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Purpose R 2 ∗ imaging of brain white matter is well known for being sensitive to the orientation of nerve fibers with respect to the B0 field of the MRI scanner. The goal of this study was to evaluate whether and to which extent fiber orientation dependent R 2 ∗ differs between in vivo and post mortem in situ examinations, and to investigate the influence of varying temperatures and post mortem intervals (PMI). Methods Post mortem in situ and in vivo MRI scans were conducted at 3T. R 2 ∗ was acquired with a multi-echo gradient-echo sequence, and the orientation of white matter fibers was computed using diffusion tensor imaging (DTI). Fitting of the measured fiber orientation dependent R 2 ∗ was performed using three different formulations of a previously proposed model. Results R 2 ∗ increased with increasing fiber angle for in vivo and post mortem in situ examinations, whereby the orientation dependency was lower post mortem. The different formulations of the fiber orientation model resulted in an identical fit, but showed large variations of the estimated parameters. The higher order orientation dependent R 2 ∗ components significantly decreased with decreasing temperature, while the orientation independent R 2 ∗ components showed no significant correlation with either temperature or PMI. Conclusion Although the mean diffusivity is strongly reduced post mortem, we could successfully estimate the fiber angle using DTI. Due to the strong correlation of the higher order orientation dependent R 2 ∗ components with temperature, the decreased R 2 ∗ fiber orientation dependency post mortem in situ might primarily be attributed to the lower brain temperature.

The mechanical properties of the stomach wall help to explain its function of storing, mixing, and emptying in health and disease. However, much remains unknown about its mechanical properties, especially regarding regional heterogeneities and wall microstructure. Consequently, the present study aimed to assess regional differences in the mechanical properties and microstructure of the stomach wall. In general, the stomach wall and the different tissue layers exhibited a nonlinear stress-stretch relationship. Regional differences were found in the mechanical response and the microstructure. The highest stresses of the entire stomach wall in longitudinal direction were found in the corpus (201.5 kPa), where food is ground followed by the antrum (73.1 kPa) and the fundus (26.6 kPa). In contrast, the maximum stresses in circumferential direction were 39.7 kPa, 26.2 kPa, and 15.7 kPa for the antrum, fundus, and corpus, respectively. Independent of the fibre orientation and with respect to the biaxial loading direction, partially clear anisotropic responses were detected in the intact wall and the muscular layer. In contrast, the innermost mucosal layer featured isotropic mechanical characteristics. Pronounced layers of circumferential and longitudinal muscle fibres were found in the fundus only, whereas corpus and antrum contained almost exclusively circumferential orientated muscle fibres. This specific stomach structure mirrors functional differences in the fundus as well as corpus and antrum. Within this study, the load transfer mechanisms, connected with these wavy layers but also in total with the stomach wall’s microstructure, are discussed. Statement of significance This article examines for the first time the layer-specific mechanical and histological properties of the stomach wall attending to the location of the sample. Moreover, both mechanical behaviour and microstructure were explicitly match identifying the heterogeneous characteristics of the stomach. On the one hand, the results of this study contribute to the understanding of stomach mechanics and thus to their functional understanding of stomach motility. On the other hand, they are relevant to the fields of constitutive formulation of stomach tissue, whole stomach mechanics, and stomach-derived scaffolds i.e., tissue-engineering grafts.

The fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequence aims at suppressing the signal of the cerebrospinal fluid (CSF) by acquiring images at the time point at which the longitudinal magnetization and therefore the signal of CSF is zero. This time point is also called the null point inversion time (TI

Evidence-based teaching practices (EBPs) foster college science, technology, engineering, and mathematics (STEM) students' engagement and performance, yet our knowledge of what contributes to the effectiveness of these practices is less established. We propose a framework that links four social-cognitive variables-students' trust in their instructors, growth mindset, buy-in to instructional practices, and course engagement-to long-standing desired student outcomes of academic performance and intent to persist in science. This framework was tested in classrooms identified as having a high level of EBP implementation with a multi-institutional sample of 2102 undergraduates taught by 14 faculty members. Results indicate that the buy-in framework is a valid representation of college students' learning experiences within EBP contexts overall as well as across underrepresented student groups. In comparison to students' level of growth mindset, students' trust in their instructors was more than twice as predictive of buy-in to how the course was being taught, suggesting that students' views of their instructors are more associated with thriving in a high-EBP course environment than their views of intelligence. This study contributes to the dialogue on transforming undergraduate STEM education by providing a validated student buy-in framework as a lens to understand how EBPs enhance student outcomes.

