bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential p38-dependent signalling in response to cellular stress and mitogenic stimulation in fibroblasts
Authors: Faust Dagmar , Schmitt Christina , Oesch Franz , Oesch-Bartlomowicz Barbara , Schreck Ilona , Weiss Carsten , Dietrich Cornelia
Published: March 2012

p38 MAP kinase is known to be activated by cellular stress finally leading to cell cycle arrest or apoptosis. Furthermore, a tumour suppressor role of p38 MAPK has been proposed. In contrast, a requirement of p38 for proliferation has also been described. To clarify this paradox, we investigatedstress- andmitogen-induced p38 signalling in the same cell type using fibroblasts. We demonstrate that - in the same cell line - p38 is activated by mitogens or cellular stress, but p38-dependent signalling is different. Exposure to cellular stress, such as anisomycin, leads to a strong and persistent p38 activation independent of GTPases. As a result, MK2 and downstream the transcription factor CREB are phosphorylated. In contrast, mitogenic stimulation results in a weaker and transient p38 activation, which upstream involves small GTPases and is required for cyclin D1 induction. Consequently, the retinoblastoma protein is phosphorylated and allows G1/S transition. Our data suggest a dual role of p38 and indicate that the level and/or duration of p38 activation determines the cellular response, i.e either proliferation or cell cycle arrest.
Design of broadband beamformers with low complexity
Authors: Feng Zhiguo , Yiu Cedric Ka Fai , Teo Kok-Lay , Nordholm Sven
Published: March 2012

In this article, we consider the design of broadband beamformers with low complexity. In fact, the design problem is multi-objective in nature, trading off between speech distortion and noise suppression. Finding a balance between these two objectives is important in order to achieve a desired sound quality. These measures are introduced as the objectives here. The design can then be obtained via a bi-objective integer programming problem, where the coefficients of the filters are expressed as sums of signed powers-of-two terms. We study two different integer spaces and penalty functions for solving the problem. Then, an algorithm based on a discrete filled function is developed for finding the optimal design. In order to illustrate the effectiveness of the algorithm, real data is used and two broadband beamformers are demonstrated.
Advances in using PARP inhibitors to treat cancer
Authors: Kummar Shivaani , Chen Alice , Parchment Ralph E , Kinders Robert J , Ji Jay , Tomaszewski Joseph E , Doroshow James H
Published: March 2012

The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.
Mouse-adapted scrapie strains 139A and ME7 overcome species barrier to induce experimental scrapie in hamsters and changed their pathogenic features
Authors: Shi Qi , Zhang Bao-Yun , Gao Chen , Zhang Jin , Jiang Hui-Ying , Chen Cao , Han Jun , Dong Xiao-Ping
Published: March 2012

Background

Transmissible spongiform encephalopathy (TSE) diseases are known to be zoonotic diseases that can infect different kinds of animals. The transmissibility of TSE, like that of other infectious diseases, shows marked species barrier, either being unable to infect heterologous species or difficult to form transmission experimentally. The similarity of the amino acid sequences of PrP among species is believed to be one of the elements in controlling the transmission TSE interspecies. Other factors, such as prion strains and host's microenvironment, may also participate in the process.

Methods

Two mouse-adapted strains 139A and ME7 were cerebrally inoculated to Golden hamsters. Presences of scrapie associate fibril (SAF) and PrPSc in brains of the infected animals were tested by TEM assays and Western blots dynamically during the incubation periods. The pathogenic features of the novel prions in hamsters, including electrophoretic patterns, glycosylating profiles, immunoreactivities, proteinase K-resistances and conformational stabilities were comparatively evaluated. TSE-related neuropathological changes were assayed by histological examinations.

Results

After long incubation times, mouse-adapted agents 139A and ME7 induced experimental scrapie in hamsters, respectively, showing obvious spongiform degeneration and PrPSc deposits in brains, especially in cortex regions. SAF and PrPSc in brains were observed much earlier than the onset of clinical symptoms. The molecular characteristics of the newly-formed PrPSc in hamsters, 139A-ha and ME7-ha, were obviously distinct from the original mouse agents, however, greatly similar as that of a hamster-adapted scrapie strain 263 K. Although the incubation times and main disease signs of the hamsters of 139A-ha and ME7-ha were different, the pathogenic characteristics and neuropathological changes were highly similar.

Conclusions

This finding concludes that mouse-adapted agents 139A and ME7 change their pathogenic characteristics during the transmission to hamsters. The novel prions in hamsters' brains obtain new molecular properties with hamster-specificity.
Indicators of the need for ICU admission following suicide bombing attacks
Authors: Bala Miklosh , Willner Dafna , Keidar Asaf , Rivkind Avraham I , Bdolah-Abram Tali , Almogy Gidon
Published: March 2012

Introduction

Critical hospital resources, especially the demand for ICU beds, are usually limited following mass casualty incidents such as suicide bombing attacks (SBA). Our primary objective was to identify easily diagnosed external signs of injury that will serve as indicators of the need for ICU admission. Our secondary objective was to analyze under- and over-triage following suicidal bombing attacks.

Methods

A database was collected prospectively from patients who were admitted to Hadassah University Hospital Level I Trauma Centre, Jerusalem, Israel from August 2001-August 2005 following a SBA. One hundred and sixty four victims of 17 suicide bombing attacks were divided into two groups according to ICU and non-ICU admission.

