bluuebunny/crossref_metadata_2025_split huggingface dataset:
Female choice by electric pulse duration: attractiveness of the males'communication signal assessed by female bulldog fish,Marcusenius pongolensis(Mormyridae, Teleostei)
Authors: Machnik Peter , Kramer Bernd 
Published: May 2008

SUMMARYIn adult males of the South African weakly electric bulldog fish, Marcusenius pongolensis, the duration of the electric organ discharge(EOD) increases with body size over lifetime. Although there is experimental support for intrasexual selection (male–male competition) having shaped the males' EOD pulse duration in evolution, nothing is known about intersexual selection, such as female choice. Playback of 25 natural male EODs of pulse duration varying from 320 μs (close to the average female value) to 716μs, to eight female experimental subjects elicited approach, head butts and circling behaviour. The rate of head butts on the dipole electrode model increased significantly with stimulus pulse duration in seven out of eight experimental subjects. In ten experimental female subjects we contrasted the shortest playback pulse with simultaneous playback of one of four longer ones(424, 524, 628 and 716 μs). Pooled responses for all experimental subjects were stronger for the dipole playing back the longer pulse in a pulse pair. The difference in the number of head butts (Δhead butts) that were dealt the two dipoles per 60 s test session increased significantly with the difference in pulse duration (Δpulse duration). The increase followed a significant linear trend (P&lt;0.0001). Similar results were obtained for Δassociation time, Δcircles with head butts, andΔcircles without head butts. These results suggest that a male's reproductive success is enhanced by longer, i.e. more attractive EODs, and that both intra- and intersexual selection must have played a significant role in shaping the EOD of male M. pongolensis.
Slow desiccation improves dehydration tolerance and accumulation of compatible osmolytes in earthworm cocoons (Dendrobaena octaedraSavigny)
Authors: Petersen Christina R. , Holmstrup Martin , Malmendal Anders , Bayley Mark , Overgaard Johannes 
Published: May 2008

SUMMARYThe earthworm, Dendrobaena octaedra, is a common species in temperate and subarctic regions of the northern hemisphere. The egg capsules(`cocoons') of D. octaedra are deposited in the upper soil layers where they may be exposed to desiccation. Many previous studies on desiccation tolerance in soil invertebrates have examined acute exposure to harsh desiccating conditions, however, these animals are often more likely to be exposed to a gradually increasing drought stress. In the present study we slowly desiccated D. octaedra cocoons to simulate ecologically realistic drought conditions and the results clearly demonstrate that gradually dehydrated cocoons show an increased tolerance of extreme drought compared with acutely dehydrated cocoons. NMR spectroscopic analysis of compatible osmolytes revealed the presence of sorbitol, glucose, betaine,alanine and mannitol in dehydrated embryos. The superior drought survival of gradually desiccated embryos could partly be attributed to a higher accumulation of osmolytes (especially sorbitol). Thus, gradually and acutely desiccated embryos accumulated ∼2 mol l–1 and 1 mol l–1 total osmolytes, respectively. However, in addition to osmolyte accumulation, the gradually desiccated cocoons also tolerated a higher degree of water loss, demonstrating that gradually dehydrated D. octaedra cocoons are able to survive loss of ∼95% of the original water content. Although D. octaedra embryos can probably not be categorized as a truly anhydrobiotic organism we propose that they belong in a transition zone between the desiccation sensitive and the truly anhydrobiotic organisms. Clearly, these earthworm embryos share many physiological traits with anhydrobiotic organisms.
Redundancy of olfactory sensory pathways for odor-aversion memory in the terrestrial slug Limax valentianus
Authors: Yamagishi Miki , Ito Etsuro , Matsuo Ryota 
Published: May 2008

