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Background: Skeletal bone age assessment for medical reasons is usually performed by conventional x-ray with use of ionizing radiation. Few pilot studies have shown the possible use of magnetic resonance imaging (MRI)., Purpose: To comprehensively evaluate feasibility and value of MRI for skeletal bone age (SBA) assessment in healthy male children., Materials and Methods: In this prospective cross-sectional study, 63 male soccer athletes with mean age of 12.35 ± 1.1 years were examined. All participants underwent 3.0 Tesla MRI with coronal T1-weighted turbo spin echo (TSE), coronal proton density (PD)-weighted turbo spin echo (TSE), and T1-weighted three-dimensional (3D) volume interpolated breath-hold examination (VIBE) sequence. Subsequently, SBA was assessed by 3 independent blinded radiologists with different levels of experience using the common Greulich-Pyle (GP) atlas and the Tanner-Whitehouse (TW2) method., Results: In a mean total acquisition time of 5:04 ± 0:47 min, MR image quality was sufficient in all cases. MRI appraisal was significantly faster ( P < 0.0001) by GP with mean duration of 1:22 ± 0:08 min vs. 7:39 ± 0:28 min by TW. SBA assessment by GP resulted in mean age of 12.8 ± 1.2 years, by TW 13.0 ± 1.4 years. Interrater reliabilities were excellent for both GP (ICC = 0.912 (95% confidence interval [CI] = 0.868-0.944) and TW (ICC = 0.988 (95% CI = 0.980-0.992) and showed statistical significance ( P < 0.001). Subdivided, for GP, ICCs were 0.822 (95% CI = 0.680-0.907) and 0.843 (95% CI = 0.713-0.919) in Under 12 and Under 14 group. For TW, ICCs were 0.978 (95% CI = 0.958-0.989) in Under 12 and 0.979 (95% CI = 0.961-0.989) in Under 14 group., Conclusion: MRI is a clinically feasible, rapidly evaluable method to assess skeletal bone age of healthy male children. Using the Greulich-Pyle (GP) atlas or the Tanner-Whitehouse (TW2) method, reliable results are obtained independent of the radiologist's experience level., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Reliable talent identification and selection (TID) processes are prerequisites to accurately select young athletes with the most potential for talent development programmes. Knowledge about the agreement between scouts who play a key role in the initial TID in football is lacking. Therefore, the aim of the present study was to evaluate the agreement within four groups of a total of n  = 83 talent scouts during rank assessment of under-11 male youth football players ( n  = 24, age = 11.0 ± 0.3 years) and to describe scouts' underlying approach to assess talent. Krippendorff's α estimates indicated disagreement of scouts' rankings within all groups of scouts (α A  = 0.09, α B  = 0.03, α C  = 0.05, α D  = 0.02). Scouts reported relying mainly on their overall impression when forming their final prediction about a player. Reportings of a consistent, structured approach were less prevalent. Taken together, results indicated that different approaches to TID may be associated with disagreement on selection decisions. In order to overcome disagreement in TID, football organisations are encouraged to establish a more structured process. Future research on the elaboration and benefit of ranking guidelines incorporating decomposed and independently evaluated sub-predictors is recommended to improve the reliability of TID.

Bio-banding has been introduced to reduce the impact of inter-individual differences due to biological maturation among youth athletes. Existing studies in youth soccer have generally examined the pilot-testing application of bio-banding. This is the first study that investigated whether bio-banded (BB) versus chronological age (CA) competition affects reliable physiological and technical-tactical in-game key performance indicators (KPIs) using a randomized cross-over repeated measures design. Sixty-five youth elite soccer players from the under-13 (U 13 ) and under-14 (U 14 ) age category and with maturity offsets (MO) between -2.5 and 0.5 years, competed in both a BB and CA game. For statistical analysis, players were divided into four sub-groups according to CA and MO: U 13 MO low (CA ≤ 12.7, MO ≤ -1.4), U 13 MO high (CA ≤ 12.7, MO > -1.4), U 14 MO low (CA > 12.7, MO ≤ -1.4), U 14 MO high (CA > 12.7, MO > -1.4). The two-factor mixed ANOVA revealed significant ( p  < .05) interactions between competition format and sub-group for the KPIs high accelerations ( η p 2  = .176), conquered balls ( η p 2  = .227) and attack balls ( η p 2  = .146). Especially, U 13 MO high (i.e. early maturing players) faced a higher physiological challenge by having more high accelerations (| d | = 0.6) in BB games. Notably, U 14 MO low (i.e. late maturing players) had more opportunities to show their technical-tactical abilities during BB games with more conquered balls (| d | = 1.1) and attack balls (| d | = 1.6). Affected KPIs indicate new challenges and learning opportunities during BB competition depending on a player's individual maturity status. Bio-banding can beneficially be applied to enhance the talent development of youth elite soccer players.

The fact that potentially skilled, but biologically later-maturing athletes are less likely to be selected into talent development programmes (TDP) can represent a failure of Talent Identification (TID) in sports. To overcome maturation selection biases, maturation independent TID should be established to include less mature, but talented athletes in TDP more frequently. Using a randomised parallel-group design, this study aimed to evaluate the effect of labelling under-11 (U 11 ) Swiss male youth football players ( n = 24, age = 11.0 ± 0.3 years) via maturation-ordered shirt numbers during rank assessment by talent scouts ( n = 83, scout experience = 4.8 ± 2.4 years). Following observation of video recorded selection tournaments, player-labelling "informed" scouts were significantly more likely to rank less mature players higher on their player potential, t (81) = 2.57, p = .012, d = -0.6, 95% CI [-1.00, -0.13], than "uninformed" scouts. As altered rankings assisted less mature players, player-labelling may offer a practical and feasible strategy to improve TID by removing possible maturation selection biases. To address maturation selection biases and the potential positive impact of player-labelling more broadly, further research on both male and female athletes in various age categories and sports contexts is recommended.

