bluuebunny/crossref_metadata_2025 huggingface dataset:
Ribonucleotide Reductase Regulation in Response to Genotoxic Stress in Arabidopsis
Authors: Roa Hélène , Lang Julien , Culligan Kevin M. , Keller Murielle , Holec Sarah , Cognat Valérie , Montané Marie-Hélène , Houlné Guy , Chabouté Marie-Edith
Published: July 2009

Ribonucleotide reductase (RNR) is an essential enzyme that provides dNTPs for DNA replication and repair. Arabidopsis (Arabidopsis thaliana) encodes three AtRNR2-like catalytic subunit genes (AtTSO2, AtRNR2A, and AtRNR2B). However, it is currently unclear what role, if any, each gene contributes to the DNA damage response, and in particular how each gene is transcriptionally regulated in response to replication blocks and DNA damage. To address this, we investigated transcriptional changes of 17-d-old Arabidopsis plants (which are enriched in S-phase cells over younger seedlings) in response to the replication-blocking agent hydroxyurea (HU) and to the DNA double-strand break inducer bleomycin (BLM). Here we show that AtRNR2A and AtRNR2B are specifically induced by HU but not by BLM. Early AtRNR2A induction is decreased in an atr mutant, and this induction is likely required for the replicative stress checkpoint since rnr2a mutants are hypersensitive to HU, whereas AtRNR2B induction is abolished in the rad9-rad17 double mutant. In contrast, AtTSO2 transcription is only activated in response to double-strand breaks (BLM), and this activation is dependent upon AtE2Fa. Both TSO2 and E2Fa are likely required for the DNA damage response since tso2 and e2fa mutants are hypersensitive to BLM. Interestingly, TSO2 gene expression is increased in atr versus wild type, possibly due to higher ATM expression in atr. On the other hand, a transient ATR-dependent H4 up-regulation was observed in wild type in response to HU and BLM, perhaps linked to a transient S-phase arrest. Our results therefore suggest that individual RNR2-likecatalytic subunit genes participate in unique aspects of the cellular response to DNA damage in Arabidopsis.
Multiple Sequence Motifs in the Rubisco Small Subunit Transit Peptide Independently Contribute to Toc159-Dependent Import of Proteins into Chloroplasts
Authors: Lee Dong Wook , Lee Sumin , Oh Young Jun , Hwang Inhwan
Published: July 2009

A large number of plastid proteins encoded by the nuclear genome are posttranslationally imported into plastids by at least two distinct mechanisms: the Toc159-dependent and Toc132/Toc120-dependent pathways. Light-induced photosynthetic proteins are imported through the Toc159-dependent pathway, whereas constitutive housekeeping plastid proteins are imported into plastids through the Toc132/Toc120 pathway. However, it remains unknown which features of the plastid protein transit peptide (TP) determine the import pathway. We have discovered sequence elements of the Rubisco small subunit TP (RbcS-tp) that play a role in determining import through the Toc159-dependent pathway in vivo. We generated multiple hybrid mutants using the RbcS-tp and the E1α-subunit of pyruvate dehydrogenase TP (E1α-tp) as representative peptides mediating import through the Toc159-dependent and Toc159-independent pathways, respectively. Import experiments using these hybrid mutants in wild-type and ppi2 mutant protoplasts revealed that multiple sequence motifs in the RbcS-tp independently contribute to Toc159-dependent protein import into chloroplasts. One of these motifs is the group of serine residues located in the N-terminal 12-amino acid segment and the other is the C-terminal T5 region of the RbcS-tp ranging from amino acid positions 41 to 49. Based on these findings, we propose that multiple sequence elements in the RbcS-tp contribute independently to Toc159-dependent import of proteins into chloroplasts.
Integrated Metabolite and Transcript Profiling Identify a Biosynthetic Mechanism for Hispidol in Medicago truncatula Cell Cultures
Authors: Farag Mohamed A. , Deavours Bettina E. , de Fátima Ângelo , Naoumkina Marina , Dixon Richard A. , Sumner Lloyd W.
Published: July 2009

Metabolic profiling of elicited barrel medic (Medicago truncatula) cell cultures using high-performance liquid chromatography coupled to photodiode and mass spectrometry detection revealed the accumulation of the aurone hispidol (6-hydroxy-2-[(4-hydroxyphenyl)methylidene]-1-benzofuran-3-one) as a major response to yeast elicitor. Parallel, large-scale transcriptome profiling indicated that three peroxidases, MtPRX1, MtPRX2, and MtPRX3, were coordinately induced with the accumulation of hispidol. MtPRX1 and MtPRX2 exhibited aurone synthase activity based upon in vitro substrate specificity and product profiles of recombinant proteins expressed in Escherichia coli. Hispidol possessed significant antifungal activity relative to other M. truncatula phenylpropanoids tested but has not been reported in this species before and was not found in differentiated roots in which high levels of the peroxidase transcripts accumulated. We propose that hispidol is formed in cell cultures by metabolic spillover when the pool of its precursor, isoliquiritigenin, builds up as a result of an imbalance between the upstream and downstream segments of the phenylpropanoid pathway, reflecting the plasticity of plant secondary metabolism. The results illustrate that integration of metabolomics and transcriptomics in genetically reprogrammed plant cell cultures is a powerful approach for the discovery of novel bioactive secondary metabolites and the mechanisms underlying their generation.
DICKKOPF‐4 and ‐2 genes are upregulated in human colorectal cancer
Authors: Matsui Akira , Yamaguchi Tatsuya , Maekawa Shinya , Miyazaki Chikako , Takano Shinichi , Uetake Tomoyoshi , Inoue Taisuke , Otaka Masahiko , Otsuka Hiroyuki , Sato Tadashi , Yamashita Atsuya , Takahashi Yuka , Enomoto Nobuyuki
Published: July 2009

