Quality of health care in adolescents and adults with disorders/differences of sex development (DSD) in six European countries (dsd-LIFE).

BACKGROUND: To investigate the association between the structural quality of care and patient satisfaction with care in individuals with disorders/ differences of sex development (DSD). METHODS: A multicenter cross-sectional comparative study was conducted in 14 clinics in six European countries. We assessed the level of structural quality of care in each center using a self-constructed measure (Center Score) and the level of participant satisfaction with care using the customer satisfaction questionnaire (CSQ-4) and an adopted version of the Youth Health Care - Satisfaction, Utilization & Needs (YHC-SUN-SF). Data were obtained from individuals with Turner Syndrome (261), Klinefelter Syndrome (173), 46, XX congenital adrenal hyperplasia (190) and XY-DSD (257). RESULTS: We found large variations between the scores for structural quality of care both within a diagnostic group and within a country; the overall association between participant satisfaction with the center score was significant. CONCLUSIONS: Comparative effectiveness research across Europe can lead to more insight on beneficial structures and processes and the overall strategy to care for people with rare diseases in general and specific conditions such as disorders/ differences of sex development. Appreciation of higher levels of structural quality of the centers in this study supports the concept of comprehensive care. TRIAL REGISTRATION: German Clinical Trials Register: Registration identification number: DRKS00006072 , date of registration April 17th, 2014. DRKS00006072 (German Clinical Trials Register).

Emergence of the Reactivity Continuum of Organic Matter from Kinetics of a Multitude of Individual Molecular Constituents.

The reactivity continuum (RC) model is a powerful statistical approach for describing the apparent kinetics of bulk organic matter (OM) decomposition. Here, we used ultrahigh resolution mass spectrometry data to evaluate the main premise of the RC model, namely that there is a continuous spectrum of reactivity within bulk OM, where each individual reactive type undergoes exponential decay. We performed a 120 day OM decomposition experiment on lake water, with an untreated control and a treatment preexposed to UV light, and described the loss of bulk dissolved organic carbon with RC modeling. The behavior of individual molecular formulas was described by fitting the single exponential model to the change in peak intensities over time. The range of the empirically derived apparent exponential decay coefficients (kexp) was indeed continuous. The character of the corresponding distribution, however, differed from the conceptual expectations, due to the effects of intrinsic averaging, overlaps in formula-specific loss and formation rates, and the limitation of the RC model to include apparently accumulating compounds in the analysis. Despite these limitations, both the RC model-simulated and empirical (mass spectrometry-derived) distributions of kexp captured the effects of preexposure to UV light. Overall, we present experimental evidence that the reactivity continuum within bulk OM emerges from a range of reactivity of numerous individual components. This constitutes direct empirical support for the major assumption behind the RC model of the natural OM decomposition.

Surgical Practice in Girls with Congenital Adrenal Hyperplasia: An International Registry Study.

In this article international trends in surgical practice in girls with congenital adrenal hyperplasia (CAH) are evaluated. All cases that had been classified in the I-CAH/I-DSD registry as 46,XX CAH and who were born prior to 2017 were identified. Centers were approached to obtain information on surgical decision making. Of the 330 included participants, 208 (63.0%) presented within the first month of life, and 326 (98.8%) cases were assigned female. Genital surgery had been performed in 250 (75.8%). A total of 64.3, 89.2, and 96.8% of cases residing in Europe, South America and Asia, respectively, had at least one surgery. In a logistic regression model for the probability of surgery before the second birthday (early surgery) over time an increase of probability for early vaginal surgery could be identified, but not for clitoral surgery or both surgeries combined. Genitoplasty in girls with CAH remains controversial. This large international study provides a snapshot of current practice and reveals geographical and temporal differences. Fewer surgeries were reported for Europe, and there seems to be a significant trend towards aiming for vaginal surgery within the first 2 years of life.

Modelled phototransformation kinetics of the antibiotic sulfadiazine in organic matter-rich lakes.

Xenobiotic compounds are commonly detected in inland waters. Sunlight-induced photochemical reactions contribute to xenobiotic degradation, but the role of different photoreactions on large geographic scales remains poorly understood. Here, we used a combination of photochemical modelling and large-scale field data from 1020 lakes across Sweden to elucidate the photodegradation kinetics of the commonly used antibiotic sulfadiazine (SDZ) in organic matter-rich lakes. SDZ occurs in two forms, namely acidic HSDZ (pKa = 6.5) and basic/deprotonated SDZ-. Both species are oxidised fast by the photogenerated triplet states of natural organic matter (3NOM*). However, they also undergo efficient back reactions because the partially oxidised HSDZ (and SDZ- to a larger extent) can be reduced back to the initial compounds by the phenolic moieties contained in NOM. Typical lakes in Sweden are rich in NOM and have low pH, with the consequence that SDZ photochemistry would be dominated by HSDZ. Our simulation results showed that SDZ photodegradation kinetics in Swedish lakes would become significantly slower with increasing water depth and pH, while it depended little on latitude, which affects irradiance, or on organic matter content. As a consequence, SDZ would be particularly persistent in lakewater in some densely populated areas with relatively deep and high-pH lakes such as, most notably, the Stockholm region. Here the surface waters could be more heavily contaminated by pharmaceuticals compared to the scarcely populated regions in the centre-north of the country, where lakewater could otherwise promote an efficient photodegradation of SDZ.

