Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas

A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic approaches targeting HSP90/GRP94 have been introduced for treating cancer. We performed a comprehensive investigation of HSP and GRP expression including HSP27, phosphorylated (p)-HSP27((Ser15)), p-HSP27((Ser78)), p-HSP27((Ser82)), HSP60, HSP70, HSP90, GRP78 and GRP94 in 92 primary resected oesophageal adenocarcinomas by using reverse phase protein arrays (RPPA), immunohistochemistry (IHC) and real-time quantitative RT-PCR (qPCR). Results were correlated with pathologic features and survival. HSP/GRP protein and mRNA expression was detected in all tumours at various levels. Unsupervised hierarchical clustering showed two distinct groups of tumours with specific protein expression patterns: The hallmark of the first group was a high expression of p-HSP27((Ser15, Ser78, Ser82)) and low expression of GRP78, GRP94 and HSP60. The second group showed the inverse pattern with low p-HSP27 and high GRP78, GRP94 and HSP60 expression. The clinical outcome for patients from the first group was significantly improved compared to patients from the second group, both in univariate analysis (p = 0.015) and multivariate analysis (p = 0.029). Interestingly, these two groups could not be distinguished by immunohistochemistry or qPCR analysis. In summary, two distinct and prognostic relevant HSP/GRP protein expression patterns in adenocarcinomas of the oesophagus were detected by RPPA. Our approach may be helpful for identifying candidates for specific HSP/GRP-targeted therapies.

Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients

High-dose or dose-intensive cytotoxic chemotherapy often causes myelosuppression and severe neutropenia among cancer patients. Severe neutropenia accompanied by fever, named febrile neutropenia (FN), is the most serious manifestation of neutropenia usually requiring hospitalization and intravenous antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose reductions, which potentially compromises the effectiveness of cancer treatment and prospects for a cure. Granulocyte-macrophage (GM) and granulocyte colony-stimulating factors (G-CSFs) are administered during chemotherapy in order to prevent or reduce the incidence or the duration of FN and neutropenia.

Factors influencing subjective quality of life in patients with schizophrenia and other mental disorders: a pooled analysis

Subjective quality of life (SQOL) is an important outcome in the treatment of patients with schizophrenia. However, there is only limited evidence on factors influencing SQOL, and little is known about whether the same factors influence SQOL in patients with schizophrenia and other mental disorders. This study aimed to identify the factors associated with SQOL and test whether these factors are equally important in schizophrenia and other disorders. For this we used a pooled data set obtained from 16 studies that had used either the Lancashire Quality of Life Profile or the Manchester Short Assessment of Quality of Life for assessing SQOL. The sample comprised 3936 patients with schizophrenia, mood disorders, and neurotic disorders. After controlling for confounding factors, within-subject clustering, and heterogeneity of findings across studies in linear mixed models, patients with schizophrenia had more favourable SQOL scores than those with mood and neurotic disorders. In all diagnostic groups, older patients, those in employment, and those with lower symptom scores had higher SQOL scores. Whilst the strength of the association between age and SQOL did not differ across diagnostic groups, symptom levels were more strongly associated with SQOL in neurotic than in mood disorders and schizophrenia. The association of employment and SQOL was stronger in mood and neurotic disorders than in schizophrenia. The findings may inform the use and interpretation of SQOL data for patients with schizophrenia.

Detection of Chlamydia and complement factors in neovascular membranes of patients with age-related macular degeneration

PURPOSE To investigate whether Chlamydia pneumoniae and complement factors were present in surgically removed choroidal neovascular membranes (CNV) of patients with age-related macular degeneration (AMD). METHODS Paraffin sections of 26 CNV were stained for C. pneumoniae or the complement factors H (CFH) and C5, whereas macrophages were identified by positive CD68 staining. Clinical characteristics have been correlated to the immunohistochemical findings. RESULTS C. pneumoniae was found in 68% of the investigated membranes, and 88% of these membranes were also positive for CD68. Staining for CFH and C5 gave a positive reaction in 68 and 41% of the membranes, respectively. Patients with C5-positive membranes had significantly larger CNV mean area and were younger than patients with CFH-positive membranes at the operation time point. CONCLUSIONS Correlations between clinical symptoms and complement factor C5 could be shown. The results strengthen the hypothesis of an involvement of the complement system in AMD.

Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group

GOAL OF THE WORK: Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy. MATERIALS AND METHODS: We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression. MAIN RESULTS: Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar. CONCLUSIONS: Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.

Differentiating hippocampal subregions by means of quantitative magnetization transfer and relaxometry: preliminary results

The hippocampal formation (HF) of healthy control subjects and schizophrenic patients was examined using an MRI experiment that implements sequences for relaxometry and magnetization transfer (MT) quantification. In addition to the semi-quantitative magnetization transfer ratio (MTR), all of the observable properties of the binary spin bath model were included. The study demonstrates that, in contrast to the MTR, quantitative MT parameters (especially the T2 relaxation time of restricted protons, T2b) are capable to differentiate functionally significant subregions within the HF. The MT methodology appears to be a promising new tool for the differential microstructural evaluation of the HF in neuropsychiatric disorders accompanied by memory disturbances.

The silent loss of neuronavigation accuracy: a systematic retrospective analysis of factors influencing the mismatch of frameless stereotactic systems in cranial neurosurgery

BACKGROUND Neuronavigation has become an intrinsic part of preoperative surgical planning and surgical procedures. However, many surgeons have the impression that accuracy decreases during surgery. OBJECTIVE To quantify the decrease of neuronavigation accuracy and identify possible origins, we performed a retrospective quality-control study. METHODS Between April and July 2011, a neuronavigation system was used in conjunction with a specially prepared head holder in 55 consecutive patients. Two different neuronavigation systems were investigated separately. Coregistration was performed with laser-surface matching, paired-point matching using skin fiducials, anatomic landmarks, or bone screws. The initial target registration error (TRE1) was measured using the nasion as the anatomic landmark. Then, after draping and during surgery, the accuracy was checked at predefined procedural landmark steps (Mayfield measurement point and bone measurement point), and deviations were recorded. RESULTS After initial coregistration, the mean (SD) TRE1 was 2.9 (3.3) mm. The TRE1 was significantly dependent on patient positioning, lesion localization, type of neuroimaging, and coregistration method. The following procedures decreased neuronavigation accuracy: attachment of surgical drapes (DTRE2 = 2.7 [1.7] mm), skin retractor attachment (DTRE3 = 1.2 [1.0] mm), craniotomy (DTRE3 = 1.0 [1.4] mm), and Halo ring installation (DTRE3 = 0.5 [0.5] mm). Surgery duration was a significant factor also; the overall DTRE was 1.3 [1.5] mm after 30 minutes and increased to 4.4 [1.8] mm after 5.5 hours of surgery. CONCLUSION After registration, there is an ongoing loss of neuronavigation accuracy. The major factors were draping, attachment of skin retractors, and duration of surgery. Surgeons should be aware of this silent loss of accuracy when using neuronavigation.

Factors influencing the quality of the consultation process

Sport psychology services have become to be an important brick stone when building athletic success. The strive for better performance is not only a characteristic of athletes, but of the whole support system in top level sport including sport psychology. Sport psychology consultants are permanently challenged to deliver highest quality services to their clients if they do not want to lose their contracts. Sport psychologists are continuously improving their consulting skills, learn new intervention techniques, read scientific papers and, last but not least, gain experience by accumulating hours of deliberate practice (Ericsson) in sport psychology. Even with increasing experience, the consultant has a certain number of degrees of freedom and has to make a series of decisions about how he or she wants to work. Quality, however, depends on a number of issues, and not all of them are under direct control of the consultant. It is argued that, in order for these choices being good, the following factors - among others - must be considered: Who is seeking assistance? What are the "issues and problems" (Gardner & Moore, 2006) the athlete is confronted with? What kind of approaches do fit with the client's need? Who is the 'client' the sport psychologist is supposed to work with? If it is a team, is the sport psychologist supposed to work with a number of individuals, with the coach, or with the whole system? Where are the boundaries of the system? What is the role of the sport psychologist in the sport system? All these issues directly affect the process and outcome quality of the sport psychology consultant. A sound theoretical basis, in connection with a distinct philosophy of the intervention, is an important cornerstone for the quality of sport psychology consultation.