The influence of biological maturity status (BMS) on talent identification and development within elite youth soccer is critically debated. During adolescence, maturity-related performance differences within the same age group may cause greater chances of being selected for early maturing players. Therefore, coaches need to consider players' BMS. While standard methods for assessing BMS in adolescents are expensive and time-consuming imaging techniques (i.e., X-ray and MRI), there also exist more pragmatic procedures. This study aimed to evaluate commonly used methods to assess BMS within a highly selected sample of youth soccer players. A total of N = 63 elite male soccer players (U12 and U14) within the German Soccer Association's talent promotion program completed a test battery assessing BMS outcomes. Utilizing MRI diagnostics, players' skeletal age (SA MRI ) was determined by radiologists and served as the reference method. Further commonly used methods included skeletal age measured by an ultrasound device (SA US ), the maturity offset (MO MIR ), and the percentage of adult height (PAH KR ). The relation of these alternative BMS outcomes to SA MRI was examined using different perspectives: performing bivariate correlation analyses (1), modeling BMS as a latent variable (BMS lat ) based on the multiple alternative diagnostics (2), and investigating individual differences in agreement (3). (1) Correlations of SA MRI and the further BMS variables ranked from r = 0.80 to r = 0.84 for the total sample and were lower for U12 (0.56 ≤ r ≤ 0.66), and U14 (0.61 ≤ r ≤ 0.74) (2). The latent structural equation modeling (SEM) ( R 2 = 51%) revealed a significant influence on BMS lat for MO MIR (β = 0.51, p <0.05). The additional contribution of PAH KR (β = 0.27, p = 0.06) and SA US (β = -0.03, p = 0.90) was rather small (3). The investigation of individual differences between the reference method and alternative diagnostics indicated a significant bias for MO MIR ( p <0.01). The results support the use of economical and time-efficient methods for assessing BMS within elite youth soccer. Bivariate correlation analyses as well as the multivariate latent variable approach highlight the measures' usefulness. However, the observed individual level differences for some of the utilized procedures led to the recommendation for practitioners to use at least two alternative assessment methods in order to receive more reliable information about players' BMS within the talent promotion process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Leyhr, Murr, Basten, Eichler, Hauser, Lüdin, Romann, Sardo and Höner.)

Objective: Bio-banding (BB) has been introduced to account for varying maturity and to improve the talent development of junior soccer players. To date, research that investigated the physiological and technical effects of BB is sparse. Therefore, the aim of the study was to compare effects of BB with CA on selected technical and tactical parameters in U13 and U14 soccer players., Results: BB significantly increased the number of duels (p = 0.024) and set pieces (p = 0.025) compared to chronological age. The mean time of ball possession per action was reduced (p = 0.021) and the rate of successful passes was lower with BB (p = 0.001). Meanwhile, the total number of passes was unaffected (p = 0.796), and there was a trend towards a lower difference in ball possession between BB teams (p = 0.058). In addition, BB reduced the distances covered while jogging (p = 0.001), running (p = 0.038) and high-speed running (p = 0.035). With BB, an increased number of duels, unsuccessful passes and set pieces resulted in a quicker change of match play situations between teams. While physical demand was reduced, BB seems to result in a more technically and tactically challenging game. Benefits in long-term player development, however, require further investigation.

This actigraphy study tests whether daily work stressors (time pressure, social stressors), work resources (control, social support) and mental detachment from work predict sleep quality, when controlling for demands and control after work. Fifty-two railway employees participated during five consecutive workdays by completing diary questionnaires and wearing an actigraphy device. The results confirmed that social stressors from supervisors predicted more frequent sleep fragmentation and lower sleep efficiency the following night. Higher levels of daily time control at work predicted shorter sleep-onset latency and better self-reported sleep quality. Leisure time control as a covariate turned out to be a private resource, followed by fewer awakenings the following night. Detachment after work related negatively to social stressors and time pressure at work but was unrelated to indicators of sleep quality; detachment after work neither mediated nor moderated the relationship between social stressors from supervisors and sleep quality. Work redesign to increase time control and reduce social stressors is recommended to preserve daily recovery in railway employees. Practitioner summary: Sleep is important to renew health- and safety-related resources in railway employees. This diary and actigraphy study shows that higher daily work stressors were antecedents of lower sleep quality the following night, while more time control was followed by better sleep quality. Work redesign could promote health and safety by improving sleep quality.