To comprehensively screen for genetic events underlying colorectal cancer, we performed suppression subtraction hybridization analysis on an advanced colon cancer. Because Dickkopf‐4, a member of the Dickkopf family acting as a Wnt‐signaling modulator, was identified as one of the upregulated genes in this specimen, we investigated expression profiles of all the Dickkopf family members in 55 colorectal tumors (21 cancers and 34 adenomas). We also investigated mechanisms regulating the expression of Dickkopf‐4 in these cancers in vitro and in vivo. Compared with normal adjacent mucosae, Dickkopf‐4 (median 27.4, P < 0.01) and ‐2 (median 51.4, P < 0.01) were strongly expressed in colorectal cancers. The level of Dickkopf‐4 was positively correlated with fibroblast growth factor‐20 (rs = 0.61, P = 0.00017), a representative β‐catenin transcriptional target gene, and with the degree of nuclear accumulation of β‐catenin in colorectal tumors. Dickkopf‐4 was induced by activated β‐catenin in vitro. Reciprocally, recombinant Dickkopf‐4 significantly inhibited T‐cell factor/lymphocyte enhancer factor reporter activity stimulated by recombinant Wnt3a in human embryonic kidney 293 cells. We conclude that Dickkopf‐4 and ‐2 are significantly upregulated in most colorectal tumors, and that Dickkopf‐4 upregulation reflects activation of the Wnt/canonical pathway. (Cancer Sci 2009; 100: 1923–1930)
Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non‐small‐cell lung cancer for gefitinib treatment
Authors: Jida Masaru , Toyooka Shinichi , Mitsudomi Tetsuya , Takano Toshimi , Matsuo Keitaro , Hotta Katsuyuki , Tsukuda Kazunori , Kubo Takafumi , Yamamoto Hiromasa , Yamane Masaomi , Oto Takahiro , Sano Yoshifumi , Kiura Katsuyuki , Yatabe Yasushi , Ohe Yuichiro , Date Hiroshi , Miyoshi Shinichiro
Published: July 2009

We examined the diagnostic accuracy of the cumulative smoking dose for identifying the epidermal growth factor receptor (EGFR) exon 19 deletion and L858R mutation among Japanese patients with non‐small‐cell lung cancer (NSCLC). EGFR mutations in exon 19 and exon 21 were determined in 1001 NSCLC patients. A receiver–operating characteristic (ROC) curve methodology was applied to estimate the diagnostic accuracy. EGFR mutations were detected in 314 patients (31.4%). A cumulative smoking dose of less than 13 pack‐years (PY) was the optimal cut‐off point for predicting a positive EGFR mutation status, producing a balance between the sensitivity (73.5%) and the specificity (77%). The area under the ROC curve was 0.77, indicating that the smoking dose had a moderate diagnostic accuracy. The median survival time or the median progression‐free survival time of patients who had smoked less than 13 pack‐years (PY) were 18.6 and 6.3 months, respectively, while those of patients with equal to or more than 13 PY were 9.6 and 2.4 months, respectively. The overall survival (OS) and progression‐free survival (PFS) rates were significantly different between the two groups (OS: hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.51–0.80, P = 0.0001) (PFS: HR = 0.58, 95% CI = 0.47–0.71, P < 0.0001). Our study indicated that the smoking dose predicted EGFR mutations with a moderate diagnostic accuracy. Thus, patients who have smoked less than 13 PY might be candidates for gefitinib treatment when EGFR mutation status cannot be determined. (Cancer Sci 2009; 100: 1931–1934)
Review article: gastric electrical stimulation for gastroparesis – physiological foundations, technical aspects and clinical implications
Authors: SOFFER E. , ABELL T. , LIN Z. , LORINCZ A. , MCCALLUM R. , PARKMAN H. , POLICKER S. , ORDOG T.
Published: July 2009

Background  Application of electrical stimulation to the gut, primarily the stomach, has rapidly advanced in the last two decades, from mostly animal studies to the clinical arena. Most studies focused on the use of electrical stimulation for gastroparesis, the only approved indication for such intervention.

Aim  To review the physiological basis of gastric electrical activity and the technical aspects and clinical outcome of gastric electrical stimulation (GES) for gastroparesis.

Methods  PubMed search from 1966 to 2009, using gastroparesis and GES as search terms. Areas in focus were systematically reviewed.

Results  The literature consists of open‐label studies, mostly from single centres, published in the last decade. Improvement in symptoms, quality of life and nutritional status was reported by most studies. Physiologically, stimulation parameters approved in clinical practice do not regulate gastric slow wave activity and have inconsistent effect on gastric emptying. The mechanism of action of GES is not fully known, but data support modulation of gastric biomechanical activity and afferent neural mechanisms.

