Electron-Scale Reconnection in Three-Dimensional Shock Turbulence.

Magnetic reconnection has been observed in the transition region of quasi-parallel shocks. In this work, the particle-in-cell method is used to simulate three-dimensional reconnection in a quasi-parallel shock. The shock transition region is turbulent, leading to the formation of reconnecting current sheets with various orientations. Two reconnection sites with weak and strong guide fields are studied, and it is shown that reconnection is fast and transient. Reconnection sites are characterized using diagnostics including electron flows and magnetic flux transport. In contrast to two-dimensional simulations, weak guide field reconnection is realized. Furthermore, the current sheets in these events form in a direction almost perpendicular to those found in two-dimensional simulations, where the reconnection geometry is constrained.

Electron-scale dynamics of the diffusion region during symmetric magnetic reconnection in space.

Magnetic reconnection is an energy conversion process that occurs in many astrophysical contexts including Earth's magnetosphere, where the process can be investigated in situ by spacecraft. On 11 July 2017, the four Magnetospheric Multiscale spacecraft encountered a reconnection site in Earth's magnetotail, where reconnection involves symmetric inflow conditions. The electron-scale plasma measurements revealed (i) super-Alfvénic electron jets reaching 15,000 kilometers per second; (ii) electron meandering motion and acceleration by the electric field, producing multiple crescent-shaped structures in the velocity distributions; and (iii) the spatial dimensions of the electron diffusion region with an aspect ratio of 0.1 to 0.2, consistent with fast reconnection. The well-structured multiple layers of electron populations indicate that the dominant electron dynamics are mostly laminar, despite the presence of turbulence near the reconnection site.

Electron Crescent Distributions as a Manifestation of Diamagnetic Drift in an Electron-Scale Current Sheet: Magnetospheric Multiscale Observations Using New 7.5 ms Fast Plasma Investigation Moments.

We report Magnetospheric Multiscale observations of electron pressure gradient electric fields near a magnetic reconnection diffusion region using a new technique for extracting 7.5 ms electron moments from the Fast Plasma Investigation. We find that the deviation of the perpendicular electron bulk velocity from E × B drift in the interval where the out-of-plane current density is increasing can be explained by the diamagnetic drift. In the interval where the out-of-plane current is transitioning to in-plane current, the electron momentum equation is not satisfied at 7.5 ms resolution.

Infectious diseases in dogs rescued during dogfighting investigations.

Dogs used for dogfighting often receive minimal preventive health care, and the potential for spread of infectious diseases is high. The purpose of this study was to describe the prevalence of infectious diseases in dogs rescued from fighting operations to guide medical protocols for their immediate and long-term care. A total of 269 pit bull-type dogs were seized in a multi-state investigation. Fleas were present on most dogs, but few ticks were observed. Testing performed at intake included packed cell volume (PCV), serology and PCR for vector-borne pathogens, and fecal analysis. The most common infections were Babesia gibsoni (39%), 'Candidatus Mycoplasma haematoparvum' (32%), Mycoplasma haemocanis (30%), Dirofilaria immitis (12%), and Ancylostoma (23%). Anemia was associated with B. gibsoni infection (63% of infected dogs, odds ratio = 2.5, P <0.001), but not with hemotropic mycoplasmas or Ancylostoma. Pit bull heritage and dogfighting are known risk factors for B. gibsoni infection, possibly via blood transmission from bites and vertical transmission. Hemotropic mycoplasmas have a similar risk pattern. Empirical care for dogs from dogfighting cases should include broad-spectrum internal and external parasiticides and monitoring for anemia. Dogfighting case responders should be prepared for mass screening and treatment of B. gibsoni and heartworm infections and should implement protocols to prevent transmission of infectious and zoonotic diseases in the shelter and following adoption. Former fighting dogs and dogs with possible dog bite scars should not be used as blood donors due to the risk of vector-borne pathogens that can escape detection and for which curative treatment is difficult to document.

Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes.