Post mortem in situ and in vivo MRI scans were conducted at 3T.Although the mean diffusivity is strongly reduced post mortem, we could successfully estimate the fiber angle using DTI. Due to the strong correlation of the higher order orientation dependent

Objective MRI temperature sensitivity presents a major issue in in situ post mortem MRI (PMMRI), as the tissue temperatures differ from living persons due to passive cooling of the deceased. This study aims at computing brain temperature effects on the MRI parameters to correct for temperature in PMMRI, laying the foundation for future projects on post mortem validation of in vivo MRI techniques. Materials and methods Brain MRI parameters were assessed in vivo and in situ post mortem using a 3 T MRI scanner. Post mortem brain temperature was measured in situ transethmoidally. The temperature effect was computed by fitting a linear model to the MRI parameters and the corresponding brain temperature. Results Linear positive temperature correlations were observed for T1, T2* and mean diffusivity in all tissue types. A significant negative correlation was observed for T2 in white matter. Fractional anisotropy revealed significant correlations in all gray matter regions except for the thalamus. Discussion The linear models will allow to correct for temperature in post mortem MRI. Comparing in vivo to post mortem conditions, the mean diffusivity, in contrast to T1 and T2, revealed additional effects besides temperature, such as cessation of perfusion and active diffusion.

Background and objective Pain spans a broad spectrum of diseases and types that are highly prevalent and cause substantial disease burden for individuals and society. Up to 40% of people affected by pain receive no or inadequate treatment. Providing a scalable, time-, and location-independent way for pain diagnostic, management, prevention and treatment mobile health applications (MHA) might be a promising approach to improve health care for pain. However, the commercial app market is rapidly growing and unregulated, resulting in an opaque market. Studies investigating the content, privacy and security features, quality and scientific evidence of the available apps are highly needed, to guide patients and clinicians to high quality MHA. Contributing to this challenge, the present study investigates the content, quality, and privacy features of pain apps available in the European app stores. Methods An automated search engine was used to identify pain apps in the European Google Play and Apple App store. Pain apps were screened and checked for systematic criteria (pain-relatedness, functionality, availability, independent usability, English or German). Content, quality and privacy features were assessed by two independent reviewers using the German Mobile Application Rating Scale (MARS-G). The MARS-G assesses quality on four objectives (engagement, functionality, aesthetics, information quality) and two subjective scales (perceived impact, subjective quality). Results Out of 1034 identified pain apps 218 were included. Pain apps covered eight different pain types. Content included basic information, advice, assessment and tracking, and stand-alone interventions. The overall quality of the pain apps was average M = 3.13 (SD = 0.56, min = 1, max = 4.69). The effectiveness of less than 1% of the included pain apps was evaluated in a randomized controlled trial. Major problems with data privacy were present: 59% provided no imprint, 70% had no visible privacy policy. Conclusion A multitude of pain apps is available. Most MHA lack scientific evaluation and have serious privacy issues, posing a potential threat to users. Further research on evidence and improvements privacy and security are needed. Overall, the potential of pain apps is not exploited., Highlights • A multitude of mobile health apps for pain is available in the app stores. • Less than 1% of the available apps have been evaluated in an RCT. • Major issues with data privacy are present. • Overall quality of engagement, functionality aesthetics and content is moderate. • The potential of apps for pain is not exploited.

In response to the outbreak of COVID-19 the national landscape of higher education changed quickly and dramatically to move “online” in the Spring semester of 2020 While distressing to both faculty and students, it presents a unique opportunity to explore how students responded to this unexpected and challenging learning situation In four undergraduate STEM courses that incorporated course-based undergraduate research experiences (CUREs)—which are often focused on discovery learning and laboratory research—we had an existing study in progress to track students' interest development at five time points over the Spring 2020 semester Via this ongoing study we were able to investigate how students stay engaged in their college science courses when facing unexpected challenges and obstacles to their learning Longitudinal survey data from 41 students in these CURE courses demonstrated that students' situational interest dropped significantly when their CURE courses unexpectedly shifted from hands-on, discovery-based, and laboratory-based instruction to online instruction Although we observed a dramatic decline in student interest in general after the CURE courses moved fully online, the decline rates varied across students Students who were able to make meaningful connections between the learning activities and their personal or career goals were more likely to maintain a higher level of interest in the course Implications for practice are discussed © Copyright © 2020 Wang, Bauer, Burmeister, Hanauer and Graham