Conclusions  Gastric electrical stimulation is a helpful intervention in recalcitrant gastroparesis. Controlled studies and better understanding of mechanisms of action of electrical stimulation are needed to evaluate further the clinical utility of this intervention and to exploit its therapeutic potential better.
Therapeutic intent of proton pump inhibitor prescription among elderly nonsteroidal anti‐inflammatory drug users
Authors: DRIES A. M. , RICHARDSON P. , CAVAZOS J. , ABRAHAM N. S.
Published: July 2009

Background  Prescription of proton pump inhibitors (PPIs) has increased dramatically.

Aim  To assess therapeutic intent of PPI prescription among elderly veterans prescribed nonsteroidal anti‐inflammatory drugs.

Methods  Medical‐record abstraction identified therapeutic intent of PPI prescription. An ‘appropriate therapeutic intent’ was defined as symptomatic gastro‐oesophageal reflux disease or endoscopic oesophagitis, Zollinger–Ellison disease, dyspepsia, upper gastrointestinal event, Helicobacter pylori infection or nonsteroidal anti‐inflammatory drug gastroprotection. Logistic regression predicted the outcome while adjusting for clinical characteristics.

Results  Of 1491 patients [mean 73 years (s.d. 5.6), 73% white and 99.8% men], among those charts which did document a therapeutic indication, 88.8% were appropriate. Prior gastroscopy was predictive of an appropriate therapeutic intent (OR 2.7; 95% CI: 1.9–3.7). Prescription to patients who used VA pharmacy services only, to in‐patients, or by a cardiologist or an otolaryngologist were less likely to be appropriate. Gastroprotection was poorly recognized as an indication for PPI prescription, except by rheumatologists (OR 46.7; 95% CI: 15.9–136.9), or among highly co‐morbid patients (OR 1.8; 95% CI: 1.1–2.9). Among in‐patients, 45% of PPI prescriptions were initiated for unknown or inappropriate reasons.

Conclusions  Type of provider predicts appropriate PPI use. In‐patient prescription is associated with poor recognition of necessary gastroprotection and unknown therapeutic intent.
Carbon source for reproduction in a spring ephemeral herb, Corydalis ambigua (Papaveraceae)
Authors: Kudo Gaku , Ida Takashi Y.
Published: July 2009

1. The carbon source for reproduction in plants may differ between flowering and fruiting stages. To clarify how spring ephemerals use current photosynthetic products for reproduction, the allocation patterns of photosynthate at flowering and fruiting and the effects of resource limitation on reproductive performance in Corydalis ambigua were assessed.

2. A 13C tracing experiment revealed that about 20% of the current photosynthetic carbon was used for reproduction at both flowering and fruiting. The proportion of 13C allocated to fruits was constant irrespective of the light level. In contrast, 13C translocation to tubers increased at fruiting, and this trend was accelerated when plants were shaded.

3. Defoliation treatment significantly reduced nectar production and tuber mass, while seed production was not affected. Therefore, when carbon assimilation was limited, carbon was preferentially allocated to current reproduction (seeds) rather than to pollinator attraction (nectar) or storage (tuber).

4. If seed production is partly supported by carbohydrate reserved in the old tissue of tubers, nectar and seed production may not compete strongly for carbon sources. In contrast to the ability of high seed production, the susceptibility of nectar production to current photosynthesis indicates that seed production of this species is basically limited by pollen capture.

5. Therefore, temporal separation of resource pool for reproduction may mitigate the joint limitation of seed production between pollinator attraction and resource availability. Temporal variation of the sink–source balance of storage organ is crucial to understand the cost of reproduction in perennial plants.
Mechanism and cost of synchronous hatching
Authors: Colbert Paul L. , Spencer Ricky‐John , Janzen Fredric J.
Published: July 2009

1.Synchrony in the timing of births is thought to have evolved as a general predator avoidance strategy. In turtles, synchronous hatching may facilitate group emergence from the nest, which in turn, may limit predation by diluting an individual’s risk of predation or by simply swamping predators upon emergence. However, synchronizing hatching should not be easily achieved in natural nests because of thermal gradients affecting developmental rates.

2.We evaluated pipping synchrony in the painted turtle (Chrysemys picta), where the drive to hatch synchronously may be reduced, because in many populations, hatching and emergence are dissociated through hatchlings overwintering within a nest.

3.We also assessed developmental mechanisms through which synchrony occurs and explored potential trade‐offs between pipping synchrony and individual fitness by determining potential short and long‐term neuromuscular developmental costs to hatching prematurely. These data were also used to develop a theoretical model to determine how differential embryonic maturation rates affect hatching synchrony.

4.Underdeveloped embryos pipped much earlier than expected and at similar times to their more advanced sibs. In addition, a trade‐off between hatching synchronously and neuromuscular development (motility) was evident several days after hatching and up to 9 months later, after the overwintering period.

5.Synchronous hatching is an ancestral trait in turtles, but its relevance today is not solely for predator avoidance in all species.