SUMMARY
Terrestrial slugs have the ability to learn and remember a food odor paired with an aversive stimulus. Olfaction in slugs involves the tips of two pairs of tentacles, the superior and the inferior tentacles. Sensory nerves in both pairs of the tentacles transmit olfactory information to the structure in the CNS, the procerebrum where learning and memory formation occur. We investigated the role of each pair of tentacles in odor-aversion learning, and examined the ability of slugs to recall memory after selective surgical amputation. Our results show that memory formation was not altered by the amputation of either one of the pairs before or after odor-aversion learning,while the odor sensibility of the slugs was maintained. These data suggest that either pair of tentacles is sufficient for the acquisition and retrieval of aversive olfactory memory.
Media influence on Herceptin subsidization in Australia: application of the rule of rescue?
Authors: MacKenzie Ross , Chapman Simon , Salkeld Glenn , Holding Simon 
Published: May 2008

Summary Background In August 2006, the Australian government announced that Herceptin (Trastuzumab) would be added to the national Pharmaceutical Benefits Scheme (PBS) of government-subsidized drugs, for treatment with adjuvant chemotherapy of HER2 breast cancer. Following initial reticence, the health minister responded to a campaign by patients and patient advocacy groups by announcing PBS subsidization which lowered the cost of a weekly dose from A$1000 to A$30. The cost to the government would be A$470 million over three years for treatment of an estimated 2100 women annually. Design We analysed the news frames used in all direct and attributed statements ( n=239) in television news coverage of the discourse preceding the Herceptin decision by the Australian government. Setting Five Sydney free-to-air channels between October 2005 and August 2006. Main outcome measures News frames or themes. Results Of five news frames identified, one (‘desperate, sick women in double jeopardy because of callous government/incompetent bureaucracy’) accounted for 54% of all reported statements. Government financial parsimony was framed as responsible for the women's plight, with drug industry pricing never mentioned. Claimed benefits of Herceptin often conflated cancer non-recurrence and survival and favoured quantification rhetoric which emphasized percentage increases in improvement rather than the more modest increases in absolute survival. Conclusions News frames invoking key tenets of the ‘rule of rescue’ dominated television discourse on Herceptin. Clinicians, patients, their families and patient advocacy groups invoking the rule of rescue can increase the likelihood of achieving their objective of gaining access to expensive healthcare such as pharmaceuticals. Rational, criteria-based public health policy will find it hard to resist the rule of rescue imperative.
Setting up non-commercial clinical trials takes too long in the UK: findings from a prospective study
Authors: Hackshaw Allan , Farrant Hannah , Bulley Sue , Seckl Michael J , Ledermann Jonathan A 
Published: May 2008

Summary Objective To evaluate the specific components of setting up a simple multicentre clinical study four years after the new UK law on clinical trials was implemented in 2004. Design Timelines associated with activating a randomized multicentre trial in lung cancer patients using an investigational medicinal product (statins) were prospectively recorded. Setting 84 trial centres in the UK. Main outcome measures The time taken to go through the three stages necessary to activate a trial at a centre was examined: that is, the time from when Site Specific Information was electronically transferred to a participating centre until local research ethics committee (LREC) or research and development (R&D) approvals were obtained, and a signed Clinical Trials Site Agreement (CTSA) was received. Results It took at least six months to obtain LREC approval in 21% of centres and R&D approval in 52% of centres. Twelve centres (14%) took at least 12 months to obtain R&D approval. 31% of centres took at least three months to return a signed CTSA. Although 52% of centres took at least six months to be activated, 13% were able to complete all three stages in two months or less. Conclusions While some centres can activate trials relatively quickly, there is considerable variation the time taken to set up a trial, much of which is due to the delay in obtaining R&D approval. This is having a major adverse effect on UK health research. There is a national need to streamline the process for considering multi-centre non-commercial clinical trials, in particular, having fixed timelines for R&D assessment. Without this, the costs of trials will increase because of extended duration, and the time to answer a research question and alter clinical practice will be significantly prolonged.
Ciceronian and Hermogenean Influences on George of Trebizond's Rhetoricorum Libri V
Authors: Montefusco Lucia Calboli 
Published: May 2008

