The frequency of epstein-barr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children

Twenty cases of Epstein-Barr virus (EBV)-associated lymphoproliferative syndrome (LPS), defined by the presence of EBV nuclear antigen and/or EBV DNA in tissues, were diagnosed in 1467 transplant recipients in Pittsburgh from 1981—1985. The frequency of occurrence in pediatric transplant recipients was 4% (10/ 253), while in adults it was 0.8% (10/1214) (P < .0005). The frequency of LPS in adults declined after 1983 coincidental with the introduction of cyclosporine monitoring. However there was no apparent decline of LPS in children. We describe these ten pediatric cases and one additional case of LPS in a child who received her transplant before 1981. The frequency of EBV infection in 92 pediatric liver recipients was 63%. Of these subjects, 49% were sero-negative and 77% of those acquired primary infection. Of 11 cases of pediatric EBV-associated LPS, 10 were in children who had primary infection shortly before or after transplantation. These results reinforce the impor-tance of primary EBV infection in producing LPS, which was previously shown in adults. Children are at greater risk because they are more likely to be seronegative for EBV and to acquire primary infection. Three clinical types of LPS were recognized in children. The first (5 cases) was a self-limited mononucleo-sislike syndrome. The second syndrome (4 cases) began similarly, but then progressed over the next two months to widespread lymphoproliferation in internal organs and death. The third type (2 cases) was an extranodal intestinal monoclonal B cell lymphoma, occurring late after primary infection. © 1988 by The Williams and Wilkins Co

Is overweight and obesity in 9–10-year-old children in Liverpool

Objectives: To determine whether weight problems in children (overweight, obesity and overweight or obesity) were related to deprivation indices when attributed only according to electoral ward of the school attended. To determine whether children with weight problems were more likely to be found in some wards rather than others, and to compare the distribution for boys and girls. Design: Retrospective, cross-sectional, observational study. Setting: One hundred and six primary schools from all parts of Liverpool city. Subjects: Five cohorts of 9–10-year-old children between 1998 and 2003. Main outcome measures: Body mass index (BMI) for each child to estimate proportions overweight, obese and overweight or obese according to international criteria. Results: Between January 1998 and March 2003, the heights and weights of 7902 boys and 7514 girls were measured and BMI calculated. The prevalence of boys and girls categorised as overweight or obese was very high (1620, 20.6% and 1909, 25.7%, respectively). Prevalence was not related to deprivation and varied between wards only for the girls; some wards had very different prevalence rates for boys and girls (Picton: 59 boys, 23.4%; 106 girls, 36.6%). The most deprived ward did not have a remarkable prevalence of overweight or obesity (Speke: 32 boys, 15.3%; 40 girls, 19.8%). Conclusions: Obesity is a major problem and requires urgent action but targeting intervention on the basis of administrative areas may be very wasteful. Different factors seem to lead to obesity in boys and girls, and attention should be paid to the role of the physical environment

Health‐related quality of life in survivors of advanced melanoma treated with anti‐PD1‐based immune checkpoint inhibitors

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma but are associated with immune-related adverse events (irAEs). This single center, cross-sectional survey aimed to describe the long-term symptom burden and impact on health-related quality of life (HRQL) of advanced melanoma patients with sustained disease control following treatment with ICIs. Methods: Advanced melanoma patients (stage IIB, III or IV, AJCCv8), treated with anti-PD1-based ICIs, who were off-treatment and had at least 6 months follow-up from their last infusion with an ongoing response in the metastatic setting or no evidence of disease recurrence in the adjuvant setting. A paper-based questionnaire, consisting of the EORTC QLQ-C30, EORTC QLQ-FA12, and the PRO-CTCAE was administered. Results: Of 90 participants, 61 (68%) completed the questionnaire; 40 received single-agent anti-PD1, and 21 anti-PD1/anti-CTLA4. Thirty-three (54%) were treated in the adjuvant setting. At the time of enrolment, 31 (51%) participants had active treatment for a previous irAE. Overall, 18/61 (30%) participants reported long-term symptoms and trouble in physical and emotional functioning. Physical fatigue was common and interfered with daily activities (n = 12, 20%). In the PRO-CTCAE questionnaire, muscle ache (n = 12, 20%) and joint ache (n = 9, 15%) were commonly reported. Despite this, participants reported overall good health (6.00, range 2.00-7.00) and reasonable level of HRQL (6.00, range 3.00-7.00). Discussion: Melanoma survivors experience long-term symptoms in physical and psychosocial HRQL domains after ICI treatment. These results underline the importance to address existing gaps in survivorship care, implement these findings in clinical practice and increase awareness for long-term symptoms in these patients

Targeting Policy for Obesity Prevention: Identifying the Critical Age for Weight Gain in Women

The obesity epidemic requires the development of prevention policy targeting individuals most likely to benefit. We used self-reported prepregnancy body weight of all women giving birth in Nova Scotia between 1988 and 2006 to define obesity and evaluated socioeconomic, demographic, and temporal trends in obesity using linear regression. There were 172,373 deliveries in this cohort of 110,743 women. Maternal body weight increased significantly by 0.5 kg per year from 1988, and lower income and rural residence were both associated significantly with increasing obesity. We estimated an additional 82,000 overweight or obese women in Nova Scotia in 2010, compared to the number that would be expected from obesity rates of just two decades ago. The critical age for weight gain was identified as being between 20 and 24 years. This age group is an important transition age between adolescence and adulthood when individuals first begin to accept responsibility for food planning, purchasing, and preparation. Policy and public health interventions must target those most at risk, namely, younger women and the socially deprived, whilst tackling the marketing of low-cost energy-dense foods at the expense of healthier options