Simulation of photoreactive transients and of photochemical transformation of organic pollutants in sunlit boreal lakes across 14 degrees of latitude: A photochemical mapping of Sweden.

Lake water constituents, such as chromophoric dissolved organic matter (CDOM) and nitrate, absorb sunlight which induces an array of photochemical reactions. Although these reactions are a substantial driver of pollutant degradation in lakes they are insufficiently understood, in particular on large scales. Here, we provide for the first time comprehensive photochemical maps covering a large geographic region. Using photochemical kinetics modeling for 1048 lakes across Sweden we simulated the steady-state concentrations of four photoreactive transient species, which are continuously produced and consumed in sunlit lake waters. We then simulated the transient-induced photochemical transformation of organic pollutants, to gain insight into the relevance of the different photoreaction pathways. We found that boreal lakes were often unfavorable environments for photoreactions mediated by hydroxyl radicals (OH) and carbonate radical anions (CO3-), while photoreactions mediated by CDOM triplet states (3CDOM*) and, to a lesser extent, singlet oxygen (1O2) were the most prevalent. These conditions promote the photodegradation of phenols, which are used as plastic, medical drug and herbicide precursors. When CDOM concentrations increase, as is currently commonly the case in boreal areas such as Sweden, 3CDOM* will also increase, promoting its importance in photochemical pathways even more.

Clinical and molecular characterization of patients with heterozygous mutations in wilms tumor suppressor gene 1.

BACKGROUND AND OBJECTIVES: The Wilms tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Genotype/phenotype correlations of WT1 mutations with renal function and proteinuria have been observed in world-wide cohorts with nephrotic syndrome or Wilms tumor (WT). This study analyzed mid-European patients with known constitutional heterozygous mutations in WT1, including patients without proteinuria or WT. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Retrospective analysis of genotype, phenotype, and treatment of 53 patients with WT1 mutation from all pediatric nephrology centers in Germany, Austria, and Switzerland performed from 2010 to 2012. RESULTS: Median age was 12.4 (interquartile range [IQR], 6-19) years. Forty-four of 53 (83%) patients had an exon mutation (36 missense, eight truncating), and nine of 53 (17%) had an intronic lysine-threonine-serine (KTS) splice site mutation. Fifty of 53 patients (94%) had proteinuria, which occurred at an earlier age in patients with missense mutations (0.6 [IQR, 0.1-1.5] years) than in those with truncating (9.7 [IQR, 5.7-11.9]; P<0.001) and splice site (4.0 [IQR, 2.6-6.6]; P=0.004) mutations. Thirteen of 50 (26%) were treated with steroids and remained irresponsive, while three of five partially responded to cyclosporine A. Seventy-three percent of all patients required RRT, those with missense mutations significantly earlier (at 1.1 [IQR, 0.01-9.3] years) than those with truncating mutations (16.5 [IQR, 16.5-16.8]; P<0.001) and splice site mutations (12.3 [IQR, 7.9-18.2]; P=0.002). Diffuse mesangial sclerosis was restricted to patients with missense mutations, while focal segmental sclerosis occurred in all groups. WT occurred only in patients with exon mutations (n=19). Fifty of 53 (94%) patients were karyotyped: Thirty-one (62%) had XY and 19 (38%) had XX chromosomes, and 96% of male karyotypes had urogenital malformations. CONCLUSIONS: Type and location of WT1 mutations have predictive value for the development of proteinuria, renal insufficiency, and WT. XY karyotype was more frequent and associated with urogenital malformations in most cases.

Selective loss and preservation of lake water dissolved organic matter fluorescence during long-term dark incubations.

The biogeochemical processing of dissolved organic matter (DOM) in inland waters is inherently related to its molecular structure and ecological function. Controlled bioassays are a valuable tool to analyze these relationships, but are seldom conducted and compared at temporal scales that typically prevail in natural inland waters. Here we incubated water from six boreal lakes in the dark and examined changes to the initial fluorescence and absorbance after 3.5 years. We identified five fluorescence components with parallel factor (PARAFAC) analysis (C(C,) C(M), C(A), C(X) and C(T)) and found a consistent change in the relative intensity of two dominant PARAFAC components (increase in C(A):C(C), corresponding to Peak A:Peak C), commonly found in lake water, that represent terrestrially-derived DOM. Surprisingly, we only found minor changes to specific absorbance (SUVA), and did not find any changes to other spectral indexes including the fluorescence index, humification index and freshness index. By incorporating lakes spanning a wide range of initial total organic carbon concentrations (3.7 to 32.5 mg L(-1)), water residence times, and spectral characteristics (e.g. SUVA 1.13 to 3.77 L·mg C(-1)·m(-1)), we found that the relative intensities of two humic-like peaks were the most revealing of changes to DOM structure during dark incubations. We also verified that inner filter effects were adequately corrected within the concentration range of incubated samples. Thus, the processing of DOM under dark conditions, including microbial decomposition and flocculation, may have a greater influence on the humic-like peaks, particularly C(C) (Peak C), with negligible changes to more commonly used spectral indexes.