bluuebunny/crossref_metadata_2025 huggingface dataset:
Too Much Balance in Unbalanced Bidding
Authors: Mandell Svante , Nyström Johan
Published: August 2013

This article adds to the theoretical base of unbalanced bidding in auction theory. The importance of this concept is justified by being a decisive feature in the make-or-buy decision of a client who cannot rely on repeated interaction, often the case in public procurement, for example. Earlier theoretical models on unbalanced bidding often predict corner solutions, that is, zero bids for unit prices of expected overestimated quantities. However, anecdotal evidence indicates a lack of zero bids in the actual contracts. The article offers a possible explanation for this anomaly by focusing on the risk-aversion of the contractor. Using a simple model, it shows that a contractor with superior information may exploit this in the bidding process to increase her expected revenue. This increases risk exposure. A risk-averse contractor will typically avoid a corner solution to reach an optimal balance between risk and expected return.
Evolution in Bayesian Supermodular Population Games
Authors: Lahkar Ratul
Published: August 2013

We study evolution in Bayesian supermodular population games. We define such games in the context of large populations of agents and establish the existence of a maximum and a minimum pure strategy Nash equilibria which are monotone in types. To study evolution in such games, we introduce Bayesian perturbed best response dynamics and the corresponding aggregate perturbed best response dynamic. Using the theory of cooperative dynamical systems, we show that solution trajectories of the aggregate perturbed best response dynamic converge to the set of perturbed equilibrium distributions. Using results from Ely and Sandholm (2005), we then conclude that the L1 solution trajectories of the Bayesian perturbed best response dynamic also converge to the set of Bayesian perturbed equilibria.
When Consumers and Firms Share Transportation Costs
Authors: Kyureghian Hrachya , Plotnikova Maria , Sarangi Sudipta
Published: August 2013

We consider a standard linear city model with two firms, where firms and consumers both incur transport costs. This is done by assuming that the total transport cost is shared by the buyers and sellers according to an exogenously given rule. In the model, firms choose locations and prices, with the transportation cost being linear in distance. We first derive the profit function for the two-stage transport cost sharing game and find that it has a complex form. We then invoke simplifying assumptions and solve for two different games. We provide a complete characterization for the equilibrium of the location game between the two firms by assuming fixed prices. We then examine the price game when the two firms are constrained to locate at the same spot. The equilibria of these two games provide insights about the complex two-stage game.
TGFβ and CCN2/CTGF mediate actin related gene expression by differential E2F1/CREB activation
Authors: Faherty Noel , O’Donovan Helen , Kavanagh David , Madden Stephen , McKay Gareth J , Maxwell Alexander P , Martin Finian , Godson Catherine , Crean John
Published: August 2013

Background

CCN2/CTGF is an established effector of TGFβ driven responses in diabetic nephropathy. We have identified an interaction between CCN2 and TGFβ leading to altered phenotypic differentiation and inhibited cellular migration. Here we determine the gene expression profile associated with this phenotype and define a transcriptional basis for differential actin related gene expression and cytoskeletal function.

Results

From a panel of genes regulated by TGFβ and CCN2, we used co-inertia analysis to identify and then experimentally verify a subset of transcription factors, E2F1 and CREB, that regulate an expression fingerprint implicated in altered actin dynamics and cell hypertrophy. Importantly, actin related genes containing E2F1 and CREB binding sites, stratified by expression profile within the dataset. Further analysis of actin and cytoskeletal related genes from patients with diabetic nephropathy suggests recapitulation of this programme during the development of renal disease. The Rho family member Cdc42 was also found uniquely to be activated in cells treated with TGFβ and CCN2; Cdc42 interacting genes were differentially regulated in diabetic nephropathy.

Conclusions

TGFβ and CCN2 attenuate CREB and augment E2F1 transcriptional activation with the likely effect of altering actin cytoskeletal and cell growth/hypertrophic gene activity with implications for cell dysfunction in diabetic kidney disease. The cytoskeletal regulator Cdc42 may play a role in this signalling response.
Complete genome sequence and comparative analysis of Acetobacter pasteurianus 386B, a strain well-adapted to the cocoa bean fermentation ecosystem
Authors: Illeghems Koen , De Vuyst Luc , Weckx Stefan
Published: August 2013

Background

Acetobacter pasteurianus 386B, an acetic acid bacterium originating from a spontaneous cocoa bean heap fermentation, proved to be an ideal functional starter culture for coca bean fermentations. It is able to dominate the fermentation process, thereby resisting high acetic acid concentrations and temperatures. However, the molecular mechanisms underlying its metabolic capabilities and niche adaptations are unknown. In this study, whole-genome sequencing and comparative genome analysis was used to investigate this strain’s mechanisms to dominate the cocoa bean fermentation process.