The meromictic Lake Cadagno is characterized by a compact chemocline with high concentrations of anoxygenic phototrophic purple and green sulfur bacteria. However, a complete picture of the bacterial diversity, and in particular of effects of seasonality and compartmentalization is missing. To characterize bacterial communities and elucidate relationships between them and their surrounding environment high-throughput 16S rRNA gene pyrosequencing was conducted. Proteobacteria, Chlorobi, Verrucomicrobia, and Actinobacteria were the dominant groups in Lake Cadagno water column. Moreover, bacterial interaction within the chemocline and between oxic and anoxic lake compartments were investigated through fluorescence in situ hybridization (FISH) and flow cytometry (FCM). The different populations of purple sulfur bacteria (PSB) and green sulfur bacteria (GSB) in the chemocline indicate seasonal dynamics of phototrophic sulfur bacteria composition. Interestingly, an exceptional bloom of a cyanobacteria population in the oxic-anoxic transition zone affected the common spatial distribution of phototrophic sulfur bacteria with consequence on chemocline location and water column stability. Our study suggests that both bacterial interactions between different lake compartments and within the chemocline can be a dynamic process influencing the stratification structure of Lake Cadagno water column., Competing Interests: We have the following interests. Matthieu Bueche is affiliated to Bueche μlab. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Bacterial strains used as starter cultures in the production of fermented foods may act as reservoirs for antibiotic resistance (AbR) genes. To avoid the introduction of such genes into the food chain, the presence of acquired AbR in bacterial strains added to food must be tested. Standard protocols and microbiological cut-off values have been defined to provide practitioners with a basis for evaluating whether their bacterial isolates harbor an acquired resistance to a given antibiotic. Here, we tested the AbR of 24 strains of Pediococcus acidilactici by using the standard protocol and microbiological cut-off values recommended by the European Food Safety Authority. Phenotypic data were complemented by searching for known AbR genes using an in silico analysis of whole genomes. The majority (54.2%) of the strains were able to grow at a tetracycline concentration above the defined cut-off, even though only one strain carried a known tetracycline resistance gene, tetM. The same strain also carried the AbR gene of an erythromycin resistance methylase, ermA, and displayed resistance toward clindamycin and erythromycin. Our results bolster the scarce data on the sensitivity of P. acidilactici to tetracycline and suggest that the microbiological cut-off recommended by the European Food Safety Authority for this antibiotic should be amended.

Background: In Switzerland, the invasive Asian tiger mosquito, Aedes albopictus, is firmly established in the Canton of Ticino, south of the Alps. According to a large-scale distribution model developed in 2013, suitable climatic conditions for the establishment of Ae. albopictus north of the Alps are found in Basel and Geneva while Zurich appears to be characterized by winters currently being too cold for survival of diapausing eggs. However, the spatial resolution of large-scale distribution models might not be sufficient to detect particular climatic conditions existing in urban settings, such as the presence of microclimatic temperatures, which may positively influence the probability of diapausing eggs to overwinter. In order to investigate this, microclimatic monitoring of potential diapausing sites (i.e. catch basins) and external controls was performed in January 2017 in Ticino and within the cities of Basel, Geneva and Zurich., Results: Mean January temperatures in catch basins of Basel, Geneva and Zurich were always higher than the -1 °C temperature threshold previously set for survival probability of diapausing eggs, while mean January temperatures were below -1 °C in several catch basins south of the Alps, where Ae. albopictus eggs currently overwinter. The catch basin absolute January daily minimum temperatures both south and north of the Alps were in general higher than the external control temperatures. Absolute January daily minimum temperatures in catch basins in Basel, Geneva and Zurich were always above -10 °C, indicating that diapausing Ae. albopictus eggs could potentially survive winter nights in urban areas north of the Alps., Conclusions: The findings confirmed previous conclusions that urban catch basins can provide favourable conditions for overwintering of diapausing eggs compared to more cold-exposed sites. The results confirmed the presence of suitable winter conditions for the establishment of Ae. albopictus in the cities of Basel and Geneva. In addition, the microclimate-scale analysis added new information compared to the previous large-scale prevision model by showing that also the city of Zurich could provide winter conditions suitable for the establishment of Ae. albopictus. This illustrates the importance of the resolution of climate data in using models to predict Ae. albopictus distribution.

The meromictic Lake Cadagno is characterized by a compact chemocline with high concentrations of anoxygenic phototrophic purple sulfur bacteria (PSB) and green sulfur bacteria (GSB). The co-occurrence of phylogenetically distant bacterial groups such as PSB and GSB in the same ecological niche, makes the chemocline of Lake Cadagno an ideal system for studying the conditions and consequences of coexistence of photosynthetic bacteria populations. In this study, we applied flow cytometry (FCM) as a fast tool to identify metabolic changes due to the production and consumption of inclusion bodies such as sulfur globules (SGBs), and follow population dynamics of closely related anoxygenic photosynthetic sulfur bacteria in their natural environment. Large-celled PSB Chromatium okenii and GSB Chlorobium populations were reliably separated and identified due to differences in auto-fluorescence and cell size. Moreover, we showed that these dominant taxa share the same ecological niche over seasonal periods. Taking advantage of FCM detection of dynamic cellular complexity variation during phases of photosynthetic activity, we identified an unexpected alternation in PSB versus GSB metabolic activity, indicating dynamic interspecific interactions between these two populations.

The manufacture of traditional Swiss-type cheeses adheres to strict rules, so as to guarantee quality and purity of the end product. This raises production costs and means consumers pay more. It also opens the door to cut-rate forgeries claiming to be made to the stringent standards and causing considerable economic losses to the entire dairy sector. In order to combat product counterfeiting, Agroscope has developed proof-of-origin cultures that allow the identification of copycats. Carefully selected lactic acid bacteria, having uniquely located insertion sequence elements, are proliferated by fermentation and subsequently dried by lyophilization. The proof-of-origin culture is added during the cheese production process and sustains maturation. These so-called 'biological markers' can be traced using polymerase chain reaction (PCR) methods, which allow authentication even if the cheese is cut into pieces or grated. They do not lead to any alteration of the cheese's taste or texture, and are compatible with the strict 'protected designation of origin' (PDO) specifications. The proof-of-origin cultures are used for the protection of several traditional Swiss-cheese varieties, such as Emmental PDO, Tête de Moine PDO, and Appenzeller(®). A market survey of Emmental PDO showed that the system is effective in revealing fraud and has the power to enforce corrective measures.

