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Summary: Hip fracture risk assessment is an important but challenging task. Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur. We developed a global FEA-computed fracture risk index to increase the prediction accuracy of hip fracture incidence. Purpose: Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur to compute the force (fracture load) and energy necessary to break the proximal femur in a particular loading condition. The fracture loads and energies-to-failure are individually associated with incident hip fracture, and provide different structural information about the proximal femur. Methods: We used principal component analysis (PCA) to develop a global FEA-computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies-to-failure in four loading conditions of 110 hip fracture subjects and 235 age- and sex-matched control subjects from the AGES-Reykjavik study. Using a logistic regression model, we compared the prediction performance for hip fracture based on the stratified resampling. Results: We referred the first principal component (PC1) of the FE parameters as the global FEA-computed fracture risk index, which was the significant predictor of hip fracture (p-value < 0.001). The area under the receiver operating characteristic curve (AUC) using PC1 (0.776) was higher than that using all FE parameters combined (0.737) in the males (p-value < 0.001). Conclusions: The global FEA-computed fracture risk index increased hip fracture risk prediction accuracy in males. [ABSTRACT FROM AUTHOR]

A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA (n = 132) or to the study group arms (n = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60–87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45–64)) and the study group arms (53% (95%CI: 47–60) and 59% (95%CI: 58–63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7–14.0) in the CSA, 7.6% (95%CI: 4.5–12.8) in study group A and 11.1% (95%CI: 9.0–13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0–26.9), 17.0% (95%CI: 2.0–23.9), and 19.5% (95%CI: 16.7–22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA. [ABSTRACT FROM AUTHOR]

Background and objectives: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. Methods: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. Results: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). Discussion: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

Dumped munitions contain various harmful substances which can affect marine biota like fish. One of them is mercury (Hg), included in the common explosive primer Hg fulminate. There is still a lack of knowledge whether dumped munitions impact the Hg concentrations in the Baltic Sea environment. This study aims to answer the question if dab caught at the dump site Kolberger Heide show higher Hg concentrations released from munition sources and whether Hg in fish is a usable marker for munition exposure. Therefore, a total of 251 individual dab (Limanda limanda) were analysed including 99 fish from the dump site. In fish from the Kolberger Heide, no elevated Hg concentrations were found compared to reference sites when age-dependent bioaccumulation of mercury was considered. Therefore we conclude that Hg in fish is no suitable indicator for exposure to munition dumping, e.g. in the frame of possible future monitoring studies as Hg exposure originating from dumped munition is only a small contributor to overall Hg exposure of fish. [ABSTRACT FROM AUTHOR]

Purpose: Patients with non-Hodgkin lymphoma (NHL) have a median age of 67, with 70% surviving over 5 years. Chemotherapy for aggressive NHL includes cyclophosphamide, anthracycline, and high doses of corticosteroids, which can impair bone health. By reviewing clinical characteristics and standard-of-care CT scans, we evaluate the prevalence and incidence of fractures and the clinical correlates of fractures in patients treated for aggressive B-cell NHL. Methods: We retrospectively reviewed patients seen at the University of California San Francisco lymphoma clinic from January 1, 2016, to March 31, 2017 who had (1) aggressive B-cell NHL, (2) received first-line therapy with R-CHOP-like regimens, and had (3) CT scans pre- and post-treatment available for review. Associations between clinical variables and vertebral, rib, and pelvic fracture outcomes were assessed, and multivariate logistic regression models were used to identify predictors of prevalent and incident fractures. Results: We identified 162 patients who met the inclusion criteria. Median age at diagnosis was 60 years. Of the 162 patients, 38 patients (28%) had prevalent fractures prior to receiving chemotherapy. Within 1 year after treatment, 16 patients (10%) developed new fractures. Having a prevalent fracture strongly predicted developing a new fracture after treatment, with incident fractures occurring in 12 of 38 patients with prevalent fractures versus 4 of 124 without prevalent fractures (odds ratio 10.45, p<0.0005). Conclusion: Our results suggest that patients with aggressive B-cell NHL who receive R-CHOP-like therapy should be screened for fractures prior to treatment and those with existing fractures should be considered for therapy to decrease risk of new fractures. [ABSTRACT FROM AUTHOR]

Quantum simulation using synthetic systems is a promising route to solve outstanding quantum many-body problems in regimes where other approaches, including numerical ones, fail1. Many platforms are being developed towards this goal, in particular based on trapped ions2–4, superconducting circuits5–7, neutral atoms8–11 or molecules12,13. All of these platforms face two key challenges: scaling up the ensemble size while retaining high-quality control over the parameters, and validating the outputs for these large systems. Here we use programmable arrays of individual atoms trapped in optical tweezers, with interactions controlled by laser excitation to Rydberg states11, to implement an iconic many-body problem—the antiferromagnetic two-dimensional transverse-field Ising model. We push this platform to a regime with up to 196 atoms manipulated with high fidelity and probe the antiferromagnetic order by dynamically tuning the parameters of the Hamiltonian. We illustrate the versatility of our platform by exploring various system sizes on two qualitatively different geometries—square and triangular arrays. We obtain good agreement with numerical calculations up to a computationally feasible size (approximately 100 particles). This work demonstrates that our platform can be readily used to address open questions in many-body physics.Programmable quantum simulation of two-dimensional antiferromagnets is achieved with up to 196 neutral atoms, and the capability of the platform is demonstrated on square and triangular arrays. [ABSTRACT FROM AUTHOR]