Patterns and controls of sediment production, transfer and yield in the Illgraben

Quantification of the volumes of sediment removed by rock–slope failure and debris flows and identification of their coupling and controls are pertinent to understanding mountain basin sediment yield and landscape evolution. This study captures a multi-decadal period of hillslope erosion and channel change following an extreme rock avalanche in 1961 in the Illgraben, a catchment prone to debris flows in the Swiss Alps. We analyzed photogrammetrically-derived datasets of hillslope and channel erosion and deposition along with climatic and seismic variables for a 43 year period from 1963 to 2005. Based on these analyses we identify and discuss (1) patterns of hillslope production, channel transfer and catchment sediment yield, (2) their dominant interactions with climatic and seismic variables, and (3) the nature of hillslope–channel coupling and implications for sediment yield and landscape evolution in this mountain basin. Our results show an increase in the mean hillslope erosion rate in the 1980s from 0.24 ± 0.01 m yr− 1 to 0.42 ± 0.03 m yr− 1 that coincided with a significant increase in air temperature and decrease in snow cover depth and duration, which we presume led to an increase in the exposure of the slopes to thermal weathering processes. The combination of highly fractured slopes close to the threshold angle for failure, and multiple potential triggering mechanisms, means that it is difficult to identify an individual control on slope failure. On the other hand, the rate of channel change was strongly related to variables influencing runoff. A period of particularly high channel erosion rate of 0.74 ± 0.02 m yr− 1 (1992–1998) coincided with an increase in the frequency and magnitude of intense rainfall events. Hillslope erosion exceeded channel erosion on average, indicative of a downslope-directed coupling relationship between hillslope and channel, and demonstrating the first order control of rock–slope failure on catchment sediment yield and landscape evolution.

Factors controlling decomposition rates of fine root litter in temperate forests and grasslands

Background and aims Fine root decomposition contributes significantly to element cycling in terrestrial ecosystems. However, studies on root decomposition rates and on the factors that potentially influence them are fewer than those on leaf litter decomposition. To study the effects of region and land use intensity on fine root decomposition, we established a large scale study in three German regions with different climate regimes and soil properties. Methods In 150 forest and 150 grassland sites we deployed litterbags (100 μm mesh size) with standardized litter consisting of fine roots from European beech in forests and from a lowland mesophilous hay meadow in grasslands. In the central study region, we compared decomposition rates of this standardized litter with root litter collected on-site to separate the effect of litter quality from environmental factors. Results Standardized herbaceous roots in grassland soils decomposed on average significantly faster (24 ± 6 % mass loss after 12 months, mean ± SD) than beech roots in forest soils (12 ± 4 %; p < 0.001). Fine root decomposition varied among the three study regions. Land use intensity, in particular N addition, decreased fine root decomposition in grasslands. The initial lignin:N ratio explained 15 % of the variance in grasslands and 11 % in forests. Soil moisture, soil temperature, and C:N ratios of soils together explained 34 % of the variance of the fine root mass loss in grasslands, and 24 % in forests. Conclusions Grasslands, which have higher fine root biomass and root turnover compared to forests, also have higher rates of root decomposition. Our results further show that at the regional scale fine root decomposition is influenced by environmental variables such as soil moisture, soil temperature and soil nutrient content. Additional variation is explained by root litter quality.