Results

The genome sequence of A. pasteurianus 386B is composed of a 2.8-Mb chromosome and seven plasmids. The annotation of 2875 protein-coding sequences revealed important characteristics, including several metabolic pathways, the occurrence of strain-specific genes such as an endopolygalacturonase, and the presence of mechanisms involved in tolerance towards various stress conditions. Furthermore, the low number of transposases in the genome and the absence of complete phage genomes indicate that this strain might be more genetically stable compared with other A. pasteurianus strains, which is an important advantage for the use of this strain as a functional starter culture. Comparative genome analysis with other members of the Acetobacteraceae confirmed the functional properties of A. pasteurianus 386B, such as its thermotolerant nature and unique genetic composition.

Conclusions

Genome analysis of A. pasteurianus 386B provided detailed insights into the underlying mechanisms of its metabolic features, niche adaptations, and tolerance towards stress conditions. Combination of these data with previous experimental knowledge enabled an integrated, global overview of the functional characteristics of this strain. This knowledge will enable improved fermentation strategies and selection of appropriate acetic acid bacteria strains as functional starter culture for cocoa bean fermentation processes.
Addressing the deficiencies in the evidence-base for primary practice in regional Australia - sentinel practices data sourcing (SPDS) project: a pilot study
Authors: Ghosh Abhijeet , Charlton Karen E , Girdo Lisa , Batterham Marijka J , McDonald Keith
Published: August 2013

Background

Chronic disease risk on a population level can be quantified through health surveys, either continuous or periodic. To date, information gathered from primary care interactions, using sentinel sites, has not been investigated as a potentially valuable surveillance system in Australia.

Methods

A pilot study was conducted in a single General Practice in a regional area of New South Wales, Australia to assess the feasibility of accessing data obtained through a computerised chronic disease management program that has been designed for desktop application (Pen Computer Systems (PCS) Clinical Audit Tool: ™ PCS CAT). Collated patient data included information on chronic disease management and prevention, prevalence of overweight and obesity, mental health indicators, medication profiling and home medicine reviews, as well as uptake of preventive health services (immunisation and cervical cancer screening).

Results

Higher than national average estimates were found for the age-adjusted prevalence of chronic diseases such as hypertension (14.3% for sample vs 10.4%, nationally), anxiety disorders (4.4% vs 3.8%) and obesity/overweight (67.1 vs 63.4%). Preventive health assessment items were undersubscribed, ranging from 6–20% in eligible patients.

Conclusions

This pilot study has demonstrated that the scope of data collected by patient visits to their General Practitioners, facilitated through the Medicare-funded primary health care system in Australia, offers a feasible opportunity for monitoring of chronic disease prevalence and its associated risk factors. The inclusion of a larger number of sentinel sites that are generalizable to the population being served would provide an accurate and region-specific system for the purposes of population health planning at the primary care level in order to improve the overall health of the community.
Efficacy of a mobile application for smoking cessation in young people: study protocol for a clustered, randomized trial
Authors: Valdivieso-López Empar , Flores-Mateo Gemma , Molina-Gómez Juan-Domingo , Rey-Reñones Cristina , Barrera Uriarte María-Luisa , Duch Jordi , Valverde Araceli
Published: August 2013

Background

Tobacco consumption is the most preventable cause of morbidity-mortality in the world. One aspect of smoking cessation that merits in-depth study is the use of an application designed for smartphones (app), as a supportive element that could assist younger smokers in their efforts to quit. To assess the efficacy of an intervention that includes the assistance of a smoking cessation smartphone application targeted to young people aged 18 to 30 years who are motivated to stop smoking.

Methods/design

Cluster randomised clinical trial. Setting: Primary Health Care centres (PHCCs) in Catalonia. Analyses based on intention to treat. Participants: motivated smokers of 10 or more cigarettes per day, aged 18 to 30 years, consulting PHCCs for any reason and who provide written informed consent to participate in the trial. Intervention group will receive a 6-month smoking cessation programme that implements recommendations of a Clinical Practice Guideline, complemented with a smartphone app designed specifically for this programme. Control group will receive the usual care. The outcome measure will be abstinence at 12 months confirmed by exhaled-air carbon monoxide concentration of at least 10 parts per million at each control test.

Discussion

To our knowledge this is the first randomised controlled trial of a programme comparing the efficacy of usual care with a smoking cessation intervention involving a mobile app. If effective, the modality could offer a universal public health management approach to this common health concern.

Trial registration

NCT01734421
Studies on bioflocculant production by a mixed culture of Methylobacterium sp. Obi and Actinobacteriumsp. Mayor
Authors: Luvuyo Ntsaluba , Nwodo Uchechukwu U , Mabinya Leonard V , Okoh Anthony I
Published: August 2013

Background

Bioflocculants effect the aggregation of suspended solutes in solutions thus, a viable alternative to inorganic poly-ionic and synthetic organic flocculants which are associated with deleterious health problems. Consequently, a consortium of two bacteria species were evaluated for optimized bioflocculant yield following the inadequacies of axenic cultures.

Results

16S rDNA nucleotide sequencing and BLAST analysis of nucleotide sequences were used to identify the bacterial species, carbon and nitrogen sources optimally supporting bioflocculant production were assessed and the purified bioflocculant characterized.