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense. Trial Registration Number: ISRCTN80046034. [ABSTRACT FROM AUTHOR]

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation—DNA methyltransferases (DNMTs)—has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder. [ABSTRACT FROM AUTHOR]

Studies using quantitative computed tomography (QCT) and data-driven image analysis techniques have shown that trabecular and cortical volumetric bone mineral density (vBMD) can improve the hip fracture prediction of dual-energy X-ray absorptiometry areal BMD (aBMD). Here, we hypothesize that (1) QCT imaging features of shape, density and structure derived from data-driven image analysis techniques can improve the hip fracture discrimination of classification models based on mean femoral neck aBMD (Neck.aBMD), and (2) that data-driven cortical bone thickness (Ct.Th) features can improve the hip fracture discrimination of vBMD models. We tested our hypotheses using statistical multi-parametric modeling (SMPM) in a QCT study of acute hip fracture of 50 controls and 93 fragility fracture cases. SMPM was used to extract features of shape, vBMD, Ct.Th, cortical vBMD, and vBMD in a layer adjacent to the endosteal surface to develop hip fracture classification models with machine learning logistic LASSO. The performance of these classification models was evaluated in two aspects: (1) their hip fracture classification capability without Neck.aBMD, and (2) their capability to improve the hip fracture classification of the Neck.aBMD model. Assessments were done with 10-fold cross-validation, areas under the receiver operating characteristic curve (AUCs), differences of AUCs, and the integrated discrimination improvement (IDI) index. All LASSO models including SMPM-vBMD features, and the majority of models including SMPM-Ct.Th features performed significantly better than the Neck.aBMD model; and all SMPM features significantly improved the hip fracture discrimination of the Neck.aBMD model (Hypothesis 1). An interesting finding was that SMPM-features of vBMD also captured Ct.Th patterns, potentially explaining the superior classification performance of models based on SMPM-vBMD features (Hypothesis 2). Age, height and weight had a small impact on model performances, and the model of shape, vBMD and Ct.Th consistently yielded better performances than the Neck.aBMD models. Results of this study clearly support the relevance of bone density and quality on the assessment of hip fracture, and demonstrate their potential on patient and healthcare cost benefits. [ABSTRACT FROM AUTHOR]

Although cognitive behavioral therapy (CBT) is highly effective in the treatment of anxiety disorders, many patients still do not benefit. This study investigates whether a history of traumatic event experience is negatively associated with outcomes of CBT for panic disorder. The moderating role of the monoamine oxidase A (MAOA) gene and depression symptoms as well as the association between trauma history and fear reactivity as a potential mechanism are further analyzed. We conducted a post-hoc analysis of 172 male and 60 female patients with panic disorder treated with CBT in a multi-center study. Treatment outcome was assessed at post-treatment using self-report and clinician rating scales. Fear reactivity before treatment was assessed via heart rate and self-reported anxiety during a behavioral avoidance test. Among females, we did not find any differences in treatment response between traumatized and non-traumatized individuals or any two-way interaction trauma history × MAOA genotype. There was a significant three-way interaction trauma history × MAOA genotype × depression symptoms on all treatment outcomes indicating that in traumatized female patients carrying the low-activity allele, treatment effect sizes decreased with increasing depression symptoms at baseline. No such effects were observed for males. In conclusion, we found no evidence for a differential treatment response in traumatized and non-traumatized individuals. There is preliminary evidence for poorer treatment outcomes in a subgroup of female traumatized individuals carrying the low-active variant of the MAOA gene. These patients also report more symptoms of depression symptomatology and exhibit a dampened fear response before treatment which warrants further investigation. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine if clinical dynamic PET/CT imaging with 11C-L-methyl-methionine (11C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13C6] phenylalanine (13C6-Phe).Methods: Healthy older women (73 ± 5 years) completed both dynamic PET/CT imaging with 11C-MET and a stable isotope infusion of 13C6-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient Ki from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle.Results: Post-prandial values [mean ± standard error of the mean (SEM)] were higher than post-absorptive values for both Ki (0.0095 ± 0.001 vs. 0.00785 ± 0.001 min-1, p < 0.05) and FSR (0.083 ± 0.008 vs. 0.049 ± 0.006%/h, p < 0.001) in response to the whey protein supplement. The percent increase in Ki and FSR in response to the whey protein supplement was significantly correlated (r = 0.79, p = 0.015).Conclusions: Dynamic PET/CT imaging with 11C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis. [ABSTRACT FROM AUTHOR]

