Bystander Narratives: The Fiction of J.M. Coetzee and the Holocaust

J.M. Coetzee’s novels are suffused with a pervasive, though often oblique, Holocaust awareness. Direct references to the event and to the historical era to which it belongs, subtle stylistic and thematic echoes of Holocaust writing, and the recurrent mobilization of Holocaust imagery in Coetzee’s novels all contribute to suggest the significance of the event to the author’s work and thought. Providing Coetzee with a lens through which to view the contemporary situation, both local and global, the Holocaust offers Coetzee a means by which difficult and complex questions of ethics and historiographical truth may be approached. Above all, the Holocaust and its representation contribute to Coetzee’s exploration of the dilemmas of translating the traumatic lived experience of atrocity – including, but not limited to, life in apartheid South Africa – into narrative form. Taken as a whole, Coetzee’s oeuvre initially anticipates and later responds to, in characteristically oblique fashion, the narrative project(s) facing post-apartheid South Africa as the newly-democratic nation sought to make sense of its past through a variety of means, the most important of which was the country’s Truth and Reconciliation Commission. Implicitly challenging the TRC’s findings as well as its narrative assumptions, the Coetzean oeuvre accordingly invites being read as offering a continuous and evolving counter-narrative to the TRC and its construction of a narrative of the apartheid past for the post-apartheid nation. In utilizing the Holocaust, its representations, and the reception thereof to frame his response to apartheid, Coetzee implicates both in a critique of the Western model of modernity, suggesting, in the process, the importance of reconfiguring modernity in a more ethical shape.

Cyclooxygenase-2 expression correlates with phaeochromocytoma malignancy.

Abstract Aims: Phaeochromocytomas are rare but potentially life-threatening neuroendocrine tumours of the adrenal medulla or sympathetic nervous system ganglia. There are no histological features which reliably differentiate benign from malignant phaeochromocytomas. The current study evaluated cyclooxygenase-2 (Cox-2) and Bcl-2 as tissue-based biomarkers of phaeochromocytoma prognosis. Methods and Results: Cox-2 and Bcl-2 expression were examined immunohistochemically in tissue from forty-one sporadic phaeochromocytoma patients followed up for a minimum of five years after diagnosis. There was a statistically significant association between Cox-2 histoscore (intensity x porportion) and the development of tumour recurrence or metastases (p=0.006). A significant relationship between the co-expression of Cox-2 and Bcl-2 in the primary tumour and the presence of recurrent disease was observed (p=0.034). A highly significant association was observed between, (i) the tumour-associated expression of these two oncoproteins (p=0.001) and, (ii) Cox-2 histoscore and the presence of Bcl-2 expression (p=0.002). Cox regression analysis demonstrated no significant relationship between, (i) the presence or absence of either Cox-2 or Bcl-2 and patient survival or, (ii) between Cox-2 histoscore and patient survival. Conclusions: These results suggest that Cox-2 and Bcl-2 may promote phaeochromocytoma malignancy and that these oncoproteins may be valuable surrogate markers of an aggressive tumour phenotype.

The pathogenesis of venous thromboembolism in cancer: emerging links with tumour biology.

Venous thromboembolism (VTE) is a frequent complication in individuals with cancer and is considered to be a cause of substantial mortality. Epidemiological studies identify malignancy as an independent VTE risk factor and show that cancer patients are at increased risk of both initial and recurrent VTE events. The risk due to cancer is compounded by the effects of chemotherapy and other treatments. The pathogenesis of cancer-associated VTE is complex involving multiple interactions between tumours and various components of haemostasis. The development of a systemic hypercoagulable state is considered a key pathogenetic feature and is attributed to tumour expression of tissue factor and other procoagulants, activation of vascular cells by tumour-derived cytokines and adhesive interactions between tumour cells and host cells. An increasing body of evidence indicates that the activation of haemostasis in malignant disease contributes to tumour growth and progression by stimulation of intracellular signalling pathways. The interaction of tissue factor, thrombin and other coagulation factors with protease activated receptor (PAR) proteins expressed by tumour cells and host vascular cells leads to the induction of genes related to the processes of angiogenesis, cell survival and cell adhesion and migration.

