bluuebunny/crossref_metadata_2025 huggingface dataset:
Dubrovnik’s Artistic Patrimony, and its Role in War Reporting (1991)
Authors: Pearson Joseph
Published: March 2010

Journalist reports of the siege of Dubrovnik by the Yugoslav National Army (1991) were misleading and exaggerated the extent of damage to the old city in order to encourage international intervention to protect cultural property. This article examines the extent of this destruction and how it was reported by British correspondents in the field and editors at home. It uses a rhetorical frame of analysis to engage current theoretical debates about Western actors, their depiction of the Yugoslav war and the nationalities involved. Interview material, with correspondents and editors such as Alex Russell and Max Hastings, supplements documentary analysis of press sources positioned within the secondary literature. The enquiry also considers how these reports influence memory and later histories of Dubrovnik’s fate in the Yugoslav wars, and public responses to humanitarian intervention.
Event-related brain potentials and second language learning: syntactic processing in late L2 learners at different L2 proficiency levels
Authors: van Hell Janet G. , Tokowicz Natasha
Published: March 2010

There are several major questions in the literature on late second language (L2) learning and processing. Some of these questions include: Can late L2 learners process an L2 in a native-like way? What is the nature of the differences in L2 processing among L2 learners at different levels of L2 proficiency? In this article, we review studies that addressed these questions using event-related brain potentials (ERPs) in late learners and that focused on syntactic processing. ERPs provide an on-line, millisecond-by-millisecond record of the brain’s electrical activity during cognitive processing. ERP measures can thus provide valuable information on the timing and degree of neural activation as language processing (here: syntactic processing in L2) unfolds over time. After discussing the use of ERPs for the study of L2 learning and processing, we review electrophysiological studies on syntactic and morphosyntactic processing in late L2 learners with different levels of L2 proficiency. The currently available evidence indicates that patterns of neural activity in the brain during syntactic and morphosyntactic processing can be modulated by various, possibly interrelated, factors including the similarity or dissimilarity of syntactic structures in L2 and L1, the exact nature of the syntactic structure L2 learners seek to comprehend and the concomitant expectancies they can generate with regard to violations in this structure, and the L2 learners’ level of L2 proficiency. Together these studies show that ERPs can successfully elucidate subtle differences in syntactic processing between L2 learners and native speakers, and among L2 learners at different levels of L2 proficiency, which are difficult to detect or that might have remained undetected with behavioural measures.
Does functional change predict the course of improvement in geriatric inpatient rehabilitation?
Authors: Denkinger Michael D , Igl Wilmar , Jamour Michael , Bader Anne , Bailer Stefanie , Lukas Albert , Nikolaus Thorsten
Published: March 2010

Objective: The evaluation of rehabilitation success as measured by different tools is becoming increasingly important in terms of time and money allocation. We wanted to know whether functional change in the first week predicts subsequent improvement in a geriatric inpatient rehabilitation clinic.

Design: Observational longitudinal study.

Setting: Geriatric inpatient rehabilitation clinic in Germany.

Subjects: One hundred and sixty-one inpatients (117 women) with a median age of 82 years, capable of walking at baseline.

Main measures: Weekly assessments of physical function were performed from admission until three weeks later. We used a self-rated tool (the function component of the Short Form — Late Life Function and Disability Index), a proxy-rated tool (the Barthel Index) and a performance-based tool (gait speed). We set up linear regression models to estimate the predictive capacity of change in physical function within the first week on change in physical function within the following two weeks.

Results: Positive correlations were found between functional change within the first week and total change within three weeks. However, correlations of the same periods of change with subsequent change were negative. Correlations were highly significant for both analysis with P-values <0.0001 when the same measures for prediction and outcome were used. Correlations were inconsistent when prediction and outcome were different.

Conclusions: Improvement within the first week of inpatient rehabilitation is negatively correlated with subsequent functional change.
Lehmann Family of ROC Curves
Authors: Gönen Mithat , Heller Glenn
Published: March 2010

Receiver operating characteristic (ROC) curves evaluate the discriminatory power of a continuous marker to predict a binary outcome. The most popular parametric model for an ROC curve is the binormal model, which assumes that the marker, after a monotone transformation, is normally distributed conditional on the outcome. Here, the authors present an alternative to the binormal model based on the Lehmann family, also known as the proportional hazards specification. The resulting ROC curve and its functionals (such as the area under the curve and the sensitivity at a given level of specificity) have simple analytic forms. Closed-form expressions for the functional estimates and their corresponding asymptotic variances are derived. This family accommodates the comparison of multiple markers, covariate adjustments, and clustered data through a regression formulation. Evaluation of the underlying assumptions, model fitting, and model selection can be performed using any off-the-shelf proportional hazards statistical software package.
Treatment Evolution and New Standards of Care
Authors: Shechter Steven M.
Published: March 2010