Trk receptors and gene fusions of NTRK are targets in precision oncology. Classical Trk signalling concepts fail to explain ligand-independent signalling of intracellular TrkB or NTRK fusion proteins. Here, we show that abundance of the intracellular domain of TrkB is sufficient for ligand-independent autophosphorylation. This constitutive TrkB signalling reduced actin filopodia dynamics, could phosphorylate FAK, and changed cell morphology. Mutating Y705 in the kinase domain of TrkB alone specifically blocked these pathways. Engineered intracellular kinase domain proteins and a cancer-related intracellular NTRK2-fusion protein (SQSTM1-NTRK2) also underwent constitutive activation. In migrating glioblastoma-like U87MG cells, self-active TrkB kinase reduced cell migration. Moreover, we found evidences for constitutively active, intracellular TrkB in tissue of human grade IV glioblastoma. Structural modelling of the kinase domain let us postulate that ‘release from cis-autoinhibition by abundance’ is sufficient for TrkB/FAK/Actin signalling via Y705. These constitutive signalling pathways could be fully blocked within minutes by clinically approved, anti-tumorigenic Trk inhibitors. In conclusion, our data provide an explanation and biological function for TrkB kinase domain signalling in the absence of a ligand.

The post mortem evaluation of a brain edema is routinely performed by pathologists based on the macroscopic signs during autopsy. This method represents the current gold standard, but is subjective and observer dependent. Therefore, three post mortem evaluation methods of brain samples were analyzed in this work: histology, wet-dry weight and normalized cerebral weight, which was described in 2020 by Bauer et al. Tissue samples from six different regions of 34 brains were collected and examined both by rating of histological slides and by measuring the water content by using a drying oven. The rating of the histological slides, stained with hematoxylin and eosin, was performed by two pathologists independently. For the water content, the wet weight and the dry weight of each sample were set in relation. The normalized cerebral weight was calculated by dividing the brain weight by the brain volume, which were both determined during autopsy and in computed tomography images, respectively. A fair to moderate interrater agreement was obtained for the histologic evaluation and a significant correlation was present between one rater and the wet-dry weight and the normalized cerebral weight method. When classifying according to the gold standard, a significant difference was detected between the edematous and nonedematous cases by using the wet-dry weight method in the cerebral cortex and by using the normalized cerebral weight method. However, the significant correlations and group differences were limited to the aforementioned results. In conclusion, both the histological and the wet-dry weight method show limited benefits for the classification of brain edema and the histology analysis is highly observer dependent. The normalized cerebral weight method, however, reveals a significant effect between the edematous and nonedematous cases when classifying according to the gold standard. Therefore, we suggest to apply this method for the assessment of brain edema since it is objective and rater independent. Nevertheless, the exact evaluation of brain edema remains a challenging task, especially due to the continuous transition between no edema and edema.

This convergent mixed methods study was designed to examine the skills and attitudes toward using an iPad to deliver nursing curriculum and enhance active learning strategies for sophomore Bachelor of Science in Nursing (BSN) and Doctor of Nursing Practice (DNP) students at a Midwestern university. Quantitative data were collected using an investigator-developed survey to identify student perceived iPad skill levels and attitudes towards the iPad before, during, and after the first year of the implementation of a one-to-one iPad requirement (i.e., the iPad Initiative). Focus groups were used to collect qualitative data to identify factors that contribute to students’ attitude and skill levels. Initial data were collected from participants during the iPad orientations in August of 2013 (sophomore BSN n = 158; DNP n = 29). Follow-up sessions occurred at the end of fall semester 2013 (survey only) and spring semester (survey and focus groups) 2014. Qualitative and quantitative data were rigorously analyzed. Findings of the study (meta-inference) was informed by all data sets from all participant groups. Significant improvement was seen in quantitative data with students’ perception of their technology proficiency. However, students reported significantly less use of the iPad than they had predicted in the fall. Analysis of qualitative data resulted in a variety of themes that were grouped by three predominant categories: drivers, moderators and speed bumps. Each category demonstrated theme that acted to improve the student experience (drivers), moderate the student experience (moderators) or detract from the student experience (speed bumps). The implication of the study elucidated challenges inherent in being early adopters of technology in education.