Urinary tract infections (UTIs), predominantly caused by uropathogenic Escherichia coli (UPEC), belong to the most prevalent infectious diseases worldwide. The attachment of UPEC to host cells is mediated by FimH, a mannose-binding adhesin at the tip of bacterial type 1 pili. To date, UTIs are mainly treated with antibiotics, leading to the ubiquitous problem of increasing resistance against most of the currently available antimicrobials. Therefore, new treatment strategies are urgently needed. Here, we describe the development of an orally available FimH antagonist. Starting from the carboxylate substituted biphenyl α-d-mannoside 9, affinity and the relevant pharmacokinetic parameters (solubility, permeability, renal excretion) were substantially improved by a bioisosteric approach. With 3'-chloro-4'-(α-d-mannopyranosyloxy)biphenyl-4-carbonitrile (10j) a FimH antagonist with an optimal in vitro PK/PD profile was identified. Orally applied, 10j was effective in a mouse model of UTI by reducing the bacterial load in the bladder by about 1000-fold.

We developed quantitative fimA genotype assays and applied them in a pilot study investigating the fimbrial genotype distribution of Porphyromonas gingivalis in European subjects with or without chronic periodontitis. P. gingivalis was found in 71% and 9% of the samples from patients and healthy subjects, respectively. Enumeration of total P. gingivalis cell numbers by polymerase chain reaction and immunofluorescence showed excellent correspondence (r = 0.964). 73% of positive samples contained multiple fimA genotypes, but generally one genotype predominated by one to three orders of magnitude. Genotype II predominated in 60% of the samples. Genotype IV occurred with similar prevalence (73%) as genotype II but predominated in only 20% of the samples. Genotypes I, III and V were of much lower prevalence and cell densities of the latter two remained sparse. Our results suggest marked differences among the fimA genotypes' ability to colonize host sites with high cell numbers.

Objective: Our objective was to investigate the clinical pharmacologic characteristics of saquinavir given as a soft gelatin capsule, either alone or in combination with nelfinavir, to children and adolescents with human immunodeficiency virus infection., Methods: The pharmacokinetics of 50 mg/kg saquinavir 3 times a day (tid) alone versus 33 mg/kg saquinavir tid plus 30 mg/kg nelfinavir tid was assessed after single-dose administration and after short- and long-term administration. The single-dose pharmacokinetics of fixed (1200 mg) versus unrestricted weight-adjusted dosing (50 mg/kg) was also investigated., Results: Saquinavir as the sole protease inhibitor resulted in lower saquinavir exposure in children (steady-state geometric mean area under the concentration-time curve from time zero to 24 hours [AUC (0-24 h)], 5790 ng x h/ml; steady-state concentration 8 hours after drug administration [C(8h,SS)], 65 ng/ml) and adolescents [steady-state geometric mean AUC(0-24 h), 5914 ng x h/ml] than that reported in adults treated with 1200 mg tid [steady-state geometric mean AUC(0-24 h), 21,700 ng x h/ml; C(8h,SS), 223 ng/ml]. This finding appeared to be attributable to markedly higher apparent oral clearance, potentially as a result of increased systemic clearance and reduced oral bioavailability. Nelfinavir combined with saquinavir reduced apparent oral clearance, increasing saquinavir exposure in children [steady-state geometric mean AUC(0-24 h), 11,070 ng x h/ml; C(8h,SS), 380 ng/ml] to levels that approach those observed in adults. A significant correlation between average trough concentration and sustained viral load suppression was observed in children. The apparent threshold for maintaining viral load suppression was a mean trough saquinavir concentration above 200 ng/ml., Conclusions: The pharmacokinetics of saquinavir in children is different from that of adults, and administration of saquinavir alone will not give consistently efficacious plasma levels. The best way of improving saquinavir exposure in children is through combination therapy with other protease inhibitors that inhibit saquinavir metabolism.

Objective: The aim of this study was to compare the effect of ketoconazole, erythromycin and rifampicin on the pharmacokinetics of saquinavir soft-gelatin formulation (Fortovase; FTV) in healthy volunteers with that in HIV-infected patients at steady state after administration of 1200 mg three times daily., Methods: In two open-labelled, randomised, crossover studies pharmacokinetic parameters were calculated in healthy volunteers who received on one occasion multiple doses of 1200 mg FTV three times daily alone and on the other occasion in combination with multiple doses of either 400 mg ketoconazole once daily or 600 mg rifampicin once daily. In another open-labelled, multicentre study, 33 HIV-infected patients underwent a pharmacokinetic assessment after 36-51 weeks of treatment with FTV and were then given additionally multiple doses of either 200 mg ketoconazole once daily, 250 mg erythromycin four times daily or 600 mg rifampicin once daily. Pharmacokinetic parameters of saquinavir were determined again at the end of the combination treatment., Results: In healthy volunteers, coadministration of ketoconazole increased saquinavir area under the curve from time 0 to 8 h (AUC0-8 h) by 190% (95% CI: 90-343) whereas coadministration with rifampicin resulted in a decrease for AUC0-8 h by 70% (95% CI: 50-82). In HIV-infected patients, coadministration of ketoconazole and erythromycin increased AUC0-8 h of saquinavir by 69% (95% CI: 14-150) and 99% (95% CI: 33-198), respectively. When saquinavir was given together with rifampicin, exposure of saquinavir in terms of AUC0-8 h was decreased by 46% (95% CI: 18-65) compared with the baseline assessment., Conclusion: Interactions of saquinavir with ketoconazole, erythromycin and rifampicin were observed in healthy volunteers as well as patients. The effects observed in patients, however, appear to be less pronounced. The enzyme induction caused by rifampicin might lead to subtherapeutic levels of saquinavir and this finding appears to be of clinical relevance.