Background. Traditional approaches to cost-effectiveness analysis have not considered the downstream possibility of a new standard of care coming out of the research and development pipeline. However, the treatment landscape for patients may change significantly over the course of their lifetimes. Objective. To present a Markov modeling framework that incorporates the possibility of treatment evolution into the incremental cost-effectiveness ratio (ICER) that compares treatments available at the present time. Design. Markov model evaluated by matrix algebra. Measurements. The author evaluates the difference between the new and traditional ICER calculations for patients with chronic diseases facing a lifetime of treatment. Results. The bias of the traditional ICER calculation may be substantial, with further testing revealing that it may be either positive or negative depending on the model parameters. The author also performs probabilistic sensitivity analyses with respect to the possible timing of a new treatment discovery and notes the increase in the magnitude of the bias when the new treatment is likely to appear sooner rather than later. Limitations. The modeling framework is intended as a proof of concept and therefore makes simplifying assumptions such as time stationarity of model parameters and consideration of a single new drug discovery. Conclusions. For diseases with a more active research and development pipeline, the possibility of a new treatment paradigm may be at least as important to consider in sensitivity analysis as other parameters that are often considered.
ONESVIEW: An Integrated System for One-Stop Virtual Design Review
Authors: SangSu Choi  , HyunJei Jo  , Boehm Stefan , Sang Do Noh
Published: March 2010

The influence of design aspects on the commercial success of a product is increasingly important nowadays. For many consumer products, such as television sets and mobile phones, an appealing design is often even more important for the purchase decisions of customers than functional aspects. This observation stresses the importance of adequate design decisions early in the creative process for a new product. Progress in virtual reality technology enables us nowadays to observe and evaluate virtual prototypes of products; thereby, we obtain a realistic impression of the design and properties of their physical equivalents. These prospects raise the need for an integrated design process from product data management (PDM) to virtual reality. In this article, we introduce ONE-Stop VIrtual dEsign revieW (ONESVIEW), which is a novel approach for an integrated virtual design review system that consists of several interrelated subsystems developed in this article, namely, Middleware for Exchanging Machinery and Product Data in Highly Immersive Systems (MEMPHIS), Virtual Material Laboratory (VMLab), Collaborative Design Review System (CORE), and Mixed Reality In Virtual Engineering (MRIVE). By MEMPHIS and VMLab, realistic virtual prototypes can be created more quickly, conveniently, and efficiently. Using CORE, the design review can be carried out in collaboration. Finally, through MRIVE, we can evaluate and determine the final design in a real-world environment. All the data involved in this process can be managed by the revision control system of CORE and the entire process, from PDM to the selection of the design, is a one-stop process. As a result of this study, it is possible that decision making can be done effectively at an early stage within the design process.
Interleukin 18 Receptor 1 expression distinguishes patients with multiple sclerosis
Authors: Gillett Alan , Thessen Hedreul Melanie , Khademi Mohsen , Espinosa Alexander , Beyeen Amennai D , Jagodic Maja , Kockum Ingrid , Harris Robert A , Olsson Tomas
Published: March 2010

Definition of dysregulated immune components in multiple sclerosis may help in the identification of new therapeutic targets. Deviation of the interleukin 18 receptor 1 (IL18R1) is of particular interest since the receptor is critical for experimental neuroinflammation. The objective of this study was to determine whether expression of IL18R1 varies between multiple sclerosis patients and controls, and to test genetic association of IL18R1 with multiple sclerosis. We used quantitative real-time PCR to assess mRNA levels of IL18R1 in cerebrospinal fluid and peripheral blood mononuclear cells of 191 patients with multiple sclerosis, 61 patients with clinically isolated syndrome and 168 controls having other neurological disorders. Association was tested in 2153 patients with multiple sclerosis and 1733 controls using 13 tagging single nucleotide polymorphisms within the IL18R1 gene. We found that patients with multiple sclerosis had increased IL18R1 mRNA expression in both cerebrospinal fluid cells ( p < 0.05) and peripheral blood mononuclear cells ( p < 0.05) compared with controls. Patients with clinically isolated syndrome had elevated levels compared with controls in cerebrospinal fluid cells ( p < 0.001) but not in peripheral blood mononuclear cells. The gene was not associated to multiple sclerosis. We conclude that the increased expression of IL18R1 may contribute pathogenically to disease and is therefore a potential therapeutic target. The absence of a genetic association in the IL18R1 gene itself suggests regulation from other parts of the genome, or as part of the inflammatory cascade in multiple sclerosis without a prime genetic cause.
Remembering the Red Army Faction
Authors: Bielby Clare
Published: March 2010

This article considers how Germany’s period of left-wing terrorism, particularly the so-called German Autumn, tends to be feminized and allegorized in contemporary public discourses, particularly those of the print media. The most striking example of this is the use of a pram as memory object at the permanent exhibition of the German History Museum. I explore how the 30th anniversary of the German Autumn was covered in the print media, particularly in Der Spiegel, Stern and Die Zeit, in 2007 and trace these representational strategies back to the print media of the 1970s with its preoccupation with the figure of the woman terrorist. I then situate the feminizing and allegorizing strategy in the context of other representational strategies that seek to distance the contemporary Federal Republic from a past which fails to disappear.
Extending Emotion Science to the Study of Discrete Emotions in Infants
Authors: Izard Carroll E. , Woodburn Elizabeth M. , Finlon Kristy J.
Published: March 2010