Investigating the influence of Fe speciation on N2O decomposition over Fe–ZSM-5 catalysts

The influence of Fe speciation on the decomposition rates of N2O over Fe–ZSM-5 catalysts prepared by Chemical Vapour Impregnation were investigated. Various weight loadings of Fe–ZSM-5 catalysts were prepared from the parent zeolite H-ZSM-5 with a Si:Al ratio of 23 or 30. The effect of Si:Al ratio and Fe weight loading was initially investigated before focussing on a single weight loading and the effects of acid washing on catalyst activity and iron speciation. UV/Vis spectroscopy, surface area analysis, XPS and ICP-OES of the acid washed catalysts indicated a reduction of ca. 60% of Fe loading when compared to the parent catalyst with a 0.4 wt% Fe loading. The TOF of N2O decomposition at 600 °C improved to 3.99 × 103 s−1 over the acid washed catalyst which had a weight loading of 0.16%, in contrast, the parent catalyst had a TOF of 1.60 × 103 s−1. Propane was added to the gas stream to act as a reductant and remove any inhibiting oxygen species that remain on the surface of the catalyst. Comparison of catalysts with relatively high and low Fe loadings achieved comparable levels of N2O decomposition when propane is present. When only N2O is present, low metal loading Fe–ZSM-5 catalysts are not capable of achieving high conversions due to the low proximity of active framework Fe3+ ions and extra-framework ɑ-Fe species, which limits oxygen desorption. Acid washing extracts Fe from these active sites and deposits it on the surface of the catalyst as FexOy, leading to a drop in activity. The Fe species present in the catalyst were identified using UV/Vis spectroscopy and speculate on the active species. We consider high loadings of Fe do not lead to an active catalyst when propane is present due to the formation of FexOy nanoparticles and clusters during catalyst preparation. These are inactive species which lead to a decrease in overall efficiency of the Fe ions and consequentially a lower TOF

The formation of methanol from glycerol bio-waste over doped ceria based catalysts

A series of ceria-based solid-solution metal oxides were prepared by co-precipitation and evaluated as catalysts for glycerol cleavage, principally to methanol. The catalyst activity and selectivity to methanol were investigated with respect to the reducibility of the catalysts. Oxides comprising of Ce-Pr and Ce-Zr were prepared, calcined and compared to CeO2, Pr6O11 and ZrO2. The oxygen storage capacity of the catalysts was examined with analysis of Raman spectroscopic measurements and a temperature programmed reduction, oxidation and reduction cycle. The incorporation of Pr resulted in significant defects, as evidenced by Raman spectroscopy. The materials were evaluated as catalysts for the glycerol to methanol reaction and it was found that an increased defect density or reducibility was beneficial. The space time yield of methanol normalised to surface area over CeO2 was found to be 0.052 mmolMeOH m-2 h-1 and over CeZrO2 and CePrO2 this was to 0.029 and 0.076 mmolMeOH m-2 h-1 respectively. The inclusion of Pr reduced the surface area, however, the carbon mole selectivity to methanol and ethylene glycol remained relatively high, suggesting a shift in the reaction pathway compared to that over ceria. This article is part of a discussion meeting issue “Science to enable the circular economy”

In vivo E2F reporting reveals efficacious schedules of MEK1/2–CDK4/6 targeting and mTOR–s6 resistance mechanisms

Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein. These data were supported by phospho-S6 staining of melanoma biopsies from patients treated with CDK4/6i plus targeted inhibitors. Enhanced phospho-S6 in resistant tumors provided a therapeutic window for the mTORC1/2 inhibitor AZD2014. Mechanistically, upregulation or mutation of NRAS was associated with resistance in in vivo models and patient samples, respectively, and mutant NRAS was sufficient to enhance resistance. This study utilizes an in vivo reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance. SIGnIFICAnCE: Mutant BRAF and NRAS melanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling. This resistance mechanism provides the preclinical basis to utilize mTORC1/2 inhibitors to improve MEKi plus CDK4/6i drug regimens

Ammonia decomposition enhancement by Cs-Promoted Fe/Al2O3 catalysts

A range of Cs-doped Fe/Al2O3 catalysts were prepared for the ammonia decomposition reaction. Through time on-line studies it was shown that at all loadings of Cs investigated the activity of the Fe/Al2O3 catalysts was enhanced, with the optimum Cs:Fe being ca. 1. Initially, the rate of NH3 decomposition was low, typically < 10% equilibrium conversion (99.7%@500°C) recorded after 1 h. All catalysts exhibited an induction period (typically ca. 10 h) with the conversion reaching a high of 67% equilibrium conversion for Cs:Fe = 0.5 and 1. The highest rate of decomposition observed was attributed to the balance between increasing the concentration of Cs without blocking the active site. Analysis of H2-TPR and XPS measurements indicated that Cs acts as an electronic promoter. Previously, Cs has been shown to act as a promoter for Ru, where Cs alters the electron density of the active site, thereby facilitating the recombination of N2 which is considered the rate determining step. In addition, XRD and N2 adsorption measurements suggest that with higher Cs loadings deactivation of the catalytic activity is due to a layer of CsOH that forms on the surface and blocks active sites