The fragmentation of natural habitats is generally considered to be a major threat to biodiversity. We investigated short-term responses of vascular plants (grasses and forbs) and four groups of invertebrates (ants, butterflies, grasshoppers and gastropods) to experimental fragmentation of calcareous grassland in the north-western Jura mountains, Switzerland. Three years after the initiation of fragmentation - which was created and maintained by mowing the area between the fragments - we compared species richness, diversity and composition of the different groups and the abundance of single species in fragments of different size (area: 20.25 m 2 , 2.25 m 2 and 0.25 m 2 ) with those in corresponding control plots. The abundances of 19 (29%) of the 65 common species examined were affected by fragmentation. However, the experimental fragmentation affected different taxonomic groups and single species to a different extent. Butterflies, the most mobile animals among the invertebrates studied, reacted most sensitively: species richness and foraging abundances of single butterfly species were lower in fragments than in control plots. Of the few other taxonomic groups or single species that were affected by the experimental fragmentation, most had a higher species richness or abundance in fragments than in control plots. This is probably because the type of fragmentation used is beneficial to some plants via decreased competition intensity along the fragment edges, and because some animals may use fragments as retreats between foraging bouts into the mown isolation area.

Background: Low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefit of lower blood cholesterol., Objective: The aim of our study was to evaluate the association between low blood cholesterol (<5.16 mmol/L) and cancer at sites that have rarely been evaluated. We placed special emphasis on the potential confounding effect of antioxidant vitamins., Design: Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-1973 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed., Results: Two hundred ninety of the participants had died from cancer, 87 from lung, 30 from prostate, 28 from stomach, and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking, and age accounted for in a Cox model, an increase in total cancer mortality in lung, prostate, and colon but not in stomach cancer mortality was observed in men >60 y of age with low plasma cholesterol. When data from the first 2 y of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer but decreased for colon, prostate, and overall cancer., Conclusions: Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of preexisting cancer.

Background: Prostate cancer has one of the highest incidence rates of all cancers. Vitamin intake and tobacco use may have an impact on incidence and mortality, but epidemiologic evidence is scarce and inconsistent., Methods: Plasma vitamins C, E, retinol, and carotene were measured in 1971-1973 in 2,974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed., Results: Two hundred and ninety men had died from cancer, including 30 with prostate cancer. On average, prostate cancer cases were 15 years older and smoked slightly more frequently than survivors. The mean values of plasma carotene, and of vitamin C, were nonsignificantly lower in prostate cancer cases than in survivors. After calculation of relative risk using the Cox model with exclusion of mortality during the first 2 years of follow-up, low vitamin E levels in smokers were related to an increased risk for prostate cancer. Relative risks of low vitamin C and carotene levels were about 1. A slightly but nonsignificantly increased risk was observed for low levels of retinol., Conclusions: Given the profound implication if the risk of prostatic cancer could be reduced, the relationship with vitamin E and smoking requires further study.

During the past 7 years 45 patients have been operated upon using the Childs-Phillips method. Of those, 37 were subsequently examined for the study--7 patients had died in the meantime. None of the deaths occurred as a direct result of transmesenteric small-bowel plication. An early recurrence of intestinal obstruction occurred in 4.4% and a laparotomy was repeated. During the most recent examinations 86.5% of those patients checked had (virtually) no complaints--91.9% based upon the Visick classification. A subtotal intestinal obstruction occurred during the period of the study in 8.1% of cases, but could be conservatively treated. Up until the most recent examination there were still no instances of a late recurrence. Most intestinal obstruction recurrences are due to errors specific to the technique and are early recurrences. On the basis of our results, we are of the opinion that plication in the presence of existing peritonitis, as well as partial plication, is acceptable.

Plasma vitamins C, E, retinol and carotene were measured in 1971-1973 in 2,974 men working in Basel Switzerland. In 1990, the vital status of all participants was assessed. A total of 290 men had died from cancer during the 17 years of follow-up, including 87 with lung cancer, 30 with prostate cancer, 28 with stomach cancer and 22 with colon cancer. Overall mortality from cancer was associated with low mean plasma levels of carotene (adjusted for cholesterol) and of vitamin C. Lung and stomach cancers were associated with low mean plasma carotene level. After calculation of the relative risk, using the Cox model, with exclusion of mortality during the first 2 years of follow-up, simultaneously low levels of plasma carotene (below quartile I) and lipid-adjusted retinol were related to a significantly increased mortality risk for all cancers and for lung cancer. Simultaneously, low levels of plasma vitamin C and lipid-adjusted vitamin E also were associated with a significantly increased risk for lung cancer. Additionally, low vitamin E levels in smokers were related to an increased risk for prostate cancer. It is concluded that low plasma levels of the vitamins C, E, retinol and carotene are related to increased risk of subsequent overall and lung-cancer mortality and that low levels of vitamin E in smokers are related to an increased risk of prostate-cancer mortality.

Between 1976 and 1994 we performed 26 thoracic sympathectomies for treatment of therapy-resistant palmar hyperhidrosis. Until the end of 1992 the operation was performed using an open transaxillary approach, since 1993 sympathectomy was done by video-assisted thoracoscopy. Both procedures consisted in excision of the thoracic ganglia T2 to T5. The only complication was a pneumothorax in the open surgery group (successfully treated by drainage). Compensatory sweating occurred in 70% of our patients, compared to results in the literature of 60-90%. We did not note further complications, e.g. no Horner's syndrome. All of our patients were satisfied with the result of the operation. Comparison of the two collectives shows significant advantages for video-assisted thoracoscopic surgery. the procedure is easier to perform, exposure is better, cosmetic results are favourable, operation-time and hospital stay are reduced.

