Implementation of Public Health England infection prevention and control guidance in maternity units in response to the COVID-19 pandemic.

BACKGROUND: This study aimed to explore the successes and barriers to the implementation of Public Health England (PHE) infection prevention and control guidance in English maternity units during the COVID-19 pandemic. METHODS: Qualitative semi-structured interviews with obstetricians, midwives and neonatologists who worked in a maternity unit in England, UK, between March 2020 and July 2021. A thematic analysis was performed. RESULTS: Successes to the implementation of PHE guidance were related to existing infrastructure, training satisfaction, and organisational culture where subthemes considered the importance of a multidisciplinary approach, COVID-19 dedicated roles and hospital-wide communication. Barriers to implementation related to the applicability of the guidance with subthemes highlighting contradictions between updates, specialties and hospitals, undesirable timings and frequency of guidance updates, reductions in staff compliance and delayed implementation. Finally, the layout of some units made it difficult to implement various aspects of the guidance (e.g., social distancing), and many detailed issues related to information technology compatibility, a lack of availability and accessibility to appropriate personal protective equipment (PPE), and variations in testing arrangements between units. CONCLUSIONS: This research provides information on the experiences of healthcare professionals working on maternity units during the COVID-19 pandemic. Findings illustrate the importance of effective hospital-wide communication and the need for consistent, easily understood guidance. These results will be used to inform the content of an expert panel consensus meeting.

WAND2-A versatile wide angle neutron powder/single crystal diffractometer.

Wide Angle Neutron Diffractometer Squared is a high-flux versatile diffractometer with a 2-Dimensional Position Sensitive Detector at the High Flux Isotope Reactor. The instrument has strengths in both powder and single crystal diffraction. It is a unique instrument in the neutron scattering landscape of North America, and its capabilities are at least equal to similar instruments in the world.

Vitamin D status is not associated with the risk of hospitalization for acute bronchiolitis in early childhood.

The association between vitamin D status and susceptibility to acute lower respiratory tract infection (ALRI) was studied in young Canadian children. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured in patients aged 1-25 months admitted to hospital with uncomplicated ALRI (primarily viral bronchiolitis) as well as in healthy, similarly aged patients without a history of hospitalization for ALRI (controls). Serum 25(OH)D concentrations were similar among cases and controls (77.0 versus 77.2 nmol l(-1); P=0.960), and there was no case-control difference in the prevalence of vitamin D insufficiency using two thresholds (<40 nmol l(-1): 4.7 versus 1.5%, P=0.365; <80 nmol l(-1): 51.6 versus 56.9%, P=0.598). Vitamin D status was not associated with the risk of hospitalization for ALRI in this population.

Fluticasone versus HFA-beclomethasone dipropionate for chronic asthma in adults and children.

BACKGROUND: The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant. OBJECTIVES: To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of January 2006. SELECTION CRITERIA: Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity. MAIN RESULTS: Eight studies (1260 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event. AUTHORS' CONCLUSIONS: There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

Fluticasone versus HFA-beclomethasone dipropionate for chronic asthma in adults and children.

BACKGROUND: The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant. OBJECTIVES: To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of March 2005. SELECTION CRITERIA: Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity. MAIN RESULTS: Seven studies (1230 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event. AUTHORS' CONCLUSIONS: There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

A novel technique of concurrent esophagoscopy and transgastrostomy gastroscopy to dilate a completely obstructed distal esophageal stricture in a child following fundoplication.

We report a successful dilation of a completely obstructed distal esophageal stricture in a 4-year-old boy with combined immune deficiency syndrome, at 2 and half years after fundoplication and gastrostomy tube insertion. Barium studies and esophagoscopy had revealed complete obstruction of the lower esophagus. Transgastrostomy gastroscopy demonstrated a pinhole lumen through the fundoplication wrap; a guide wire was passed into the esophagus; and the stricture was dilated with Savary dilators. We presumed that the stricture was secondary to chronic esophagitis. The stricture was identified and successfully dilated using a novel technique of concurrent esophagoscopy and transgastrostomy gastroscopy.

A synthesis of dominant ecological processes in intensive shrimp ponds and adjacent coastal environments in NE Australia.

