Mendelssohn and The Schübler Chorales (BWV 645-650):A New Source found in the Riemenschneider Bach Institute Collection

This article discusses a hitherto-unknown printed edition of Bach's Schübler Chorales edited by Mendelssohn, and considers its meaning and significance for Bach-Mendelssohn scholarship. Facsimile of the edition is also included.

Validation of Next Generation Sequencing Technologies in Comparison to Current Diagnostic Gold Standards for BRAF, EGFR and KRAS Mutational Analysis

Next Generation Sequencing (NGS) has the potential of becoming an important tool in clinical diagnosis and therapeutic decision-making in oncology owing to its enhanced sensitivity in DNA mutation detection, fast-turnaround of samples in comparison to current gold standard methods and the potential to sequence a large number of cancer-driving genes at the one time. We aim to test the diagnostic accuracy of current NGS technology in the analysis of mutations that represent current standard-of-care, and its reliability to generate concomitant information on other key genes in human oncogenesis. Thirteen clinical samples (8 lung adenocarcinomas, 3 colon carcinomas and 2 malignant melanomas) already genotyped for EGFR, KRAS and BRAF mutations by current standard-of-care methods (Sanger Sequencing and q-PCR), were analysed for detection of mutations in the same three genes using two NGS platforms and an additional 43 genes with one of these platforms. The results were analysed using closed platform-specific proprietary bioinformatics software as well as open third party applications. Our results indicate that the existing format of the NGS technology performed well in detecting the clinically relevant mutations stated above but may not be reliable for a broader unsupervised analysis of the wider genome in its current design. Our study represents a diagnostically lead validation of the major strengths and weaknesses of this technology before consideration for diagnostic use.

Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia

FLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD mutations. PRL-3 expression is upregulated by the FLT3-STAT5 signalling pathway in leukaemia cells, leading an activation of AP-1 transcription factors via ERK and JNK pathways. PRL-3-depleted AML cells showed a significant decrease in cell growth. Clinically, high PRL-3 mRNA expression was associated with FLT3-ITD mutations in four independent AML datasets with 1158 patients. Multivariable Cox-regression analysis on our Cohort 1 with 221 patients identified PRL-3 as a novel prognostic marker independent of other clinical parameters. Kaplan-Meier analysis showed high PRL-3 mRNA expression was significantly associated with poorer survival among 491 patients with normal karyotype. Targeting PRL-3 reversed the oncogenic effects in FLT3-ITD AML models in vitro and in vivo. Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients.

Being observant and observed: embodied citizenship training in the Home Guard and the Boy Scout Movement, 1907-1945

Building upon recent studies by geographers and social scientists on the everyday practices of (scientific) observation, this paper focuses on the role of two distinct, yet similar organisations that held observation as an essential and 'automatic' embodied skill. Utilising the examples of Home Guard camouflage and the Boy Scout Movement, the paper critically examines how these organisations sought to articulate the individual as both observer and observed, thereby exposing a much more complex entanglement of different visual positions and practices hitherto neglected in studies of observation. Moreover, the paper emphasises the importance of the act of 'not-being-seen' as a complementary and fundamental aspect of (non-)observational practice, accentuated and promoted by civic institutions in terms of duty and responsibility. Finally, the paper considers the evolutionary aspects of observation through the lifecourse, revealing a complex, relational geography of expertise, experience and skill that crossed age-distinctions. © 2012 Elsevier Ltd.

The health status and health service needs of primary caregivers of cancer survivors: a mixed methods approach

This study aimed to measure the health status and care needs of people who provide informal care to cancer survivors in the UK. Semi-structured interviews were conducted with a purposive sample of 24 cancer professionals to identify the care needs of caregivers. In addition, we conducted a postal survey measuring the health and wellbeing (SF-36) and health service utilisation of 98 primary caregivers of a random sample of cancer survivors, 2-20 years post-treatment. Interviews indicated that caregivers’ needs were largely unmet. In particular, there appeared to be a need in relation to statutory health care provision, information, psychological support and involvement in decision making. There were no significant differences between survivors and caregivers in terms of mental health scores; and caregivers performed better on physical health domains compared to cancer survivors. Compared to UK norms and norms for caregivers of other chronic conditions, cancer caregivers had substantially lower scores on each SF-36 health domain. Cancer may impact negatively on an informal caregiver’s health long after treatment has ended. Providing appropriate and cancer specific information may alleviate difficulties and improve health and wellbeing. Specific concentration should be given to the development and delivery of information support for caregivers of post-treatment cancer survivors.