Results

There were 86 patients in the ICU group (52.4%) and 78 patients in the non-ICU group (47.6%). Patients in the ICU group required significantly more operating room time compared with patients in the non-ICU group (59.3% vs. 25.6%, respectively, p = 0.0003). For the ICU group, median ICU stay was 4 days (IQR 2 to 8.25 days). On multivariable analysis only the presence of facial fractures (p = 0.014), peripheral vascular injury (p = 0.015), injury ≥ 4 body areas (p = 0.002) and skull fractures (p = 0.017) were found to be independent predictors of the need for ICU admission. Sixteen survivors (19.5%) in the ICU group were admitted to the ICU for one day only (ICU-LOS = 1) and were defined as over-triaged. Median ISS for this group was significantly lower compared with patients who were admitted to the ICU for > 1 day (ICU-LOS > 1). This group of over-triaged patients could not be distinguished from the other ICU patients based on external signs of trauma. None of the patients in the non-ICU group were subsequently transferred to the ICU.

Conclusions

Our results show that following SBA, injury to ≥ 4 areas, and certain types of injuries such as facial and skull fractures, and peripheral vascular injury, can serve as surrogates of severe trauma and the need for ICU admission. Over-triage rates following SBA can be limited by a concerted, focused plan implemented by dedicated personnel and by the liberal utilization of imaging studies.
Current and emerging therapeutic strategies for Fanconi anemia
Authors: Shukla Pallavi , Ghosh Kanjaksha , Vundinti Babu R
Published: March 2012

Fanconi Anemia (FA) is a rare disorder with incidence of 1in 350,000 births. It is characterized by progressive bone marrow failure leading to death of many patients in their childhood while development of cancer at later stages of life in some. The treatment of FA is still a medical challenge. Current treatments of FA include androgen administration, hematopoietic growth factors administration and hematopoietic stem cell transplantation (HSCT). Clinical gene therapy trials are still ongoing. The partial success of current therapies has renewed interest in the search for new treatments. Generation of patient-specific induced pluripotent stem (iPS) has shown promising results for cell and gene based therapy. Small molecule interventions have been observed to delay tumor onset in FA. Tumors deficient in FA pathway can be treated by profiling of DNA repair pathway through synthetic lethality mechanism. Targeting toll-like receptor 8 (TLR8) dependent TNFα overexpression is yet another upcoming therapeutic approach to treat FA patients. In conclusion, in the present scenario of treatments available for FA, a proper algorithm of treatment decisions must be followed for better management of FA patients and to ensure their increased survival. Innovative therapeutic approaches that can prevent both anemia and cancer should be developed for more effective treatment of FA.
Is IL-6 an appropriate target to treat spondyloarthritis patients refractory to anti-TNF therapy? a multicentre retrospective observational study
Authors: Lekpa Fernando Kemta , Poulain Cécile , Wendling Daniel , Soubrier Martin , De Bandt Michel , Berthelot Jean Marie , Gaudin Philippe , Toussirot Eric , Goupille Philippe , Pham Thao , Sellam Jérémie , Bruckert Rémy , Paul Muriel , Farrenq Valérie , Claudepierre Pascal ,   the Club Rhumatismes et Inflammation
Published: March 2012

Introduction

The aim of this study was to evaluate, under real-life conditions, the safety and efficacy of tocilizumab in patients having failed anti-TNFα therapy for spondyloarthritis.

Methods

French rheumatologists and internal-medicine practitioners registered on the Club Rhumatismes et Inflammations website were asked to report on patients given tocilizumab (4 or 8 mg/kg) to treat active disease meeting Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral spondyloarthritis, after anti-TNFα treatment failure. Safety and efficacy after 3 and 6 months were assessed retrospectively using standardised questionnaires.

Results

Data were obtained for 21 patients, 13 with axial spondyloarthritis (46% men; median age, 42 years; disease duration, 11 years; HLA-B27-positive, 92.3%) and eight with peripheral spondyloarthritis (25% men; median age, 40 years; disease duration, 10 years; HLA-B27-positive, 62.5%). No patients with axial disease had at least a 20 mm decrease in the BASDAI, nor a BASDAI50 response or major ASAS-endorsed disease activity score improvements after 3 or 6 months; an ASAS-endorsed disease activity score clinically important improvement was noted at month 3 in five of 13 patients and at month 6 in one of four patients. A good DAS28 response was achieved in four patients with peripheral disease, including one in EULAR remission at month 3. Four patients were still taking tocilizumab at month 6, including one in EULAR remission and one with a good DAS28 response. Tocilizumab was well tolerated, with no serious adverse events. Initially elevated acute-phase reactants declined during tocilizumab therapy.