Many emotion researchers would probably agree that at least some aspects of discrete emotions are evolutionarily conserved (e.g., the sensation/feeling component cannot be learned). Such agreement probably extends to the notion that aspects of emotions emerge in ontogeny as a function of developmental, learning, and cultural processes. Determining when and under what circumstances they emerge seems largely a matter for empirical research, though theories differ in their predictions and in the way they describe the relevant emotional-, cognitive-, and neuro-developmental processes.
Recognizing Desirability: Is Goal Comparison Necessary?
Authors: Parkinson Brian
Published: March 2010

Moors and colleagues’ clever studies demonstrate that goal-relevant stimuli can produce rapid, unintentional affective priming, but not necessarily that primes are compared with goal representations following onset. Instead, prior attunements based on changing concerns may prespecify reward value. Even if both these processes count as emotion-relevant appraisal, none of the evidence rules out appraisal-independent emotion under other, unsampled, circumstances, including those where emotions develop as cumulative responses to unfolding and responsive environments rather than as momentary reactions to briefly-presented simple stimuli. Although the functional relations between inputs and outputs may imply “constructive” processes at one level, these processes may be implemented by sequential lower-level mechanisms.
Beyond Breaches and Battles: Clarifying Important Misconceptions about Emotion
Authors: Campos Joseph J. , Dahl Audun , Minxuan He
Published: March 2010

While we share many of the views on emotion research put forth in Kagan’s article “Once More into the Breach,” our commentary focuses on two points of disagreement. First, we argue for the importance of a priori principles. In particular, emotions cannot be understood without reference to final and formal cause, and the related principles of equifinality and equipotentiality. Secondly, although we agree the term “basic emotions” is misleading, we maintain that the emotions traditionally called “basic” should still be seen as a distinct set of emotions by virtue of their being constitutive for other, derived emotions. In conclusion we argue for moving beyond the strict empiricist approach proposed by Kagan and many thinkers before him.
The effectiveness of health communication strategies in health education in Kushima, Japan
Authors: Ebina Ryoko , Kawasaki Fumiko , Taniguchi Izumi , Togari Taisuke , Yamazaki Yoshihiko , Sparks Michael
Published: March 2010

Japan’s 2008 health policy focuses more than ever on health education for behaviour change and outcome measures for physical health status. This is at odds with contemporary health promotion and health education, which frame health as a resource for everyday life and indicate that the evaluation of interventions should measure broader aspects of health rather than just physical aspects. The application of a combination of different health communication models and theories allows for a customized approach, depending on the types of change that are being sought, and can lead to increased relevance as well as a better fit when it comes to evaluating the achievement of broad health promotion goals. This article explores the application of the Outcome Model for Health Promotion to a two-year health education intervention in Kushima, Japan. This model measures program effectiveness from four aspects: physical health outcomes; intermediate health outcomes; health promotion outcomes; and health promotion actions. A quantitative and qualitative longitudinal, mixed model study design and methods were used for the analysis. Data was taken from health exams, structured interviews, and participant observations collected from 67 participants at four times over two years. This intervention relied primarily on health education and communication to achieve mental and social health outcomes more significantly and faster than physical health outcomes. The importance of moving outcome measurement beyond direct health achievements is discussed in light of the relationships between physical, mental, and social health and its determinants, and our results. (Global Health Promotion, 2010; 17 (1): pp. 5—15)
The uncompassionate elements of the Compassionate Care Benefits Program: a critical analysis
Authors: Flagler Jenny , Weizhen Dong
Published: March 2010

Palliative care is a heavy burden to many Canadians who have dying relatives or friends. The Canadian government implemented a sub-program under the Employment Insurance — Compassionate Care Benefits Program (CCBs) to financially assist informal end-of-life caregivers (1). Since the current Employment Insurance Program’s regulations pose a number of barriers for non-standard employees, many informal caregivers are automatically excluded from its sub-program; the CCBs program. This is especially true for those who belong to disadvantaged social groups, and women. This article explores whether a program designed as part of Employment Insurance can provide comprehensive support to those informal end-of-life care-givers, and whether it is equally accessible to all Canadians. The authors argue that, in order to make the CCBs program effective, it needs to be made independent from Canada’s Employment Insurance Program and hence become a true compassionate program that supports all the informal caregivers equally. (Global Health Promotion, 2010; 17(1): pp. 50—59)
BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia
Authors: van Galen Joost C. , Kuiper Roland P. , van Emst Liesbeth , Levers Marloes , Tijchon Esther , Scheijen Blanca , Waanders Esmé , van Reijmersdal Simon V. , Gilissen Christian , van Kessel Ad Geurts , Hoogerbrugge Peter M. , van Leeuwen Frank N.
Published: March 2010