6.Abiotic factors during incubation (e.g. temperature regime and moisture) have long‐term effects on reptiles during ontogeny but it is also clear that incubation behaviour is major factor for the persistence of these developmental costs.
Global bottlenecks in the distribution of marine Crustacea: temperature constraints in the family Lithodidae
Authors: Hall Sally , Thatje Sven
Published: July 2009

Aim  Members of the crustacean family Lithodidae share preferences for cold‐water environments; however, the specific role of temperature in governing lithodid biogeography has not been examined to date. In the present study this relationship was quantified through the analysis of habitat data, and the results were interpreted in the light of previous physiological studies. It was hypothesized that lineage‐specific temperature thresholds underlie differences in the distribution of the two lithodid subfamilies.

Location  The family Lithodidae is divided into the subfamilies Hapalogastrinae and Lithodinae. The Hapalogastrinae inhabit depths of between 0 and 200 m in the North Pacific. The Lithodinae are distributed globally in the deep sea, with a few genera occurring intertidally at high latitudes.

Methods  Descriptions of 86 species of lithodids, sampled at 627 locations worldwide, were obtained from a wide range of published and original sources. For each specimen, the water temperature at the time and locality of collection was recorded. Molecular sequence data for the 16S, cytochrome c oxidase subunit I (COI) and 28S genes were analysed to construct a phylogenetic tree for the major lithodid genera, using a maximum likelihood method in the program paup*. Further analyses examined the link between the habitat temperature range and the position of taxa within the lithodid phylogeny.

Results  Phylogenetic evidence indicated that the deep‐water lithodid lineages had ancestors that inhabited the coastal waters of the North Pacific. Adults of North Pacific lithodid taxa were found in regions where water temperatures ranged from 0 to 25°C; however, deep‐water lineages of the Lithodinae were excluded from waters exceeding temperatures of 13°C. Despite the higher temperatures tolerated by adults, North Pacific intertidal/subtidal genera were restricted to regions that had water temperatures lower than 16°C during periods of larval development.

Main conclusions  Temperature has restricted the range of most shallow‐water genera of Lithodidae to the coastline of the North Pacific since the early history of the family. Distribution in these groups remains constrained by the detrimental effects of temperature extremes on early life‐history stages. Deep‐water lineages moved away from seasonal temperature fluctuations, and underwent at least three radiations into water bodies outside the North Pacific. Species from within the deep‐water lineages currently live close to the threshold of their temperature tolerance in the Southern Ocean, and their future distribution may be affected by increases in ocean temperature.
Foxp3 expression in lesions of the different clinical forms of American tegumentary leishmaniasis
Authors: CARNEIRO F. P. , DE MAGALHÃES A. V. , DE JESUS ABREU ALMEIDA COUTO M. , BOCCA A. L. , MUNIZ‐JUNQUEIRA M. I. , RIBEIRO SAMPAIO R. N.
Published: July 2009

As the diversity in clinical presentation of American tegumentary leishmaniasis (ATL) is determined mainly by the immune response of host, our aim was to evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in lesions of the different clinical forms of ATL. Foxp3+ cells were observed in 39·5% (32/81) of the samples and the number of positive cells was low in all the clinical forms. Even presenting a significantly lower number of CD4+ T cells, diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). In LCL and MCL, the number of Foxp3+ cells correlated positively with the number of apoptotic cells (active caspase‐3+ cells). A positive correlation was also observed between the expression of active caspase‐3 and FasL in these clinical forms. Our data suggest that increased number of Treg cells may be associated to the hyporesponsiveness observed in DCL and also indicate that the apoptosis may be a possible mechanism of action of Foxp3+ Treg cell in LCL and MCL. However, further studies are required to better understand the mechanism of action of Treg cell.
Immunospecific immunoglobulins and IL‐10 as markers for Trypanosoma brucei rhodesiense late stage disease in experimentally infected vervet monkeys
Authors: Ngotho M. , Kagira J. M. , Jensen H. E. , Karanja S. M. , Farah I. O. , Hau J.
Published: July 2009

Objective  To determine the usefulness of IL‐10 and immunoglobulin M (IgM) as biomarkers for staging HAT in vervet monkeys, a useful pathogenesis model for humans.

Methods  Vervet monkeys were infected with Trypanosoma brucei rhodesiense and subsequently given sub‐curative and curative treatment 28 and 140 days post‐infection (dpi) respectively. Matched serum and CSF samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) and IL‐10 were quantified by ELISA.

Results  There was no detectable immunospecific IgM and IgG in the CSF before 49 dpi. CSF IgM and IgG and serum IgM were significantly elevated with peak levels coinciding with meningoencephalitis 98 dpi. The serum IL‐10 was upregulated in both early and late disease stage, coinciding with primary and relapse parasitaemia respectively. CSF white cell counts (CSF WCC) were elevated progressively till curative treatment was given. After curative treatment, there was rapid and significant drop in serum IgM and IL‐10 concentration as well as CSF WCC. However, the CSF IgM and IgG remained detectable to the end of the study.