Conclusion

In patients having failed anti-TNFα therapy, tocilizumab decreased acute-phase reactants but failed to substantially improve axial spondyloarthritis and was inconsistently effective in peripheral spondyloarthritis.
Immunohistochemical detection of Polo-like kinase-1 (PLK1) in primary breast cancer is associated with TP53mutation and poor clinical outcome
Authors: King Sharon I , Purdie Colin A , Bray Susan E , Quinlan Philip R , Jordan Lee B , Thompson Alastair M , Meek David W
Published: March 2012

Introduction

Polo-like kinase-1 (PLK1) is a crucial driver of cell cycle progression and its down-regulation plays an important checkpoint role in response to DNA damage. Mechanistically, this is mediated by p53 which represses PLK1 expression through chromatin remodelling. Consistent with this model, cultured cells lacking p53 fail to repress PLK1 expression. This study examined PLK1 expression, p53 mutation and clinical outcome in breast cancer.

Methods

Immunohistochemistry was performed using antibodies to PLK1, MDM2 and Ki67 on Tissue Micro-Array (TMA) slides of a cohort of 215 primary breast cancers. The TP53 gene (encoding p53) was sequenced in all tumour samples. Protein expression scored using the "Quickscore" method was compared with clinical and pathological data, including survival.

Results

Staining of PLK1 was observed in 11% of primary breast tumours and was significantly associated with the presence of TP53 mutation (P = 0.0063). Moreover, patients with both PLK1 expression and TP53 mutation showed a significantly worse survival than those with either PLK1 expression or TP53 mutation alone. There was also a close association of elevated PLK1 with triple negative tumours, considered to be poor prognosis breast cancers that generally harbour TP53 mutation. Further association was observed between elevated PLK1 levels and the major p53 negative regulator, MDM2.

Conclusions

The significant association between elevated PLK1 and TP53 mutation in women with breast cancer is consistent with escape from repression of PLK1 expression by mutant p53. Tumours expressing elevated PLK1, but lacking functional p53, may be potential targets for novel anti-PLK1-targeted drugs.
Aromatase inhibitors, estrogens and musculoskeletal pain: estrogen-dependent T-cell leukemia 1A (TCL1A) gene-mediated regulation of cytokine expression
Authors: Liu Mohan , Wang Liewei , Bongartz Tim , Hawse John R , Markovic Svetomir N , Schaid Daniel J , Mushiroda Taisei , Kubo Michiaki , Nakamura Yusuke , Kamatani Naoyuki , Goss Paul E , Ingle James N , Weinshilboum Richard M
Published: March 2012

Introduction

Arthralgias and myalgias are major side effects associated with aromatase inhibitor (AI) therapy of breast cancer. In a recent genome-wide association study, we identified SNPs - including one that created an estrogen response element near the 3' end of the T-cell leukemia 1A (TCL1A) gene - that were associated with musculoskeletal pain in women on adjuvant AI therapy for breast cancer. We also showed estrogen-dependent, SNP-modulated variation in TCL1A expression and, in preliminary experiments, showed that TCL1A could induce IL-17RA expression. In the present study, we set out to determine whether these SNPs might influence cytokine expression and effect more widely, and, if so, to explore the mechanism of TCL1A-related AI-induced side effects.

Methods

The functional genomic experiments performed included determinations of TCL1A, cytokine and cytokine receptor expression in response to estrogen treatment of U2OS cells and lymphoblastoid cell lines that had been stably transfected with estrogen receptor alpha. Changes in mRNA and protein expression after gene knockdown and overexpression were also determined, as was NF-κB transcriptional activity.

Results

Estradiol (E2) increased TCL1A expression and, in a TCL1A SNP-dependent fashion, also altered the expression of IL-17, IL-17RA, IL-12, IL-12RB2 and IL-1R2. TCL1A expression was higher in E2-treated lymphoblastoid cell lines with variant SNP genotypes, and induction of the expression of cytokine and cytokine receptor genes was mediated by TCL1A. Finally, estrogen receptor alpha blockade with ICI-182,780 in the presence of E2 resulted in greatly increased NF-κB transcriptional activity, but only in cells that carried variant SNP genotypes. These results linked variant TCL1A SNP sequences that are associated with AI-dependent musculoskeletal pain with increased E2-dependent TCL1A expression and with downstream alterations in cytokine and cytokine receptor expression as well as NF-κB transcriptional activity.

Conclusions

SNPs near the 3' terminus of TCL1A were associated with AI-dependent musculoskeletal pain. E2 induced SNP-dependent TCL1A expression, which in turn altered IL-17, IL-17RA, IL-12, IL-12RB2, and IL-1R2 expression as well as NF-κB transcriptional activity. These results provide a pharmacogenomic explanation for a clinically important adverse drug reaction as well as insights into a novel estrogen-dependent mechanism for the modulation of cytokine and cytokine receptor expression.
Introduction to this special section: Mining geophysics
Authors: Goodway Bill
Published: March 2012

It has been almost exactly four years since the last TLE special section on mining was published and at that time the OECD was on the brink of the worldwide “great recession” brought on by the collapse of the U.S. housing market and consequent bank insolvency such as the Lehman's bankruptcy in September of that year. Just prior to this event, energy, metals, and food commodities had spiked to their highest relative price since the late 1970s (Figure 1).
Inverting airborne geophysical data for mega-cell and giga-cell 3D Earth models
Authors: Wilson Glenn A. , Cox Leif H. , Čuma Martin , Zhdanov Michael S.
Published: March 2012

