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SummaryMembers of the European Society for Immunodeficiencies (ESID) and other colleagues have updated the multi-stage expert-opinion-based diagnostic protocol for non-immunologists incorporating newly defined primary immunodeficiency diseases (PIDs). The protocol presented here aims to increase the awareness of PIDs among doctors working in different fields. Prompt identification of PID is important for prognosis, but this may not be an easy task. The protocol therefore starts from the clinical presentation of the patient. Because PIDs may present at all ages, this protocol is aimed at both adult and paediatric physicians. The multi-stage design allows cost-effective screening for PID of the large number of potential cases in the early phases, with more expensive tests reserved for definitive classification in collaboration with a specialist in the field of immunodeficiency at a later stage.

SummaryEfficient early identification of primary immunodeficiency disease (PID) is important for prognosis, but is not an easy task for non-immunologists. The Clinical Working Party of the European Society for Immunodeficiencies (ESID) has composed a multi-stage diagnostic protocol that is based on expert opinion, in order to increase the awareness of PID among doctors working in different fields. The protocol starts from the clinical presentation of the patient; immunological skills are not needed for its use. The multi-stage design allows cost-effective screening for PID within the large pool of potential cases in all hospitals in the early phases, while more expensive tests are reserved for definitive classification in collaboration with an immunologist at a later stage. Although many PIDs present in childhood, others may present at any age. The protocols presented here are therefore aimed at both adult physicians and paediatricians. While designed for use throughout Europe, there will be national differences which may make modification of this generic algorithm necessary.

Age-matched reference values for lymphocyte subpopulations are generally obtained via cross-sectional studies, whereas patients are followed longitudinally. We performed a detailed longitudinal analysis of the changes in lymphocyte subpopulations in a group of 11 healthy infants followed from birth up to 1 y of age, with special attention for early developmental markers, markers of maturation, and markers of activation. We found that T and B lymphocytes increased at 1 and 6 wk of age, respectively. In contrast, NK cells showed a sharp decline directly after birth, suggesting that they are more important during pregnancy than thereafter. CD45RAϩ -mainly CD4 ϩ -naive T lymphocytes were high at birth, and increased further during the first year of life; they form a large expanding pool of cells, ready for participation in primary immune responses. The absolute counts of CD45RO ϩ memory T lymphocytes were similar in infants and adults, albeit with a lower level of expression of CD45RO on infant T lymphocytes. Almost all infant T lymphocytes expressed CD38 throughout the first year of life. The abundant expression of CD38 on an infant's T lymphocytes might be related to a greater metabolic need of the large population of naive untriggered cells that are continually involved in primary immune responses during the first year of life. The high B lymphocyte counts in infants mainly concerned CD38 ϩ B lymphocytes throughout the first year of life. Also, the relative frequencies of CD1c ϩ and CD5 ϩ B lymphocytes were higher throughout the first year of life than in adults. Therefore, CD1c, CD5, and CD38 could be markers of untriggered B lymphocytes. Immunophenotyping of blood lymphocyte subpopulations is an important tool in the diagnosis and follow-up of children with immune disorders. Correct interpretation of the obtained results requires knowledge of the normal development of the immune system during the first years of life.For this purpose, several sets of age-matched reference values of relative frequencies and absolute counts of lymphocyte subpopulations in childhood have been reported (1-5). Because of the higher blood lymphocyte counts in neonates and infants compared with adults (1, 6), differences in lymphocyte subpopulations are better reflected by comparison of absolute counts than relative frequencies. In that way, trends are observed that are missed when only relative frequencies are used (1). These absolute lymphocyte counts are more accurately determined by the lysed whole blood technique than by analysis after density gradient separation (7,8).To date, age-matched reference values for lymphocyte subpopulations were all obtained in cross-sectional studies. Longitudinal studies in individual children are more informative about the pattern of lymphocyte subpopulation development as a function of time. Children with immune disorders are also followed longitudinally. Therefore, it is useful to compare patient data with data from studies on longitudinal development of lymphocyte subpopulations in healthy childr...

Seed predation is an important component of seed mortality of weeds in agro-ecosystems, but the agronomic use and management of this natural weed suppression is hampered by a lack of insight in the underlying ecological processes. In this paper, we investigate whether and how spatial and temporal variation in activity-density of granivorous ground beetles (Coleoptera: Carabidae) results in a corresponding pattern of seed predation. Activity-density of carabids was measured by using pitfall traps in two organic winter wheat fields from March to July 2004. Predation of seeds (Capsella bursa-pastoris, Lamium amplexicaule, Poa annua and Stellaria media) was assessed using seed cards at the same sites and times. As measured by pitfall traps, carabids were the dominant group of insects that had access to the seed cards. In the field, predation of the four different species of seed was in the order: C. bursa-pastoris > P. annua > S. media > L. amplexicaule; and this order of preference was confirmed in the laboratory using the dominant species of carabid. On average, seed predation was higher in the field interior compared to the edge, whereas catches of carabids were highest near the edge. Weeks with elevated seed predation did not concur with high activity-density of carabids. Thus, patterns of spatial and temporal variation in seed predation were not matched by similar patterns in the abundance of granivorous carabid beetles. The lack of correspondence is ascribed to effects of confounding factors, such as weather, the background density of seeds, the composition of the carabid community, and the phenology and physiological state of the beetles. Our results show that differences in seed loss among weed species may be predicted from laboratory trials on preference. However, predator activity-density, as measured in pitfall traps, is an insufficient predictor of seed predation over time and space within a field.

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Background Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. Methods We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). Results We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. Conclusions Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.