Granulocyte colony-stimulating factor (G-CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G-CSF to impact type 1 diabetes (T1D) progression in patients with recent-onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G-CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (Treg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C-peptide production. Although treatment was well tolerated, G-CSF monotherapy did not affect C-peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G-CSF treatment increased circulating neutrophils during the 12-week course of therapy (P < 0·01) but did not alter Treg frequencies. No effects were observed for CD4(+) : CD8(+) T cell ratio or the ratio of naive : memory (CD45RA(+)/CD45RO(+)) CD4(+) T cells. As expected, manageable bone pain was common in subjects receiving G-CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G-CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C-peptide.

The value of routine evaluation of gastric residuals in very low birth weight infants.

OBJECTIVE: Little information exists regarding gastric residual (GR) evaluation prior to feedings in premature infants. The purpose of this study was to compare the amount of feedings at 2 and 3 weeks of age, number of days to full feedings, growth and incidence of complications between infants who underwent RGR (routine evaluation of GR) evaluation versus those who did not. STUDY DESIGN: Sixty-one premature infants were randomized to one of two groups. Group 1 received RGR evaluation prior to feeds and Group 2 did not. RESULT: There was no difference in amount of feeding at 2 (P=0.66) or 3 (P=0.41) weeks of age, growth, days on parenteral nutrition or complications. Although not statistically significant, infants without RGR evaluation reached feeds of 150 ml kg(-1) per day 6 days earlier and had 6 fewer days with central venous access. CONCLUSION: RESULTs suggest RGR evaluation may not improve nutritional outcomes in premature infants.

Packed red blood cell transfusion is not associated with increased risk of necrotizing enterocolitis in premature infants.

OBJECTIVE: Recent reports have posited a temporal association between blood transfusion with packed red blood cells (BT) and necrotizing enterocolitis (NEC). We evaluated the relationship between BT and NEC among infants at three hospitals who were consented at birth into a prospective observational study of NEC. STUDY DESIGN: We used a case-control design to match each case of NEC in our study population of infants born at<33 weeks postmenstrual age (PMA) to one control infant using hospital of birth, PMA, birth weight and date of birth. RESULT: The number of transfusions per infant did not differ between 42 NEC cases and their controls (4.0 ± 4.6 vs 5.4 ± 4.1, mean ± s.d., P = 0.063). A matched-pair analysis did not identify an association of transfusion with NEC in either the 48-h or 7-day time periods before the onset of NEC. Stratifying on matched-sets, the Cox proportional hazard model did not identify any difference in the total number of BTs between the two groups (hazard ratio 0.78, 95% confidence interval 0.57 to 1.07, P = 0.11). CONCLUSION: In contrast to previous studies, our case-control study did not identify a significant temporal association between BT and NEC. Additional large prospective randomized studies are needed to clarify the relationship between BT and NEC.

Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors.

BACKGROUND: Recurrent malignant brain tumors (RMBTs) carry a poor prognosis. Dichloroacetate (DCA) activates mitochondrial oxidative metabolism and has shown activity against several human cancers. DESIGN: We conducted an open-label study of oral DCA in 15 adults with recurrent WHO grade III - IV gliomas or metastases from a primary cancer outside the central nervous system. The primary objective was detection of a dose limiting toxicity for RMBTs at 4 weeks of treatment, defined as any grade 4 or 5 toxicity, or grade 3 toxicity directly attributable to DCA, based on the National Cancer Institute's Common Toxicity Criteria for Adverse Events, version 4.0. Secondary objectives involved safety, tolerability and hypothesis-generating data on disease status. Dosing was based on haplotype variation in glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI), which participates in DCA and tyrosine catabolism. RESULTS: Eight patients completed at least 1 four week cycle. During this time, no dose-limiting toxicities occurred. No patient withdrew because of lack of tolerance to DCA, although 2 subjects experienced grade 0-1 distal parasthesias that led to elective withdrawal and/or dose-adjustment. All subjects completing at least 1 four week cycle remained clinically stable during this time and remained on DCA for an average of 75.5 days (range 26-312). CONCLUSIONS: Chronic, oral DCA is feasible and well-tolerated in patients with recurrent malignant gliomas and other tumors metastatic to the brain using the dose range established for metabolic diseases. The importance of genetic-based dosing is confirmed and should be incorporated into future trials of chronic DCA administration.

