New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population.

BACKGROUND Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. The current reference values for 24-hour urinary creatinine excretion rely on observations performed in the 1960s and 1970s in relatively small and mostly selected groups, and may thus poorly fit to the present-day general European population. The aim of this study was to establish and validate anthropometry-based age- and sex-specific reference values of the 24-hour urinary creatinine excretion on adult populations with preserved renal function. METHODS We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2) and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). Based on current reference values (177 to 221 μmol/kg/24 hours in men and 133 to 177 μmol/kg/24 hours in women), 56% of the urinary collections in the whole population and 67% in people >60 years old would have been considered as inaccurate. A linear regression model with sex, BMI and age as predictor variables was found to provide the best prediction of the observed values and showed a good fit when applied to the validation population. CONCLUSIONS We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Holocene vegetation development in the catchment of Sagistalsee (1935 m asl), a small lake in the Swiss Alps

Pollen and plant macrofossils were analysed at Sägistalsee (1935 m asl), a small lake near timber-line in the Swiss Northern Alps. Open forests with Pinus cembra and Abies alba covered the catchment during the early Holocene (9000–6300 cal. BP), suggesting subcontinental climate conditions. After the expansion of Picea abies between 6300 and 6000 cal. BP the subalpine forest became denser and the tree-line reached its maximum elevation at around 2260 m asl. Charcoal fragments in the macrofossil record indicate the beginning of Late-Neolithic human impact at ca. 4400 cal. BP, followed by a extensive deforestation and lowering of the forest-limit in the catchment of Sägistalsee at 3700 cal. BP (Bronze Age). Continuous human activity, combined with a more oceanic climate during the later Holocene, led to the local extinction of Pinus cembra and Abies alba and favoured the mass expansion of Picea and Alnus viridis in the subalpine area of the Northern Alps. The periods before 6300 and after 3700 cal. BP are characterised by high erosion activity in the lake's catchment, whereas during the phase of dense Picea-Pinus cembra-Abies forests (6300–3700 cal. BP) soils were stable and sediment-accumulation rates in the lake were low. Due to decreasing land-use at higher altitudes during the Roman occupation and the Migration period, forests spread beween ca. 2000 and 1500 cal. BP, before human impact increased again in the early Middle Ages. Recent reforestation due to land-use changes in the 20th century is recorded in the top sediments. Pollen-inferred July temperature and annual precipitation suggest a trend to cooler and more oceanic climate starting at about 5500 cal. BP.

Climate-pollen relationships AD 1901-1996 in two small mires near the forest limit in the northern and central Swiss Alps

Climatic relationships were established in two 210Pb dated pollen sequences from small mires closely surrounded by forest just below actual forest limits (but about 300 m below potential climatic forest limits) in the northern Swiss Alps (suboceanic in climate; mainly with Picea) and the central Swiss Alps (subcontinental; mainly Pinus cembra and Larix) at annual or near-annual resolution from ad 1901 to 1996. Effects of vegetational succession were removed by splitting the time series into early and late periods and by linear detrending. Both pollen concentrations detrended by the depth-age model and modified percentages (in which counts of dominant pollen types are down-weighted) are correlated by simple linear regression with smoothed climatic parameters with one-and two-year timelags, including average monthly and April/September daylight air temperatures and with seasonal and annual precipitation sums. Results from detrended pollen concentrations suggest that peat accumulation is favoured in the northern-Alpine mire either by early snowmelt or by summer precipitation, but in the central-Alpine mire by increased precipitation and cooler summers, suggesting a position of the northern-Alpine mire near the upper altitudinal limit of peat formation, but of the central-Alpine mire near the lower limit. Results from modified pollen percentages indicate that pollen pro duction by plants growing near their upper altitudinal limit is limited by insufficient warmth in summer, and pollen production by plants growing near their lower altitudinal limit is limited by too-high temperatures. Only weakly significant pollen/climate relationships were found for Pinus cembra and Larix, probably because they experience little climatic stress growing 300 m below the potential climatic forest limit.

AMS-C14 analysis of graphite obtained with an Automated Graphitization Equipment (AGE III) from aerosol collected on quartz filters

AMS-14C applications often require the analysis of small samples. Such is the case of atmospheric aerosols where frequently only a small amount of sample is available. The ion beam physics group at the ETH, Zurich, has designed an Automated Graphitization Equipment (AGE III) for routine graphite production for AMS analysis from organic samples of approximately 1 mg. In this study, we explore the potential use of the AGE III for graphitization of particulate carbon collected in quartz filters. In order to test the methodology, samples of reference materials and blanks with different sizes were prepared in the AGE III and the graphite was analyzed in a MICADAS AMS (ETH) system. The graphite samples prepared in the AGE III showed recovery yields higher than 80% and reproducible 14C values for masses ranging from 50 to 300 lg. Also, reproducible radiocarbon values were obtained for aerosol filters of small sizes that had been graphitized in the AGE III. As a study case, the tested methodology was applied to PM10 samples collected in two urban cities in Mexico in order to compare the source apportionment of biomass and fossil fuel combustion. The obtained 14C data showed that carbonaceous aerosols from Mexico City have much lower biogenic signature than the smaller city of Cuernavaca.