HR-pQCT enables in vivo multi-parametric assessments of bone microstructure in the distal radius and distal tibia. Conventional HR-pQCT image analysis approaches summarize bone parameters into global scalars, discarding relevant spatial information. In this work, we demonstrate the feasibility and reliability of statistical parametric mapping (SPM) techniques for HR-pQCT studies, which enable population-based local comparisons of bone properties. We present voxel-based morphometry (VBM) to assess trabecular and cortical bone voxel-based features, and a surface-based framework to assess cortical bone features both in cross-sectional and longitudinal studies. In addition, we present tensor-based morphometry (TBM) to assess trabecular and cortical bone structural changes. The SPM techniques were evaluated based on scan-rescan HR-pQCT acquisitions with repositioning of the distal radius and distal tibia of 30 subjects. For VBM and surface-based SPM purposes, all scans were spatially normalized to common radial and tibial templates, while for TBM purposes, rescans ( follow- up) were spatially normalized to their corresponding scans ( baseline). VBM was evaluated based on maps of local bone volume fraction (BV/TV), homogenized volumetric bone mineral density (vBMD), and homogenized strain energy density (SED) derived from micro-finite element analysis; while the cortical bone framework was evaluated based on surface maps of cortical bone thickness, vBMD, and SED. Voxel-wise and vertex-wise comparisons of bone features were done between the groups of baseline and follow- up scans. TBM was evaluated based on mean square errors of determinants of Jacobians at baseline bone voxels. In both anatomical sites, voxel- and vertex-wise uni- and multi-parametric comparisons yielded non-significant differences, and TBM showed no artefactual bone loss or apposition. The presented SPM techniques demonstrated robust specificity thus warranting their application in future clinical HR-pQCT studies. [ABSTRACT FROM AUTHOR]

Organic and metal contaminants and biological effects were investigated in flounder, mussels, and sediments in the southern Baltic Sea coastal area in order to assess environmental quality status in that area. Four sites were selected, including two within the Gulf of Gdańsk (GoG). In biota and sediment at each site, DDTs dominated over PCBs and PBDEs were the least abundant among organic contaminants. Their concentrations decreased progressively outward from GoG. Among metal contaminants, the levels of Hg, Pb, and Cd were elevated in GoG. Biomarkers in flounder, EROD activity and DNA SB, showed moderate positive correlations with organic and metal contaminants. In flounder, the integrated biomarker index (IBR/n) presented a spatial trend coherent with chemical pollution index (CPI), but there was no clear spatial correspondence between IBR/n and CPI in mussels nor between sediment toxicity index (STI) and sediment CPI. The integrated assessment of contaminant and biological effect data against available assessment criteria indicated that in biota, the contaminant assessment thresholds were most often exceeded by CB-118, heptachlor, PBDE, and Hg (in the GoG sediments by p, p′-DDT, Hg and Cd), while of the biological determinants, the threshold was breeched by AChE activity in mussels in GoG. Applying the ICES/OSPAR traffic-light approach showed that of the 50 parameters assessed at each site, there were 18% of determinants in the red color category in the two GoG sites and 8% of determinants in the two sites outside GoG, which indicated that none of the four investigated sites attained good environmental status (GES). [ABSTRACT FROM AUTHOR]

Adaption to changing environments is evolutionarily advantageous. Studies that link genetic and phenotypic expression of flexible adjustment to one's context are largely lacking. In this study, we tested the importance of psychological flexibility, or goal-related context sensitivity, in an interaction between psychotherapy outcome for panic disorder with agoraphobia (PD/AG) and a genetic polymorphism. Given the established role of the 5HTT-LPR polymorphism in behavioral flexibility, we tested whether this polymorphism (short group vs. long group) impacted therapy response as a function of various endophenotypes (i.e., psychological flexibility, panic, agoraphobic avoidance, and anxiety sensitivity). Patients with PD/AG were recruited from a large multicenter randomized controlled clinical trial on cognitive-behavioral therapy. Pre- to post-treatment changes by 5HTT polymorphism were analyzed. 5HTT polymorphism status differentiated pre- to post-treatment changes in the endophenotype psychological flexibility (effect size difference d = 0.4, p < 0.05), but none of the specific symptom-related endophenotypes consistently for both the intent-to-treat sample ( n = 228) and the treatment completers ( n = 194). Based on the consistency of these findings with existing theory on behavioral flexibility, the specificity of the results across phenotypes, and the consistency of results across analyses (i.e., completer and intent to treat), we conclude that 5HTT polymorphism and the endophenotype psychological flexibility are important variables for the treatment of PD/AG. The endophenotype psychological flexibility may help bridge genetic and psychological literatures. Despite the limitation of the post hoc nature of these analyses, further study is clearly warranted. [ABSTRACT FROM AUTHOR]