Nucleotide sequences showed 97% and 96% similarity to Methylobacterium sp. AKB-2008-KU9 and Methylobacterium sp. strain 440. The second isolate, likewise, showed 98% similarity to Actinobacterium OR-221. The sequences were deposited in GenBank as Methylobacterium sp. Obi [accession number HQ537130] and Actinobacterium sp. Mayor [accession number JF799090]. Flocculating activity of 95% was obtained in the presence of Ca2+ and heat-stability was exhibited with retention of above 70% activity at 100°C in 30 min. In addition, bioflocculant yield was about 8.203 g/l. A dose of 1 mg/ml of purified bioflocculant was optimal for the clarification of Kaolin suspension (100 ml) following Jar test. FTIR spectrum revealed the presence of carboxyl and hydroxyl functional groups amongst others.

Conclusions

The mixed culture produced bioflocculant with high flocculating activity and an improved yield. The efficiency observed with jar test may imply industrial applicability.
Lupin protein positively affects plasma LDL cholesterol and LDL:HDL cholesterol ratio in hypercholesterolemic adults after four weeks of supplementation: a randomized, controlled crossover study
Authors: Bähr Melanie , Fechner Anita , Krämer Julia , Kiehntopf Michael , Jahreis Gerhard
Published: August 2013

Background

A couple of studies indicate a favorable impact of lupin protein on cardiovascular risk factors in humans. These studies, however, used relatively high doses of > 33 g/d, which can hardly be consumed under physiological conditions. Therefore, we investigated the effect of 25 g/d lupin protein isolate (LPI) on selected cardiovascular markers and on serum amino acids.

Methods

A total of 33 hypercholesterolemic subjects participated in a randomized, controlled, double-blind crossover study. LPI and the active comparator milk protein isolate (MPI) were incorporated in protein drinks and consumed over 8 wk separated by a 4 wk washout period. Anthropometric data, blood pressure, and nutrient intake were assessed at baseline and after 8 wk of both protein interventions. Blood was sampled at baseline, wk 4 and wk 8. All 33 subjects were included in final statistical analyses using repeated measures ANOVA with the general linear model or using linear mixed model.

Results

Except for higher HDL cholesterol at wk 4 of LPI (P ≤ 0.036), anthropometric parameters, blood pressure, and plasma lipids did not differ among LPI and MPI intervention. Compared to baseline, the primary outcome LDL cholesterol was significantly reduced after 4 wk of both interventions (P ≤ 0.008), while LDL:HDL cholesterol ratio was decreased only by LPI (P = 0.003). These time effects were restricted to subjects with higher hypercholesterolemia and disappeared after 8 wk. Blood pressure was reduced after 8 wk of LPI (P ≤ 0.044). Almost all serum amino acids were higher at wk 4 but not at wk 8 of MPI compared to LPI. Following 4 wk and 8 wk of LPI intervention, most amino acids remained unchanged. Both interventions caused a slight, but significant rise in body weight and body fat after 8 wk (P ≤ 0.045).

Conclusion

In conclusion, 25 g LPI can beneficially modulate plasma LDL cholesterol at least over short-term. Using appropriate dietetic conditions that improve consumer compliance and avoid changes in energy intake as well as in body composition, lupin protein could positively impact cardiovascular risk factors particularly in individuals with higher hypercholesterolemia.

Trial registration

ClinicalTrials.gov: NCT01304992
Access to antiretroviral treatment, issues of well-being and public health governance in Chad: what justifies the limited success of the universal access policy?
Authors: Azétsop Jacquineau , Diop Blondin A
Published: August 2013

Universal access to antiretroviral treatment (ART) in Chad was officially declared in December 2006. This presidential initiative was and is still funded 100% by the country’s budget and external donors’ financial support. Many factors have triggered the spread of AIDS. Some of these factors include the existence of norms and beliefs that create or increase exposure, the low-level education that precludes access to health information, social unrest, and population migration to areas of high economic opportunities and gender-based discrimination. Social forces that influence the distribution of dimensions of well-being and shape risks for infection also determine the persistence of access barriers to ART. The universal access policy is quite revolutionary but should be informed by the systemic barriers to access so as to promote equity. It is not enough to distribute ARVs and provide health services when health systems are poorly organized and managed. Comprehensive access to ART raises many organizational, ethical and policy problems that need to be solved to achieve equity in access. This paper argues that the persistence of access barriers is due to weak health systems and a poor public health leadership. AIDS has challenged health systems in a manner that is essentially different from other health problems.
The fate of lignin during hydrothermal pretreatment
Authors: Trajano Heather L , Engle Nancy L , Foston Marcus , Ragauskas Arthur J , Tschaplinski Timothy J , Wyman Charles E
Published: August 2013

Background

Effective enzymatic hydrolysis of lignocellulosic biomass benefits from lignin removal, relocation, and/or modification during hydrothermal pretreatment. Phase transition, depolymerization/repolymerization, and solubility effects may all influence these lignin changes. To better understand how lignin is altered,Populus trichocarpaxP. deltoideswood samples and cellulolytic enzyme lignin (CEL) isolated fromP. trichocarpa x P. deltoideswere subjected to batch and flowthrough pretreatments. The residual solids and liquid hydrolysate were characterized by gel permeation chromatography, heteronuclear single quantum coherence NMR, compositional analysis, and gas chromatography–mass spectrometry.