Today's mineral exploration is driven by the simple fact that discovery rates have not kept pace with the depletion of existing reserves. To improve discovery rates, there is an industry-wide consensus on the need to increase the “discovery space” by exploring under cover and to greater depths. This attracts increased risks which may be mitigated by improved targeting. To do this, mining geophysics needs to shift toward 3D geological models founded upon improved petrophysical understanding and geophysical inversion. Regardless of the inversion methodology used, all geological constraints manifest themselves in the user's prejudice of an a priori model, upper and lower bounds, and choice of regularization. However, the practice of geologically constrained inversion is not the major problem needing to be addressed. It is known (and accepted) that geology is inherently 3D, and is a result of complex, overlapping processes related to genesis, metamorphism, deformation, alteration and/or weathering. Yet, the mining geophysics community to date has not fully accepted that geophysics should also be 3D, and most often relies on qualitative analysis, 1D inversion, and deposit-scale 2D or 3D inversion. There are many reasons for this unfortunate deficiency, not the least of which has been the lack of capacity of existing 3D inversion algorithms. To date, these have not been able to invert entire surveys with sufficient resolution in sufficient time to practically affect exploration decisions.
Constrained full-waveform inversion by model reparameterization
Authors: Guitton Antoine , Ayeni Gboyega , Díaz Esteban
Published: March 2012

The waveform inversion problem is inherently ill-posed. Traditionally, regularization schemes are used to address this issue. For waveform inversion, where the model is expected to have many details reflecting the physical properties of the Earth, regularization and data fitting can work in opposite directions: the former smoothing and the latter adding details to the model. We propose constraining estimated velocity fields by reparameterizing the model. This technique, also called model-space preconditioning, is based on directional Laplacian filters: It preserves most of the details of the velocity model while smoothing the solution along known geological dips. Preconditioning also yields faster convergence at early iterations. The Laplacian filters have the property to smooth or kill local planar events according to a local dip field. By construction, these filters can be inverted and used in a preconditioned waveform inversion strategy to yield geologically meaningful models. We illustrate with 2D synthetic and field data examples how preconditioning with nonstationary directional Laplacian filters outperforms traditional waveform inversion when sparse data are inverted and when sharp velocity contrasts are present. Adding geological information with preconditioning could benefit full-waveform inversion of real data whenever irregular geometry, coherent noise and lack of low frequencies are present.
Use of second-person pronouns and schizophrenia
Authors: Watson Andrew R. , Defteralı Çaǧla , Bak Thomas H. , Sorace Antonella , McIntosh Andrew M. , Owens David G. C. , Johnstone Eve C. , Lawrie Stephen M.
Published: March 2012

A masked analysis of videotaped assessments of people at high genetic risk of schizophrenia revealed that those who subsequently went on to develop schizophrenia used significantly more second-person pronouns. This was evident before diagnosis, at two separate assessments approximately 18 months apart. This supports the view that people who go on to develop schizophrenia may have an abnormality in the deictic frame of interpersonal communication – that is, the distinction between concepts being self-generated or from elsewhere may be blurred prior to the onset of a diagnosis of schizophrenia.
Suicide and non-suicide mortality after self-harm in Taipei
City, Taiwan
Authors: Kuo Chian-Jue , Gunnell David , Chen Chiao-Chicy , Yip Paul S. F. , Chen Ying-Yeh
Published: March 2012

Background

Most previous studies of long-term mortality risk following self-harm
have been conducted in Western countries with few studies from Asia.

Aims

To investigate suicide and non-suicide mortality after non-fatal
self-harm in Taipei City, Taiwan.

Method

Prospective cohort study (median follow-up 3.3 years) of 7601 individuals
presenting to hospital with self-harm (January 2004 to December 2006).
Standardised mortality ratios (SMRs) for suicide and non-suicide
mortality were calculated.

Results

Suicide risk in the year following self-harm was over 100 times higher
than in the general population (SMR = 119.6, 95% CI 99.6–142.5). Males
and middle-aged and older adults had the highest subsequent risk of
suicide. Compared with people who took an overdose, individuals who used
hanging or charcoal burning in their index episode had the highest risk
of suicide. For non-suicide mortality the SMRs were 6.7 (95% CI 5.7–7.8)
in the first year and 4.4 (95% CI 3.9–4.9) during the whole follow-up
period.

Conclusions

Patterns of increased all-cause and suicide mortality following an
episode of self-harm are similar in Taipei City to those seen in Western
countries. Designing better aftercare following non-fatal self-harm,
particularly for those with underlying physical disorders or who have
used lethal self-harm methods, should be a priority for suicide
prevention programmes in Asia.
Parent psychopathology and offspring mental disorders: Results from the WHO World Mental Health Surveys
Authors: McLaughlin Katie A. , Gadermann Anne M. , Hwang Irving , Sampson Nancy A. , Al-Hamzawi Ali , Andrade Laura Helena , Angermeyer Matthias C. , Benjet Corina , Bromet Evelyn J. , Bruffaerts Ronny , Caldas-de-Almeida José Miguel , de Girolamo Giovanni , de Graaf Ron , Florescu Silvia , Gureje Oye , Haro Josep Maria , Hinkov Hristo Ruskov , Horiguchi Itsuko , Hu Chiyi , Karam Aimee Nasser , Kovess-Masfety Viviane , Lee Sing , Murphy Samuel D. , Nizamie S. Haque , Posada-Villa José , Williams David R. , Kessler Ronald C.
Published: March 2012

Background

Associations between specific parent and offspring mental disorders are likely to have been overestimated in studies that have failed to control for parent comorbidity.

