes of FHCS other than N. gonorrhoeae and C. trachomatis. Because FHCS may represent various clinical phases, other considerations and clinical classifications are necessary for treatment.

Electrical properties and surface morphology of SiO(x)-Pt nano-composite thin films.

Recently, ceramic metals (cermets) have been widely investigated for use as embedded resistor materials. In this study, SiO-Pt nano-composite cermets were developed to control the resitivity and temperature coefficients of resistance (TCR) of embedded thin film resistors. The SiO-Pt nano-composite was prepared by the co-sputtering of a SiO(x) target and Pt chips onto glass. The experiments were conducted Pt concentrations in order to find the optimum conditions to achieve a high resistivity and low TCR. The electrical properties of the sputtered SiO-Pt thin films were investigated by probe station and their crystal structures were observed by X-Ray Diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS). The surface morphology was observed by field emission scanning electron microscopy (FE-SEM) and high resolution transmission electron microscopy (HR-TEM). It was found that the Pt particles with a size of 3 approximately 5 nm were uniformly dispersed in the SiO matrix. A stable resistivity value of 26000 approximately 57000 microomega x cm and TCR value of -197 approximately -322 ppm/K were obtained at 3.5 approximately 3.7 at.% Pt.

Short-term influence of phosphate and nitrate on heavy metal accumulation by red alga Acrosorium uncinatum.

Heavy metal accumulation (Cu, Zn, Ni, and Pb) in common marine macroalga, Acrosorium uncinatum under nutrient (phosphate and nitrate) enriched (experiment 1) and starved (experiment 2) conditions over a short exposure period (12 h) were examined in this study. Control was maintained in seawater contained nutrient solution without addition of metals and in seawater alone for experiment 1 and 2, respectively. Among the four metals studied, the accumulation of Zn, Ni, and Pb was considerably lower than Cu. The accumulation factor for all metals varies greatly in different nutrient concentrations, but it increases as the exposure of metal concentration decreases in both the experiments. The results of the present findings established that this macroalga is an accumulator of metals Cu, Zn, Ni, and Pb and have the potential to accumulate these metals even in a short time exposure period (12 h). Even though metal accumulation by A. uncinatum largely depends on the available concentration in the medium, nutrients like phosphate and nitrate can affect the accumulation significantly.

Long-term effects of passive integrated transponder (PIT) tagging on the kelp grouper Epinephelus bruneus.

The effects of passive integrated transponder (PIT) tagging on the growth and survival of kelp grouper Epinephelus bruneus was examined over 1 year. The overall average mass gain for the 1 year period of the abdominal cavity tagged group was higher than the dorsal muscle tagged group. No significant differences were found in overall specific growth rate and food conversion between control and treatment groups.

Machine learning methods applied to pharmacokinetic modelling of remifentanil in healthy volunteers: a multi-method comparison.

This study compared the blood concentrations of remifentanil obtained in a previous clinical investigation with the predicted remifentanil concentrations produced by different pharmacokinetic models: a non-linear mixed effects model created by the software NONMEM; an artificial neural network (ANN) model; a support vector machine (SVM) model; and multi-method ensembles. The ensemble created from the mean of the ANN and the non-linear mixed effects model predictions achieved the smallest error and the highest correlation coefficient. The SVM model produced the highest error and the lowest correlation coefficient. Paired t-tests indicated that there was insufficient evidence that the predicted values of the ANN, SVM and two multi-method ensembles differed from the actual measured values at alpha = 0.05. The ensemble method combining the ANN and non-linear mixed effects model predictions outperformed either method alone. These results indicated a potential advantage of ensembles in improving the accuracy and reducing the variance of pharmacokinetic models.