Zoographical distribution of metazoan fish parasites in herring, Clupea harengus, from the Baltic Sea was analysed in order to use them as potential biological indicators. A total of 210 herring from six different sampling sites were investigated, harbouring 12 different parasite species [five digeneans (D), one cestode (C), three nematodes (N) and three acanthocephalans (A)]. The distribution of the parasite species differed according to region, with a distinct gradient of decreasing species richness towards the east of the Baltic Sea. The western localities at Kiel Bay, Rügen and Poland had the highest parasite diversity, including the marine parasite species Anisakis simplex (s.s.) (N), Brachyphallus crenatus and Hemiurus luehei (both D). The eastern localities had low parasite species richness, predominated by the freshwater digenean Diplostomum spathaceum. We could identify three different Baltic herring stocks, the spring-spawning herring of the western Baltic reaching from the Kattegat to the German and Polish coast, the stock of the central Baltic proper and the northern stock of C. harengus var. membras of the Gulf of Finland. The limited distribution of the herring parasites within the Baltic Sea enables their use as biological indicators for migration patterns and stock separation. The acanthocephalan Pomphorhynchus laevis that has already been used as an accumulation bioindicator for heavy metals was only recorded for the western herring stocks. However, the presence of mainly generalistic parasites and their uneven distribution patterns make their use as indicators for regional environmental and global change more difficult. [ABSTRACT FROM AUTHOR]

Background: To determine if metal artefact reduction (MAR) combined with a priori knowledge of prosthesis material composition can be applied to obtain CT-based attenuation maps with sufficient accuracy for quantitative assessment of F-fluorodeoxyglucose uptake in lesions near metallic prostheses. Methods: A custom hip prosthesis phantom with a lesion-sized cavity filled with 0.2 ml F-FDG solution having an activity of 3.367 MBq adjacent to a prosthesis bore was imaged twice with a chrome-cobalt steel hip prosthesis and a plastic replica, respectively. Scanning was performed on a clinical hybrid PET/CT system equipped with an additional external Cs transmission source. PET emission images were reconstructed from both phantom configurations with CT-based attenuation correction (CTAC) and with CT-based attenuation correction using MAR (MARCTAC). To compare results with the attenuation-correction method extant prior to the advent of PET/CT, we also carried out attenuation correction with Cs transmission-based attenuation correction (TXAC). CTAC and MARCTAC images were scaled to attenuation coefficients at 511 keV using a trilinear function that mapped the highest CT values to the prosthesis alloy attenuation coefficient. Accuracy and spatial distribution of the lesion activity was compared between the three reconstruction schemes. Results: Compared to the reference activity of 3.37 MBq, the estimated activity quantified from the PET image corrected by TXAC was 3.41 MBq. The activity estimated from PET images corrected by MARCTAC was similar in accuracy at 3.32 MBq. CTAC corrected PET images resulted in nearly 40 % overestimation of lesion activity at 4.70 MBq. Comparison of PET images obtained with the plastic and metal prostheses in place showed that CTAC resulted in a marked distortion of the F-FDG distribution within the lesion, whereas application of MARCTAC and TXAC resulted in lesion distributions similar to those observed with the plastic replica. Conclusions: MAR combined with a trilinear CT number mapping for PET attenuation correction resulted in estimates of lesion activity comparable in accuracy to that obtained with Cs transmission-based attenuation correction, and far superior to estimates made without attenuation correction or with a standard CT attenuation map. The ability to use CT images for attenuation correction is a potentially important development because it obviates the need for a Cs transmission source, which entails extra scan time, logistical complexity and expense. [ABSTRACT FROM AUTHOR]

The need to develop biological effects monitoring to facilitate a reliable assessment of hazardous substances has been emphasized in the Baltic Sea Action Plan of the Helsinki Commission. An integrated chemical-biological approach is vitally important for the understanding and proper assessment of anthropogenic pressures and their effects on the Baltic Sea. Such an approach is also necessary for prudent management aiming at safeguarding the sustainable use of ecosystem goods and Services. The BEAST project (Biological Effects of Anthropogenic Chemical Stress: Tools for the Assessment of Ecosystem Health) set out to address this topic within the BONUS Programme. BEAST generated a large amount of quality-assured data on several biological effects parameters (biomarkers) in various marine species in different sub-regions of the Baltic Sea. New indicators (biological response measurement methods) and management tools (integrated indices) with regard to the integrated monitoring approach were suggested. [ABSTRACT FROM AUTHOR]

The development of fluorescent probes for sensing of anions in biological environments is still a demanding task. Due to the structural versatility of biological active anions there are many challenges to cope with compared to fluoroionophores for the determination of metal cations. This concerns particularly the design of the recognition element, which has to provide a selective response, preferably unaffected by alterations of pH and ionic strength. Polyphosphate anions such as ATP are interesting targets in bioanalysis because they are involved in many enzymatic reactions and bear versatile biological functions. Zinc dipicolylamine complexes attached to fluorophores have been turned out to be promising candidates for ATP sensing with sufficient sensitivity and selectivity. We now report the first NIR probe that responds to ATP based on a zinc dipicolylethylenediamine receptor. It shows a 'turn-on' fluorescence behavior which is selective to other polyphosphate species even at high ionic strength of the sample solution. [ABSTRACT FROM AUTHOR]