Adoption of Materials Science and Engineering (MSE) into the pre-college classroom is an ideal strategy for addressing Next Generation Science Standards (NGSS), specifically the Science and Engineering Practices. MSE offers core science and engineering topics that can be incorporated into existing Science, Technology, Engineering, and Mathematic (STEM) curricula through teaching modules. Using MSE as a teaching vehicle, the Center for Research on Interface Structures and Phenomena (CRISP) conducted a series of small-scale studies of its teacher professional development workshops and a student summer program, along with related teaching modules, in an effort to measure the contribution MSE has on students and K-12 STEM educators. Based on participant survey feedback, CRISP found improvement in students’ MSE knowledge, interests, and career goals. For teachers, in addition to improving their MSE knowledge, they also increased their comfort and confidence in teaching MSE concepts in their classroom. These results provide evidence for the use of MSE modules as productive teaching tools for NGSS Science and Engineering Practices, as well as producing workforce-competitive STEM students.

// Martina Kluth 1, * , David Meyer 1, * , Antje Krohn 1 , Fabian Freudenthaler 1 , Melanie Bauer 1 , Georg Salomon 2 , Hans Heinzer 2 , Uwe Michl 2 , Stefan Steurer 1 , Ronald Simon 1 , Guido Sauter 1 , Thorsten Schlomm 2, 3 , Sarah Minner 1 1 Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 2 Prostate Cancer Center, Martini-Clinic, Hamburg, Germany 3 Department of Urology, Section for Translational Prostate Cancer Research at University Medical Center Hamburg-Eppendorf, Hamburg, Germany * These authors contributed equally to this work Correspondence to: Ronald Simon, e-mail: r.simon@uke.de Keywords: 6q deletion, prostate cancer, ERG, MAP3K7, heterogeneity Received: August 27, 2015 Accepted: November 22, 2015 Published: December 14, 2015 ABSTRACT Prostate cancer is notorious for its heterogeneity, which poses a problem for the applicability of diagnostic molecular markers. However, heterogeneity analysis can provide valuable information on the chronology in which molecular alterations arise. Here, we constructed a heterogeneity tissue microarray (TMA) comprising samples from 10 different tumor areas of 189 prostate cancers each in order to study the sequence of two frequent molecular alterations, i.e. 6q15 deletion and TMPRSS2:ERG fusion. Previous work shows a marked inverse relationship between these alterations, suggesting that presence of one of these alterations might impact development of the other. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG-expression by immunohistochemistry. Only 6.6% of 334 ERG-positive but 28.4% of 440 ERG-negative TMA spots showed 6q15 deletions ( p < 0.0001). A breakdown of these data to the level of tumor foci revealed 6q deletions in 138 tumor foci that were large enough to have at least 3 analyzable TMA spots. These included 42 tumor foci with homogeneous ERG positivity and 16 with homogeneous 6q15 deletions. Remarkably, six of the 42 homogeneously ERG -positive tumor foci (14.3%) harbored small 6q15-deleted areas, but none of the 34 6q15-deleted foci showed areas of ERG positivity ( p = 0.022). In conclusion, our data suggest that ERG -fusion can precede 6q15 deletion, but not vice versa. The complete absence of ERG-positive tumor areas in 6q15-deleted tumor foci further suggest that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions.

Visual representations, such as pathway models, are increasingly being used to both communicate higher education science, technology, engineering, and mathematics (STEM) education program evaluation plans as well as accurately represent complex programs and the systems within which the educational programs reside. However, these representations can be overwhelming to audiences that are not familiar with the program’s structure or engaged in the evaluation process. The goal of this methods essay is to help both evaluators and discipline-based education researchers improve communication about program evaluation with a variety of stakeholders. We propose a three-stage method for developing progressively less complex visualizations to build affordances that help make the program evaluation process and statements of program impact more meaningful to a wider range of audiences. The creation of less complex visualizations can facilitate understanding by allowing a stakeholder to more easily “see” the structure of the program and thereby may evoke a greater willingness to take action and make meaningful programmatic changes based on strategic evaluation planning. To aid readers, we describe how we modified the Systems Evaluation Protocol (SEP) to develop simplified visualizations when evaluating a long-standing college science faculty development program, the Summer Institutes on Scientific Teaching.