One of the key environmental concerns about shrimp farming is the discharge of waters with high levels of nutrients and suspended solids into adjacent waterways. In this paper we synthesize the results of our multidisciplinary research linking ecological processes in intensive shrimp ponds with their downstream impacts in tidal, mangrove-lined creeks. The incorporation of process measurements and bioindicators, in addition to water quality measurements, improved our understanding of the effect of shrimp farm discharges on the ecological health of the receiving water bodies. Changes in water quality parameters were an oversimplification of the ecological effects of water discharges, and use of key measures including primary production rates, phytoplankton responses to nutrients, community shifts in zooplankton and delta15N ratios in marine plants have the potential to provide more integrated and robust measures. Ultimately, reduction in nutrient discharges is most likely to ensure the future sustainability of the industry.

Photoallergic contact dermatitis is uncommon.

BACKGROUND: Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare. OBJECTIVES: To analyse the data from 2715 patients who underwent photopatch testing at St John's Institute of Dermatology during the period 1983-98. METHODS: A retrospective analysis of all positive photopatch test episodes was undertaken with the results retrieved from the environmental dermatology database and further verified with the original archived patch test documentation for each individual patient. RESULTS: In 111 patients with positive reactions (4.1%), there were 155 AC or PA reactions to allergens in the photopatch test series. Eighty PA reactions were observed in 62 (2.3%) patients (32 men and 30 women, age range 28-75 years), with UV filters accounting for 52 positive reactions (65%), drugs 16 (20%), musk ambrette 11 (14%) and the antiseptic trichlorocarbanilide one (1%). The most common UV filter photoallergen was benzophenone-3 with 14 positive results, followed by benzophenone-10 (n = 9), isopropyl dibenzoylmethane (n = 6), p-aminobenzoic acid (PABA) (n = 5), octyl dimethyl PABA (n = 5), butyl methoxydibenzoylmethane (n = 4), isoamyl methoxycinnamate (n = 2), ethyl methoxycinnamate (n = 2), octyl methoxycinnamate (n = 2), amyl dimethyl PABA (n = 2) and phenylbenzimidazole sulphonic acid (n = 1). A similar number of AC reactions to UV filters was detected in this study. Thus 49 patients (1.8%) had a total of 75 reactions: 51 due to UV filters and 24 as a result of exposure to fragrances and therapeutic agents. Benzophenone-10 accounted for 13 AC reactions and benzophenone-3 for eight reactions. Twenty-two patients had a PA reaction alone, whereas 19 patients had chronic actinic dermatitis and 15 patients polymorphic light eruption (PLE) in addition. Thus, 34 of the 62 patients (55%) had a preceding underlying photodermatosis. CONCLUSIONS: These results show a low yield of positive photopatch tests. Thus, despite the large increase in the use of UV filters over the last decade, the development of PA reactions remains rare. Furthermore, most of the common UV filter photoallergens identified in this study, including PABA, amyl dimethyl PABA and benzophenone-10, are now rarely used in sunscreen manufacture, while isopropyl dibenzoylmethane was voluntarily removed from the market in 1993. Currently, benzophenone-3 is the commonest contact photoallergen still in widespread use. In contrast, the UVB filter octyl methoxycinnamate, used in a number of sunscreens, produced only two positive PA reactions in 12 years of testing. Nevertheless, although these reactions are extremely rare, patients with photodermatoses such as PLE and chronic actinic dermatitis do represent a group of patients at increased risk of developing photoallergy. Further photopatch test series should be regularly reviewed and updated, as the relevance of individual photoallergens changes over time. Currently, there is no evidence that PA reactions represent a common clinical problem.

Gastroesophageal reflux in infants and children. When to reassure and when to go further.