Amorphous silica nanoparticles (aSNPs) gain increasing popularity for industrial and therapeutic claims. The lung with its surface area of 100-140 m displays an ideal target for therapeutic approaches, but it represents also a serious area of attack for harmful nanomaterials. The exact nature of the cytotoxic effects of NPs is still unknown. Furthermore, cellular pathways and the destiny of internalized NPs are still poorly understood. Therefore, we examined the cytotoxicity (MTS, LDH) and inflammatory responses (IL-8) for different-sized aSNPs (30, 70, 300 nm) on our lung epithelial cells line NCI H441 and endothelial cell line ISO-HAS-1. Additionally, colocalization studies have been conducted via immunofluorescence staining for flotillin-1- and flotillin-2-bearing endocytic vesicles. Subsequently, the relevance of flotillins concerning the viability of aSNP-exposed epithelial cells has been evaluated using flotillin-1/2 depleted cells ( siRNA). This study reveals the relevance of the nanoparticle size regarding cytotoxicity (MTS, LDH) and inflammatory responses (IL-8), whereat the smaller the size of the nanoparticle is, the more harmful are the effects. All different aSNP sizes have been incorporated in flotillin-1- and flotillin-2-labelled vesicles in lung epithelial and endothelial cells, which display a marker for late endosomal or lysosomal structures and appear to exhibit a clathrin- or caveolae-independent mode of endocytosis. Flotillin-depleted H441 showed a clearly decreased uptake of aSNPs. Additionally, the viability of aSNP-exposed cells was reduced in these cells. These findings indicate a contribution of flotillins in as yet unknown (clathrin or caveolae-independent) endocytosis mechanisms and (or) endosomal storage. [ABSTRACT FROM AUTHOR]

In a cross-sectional study we investigated the relationship between muscle and bone parameters in the mid-thigh in older people using data from a single axial computed tomographic section through the mid-thigh. Additionally, we studied the association of these variables with incident low-trauma lower limb fractures. A total of 3,762 older individuals (1,838 men and 1,924 women), aged 66-96 years, participants in the AGES-Reykjavik study, were studied. The total cross-sectional muscular area and knee extensor strength declined with age similarly in both sexes. Muscle parameters correlated most strongly with cortical area and total shaft area (adjusted for age, height, and weight) but explained <10 % of variability in those bone parameters. The increment in medullary area (MA) and buckling ratio (BR) with age was almost fourfold greater in women than men. The association between MA and muscle parameters was nonsignificant. During a median follow-up of 5.3 years, 113 women and 66 men sustained incident lower limb fractures. Small muscular area, low knee extensor strength, large MA, low cortical thickness, and high BR were significantly associated with fractures in both sexes. Our results show that bone and muscle loss proceed at different rates and with different gender patterns. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms of human ABC-transporter genes have been suggested to modulate breast cancer risk in the general population. In particular ABCC11 (MRP8), which is highly expressed in breast cancer tissue and involved in the efflux of conjugated estrogen metabolites such as estrone-3-sulfate and estradiol-17beta-glucuronide, has recently been proposed as a potential risk factor for female breast cancer. The wet earwax-associated G-allele of the c.538G>A polymorphism was associated with an increased risk for breast cancer in Japanese women. In contrast, no evidence for such an association could be observed in Caucasian women. We aimed to confirm/refute the association of the c.538G>A variant in ABCC11 with breast cancer risk and/or histo-pathological tumor characteristics in an independent population-based breast cancer case-control study from Germany comprising 1021 cases and 1015 age-matched controls. No association for allele and genotype frequencies of the 538G>A variant in ABCB11 with breast cancer risk was found. Our data suggest that the c.538G>A variation in ABCC11 does not contribute to breast carcinogenesis in women of European descent. [ABSTRACT FROM AUTHOR]

Astronauts experience bone loss after the long spaceflight missions. Identifying specific regions that undergo the greatest losses (e.g. the proximal femur) could reveal information about the processes of bone loss in disuse and disease. Methods for detecting such regions, however, remains an open problem. This paper focuses on statistical methods to detect such regions. We perform statistical parametric mapping to get t-maps of changes in images, and propose a new cross-validation method to select an optimum suprathreshold for forming clusters of pixels. Once these candidate clusters are formed, we use permutation testing of longitudinal labels to derive significant changes. [ABSTRACT FROM AUTHOR]

The article presents the study on the biological effect monitoring in dab (Limanda limanda) using gene transcript of CYP1A1 or biomarker ethoxyresorufin-Ο-deethylase (EROD). The study primarily makes a comparison between EROD activity and CYP1A1 mRNA expression in monitoring fish species dab. It also targets to answer whether these parameters reflect the polycyclic aromatic hydrocarbon contamination of the fish. Detailed results of the study are presented, showing a considerable individual variation in the levels for CYP1A1 mRNA and EROD.

