Clinical laboratory reference values amongst children aged 4 weeks to 17 months in Kilifi, Kenya: A cross sectional observational study

Reference intervals for clinical laboratory parameters are important for assessing eligibility, toxicity grading and management of adverse events in clinical trials. Nonetheless, haematological and biochemical parameters used for clinical trials in sub-Saharan Africa are typically derived from industrialized countries, or from WHO references that are not region-specific. We set out to establish community reference values for haematological and biochemical parameters amongst children aged 4 weeks to 17 months in Kilifi, Kenya. We conducted a cross sectional study nested within phase II and III trials of RTS, S malaria vaccine candidate. We analysed 10 haematological and 2 biochemical parameters from 1,070 and 423 community children without illness prior to experimental vaccine administration. Statistical analysis followed Clinical and Laboratory Standards Institute EP28-A3c guidelines. 95% reference ranges and their respective 90% confidence intervals were determined using non-parametric methods. Findings were compared with published ranges from Tanzania, Europe and The United States. We determined the reference ranges within the following age partitions: 4 weeks to <6 months, 6 months to less than <12 months, and 12 months to 17 months for the haematological parameters; and 4 weeks to 17 months for the biochemical parameters. There were no gender differences for all haematological and biochemical parameters in all age groups. Hb, MCV and platelets 95% reference ranges in infants largely overlapped with those from United States or Europe, except for the lower limit for Hb, Hct and platelets (lower); and upper limit for platelets (higher) and haematocrit(lower). Community norms for common haematological and biochemical parameters differ from developed countries. This reaffirms the need in clinical trials for locally derived reference values to detect deviation from what is usual in typical children in low and middle income countries

Annex to Quirke et al. Quality assurance in pathology in colorectal cancer screening and diagnosis: annotations of colorectal lesions

Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document includes a chapter on pathology with pan-European recommendations which take into account the diversity and heterogeneity of health care systems across the EU. The present paper is based on the annex to the pathology chapter which attempts to describe in greater depth some of the issues raised in the chapter in greater depth, particularly details of special interest to pathologists. It is presented here to make the relevant discussion known to a wider scientific audience

Measuring 129Xe transfer across the blood‐brain barrier using MR spectroscopy

Purpose This study develops a tracer kinetic model of xenon uptake in the human brain to determine the transfer rate of inhaled hyperpolarized 129Xe from cerebral blood to gray matter that accounts for the effects of cerebral physiology, perfusion and magnetization dynamics. The 129Xe transfer rate is expressed using a tracer transfer coefficient, which estimates the quantity of hyperpolarized 129Xe dissolved in cerebral blood under exchange with depolarized 129Xe dissolved in gray matter under equilibrium of concentration. Theory and Methods Time‐resolved MR spectra of hyperpolarized 129Xe dissolved in the human brain were acquired from three healthy volunteers. Acquired spectra were numerically fitted with five Lorentzian peaks in accordance with known 129Xe brain spectral peaks. The signal dynamics of spectral peaks for gray matter and red blood cells were quantified, and correction for the 129Xe T1 dependence upon blood oxygenation was applied. 129Xe transfer dynamics determined from the ratio of the peaks for gray matter and red blood cells was numerically fitted with the developed tracer kinetic model. Results For all the acquired NMR spectra, the developed tracer kinetic model fitted the data with tracer transfer coefficients between 0.1 and 0.14. Conclusion In this study, a tracer kinetic model was developed and validated that estimates the transfer rate of HP 129Xe from cerebral blood to gray matter in the human brain