Results

Changes in the structure of the solids recovered after the pretreatment of CEL and the production of aromatic monomers point strongly to depolymerization and condensation being primary mechanisms for lignin extraction and redeposition. The differences in lignin removal and phenolic compound production from nativeP. trichocarpa x P. deltoidesand CEL suggested that lignin-carbohydrate interactions increased lignin extraction and the extractability of syringyl groups relative to guaiacyl groups.

Conclusions

These insights into delignification during hydrothermal pretreatment point to desirable pretreatment strategies and plant modifications. Because depolymerization followed by repolymerization appears to be the dominant mode of lignin modification, limiting the residence time of depolymerized lignin moieties in the bulk liquid phase should reduce lignin content in pretreated biomass. In addition, the increase in lignin removal in the presence of polysaccharides suggests that increasing lignin-carbohydrate cross-links in biomass would increase delignification during pretreatment.
XIST-induced silencing of flanking genes is achieved by additive action of repeat a monomers in human somatic cells
Authors: Minks Jakub , Baldry Sarah EL , Yang Christine , Cotton Allison M , Brown Carolyn J
Published: August 2013

Background

The establishment of facultative heterochromatin by X-chromosome inactivation requires the long non-coding RNA XIST/Xist. However, the molecular mechanism by which the RNA achieves chromosome-wide gene silencing remains unknown. Mouse Xist has been shown to have redundant domains for cis-localization, and requires a series of well-conserved tandem ‘A’ repeats for silencing. We previously described a human inducible XIST transgene that is capable of cis-localization and suppressing a downstream reporter gene in somatic cells, and have now leveraged these cells to dissect the sequences critical for XIST-dependent gene silencing in humans.

Results

We demonstrated that expression of the inducible full-length XIST cDNA was able to suppress expression of two nearby reporter genes as well as endogenous genes up to 3 MB from the integration site. An inducible construct containing the repeat A region of XIST alone could silence the flanking reporter genes but not the more distal endogenous genes. Reporter gene silencing could also be accomplished by a synthetic construct consisting of nine copies of a consensus repeat A sequence, consistent with previous studies in mice. Progressively shorter constructs showed a linear relationship between the repeat number and the silencing capacity of the RNA. Constructs containing only two repeat A units were still able to partially silence the reporter genes and could thus be used for site-directed mutagenesis to demonstrate that sequences within the two palindromic cores of the repeat are essential for silencing, and that it is likely the first palindrome sequence folds to form a hairpin, consistent with compensatory mutations observed in eutherian sequences.

Conclusions

Silencing of adjacent reporter genes can be effected by as little as 94 bp of XIST, including two ‘monomers’ of the A repeat. This region includes a pair of essential palindromic sequences that are evolutionarily well-conserved and the first of these is likely to form an intra-repeat hairpin structure. Additional sequences are required for the spread of silencing to endogenous genes on the chromosome.
Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders
Authors: Chien Wei-Hsien , Gau SusanShur-Fen , Liao Hsiao-Mei , Chiu Yen-Nan , Wu Yu-Yu , Huang Yu-Shu , Tsai Wen-Che , Tsai Ho-Min , Chen Chia-Hsiang
Published: August 2013

Background

We recently reported a terminal deletion of approximately 2.4 Mb at chromosome 8p23.2-pter in a boy with autism. The deleted region contained the DLGAP2 gene that encodes the neuronal post-synaptic density protein, discs, large (Drosophila) homolog-associated protein 2. The study aimed to investigate whether DLGAP2 is genetically associated with autism spectrum disorders (ASD) in general.

Methods

We re-sequenced all the exons of DLGPA2 in 515 patients with ASD and 596 control subjects from Taiwan. We also conducted bioinformatic analysis and family study of variants identified in this study.

Results

We detected nine common single nucleotide polymorphisms (SNPs) and sixteen novel missense rare variants in this sample. We found that AA homozygotes of rs2906569 (minor allele G, alternate allele A) at intron 1 (P = 0.003) and CC homozygotes of rs2301963 (minor allele A, alternate allele C) at exon 3 (P = 0.0003) were significantly over-represented in the patient group compared to the controls. We also found no differences in the combined frequency of rare missense variants between the two groups. Some of these rare variants were predicted to have an impact on the function of DLGAP2 using informatics analysis, and the family study revealed most of the rare missense mutations in patients were inherited from their unaffected parents.

Conclusions

We detected some common and rare genetic variants of DLGAP2 that might have implication in the pathogenesis of ASD, but they alone may not be sufficient to lead to clinical phenotypes. We suggest that further genetic or environmental factors in affected patients may be present and determine the clinical manifestations.