Abstract
Giorgio Trebisonda era un emigrante Greco che già nel suo paese aveva imparato molto bene la grammatica e la retorica. Arrivò a Venezia molto giovane per lavorare nella biblioteca di Francesco Barbaro e passò gran parte della sua vita in Italia insegnando. Nell'ultimo libro del suo manuale, Rhetoricorum Libri V, egli, dedicando un'attenzione particolare all'elocutio, elabora un insieme molto interessante di precetti, intrecciando la teoria degli stili con la dottrina ermogenea delle ιδεαι fino ad allora sconosciuta agli autori di manuali latini. Giorgio Trebisonda aveva già trattato brevemente questa questione, una prima volta, in una lettera indirizzata al suo maestro Vittorino da Feltre e concernente esplicitamente i genera dicendi, una seconda volta, in una lunga lettera mandata a Girolamo Bragadin per dargli consigli su come ottenere la suavitas dicendi. Lamentando di non potere fare riferimento a fonti latine e di conseguenza di trovarsi nella duplice difficoltà di dovere tradurre in latino la terminologia specifica della dottrina Ermogenea e di dovere trovare esempi latini per illustrarla, Giorgio Trebisonda cerca di superare questa difficoltà sostituendo a Demostene, l'autore paradigmatico in Ermogene, Cicerone, dalle cui opere attinge la maggior parte del materiale che inserisce nella dottrina Ermogenea con un risultato veramente eccezionale.
Subclinical thyroid dysfunction and mortality: an estimate of relative and absolute excess all-cause mortality based on time-to-event data from cohort studies
Authors: Haentjens Patrick , Van Meerhaeghe Alain , Poppe Kris , Velkeniers Brigitte 
Published: May 2008

ObjectivesTo what extent persons with subclinical hyper- or hypothyroidism are more (or less) likely to die than euthyroid control subjects remains a matter of controversy.MethodsWe searched electronic reference databases up to July 31, 2007. Three reviewers independently assessed eligibility. Cohort studies published in full that reported data on the hazard ratio (HR) for mortality from all causes in persons with subclinical thyroid dysfunction versus euthyroid controls were included.ResultsBased on seven cohorts including 290 participants with subclinical hyperthyroidism, random-effects models estimated that the pooled HR for all-cause mortality was 1.41 (95% confidence interval (CI), 1.12–1.79; P=0.004). Using the pooled HR and standard life-table methods applied to a US reference population, we estimated that a white US woman, when diagnosed with subclinical hyperthyroidism at age of 70, has an excess mortality of 1.5, 4.0, and 8.7% at 2, 5, and 10 years respectively after diagnosis. Likewise, a white US man has an excess mortality of 2.3, 5.7, and 10.7%. For the nine cohorts including 1580 participants with subclinical hypothyroidism, observed heterogeneity (Q test P=0.006; I2=63%) disappeared after pooling cohorts in predefined subgroups according to the presence or absence of a comorbid condition. In doing so, the pooled HR for all-cause mortality was 1.03 (95% CI, 0.78–1.35; P=0.83) in cohorts from the community and 1.76 (95% CI, 1.36–2.30; P<0.001) in cohorts of participants with comorbidities (P=0.014 for heterogeneity among study groups).ConclusionsIndividuals with subclinical hyperthyroidism demonstrate a 41% increase in relative mortality from all causes versus euthyroid control subjects. Mathematical modeling suggests that absolute excess mortality after diagnosis might depend on age, with an increase beyond the age of 60, especially in aging men. For patients with subclinical hypothyroidism, the relative risk of all-cause mortality is increased only in patients with comorbid conditions.
Exploring the use of recombinant human TSH in the diagnosis of central hypothyroidism
Authors: Filipsson Helena , Nyström Ernst , Johannsson Gudmundur 
Published: May 2008