Conclusions  Serum and CSF concentrations of immunospecific IgM and CSF IgG changes followed a pattern that mimics the progression of the disease and may present reliable and useful biomarkers of the disease stage. Due to rapid decline, serum IgM and IL‐10 are, additionally, potential biomarkers of the success of chemotherapy.
The angiosperm radiation revisited, an ecological explanation for Darwin’s ‘abominable mystery’
Authors: Berendse Frank , Scheffer Marten
Published: July 2009

One of the greatest terrestrial radiations is the diversification of the flowering plants (Angiospermae) in the Cretaceous period. Early angiosperms appear to have been limited to disturbed, aquatic or extremely dry sites, suggesting that they were suppressed in most other places by the gymnosperms that still dominated the plant world. However, fossil evidence suggests that by the end of the Cretaceous the angiosperms had spectacularly taken over the dominant position from the gymnosperms around the globe. Here, we suggest an ecological explanation for their escape from their subordinate position relative to gymnosperms and ferns. We propose that angiosperms due to their higher growth rates profit more rapidly from increased nutrient supply than gymnosperms, whereas at the same time angiosperms promote soil nutrient release by producing litter that is more easily decomposed. This positive feedback may have resulted in a runaway process once angiosperms had reached a certain abundance. Evidence for the possibility of such a critical transition to angiosperm dominance comes from recent work on large scale vegetation shifts, linking long‐term field observations, large scale experiments and the use of simulation models.
Osmotic adjustment and requirement for sodium in marine protist thraustochytrid
Authors: Shabala Lana , McMeekin Tom , Shabala Sergey
Published: July 2009

A non‐invasive ion‐selective microelectrode technique was used to elucidate the ionic mechanisms of osmotic adjustment in a marine protist thraustochytrid. Hypoosmotic stress caused significant efflux of Na+, Cl– and K+ from thraustochytrid cells. Model calculations showed that almost complete osmotic adjustment was achieved within the first 30 min after stress onset. Of these, sodium was the major contributor (more than half of the total osmotic adjustment), with chloride being the second major contributor. The role of K+ in the process of osmotic adjustment was relatively small. Changes in Ca2+ and H+ flux were attributed to intracellular signalling. Ion flux data were confirmed by growth experiments. Thraustochytrium cells showed normal growth patterns even when grown in a sodium‐free solution provided the medium osmolality was adjusted by mannitol to one of the seawater. That suggests that the requirement of sodium for thraustochytrid growth cycle is due to its role in cell osmotic adjustment rather than because of the direct Na+ involvement in cell metabolism. Altogether, these data demonstrate the evidence for turgor regulation in thraustochytrids and suggest that these cells may be grown in the absence of sodium providing that cell turgor is adjusted by some other means.
Are prostate needle biopsies predictive of the laterality of significant cancer and positive surgical margins?
Authors: Frota Rodrigo , Stein Robert J. , Turna Burak , Kamoi Kazumi , Lin Yi‐Chia , Magi‐Galluzzi Cristina , Aron Monish , Gill Inderbir S.
Published: July 2009

OBJECTIVE

To determine whether data obtained from preoperative prostate needle biopsy can predict the laterality of significant cancer and positive surgical margins on final‐specimen pathology after laparoscopic radical prostatectomy (LRP).

PATIENTS AND METHODS

Data from 490 patients undergoing LRP by one surgeon were reviewed retrospectively. The demographic characteristics, intraoperative data and pathological results were analysed. Univariate and multivariate analyses were used to determine which factors before and during LRP influenced the positive surgical margin status.

RESULTS

There was only minor agreement between the laterality of positive needle biopsies and laterality of any cancer and significant cancer on final‐specimen pathology (κ = 0.135 and 0.151, respectively). This was irrespective of the number of needle cores obtained or final‐specimen Gleason grade. Similarly, the laterality of dominant cancer on needle biopsy had only a minor agreement with the location of positive surgical margins (κ = 0.050) and fair agreement with the location of extracapsular extension on final‐specimen pathology (κ = 0.235).

CONCLUSIONS

Preoperative needle biopsy data have only a minor correlation with the laterality of significant cancer and positive surgical margins at final pathology of LRP specimens. Recognition of this fact, and the frequent bilaterality of significant cancer, with its potential for contralateral positive surgical margins even when the biopsies are positive only unilaterally, is an important consideration when planning nerve‐sparing, and potentially for focal therapy.
Bladder neck contracture after retropubic radical prostatectomy: incidence and risk factors from a large single‐surgeon experience
Authors: Erickson Bradley A. , Meeks Joshua J. , Roehl Kimberly A. , Gonzalez Christopher M. , Catalona William J.
Published: July 2009

OBJECTIVE

To examine a large, single‐surgeon series of patients with prostate cancer who underwent retropubic radical prostatectomy (RRP) for men with postoperative bladder neck contractures (BNCs).

PATIENTS AND METHODS

From 1983 to 2007, 4132 men underwent RRP for prostate cancer by one surgeon. All patients had BN reconstruction with mucosal eversion. The bladder to membranous urethral anastomosis was made using six 2/0 chromic catgut sutures over an 18 F Foley catheter. The catheter was left in place for 10 days. Data from these men is stored in a prospective database, which was reviewed in this study for men with BNCs after RRP. Men with BNCs were compared with all other men in the series to determine risk factors for BNC development.