Several parameters (pH, osmotic pressure) influencing the local tolerance of injectable drugs have been well-documented; however, little attention has been paid to pain following an injection--a common problem in clinical practice. A pain questionnaire was used to record pain up to 24 h after a deep ventrogluteal injection. Two groups of healthy volunteers were recruited: the first group (n = 6) received 3 different cotrimoxazole preparations and placebo and the second group (n = 10) received 4 different multivitamin preparations and placebo (double-blind, cross-over). Parameters monitored during and after injection included pain localization (line drawing), pain intensity (visual-analog scale: VAS) and verbal description of pain (pain rating index: PRI). In both groups, the equality of pain (VAS, PRI) induced by the preparations was rejected in all cases (Friedman's test, p < or = 1%). The pairwise comparisons of the groups showed significant differences (p < or = 5%) between various preparations. The correlation (Spearman's rank correlation) between pain parameters VAS and PRI was high. The present investigations have shown that the pain questionnaire is a valuable tool to investigate the subjective pain symptoms during and after the injection of different preparations.

For the prolongation of life expectancy and reduction of ischemic heart disease (IHD) dietary guidelines generally recommend lowering saturated mammalian fat with partial replacement by vegetable oils and increasing generously vegetables, legumes, and fruits, which provide more essential antioxidants. Plasma antioxidants as assayed in epidemiological studies of complementary type (ie the cross-cultural MONICA Vitamin Substudy reevaluation considering the "Finland-Factor", the Edinburgh Angina-Control Study, and the Basel Prospective Study) consistently revealed an increased risk of IHD (and stroke) at low plasma concentrations of antioxidants, with the rank order as follows: lipid-standardized vitamin E >> carotene = vitamin C > vitamin A, independently of classical IHD risk factors. Decreasing IHD risk through nutrition may be possible when plasma concentrations have the following values: > 27.5-30.0 mumol vitamin E/L, 0.4-0.5 mumol carotene/L, 40-50 mumol vitamin C/L and 2.2-2.8 mumol vitamin A/L. Thus, previous prudent regimens may now be updated, aiming at an optimal status of all essential and synergistically linked antioxidants.

Reocclusion of infarct-related coronary arteries within 2 weeks of thrombolytic therapy varies from 5% to 45% and neither clinical nor angiographic variables have been proved to be predictive of reocclusion. The goal of the present study was to evaluate whether aspirin could prevent coronary reocclusion and recurrent ischemia after thrombolysis. For this purpose, a meta-analysis including 32 studies was performed. Although the studies showed very similar demographic data, the reocclusion rate assessed by angiography in 419 patients treated with aspirin was 11% compared with 25% in 513 patients without aspirin therapy (p less than 0.001). Recurrent ischemic events were present in 25% of 2,977 patients treated with aspirin and 41% of 721 patients treated without aspirin (p less than 0.001). The effect of aspirin was similar in trials with either streptokinase or recombinant tissue-type plasminogen activator (rt-PA). Thus, aspirin in the presence of heparin might prevent coronary reocclusion after thrombolysis.

The effectiveness of any therapy in acute acoustic trauma or sudden hearing loss of unknown origin has not been demonstrated convincingly. The assessment is difficult because of a relatively high rate of spontaneous recovery. Nevertheless, many different forms of treatment are recommended. We tested one form, treatment with rheoactive substances, in a prospective, randomized, double-blind trial and compared treatment with (a) infusions of dextran-40 with pentoxifylline, (b) saline infusions with pentoxifylline, and (c) saline infusions with placebo medication. Pure-tone hearing thresholds served as control parameters and were taken before treatment and at 1 and 4 weeks after the onset of therapy. Three hundred eighty-two patients were included in the trial, 331 (87%) could be analyzed, 184 patients were treated because of sudden hearing loss, 147 because of acute acoustic trauma. The three treatment groups were comparable in their basic characteristics including the amount of initial hearing loss. In patients with sudden hearing loss, no significant differences of hearing recovery were detected between the three treatment groups. Hearing recovery was also similar in patients with acute acoustic trauma. A power analysis of the study revealed that possible true treatment differences of a hearing recovery of 10 dB would have lead to significance with a probability of over 90%. It is concluded that there were, in fact, no clinically relevant differences in hearing gains of sudden hearing loss or acute acoustic trauma between treatments with saline infusions together with placebo medication and treatment with dextran-40 and/or pentoxifylline.

Plasma antioxidant vitamins A, C, and E and carotene were measured in a group of 2,974 men participating in the third examination of the prospective Basel Study in 1971-1973. In 1985, the vital status and mortality of all participants were assessed. A total of 204 men had died from cancer, including 68 with bronchus cancer and 37 with gastrointestinal cancer (20 with stomach cancer and 17 with large bowel cancer excluding cancer of the rectum). Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer also had lower mean vitamin C and lipid-adjusted vitamin A levels than did survivors (p less than 0.05). After calculation of the relative risk using the Cox model with exclusion of mortality during the first 2 years of follow-up, low plasma carotene (below quartile 1) was associated with a significantly increased risk for bronchus cancer (relative risk (RR) = 1.8, p less than 0.05), low plasma levels of carotene and vitamin A with all cancers (RR = 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than age 60 years) with lung cancer (RR = 2.17, p less than 0.05). Low levels of vitamin C increased the risk of stomach cancer (RR = 2.38) and gastrointestinal cancer (RR = 2.46) in older subjects, but only significantly with the inclusion of the first 2 years. The authors conclude that low plasma levels of antioxidant vitamins are associated with an increased risk of subsequent cancer mortality. This effect was stronger in men above age 60 years at blood sampling, and the effect seems to be site-specific.