Trial registration

ClinicalTrial.gov, NCT00494754
Measuring microRNA reporter activity in skeletal muscle using hydrodynamic limb vein injection of plasmid DNA combined with in vivo imaging
Authors: Guess Martin G , Barthel Kristen KB , Pugach Emily K , Leinwand Leslie A
Published: August 2013

Background

microRNA regulation plays an important role in the remodeling that occurs in response to pathologic and physiologic stimuli in skeletal muscle. In response to stress, microRNAs are dynamically regulated, resulting in a widespread “fine-tuning” of gene expression. An understanding of this dynamic regulation is critical to targeting future therapeutic strategies. Experiments elucidating this dynamic regulation have typically relied on in vitro reporter assays, ex vivo sample analysis, and transgenic mouse studies. Surprisingly, no experimental method to date allows rapid in vivo analysis of microRNA activity in mammals.

Methods

To improve microRNA studies we have developed a novel reporter assay for the measurement of skeletal muscle microRNA activity in vivo. To minimize muscle damage, hydrodynamic limb vein injection was used for the introduction of plasmid DNA encoding bioluminescent and fluorescent reporters, including click-beetle luciferase and the far-red fluorescent protein mKATE. We then applied this technique to the measurement of miR-206 activity in dystrophic mdx4cv animals.

Results

We found that hydrodynamic limb vein injection is minimally damaging to myofibers, and as a result no induction of muscle-specific miR-206 (indicative of an injury response) was detected. Unlike intramuscular injection or electroporation, we found that hydrodynamic limb vein injection results in dispersed reporter expression across multiple hindlimb muscle groups. Additionally, by utilizing click-beetle luciferase from Pyrophorus plagiophthalamus as a reporter and the far-red fluorescent protein mKATE for normalization, we show as a proof of principle that we can detect elevated miR-206 activity in mdx4cv animals when compared to C57Bl/6 controls.

Conclusion

Hydrodynamic limb vein injection of plasmid DNA followed by in vivo bioluminescent imaging is a novel assay for the detection of reporter activity in skeletal muscle in vivo. We believe that this method will allow for the rapid and precise detection of both transcriptional and post-transcriptional regulation of gene expression in response to skeletal muscle stress. Additionally, given the post-mitotic status of myofibers and stable expression of plasmid DNA, we believe this method will reduce biological variability in animal studies by allowing longitudinal studies of the same animal cohort.
The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus
Authors: Aubry Jean-Francois , Pauly Kim Butts , Moonen Chrit , Haar Gailter , Ries Mario , Salomir Rares , Sokka Sham , Sekins Kevin Michael , Shapira Yerucham , Ye Fangwei , Huff-Simonin Heather , Eames Matt , Hananel Arik , Kassell Neal , Napoli Alessandro , Hwang Joo Ha , Wu Feng , Zhang Lian , Melzer Andreas , Kim Young-sun , Gedroyc Wladyslaw M
Published: August 2013

Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer.
CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis
Authors: Lampinen Maria , Waddell Amanda , Ahrens Richard , Carlson Marie , Hogan Simon P
Published: August 2013

This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66bhigh) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14+CD33+ cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14+CCL11+ mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14+CD33+ myeloid cells, CCL11, and eosinophils in adult UC.
How can the service user voice be best heard at psychiatric meetings?
Authors: Burns Tom , Rose Diana
Published: August 2013

Service user contributions to mental health conferences are now routine. How effective they are at promoting dialogue is not clear. We report a difficult exchange following a presentation about coercive treatment, with our individual reflections on what we learnt.

Suggestions are made to improve both the clinical practice and the dialogue.
Collaborative care at the crossroads
Authors: Roy-Byrne Peter
Published: August 2013

Collaborative care is a well-studied and effective model of integrating behavioural healthcare into primary care medical settings. Despite evidence of its effectiveness, it has been difficult to implement into the US healthcare system. The upcoming reorganisation of US healthcare will rely heavily on adaptations of this model to improve its uptake and cost-effectiveness.
Dropping out of dialectical behaviour therapy in the NHS: the role of care coordination
Authors: Gaglia Amy , Essletzbichler Jurgen , Barnicot Kirsten , Bhatti Nyla , Priebe Stefan
Published: August 2013

Aims and method

Dialectical behaviour therapy (DBT) is associated with particularly high drop-out rates in the National Health Service (NHS). This paper seeks to investigate the characteristics of patients with borderline personality disorder dropping out from DBT and the role of care coordination in this phenomenon. Data for the 102 patients receiving DBT in east London, 58% of whom had dropped out of treatment prematurely, were analysed.

Results

In a multivariable analysis, a history of care coordination was the only variable significantly correlated with drop out: 88% of patients with a history of care coordination dropped out prematurely compared with 52% of patients without such history.