RESULTS

Overall, BNCs developed in 110 patients (2.5%). Examining our last 500 patients there was a contemporary BNC rate of <1%. The median (range) follow‐up was 44  (12–233) months. Tumour characteristics were similar in the men with BNCs and those with no BNCs, and the rates of organ‐confined disease were also similar (65% vs 70%, P = 0.27). Men with BNCs had higher median preoperative prostate‐specific antigen (PSA) levels (6.7 vs 5.7 mg/dL; P = 0.009) and were more likely to have PSA failure after RRP (30% vs 16%, P < 0.001). On multivariate analysis, non‐nerve sparing (P = 0.003) and a surgical date before 1992 (P < 0.001) were significant predictors of BNC. Patients with BNCs had lower potency rates (49% vs 63%, P < 0.003) and continence rates (88% vs 94%, P = 0.07) at the 18‐month follow‐up.

CONCLUSIONS

BNCs are rare, occurring in <1% in our modern series. The important surgical factors in preventing BNCs are to avoid closing the BN too tightly and attaining good apposition of the BN with the urethral stump with a watertight closure. BNCs are more common with non‐nerve‐sparing surgery and early in a surgeon’s experience.
Current salvage methods for recurrent prostate cancer after failure of primary radiotherapy
Authors: Kimura Masaki , Mouraviev Vladimir , Tsivian Matvey , Mayes Janice M. , Satoh Takefumi , Polascik Thomas J.
Published: July 2009

We reviewed the current salvage methods for patients with local recurrent prostate cancer after primary radiotherapy (RT), using a search of relevant Medline/PubMed articles published from 1982 to 2008, with the following search terms: ‘radiorecurrent prostate cancer, local salvage treatment, salvage radical prostatectomy (RP), salvage cryoablation, salvage brachytherapy, salvage high‐intensity focused ultrasound (HIFU)’, and permutations of the above. Only articles written in English were included. The objectives of this review were to analyse the eligibility criteria for careful selection of appropriate patients and to evaluate the oncological results and complications for each method. There are four whole‐gland re‐treatment options (salvage RP, salvage cryoablation, salvage brachytherapy, salvage HIFU) for RT failure, although others might be in development or investigations. Salvage RP has the longest follow‐up with acceptable oncological results, but it is a challenging technique with a high complication rate. Salvage cryoablation is a feasible option, especially using third‐generation technology, whereby the average biochemical disease‐free survival rate is 50–70% and there are fewer occurrences of severe complications such as recto‐urethral fistula. Salvage brachytherapy, with short‐term cancer control, is comparable to other salvage methods but depends on cumulative dosage limitation to target tissues. HIFU is a relatively recent option in the salvage setting. Both salvage brachytherapy and HIFU require more detailed studies with intermediate and long‐term follow‐up. As these are not prospective, randomized studies and the definitions of biochemical failure varied, there are limited comparisons among these different salvage methods, including efficacy. In the focal therapy salvage setting, the increased use of thermoablative methods for eligible patients might contribute to reducing complications and maintaining quality of life. The problem to effectively salvage patients with locally recurrent disease after RT is the lack of diagnostic examinations with sufficient sensitivity and specificity to detect local recurrence at an early curable stage. Therefore, a more strict definition of biochemical failure, improved imaging techniques, and accurate specimen mapping are needed as diagnostic tools. Furthermore, universal selection criteria and an integrated definition of biochemical failure for all salvage methods are required to determine which provides the best oncological efficacy and least comorbidity.
Establishing family inclusive acute inpatient mental health services: a staff training programme in Somerset
Authors: Stanbridge Roger I. , Burbach Frank R. , Leftwich Simon H.
Published: July 2009

In spite of policies advocating the involvement of families in the care of mental health service users in the UK there are few examples of training initiatives to bring this about. This article describes the delivery of a whole‐team training initiative to promote family inclusive working in all acute inpatient units in Somerset. The three‐day staff‐training programme is described and training outcomes are reported. Staff reported a significant increase in confidence in their skills for working with families, and a pre‐ and post‐training case note audit showed an increased consideration of the needs of families. This was accompanied by a modest increase in the average number of family meetings. Obstacles to family inclusive ways of working on inpatient units are described, and strategies to overcome these are discussed.
Integrating family therapy in adolescent depression: an ethical stance
Authors: Larner Glenn
Published: July 2009

Adolescent depression, particularly where suicidal behaviour is involved, is a complex and pressing mental health problem and demanding for families, therapists and services alike. This article reviews the evidence‐based literature for adolescent depression including family therapy approaches. It suggests an integrative treatment approach that includes individual psychological treatment like CBT, medication where required and a family therapy intervention is supported by the literature. The focus of the latter is psychoeducation, building resilience and hope, enhancing communication, reducing relational conflict between parents and adolescents and addressing attachment and relationship issues. A systemic framework for integrating family therapy in the evidence‐ based treatment of adolescent depression is described. This is based on an ethic of hospitality towards different languages of therapy, which is illustrated by a detailed example from family therapy practice.
Self‐Interest, Symbolic Attitudes, and Support for Public Policy: A Multilevel Analysis
Authors: Lau Richard R. , Heldman Caroline
Published: July 2009