Resistance to glucocorticoids (GCs) is a major clinical problem in the treatment of acute lymphoblastic leukemia (ALL), but the underlying mechanisms are not well understood. Although mutations in the glucocorticoid receptor (GR) gene can give rise to therapy resistance in vitro, acquired somatic mutations in the GR are rarely encountered in patients. Here we report that the protein encoded by the BTG1 gene, which is frequently deleted in (pediatric) ALL, is a key determinant of GC responsiveness. Using RNA interference, we show that loss of BTG1 expression causes GC resistance both by decimating GR expression and by controlling GR-mediated transcription. Conversely, reexpression of BTG1 restores GC sensitivity by potentiating GC-induced GR expression, a phenomenon known as GR autoinduction. In addition, the arginine methyltransferase PRMT1, a BTG1-binding partner and transcriptional coactivator, is recruited to the GR gene promoter in a BTG1-dependent manner. These results implicate the BTG1/PRMT1 complex in GR-mediated gene expression and reveal that deregulation of a nuclear receptor coactivator complex can give rise to GC resistance. Further characterization of this complex as part of the GR regulatory circuitry could offer novel opportunities for improving the efficacy of GC-based therapies in ALL and other hematologic malignancies.
The importance of vicinal cysteines, C1669 and C1670, for von Willebrand factor A2 domain function
Authors: Luken Brenda M. , Winn Luke Y. N. , Emsley Jonas , Lane David A. , Crawley James T. B.
Published: March 2010

The von Willebrand factor (VWF) A2 crystal structure has revealed the presence of a rare vicinal disulfide bond between C1669 and C1670, predicted to influence domain unfolding required for proteolysis by ADAMTS13. We prepared VWF A2 domain fragments with (A2-VicCC, residues 1473-1670) and without the vicinal disulfide bond (A2-ΔCC, residues 1473-1668). Compared with A2-ΔCC, A2-VicCC exhibited impaired proteolysis and also reduced binding to ADAMTS13. Circular dichroism studies revealed that A2-VicCC was more resistant to thermal unfolding than A2-ΔCC. Mutagenesis of C1669/C1670 in full-length VWF resulted in markedly increased susceptibility to cleavage by ADAMTS13, confirming the important role of the paired vicinal cysteines in VWF A2 domain stabilization.
High frequency of lactose intolerance in a prehistoric hunter-gatherer population in northern Europe
Authors: Malmström Helena , Linderholm Anna , Lidén Kerstin , Storå Jan , Molnar Petra , Holmlund Gunilla , Jakobsson Mattias , Götherström Anders
Published: March 2010

Background

Genes and culture are believed to interact, but it has been difficult to find direct evidence for the process. One candidate example that has been put forward is lactase persistence in adulthood, i.e. the ability to continue digesting the milk sugar lactose after childhood, facilitating the consumption of raw milk. This genetic trait is believed to have evolved within a short time period and to be related with the emergence of sedentary agriculture.

Results

Here we investigate the frequency of an allele (-13910*T) associated with lactase persistence in a Neolithic Scandinavian population. From the 14 individuals originally examined, 10 yielded reliable results. We find that the T allele frequency was very low (5%) in this Middle Neolithic hunter-gatherer population, and that the frequency is dramatically different from the extant Swedish population (74%).

Conclusions

We conclude that this difference in frequency could not have arisen by genetic drift and is either due to selection or, more likely, replacement of hunter-gatherer populations by sedentary agriculturalists.
Evaluation of the hyplex® TBC PCR test for detection of Mycobacterium tuberculosis complex in clinical samples
Authors: Hofmann-Thiel Sabine , Turaev Laziz , Hoffmann Harald
Published: March 2010

Background

Tuberculosis (TB) is one of the major public health concerns worldwide. The detection of the pathogen Mycobacterium tuberculosis complex (MTBC) as early as possible has a great impact on the effective control of the spread of the disease. In our study, we evaluated the hyplex® TBC PCR test (BAG Health Care GmbH), a novel assay using a nucleic acid amplification technique (NAAT) with reverse hybridisation and ELISA read out for the rapid detection of M. tuberculosis directly in clinical samples.

Results

A total of 581 respiratory and non-respiratory specimens from our pneumological hospital and the National TB Institute of Uzbekistan were used for the evaluation of the PCR assay. Of these, 292 were classified as TB samples and 289 as non-TB samples based on the results of the TB cultures as reference method. The PCR results were initially used to optimise the cut-off value of the hyplex® TBC test system by means of a ROC analysis. The overall sensitivity of the assay was determined to be 83.1%. In smear-positive TB samples, the sensitivity of the hyplex® TBC PCR test was estimated to 93.4% versus 45.1% in smear-negative samples. The specificity of the test was 99.25%. Of the two specimens (0.75%) with false-positive PCR results, one yielded a culture positive for non-tuberculous mycobacteria. Based on the assumption of a prevalence of 8% TB positives among the samples in our diagnostic TB laboratory, the positive and negative predictive values were estimated to 90.4% and 98.5%, respectively.

Conclusions

The hyplex® TBC PCR test is an accurate NAAT assay for a rapid and reliable detection of M. tuberculosis in various respiratory and non-respiratory specimens. Compared to many other conventional NAAT assays, the hyplex® TBC PCR test is in a low price segment which makes it an attractive option for developing and emerging countries with high TB burdens.
A full-length enriched cDNA library and expressed sequence tag analysis of the parasitic weed, Striga hermonthica
Authors: Yoshida Satoko , Ishida Juliane K , Kamal Nasrein M , Ali Abdelbagi M , Namba Shigetou , Shirasu Ken
Published: March 2010

Background

The obligate parasitic plant witchweed (Striga hermonthica) infects major cereal crops such as sorghum, maize, and millet, and is the most devastating weed pest in Africa. An understanding of the nature of its parasitism would contribute to the development of more sophisticated management methods. However, the molecular and genomic resources currently available for the study of S. hermonthica are limited.