OBJECTIVE: To review current understanding and approach to diseases resulting from gastroesophageal reflux (GER) in infants and children. QUALITY OF EVIDENCE: Very few randomized or blinded controlled trials have been reported in this area. MEDLINE searches for gastroesophageal reflux, gastroesophageal reflux disease, esophagitis, and pulmonary aspiration, using age-limited (all childhood) data, find most articles. Very thorough reviews undertaken by both European and North American societies for pediatric gastroenterology provide up-to-date consensus statements. MAIN MESSAGE: Gastroesophageal reflux is a normal phenomenon recognized in infants as "spitting up." Understanding the mechanism of transient lower esophageal relaxation episodes allows physicians to counsel concerned parents that reflux and spitting up occur universally, but are less visible in children older than 6 to 12 months. In infants and children, GER can result in a variety of diseases and can cause esophageal and tracheopulmonary damage. Investigation of these diseases can be specific and accurate. Therapy is available, but no drug will stop reflux. Some children suffer intractable GER with secondary complications (GERD) despite medical treatment. Failure of therapy could mean patients require surgical intervention. CONCLUSION: Visible GER is very common in infants and children and can usually be managed with explanation, reassurance, and simple measures. Diseases caused by GER can be investigated specifically and managed with accurately defined therapy.

Peroxisome proliferator-activated receptor (PPAR) modulators: diabetes and beyond.

Peroxisome proliferator-activated receptors (PPARs) are a class of ligand modulated transcription factors with a prominent role in the regulation of metabolic processes. This report is intended to provide a limited introduction to the PPAR field, sketched with reference to one early series of PPAR ligands.

Identification of a novel psoriasis susceptibility locus at 1p and evidence of epistasis between PSORS1 and candidate loci.

The pathogenesis of all forms of psoriasis remains obscure. Segregation analysis and twin studies together with ethnic differences in disease frequency all point to an underlying genetic susceptibility to psoriasis, which is both complex and likely to reflect the action of a number of genes. We performed a genome wide analysis using a total of 271 polymorphic autosomal markers on 284 sib relative pairs identified within 158 independent families. We detected evidence for linkage at 6p21 (PSORS1) with a non-parametric linkage score (NPL)=4.7, p=2 x 10(-6) and at chromosome 1p (NPL=3.6, p=1.9 x 10(-4)) in all families studied. Significant excess (p=0. 004) paternal allele sharing was detected for markers spanning the PSORS1 locus. A further three regions reached NPL scores of 2 or greater, including a region at chromosome 7 (NPL 2.1), for which linkage for a number of autoimmune disorders has been reported. Partitioning of the data set according to allele sharing at 6p21 (PSORS1) favoured linkage to chromosomes 2p (NPL 2.09) and 14q (NPL 2.0), both regions implicated in previous independent genome scans, and suggests evidence for epistasis between PSORS1 and genes at other genomic locations. This study has provided linkage evidence in favour of a novel susceptibility locus for psoriasis and provides evidence of the complex mechanisms underlying the genetic predisposition to this common skin disease.

Discovery of a potent, highly selective, and orally efficacious small-molecule activator of the insulin receptor.

A series of 3,6-diaryl-2,5-dihydroxybenzoquinones were synthesized and evaluated for their abilities to selectively activate human insulin receptor tyrosine kinase (IRTK). 2, 5-Dihydroxy-6-(1-methylindol-3-yl)-3-phenyl-1,4-benzoquinone (2h) was identified as a potent, highly selective, and orally active small-molecule insulin receptor activator. It activated IRTK with an EC(50) of 300 nM and did not induce the activation of closely related receptors (IGFIR, EGFR, and PDGFR) at concentrations up to 30 000 nM. Oral administration of the compound to hyperglycemic db/db mice (0.1-10 mg/kg/day) elicited substantial to nearly complete correction of hyperglycemia in a dose-dependent manner. In ob/ob mice, the compound (10 mg/kg) caused significant reduction in hyperinsulinemia. A structurally related compound 2c, inactive in IRTK assay, failed to affect blood glucose level in db/db mice at equivalent exposure levels. Results from additional studies with compound 2h, aimed at evaluating classical quinone-related phenomena, provided sufficient grounds for optimism to allow more extensive toxicologic evaluation.

Activation of insulin signal transduction pathway and anti-diabetic activity of small molecule insulin receptor activators.