This paper examines the role of self‐interest and symbolic attitudes as predictors of support for two domestic policy issues—guaranteed jobs and incomes and national health insurance—in the American National Election Survey (ANES) between 1972 and 2004. As was the case in 1976 when Sears, Lau, Tyler, and Allen (1980) first explored this topic, symbolic attitudes continue to be much more important predictors of policy attitudes than various indicators of self‐interest over the 30 years we analyze. We explore this finding further to determine whether any individual/internal and external/contextual variables affect the magnitude of self‐interest effects on policy support. Five possible internal moderators of self‐interest effects are examined: (1) political knowledge, (2) issue publics, (3) political values, (4) social identifications, and (5) emotions, but none are found to boost the magnitude of the self‐interest effect. However, we do find some evidence that contextual variables representing the social/information environment moderate the impact of self‐interest on public opinion.
The Crystallization of Contemporary Racial Prejudice across the Lifespan
Authors: Henry P. J. , Sears David O.
Published: July 2009

The conventional wisdom is that racial prejudice remains largely stable through adulthood. However, very little is known about the development of contemporary racial attitudes like symbolic racism. The growing crystallization of symbolic racism through the lifespan is tested using two data sets that measure the stability, consistency, and predictive validity of symbolic racism in samples ranging in age from young adults to the elderly. The results provide evidence that the crystallization of symbolic racism generally takes on a curvilinear trajectory across the lifespan, showing that it is already largely crystallized by voting age, that it continues to crystallize still further through adulthood and that it begins to decline in coherence in late adulthood. The results generally provide evidence confirming early speculations of symbolic racism theorists concerning the crystallization of symbolic racism across the lifespan and are discussed in terms of different theoretical perspectives on the relationship between aging and attitudes more generally.
Selective Exposure in the Internet Age: The Interaction between Anxiety and Information Utility
Authors: Valentino Nicholas A. , Banks Antoine J. , Hutchings Vincent L. , Davis Anne K.
Published: July 2009

The rise of the Internet forces scholars to reevaluate the frequency and nature of political information seeking in the contemporary period. The functionality of the Internet makes passive exposure more difficult, and selective information seeking easier, than in the past. However, people may also use the Internet in a new and directed way—to arm themselves with information to express and defend their views either online or in the real world. The central question we explore in this paper is what explains balanced versus biased information seeking in the era of the Internet? We combine insights fromSears and Freedman (1967) with newer work on emotion to predict motivated selectivity: focusing specifically on the interaction between anxiety and information utility. Our central theoretical claim is that anxiety does not simply boostanyinformation seeking; it triggers information seeking that isuseful for addressing the problem at hand. Anxiety alone, therefore, does not guarantee abalancedinformation search. When counterattitudinal information is useful for some reason—for example, to defend their own opinions to others who may disagree—anxious citizens should seek it out. As a consequence, these subjects should learn more specific information about where each candidate stands on the issues. In an experiment we find support for these hypotheses. We conclude that while today's flexible Internet environment may permit selectivity, balanced seeking should still occur under a fairly common set of circumstances.
Does Discussion Group Composition Affect Policy Preferences? Results from Three Randomized Experiments
Authors: Farrar Cynthia , Green Donald P. , Green Jennifer E. , Nickerson David W. , Shewfelt Steven
Published: July 2009

We report the results of three randomized experiments designed to assess whether participants' political attitudes are affected by the prediscussion opinions of their discussion mates. The experiments took place during three multisite Deliberative Polls in 2004 and 2005. Participants discussed current political issues within 330 groups of approximately 10 people each. Because the composition of the groups was determined randomly within each location, the demographic and ideological complexion of the discussion groups varied randomly. This paper examines the effects of randomly varying group composition on political opinions expressed after daylong discussion. We find only sporadic evidence of group composition effects. These results run counter to—or at least qualify—a substantial body of theory and laboratory evidence on the influence of group discussion.
Symbols Build Communication and Thought: The Role of Gestures and Words in the Development of Engagement Skills and Social‐emotional Concepts during Toddlerhood
Authors: Vallotton Claire D. , Ayoub Catherine C.
Published: July 2009

Social skills and symbol skills are positively associated in middle childhood, but the relation between these domains is less clear in newly verbal toddlers. Vygotsky proposed that symbols are both tools for interaction and mental tools for thought. Do symbols help even very young children build skills for interacting with and conceptualizing the social world? Longitudinal data from 108 children and mothers were collected when children were 14, 24, and 36 months. Children's gestures and words during mother–child interactions were used as symbol skill indicators to predict children's abilities to engage others and the number of social‐emotional concepts children portray during play. In a series of growth models, words had a stronger effect on engagement skills whereas early gesture use predicted later development of social‐emotional concepts. Therefore, even in early development, symbols serve as both communication tools and mental tools to construct understanding of the social‐emotional world.
10. Using Instrumental Variable Tests to Evaluate Model Specification in Latent Variable Structural Equation Models
Authors: Kirby James B. , Bollen Kenneth A.
Published: July 2009

Structural equation modeling (SEM) with latent variables is a powerful tool for social and behavioral scientists, combining many of the strengths of psychometrics and econometrics into a single framework. The most common estimator for SEM is the full-information maximum likelihood (ML) estimator, but there is continuing interest in limited information estimators because of their distributional robustness and their greater resistance to structural specification errors. However, the literature discussing model fit for limited information estimators for latent variable models is sparse compared with that for full-information estimators. We address this shortcoming by providing several specification tests basedon the 2SLS estimator for latent variable structural equation models developed by Bollen (1996). We explain how these tests can be used not only to identify a misspecified model but to help diagnose the source of misspecification within a model. We present and discuss results from a Monte Carlo experiment designed to evaluate the finite sample properties of these tests. Our findings suggest that the 2SLS tests successfully identify most misspecified models, even those with modest misspecification, and that they provide researchers with information that can help diagnose the source of misspecification.
Spillovers from Multinationals to Heterogeneous Domestic Firms: Evidence from Hungary
Authors: Békés Gábor , Kleinert Jörn , Toubal Farid
Published: July 2009