Results

We constructed a full-length enriched cDNA library of S. hermonthica, sequenced 37,710 clones from the library, and obtained 67,814 expressed sequence tag (EST) sequences. The ESTs were assembled into 17,317 unigenes that included 10,319 contigs and 6,818 singletons. The S. hermonthica unigene dataset was subjected to a comparative analysis with other plant genomes or ESTs. Approximately 80% of the unigenes have homologs in other dicotyledonous plants including Arabidopsis, poplar, and grape. We found that 589 unigenes are conserved in the hemiparasitic Triphysaria species but not in other plant species. These are good candidates for genes specifically involved in plant parasitism. Furthermore, we found 1,445 putative simple sequence repeats (SSRs) in the S. hermonthica unigene dataset. We tested 64 pairs of PCR primers flanking the SSRs to develop genetic markers for the detection of polymorphisms. Most primer sets amplified polymorphicbands from individual plants collected at a single location, indicating high genetic diversity in S. hermonthica. We selected 10 primer pairs to analyze S. hermonthica harvested in the field from different host species and geographic locations. A clustering analysis suggests that genetic distances are not correlated with host specificity.

Conclusions

Our data provide the first extensive set of molecular resources for studying S. hermonthica, and include EST sequences, a comparative analysis with other plant genomes, and useful genetic markers. All the data are stored in a web-based database and freely available. These resources will be useful for genome annotation, gene discovery, functional analysis, molecular breeding, epidemiological studies, and studies of plant evolution.
Metastatic lymph node in gastric cancer; Is it a real distant metastasis?
Authors: Lim Do Hyoung , Kim Hyeong Su , Park Young Suk , Lee Jeeyun , Park Se Hoon , Lim Ho Yeong , Ji Sang Hoon , Park Min Jae , Yi Seong Yoon , An Ji Yeong , Sohn Tae Sung , Noh Jae Hyoung , Bae Jae Moon , Kim Sung , Park Cheol Keun , Kang Won Ki
Published: March 2010

Background

Currently, the TNM staging system is a widely accepted method for assessing the prognosis of the disease and planning therapeutic strategies for cancer. Of the TNM system, the extent of lymph node involvement is the most important independent prognostic factor for gastric cancer. The aim of our study is to evaluate the survival and prognosis of gastric cancer patients with LN#12 or #13 involvement only and to assess the impact of anatomic regions of primary gastric tumor on survival in this particular subset of patients.

Methods

Among data of 1,008 stage IV gastric cancer patients who received curative R0 gastrectomy, a total of 79 patients with LN#12 (n = 68) and/or #13 (n = 11) were identified. All patients performed gastrectomy with D2 or D3 lymph node dissection.

Results

In 79 patients with LN#12/13 involvement, the estimated one-, three- and five-year survival rate was 77.2%, 41.8% and 26.6% respectively. When we compared the patients with LN#12/13 involvement to those without involvement, there was no significant difference in OS (21.0 months vs. 25.0 months, respectively; P = 0.140). However, OS was significantly longer in patients with LN#12/13 involvement only than in those with M1 lymph node involvement (14.3 months; P = 0.001). There was a significant difference in survival according to anatomic locations of the primary tumor (lower to mid-body vs. high body or whole stomach): 26.5 vs. 9.2 months (P = 0.009). In Cox proportional hazard analysis, only N stage (p = 0.002) had significance to predict poor survival.

Conclusion

In this study we found that curatively resected gastric cancer patients with pathologic involvement of LN #12 and/or LN #13 had favorable survival outcome, especially those with primary tumor location of mid-body to antrum. Prospective analysis of survival in gastric cancer patients with L N#12 or #13 metastasis is warranted especially with regards to primary tumor location.
Contraception for adolescents with lupus
Authors: Tesher Melissa S , Whitaker Amy , Gilliam Melissa , Wagner-Weiner Linda , Onel Karen B
Published: March 2010

Sexually active adolescents, including young women with lupus, are at high risk for unplanned pregnancy. Unplanned pregnancy among teens with lupus is associated with an elevated risk of poor maternal and fetal outcomes. The provision of effective contraception is a crucial element of care for a sexually-active young woman with lupus. Unfortunately, providers may be hesitant to prescribe contraception to this group due to concerns about increasing the risk of lupus complications. This article reviews the risks and benefits of currently-available contraceptives for young women with lupus. Providers are encouraged to consider long-term, highly-effective contraception, such as implantables and intrauterine devices, for appropriately selected adolescents with lupus.
Transient Receptor Potential Vanilloid 1 is Essential for Cisplatin-Induced Heat Hyperalgesia in Mice
Authors: Ta Lauren E , Bieber Allan J , Carlton Susan M , Loprinzi Charles L , Low Philip A , Windebank Anthony J
Published: March 2010

Background:

Cisplatin is primarily used for treatment of ovarian and testicular cancer. Oxaliplatin is the only effective treatment for metastatic colorectal cancer. Both are known to cause dose related, cumulative toxic effects on the peripheral nervous system and thirty to forty percent of cancer patients receiving these agents experience painful peripheral neuropathy. The mechanisms underlying painful platinum-induced neuropathy remain poorly understood. Previous studies have demonstrated important roles for TRPV1, TRPM8, and TRPA1 in inflammation and nerve injury induced pain.