A reduced-energy intake, well-balanced diet improves weight control in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi syndrome (PWS) have a predictable pattern of weight gain, with obesity beginning in early childhood and worsening as they get older and hyperphagia increases. Data on the most effective dietary modifications are scant and primarily anecdotal. As part of a longitudinal study investigating the natural history of PWS, we evaluated the effect of a well-balanced, energy-restricted diet on body composition and weight in young children with PWS. METHODS: Sixty-three children, aged 2-10 years, with genetically proven PWS participated in the present study. These children had measurements of body composition by dual-energy X-ray absorptiometry and resting energy expenditure (REE), as well as a 3-day diet history analysis both before and after intervention. Energy calculations were based on the individual's REE, with the recommendation that the macronutrients of the diet consist of 30% fat, 45% carbohydrates and 25% protein, with at least 20 g of fibre per day. RESULTS: Thirty-three families adhered to our dietary recommendations for both energy intake and macronutrient distribution. Those 33 children had lower body fat (19.8% versus 41.9%; P < 0.001) and weight management (body mass index SD score 0.3 versus 2.23; P < 0.001) than those whose parents followed the energy intake recommendations but did not alter the macronutrient composition of the diet. Those who followed our recommendations also had a lower respiratory quotient (0.84 versus 0.95; P = 0.002). CONCLUSIONS: Our recommendation for an energy-restricted diet with a well-balanced macronutrient composition and fibre intake improves both weight and body composition in children with PWS compared to a simple energy-restricted diet.

Urinary CTX-II concentrations are elevated and associated with knee pain and function in subjects with ACL reconstruction.

OBJECTIVE: Post-traumatic knee osteoarthritis (OA) is prevalent after anterior cruciate ligament reconstruction (ACLR). Biomarkers that identify individuals likely to develop OA, especially symptomatic OA, can help target preventative and therapeutic strategies. This study examined the magnitude and change over time in urinary CTX-II (uCTX-II) concentrations shortly after ACL reconstruction, and, secondarily, the associations with knee pain and function. DESIGN: Subjects were 28 patients with ACLR and 28 age- and sex-matched controls (CNTRL). Testing was conducted at four time points spaced 4 weeks apart (4, 8, 12 and 16 weeks post-operative in ACLR). Measures included demographics, urine samples, Numeric Pain Rating Scale (NPRS) and International Knee Documentation Committee Subjective Knee Form (IKDC-SKF). uCTX-II concentrations were determined with competitive enzyme-linked immunosorbent assay (ELISA). uCTX-II concentrations at each time point in ACLR were compared to the mean concentration over time in CNTRL, with and without adjustment for body mass index (BMI). Changes over time in each measure and correlations between the slopes of change were examined. RESULTS: uCTX-II concentrations were significantly higher in ACLR than CNTRL through 16 weeks post-operative when adjusted for BMI. In ACLR, uCTX-II concentrations significantly decreased over time, and the slope was associated with NPRS (r = 0.406, P = 0.039) and IKDC-SKF (r = -0.402, P = 0.034) slopes. CONCLUSION: uCTX-II concentrations shortly after ACLR were elevated compared to CNTRL and declined over time. Decreasing uCTX-II concentrations were associated with decreasing knee pain and improving function. uCTX-II may have a role as a prognostic marker following ACLR and warrants further investigation.

The preservation and degradation of filamentous bacteria and biomolecules within iron oxide deposits at Rio Tinto, Spain.