THIS ARTICLE provides an overview of the successful laptop implementation in the College of Education at the University of South Florida (USF). The pilot initiative began with one cohort of preservice teachers in 2003; since then, the program has expanded throughout the college. Through a chronological outline of the issues, formative evaluations, modifications, and expansion of the project as it progressed through the years, this article shares lessons learned related to the process and outcomes. For example, initial implementation decisions included issues such as whether participation should be voluntary or mandatory, which computer platforms would be supported, and how training and support would be provided. As the project expanded, questions related to ongoing maintenance, financial aid, and other issues were addressed. [ABSTRACT FROM AUTHOR]

Chronic treatment with glucocorticoids (GCs) leads to significant bone loss and increased risk of fractures. In chronically GC-treated patients, hip fracture risk is nearly 50%. The purpose of this investigation was to determine if there are differences in the quantities of trabecular and cortical bone and bone strength of the hip between GC-treated osteoporotic patients and controls. Methods: Study subjects were GC-treated osteoporotic postmenopausal women, and controls were postmenopausal women, recruited for separate clinical trials. Quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) of the hip were obtained from all subjects. QCT outcome variables measured included total, cortical, and trabecular BMD of hip subregions (femoral neck and trochanter) and total hip. In addition, finite element modeling (FEM) was performed on a subset of 19 cases and 38 controls, matched on age (± 5 years), weight (± 5 kg), and history of hormone replacement (>1 year use) to assess failure load in stance and fall loading conditions. Generalized linear models were used to adjust the QCT variables for covariates between groups. Multiple regression was performed to identify independent predictors of bone strength from the QCT variables. Results: Compared with controls, GC-treated subjects were significantly (p<0.05) younger, weighed less, and had more years of hormone replacement. QCT of the hip in GC-treated subjects for total femoral integral, cortical, and trabecular BMD averaged 4.9-23.2% (p<0.002) less than controls, and similar results were seen by hip subregion including the trochanter and femoral neck. DXA of the total hip was 17% lower in GC subjects than controls (p<0.05). Compared with controls, FEM failure load in GC subjects was 15% (p<0.05) and 16% (p=0.07) lower for stance and fall loading conditions, respectively. Multiple regression analysis demonstrated that a combination of QCT measures was correlated with bone strength as measured by FEM. Conclusions: Chronic GC treatment in postmenopausal women resulted in significantly decreased BMD of the hip, measured by QCT, with loss of both trabecular and cortical bone. In addition, GC treatment decreased bone strength as determined by FEM. The reduced cortical and trabecular bone mass in the hip may contribute to the disproportionately high hip fracture rates observed in GC-treated subjects. [ABSTRACT FROM AUTHOR]

Ethoxyresorufin-O-deethylase (EROD) is a well-accepted marker for biological effects in fish and is, therefore, part of numerous monitoring programmes. EROD activity was measured in livers of dab (Limanda limanda) from the German Bight (North Sea) from 1995 to 2003. The aim of the present long-term study was (a) time trend monitoring of EROD activity of dab from the German Bight and (b) to elucidate the needs for a successful application of EROD activity as an early warning system. Methods. EROD activities were determined fluorimetrically in dab liver microsomes, using resorufin as an external standard. The limit of detection (LD) and the limit of quantification (LQ) were calculated. Results were referred to protein concentrations. Results and Discussion. EROD activities of 610 female dab caught in different seasons between January 1995 and August 2003 were analyzed individually. Activities varied from 〈 LD to 1768 pmol/(min mg protein) and showed an annual cycle as well as significant differences between the years. Highest EROD activities were observed in early summer and lowest activities during the winter period. In autumn 2002, significantly elevated EROD activities were detected, possibly related to effects of the River Elbe flood event. Two scenarios with different EROD baseline data are presented to discuss the prerequisites for the use of EROD as a monitoring tool. The comparison of these scenarios underlines the importance of appropriate season-specific baseline data. Conclusion. The use of EROD as an early warning tool for contaminant effects in dab in the German Bight has different prospects during the year, because, due to the high background variability, elevated EROD activities are less easy to detect in spring/summer than during the remaining times of the year. Recommendation and Outlook. The availability of site-specific data on the EROD baseline level, its random variation and its annual cycle is a necessary prerequisite for monitoring. If monitoring is to be carried out only for a limited time period of the year, a season with low background variability in EROD activity (autumn) should be chosen to avoid the need for a compensation of the temperature-triggered shift in sexual cycles and the resulting changes in EROD activity. [ABSTRACT FROM AUTHOR]

Objective: The organizational structure of health care facilities has been shown to affect outcome in critically ill patients. We evaluated the association between structures, treatments and outcomes in a large cohort of critically ill patients.Design: Prospective multicentre cohort study.Patients and Setting: A total of 26,186 patients consecutively admitted to 31 intensive care units (ICUs) in Austria from January 1998 through December 2000.Measurements and Results: The ICUs were divided into three groups according to the size and function of the hospital: community hospitals and specialized trauma centers (group A); central referral hospitals (group B); and teaching hospitals (group C). Group C patients exhibited a significantly higher risk-adjusted mortality (O/E ratio). Although severity of illness at admission in groups B and C was similar, group C patients received significantly more invasive diagnostic and therapeutic interventions throughout their ICU stay: For 7 of 10 invasive interventions identified, odds ratios for group C vs group B patients were significantly increased, even after adjustment for age, gender, severity of illness and reason for admission (odds ratios 1.2-13.1; all 95% CIs >1). Risk-adjusted multivariate analysis confirmed that six of these invasive interventions were independently associated with mortality. Furthermore, nurse-to-patient ratios did not differ between groups, leading to a significantly increased nursing workload in group C ICUs.Conclusions: Several invasive interventions were independently associated with increased mortality. Our results provide strong evidence that this association was responsible in part for the increased risk-adjusted mortality in group C patients. [ABSTRACT FROM AUTHOR]