Results:

In this study, using real-time, reverse transcriptase, polymerase chain reaction (RT-PCR), we analyzed the expression of TRPV1, TRPM8, and TRPA1 induced by cisplatin or oxaliplatin in vitro and in vivo. For in vitro studies, cultured E15 rat dorsal root ganglion (DRG) neurons were treated for up to 48 hours with cisplatin or oxaliplatin. For in vivo studies, trigeminal ganglia (TG) were isolated from mice treated with platinum drugs for three weeks. We show that cisplatin and oxaliplatin-treated DRG neurons had significantly increased in TRPV1, TRPA1, and TRPM8 mRNA expression. TG neurons from cisplatin treated mice had significant increases in TRPV1 and TRPA1 mRNA expression while oxaliplatin strongly induced only TRPA1. Furthermore, compared to the cisplatin-treated wild-type mice, cisplatin-treated TRPV1-null mice developed mechanical allodynia but did not exhibit enhancement of noxious heat- evoked pain responses. Immunohistochemistry studies showed that cisplatin-treated mice had no change in the proportion of the TRPV1 immunopositive TG neurons.

Conclusion:

These results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRPV1 has a crucial role in cisplatin-induced thermal hyperalgesia in vivo.
Thermodynamic quantities and Urmia Sea water evaporation
Authors: Heidari Nosrat , Roudgar Mina , Ebrahimpour Neda
Published: March 2010

The relation between climatic parameters (relative air humidity) and the water activity of the Urmia Sea water determines the possible maximum evaporation of the lake. Using the Pitzer thermodynamic approach, the activity of the Urmia Lake water during evaporation was calculated and compared to the present relative air humidity above the water. Present climatic conditions allow the Urmia Sea water to evaporate down to water with activity of 0.55, corresponding to the lowest air humidity measured over the lake. This water activity falls in the range of halite precipitation, while carnalite precipitation starts at somewhat lower (a H2O = 0.499) point. Our dynamic model predicts that for air humidity as low as 55% (reflecting present climate conditions), the Urmia Sea level may drop to as low as 1270 m (i. e., 1270 m above mean sea level). At that point, the lake water volume will have a volume of 11 km3. For the sake of comparison, at the beginning of 1990, the level of the lake was 1275 m, its volume was 25 km3, and its surface area was 5145 km2.
Peripheral and gastrointestinal immune systems of healthy cattle raised outdoors at pasture or indoors on a concentrate-based ration
Authors: Lejeune Alexandre , Monahan Frank J , Moloney Aidan P , Earley Bernadette , Black Alistair D , Campion Deirdre P , Englishby Tanya , Reilly Petrina , O'Doherty John , Sweeney Torres
Published: March 2010

Background

Despite an increasing preference of consumers for beef produced from more extensive pasture-based production systems and potential human health benefits from the consumption of such beef, data regarding the health status of animals raised on pasture are limited. The objective of this study was to characterise specific aspects of the bovine peripheral and the gastrointestinal muscosal immune systems of cattle raised on an outdoor pasture system in comparison to animals raised on a conventional intensive indoor concentrate-based system.

Results

A number ofin vitrofunctional tests of immune cells suggested subtle differences between the animals on the outdoor versus indoor production systems. There was a decrease in the number of neutrophils and monocytes engaged in phagocytosis in outdoor cattle (P< 0.01 andP< 0.05, respectively) in comparison to those indoors. Following mitogen stimulation, a lower level of interferon-γ was produced in leukocytes from the outdoor animals (P< 0.05). There was evidence of a gastrointestinal nematode infection in the outdoor animals with elevated levels of serum pepsinogen (P< 0.001), a higher number of eosinophils (P< 0.05) and a higher level of interleukin-4 and stem cell factor mRNA expression (P< 0.05) in the outdoor animals in comparison to the indoor animals. Lower levels of copper and iodine were measured in the outdoor animals in comparison to indoor animals (P< 0.001).

Conclusion

Despite distinctly contrasting production systems, only subtle differences were identified in the peripheral immune parameters measured between cattle raised at pasture in comparison to animals raised on a conventional intensive indoor concentrate-based production system.
Outcomes of occasional cannabis use in adolescence: 10-year follow-up study in Victoria, Australia
Authors: Degenhardt Louisa , Coffey Carolyn , Carlin John B. , Swift Wendy , Moore Elya , Patton George C.
Published: March 2010

Background

Regular adolescent cannabis use predicts a range of later drug use and psychosocial problems. Little is known about whether occasional cannabis use carries similar risks.