Aims

To examine the associations of parent with respondent disorders.

Method

Data come from the World Health Organization (WHO) World Mental Health Surveys (n = 51 507). Respondent disorders were assessed with the Composite International Diagnostic Interview and parent disorders with informant-based Family History Research Diagnostic Criteria interviews.

Results

Although virtually all parent disorders examined (major depressive, generalised anxiety, panic, substance and antisocial behaviour disorders and suicidality) were significantly associated with offspring disorders in multivariate analyses, little specificity was found. Comorbid parent disorders had significant sub-additive associations with offspring disorders. Population-attributable risk proportions for parent disorders were 12.4% across all offspring disorders, generally higher in high- and upper-middle- than low-/lower-middle-income countries, and consistently higher for behaviour (11.0–19.9%) than other (7.1–14.0%) disorders.

Conclusions

Parent psychopathology is a robust non-specific predictor associated with a substantial proportion of offspring disorders.
The usefulness of combined measurements of squamous cell carcinoma antigens 1 and 2 in diagnosing atopic dermatitis
Authors: Ohta Shoichiro , Shibata Rumiko , Nakao Yoshifumi , Azuma Yoshinori , Taniguchi Kazuto , Arima Kazuhiko , Suzuki Shoichi , Shiraishi Hiroshi , Iwasaka Tsuyoshi , Izuhara Kenji
Published: March 2012

Background

The squamous cell carcinoma antigen (SCCA) is widely used as a serological biomarker for various cancers. There are two known SCCA molecules, SCCA1 and SCCA2. We previously found that interleukin-4 or interleukin-13, two related Th2-type cytokines that play an important role in allergic diseases, induce expression of SCCA1 and SCCA2. In this study, we examined whether combined measurements of SCCA1 and SCCA2 are useful for diagnosing atopic dermatitis (AD).

Methods

We established new enzyme-linked immunosorbent assays (ELISAs) to specifically detect SCCA1 or SCCA2. We applied serum samples from AD patients with food allergies and from cervical cancer patients to these ELISAs. We performed receiver operating characteristic analyses to diagnose AD and to distinguish AD from cervical cancer.

Results

Serum concentrations of both SCCA1 and SCCA2 were elevated in AD patients. The serum concentrations of SCCA1 and SCCA2 positively correlated with the clinical severity of AD, showing high specificity (0.86–0.88) and sensitivity (0.86) against control donors. The serum concentrations of SCCA1 and SCCA2 were elevated in cervical cancer patients; however, the SCCA2/SCCA1 ratios clearly distinguished AD patients from cervical cancer patients with high specificity (0.87) and sensitivity (0.87). Expression of SCCA2 was predominant in AD patients, whereas cervical cancer patients showed a predominance of SCCA1.

Conclusions

Combined measurements of SCCA1 and SCCA2 are very useful in estimating the severity of allergic diseases, making it possible to distinguish allergic diseases from cancers.
Recommendations for standardized reporting of protein electrophoresis in Australia and New Zealand
Authors: Tate Jillian , Caldwell Grahame , Daly James , Gillis David , Jenkins Margaret , Jovanovich Sue , Martin Helen , Steele Richard , Wienholt Louise , Mollee Peter
Published: March 2012

Background

Although protein electrophoresis of serum (SPEP) and urine (UPEP) specimens is a well-established laboratory technique, the reporting of results using this important method varies considerably between laboratories. The Australasian Association of Clinical Biochemists recognized a need to adopt a standardized approach to reporting SPEP and UPEP by clinical laboratories.

Methods

A Working Party considered available data including published literature and clinical studies, together with expert opinion in order to establish optimal reporting practices. A position paper was produced, which was subsequently revised through a consensus process involving scientists and pathologists with expertise in the field throughout Australia and New Zealand.

Results

Recommendations for standardized reporting of protein electrophoresis have been produced. These cover analytical requirements: detection systems; serum protein and albumin quantification; fractionation into alpha-1, alpha-2, beta and gamma fractions; paraprotein quantification; urine Bence Jones protein quantification; paraprotein characterization; and laboratory performance, expertise and staffing. The recommendations also include general interpretive commenting and commenting for specimens with paraproteins and small bands together with illustrative examples of reports.

Conclusions

Recommendations are provided for standardized reporting of protein electrophoresis in Australia and New Zealand. It is expected that such standardized reporting formats will reduce both variation between laboratories and the risk of misinterpretation of results.
Amyloidosis
Authors: Pinney Jennifer H , Hawkins Philip N
Published: March 2012

