X‐ray microdensitometry on annually resolved tree‐ring samples has gained an exceptional position in last‐millennium paleoclimatology through the maximum latewood density (MXD) parameter, but also increasingly through other density parameters. For 50 years, X‐ray based measurement techniques have been the de facto standard. However, studies report offsets in the mean levels for MXD measurements derived from different laboratories, indicating challenges of accuracy and precision. Moreover, reflected visible light‐based techniques are becoming increasingly popular, and wood anatomical techniques are emerging as a potentially powerful pathway to extract density information at the highest resolution. Here we review the current understanding and merits of wood density for tree‐ring research, associated microdensitometric techniques, and analytical measurement challenges. The review is further complemented with a careful comparison of new measurements derived at 17 laboratories, using several different techniques. The new experiment allowed us to corroborate and refresh “long‐standing wisdom” but also provide new insights. Key outcomes include (i) a demonstration of the need for mass/volume‐based recalibration to accurately estimate average ring density; (ii) a substantiation of systematic differences in MXD measurements that cautions for great care when combining density data sets for climate reconstructions; and (iii) insights into the relevance of analytical measurement resolution in signals derived from tree‐ring density data. Finally, we provide recommendations expected to facilitate futureinter‐comparability and interpretations for global change research.

Pseudohypoaldosteronismus Typ 1 (PHA1) ist eine seltene Erkrankung, die durch Hyponatriämie, Hyperkaliämie und metabolische Azidose bei hohen Aldosteron- und Renin-Spiegeln charakterisiert ist. Die Aldosteron-Resistenz kann durch Mutationen des epithelialen Natriumkanals (ENaC) (autosomal-rezessiv) oder des Mineralokortikoidrezeptors (autosomal-dominant) verursacht sein.

Einleitung: Geburtstraumatische Zwerchfellparesen treten isoliert oder im Rahmen einer Armplexusparese auf. Die rechte Seite ist in etwa 80% der Fälle betroffen, weniger als 10% treten bilateral auf.

The interpretation of the atopy patch test (APT) to foods is not standardized. This study aimed to validate the reading of the APT in terms of the diagnostic accuracy of individual skin signs. Eighty-seven children (mean age 2.4 +/- 2.5 yr, range 0.5-13.5; 57 male) with atopic dermatitis (AD) and suspected food allergies underwent APT to cow's milk, hen's egg, wheat and soy. Twelve-millimetre Finn chambers were applied for 48 h, and results were read after 48 and 72 h. Skin changes were graded for erythema, induration, papule formation and 'crescendo' phenomenon (increase of skin sign severity from 48 to 72 h). Food allergy was assessed by double blind, placebo-controlled food challenges (DBPCFC). Sensitivity, specificity and predictive values were calculated for each skin signs in relation to challenge outcome. Of 165 DBPCFC children, 75 (45%) were positive. The combination of any skin induration plus papules (seven or more), or of moderate erythema plus any induration plus seven or more papules had a positive predictive value (PPV) and specificity for the challenge outcome of 100%; however, the sensitivity was low (8% and 15%). The best diagnostic accuracy for single signs was found for induration beyond the Finn chamber margin (PPV 88%, specificity 99%, sensitivity 9%) and presence of at least seven papules (PPV 80%, specificity 96% sensitivity 21%). Presence of both induration and of at least seven papules at 72 h were the APT skin signs with the greatest diagnostic accuracy for food allergy in children with AD.

Background: There is an increasing need to develop test instruments that make oral food challenges superfluous.Objective: We sought to study the utility of atopy patch tests (APTs) in the diagnostic workup of food allergy.Methods: We investigated 437 children (median age, 13 months; 90% with atopic dermatitis) referred for evaluation of suspected food allergy. Specific serum IgE (sIgE) measurements, skin prick tests (SPTs), APTs, and controlled oral food challenges were performed.Results: We analyzed 873 oral challenges with cow's milk, hen's egg, wheat, and/or soy. One thousand seven hundred single APTs were performed. As a single parameter, the APTs showed the best specificity compared with sIgE measurements, SPTs, or both. Combining the APT with either the SPT or sIgE measurement resulted in improved sensitivity and specificity. Decision points for sIgE measurement and for the SPT showed lower values when combined with a positive APT result. Correctly bypassing an oral food challenge with combined testing, including APTs, only between 0.5% and 7% (99% predicted probability) and between 6% and 14% (using 95% predicted probability) of children would fulfill the criteria for avoiding an oral food challenge.Conclusion: Although the predictive capacity of the APT is improved when combined with sIgE measurement or the SPT, oral food challenges become superfluous in only 0.5% to 14% of study patients. In addition, the APT is time consuming and demands a highly experienced test evaluator.Clinical implications: For daily clinical practice, the APT adds only a small predictive value to the standard SPT and sIgE measurement in the diagnostic workup of suspected food-related symptoms in our study population.