Incorporation of chitosan in acrylic bone cement: Effect on antibiotic release, bacterial biofilm formation and mechanical properties

Bacterial infection remains a significant problem following total joint replacement. Efforts to prevent recurrent implant infection, including the use of antibiotic-loaded bone cement for implant fixation at the time of revision surgery, are not always successful. In this in vitro study, we investigated whether the addition of chitosan to gentamicin-loaded Palacos® R bone cement increased antibiotic release and prevented bacterial adherence and biofilm formation by Staphylococcus spp. clinical isolates. Furthermore, mechanical tests were performed as a function of time post-polymerisation in pseudo-physiological conditions. The addition of chitosan to gentamicin-loaded Palacos® R bone cement significantly decreased gentamicin release and did not increase the efficacy of the bone cement at preventing bacterial colonisation and biofilm formation. Moreover, the mechanical performance of cement containing chitosan was significantly reduced after 28 days of saline degradation with the compressive and bending strengths not in compliance with the minimum requirements as stipulated by the ISO standard for PMMA bone cement. Therefore, incorporating chitosan into gentamicin-loaded Palacos® R bone cement for use in revision surgery has no clinical antimicrobial benefit and the detrimental effect on mechanical properties could adversely affect the longevity of the prosthetic joint.

In vitro study of the efficacy of acrylic bone cement loaded with supplementary amounts of gentamicin: Effect on mechanical properties, antibiotic release, and biofilm formation

Background: Infection remains a severe complication following a total hip replacement. If infection is suspected when revision surgery is being performed, additional gentamicin is often added to the cement on an ad hoc basis in an attempt to reduce the risk of recurrent infection.

Methods and results: In this in vitro study, we determined the effect of incorporating additional gentamicin on the mechanical properties of cement. We also determined the degree of gentamicin release from cement, and also the extent to which biofilms of clinical Staphylococcus spp. isolates form on cement in vitro. When gentamicin was added to unloaded cement (1–4 g), there was a significant reduction in the mechanical performance of the loaded cements compared to unloaded cement. A significant increase in gentamicin release from the cement over 72 h was apparent, with the amount of gentamicin released increasing significantly with each additional 1 g of gentamicin added. When overt infection was modeled, the incorporation of additional gentamicin did result in an initial reduction in bacterial colonization, but this beneficial effect was no longer apparent by 72 h, with the clinical strains forming biofilms on the cements despite the release of high levels of gentamicin.

Interpretation: Our findings indicate that the addition of large amounts of gentamicin to cement is unlikely to eradicate bacteria present as a result of an overt infection of an existing implant, and could result in failure of the prosthetic joint because of a reduction in mechanical performance of the bone cement.

Limpet grazing and loss of Ascophyllum nodosum canopies on decadal time scales

The role of limpet grazing in preventing the development of algal canopies is a recurrent theme in intertidal ecology. Less is known about interactions of limpets with the long-term dynamics of established canopies. Aerial photographs indicate that intertidal canopy cover has declined over the past 44 yr in Strangford Lough, Northern Ireland. There has been a loss of the previously continuous cover of Ascophyllum nodosum (L.) Le Jolis in the mid-shore. A barnacles dominated assemblage now fills gaps in the A. nodosum canopy. The rates at which barnacle patches become established and grow have increased since 1990. Changes in canopy cover have been accompanied by increases in limpet densities since the 1980s. Measurements between 2003 and 2004 showed no increase in length of A. nodosum fronds when limpets Patella vulgata had access to the algal holdfasts. In contrast, when limpets were experimentally excluded from the holdfasts, there was net frond growth. In the Isle of Man, which is climatically similar to Strangford Lough but has fewer limpets, growth occurred regardless of limpet grazing. The breaking force for A. nodosum declined with increasing local densities of limpets. A. nodosum is a sheltered shore species, potentially vulnerable to changes in wave exposure. There is no evidence, however, that Strangford Lough has become windier over the past 3 decades. Variation in wave exposure among locations within the lough was not related to rates of barnacle patch creation or expansion, Limpet population density has increased following a series of mild winters. Climate change may have a role in causing canopy loss, not by direct effects on the limpet populations.

Abnormal Functional Connectivity of Hippocampus During Episodic Memory Retrieval Processing Network in Amnestic Mild Cognitive Impairment.

BACKGROUND: Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. METHODS: Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. RESULTS: Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. CONCLUSIONS: aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.

Reflexiones y representaciones del exilio: de El canto del peregrino (1999) a "El sefardí romántico" (2005)