The term amyloid describes the deposition in the extracellular space of certain proteins in a highly characteristic, insoluble fibrillar form. Amyloidosis describes the various clinical syndromes that occur as a result of damage by amyloid deposits in tissues and organs throughout the body. The clinical significance of amyloid varies enormously, ranging from incidental asymptomatic deposits to localized disease through to rapidly fatal systemic forms that can affect multiple vital organs. Currently available therapy is focused on reducing the supply of the respective amyloid fibril precursor protein and supportive medical care, which together have greatly improved survival. Chemotherapy and anti-inflammatory treatment for the disorders that underlie AL and AA amyloidosis are guided by serial measurements of the respective circulating amyloid precursor proteins, i.e. serial serum free light chains in AL and serum amyloid A protein in AA type. Quality of life and prognosis of some forms of hereditary systemic amyloidosis can be improved by liver and other organ transplants. Various new therapies, ranging from silencing RNA, protein stabilizers to monoclonal antibodies, aimed at inhibiting fibril precursor supply, fibril formation or the persistence of amyloid deposits, are in development; some are already in clinical phase.
Computer-aided detection system performance on current and previous digital mammograms in patients with contralateral metachronous breast cancer
Authors: Kim Seung Ja , Moon Woo Kyung , Cho Nariya , Chang Jung Min
Published: March 2012

Background

The computer-aided detection (CAD) system is widely used for screening mammography. The performance of the CAD system for contralateral breast cancer has not been reported for women with a history of breast cancer.

Purpose

To retrospectively evaluate the performance of a CAD system on current and previous mammograms in patients with contralateral metachronous breast cancer.

Material and Methods

During a 3-year period, 4945 postoperative patients had follow-up examinations, from whom we selected 55 women with contralateral breast cancers. Among them, 38 had visible malignant signs on the current mammograms. We analyzed the sensitivity and false-positive marks of the system on the current and previous mammograms according to lesion type and breast density.

Results

The total visible lesion components on the current mammograms included 27 masses and 14 calcifications in 38 patients. The case-based sensitivity for all lesion types was 63.2% (24/38) with false-positive marks of 0.71 per patient. The lesion-based sensitivity for masses and calcifications was 59.3% (16/27) and 71.4% (10/14), respectively. The lesion-based sensitivity for masses in fatty and dense breasts was 68.8% (11/16) and 45.5% (5/11), respectively. The lesion-based sensitivity for calcifications in fatty and dense breasts was 100.0% (3/3) and 63.6% (7/11), respectively. The total visible lesion components on the previous mammograms included 13 masses and three calcifications in 16 patients, and the sensitivity for all lesion types was 31.3% (5/16) with false-positive marks of 0.81 per patient. On these mammograms, the sensitivity for masses and calcifications was 30.8% (4/13) and 33.3% (1/3), respectively. The sensitivity in fatty and dense breasts was 28.6% (2/7) and 33.3% (3/9), respectively.

Conclusion

In the women with a history of breast cancer, the sensitivity of the CAD system in visible contralateral breast cancer was lower than in most previous reports using the same CAD system probably due to the relatively small size, subtlety of the lesion findings, and dense parenchymal pattern.
Transcatheter renal artery embolization with N-butyl cyanoacrylate
Authors: Kim Jinoo , Shin Ji Hoon , Yoon Hyun-Ki , Ko Gi-Young , Gwon Dong II , Kim Eun-Young , Sung Kyu-Bo
Published: March 2012

Background

Despite its long history, the application of N-butyl cyanoacrylate (NBCA) has been limited compared to other materials such as particulate agents and coils. This possibly owes to a widespread misconception that NBCA is difficult to handle and carries a high risk of complications due to its liquid nature and rapid polymerization time. However, recent reports have shown that, with knowledge and experience, NBCA is safe and effective to use in visceral arteries.

Purpose

To review the outcome of transcatheter embolization of the renal artery using NBCA for varied etiologies in the kidney.

Material and Methods

Fourteen patients with varied etiologies in the kidney underwent renal artery embolization using NBCA as the sole embolic agent (64%) or in combination with an additional embolic material (36%). A review of medical charts and images were performed to gather information regarding underlying etiologies, clinical presentation, and outcome of embolization.

Results

Technical success was achieved in all patients (100%) while clinical success was achieved in 12 (85.7%). One failed case was managed by repeat embolization using microcoils, while the other underwent partial nephrectomy after failed reattempt at embolization. Three patients with recurrent bleeding after previously having undergone embolization using microcoils or gelatin sponge particles were successfully managed the second time using NBCA. NBCA embolization was also effective in three patients with hemostatic abnormality. Complications attributable to NBCA embolization were renal atrophy in one patient and microcatheter tip fracture in another.

Conclusion

The application of NBCA for transcatheter embolization of varied etiologies involving the renal artery is feasible and safe in the hands of an experienced interventional radiologist. It offers immediate and effective occlusion of the pathologic vessel and, while it can be used exclusively on its own, it can also be used to complement other embolic materials.
Managing Acute Medical Admissions: The Plight of the Medical Boarder
Authors: Mcknight J A , Espie C
Published: March 2012

In an ideal system, patients admitted acutely to hospital should have their care provided in an area with the most appropriate ward-based medical, nursing and allied professional staff profile. Frequently this does not happen due to the physical structure and organisation of our hospitals in Scotland. Acute medical admissions may be fitted in to the end of many different speciality ward areas while still under the care of a single internal medicine team – as ‘medical boarders’. A survey of local medical and nursing staff revealed that a majority would not wish their relatives to be cared for in this way. It remains important to provide speciality beds for those patients who require them, but it is also necessary to develop a system that enables more patients to receive optimal care in the correct environment. In this article, we describe the issue, the problems created and some possible solutions.
Pyogenic Ventriculitis following Enteral Bacterial Translocation in a Patient with Small Bowel Obstruction
Authors: Hansom D , Littlejohn M G , Clancy M J
Published: March 2012