Aims

To examine associations between occasional cannabis use during adolescence and psychosocial and drug use outcomes in young adulthood; and modification of these associations according to the trajectory of cannabis use between adolescence and age 20 years, and other potential risk factors.

Method

A 10-year eight-wave cohort study of a representative sample of 1943 secondary school students followed from 14.9 years to 24 years.

Results

Occasional adolescent cannabis users who continued occasional use into early adulthood had higher risks of later alcohol and tobacco dependence and illicit drug use, as well as being less likely to complete a post-secondary qualification than non-users. Those using cannabis at least weekly either during adolescence or at age 20 were at highest risk of drug use problems in young adulthood. Adjustment for smoking in adolescence reduced the association with later educational achievement, but associations with drug use problems remained.

Conclusions

Occasional adolescent cannabis use predicts later drug use and educational problems. Partial mediation by tobacco use raises a possibility that differential peer affiliation may play a role.
Autism, ethnicity and maternal immigration
Authors: Keen D. V. , Reid F. D. , Arnone D.
Published: March 2010

Background

A growing number of European studies, particularly from Nordic countries, suggest an increased frequency of autism in children of immigrant parents. In contrast, North American studies tend to conclude that neither maternal ethnicity nor immigrant status are related to the rate of autism-spectrum disorders.

Aims

To examine the hypotheses that maternal ethnicity and/or immigration are linked to the rate of childhood autism-spectrum disorders.

Method

Retrospective case-note analysis of all 428 children diagnosed with autism-spectrum disorders presenting to the child development services in two centres during a 6-year period.

Results

Mothers born outside Europe had a significantly higher risk of having a child with an autism-spectrum disorder compared with those born in the UK, with the highest risk observed for the Caribbean group (relative risks (RRs) in the two centres: RR = 10.01, 95% CI 5.53–18.1 and RR = 8.89, 95% CI 5.08–15.5). Mothers of Black ethnicity had a significantly higher risk compared with White mothers (RR = 8.28, 95% CI 5.41–12.7 and RR = 3.84, 95% CI 2.93–5.02). Analysis of ethnicity and immigration factors together suggests the increased risk is predominately related to immigration.

Conclusions

Maternal immigration is associated with substantial increased risk of autism-spectrum disorders with differential risk according to different region of birth and possibly ethnicity.
Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk
Authors: Owens David Cunningham , Johnstone Eve C. , Miller Patrick , Macmillan J. Fiona , Crow Timothy J.
Published: March 2010

Background

The nature of the relationship between duration of the pre-diagnostic interval in schizophrenia and better outcomes remains unclear.

Aims

To re-examine data from one of the earliest studies suggesting an association between long pre-treatment interval and compromised outcome, assessing the relationship between symptomatic and social variables and increased relapse risk at 1 year.

Method

Symptomatic, social and demographic data from participants in the Northwick Park Study of First Episodes who completed 12-month follow-up (n= 101) were re-analysed in the context of duration of untreated illness (DUI).

Results

At admission, those with long DUI were more likely to have lower scores on tension derived from the Present State Examination, exhibited more behaviour threatening to others and more bizarre behaviour, were more likely to be single, to live alone or dependently, to be unemployed and to have experienced more adverse life events prior to admission. Logistic regression showed that diminished tension, bizarre behaviour and unemployed status independently increased the risk of relapse, bizarre behaviour making the single biggest contribution. Tension did not remain significant with log-transformation of data.

Conclusions

Findings are consistent with the conclusion that long DUI can reflect characteristics of the psychosis itself rather than delay in treatment.
Cost-effectiveness of a stepped care intervention to prevent
depression and anxiety in late life: randomised trial
Authors: van't Veer-Tazelaar Petronella , Smit Filip , van Hout Hein , van Oppen Patricia , van der Horst Henriette , Beekman Aartjan , van Marwijk Harm
Published: March 2010

Background

There is an urgent need for the development of cost-effective preventive
strategies to reduce the onset of mental disorders.

Aims

To establish the cost-effectiveness of a stepped care preventive
intervention for depression and anxiety disorders in older people at high
risk of these conditions, compared with routine primary care.

Method

An economic evaluation was conducted alongside a pragmatic randomised
controlled trial (ISRCTN26474556). Consenting individuals presenting with
subthreshold levels of depressive or anxiety symptoms were randomly
assigned to a preventive stepped care programme (n = 86)
or to routine primary care (n = 84).

Results

The intervention was successful in halving the incidence rate of
depression and anxiety at €563 (£412) per recipient and €4367 (£3196) per
disorder-free year gained, compared with routine primary care. The latter
would represent good value for money if the willingness to pay for a
disorder-free year is at least €5000.

Conclusions

The prevention programme generated depression- and anxiety-free survival
years in the older population at affordable cost.
Utility of computerised cognitive–behavioural therapy for
depression
Authors: Andrews Gavin
Published: March 2010

A recent study found that people with depression identified in the
community recovered equally well given unsupported computerised
cognitive–behavioural therapy (CBT), general practitioner treatment or a
combination of the two, even if they did not comply. The results are
different from those reported elsewhere. Could natural remission explain
the finding?
Use of psychotropic medication in seven English psychiatric intensive care units
Authors: Brown Steve , Chhina Navjyoat , Dye Stephen
Published: March 2010

Aims and method

To describe the psychotropic medication given to 332 patients admitted consecutively to seven English psychiatric intensive care units (PICUs) by prospective, multicentre case-note analysis.