Constraining age distributions of groundwater from public supply wells in diverse hydrogeological settings in Scania, Sweden

Twenty-five public supply wells throughout the hydrogeologically diverse region of Scania, southern Sweden are subjected to environmental tracer analysis (³H–³He,⁴He, CFCs, SF₆ and for one well only also ⁸⁵Kr and ³⁹Ar) to study well and aquifer vulnerability and evaluate possibilities of groundwater age distribution assessment. We find CFC and SF₆ concentrations well above solubility equilibrium with modern atmosphere, indicating local contamination, as well as indications of CFC degradation. The tracer-specific complications considerably constrain possibilities for sound quantitative regional ground- water age distribution assessment and demonstrate the importance of initial qualitative assessment of tracer-specific reliability, as well a need for additional, complementary tracers (e.g. ⁸⁵Kr,³⁹Ar and potentially also ¹⁴C). Lumped parameter modelling yields credible age distribution assessments for representative wells in four type aquifers. Pollution vulnerability of the aquifer types was based on the selected LPM models and qualitative age characterisation. Most vulnerable are unconfined dual porosity and fractured bedrock aquifers, due to a large component of very young groundwater. Unconfined sedimentary aquifers are vulnerable due to young groundwater and a small pre-modern component. Less vulnerable are semi-confined sedimentary or dual-porosity aquifers, due to older age of the modern component and a larger pre-modern component. Confined aquifers appear least vulnerable, due an entirely pre-modern groundwater age distribution (recharged before 1963). Tracer complications aside, environmental tracer analyses and lumped parameter modelling aid in vulnerability assessment and protection of regional groundwater resources.

Jejunitis and brown bowel syndrome with multifocal carcinogenesis of the small bowel

This is the first report describing a case where prolonged, severe malabsorption from brown bowel syndrome progressed to multifocally spread small bowel adenocarcinoma. This case involves a female patient who was initially diagnosed with chronic jejunitis associated with primary diffuse lymphangiectasia at the age of 26 years. The course of the disease was clinically, endoscopically, and histologically followed for 21 years until her death at the age 47 due to multifocal, metastasizing adenocarcinoma of the small bowel. Multiple lipofuscin deposits (so-called brown bowel syndrome) and severe jejunitis were observed microscopically, and sections of the small bowel showed dense lymphoplasmacytic infiltration of the lamina propria as well as blocked lymphatic vessels. After several decades, multifocal nests of adenocarcinoma cells and extensive, flat, neoplastic mucosal proliferations were found only in the small bowel, along with a loss of the mismatch repair protein MLH1 as a long-term consequence of chronic jejunitis with malabsorption. No evidence was found for hereditary nonpolyposis colon carcinoma syndrome. This article demonstrates for the first time multifocal carcinogenesis in the small bowel in a malabsorption syndrome in an enteritis-dysplasia-carcinoma sequence.

Relative Age Effect in Young Swiss Alpine Skiers From 2004 to 2011

PURPOSE To verify whether the relative age effects (RAEs) occur among young male and female Swiss alpine skiers of different age groups and performance levels. Additionally, the efficacy of normalizing performance in physical tests to height and body mass to attenuate RAEs eventually present was tested. METHODS The Swiss-Ski Power Test consists of anthropometric measures and physical tests for coordination and speed, endurance and strength and is used since 2004 to evaluate 11- to 19-years old Swiss competitive alpine skiers. We analysed the distribution of 6996 tests performed by 1438 male and 1031 female alpine skiers between 2004 and 2011 according to the athlete's relative age quartile (Q). Differences in anthropometric measures and performance in physical tests according to Q were assessed and the possibility of attenuating eventual RAEs on performance by normalization of results to height and body mass was tested. RESULTS RAEs were found among all female and male age groups, with no differences between age groups. While performance level did not affect RAE for male skiers, it influenced RAE among female skiers. RAEs also influenced results in all physical tests except upper limbs strength. Normalization of results to body mass attenuated most RAEs identified. CONCLUSION small RAEs are present among young Swiss competitive alpine skiers and should be taken into account in training and selection settings, avoiding the waste of possible future talents. When ranking junior athletes according to their performance in physical tests, normalization of results to body mass decreases the bias caused by RAEs.

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

PURPOSE Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. METHODS AND MATERIALS Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. RESULTS The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). CONCLUSIONS The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.

Surgery for Stage IIIA Non-Small-cell Lung Cancer: Lack of Predictive and Prognostic Factors Identifying Any Subgroup of Patients Benefiting From It.