We recently described the identification of a non-peptidyl fungal metabolite (l-783,281, compound 1), which induced activation of human insulin receptor (IR) tyrosine kinase and mediated insulin-like effects in cells, as well as decreased blood glucose levels in murine models of Type 2 diabetes (Zhang, B., Salituro, G., Szalkowski, D., Li, Z., Zhang, Y., Royo, I., Vilella, D., Diez, M. T. , Pelaez, F., Ruby, C., Kendall, R. L., Mao, X., Griffin, P., Calaycay, J., Zierath, J. R., Heck, J. V., Smith, R. G. & Moller, D. E. (1999) Science 284, 974-977). Here we report the characterization of an active analog (compound 2) with enhanced IR kinase activation potency and selectivity over related receptors (insulin-like growth factor I receptor, epidermal growth factor receptor, and platelet-derived growth factor receptor). The IR activators stimulated tyrosine kinase activity of partially purified native IR and recombinant IR tyrosine kinase domain. Administration of the IR activators to mice was associated with increased IR tyrosine kinase activity in liver. In vivo oral treatment with compound 2 resulted in significant glucose lowering in several rodent models of diabetes. In db/db mice, oral administration of compound 2 elicited significant correction of hyperglycemia. In a streptozotocin-induced diabetic mouse model, compound 2 potentiated the glucose-lowering effect of insulin. In normal rats, compound 2 improved oral glucose tolerance with significant reduction in insulin release following glucose challenge. A structurally related inactive analog (compound 3) was not effective on insulin receptor activation or glucose lowering in db/db mice. Thus, small molecule IR activators exert insulin mimetic and sensitizing effects in cells and in animal models of diabetes. These results have implications for the future development of new therapies for diabetes mellitus.

DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in fetal tissues of patas monkeys after transplacental exposure.

Transplacental genotoxicity of the heterocyclic amine food-derived mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has been investigated by (32)P-postlabeling assay for IQ-DNA adducts in maternal liver, placenta, and several fetal tissues of patas monkeys, after exposure to 15, 35, or 50 mg/kg IQ near the end of gestation or to the highest dose in the first or second trimester. Dose-dependent adduct formation occurred in all tissues, with the highest levels occurring in maternal liver. Adduct amounts were similar among fetal tissues and placenta, except for lower levels in fetal brain and slightly more adducts in fetal liver. Adducts in placenta, fetal liver, lung, kidney, skin, and adrenal gland, but not in maternal liver or fetal brain, increased significantly as gestation progressed. Pretreatment with phenobarbital, which induces CYP enzymes that detoxify IQ, decreased adducts in maternal liver and possibly placenta, but not in fetal tissues. The CYP inducer beta-naphthoflavone caused a significant increase in IQ-DNA adducts in fetal lungs. Regression analysis suggested that IQ activation in maternal and fetal liver and possibly placenta contributed to adduct formation in fetal tissues; adducts in placenta and/or fetal liver were strong predictors for those in most fetal tissues. The results indicate that exposure of pregnant primates to IQ results in DNA adduct formation in most fetal tissues, especially late in gestation; that upregulation of maternal detoxification does not provide fetal protection; and that adducts in placenta indicate adduct levels in fetal tissues.

The basal SAR of a novel insulin receptor activator.

The synthesis and SAR of analogues prepared from novel insulin receptor activator 1 are described. Changes to the dihydroxyquinone core were not tolerated while functionalization of the two indoles contained in 1 resulted in little effect upon activation of the insulin receptor.

Oxidative DNA damage in fetal tissues after transplacental exposure to 3'-azido-3'-deoxythymidine (AZT).

The nucleoside analogue 3'-azido-3'-deoxythymidine (AZT) has been used successfully to reduce the incidence of transplacental and perinatal transmission of the HIV virus. However, prolonged treatment with high doses of AZT is utilized in this therapy, and AZT has been found to be a perinatal carcinogen in mice. Any possible perinatal carcinogenic side effects in the human can best be managed if the mechanism is understood. AZT targets mitochondria and might cause increased intracellular production of reactive oxygen species (ROS). We tested whether transplacental AZT may cause oxidative damage in nuclear DNA of fetal tissues. CD-1 Swiss pregnant mice were treated with the transplacental carcinogenesis regimen (25 mg/day AZT, for gestation days 12-18) and tissues collected on the day of birth. Significant increases in 8-oxo-2'-deoxyguano- sine (8-oxo-dG) were found in the livers, a target tissue for transplacental carcinogenesis, and in the kidneys. A non-significant increase occurred in brain, with no change in lung. Tissues were also obtained from fetal patas monkeys (Erythrocebus patas), whose mothers had received 10 mg AZT/day during the last half of gestation. Although limited numbers of samples were available, possible increases in 8-oxo-dG were noted, relative to controls, for placenta and for fetal lung and brain (P = 0.055 for treatment-related increases in these tissues). These results suggest that an increase in reactive oxygen species could contribute to the mechanism of transplacental carcinogenesis by AZT in mice, and that this may also occur in primates.