Clinical implications

The experience of comprehensive care within the care programme approach, particularly care coordination at the start of DBT, affects the retention of patients in DBT. Further qualitative research is required to understand how care coordination and DBT drop out are related, which could lead to changes in how the therapy is delivered in the UK and influence decisions regarding the use of care coordination with patients with borderline personality disorder.
Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling
Authors: Novikov Natasha , Evans Todd
Published: August 2013

Biphasic control of WNT signaling is essential during cardiogenesis, but how the pathway switches from promoting cardiac mesoderm to restricting cardiomyocyte progenitor fate is unknown. We identified genes expressed in lateral mesoderm that are dysregulated in zebrafish when both gata5 and gata6 are depleted, causing a block to cardiomyocyte specification. This screen identified tmem88a, which is expressed in the early cardiac progenitor field and was previously implicated in WNT modulation by overexpression studies. Depletion of tmem88a results in a profound cardiomyopathy, secondary to impaired cardiomyocyte specification. In tmem88a morphants, activation of the WNT pathway exacerbates the cardiomyocyte deficiency, whereas WNT inhibition rescues progenitor cells and cardiogenesis. We conclude that specification of cardiac fate downstream of gata5/6 involves activation of the tmem88a gene to constrain WNT signaling and expand the number of cardiac progenitors. Tmem88a is a novel component of the regulatory mechanism controlling the second phase of biphasic WNT activity essential for embryonic cardiogenesis.
Transcription factors lhx1/5-1 and pitx are required for the maintenance and regeneration of serotonergic neurons in planarians
Authors: Currie Ko W. , Pearson Bret J.
Published: August 2013

In contrast to most adult organisms, freshwater planarians can regenerate any injured body part, including their entire nervous system. This allows for the analysis of genes required for both the maintenance and regeneration of specific neural subtypes. In addition, the loss of specific neural subtypes may uncover previously unknown behavioral roles for that neural population in the context of the adult animal. Here we show that two homeodomain transcription factor homologs, Smed-lhx1/5-1 and Smed-pitx, are required for the maintenance and regeneration of serotonergic neurons in planarians. When either lhx1/5-1 or pitx was knocked down by RNA interference, the expression of multiple canonical markers for serotonergic neurons was lost. Surprisingly, the loss of serotonergic function uncovered a role for these neurons in the coordination of motile cilia on the ventral epidermis of planarians that are required for their nonmuscular gliding locomotion. Finally, we show that in addition to its requirement in serotonergic neurons, Smed-pitx is required for proper midline patterning during regeneration, when it is required for the expression of the midline-organizing molecules Smed-slit in the anterior and Smed-wnt1 in the posterior.
Phosphorylation of chemoattractant receptors regulates chemotaxis, actin re-organization, and signal-relay
Authors: Brzostowski Joseph A. , Sawai Satoshi , Rozov Orr , Liao Xin-hua , Imoto Daisuke , Parent Carole A. , Kimmel Alan R.
Published: August 2013

Migratory cells, like mammalian leukocytes and Dictyostelium, utilize G protein coupled receptor (GPCR) signaling to regulate MAPK/ERK, PI3K, TORC2/AKT, adenylyl cyclase, and actin polymerization, which collectively direct chemotaxis. Upon ligand binding, mammalian GPCRs are phosphorylated at cytoplasmic residues, uncoupling G protein pathways, but activating others. Still, connections between GPCR phosphorylation and chemotaxis are unclear. In developing Dictyostelium, secreted cAMP serves as a chemoattractant, with extracellular cAMP propagated as oscillating waves to ensure directional migratory signals. cAMP oscillations derive from transient excitatory responses of adenylyl cyclase, which then rapidly adapts. We have studied chemotactic signaling in Dictyostelium that express non-phosphorylatable cAMP receptors and show through chemotaxis modeling, single-cell FRET imaging, pure and chimeric population wavelet quantification, biochemical analyses, and TIRF microscopy, that receptor phosphorylation is required to regulate adenylyl cyclase adaptation, long-range oscillatory cAMP wave production, and cytoskeletal actin response. Phosphorylation defects, thus, promote hyperactive actin polymerization at the cell periphery, misdirected pseudopodia, and the loss of directional chemotaxis. Our data indicate that chemoattractant receptor phosphorylation is required to co-regulate essential pathways for migratory cell polarization and chemotaxis. Our results significantly extend the understanding of GPCR phosphorylation function, providing strong evidence that this evolutionarily conserved mechanism is required in a signal attenuation pathway that is necessary to maintain persistent directional movement of Dictyostelium, neutrophils, and other migratory cells.
Magnesium-Promoted Reductive Silylation and Acylation of Tropone and Tropone Acetal
Authors: Maekawa Hirofumi , Nagakubo Keisuke , Nishi Midori , Nishimura Makoto , Nagahara Daisuke
Published: August 2013

Magnesium-promoted reductive coupling of chlorotrialkylsilanes and tropone or tropone acetal in DMF, followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in benzene gives 2-trialkylsilyltropones as the main product, and the reductive coupling of tropone with acid anhydrides under similar reaction conditions yields benzene derivatives after ring contraction.
Detection of High-frequency Ultrasound-induced Singlet Oxygen by the ESR Spin-trapping Method
Authors: Matsumura Yuriko , Iwasawa Atsuo , Kobayashi Toshihiro , Kamachi Toshiaki , Ozawa Toshihiko , Kohno Masahiro
Published: August 2013

Singlet oxygen (1O2) generated by high-frequency (1.65 MHz) ultrasonic irradiation of an aqueous solution was detected using the electron spin resonance (ESR) spin-trapping method.
Wundauflagen in der Therapie chronischer Wunden
Authors: Schreml S. , Klein S. M. , Babilas P. , Karrer S.
Published: August 2013

Einleitung: Die nicht heilende Wunde stellt einen zunehmenden Kostenfaktor im Gesundheitssystem dar. Ziel der fachgerechten Wundtherapie ist es, die gestörte Wundhei-lung zu durchbrechen, um das Durchlaufen der physiologischen Abheilung zu ermögli-chen.