Although a trimodality regimen for patients with stage IIIA/pN2 non-small-cell lung cancer (NSCLC) has been variably used owing to limited evidence for its benefits, it remains unknown whether any patient subgroup actually receives benefit from such an approach. To explore this question, the published data were reviewed from 1990 to 2015 to identify the possible predictors and prognosticators in this setting. Overall survival was the endpoint of our study. Of 27 identified studies, none had studied the predictors of improved outcomes with trimodality treatment. Of the potential patient- and tumor-related prognosticators, age, gender, and histologic type were the most frequently formally explored. However, none of the 3 was found to influence overall survival. The most prominent finding of the present review was the substantial lack of data supporting a trimodality treatment approach in any patient subgroup. As demonstrated in completed prospective randomized studies, the use of surgery for stage IIIA NSCLC should be limited to well-defined clinical trials.

Small-diameter titanium grade IV and titanium-zirconium implants in edentulous mandibles: five-year results from a double-blind, randomized controlled trial.

BACKGROUND The aim of this study was to compare the 5-year survival and success rates of 3.3 mm dental implants either made from titanium-zirconium (TiZr) alloy or from Grade IV titanium (Ti Grade IV) in mandibular implant-based removable overdentures. METHODS The core study had a follow-up period of 36 months and was designed as a randomized, controlled, double-blind, split-mouth multicenter clinical trial. Patients with edentulous mandibles received two Straumann Bone Level implants (diameter 3.3 mm, SLActive®), one of TiZr (test) and one of Ti Grade IV (control), in the interforaminal region. This follow-up study recruited patients from the core study and evaluated the plaque and sulcus bleeding indices, radiographic crestal bone level, as well as implant survival and success 60 months after implant placement. RESULTS Of the 91 patients who initially received implants, 75 completed the 36 month follow-up and 49 were available for the 60 month examination. Two patients were excluded so that a total of 47 patients with an average age of 72 ± 8 years were analysed. The characteristics and 36-month performance of the present study cohort did not differ from the non-included initial participants (p > 0.05). In the period since the 36-month follow-up examination, no implant was lost. The cumulative implant survival rate was 98.9 % for the TiZr group and 97.8 % for the Ti Grade IV group. Crestal bone level changes at 60 months were not different in the test and control group (TiZr -0.60 ± 0.69 mm and Ti Grade IV -0.61 ± 0.83 mm; p = 0.96). The cumulative implant success rate after 60 months was 95.8 and 92.6 % for TiZr and Ti Grade IV, respectively. CONCLUSIONS After 60 months, the positive outcomes of the 36 month results for TiZr and Ti Grade IV implants were confirmed, with no significant differences with regard to crestal bone level change, clinical parameters and survival or success rates. TiZr implants performed equally well compared to conventional Ti Grade IV 3.3 mm diameter-reduced implants for mandibular removable overdentures. TRIAL REGISTRATION Registered on www.clinicaltrials.gov: NCT01878331.

Influence of the gestational stage on the clinical course, lesional development and parasite distribution in experimental ovine neosporosis.

Neospora caninum is considered one of the main causes of abortion in cattle, yet recent studies have also emphasised its relevance as an abortifacient in small ruminants. In order to gain deeper insight into the pathogenesis of ovine neosporosis, pregnant ewes were intravenously inoculated with 10(6) tachyzoites of the Nc-Spain7 isolate at days 40, 90 or 120 of gestation. Infection during the first term resulted in the death of all foetuses between days 19 and 21 post-infection, showing mainly necrotic lesions in foetal liver and the highest parasite DNA detection and burden in both placenta and foetal viscera. After infection at day 90, foetal death was also detected in all ewes, although later (34-48 days post-infection). In this group, lesions were mainly inflammatory. Foetal livers showed the lowest frequency of lesions, as well as the lowest parasite detection and burden. All ewes infected at day 120 delivered viable lambs, although 3 out of 9 showed weakness and recumbency. Neospora DNA was detected in all lambs but one, and parasite burden was similar to that observed in day 90 group. Lesions in this group showed more conspicuous infiltration of inflammatory cells and higher frequency in foetal brain and muscle when compared to both previous groups. These results highlight the crucial role that the stage of gestation plays on the course of ovine neosporosis, similar to that reported in bovine neosporosis, and open the doors to consider sheep as a valid model for exogenous transplacental transmission for ruminant neosporosis.

Stratospheric age of air variations between 1600 and 2100

The current understanding of preindustrial stratospheric age of air (AoA), its variability, and the potential natural forcing imprint on AoA is very limited. Here we assess the influence of natural and anthropogenic forcings on AoA using ensemble simulations for the period 1600 to 2100 and sensitivity simulations for different forcings. The results show that from 1900 to 2100, CO₂ and ozone-depleting substances are the dominant drivers of AoA variability. With respect to natural forcings, volcanic eruptions cause the largest AoA variations on time scales of several years, reducing the age in the middle and upper stratosphere and increasing the age below. The effect of the solar forcing on AoA is small and dominated by multidecadal total solar irradiance variations, which correlate negatively with AoA. Additionally, a very weak positive relationship driven by ultraviolett variations is found, which is dominant for the 11 year cycle of solar variability.