BACKGROUND:Specific serum IgE is considered as one of the important diagnostic measures in the diagnostic work-up of food allergy. OBJECTIVE:To evaluate the role of specific serum IgE in predicting the outcome of oral food challenges, and to determine threshold concentrations of specific serum IgE that could render double-blind, placebo-controlled food challenges unnecessary. METHODS:In 501 children (median age 13 months), 992 controlled oral challenges were performed with cow's milk (CM), hen's egg (HE), wheat and soy. 440/501 (88%) children suffered from atopic dermatitis. For all children, specific IgE concentrations in serum were determined. Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics-curves as well as predictive decision points were calculated. RESULTS:Four hundred and forty-five out of 992 oral food challenges with allergens were assessed as positive. Sensitivity of specific serum IgE was 97% for HE, 83% for CM, 69% for soy, and 79% for wheat. Specificity was 51% for HE, 53% for CM, 50% for soy, and 38% for wheat. Calculating 90%, 95% and 99% predicted probabilities using logistic regression revealed predictive decision points of 6.3, 12.6, and 59.2 kU/L for HE, respectively. Subdividing our children in those of below or above 1 year of age resulted in a markedly different predicted probability for HE. For CM, only the 90% predicted probability (88.8 kU/L) could be calculated. No decision points could be determined for CM, wheat and soy. CONCLUSION:In general, specific serum IgE levels showed a correlation with the outcome of positive oral food challenges for CM and HE. Meaningful predictive decision points can be calculated for HE, which may help to avoid oral food challenges in some cases. However, data need to be ascertained for each allergen separately. Furthermore, the age of the patient population under investigation must also be taken into account.

Background The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of food allergy.Objective To evaluate the diagnostic capacity of the SPT in predicting the outcome of oral food challenges, and to determine decision points for the weal size and the skin index (SI) that could render double-blind, placebo-controlled food challenges unnecessary.Methods In 385 children (median age 22 months), 735 controlled oral challenges were performed with cow's milk (CM), hen's egg (HE), wheat and soy. Three hundred and thirty-six of 385 (87%) children suffered from atopic dermatitis. SPT was performed in all children. Diagnostic capacity, receiver-operator characteristics (ROC) curves and predictive decision points were calculated for the mean weal size and the calculated SI.Results Three hundred and twelve of 735 (43%) oral food challenges were assessed to be positive. Calculation of 95% and 99% predicted probabilities using logistic regression revealed predictive decision points of 13.0 and 17.8 mm for HE, and 12.5 and 17.3 mm for CM, respectively. However, using the SI, the corresponding cut-off levels were 2.6 and 3.7, respectively, for HE, and 2.7 and 3.7 for CM. For wheat, 95% and 99% decision points of 2.2 and 3.0 were found in children below 1 year of age.Conclusion Predictive decision points for a positive outcome of food challenges can be calculated for HE and CM using weal size and SI. They may help to avoid oral food challenges.

RATIONALE: The interpretation of the atopy patch test (APT) to foods is subjective and not standardised. This study aimed to validate the diagnostic accuracy of individual APT skin signs. METHODS: 87 children (mean age 2.4±2.53 years, range 0.5 to 13.5; 57 male) with suspected food allergies underwent APT to cow milk, egg, soy and wheat flour. Skin changes were graded at 48 and 72 hours for erythema, induration, papule formation, vesiculation and 'crescendo' (increase of lesions from 48 to 72 hours). Food allergy was assessed by double-blind placebo-controlled challenges (DBPCFC). Sensitivity, specificity and positive predictive value (PPV) were calculated for each individual skin sign, in relation to DBPCFC outcome. RESULTS: Of 165 DBPCFC, 70 (38%) were positive. At 72 hours, presence of any erythema (sensitivity 77%) or any papules (sensitivity 59%) were the most sensitive parameters. Moderate erythema, skin induration or presence of ≥7 papules at 72 hours had a specificity of ≥95%. Induration with blurred margins and vesicular lesions were the most specific changes (specificity ≥99%), but lacked sensitivity (4-10%). Although a 'crescendo' was highly specific (91%), its PPV was only 44%. The highest PPV's at 72 hours were found for ≥7 papules (76%), induration with blurred margins (88%) and vesicular lesions (100%). The combination of moderate erythema and presence of ≥7 papules at 72 hours provided the best PPV (76%) and specificity (95%). CONCLUSION: Presence of moderate erythema and ≥7 papules at 72 hours was the skin sign combination with the highest PPV and specificity in the diagnosis of food allergy.