The authors present a rare case of ventriculitis secondary to cerebro spinal fluid (CSF) colonization with Escherichia coli species in a 65-year-old woman. Passage of bacterial organisms from the lumen of the gastrointestinal tract to the bloodstream or lymphatic tissue is known as translocation. Once in the bloodstream, particular bacteria are able to cross the blood–brain barrier and migrate to CSF. Elective abdominal surgery, intestinal obstruction, colorectal cancer, ischaemic reperfusion injury and pancreatitis have all increased the risk of this phenomenon. This account highlights particular events in presentation and management of such a case, followed by a brief literature review.
Audio-induced Psychogenic Non-epileptic Seizures
Authors: Young A M H , Stoker T B
Published: March 2012

A 45-year-old woman presented with vague attacks, which consisted of headaches, confusion and sleepiness. An electroencephalograph was normal, but subsequent scans revealed the presence of a right-sided convexity meningioma. This was excised and complications led to the removal of an infected bone flap in a separate procedure the following year. Various types of ‘seizures’ resulted from the operation. These were described to involve both tonic-clonic and absence seizures. This continued for 18 years, unaffected by medication, until a specialist diagnosed pseudo-epilepsy, by fortune of a hospital fire alarm. The patient began a psychological intervention programme including cognitive-behavioural therapy, which has significantly reduced episodes. In conclusion, psychogenic non-epileptic seizures may develop after intracranial neurosurgery undertaken for indications other than the control of refractory epileptic seizures. A diagnosis of psychogenic non-epileptic seizures should be considered in patients who develop refractory seizures after neurosurgery and managed appropriately.
Smouldering Systemic Mastocytosis Presenting with Cryptic Life-threatening Crises: Case Report and Literature Review
Authors: Shah M , Holyoake T L , Jackson B , Drummond M
Published: March 2012

Systemic mastocytosis (SM) is a rare, clonal disorder of the mast cell (MC) and its precursor cells. It is characterized by proliferation and accumulation of MCs within various organs, most commonly the skin. The clinical course is variable with indolent or smouldering and aggressive forms being described. We report the case of a middle-aged male patient with smouldering SM presenting with atypical recurrent life-threatening crises. The patient reported a 19-year history of chronic symptoms. The patient had four inpatient stays due to atypical life-threatening crises, during which he has shown end organ damage (cardiac and renal). With each crisis the patient reported acute symptoms. The management of each of these episodes was complex and made more challenging by the patient's longstanding history of hypertension and ischaemic heart disease. In short, SM can present with unexplained life-threatening crises which can be confused for an infectious disease being acute in nature.
Quality of Life and Behavioural Adjustment in Childhood Hydrocephalus
Authors: Sumpter R , Dorris L , Brannan G , Carachi R
Published: March 2012

The aim of the paper is to describe parent and teacher reported behavioural outcomes and quality of life in childhood hydrocephalus, and to consider the implications for future service planning. A community sample of 235 school-aged children with hydrocephalus (5–16 years) were identified via a database of service users, held by the Scottish Spina Bifida Association. Parent and teacher reports of behaviour on the Strengths and Difficulties Questionnaire (SDQ), and parent reports of quality of life on the Paediatric Quality-of-Life Generic Core (PedsQL Core) and Paediatric Quality-of-Life Fatigue (PedsQL Fatigue) were obtained, as were reports of service use and satisfaction. In total, 35% (n = 76) of parents and 86% (n = 47) of teachers who were contacted participated in the study. Parents reported behavioural difficulties in 57% and teachers in 33% of children. Quality of life was significantly reduced in comparison to published norms. Children whose parents reported unmet needs had poorer psychosocial outcomes, but families rarely accessed appropriate specialist services. In conclusion, hydrocephalus is associated with high rates of behaviour problems and markedly reduced quality of life. It is important to increase professional awareness of psychological need in this chronic neurological condition, and to increase access to appropriate psychosocial services.
Effect of a Multistage Ultraendurance Triathlon on Aldosterone, Vasopressin, Extracellular Water and Urine Electrolytes
Authors: Knechtle B , Morales N P Hernández , González E Ruvalcaba , Gutierrez A A Aguirre , Sevilla J Noriega , Gómez R Amézquita , Robledo A R Estrada , Rodríguez A L Marroquín , Fraire O Salas , Andonie J L , Lopez L C , Kohler G , Rosemann T
Published: March 2012

Prolonged endurance exercise over several days induces increase in extracellular water (ECW). We aimed to investigate an association between the increase in ECW and the change in aldosterone and vasopressin in a multistage ultraendurance triathlon, the ‘World Challenge Deca Iron Triathlon’ with 10 Ironman triathlons within 10 days. Before and after each Ironman, body mass, ECW, urinary [Na+], urinary [K+], urinary specific gravity, urinary osmolality and aldosterone and vasopressin in plasma were measured. The 11 finishers completed the total distance of 38 km swimming, 1800 km cycling and 422 km running within 145.5 (18.8) hours and 25 (22) minutes. ECW increased by 0.9 (1.1) L from 14.6 (1.5) L prerace to 15.5 (1.9) L postrace (P < 0.0001). Aldosterone increased from 70.8 (104.5) pg/mL to 102.6 (104.6) pg/mL (P = 0.033); vasopressin remained unchanged. The increase in ECW was related neither to postrace aldosterone nor to postrace vasopressin. In conclusion, ECW and aldosterone increased after this multistage ultraendurance triathlon, but vasopressin did not. The increase in ECW and the increase in aldosterone were not associated.
Can Telehealth Deliver for Rural Scotland? Lessons from the Argyll & Bute Telehealth Programme
Authors: Roberts A , Garrett L , Godden D J
Published: March 2012