ContextThe diagnosis of central hypothyroidism (CH) is often difficult to establish as serum TSH levels may be low, normal, or slightly increased.ObjectiveTo explore the use of recombinant human TSH (rhTSH) in the diagnosis of CH.DesignRandomized single-blind clinical trial.SettingOutpatient clinic of a tertiary care referral center.InterventionA single intramuscular injection of 0.1 and 0.9 mg rhTSH in random order with 1-week interval.ParticipantsEighteen adult patients with pituitary insufficiency and six healthy age-, sex-, and body mass index-matched controls. Six patients had untreated CH (newCH), six had treated CH (CH), and six patients were TSH sufficient (nonCH). Five weeks before TSH stimulation, levothyroxine was replaced with tri-iodothyronine (T3) for 4 weeks. One week before stimulation, treatment was withdrawn.Main outcome measuresThyroid hormones and thyroglobulin (Tg) before and 2, 3½, 7, 24, 48, and 72 h after each injection.ResultsIn the newCH group, basal free thyroxine (FT4) levels were lower than in controls (P<0.05). After 0.9 mg rhTSH, the increases in FT4 and reverse T3 (rT3) were less marked in the newCH group than in controls (FT4±s.e.m. 9.2±0.5 to 19.7±1.2 vs 11.3±0.5 to 27.8.2±2.4 pmol/l, P<0.05). The CH group exhibited reduced basal and stimulated FT4 compared with the TSH-sufficient groups. Tg increased similarly among all study groups after rhTSH injection.ConclusionIn this pilot study, patients with untreated CH had lower response to 0.9 mg rhTSH in FT4 and rT3 than controls. An rhTSH test may be useful in the diagnosis of CH, but further studies are required.
Hypoxia Causes Downregulation of Mismatch Repair System and Genomic Instability in Stem Cells
Authors: Rodríguez-Jiménez Francisco Javier , Moreno-Manzano Victoria , Lucas-Dominguez Rut , Sánchez-Puelles José-María 
Published: May 2008

Abstract
The DNA mismatch repair (MMR) system maintains genomic integrity by correcting replication errors: its malfunction causes genomic instability in several tumor types. Hypoxia-inducible factor-1α (HIF1α), the major regulator of the processes that occur in hypoxia and certain epigenetic events downregulate the expression of MMR genes in cancer cells. However, there is a lack of information regarding MMR regulation and the genetic stability of stem cells under hypoxic conditions. The expression of the MMR system is downregulated in murine and human stem cells cultured in hypoxia, which correlates with lower DNA repair activity in neural stem cells. We observed, through the use of short hairpin loop RNAi expression constructs, that HIF1α positively regulated MLH1 and MSH6 when the C17.2 neural stem cells were exposed to short-term hypoxia. However, in prolonged exposure to oxygen depletion, the reduced transcriptional activation of MMR genes was directed by specific epigenetic events. Chromatin immunoprecipitation experiments showed a hypoacetylated/hypermethylated histone H3 and lower SP1 binding within MLH1 and MSH6 adjacent promoter regions. Treatment with the histone deacetylase inhibitor trichostatin A increased histone H3 acetylation and SP1 occupancy and enhanced MMR expression. Sequencing of microsatellite markers revealed genomic instability in the murine and human stem cells grown under hypoxia. Thus, the present article reports, for the first time in the stem cell field, experimental data that indicate that hypoxic niches are an environment in which stem cells might undergo genomic instability, which could lie at the origin of subpopulations with cancer stem cell properties.
Disclosure of potential conflicts of interest is found at the end of this article.
Diverse Adult Stem Cells Share Specific Higher-Order Patterns of Gene Expression
Authors: Doherty Jason M. , Geske Michael J. , Stappenbeck Thaddeus S. , Mills Jason C. 
Published: May 2008