Identification of Gene Expression-Based Prognostic Markers in the Hematopoietic Stem Cells of Patients With Myelodysplastic Syndromes

The diagnosis of patients with myelodysplastic syndromes (MDS) is largely dependent on morphologic examination of bone marrow aspirates. Several criteria that form the basis of the classifications and scoring systems most commonly used in clinical practice are affected by operator-dependent variation. To identify standardized molecular markers that would allow prediction of prognosis, we have used gene expression profiling (GEP) data on CD34+ cells from patients with MDS to determine the relationship between gene expression levels and prognosis.

Cheetahs, Acinonyx jubatus, balance turn capacity with pace when chasing prey

Predator–prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s-1 and accelerated up to 7.5 m s-2 with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5–8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival.

Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1

Regulation of ABCB1 (P-glycoprotein/Pgp) in AML was investigated. In a historical cohort with Pgp and transcriptional regulator expression profiling data available (n=141), FOXO1 correlated with Pgp protein expression. This was confirmed in an independent cohort (n=204). Down-regulation (siRNA) or hyperactivation (nicotinamide) of FOXO1 led to corresponding changes in Pgp. Low FOXO1 expression correlated with FLT3-ITDs (p

A comparative study of biopolymers and alum in the separation and recovery of pulp fibres from paper mill effluent by flocculation

Recovery of cellulose fibres from paper mill effluent has been studied using common polysaccharides or biopolymers such as Guar gum, Xanthan gum and Locust bean gum as flocculent. Guar gum is commonly used in sizing paper and routinely used in paper making. The results have been compared with the performance of alum, which is a common coagulant and a key ingredient of the paper industry. Guar gum recovered about 3.86 mg/L of fibre and was most effective among the biopolymers. Settling velocity distribution curves demonstrated that Guar gum was able to settle the fibres faster than the other biopolymers; however, alum displayed the highest particle removal rate than all the biopolymers at any of the settling velocities. Alum, Guar gum, Xanthan gum and Locust bean gum removed 97.46%, 94.68%, 92.39% and 92.46% turbidity of raw effluent at a settling velocity of 0.5 cm/min, respectively. The conditions for obtaining the lowest sludge volume index such as pH, dose and mixing speed were optimised for guar gum which was the most effective among the biopolymers. Response surface methodology was used to design all experiments, and an optimum operational setting was proposed. The test results indicate similar performance of alum and Guar gum in terms of floc settling velocities and sludge volume index. Since Guar gum is a plant derived natural substance, it is environmentally benign and offers a green treatment option to the paper mills for pulp recycling.

Web Psychosocial Surveys in Cancer Survivorship— A Methodological Note

The number of Internet surveys is increasing, and there is a need to examine critically their value in psychosocial cancer care research. This study explored the use of an online method of recruiting and surveying people affected by cancer. An online survey was designed to measure the health status and service needs of adult cancer survivors and caregivers. The online survey received 491 page visits; only 5% of visitors (13 survivors and 14 cancer caregivers) completed the online questionnaire. The average age of survivors and caregivers was 43 and 42 years, respectively. The majority of survivor and caregiver online respondents were female (23/27, 85%) and had been affected by cancer between 1 and 3 years previously (16/27, 59%). Our online research did not appear to be an effective method for recruiting and surveying the psychosocial health of cancer survivors. This study identified potential pitfalls and obstacles of online cancer care surveys particularly in relation to the age of cancer survivors, access to the Internet and the need to ensure surveys are easily and immediately accessible. Future Internet surveys should pay particular attention to the need to advertise and improve survey access via targeted and tailored techniques.