Firms cluster their economic activities to exploit technological and informational spillovers from other firms. Spillovers from multinational firms can be particularly beneficial to firms in less developed economies, because technological superiority and management expertise of foreign multinational firms yield various opportunities for learning. Yet, the importance of foreign firms’ spillovers might vary with respect to two key features of domestic firms: their productivity level and their export status. In line with theories on the absorptive capacity of firms, we argue on the basis of an empirical analysis of Hungarian firms that larger and more productive firms are more able than smaller firms to reap spillovers from multinationals. However, the export status is found to be of minor importance once higher productivity is controlled for.
Analysis of electrocardiographic changes in partial epileptic patients by combining eigenvector methods and support vector machines
Authors: Übeyli Elif Derya
Published: July 2009

Abstract: In the present study, the diagnostic accuracy of support vector machines (SVMs) on electrocardiogram (ECG) signals is evaluated. Two types of ECG beats (normal and partial epilepsy) were obtained from the Physiobank database. Decision making was performed in two stages: feature extraction by eigenvector methods and classification using the SVM trained on the extracted features. The present research demonstrates that the power levels of the power spectral densities obtained by eigenvector methods are features which represent the ECG signals well and SVMs trained on these features achieve high classification accuracies.
Hybrid expert–fuzzy approach for evaluation of complex systems
Authors: Öztürk Veysi
Published: July 2009

Abstract: Evaluation of complex systems is generally complicated and time consuming. Evaluation is needed for nearly all engineering tasks and the obstacles related to evaluation increase in proportion to complexity. New techniques can be used to automate manual evaluation and to overcome the obstacles related to evaluation that cannot be solved (or can only be solved with great difficulty) with conventional computing. In this study, a methodology was developed to handle the heuristic knowledge of experts for evaluation purposes. In this method, knowledge was represented as a reference model of evaluation objectives, production rules, measures, methods and parameters. A ‘common evaluation process’ and ‘common evaluation model’, which simplify and speed up the evaluation process and decrease evaluation cost, were proposed and developed. A hybrid expert–fuzzy system, called ‘intelligent evaluation system’ (INES), which can be used for evaluation of complex systems was developed. To define a process and develop a system that simplifies and speeds up evaluation can save time, decrease cost and provide reusability. As the evaluation of complex systems includes uncertainty in some aspects, fuzzy logic was incorporated with an expert system for reasoning. INES was implemented successfully for the evaluation of an air defence system, which is a complex system used to protect a region from all air threats.
Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first‐line boosted highly active antiretroviral therapy based on protease inhibitors: meta‐regression analysis of 12 clinical trials in 5168 patients
Authors: Hill A , Sawyer W
Published: July 2009

Objectives

Tenofovir/emtricitabine (TDF/FTC) and abacavir/lamivudine (ABC/3TC) are widely used with ritonavir (RTV)‐boosted protease inhibitors (PIs) as first‐line highly active antiretroviral therapy (HAART), but there is conflicting evidence on their relative efficacy. The ACTG 5202 and BICOMBO trials suggested higher efficacy for TDF/FTC, whereas the HEAT trial showed no efficacy difference between the nucleoside reverse transcriptase inhibitor (NRTI) backbones.

Methods

A systematic MEDLINE search identified 21 treatment arms in 12 clinical trials of 5168 antiretroviral‐naïve patients, where TDF/FTC (n=3399) or ABC/3TC (n=1769) was used with RTV‐boosted PI. For each NRTI backbone and RTV‐boosted PI, the percentage of patients with viral load <50 HIV‐1 RNA copies/mL at week 48 by standardized Intent to Treat, Time to Loss of Virological Failure (ITT TLOVR) analysis were combined using inverse‐variance weighting. The effect of baseline HIV RNA, CD4 cell count and choice of NRTI backbone were examined using a weighted analysis of covariance.

Results

Across all the trials, HIV RNA suppression rates were significantly higher for those with baseline viral load below 100 000 copies/mL (77.2%) vs. above 100 000 copies/mL (70.9%) (P=0.0005). For the trials of lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r) and fosamprenavir/ritonavir (FAPV/r) using either TDF/FTC or ABC/3TC, the HIV RNA responses were significantly lower when ABC/3TC was used, relative to TDF/FTC, for all patients (P=0.0015) and for patients with baseline viral load <100 000 copies/mL (70.1%vs. 80.6%, P=0.0161), and was borderline for those with viral load >100 000 copies/mL (67.5%vs. 71.5%, P=0.0523).

Conclusions

This systematic meta‐regression analysis suggests higher efficacy for first‐line use of a TDF/FTC NRTI backbone with boosted PIs, relative to use of ABC/3TC. However, this effect may be confounded by differences between the trials in terms of baseline characteristics, patient management or adherence.