Abstract
Adult tissue stem cells (SCs) share functional properties regardless of their tissue of residence. It had been thought that SCs might also share expression of certain “stemness” genes, although early investigations for such genes were unsuccessful. Here, we show that SCs from diverse tissues do preferentially express certain types of genes and that SCs resemble other SCs in terms of global gene expression more than they resemble the differentiated cells (DCs) of the tissues that they supply. Genes associated with nuclear function and RNA binding were over-represented in SCs. In contrast, DCs from diverse tissues shared enrichment in genes associated with extracellular space, signal transduction, and the plasma membrane. Further analysis showed that transit-amplifying cells could be distinguished from both SCs and DCs by heightened expression of cell division and DNA repair genes and decreased expression of apoptosis-related genes. This transit-amplifying cell-specific signature was confirmed by de novo generation of a global expression profile of a cell population highly enriched for transit-amplifying cells: colonic crypt-base columnar cells responding to mucosal injury. Thus, progenitor cells preferentially express intracellular or biosynthetic genes, and differentiation correlates with increased expression of genes for interacting with other cells or the microenvironment. The higher-order, Gene Ontology term-based analysis we use to distinguish SC- and DC-associated gene expression patterns can also be used to identify intermediate differentiation states (e.g., that of transit-amplifying cells) and, potentially, any biological state that is reflected in changes in global gene expression patterns.
Disclosure of potential conflicts of interest is found at the end of this article.
Clinical Efficacy of Taxane–Trastuzumab Combination Regimens for HER-2–Positive Metastatic Breast Cancer
Authors: Bullock Karen , Blackwell Kimberly 
Published: May 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Evaluate the results of trials assessing the efficacy of monotherapy and doublet therapy of the taxanes, paclitaxel and docetaxel, plus trastuzumab in HER-2–positive MBC patients.Administer the optimal dosing schedule of taxanes in HER-2–positive MBC patients.Explain the possible benefits and toxicity of using anthracycline-sparing platinum chemotherapy in combination with taxane–trastuzumab therapy for HER-2–positive MBC.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
The taxanes docetaxel (Taxotere®; Sanofi-Aventis U.S. LLC, Bridgewater, NJ) and paclitaxel (Taxol®; Bristol-Myers Squibb, Princeton, NJ) are highly active agents in metastatic breast cancer and may represent a safer alternative to anthracycline-based regimens when combined with the human epidermal growth factor receptor (HER)-2–targeted agent trastuzumab (Herceptin®; Genentech Inc., South San Francisco, CA). A number of preclinical and early clinical studies have evaluated the feasibility, duration, and appropriate dosing schedule(s) for taxane–trastuzumab combinations in HER-2–positive metastatic breast cancer. Preclinical studies of the taxanes in combination with trastuzumab demonstrate synergistic interactions of trastuzumab with docetaxel and additive interactions with paclitaxel. Even though not supported by head-to-head studies, clinical trial results indicate the response rates with docetaxel–trastuzumab combinations may be higher than those with paclitaxel–trastuzumab, although there is a lack of clear crosstrial differences in other clinical benefits. Weekly taxane–trastuzumab regimens have been shown to offer superior disease control. Results from two large, phase III trials that examined the addition of carboplatin to a taxane–trastuzumab doublet did not demonstrate a difference in survival with carboplatin. In one study, the addition of carboplatin to paclitaxel–trastuzumab therapy resulted in a higher response rate and longer progression-free survival time; in the second study, the docetaxel–trastuzumab and docetaxel–trastuzumab–carboplatin combinations were equally effective. Ongoing correlative studies of taxanes, as well as newer formulations such as nanoparticle albumin-bound paclitaxel, in combination with trastuzumab will inform clinical practice regarding the optimal agent, schedule, and use of these highly effective regimens.
Molecular Markers and the Pathogenesis of Adrenocortical Cancer
Authors: Soon Patsy S. H. , McDonald Kerrie L. , Robinson Bruce G. , Sidhu Stan B. 
Published: May 2008

AbstractAdrenal tumors are common, with an estimated incidence of 7.3% in autopsy cases, while adrenocortical carcinomas (ACCs) are rare, with an estimated prevalence of 4–12 per million population. Because the prognoses for adrenocortical adenomas (ACAs) and ACCs are vastly different, it is important to be able to accurately differentiate the two tumor types. Advancement in the understanding of the pathophysiology of ACCs is essential for the development of more sensitive means of diagnosis and treatment, resulting in better clinical outcome. Adrenocortical tumors (ACTs) occur as a component of several hereditary tumor syndromes, which include the Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia 1, Carney complex, and congenital adrenal hyperplasia. The genes involved in these syndromes have also been shown to play a role in the pathogenesis of sporadic ACTs. The adrenocorticotropic hormone–cAMP–protein kinase A and Wnt pathways are also implicated in adrenocortical tumorigenesis. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in adrenocortical tumorigenesis, including results of comparative genomic hybridization, loss of heterozygosity, and microarray gene-expression profiling studies.