While cerebral edema is a live-threatening condition in living persons, also an edema-like fluid redistribution can occur post mortem. In deceased, usually macroscopic signs are evaluated during autopsy in order to determine the presence or absence of cerebral edema. As a quantitative and objective classification is beneficial, an already existing method (Radojevic et al., 2017), which is based on a mathematical formula using the intracranial dimensions and the cerebral weight, was compared to the evaluation of macroscopic signs in 31 cases. The results showed an excellent agreement for the comparison between the raters as well as the measurement methods (at opened skull or in CT images). However, both measurement methods only poorly agree with the macroscopic edema evaluation. In order to find a more concordant method, the normalized cerebral weight, which puts the cerebral weight in relation to the intracranial volume, was calculated for 115 cases. This method resulted in an excellent agreement with the macroscopic rating and showed a clear numerical difference between the edematous and nonedematous group. While the influence of the post mortem time and the cooling time was found to be negligible, the age at death might confound the edema classification due to pre-existing cerebral atrophy leading to lower cerebral weights. In summary, the present study compared different assessment methods to classify cerebral edema and developed a rater independent, objective and quantitative classification method, which was as reliable as the rating of the forensic pathologists.

TMPRSS2:ERG fusions, in combination with deletion of the phosphatase and tensin homolog (PTEN) tumor suppressor, have been suggested to cooperatively drive tumor progression in prostate cancer. We utilized a novel heterogeneity tissue microarray containing samples from 10 different tumor blocks of 189 prostatectomy specimens to study heterogeneity of genomic PTEN alterations in individual foci. PTEN alterations were found in 48/123 (39%) analyzable individual tumor foci, including 40 foci with deletions, 7 with deletion and rearrangement, and 1 focus with rearrangement only. PTEN was homogeneously aberrant in only 4 (8%) and heterogeneously in 44 (92%) of the foci. We found a specific sequence of molecular events from PTEN breakage followed by deletion of DNA sequences flanking the breakpoint, resulting in homozygous deletion. The observation that 16 of 19 foci with homogeneous ERG positivity had focal PTEN alterations but none of 10 foci with PTEN alterations had focal ERG positivity (P

Approximately 50% of prostate cancers are characterized by TMPRSS2 (transmembrane protease serine 2)-ERG (avian v-ets erythroblastosis virus E26 oncogene homolog) gene fusions resulting in an androgen-regulated overexpression of the transcription factor ERG. Some studies have suggested prognostic or predictive relevance of ERG status in prostate cancer. Such concepts could be impaired by extensive ERG heterogeneity in analyzed tumors. The aim of this study was to analyze the extent of heterogeneity for TMPRSS2-ERG fusion in prostate cancer. To enable large-scale studies on the extent of heterogeneity of biomarkers in prostate cancer, a heterogeneity tissue microarray containing samples from 10 different tumor blocks of 190 large prostate cancers selected from a consecutive series of 480 radical prostatectomies was developed. ERG expression was analyzed by immunohistochemistry. Positive ERG immunostaining was found in arrayed cancer-containing samples from 103 of the 178 analyzable patients (58%). ERG immunostaining was homogeneously positive in 29 prostate cancers (16%), whereas heterogeneous ERG positivity was seen in 74 cancers (42%). ERG heterogeneity was within one tumor focus (intrafocal heterogeneity) in 69 cases (93% of heterogeneous cases) and between different tumor foci (interfocal heterogeneity) in 5 cases (7%). Marked intrafocal heterogeneity challenges the concept of TMPRSS2-ERG fusion always representing an early step in prostate cancer development. Marked heterogeneity also compromises the concept of analyzing ERG status for treatment decisions in diagnostic needle core biopsies.

Quantitative estimates of the hydrologic effects of climate change are essential for understanding and solving potential transboundary water conflicts in the Zerafshan river basin, Central Asia.This paper introduces an identification of runoff generation processes and a detection of changes in hydrological regimes supporting Mann–Kendall trend analysis for streamflows.By this, the effective available and future water resources are identified for the Zerafshan.The results for the subbasins in the upper Zerafshan and for the reference station at the upper catchment outlet indicate that glacier melt is the most significant component of river runoff. The Mann–Kendall trend analysis confirms the regime analysis with the shift in the seasonality of the discharge. Furthermore, the results of the Kendall–Theil Robust Line for predicted long-term discharge trends show a decreasing annual discharge.The experience gained during this study emphasizes the fact that the summer flood, urgently required for the large irrigation projects downstream in Uzbekistan, is reduced and more water will be available in spring. Additionally, following the estimation of future discharges in 50 and 100 years the hydrological changes are affecting the seasonal water availability for irrigation. This analysis highlighted that water availability is decreasing and the timing of availability is changing. Hence, there will be more competition between upstream Tajikistan and downstream Uzbekistan. Planned projects within the basin might have to be reconsidered and the changed scenario of water availability needs to be properly taken into account for long-term basin scale water management.