Results

Overall, 104 (32%) patients received rapid tranquillisation or zuclopenthixol acetate by intramuscular injection; 72 (23%) received more than one regular antipsychotic drug simultaneously. It was reported that 20 patients received high-dose antipsychotic medication, which was probably an underestimate. The use of these interventions varied significantly between different units.

Clinical implications

Potentially risky treatments such as forcible intramuscular medication are a standard part of PICU activity. Further work is needed to clarify the reasons behind the differences in prescribing practices between different PICUs.
New Ways of Working is dead, long live New Ways of Working! Revised joint guidance on the employment of consultant psychiatrists
Authors: Clark Andrew
Published: March 2010

In 2005 the Royal College of Psychiatrists, the NHS Confederation, the National Institute for Mental Health in England and the Department of Health jointly produced the first edition of the Joint Guidance on the Employment of Consultant Psychiatrists. This was integral to the New Ways of Working initiative and outline different professional roles within mental health services. Four years on the document has been extensively revised. The new 2009 edition emphasises achieving viable and satisfying consultant posts through effective job planning and good team functioning. It also contains guidance on recruitment processes with useful examples of templates, flowcharts and good practices.
Reading about deception
Authors: Spence Sean A.
Published: March 2010

Deception is commonplace and a discipline such as psychiatry, so often reliant upon subjective accounts, may be susceptible to its effects (especially in the fields of military, liaison, medico-legal and forensic practice). However, psychiatric trainees receive little formal teaching on the subject of medical deceit. Here, I review some recent books on deception, emphasising those works that cast tangential light upon everyday psychiatric practice. Useful sources of reference include those concerning the philosophy of deceit, the recent rise of political lying and the clinical problem of feigned illness. A clinically helpful distinction emerges: that between truth (accuracy) and truthfulness (sincerity).
A Heterozygous Mutation of the Insulin-Like Growth Factor-I Receptor Causes Retention of the Nascent Protein in the Endoplasmic Reticulum and Results in Intrauterine and Postnatal Growth Retardation
Authors: Wallborn Tillmann , Wüller Stefan , Klammt Jürgen , Kruis Tassilo , Kratzsch Jürgen , Schmidt Gabriele , Schlicke Marina , Müller Eva , Schmitz van de Leur Hildegard , Kiess Wieland , Pfäffle Roland
Published: March 2010

Background: Mutations in the IGF-I receptor (IGF1R) gene can be responsible for intrauterine and postnatal growth disorders.

Objective: Here we report on a novel mutation in the IGF1R gene in a female patient. The aim of our study was to analyze the functional impact of this mutation.

Patient: At birth, the girl’s length was 47 cm [−1.82 sd score (SDS)], and her weight was 2250 g (−2.26 SDS). Clinical examination revealed microcephaly and retarded cognitive development. She showed no postnatal catch-up growth but had relatively high IGF-I levels (+1.83 to +2.17 SDS).

Results: Denaturing HPLC screening and direct DNA sequencing disclosed a heterozygous missense mutation resulting in an amino acid exchange from valine to glutamic acid at position 599 (V599E-IGF1R). Using various cell systems, we found that the V599E-IGF1R mutant was not tyrosine phosphorylated and had an impaired downstream signaling in the presence of IGF-I. Flow cytometry and live cell confocal laser scanning microscopy revealed a lack of cell surface expression due to an extensive retention of V599E-IGF1R proteins within the endoplasmic reticulum.

Conclusion: The V599E-IGF1R mutation interferes with the receptor’s trafficking path, thereby abrogating proreceptor processing and plasma membrane localization. Diminished cell surface receptor density solely expressed from the patient’s wild-type allele is supposed to lead to insufficient IGF-I signaling. We hypothesize that this mechanism results in intrauterine and postnatal growth retardation of the affected patient. The reported retention of the nascent IGF1R in the endoplasmic reticulum presents a novel mechanism of IGF-I resistance.
The role of insulin/IGF-like signaling in C. elegans longevity and aging
Authors: Kaletsky Rachel , Murphy Coleen T.
Published: March 2010

Aging is characterized by general physiological decline over time. A hallmark of human senescence is the onset of various age-related afflictions including neurodegeneration, cardiovascular disease and cancer. Although environmental and stochastic factors undoubtedly contribute to the increased incidence of disease with age, recent studies suggest that intrinsic genetic determinants govern both life span and overall health. Current aging research aims at achieving the ‘longevity dividend’, in which life span extension in humans is accomplished with a concomitant increase in the quality of life (Olshansky et al., 2007). Significant progress has been made using model organisms, especially the nematode worm Caenorhabditis elegans, to delineate the genetic and biochemical pathways involved in aging to identify strategies for therapeutic intervention in humans. In this review, we discuss how C. elegans has contributed to our understanding of insulin signaling and aging.