Policy-makers consider telehealth to be a potential solution to delivery of care in rural Scotland. Telehealth can support patients in the community and may reduce emergency admissions to hospital. The Argyll & Bute telehealth initiative, which commenced in 2007, trialled home telehealth monitoring of patients with chronic obstructive pulmonary disease (COPD), and community- and surgery-based monitoring of general wellbeing and hypertension. An evaluation in 2010 assessed staff and patient satisfaction by questionnaire, impact on hospital and general practice attendance by case record review and detailed opinions on the programme by qualitative interviews with key staff. Home monitoring for COPD was associated with high levels of patient satisfaction and a reduction in hospital admissions and other health service contacts. Delays in implementation and some technical challenges compromised evaluation of the surgery and community initiatives. Patients and staff were generally enthusiastic but also identified potential barriers to development. This paper describes the implementation and outcomes of the initiative and identifies issues that clinicians embarking on telehealth programmes must consider: technical factors; governance and security; staff profiling and training; clinical outcomes; and scalability.
Premature Mortality in Scottish Injecting Drug Users: A Life-history Approach
Authors: Copeland L , Robertson J , Mckenzie J , Kimber J , Macleod J , Hickman M , De Angelis D
Published: March 2012

In Scotland, deaths in drug users are known to be higher than in the rest of the UK and most of Europe. Reducing drug-related deaths is currently a national priority for the Scottish Government. This study aimed to present a description of the life histories of a group of injecting drug users who have recently died, with a view to highlighting areas for further research. The Edinburgh Addiction Cohort study recently carried out 432 follow-up interviews between the years 2005 and 2007. Thirty-three cases who completed this extensive interview detailing early life, education, employment, drug use, opiate substitution treatment, criminal history, mental health problems and overdose have subsequently died, leaving this source of rich information about their lives. The design of the interview used the life grid approach. Information was also compiled from full primary care records and General Register Office death certificates. Early life adversity was apparent for many cases, with a steady progression into early criminal behaviour and drug misuse. Poor adult life outcomes illustrated the lifelong damaging effects of drug injecting. Death occurred significantly earlier than in the general population or those living in deprived communities who did not use drugs. In conclusion, a clearer understanding of the life histories of problem drug users would be advantageous for healthcare professionals and policy-makers. More qualitative research studies are needed to highlight areas which might require early intervention and also complement the existing secondary data studies.
The Importance of Informed Consent in Patients with Wet Age-related Macular Degeneration considering Intravitreal Anti-vascular Endothelial Growth Factor Treatments
Authors: Mclaughlin S , Lockington D , Mansfield D
Published: March 2012

Retinal pigment epithelial (RPE) tears are now a documented potential complication following the intravitreal injection of anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration. Patients are often not well consented regarding this risk and thus we retrospectively analyzed the data from all of our patients undergoing this treatment over a six month period. Our findings highlighted the fact that the three patients (out of thirty) who had developed this RPE tear complication were initially all diagnosed with a pigment epithelial detachment (which is a type of macular degeneration in question). Therefore, we have adjusted our informed consent procedure such that all patients with “wet” macular degeneration and especially those with pigment epithelial detachments are now fully consented regarding the risks of the intravitreal treatment, which could potentially damage their vision further.
Synchronization in Vehicle Routing—A Survey of VRPs with Multiple Synchronization Constraints
Authors: Drexl Michael
Published: March 2012

This paper presents a survey of vehicle routing problems with multiple synchronization constraints. These problems exhibit, in addition to the usual task covering constraints, further synchronization requirements between the vehicles, concerning spatial, temporal, and load aspects. They constitute an emerging field in vehicle routing research and are becoming a “hot” topic. The contribution of the paper is threefold: (i) It presents a classification of different types of synchronization. (ii) It discusses the central issues related to the exact and heuristic solution of such problems. (iii) It comprehensively reviews pertinent literature with respect to applications as well as successful solution approaches, and it identifies promising algorithmic avenues.
Migration governance in the European Union: a theme and its variations
Authors: Carmel Emma
Published: March 2012

This article outlines the key features of migration governance in the European Union (EU) and the diversity of forms of governance among its member states shaping migrants’ rights and experiences, particularly, but not solely, in relation to the labour market. It explains how EU and member state policies work to jointly construct particular categories of migrant status and pathways for migrants’ ‘differential integration’ across Europe. The article clarifies the diverse pathways through which EU states offer privileged access to entry, residence, employment and citizenship to some migrants over others and shows how the EU's migration governance limits and reproduces this diversity, with significant implications for the recognition and equality of the rights of different groups of migrants within one country, and comparatively across countries.