The Vakhsh and Pyandj rivers, main tributaries of the Amu Darya River in the mountainous region of the Pamir Alay, play an important role in the water resources of the Aral Sea basin (Central Asia). In this region, the glaciers and snow cover significantly influence the water cycle and flow regime, which could be strongly modified by climate change. The present study, part of a project funded by the European Commission, analyses the hydrological situation in six benchmark basins covering areas of between 1800 and 8400km(2), essentially located in Tajikistan, with a variety of topographical situations, precipitation amounts and glacierized areas. Four types of parameter are discussed: temperature, glaciation, snow cover and river flows. The study is based mainly on a long-time series that ended in the 1990s (with the collapse of the Soviet Union) and on field observations and data collection. In addition, a short, more recent period (May 2000 to May 2002) was examined to better understand the role of snow cover, using scarce monitored data and satellite information. The results confirm the overall homogeneous trend of temperature increase in the mountain range and its impacts on the surface water regime. Concerning the snow cover, significant differences are noted in the location, elevation, orientation and morphology of snow cover in the respective basins. The changes in the river flow regime are regulated by the combination of the snow cover dynamics and the increasing trend of the air temperature.

In the often discussed Aral Sea basin (Central Asia), water availability depends essentially on the high mountains located in its eastern part, especially from the Pamir Alay Range where the Vakhsh and Pyandj Rivers, the main tributaries of the Amu Darya River, flow. In this region, the cryosphere, glaciers, and snow cover significantly impact the water cycle and the flow regime, which could be deeply modified by climate change. The present study, part of a project funded by the EU FP6, analyzes the hydrological situation in six benchmark basins covering areas between 1800 and 8400 km2, essentially located in Tajikistan, with a variety of topographical situations, precipitation amounts, and glacierized areas. Four types of parameter are discussed: temperature, glaciers, snow cover, and river flows. Two time periods are considered: (i) a long time series ending in the 1990s with the collapse of the Soviet Union and based on field observations and data collection; (ii) a May 2000 to May 2002 interval, using scarce monitored data and satellite information to follow snow cover dynamics. The results confirm the global homogeneous trend of temperature increase in the mountain range and its impacts on the surface water regimes. Concerning the snow cover, significant differences are noted regarding the location, the elevation, the orientation and the morphology of the respective basins. Finally the expected changes in the flow river regime are regulated by the combination of the snow cover dynamics and the increasing trend of the air temperature. It confirms the high sensitivity of this region to the warming as identified by the 4rd IPCC Assessment Report.

This book (the research outcome of the EU-INCO FP6 research project Jayhun: Interstate Water Resource Risk Management: Towards a Sustainable Future for the AralBasin ) focuses on and discusses the results of research done on the risk assessment levels associated with relevant regional variables in the Aral Basin and develops a strategy for an improved management of the region's water resources. The book provides current and reliable information on the rate of glacial retreat in Central Asian and the implications for future water resources in the region. The impact of global changes on annual precipitation is assessed. The rates of reservoir siltation are established by hydrographic surveys, and analyses of wastage and effectiveness of water usage in the large irrigation massifs are conducted. Water resources models are used to analyse existing and newly generated data. These are calibrated with existing data and subsequently used for simulating various possible future scenarios. The book thereby provides a risk analysis for water resources management in the Aral Basin and identifies sustainable options for improved management of the region's water resources. This title belongs to European Water Research Series . ISBN: 9781843393085 (Print) ISBN: 9781780401423 (eBook)

This paper introduces the conjunctive use of a deterministic water quality model and water balance criteria for supporting the assessment of simulation and to evaluate the effectiveness of proposed operation strategies. By this, the applicability of enhanced reservoir operation strategies addressing both water quality as well as water quantity aspects under water deficit conditions in dry years can be shown. Arguments will be developed to address stakeholders and decision makers in the context of a more conservative past operation regime. Results are presented for the Kaparas reservoir, which is located in the lower Amu Darya River, on the border of Turkmenistan and Uzbekistan. As being one out of four large reservoirs of the Tuyamuyun Hydro Complex (THC), the Kaparas reservoir could be increasingly used for drinking water supply for the lower Amu Darya region. The results for the dry year 2001 indicates that the combination of simulation together with practical assessment criteria confirm the applicability of adapted operation rules for THC reservoirs and ways can be found to supply the local population (of the lower Amu Darya region) with more potable water of higher quality even subject to a parallel reduction of water deficits. Future aggravation of water stress due to increasing population growth and water quality deterioration will require a more comprehensive consideration of water quality aspects in many arid and semi arid regions. The experience gained during this study emphasizes the fact that classical deterministic water quality models provide effective tools to address even more complex water quality problems under water stressed conditions, provided processing of results is performed, to support the decision making process.