Release of bovine serum albumin from preformed porous microspheres of poly(L-lactic acid).

Preformed porous microspheres of poly(L-lactic acid) (Accurel have been shown to sustain the release of highly water soluble solutes, like dextran and mannitol, for a time period of more than 4 months. The purpose of this investigation was to mechanistically characterize the release of a model protein, bovine serum albumin (BSA), from these highly porous microspheres. The microspheres were loaded with [14C]BSA in three different concentrations of 0.06, 0.26 and 0.59% w/w. The rate of release of [14C]BSA from microspheres was correlated to media ([3H]PBS) uptake. The release of BSA showed a biphasic pattern; an initial rapid release, followed by a sustained release. The initial burst of BSA was found to be inversely proportional to BSA loading and highly correlated to water penetration. The sustained release phase was independent of water penetration kinetics. Washing the microspheres did not remove either the surface bound BSA or the BSA incorporated in the microsphere matrix, indicating the tight binding of BSA to highly porous microspheres. Furthermore, addition of a surfactant induced a dramatic increase in the amount of BSA released, suggesting that the release is controlled by the surface binding of BSA to the polymer. Also, the release rate of BSA beyond the initial burst was found to be much slower than for the lower MW macromolecules like dextran at a similar level. The data from the present work suggests the BSA-polymer interaction to be a major contributing factor in explaining the overall BSA release kinetics.

NOF-11: a one-year pediatric randomized double-blind comparison of neoral versus sandimmune in orthotopic liver transplantation.

BACKGROUND: Although cyclosporine (CsA) has been a mainstay in liver transplantation immunosuppression the original formulation [Sandimmune (SIM)] has variable absorption, particularly in children. Neoral is a new formulation of CsA that may have improved biovailability that would be advantageous in children. This study was undertaken to assess the pharmacokinetics (PK) and effects on outcome of Neoral versus Sandimmune (SIM) in primary pediatric liver transplant recipients. METHODS: Thirty-two patients were randomized to receive Neoral (17 patients) or SIM (15 patients) in the early posttransplant period (days 1-7) in a double-blind fashion. Intravenous CsA was instituted immediately posttransplant followed by Neoral or SIM as soon as the patient was tolerating oral fluids (days 1-7). PK were compared after the first dose (1-7 days), 3 weeks, and 6 and 12 months posttransplant. In addition, side effects, effect of age and food on absorption, and rejection episodes were assessed by intent to treat analysis. Notable characteristics of this study include the use of a central laboratory for all sample analyses and the assessment of renal function using radioisotopic evaluation of glomerular filtration rates. RESULTS: At baseline the two groups were comparable. Neoral resulted in higher peak levels of CsA and total drug exposure with comparable time to peak drug levels at days 1-7 and week 3. This trend was maintained at 6 and 12 months. Time on i.v. CsA was reduced in the Neoral group (8.4 vs. 11.1 days) and the weight adjusted daily dose of SIM required to achieve target trough levels was about 2-fold more than Neoral from day 22 onward. In addition, biopsy proven and treated and steroid-resistant rejection episodes were fewer in the Neoral group (6 vs. 12; P=0.01 and 1 vs. 8: P=0.004, respectively). Side effects were comparable in both treatment groups. CONCLUSIONS: Neoral was well tolerated and had greater biovailability than SIM without any increase in the incidence of side effects. In addition fewer episodes of rejection were observed with Neoral versus SIM. We conclude that Neoral is the CsA formulation of choice for use in pediatric liver transplant recipients.