One of the keys to understanding and identifying life on other planets is to study the preservation of organic compounds and their precursor micro-organisms on Earth. Rio Tinto in southwestern Spain is a well documented site of microbial preservation within iron sulphates and iron oxides over a period of 2.1 Ma. This study has investigated the preservation of filamentous iron oxidising bacteria and organics through optical microscopy, scanning electron microscopy (SEM) and Fourier transform infra-red (FTIR) spectroscopy, from laboratory cultures of natural samples to contemporary natural materials to million-year old river terraces. Up to 40% elemental carbon and >7% nitrogen has been identified within microbial filaments and cell clusters in all samples through SEM EDS analyses. FTIR spectroscopy identified C-H(x) absorption bands between 2960 and 2800 cm(-1), Amide I and II absorption bands at 1656 and 1535 cm(-1), respectively and functional group vibrations from within nucleic acids at 917, 1016 and 1124 cm(-1). Absorption bands tracing the diagenetic transformation of jarosite to goethite to hematite through the samples are also identified. This combination of mineralogy, microbial morphology and biomolecular evidence allows us to further understand how organic fossils are created and preserved in iron-rich environments, and ultimately will aid in the search for the earliest life on Earth and potential organics on Mars.

Outcomes of Late Corticosteroid Withdrawal after Renal Transplantation in Patients Exposed to Tacrolimus and/or Mycophenolate Mofetil: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Corticosteroids are increasingly used in renal transplant patients to minimize organ rejection after transplantation. In attempts to reduce corticosteroids adverse effects, transplant professionals are customary attempted to taper off, and permanently stop corticosteroids after few months of administration with other immunosuppressants. OBJECTIVE: To evaluate clinical benefits and risks of late corticosteroid withdrawal in renal transplant patients treated with tacrolimus (TAC) or mycophenolate mofetil (MMF), or both. METHODS: A meta-analysis was performed of published randomized controlled trials that reported outcomes in kidney transplant patients who were randomized to corticosteroids maintenance or late withdrawal under concomitant immunosuppression by TAC, MMF or both. Outcomes included acute graft rejection; graft failure rate; all-cause mortality; incidence of post-transplant diabetes; change in serum creatinine and total cholesterol; and change in pediatric standardized height z-score. PubMed and Google Scholar were used in literature search between 1999 and April 1, 2010. Data were combined using unweighted random effects model. RESULTS: Nine studies randomized 1907 patients met the inclusion criteria: TAC (n=1); MMF (n=6); both (n=2). Compared to maintenance therapy, late corticosteroid withdrawal was associated with 34% increase in the risk of acute graft rejection (95% CI for OR: 0.47-3.82); 35% and 5% reductions in the risk of graft failure and patient's all-cause mortality (95% CI for OR: 0.26-1.60; 0.23-3.93, respectively); and 4% increase in post-transplant diabetes risk (95% CI for OR: 0.45-2.41). Late corticosteroid withdrawal was associated with substantial reduction in total cholesterol levels (mean difference: 18.1 mg/dL; 95% CI: 7.1-29.0 mg/dL), but did not reduce serum creatinine levels (0.00 mg/dL; 95% CI: 0.17 to 0.17). Stopping corticosteroids was associated with better pediatric growth outcomes. CONCLUSION: Late corticosteroid withdrawal under TAC and/or MMF-lead immunosuppression after kidney transplantation could provide benefits in terms of total cholesterol, patient and graft survival, and pediatric growth. This strategy, however did not reduce the risk of acute graft rejection, post-transplant diabetes mellitus, and deterioration in serum creatinine levels.

Design and statistical analysis of oral medicine studies: common pitfalls.

A growing number of articles are emerging in the medical and statistics literature that describe epidemiologic and statistical flaws of research studies. Many examples of these deficiencies are encountered in the oral, craniofacial, and dental literature. However, only a handful of methodologic articles have been published in the oral literature warning investigators of potential errors that may arise early in the study and that can irreparably bias the final results. In this study, we briefly review some of the most common pitfalls that our team of epidemiologists and statisticians has identified during the review of submitted or published manuscripts and research grant applications. We use practical examples from the oral medicine and dental literature to illustrate potential shortcomings in the design and analysis of research studies, and how these deficiencies may affect the results and their interpretation. A good study design is essential, because errors in the analysis can be corrected if the design was sound, but flaws in study design can lead to data that are not salvageable. We recommend consultation with an epidemiologist or a statistician during the planning phase of a research study to optimize study efficiency, minimize potential sources of bias, and document the analytic plan.

Hyperlipidemia in glycogen storage disease type III: effect of age and metabolic control.