The influence of the vitamin nutritional status on the immunocompetence of a group of elderly people in the city of Perugia has been investigated. The impairment of some immunological (humoral as well as innate and acquired cell-mediated) functions seemed to be mostly related to age. Statistically significant correlations between the complement component C4 and plasma levels of retinol as well as alpha-tocopherol and an inverse correlation between titers of IgG and plasma retinol have been observed (significance level alpha = 5%).

In 1971-1973 at the third examination of the Basel Study started in 1959, the major antioxidant vitamins and carotene were measured in the plasma of 2974 men. A subsample and their families were reinvestigated in 1977-79. During the 12-y observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach cancer 20; colon cancer 17, all other malignancies 99). We found significantly lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer (all P less than 0.01) compared with the 2421 survivors. The relative risk of subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all cancer (P less than 0.01) if both carotene and retinol were low. Low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk.

Diagnostic, therapeutic and prognostic aspects are interpreted on the basis of two cases of Echinococcus alveolaris. Both patients had undergone partial hepatectomy and were subsequently treated chemotherapeutically. In one case dehydroemetine and mebendazole (Vermox, Janssen), and in the other case metrifonate (Bilarcil, Bayer A.G.) were used. The diagnosis of alveococcosis of the liver was demonstrated in one case histologically on the occasion of appendectomy, and in the other case by the indirect immunofluorescence test and passive haemagglutination. In case of suspected alveococcosis these serological are imperative, as they are the most reliable methods of demonstrating this disease. The latest trend in theraphy aims at a combination of surgery and chemotherapy. Mebendazole seems to be promising as an anthelmintic agent for the treatment of alveococcosis. Remission of the disease was obtained in either case.

The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent. The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind, placebo-controlled study. Repeated neurologic examinations (Day 0, Weeks 1, 6, 12, and 24) according to a modified Mathew score were performed on 62 patients. Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke. A retrospective estimation of the Type II error of the study yielded approximately p = 0.25. A major side effect was hemolysis in 98% of patients treated with glycerol.

An interlaboratory study on the reproducibility of the CEA (Roche) RIA Test was carried out. Four different plasma pools of approximately 2, 3, 6, and 12 micrograms/l CEA were tested over a period of 4 weeks with 4 different lots of reagents in order to determine the interassay variances. At the same time we compared the lately introduced column technique with the dialysis and ultrafiltration method. Best results were obtained with the column technique which also showed best reproducibility. Only 1.4% of samples showed deviations greater than 5% between the mean of CEA duplicates and single CEA values, and these were omitted from the evaluation. On the other hand about 15% of the corresponding dialysis results showed deviations greater than 5% and were excluded from the evaluation. The methods compared showed a good correlation with a coefficient of 0.96, but the average values for the CEA determination, using the columns technique were lower than those obtained from dialysis. Interassay variances were greater for the dialysis procedures, i.e. 1.88 +/- 0.81, 3.25 +/- 0.83, 5.81 +/- 1.09, and 11-91 +/- 1.23 compared with 1.77 +/- 0.54, 2.63 +/- 0.68, 4.89 +/- 0.79, and 11.16 +/- 1.23 for the column technique. There were no systematic changes of the CEA values over the period of 4 weeks, thus giving optimal conditions for a follow up of patients.

Low-affinity receptors (Fc epsilon R) and secreted factors (IgE-BF) which bind to immunoglobulins of the IgE isotype play a key role in the regulation of human IgE synthesis. We report here the cloning of a cDNA coding for the Fc epsilon R of the human B-lymphoblast cell line RPMI 8866. The nucleotide sequence of this cDNA predicts a polypeptide with 321 amino acids and a mol. wt of 36,281 daltons. A functional Fc epsilon R capable of binding IgE was expressed in Chinese hamster ovary cells after stable transformation with the cDNA which had been cloned into a mammalian expression vector. Amino acid sequence analysis of IgE-BF purified from RPMI 8866 cells revealed an amino-terminal sequence of 19 residues which coincides with the predicted amino acid sequence of the Fc epsilon R, starting at residues 148 and 150. A computer search with the translated amino acid sequence of the Fc epsilon R revealed a domain of 120 amino acids having striking homology to the human asialoglycoprotein receptors.

In a population of 689 patients with primary total hip arthroplasties, perioperative problems and complications were investigated. A preoperative cardiovascular disease was found in 32%, obesity in 18% of the patients. The death-rate was 0.43% in a population of patients, two thirds of whom was older than 60 years, one third even older than 70 years. The importance in preoperative evaluation of health and in treatment of various diseases is emphasized. Postoperative management is crucial to reduce thromboembolisms, urinary retention and infections.

For testing the significance of dose-related effects, a test procedure was developed for the typical situation in toxicological studies where several dosage groups are compared to one control group. Using a closed testing procedure in the sense of Marcus et al. (1976), the algorithm is sensitive to the detection of toxicological effects without increase in type-one errors. Furthermore, all significance tests applied in the algorithm are based on ranks and the calculation of the error probability is performed by a random-permutation technique (Wall 1974, 1985); the algorithm is therefore also applicable to non-normally distributed data. In the case of discrete quantities, this technique takes into account tie-structures of all kinds (Lüdin 1985). An application of the proposed test-procedure is given in the work of Kistler and Hummler (1985).