BackgroundIn the Aral Sea basin, safe water resources are scarce and steadily becoming scarcer. Particularly high quality water is going to become a rare good.The object of the study was the Tuyamuyun Hydroengineering Complex (THC), a complex of artificial water reservoirs located in the lower Amu Darya River, which provides water for irrigation, industry, and drinking for the lower Amu Darya region. The focus was on operation of one of its four reservoirs, the Kaparas, which is mainly used for drinking water supply. The objective includes the investigation of impacts of conventional operation schemes on the reservoir water quality for improving drinking water quality (salinity). Basic operation rules for Kaparas, which can be considered as representative for conventional dam operation under dry year conditions, had to be identified and improved operation schemes derived.MethodsExisting data archives were analysed, and further data were acquired from field surveys, data processing and modelling studies. Historical data were identified, which are appropriate to determine representative schemes for the conventional operation. For the simulation of time-dependent and depth-dependent changes of reservoir salinisation, the reservoir water quality model Lac was used and linked with the THC model.Results and DiscussionModelling results for the simulation of temperature dynamics and density stratification showed a sufficient congruence with the measured temperature profiles. The conformity of measured and calculated salt concentration is basically ensured. The reservoir, which fill with higher saline water at the end of the summer, aggravates the entrainment of high saline water in the entire water column.ConclusionsThe current conventional operation regime mainly leads to filling the Kaparas reservoir with high saline water during the winter months. Even in the event of starting with comparable low salinity levels, the simulation demonstrates the rapid deterioration of the reservoir water quality. Under dry year conditions, the WHO standards for drinking water will be exceeded by 30% after two years, so that the impact of dry years in the context of water stress becomes visible.Recommendations and OutlookProcessed data and results are now available to identify enhanced reservoir operation strategies for salinity reduction by changing the period of reservoir filling and release, as well as to initiate a detailed analysis of how water deficits in dry years may be reduced by improved operation regimes. Using adapted and enhanced operation rules for THC reservoirs, the local population within the lower Aral Sea basin might be supplied with more potable water of higher quality in future.

Deletions at chromosome 6q15 belong one to the most frequent alterations in pros-tate cancer, and are linked to poor prognosis. Furthermore, there is a marked inverse relationship between 6q15 deletions and TMPRSS2:ERG fusions in prostate cancer. While heterogeneity may limit the applicability of diagnostic molecular markers, it is important to estimate in vivo heterogeneity and the sequel of appearance of potential prognostic markers. In case of one alteration developing after the other, we would expect a small area of cancer having both alterations within a larger area having only one (the first appearing) of these changes. In this study, we used our heterogeneity tissue microarray approach as a surrogate method to determine in vivo heterogeneity of 6q15 deletions and TMPRSS2:ERG fusions. We constructed a heterogeneity TMA containing samples taken from 10 dif-ferent tumor containing tissue blocks of 189 prostate cancers. Each prostate con-tained 1 to 6 individual cancer foci allowing the molecular analysis of more than 350 tumor foci. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG expression by immunohistochemistry. Only 6.6% of 334 ERG positive but 28.4% of 440 ERG negative TMA spots showed 6q15 deletions (p In conclusion of our study, the complete absence of ERG positive tumor foci in 6q15-deleted cancers suggests that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions. However, the development of 6q15 deletions is independent of the ERG status. Citation Format: Martina Kluth, Maria Christina Tsourlakis, David Meyer, Antje Krohn, Fabian Freudenthaler, Melanie Bauer, Georg Salomon, Hans Heinzer, Uwe Michl, Stefan Steurer, Ronald Simon, Guido Sauter, Thorsten Schlomm, Sarah Jane Pauline Minner. 6q15 deletion impede development of ERG fusion in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2216. doi:10.1158/1538-7445.AM2014-2216