While the presence of hyperlipidaemia in glycogen storage disease (GSD) type Ia and Ib is generally accepted, few investigators have adequately assessed lipid profiles of GSD III in children, in whom the presence of hyperlipidaemia may be most prominent. We analysed the lipid profiles in 44 GSD III patients from 6 months to 30 years of age. Hypertriglyceridaemia and hypercholesterolaemia were common in children younger than 3 years of age. Hypertriglyceridaemia correlated negatively with age, and may reflect increased severity of hypoglycaemia in this younger population. The presence of hyperlipidaemia during childhood in these patients identifies another GSD population that could be at risk for early cardiovascular disease (CVD). Consequently, the outcome of clinical trials investigating the vascular effect of hyperlipidaemia in GSD applies to types other than GSD I.

High sensitivity C-reactive protein in systemic lupus erythematosus: relation to disease activity, clinical presentation and implications for cardiovascular risk.

Measurement of high sensitivity C-reactive protein (hs-CRP), has been used in the assessment of disease activity in numerous rheumatic conditions including systemic lupus erythematosus (SLE). However, the utility of hs-CRP measurement in patients with lupus is uncertain. This study examined if hs-CRP can be used to assess disease activity, severity and cardiovascular risk in SLE. Serum samples from 601 visits of 213 SLE patients and 134 controls were analysed for hs-CRP by nephelometry. Detailed demographic data were obtained from all subjects and medication history and key laboratory parameters were collected. Disease activity was assessed using the SLEDAI. High sensitivity CRP was not associated with disease activity (SLEDAI), number of ACR SLE criteria or presence of any particular organ involvement. hs-CRP levels were significantly correlated with standard cardiovascular risk factors including body weight (P = 0.0002), hypertension (P = 0.001), and apolipoprotein A-I (P < 0.0001). Interestingly an inverse correlation was seen between hs-CRP levels and antimalarial use (P = 0.0018). Our results suggest that measurement of hs-CRP, though not valuable as marker of disease activity in SLE may be of some use in the assessment of cardiovascular risk. We speculate that antimalarials may help to reduce cardiovascular risk in patients with SLE.

High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: a Children's Oncology Group (COG) initiative.

Chromosome aberrations have a major role in pediatric acute lymphoblastic leukemia (ALL) risk assignment. The Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) independently assessed the significance of trisomy for chromosomes 4, 10, and 17 in National Cancer Institute (NCI) Standard- and High-Risk ALL. Data from 1582 (CCG) and 3902 (POG) patients were analyzed. Eight-year event-free survivals (EFS) of 91% (CCG) and 89% (POG) (P < 0.001) were achieved in patients assigned to NCI Standard Risk whose leukemic cells had simultaneous trisomies 4, 10, and 17. Both groups showed the degree of favorable prognostic importance increased with the actual number of favorable trisomies. POG analyses also demonstrated hyperdiploidy (> or =53 chromosomes) was less of an independently significant prognostic factor in the absence of these key trisomies. This finding supported conclusions from previous CCG and POG studies that specific trisomies are more important than chromosome number in predicting outcome in pediatric B-precursor ALL. In NCI Higher Risk patients, the number of favorable trisomies was not prognostically significant, but showed the same trend. Moreover, specific trisomies 4, 10, and 17 remain associated with favorable prognosis in Standard-Risk B-precursor ALL, even in the context of very different treatment approaches between the groups.

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.

We reported that children with B-progenitor-cell acute lymphoblastic leukemia (BpALL) treated in the early 1980s whose lymphoblasts accumulated high levels of methotrexate (MTX) and of methotrexate polyglutamates (MTXPGs) in vitro had an improved 5-year event-free survival (EFS) (65% (standard error (s.e.) 12%) vs 22% (s.e. 9%)). We repeated this study in children with BpALL treated in the early 1990s. The major change in treatment was the addition of 12 24-h infusions of 1 g/M2 MTX with leucovorin rescue (IDMTX). In 87 children treated on Pediatric Oncology Group (POG) study 9005 and POG 9006, the 5-year EFS for those whose lymphoblasts accumulated high levels of MTX and MTXPGs (79.2%, s.e. 8.3%) was not significantly different from that of patients with lesser accumulation of MTX and MTXPGs (77.7%, s.e. 5.4%). These findings support the notion that higher dose MTX therapy has contributed to increased cure, particularly for patients whose lymphoblasts accumulate the drug less well.