Influencing factors on the length of stay in lumbar spine surgery: analysis of the German spine registry

INTRODUCTION Spinal disc herniation, lumbar spinal stenosis and spondylolisthesis are known to be leading causes of lumbar back pain. The cost of low back pain management and related operations are continuously increasing in the healthcare sector. There are many studies regarding complications after spine surgery but little is known about the factors predicting the length of stay in hospital. The purpose of this study was to identify these factors in lumbar spine surgery in order to adapt the postoperative treatment. MATERIAL AND METHODS The current study was carried out as a post hoc analysis on the basis of the German spine registry. Patients who underwent lumbar spine surgery by posterior surgical access and with posterior fusion and/or rigid stabilization, whereby procedures with dynamic stabilization were excluded. Patient characteristics were tested for association with length of stay (LOS) using bivariate and multivariate analyses. RESULTS A total of 356 patients met the inclusion criteria. The average age of all patients was 64.6 years and the mean LOS was 11.9 ± 6.0 days with a range of 2-44 days. Independent factors that were influencing LOS were increased age at the time of surgery, higher body mass index, male gender, blood transfusion of 1-2 erythrocyte concentrates and the presence of surgical complications. CONCLUSION Identification of predictive factors for prolonged LOS may allow for estimation of patient hospitalization time and for optimization of postoperative care. In individual cases this may result of a reduction in the LOS.

Factors influencing the accuracy of fetal weight estimation with a focus on preterm birth at the limit of viability: a systematic literature review

BACKGROUND Fetal weight estimation (FWE) is an important factor for clinical management decisions, especially in imminent preterm birth at the limit of viability between 23(0/7) and 26(0/7) weeks of gestation. It is crucial to detect and eliminate factors that have a negative impact on the accuracy of FWE. DATA SOURCES In this systematic literature review, we investigated 14 factors that may influence the accuracy of FWE, in particular in preterm neonates born at the limit of viability. RESULTS We found that gestational age, maternal body mass index, amniotic fluid index and ruptured membranes, presentation of the fetus, location of the placenta and the presence of multiple fetuses do not seem to have an impact on FWE accuracy. The influence of the examiner's grade of experience and that of fetal gender were discussed controversially. Fetal weight, time interval between estimation and delivery and the use of different formulas seem to have an evident effect on FWE accuracy. No results were obtained on the impact of active labor. DISCUSSION This review reveals that only few studies investigated factors possibly influencing the accuracy of FWE in preterm neonates at the limit of viability. Further research in this specific age group on potential confounding factors is needed.

The importance of socio-cultural factors on sports behaviour of adolescents and young adults in Switzerland – a conceptualisation on the basis of the habitus-approach

Sport participation has often been the topic in sports science and it could be shown that in Europe the population of northern and western countries are more often physically active than southern and eastern countries (European Commission, 2014). In Switzerland the physical activity of the Swiss population also differs between the linguistic regions. The German speaking population is more often physically active than the French or Italian speaking part (Stamm & Lamprecht, 2008). To explain the differences in sport participation structural and cultural factors have been discussed. Because within a country homogenous structural conditions can be assumed, the aim of this study is to analyse how socio-cultural factors correlate with sport participation of adolescents and young adults. In order to analyse this research question, Bourdieu’s concept of habitus (1984) has been used as theoretical background. This sport-related concept of habitus considers cultural determined values, the attribution of meaning and patterns of action which is socially determined and have an influence on individual actions and therefore also on the sport practise. On this basis, a qualitative study including guideline-based interviews with German (n=5) and French (n=3) speaking adolescents and young adults at the age of 16 to 24 (M=21.4) were held in two different linguistic regions of Switzerland. To analyse the interviews the documentary method was applied (Bohnsack, 2010). Initial findings reveal that there are different sport related values, attributions of meanings and patterns of action also called framework of orientations concerning topics like body, health and leisure which correlate with the habitual sports practise in the two different linguistic regions. This study illustrates that the habitus is culturally shaped and that it could help to understand the meaning of socio-cultural factors for sport participation.