Methoden: Es erfolgte eine selektive Literaturrecherche in den Datenbanken AWMF, PubMed und Cochrane Library mit den Schlüsselwörtern „chronic wound” oder „ulcer” in Kombination mit den Begriffen alginates, hydrofibre, hydrogel, collagen, foam.

Ergebnisse: Die heute verfügbaren Wundtherapeutika erlauben es nicht, bei chronischen Wunden anstelle einer narbigen Reparatur eine physiologische Regeneration der Haut zu erreichen. Vor jeder Wundtherapie müssen mögliche Ursachen für die gestörte Wundhei-lung identifiziert werden und sofern möglich kausal therapiert werden. Zur topischen Therapie chronischer Wunden steht eine große Auswahl verschiedener Wundauflagen zur Verfügung. Die dezidierte Kenntnis dieser Wundtherapeutika ermöglicht deren differenzierten Einsatz, und ist damit die Voraussetzung für eine heilungsphasenadaptierte Anwendung.

Schlussfolgerung: Die derzeitige Studienlage erlaubt kaum Rückschlüsse auf die Überlegenheit einzelner Wundauflagen bezüglich des Endpunktes Wundverschluss. Obwohl die mangelhafte Evidenz die Entscheidung bei den Behandelnden für oder gegen die einzelnen Produkte erschwert, zeigt es auch, dass teure Wundauflagen preiswerteren Alternativen nicht eindeutig überlegen sind.
Ulcus cruris venosum auf dem Boden eines Adipositas-assoziierten Dependency-Syndroms
Authors: Altmeyer P. , Stücker M. , Doerler M.
Published: August 2013

Fallbericht: Wir beschreiben den Fall eines 42-jährigen adipösen Mannes, der sich mit fibrinös belegten Ulcera crurum in unserer Klinik vorstellte. Die Ulcera waren umgeben von Hyperpigmentierungen und einer initialen Dermatolipofasziosklerose. Duplexsonographisch zeigte sich eine Stammvarikosis der V. saphena magna am linken Bein. Am rechten Bein waren jedoch weder venöse Insuffizienzen noch Obstruktionen nachweisbar. Hinweise für eine periphere arterielle Verschlusskrankheit, ein Lymphödem oder Infektzei-chen fehlten.

Ergebnisse: Durch eine lokale Wundbehand-lung mit Polyurethan-Wundauflagen in Kombination mit einer Kompressionstherapie mit einem 2-lagigen Kompressionssystem konnte nach 8 Monaten eine vollständige Abheilung der Ulcera am rechten Bein erzielt werden. In Zusammenschau mit dem klinischen Bild stellten wir die Diagnose Ulcera crurum bei Adipositas-assoziiertem Dependency-Syndrom.

Diskussion: Das Adipositas-assoziierte Dependency Syndrom stellt eine Ursache für hydrostatische Ulcera ohne Vorhandensein von Klappeninsuffizienzen oder Obstruktionen dar und kann als funktionelle Veneninsuffizienz verstanden werden. Pathogenetisch liegt ein andauerndes Herabhängenlassen der Beine aufgrund von eingeschränkter Mobilität zugrunde. Zudem wurde eine Kompression der Beinvenen durch die abdominelle Fettschürze beschrieben. Therapeutisch stehen neben einer konsequenten Kompressionstherapie eine Remobilisierung der Patienten und eine Gewichtsreduktion im Vordergrund.

English version available at: www.phlebologieonline.de
Optimization Model for Robust Acquisition Decisions in the Norwegian Armed Forces
Authors: Fleischer Fauske Maria , Vestli Magnar , Glærum Sigurd
Published: August 2013

The Norwegian Defence Research Establishment (FFI) supports the Norwegian Ministry of Defence with quantitative analyses for its long-term defence planning. As part of this activity, FFI has developed a stochastic model for optimizing investments in materiel. The model maximizes the capabilities of the force structure (i.e., military personnel, equipment, and materiel) by allocating materiel acquisition projects over time, given certain constraints and considering the uncertainty of future-year budgets. The objective of the model is to make decisions about current acquisition projects, and also provide flexibility for future decisions. It models future budgets using a set of budget scenarios. The model helps decision makers explore project acquisition choices, and improve their knowledge of the total investment picture and of individual projects. The model has given FFI new insights into the dynamics of acquisition planning and the necessity for considering future uncertainty.
Optimal Production Management When Demand Depends on the Business Cycle
Authors: Cadenillas Abel , Lakner Peter , Pinedo Michael
Published: August 2013