El exilio es un tema recurrente en la obra de Angelina Muñiz-Huberman, miembro del llamado grupo hispanomexicano. La visión del exilio en su obra incluye no solo el exilio republicano sino también el del pueblo judío. Por eso, diferentes Diásporas históricas se superponen enriqueciendo el significado de la experiencia. En su ensayo El canto del peregrino: hacia una poética del exilio (1999) desarrolla sus pensamientos sobre el exilio y analiza numerosos trabajos de autores exiliados (judíos y republicanos españoles) centrándose en como cada uno reflejó la vivencia del exilio en su trabajo.En mi opinión, las ideas desarrolladas en el ensayo se pueden encontrar en su novela El sefardí romántico: la azarosa vida de Mateo Alemán II (2005). El título de la novela establece una conexión directa con la novela picaresca y la vida judía aludiendo al autor converso de Guzmán de Alfarache (1599-1604). Siguiendo el patrón establecido por la novela picaresca clásica, el protagonista de Muñiz-Huberman viaja por España y Europa denunciando la intolerancia que llevó a la Guerra Civil española y a la II Guerra Mundial. Las circunstancias lo llevan al exilio en México, como en el caso de Mateo Alemán. Según la teoría de Ulrich Wicks, pícaros y exiliados tienen mucho en común en su búsqueda continua de libertad, libertad que el exiliado puede encontrar solo en el idioma, como expone Muñiz-Huberman en su ensayo.

La perpetua reinvención de la identidad de los géneros en el baile flamenco

In the case of this study about flamenco dance, it is spotlighted how the matter of genders is a recurrent topic and a challenge in terms of creativity. Flamenco is in a perpetual search of a balance between tradition and contemporarily. Circumstance in which it was born, make this search and this constant mutation as part of its essence. When in a performance the representation of man and woman parts are modified according to the “traditional idea”, it brings up existential questions. Flamenco dance, like all the other contemporary forms of dance, reflects its context, contributes to its innovation and interacts with it. It is a social act.

On-line Emotion Recognition in a 3-D Activation-Valence-Time Continuum using Acoustic and Linguistic Cues

For many applications of emotion recognition, such as virtual agents, the system must select responses while the user is speaking. This requires reliable on-line recognition of the user’s affect. However most emotion recognition systems are based on turnwise processing. We present a novel approach to on-line emotion recognition from speech using Long Short-Term Memory Recurrent Neural Networks. Emotion is recognised frame-wise in a two-dimensional valence-activation continuum. In contrast to current state-of-the-art approaches, recognition is performed on low-level signal frames, similar to those used for speech recognition. No statistical functionals are applied to low-level feature contours. Framing at a higher level is therefore unnecessary and regression outputs can be produced in real-time for every low-level input frame. We also investigate the benefits of including linguistic features on the signal frame level obtained by a keyword spotter.

Ranking of microRNA target prediction scores by Pareto front analysis

Over the past ten years, a variety of microRNA target prediction methods has been developed, and many of the methods are constantly improved and adapted to recent insights into miRNA-mRNA interactions. In a typical scenario, different methods return different rankings of putative targets, even if the ranking is reduced to selected mRNAs that are related to a specific disease or cell type. For the experimental validation it is then difficult to decide in which order to process the predicted miRNA-mRNA bindings, since each validation is a laborious task and therefore only a limited number of mRNAs can be analysed. We propose a new ranking scheme that combines ranked predictions from several methods and - unlike standard thresholding methods - utilises the concept of Pareto fronts as defined in multi-objective optimisation. In the present study, we attempt a proof of concept by applying the new ranking scheme to hsa-miR-21, hsa-miR-125b, and hsa-miR-373 and prediction scores supplied by PITA and RNAhybrid. The scores are interpreted as a two-objective optimisation problem, and the elements of the Pareto front are ranked by the STarMir score with a subsequent re-calculation of the Pareto front after removal of the top-ranked mRNA from the basic set of prediction scores. The method is evaluated on validated targets of the three miRNA, and the ranking is compared to scores from DIANA-microT and TargetScan. We observed that the new ranking method performs well and consistent, and the first validated targets are elements of Pareto fronts at a relatively early stage of the recurrent procedure. which encourages further research towards a higher-dimensional analysis of Pareto fronts. (C) 2010 Elsevier Ltd. All rights reserved.

Tumor Risks and Genotype-Phenotype-Proteotype Analysis in 358 Patients With Germline Mutations in SDHB and SDHD

Succinate dehydrogenase B (SDHB) and D (SDHD) subunit gene mutations predispose to adrenal and extraadrenal pheochromocytomas, head and neck paragangliomas (HNPGL), and other tumor types. We report tumor risks in 358 patients with SDHB (n = 295) and SDHD (n = 63) mutations. Risks of HNPGL and pheochromocytoma in SDHB mutation carriers were 29% and 52%, respectively, at age 60 years and 71% and 29%, respectively, in SDHD mutation carriers. Risks of malignant pheochromocytoma and renal tumors (14% at age 70 years) were higher in SDHB mutation carriers; 55 different mutations (including a novel recurrent exon 1 deletion) were identified. No clear genotype-phenotype correlations were detected for SDHB mutations. However, SDHD mutations predicted to result in loss of expression or a truncated or unstable protein were associated with a significantly increased risk of pheochromocytoma compared to missense mutations that were not predicted to impair protein stability (most such cases had the common p.Pro81Leu mutation). Analysis of the largest cohort of SDHB/D mutation carriers has enhanced estimates of penetrance and tumor risk and supports in silicon protein structure prediction analysis for functional assessment of mutations. The differing effect of the SDHD p.Pro81Leu on HNPGL and pheochromocytoma, risks suggests differing mechanisms of tumorigenesis in SDH-associated HNPGL and pheochromocytoma. Hum Mutat 31:41-51, 2010. (C) 2009 Wiley-Liss, Inc.