Objective: To compare three scoring systems, the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Simplified Acute Physiology Score (SAPS) II and a modified Mortality Probability Model II (ICU cancer mortality model, ICMM) for their prognostic value for mortality during hospital stay in a group of cancer patients admitted to a medical ICU.Design: Prospective cohort study.Setting: Medical ICU of a tertiary care hospital.Patients: Two hundred forty-two consecutive cancer patients admitted to the ICU.Measurements and Results: Variables included in APACHE II, SAPS II and the ICMM scores as well as demographic data were assessed during the first 24 h of stay in the ICU. Hospital mortality was measured; it was 44%. Calibration for all three scoring systems was acceptable, SAPS II yielded a significantly superior discrimination between survivors and non-survivors. The areas under the receiver operating characteristic curves were 0.776 for APACHE II, 0.825 for SAPS II and 0.698 for the ICMM.Conclusion: The SAPS II was superior to APACHE II and ICMM. The newly developed ICMM does not improve mortality prediction in critically ill cancer patients. [ABSTRACT FROM AUTHOR]

This study describes a new method for the treatment of osteochondritis dissecans (OCD) in the medial talar dome. Ten cadaveric lower extremities were used to develop and evaluate a retrograde osteochondral grafting technique applying computer-assisted surgery. With the help of a computed tomography (CT)-based navigation system, a guide wire was placed from the lateral talar process into the posteromedial talar trochlea where OCD lesions are predominantly located. Cannulated reamers and arthroscopic shavers were used for the preparation of the recipient hole. The grafts, with diameters of 4.5 mm, 6.5 mm or 8.5 mm were harvested from the lateral femoral trochlea and inserted in a retrograde fashion. The last five cadavers were analyzed for accuracy of surface reconstruction and graft stability. For this purpose a medial malleolar osteotomy and a CT scan was performed. We found steps in the joint surface to range from 0.5 mm to 1.5 mm (mean 0.9 mm, SD 0.4) with the graft always below the surrounding cartilage. Graft subsidence occurred at an applied force of 26.4 +/- 4.6 N. This study indicates that osteochondral cylinders can be inserted in a retrograde fashion to reconstruct the posteromedial talus. Good surface congruency and sufficient graft stability can be achieved. [ABSTRACT FROM AUTHOR]

Objective: To evaluate risk factors in critically ill patients who were readmitted to an intensive care unit (ICU) during their hospital stay.Design: Prospective multicenter cohort study.Patients and Setting: A total of 15180 patients discharged from 30 medical, surgical and mixed ICUs in Austria over a 2-year period.Measurements and Results: The data analyzed included data on patients' clinical characteristics, Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction system (LOD), Simplified Therapeutic Intervention Scoring System (TISS-28), length of ICU stay, ICU mortality and hospital mortality. Of the 15180 patients who survived the first ICU stay, 780 patients (5.1%) were readmitted. These patients had more than a fourfold risk of dying during their hospital stay (21.7 vs 5.2%, p<0.001). For mechanically ventilated patients, the time between extubation and discharge during the first ICU stay was significantly shorter for readmitted than for non-readmitted patients (median 1 vs 2 days, p<0.001). On the day of their first ICU discharge, readmitted patients were in greater need of organ support, with more patients still requiring ventilatory, cardiovascular and renal support than non-readmitted patients.Conclusions: The results of this study provide evidence that there exists a group of patients at higher risk of readmission to the ICU. At the time of their first ICU discharge, these patients presented with residual organ dysfunctions, which were associated with an increased risk of being readmitted. Optimizing organ functions in these patients before discharge from the ICU could result in reduced readmission rates. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic adjustable gastric banding (LAGB) is now the most frequently performed gastric restriction procedure. While short- and longterm outcome have been described extensively, the relationship between eating behavior and weight reduction is still unclear. Methods: The present study examined the eating behavior of 66 selected morbidly obese subjects before and after LAGB by means of the Eating Inventory (EI), the Binge Scale Questionnaire (BSQ) and additional items. Assessments were conducted 6 months before surgery and at 3, 9, and 12 months after surgery. Results: Significant reductions of weight and BMI were observed until 9 months after surgery, with a loss of 34.5% of excess weight. Later, a slight weight regain was noted. At baseline, Cognitive Restraint (CR), Hunger (H) and Flexible Control (FC) were within the norm, whereas Disinhibition (D) and Rigid Control (RC) were significantly elevated. None of the scales were related to BMI. At follow-up, significant changes were observed between presurgery and 3 months follow-up (T2), with increased CR, FC, and RC, and decreased D, H, and Binge Eating. These changes mostly remained stable. The largest changes were observed 3 months postsurgery in Flexible Control (FC), followed by D, CR, H, and RC. At follow-up, again no correlation was found between eating behavior and the total difference of BMI. Conclusion: LAGB results in significant reductions of weight, disinhibition and hunger during the first 9 months postoperatively. The change in eating behavior after surgery is independent of BMI and characterized mostly by elevated flexible control. Results indicate also changes of other behaviors that contribute to weight loss but are difficult to control. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of the logistic organ dysfunction (LOD) system for the assessment of morbidity and mortality in multiple organ dysfunction/failure (MOD/F) in an independent database and to evaluate the use of sequential LOD measurements for the prediction of outcome.Design and Setting: Prospective, multicentric cohort study in 13 adult medical, surgical, and mixed intensive care units (ICUs) in Austria.Patients: A total of 2,893 consecutive admissions to the ICUs.Measurements and Main Results: Patient vital status at ICU and hospital discharge was recorded. Univariate analysis showed that the LOD was able to distinguish between survivors and nonsurvivors (2 vs. 6 median score). Within organ systems, higher levels of the severity of organ dysfunction were consistently associated with higher mortality. For the prediction of hospital mortality, the original prognostic LOD model did not perform well in our patients, as indicated by the goodness-of-fit C statistic. Using multiple logistic regression we developed a prognostic model with a satisfactory fit in our patients. The integration of further measurements during the ICU stay increased discrimination but not calibration.Conclusions: The LOD system is well correlated well with the numbers and levels of organ dysfunctions and discriminates well between survivors and nonsurvivors. It can thus be used to quantify the baseline severity of organ dysfunction. Moreover, after customization of the predictive equation the LOD predicted hospital mortality in our patients with high precision. It thus provides a combined measure of morbidity and mortality for critically ill patients with MOD/F. [ABSTRACT FROM AUTHOR]