In a previous study with flucytosine (5-FC) susceptibility of 40 Candida albicans isolates in vitro proved statistically correlated with response in systemic murine candidiasis in vivo, although exceptions occurred with individual isolates. For the present analogous study with ketoconazole, 58 C. albicans isolates were used of which 38 were from the 5-FC study and 20 were added to equalize the numbers of serotype A (n = 30) and B (n = 28) and to make the range of susceptibility in vitro to ketoconazole continuous and wide. The widest range of ketoconazole susceptibility was noted for the minimal inhibitory concentrations on Kimmig and Casitone agars (0.015-256 micrograms/ml) and disk zone diameters on YNB agar (0-54 mm), whereas with disk tests on other media, the range of 50% inhibitory concentrations, relative inhibition factors and MICs on serum agar remained narrow and/or showed strong ties. The Spearman's rank correlation between the in vitro activities determined with the various parameters showed wide variation consistent with p values from less than 0.001 to greater than 0.05. The serotype B isolates generally were more susceptible than the A isolates (p less than 0.02 for the majority of parameters). Evaluation of response in vivo was hampered by the low activity of ketoconazole on the murine infection with any of the isolates, the range of the ED50's being only 10- greater than 100 mg/kg. The serotype B infections exhibited significantly better response (p less than 0.05) than the serotype A infections. The overall correlation (Spearman's rank) of the susceptibility test results in vitro with the response in vivo was poor (p less than 0.05 for almost all parameters) suggesting very limited if any precise predictive values of the susceptibility tests in vitro with ketoconazole against C. albicans. However, the narrow range of the ED50 suggests relatively little variation in the response of the different isolates in vivo and similarly small variation was also noted in some of the tests in vitro.

The analytical program Delta was used to determine long-term fluctuations and accuracy of measurement of the program 31 of the Octopus when used with glaucoma patients. Program 31 examines the 30 degree field. The test locations are arranged in a square grid with 6 degree resolution. The program Delta determines and compares 1) the disturbed area in %; 2) the total loss, the total sensitivity being around 2000 dB; 3) the total loss in dB per mean number of disturbed points. 32 eyes of 22 patients with established glaucomatous field defects were examined twice within 2 to 6 days and 2 months later, twice again within this number of days. The size of the disturbed area served for classification of our sample into 3 groups: 1st group: disturbed area 1-33%; 2nd group: disturbed area 34-66%; 3rd group: disturbed area 67-100%. Long-term fluctuations and accuracy of measurement were determined as follows: 1) Disturbed area between 0.7 +/- 8% in group 3 and 1.7 +/- 13% in group 2. 2) The total loss increases proportionately to the disturbed area and was 4.9 +/- 29.2 dB in group 1 and 31.8 +/- 82.4 dB in group 3. 3) The total loss per mean number of disturbed points was 0.5 +/- 2 dB in group 1 and 0.3 +/- 1.2 dB in group 2. This means that, if the learning effect is over, changes of more than 2 dB, especially if several adjacent points are affected, are a significant loss, the learning effect, as determined in an earlier study, may go up as high as 2dB per point.

Three repeated cross-sectional surveys were undertaken among children (1 month to 15 years) of a rural community in southeastern Tanzania. The study was part of a longitudinal project on the interactions among nutrition, parasitic infections and immunity within a primary health care programme emphasizing village health workers. All children underwent interviews and parasitological, anthropometric, anamnestic and clinical examinations. Out of 550-590 children examined each year, a cohort of 170 children could be followed for three consecutive years. Malaria was holo- to hyperendemic in the community, P. falciparum accounting for greater than 90% of the infections. The parasite and spleen rates were 88% and 67%, respectively, and the average enlarged spleen index was 2.0 among children from 2-9 years in 1982. Transmission of malaria was high and stable as indicated by a parasite rate of 80% among infants between 1 month and 1 year during the whole period of study. G. lamblia, hookworm (N. americanus), Strongyloides spp. and Schistosoma haematobium were highly prevalent and annual incidence rates were high, while Entamoeba histolytica, Ascaris and Trichuris were of minor importance. Prevalence and incidence of parasitic infections did not differ by sex. Multiparasitism was very frequent and less than 11% of all children were parasite-free in each year. Not a single child remained parasite-free for three consecutive years. An anthropometric assessment showed a high degree of stunting (35-71%) and a substantial proportion of wasting (3-20%). The growth potential was normal in girls and boys during the whole period of study. There were indications that malaria was the main contributory factor to growth retardation among young children. Hookworm infection did not significantly affect the packed-cell volume of the children, probably owing to the low intensity of infection. Due to the multiparasitism and the lack of parasite-free individuals, single-parasite and single-nutrient effects were difficult to unravel. A latrine campaign followed by a single mass treatment against hookworm (single oral dose of albendazole, 400 mg) and/or G. lamblia (single oral dose of ornidazole, 40 mg/kg) only temporarily affected the prevalence and incidence of G. lamblia, and only resulted in a decrease in the intensity of hookworm infections up to six months after the interventions. As the effects of the latrine campaign and a single mass treatment on the parasite load were only transient, no sustained impact on nutritional variables was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Several pitfalls may affect studies on human IgE synthesis in vitro. In this paper, the requirement for stringent specificity of the anti-IgE antibodies used and for assessment not only of IgE detectable in culture supernatants but also as cell-associated IgE is emphasized. The use of cycloheximide-treated cultures as controls also leaves wishes open. Activated, human T cells and T cell hybridomas produce IgE-binding factors, which may be detected by a sensitive in vitro test and which may apparently also become the endeavour of synthesis by molecular biological techniques. Although the evidence available in rodents for the role of IgE-binding factors in modulating IgE synthesis has not yet been fully reproduced by us in man, the fact that classical IgE-enhancing procedures in rodents (e.g. radiotherapy, T cell suppression) also affect IgE production in man leads to believe that similar immunoregulation mechanisms apply to various mammalian species studied so far.