Precision and bias of target controlled propofol infusion for sedation.

BACKGROUND: The purpose of this study is to test precision and systematic bias of a target controlled infusion (TCI) of propofol in human volunteers at two sedative concentrations. METHODS: We studied the 'Diprifusor' model (Marsh Pharmacokinetics and a Graseby 3400 infusion pump) in 18 human volunteers at two sedative target plasma concentrations (0.5 and 1.0 microg ml(-1)). Twenty minutes after infusion start or change and 20 min after discontinuation of the infusion plasma propofol concentrations were measured using liquid chromatography-mass spectroscopy (LC-MS). Plasma propofol concentrations were compared with concentrations predicted by the TCI system. Agreement of those two measures (precision and bias) was determined using regression analysis. RESULTS: We found little systematic bias but poor precision. When setting the TCI system to deliver a plasma concentration of 1.0 microg ml(-1) one can predict the actual plasma concentration with 95% confidence only within a range of 0.44-1.38 microg ml(-1). CONCLUSIONS: This finding helps to explain differences in responses to propofol sedation; pharmacokinetic variability appears to be an important factor.

A comparison of red blood cell thiopurine metabolites in children with acute lymphoblastic leukemia who received oral mercaptopurine twice daily or once daily: a Pediatric Oncology Group study (now The Children's Oncology Group).

INTRODUCTION: Mercaptopurine is an important antimetabolite for treatment of childhood acute lymphoblastic leukemia (ALL). It has been prescribed to be given daily without therapeutic monitoring of drug levels. After first-pass metabolism by hepatic xanthine oxidase (XO), mercaptopurine is converted into two major intracellular metabolites, thioguanine nucleotide (TGN) and methylated mercaptopurine metabolites (including methylated thioinosine nucleotides), which are cytotoxic in vitro. Its short plasma half-life and S-phase-dependent pharmacokinetics suggest that biologically active concentration and exposure duration may be critical to cell kill. METHODS: Pediatric Oncology Group (POG) 9605, a randomized, open label phase III study of standard-risk ALL, was designed to compare daily with twice-daily mercaptopurine during continuation therapy. Red blood cell (RBC) TGN and methylated mercaptopurine metabolite levels were measured as surrogates of leukemic cell levels in a randomly selected subset of patients. TGN and methylated mercaptopurine metabolites were analyzed quantitatively by high-performance liquid chromatography (HPLC) and reported in ng/8 x 10.8 RBC. Statistical inferences utilized multiple linear regression. RESULTS: One hundred eighteen patients received mercaptopurine 75 mg/m(2) daily and 108 received 37.5 mg/m(2)/dose twice daily. Descriptive statistics for the daily group showed the median TGN was 42 ng (mean and standard deviation [SD] = 48 +/- 35, quartiles 29-64). For the twice daily group, it was 40 ng (mean and SD = 40 +/- 27, quartiles 26-53). For methylated mercaptopurine metabolites, the daily group median was 2,020 ng (mean and SD = 2,278 +/- 1,559, quartiles 1,247-3,162); the twice daily group median was 1,275 ng (mean and SD = 1,580 +/- 1,240, quartiles 599-2,369). When adjusted for the covariables: actual dosage, days on study, age at diagnosis, white blood cell count, gender, Black race compared with not, and Hispanic compared with not, daily dosing resulted in significantly higher average methylated mercaptopurine metabolites by 668 (standard error [SE] = 179, P = 0.001) and a trend toward higher average TGNs by 6.2 (SE = 4.2, P = 0.14). CONCLUSIONS: Daily dosing of mercaptopurine resulted in higher mean red cell methylated mercaptopurine metabolites when compared to split (twice a day dosing). The data were inconclusive with respect to TGNs. The relationships of methylated mercaptopurine metabolites and TGNs to clinical outcomes will be elucidated as part of the maturing 9605 data.