The present paper describes the medium-term results (mean follow-up period 3.01 years) achieved after surgical stabilisation of 79 patients using modified Evans tenodesis. The follow-up examination included a questionnaire for rating the subjective sense of stability, a clinical examination, stress X-rays, a modified 100-point score according to Zwipp, and kinetic gait analysis. Although joint instability was significantly improved in the radiological stress images, only 73.4% of the patients subjectively rated the stability achieved as excellent or good, compared with satisfactory in 22%, and even poor in 3.8%. In the overall result of the 100-point score, 51.9% of the patients achieved a very good, 35.4% a good, 11.4% a satisfactory, and 1.3% a poor result. Radiologically, an increase in the rate of arthrosis was verified in 17.4%. Significant deteriorations in mobility were observed for the supination. The kinetic gait analysis revealed statistically significant differences compared with the non-operated side for step length (P<0.05), relative step length (P<0.05), and in the symmetry of heel-to-toe movement (P<0.005). The modified Evans repair can restore the mechanical stability of the ankle, but it leads to impaired kinematics of the ankle, with subjective and functional restrictions and radiologically detectable degenerative changes. For this reason, modified Evans tenodesis should only be performed if anatomically orientated stabilisation operations are not possible. [ABSTRACT FROM AUTHOR]

Objectives: To validate SAPS II-AM, a recently customized version of the Simplified Acute Physiology Score II (SAPS II) in a larger cohort of Austrian intensive care patients and to evaluate the effect of the customization process on the ratio of observed to expected mortality.Design: Prospective, multicentric cohort study.Patients and Setting: A total of 2,901 patients consecutively admitted to 13 adult medical, surgical, and mixed intensive care units (ICUs) in Austria.Measurements and Results: After the database was divided randomly into a development sample (n = 1,450) and a validation sample (n = 1,451), logistic regression was used to develop a new model (SAPS II-AM2). The original SAPS II, the SAPS IIAM, and the newly developed SAPS II-AM2 were then compared by means of calibration, discrimination and O/E ratios. Differences in O/E ratios before and after customization (deltaO/E) were calculated. The Hosmer-Lemeshow goodness-of-fit H and C statistics revealed poor calibration of the original SAPS II on the database. The new model, SAPS II-AM2, performed better than the SAPS II-AM and excellent in the validation data set. However, mean O/E ratios varied widely among diagnostic categories (range 0.55-1.05 for the SAPS II). Moreover, the deltaO/E of the 13 ICUs ranged from -3.6 % to +25 %.Conclusions: Today's severity scoring systems, such as the SAPS II, are limited by not measuring (and adjusting for) a profound part of what constitutes case mix. Changes in the distribution of patient characteristics (known and unknown) therefore affect prognostic accuracy. First-level customization was not able to solve all these problems. Using O/E ratios for quality of care comparisons one must therefore be critical when using these data and should search for possible confounding factors. In the case of unsatisfactory calibration, customized severity of illness models may be useful as an adjunct for quality control. [ABSTRACT FROM AUTHOR]

Of five glycolytic enzymes tested, only the serum activity of phosphohexose isomerase (PHI) was elevated in the vast majority of 140 patients with gastrointestinal, kidney or mammary carcinomas. However, in the tumor tissues all enzymes were increased to about the same extent. Thus, the measured increase in the serum activity of PHI is not due to a specific overproduction in the malignant cells. A general rise in the glycolytic enzyme activities in the malignant tissue could be detected already in early stages without metastases and in well-differentiated tumors. Copyright © 1988 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]