We assume that the cumulative consumer demand for an item follows a Brownian motion, with both the drift and the variance parameters modulated by a continuous-time Markov chain that represents the regime of the economy. The management of the company would like to maintain the inventory level as close as possible to a target inventory level and would also like to produce at a rate that is as close as possible to a target production rate. The company is penalized for deviations from the target levels, and the objective is to minimize the total discounted penalty costs. We consider two models. In the first model the management of the company knows the state of the economy, whereas in the second model the management does not know it. We solve both problems and obtain the optimal production policy and the minimal total expected discounted cost. Furthermore, we compare the total expected discounted costs of the two models and determine the value of knowing the regime of the economy. We also solve the above problems in the case when the consumer demand rate follows a geometric Brownian motion modulated by a continuous-time Markov chain that represents the regime of the economy.
Optimal Bidding in Multi-Item Multislot Sponsored Search Auctions
Authors: Abhishek Vibhanshu , Hosanagar Kartik
Published: August 2013

We study optimal bidding strategies for advertisers in sponsored search auctions. In general, these auctions are run as variants of second-price auctions but have been shown to be incentive incompatible. Thus, advertisers have to be strategic about bidding. Uncertainty in the decision-making environment, budget constraints, and the presence of a large portfolio of keywords makes the bid optimization problem nontrivial. We present an analytical model to compute the optimal bids for keywords in an advertiser's portfolio. To validate our approach, we estimate the parameters of the model using data from an advertiser's sponsored search campaign and use the bids proposed by the model in a field experiment. The results of the field implementation show that the proposed bidding technique is very effective in practice. We extend our model to account for interactions between keywords, in the form of positive spillovers from generic keywords into branded keywords. The spillovers are estimated using a dynamic linear model framework and are used to jointly optimize the bids of the keywords using an approximate dynamic programming approach. Accounting for the interaction between keywords leads to an additional improvement in the campaign performance.
The Price of Strict and Light Robustness in Timetable Information
Authors: Goerigk Marc , Schmidt Marie , Schöbel Anita , Knoth Martin , Müller-Hannemann Matthias
Published: August 2013

In timetable information in public transport the goal is to search for a good path between an origin and a destination. Usually, the travel time and the number of transfers will be minimized. In this paper, we consider robust timetable information; i.e., we want to identify a path that will bring the passenger to the planned destination even in the case of delays. The classic notion of strict robustness leads to the problem of identifying those transfer activities that will never break in any of the expected delay scenarios. We show that this is, in general, a strongly NP-hard problem. Therefore, we propose a conservative heuristic which identifies a large subset of these strictly robust transfer activities in polynomial time by dynamic programming and so allows us to efficiently find strictly robust paths. We also transfer the notion of light robustness, originally introduced for timetabling, to timetable information. In computational experiments we then study the price of strict and light robustness: how much longer is the travel time of a robust path than of a shortest one, according to the published schedule? Based on the 2011 train schedule within Germany, we quantitatively explore the trade-off between the level of guaranteed robustness and the increase in travel time. Strict robustness turns out to be too conservative, whereas light robustness is promising: a modest level of guarantees is achievable at a reasonable price for the majority of passengers.
Thirty Years of Inventory Routing
Authors: Coelho Leandro C. , Cordeau Jean-François , Laporte Gilbert
Published: August 2013

The inventory-routing problem (IRP) dates back 30 years. It can be described as the combination of vehicle-routing and inventory management problems, in which a supplier has to deliver products to a number of geographically dispersed customers, subject to side constraints. It provides integrated logistics solutions by simultaneously optimizing inventory management, vehicle routing, and delivery scheduling. Some exact algorithms and several powerful metaheuristic and matheuristic approaches have been developed for this class of problems, especially in recent years. The purpose of this article is to provide a comprehensive review of this literature, based on a new classification of the problem. We categorize IRPs with respect to their structural variants and the availability of information on customer demand.
Dynamic ng-Path Relaxation for the Delivery Man Problem
Authors: Roberti Roberto , Mingozzi Aristide
Published: August 2013

The ng-path relaxation was introduced by Baldacci, Mingozzi, and Roberti [Baldacci R, Mingozzi A, Roberti R (2011) New route relaxation and pricing strategies for the vehicle routing problem. Oper. Res. 59(5):1269–1283] for computing tight lower bounds to vehicle routing problems by solving a relaxation of the set-partitioning formulation, where routes are not necessarily elementary and can contain predefined subtours. The strength of the achieved lower bounds depends on the subtours that routes can perform. In this paper, we introduce a new general bounding procedure called dynamic ng-path relaxation that enhances the one of Baldacci, Mingozzi, and Roberti (2011) by iteratively redefining the subtours that routes can perform. We apply the bounding procedure on the well-known delivery man problem, which is a generalization of the traveling salesman problem where costs for traversing arcs depend on their positions along the tour. The proposed bounding procedure is based on column generation and computes a sequence of nondecreasing lower bounds to the problem. The final lower bound is used to solve the problem to optimality with a simple dynamic programming recursion. An extensive computational analysis on benchmark instances from the TSPLIB shows that the new bounding procedure yields better lower bounds than those provided by the method of Baldacci, Mingozzi, and Roberti (2011). Furthermore, the proposed exact method outperforms other exact methods recently presented in the literature and is able to close five open instances with up to 150 vertices.