BACKGROUND:Double-blind, placebo-controlled food challenges are time-consuming, expensive and not without risk to patients. Therefore, an in vitro test that could accurately diagnose food allergy would be of great value.OBJECTIVE:To evaluate the utility of the ratio of specific immunoglobulin E (IgE)/total IgE compared with specific IgE (sIgE) alone in predicting symptomatic food allergy.METHODS:We retrospectively analysed 992 controlled oral food challenges performed in 501 children (median age 13 months). The ratio of sIgE/total IgE was calculated and tested for correlation with the outcome of food challenges. Receiver operator characteristics (ROC)-curves were performed; predicted probabilities and predictive decision points were calculated.RESULTS:A significant correlation was found between the ratio and the outcome of food challenges for cow's milk (CM), hen's egg (HE), and wheat, but not for soy. The ROC and predicted probability curves as well as sensitivity and specificity of the decision points of the ratio were similar to those of sIgE levels for CM, HE and wheat.CONCLUSION:In view of the greater effort needed to determine the ratio, without benefit compared with the sIgE alone, the calculation of the ratio of sIgE/total IgE for diagnosing symptomatic food allergy offers no advantage for CM, HE, wheat or soy. For the majority of cases controlled oral food challenges still remain the method of choice.

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The dysplasia of anal sphincter represents an obstructive defecation disorder. The disease is known as "anterior displaced anus" in pediatric surgery. An anorectal malformation with missing dorsal osseous fixation of the sphincter complex is the underlying cause. Beyond clinical symptoms and examination result (anterior displaced anus with palpable dorsal gap) the defect can be visualized by computered tomography. A surgical correction is possible by the simple intervention of dorsal sphincteropexy. In our trial with 48 patients (male n = 12, female n = 36, mean age 51 +/- 17 years, follow-up in 39 patients) a significant improvement of defecation could be achieved in 46 % of the patients. In correlation to a good clinical outcome a significant reduction in the defecation score was observed. 10 % of the patients had only small changes in symptoms. However, the proportion of dissatisfied patients was relatively high with 44 %. In this group patients with long-standing chronic constipation and laxative abusus were found more often and the rate of previous anal or abdominal surgery was quite higher. Dissatisfied patients showed a higher variation in symptoms of pelvic floor disorders (e. g. anal pain syndrome) besides the rectal evacuation disorder. In addition to the heterogenity of symptoms chronic alterations of pelvic floor structures might create worse results in patients with chronic constipation. In spite of a lot of publications dealing with the functional anatomy of the pelvic floor only a few investigations on the dorsal sphincter dysplasia in patients with rectal evacuation disorder are found in the literature. Further investigations on this disorder are necessary.

The dysplasia of anal sphincter represents an obstructive defecation disorder. The disease is known as "anterior displaced anus" in pediatric surgery. An anorectal malformation with missing dorsal osseous fixation of the sphincter complex is the underlying cause. Beyond clinical symptoms and examination result (anterior displaced anus with palpable dorsal gap) the defect can be visualized by computered tomography. A surgical correction is possible by the simple intervention of dorsal sphincteropexy. In our trial with 48 patients (male n = 12, female n = 36, mean age 51 17 years, follow-up in 39 patients) a significant improvement of defecation could be achieved in 46% of the patients. In correlation to a good clinical outcome a significant reduction in the defecation score was observed. 10% of the patients had only small changes in symptoms. However, the proportion of dissatisfied patients was relatively high with 44%. In this group patients with long-standing chronic constipation and laxative abusus were found more often and the rate of previous anal or abdominal surgery was quite higher. Dissatisfied patients showed a higher variation in symptoms of pelvic floor disorders (e.g. anal pain syndrome) besides the rectal evacuation disorder. In addition to the heterogenity of symptoms chronic alterations of pelvic floor structures might create worse results in patients with chronic constipation.In spite of a lot of publications dealing with the functional anatomy of the pelvic floor only a few investigations on the dorsal sphincter dysplasia in patients with rectal evacuation disorder are found in the literature. Further investigations on this disorder are necessary.

From a bovine genomic library, five overlapping clones, spanning some 50 kb, have been isolated. These clones contain the complete alphas2-casein-encoding gene (alphas2ca) and its 5' and 3' flanking regions. The nucleotide (nt) sequence of the complete gene including 25 1 0 bp of the 5' flanking region and 276 bp of the 3' region has been determined. The total length of alphas2ca appears to be 18 483 bp and, therefore, it is the longest of the four bovine casein-encoding genes. The alphas2ca gene is comprised of 18 exons ranging in size from 21 to 266 nt. There are 16 Alu-like artiodactyla retroposons inserted at ten different locations within the gene. About 14% of the gene is composed of these repetitive sequences. Although the organization of alphas2ca appears to be similar to that of the alphas1-casein-encoding gene (alphas1ca), sequence comparisons and the length of the exons indicate that it is more closely related to the beta-casein-encoding gene. Furthermore, it is shown that both genes could have evolved from a common ancestor by means of internal duplications.