The Utility of Cardiopulmonary Exercise Testing in Difficult Asthma

Background: Unexplained persistent breathlessness in patients with difficult asthma despite multiple treatments is a common clinical problem. Cardiopulmonary exercise testing (CPX) may help identify the mechanism causing these symptoms, allowing appropriate management.

Methods: This was a retrospective analysis of patients attending a specialist-provided service for difficult asthma who proceeded to CPX as part of our evaluation protocol. Patient demographics, lung function, and use of health care and rescue medication were compared with those in patients with refractory asthma. Medication use 6 months following CPX was compared with treatment during CPX.

Results: Of 302 sequential referrals, 39 patients underwent CPX. A single explanatory feature was identified in 30 patients and two features in nine patients: hyperventilation (n = 14), exercise-induced bronchoconstriction (n = 8), submaximal test (n = 8), normal test (n = 8), ventilatory limitation (n = 7), deconditioning (n = 2), cardiac ischemia (n = 1). Compared with patients with refractory asthma, patients without “pulmonary limitation” on CPX were prescribed similar doses of inhaled corticosteroid (ICS) (median, 1,300 µg [interquartile range (IQR), 800-2,000 µg] vs 1,800 µg [IQR, 1,000-2,000 µg]) and rescue oral steroid courses in the previous year (median, 5 [1-6] vs 5 [1-6]). In this group 6 months post-CPX, ICS doses were reduced (median, 1,300 µg [IQR, 800-2,000 µg] to 800 µg [IQR, 400-1,000 µg]; P < .001) and additional medication treatment was withdrawn (n = 7). Patients with pulmonary limitation had unchanged ICS doses post CPX and additional therapies were introduced.

Conclusions: In difficult asthma, CPX can confirm that persistent exertional breathlessness is due to asthma but can also identify other contributing factors. Patients with nonpulmonary limitation are prescribed inappropriately high doses of steroid therapy, and CPX can identify the primary mechanism of breathlessness, facilitating steroid reduction.

Targets of genome copy number reduction in primary breast cancers identified by integrative genomics

The identification of specific oncogenes and tumor suppressor genes in regions of recurrent aneuploidy is a major challenge of molecular cancer research. Using both oligonucleotide single-nucleotide polymorphism and mRNA expression arrays, we integrated genomic and transcriptional information to identify and prioritize candidate cancer genes in regions of increased and decreased chromosomal copy number in a cohort of primary breast cancers. Confirming the validity of this approach, several regions of previously-known copy number (CN) alterations in breast cancer could be successfully reidentified. Focusing on regions of decreased CN, we defined a prioritized list of eighteen candidate genes, which included ARPIN, FBNI, and LZTSI, previously shown to be associated with cancers in breast or other tissue types, and novel genes such as P29, MORF4LI, and TBCID5. One such gene, the RUNX3 transcription factor, was selected for further study. We show that RUNX3 is present at reduced CNs in proportion to the rest of the tumor genome and that RUNX3 CN reductions can also be observed in a breast cancer series from a different center. Using tissue microarrays, we demonstrate in an independent cohort of over 120 breast tissues that RUNX3 protein is expressed in normal breast epithelium but not fat and stromal tissue, and widely down-regulated in the majority of breast cancers (> 85%). In vitro, RUNX3 overexpression suppressed the invasive potential of MDA-MB-231 breast cancer cells in a matrigel assay. Our results demonstrate the utility of integrative genomic approaches to identify novel potential cancer-related genes in primary tumors. This article contains Supplementary Material available at http:// www.interscience.wiley.com/jpages/1045-2257/suppmat. (c) 2006 Wiley-Liss, Inc.

A Novel Multilocus Sequence Typing Scheme for the Opportunistic Pathogen Propionibacterium acnes and Characterisation of Type I Cell Surface-Associated Antigens.

We have developed a novel Multilocus Sequence Typing Scheme (MLST) and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and Random Amplification of Polymorphic DNA (RAPD) typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (ST). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB1), representing 65% of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants (SLV), which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore supports an association between acne and P. acnes strains from the type IA cluster and highlights the role of a widely disseminated clonal genotype in this condition. Characterisation of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.