bluuebunny/crossref_metadata_2025 huggingface dataset:
Thromboembolism during neoadjuvant therapy for rectal cancer: a systematic review
Authors: Smart P. J. , Burbury K. L. , Lynch A. C. , Mackay J. R. , Heriot A. G.
Published: July 2013

Aim

Thromboembolism (TE) is a common, costly and morbid complication that is also associated with decreased survival in cancer patients. However, the risk of cancer‐associated TE varies because of the multitude of patient‐, cancer‐ and treatment‐related influences. Thromboprophylaxis (TP) is currently not widely adopted in the ambulant population. A review of the literature was undertaken to determine the rate of TE and the benefit of TP in patients with rectal cancer during neoadjuvant therapy (nT).

Method

A systematic literature search of electronic databases, including PubMed and Embase, was performed (1995–2012) for all studies assessing nT in rectal cancer. Data were extracted and used to assess study design, patient demographic and clinical characteristics, treatment protocols and TE incidence. A systematic review was conducted to identify the rates of TE. The search strategy included text terms and MeSH headings for TP, rectal cancer and nT.

Results

Twelve of 86 studies met quality criteria for reporting TE complications and described 10 pulmonary emboli and three deep‐vein thromboses in 3375 patients (overall TE rate = 0.38%). Ninety per cent of pulmonary emboli reported were fatal, suggesting significant under‐reporting of TE events, even in high‐quality studies.

Conclusion

The risk of fatal pulmonary embolism in studies examining nT in rectal cancer that reported complications systematically was one in 375 (0.27%; 95% CI: 0.09–0.44%). The overall TE rate, as well as the effectiveness of TP during nT, remains unknown. TE events should be systematically reported using common terminology frameworks in cancer studies.
Spawning movements of humpback whitefish in interiorAlaska rivers
Authors: Dupuis Aaron W. , Sutton Trent M.
Published: July 2013

This study was conducted to describe the spawning movements and identify spawning areas for humpback whitefishCoregonus pidschianin theMintoFlats–ChatanikaRiver complex,Alaska, during 2008 and 2009. Radio transmitters were surgically implanted in humpback whitefish in 2008 (N = 60) and 2009 (N = 100), and fish positions were determined through a combination of boat and aerial surveys and fixed receiving stations. Two spawning areas were identified: one in theChatanikaRiver downstream of theElliotHighwayBridge and the other in theTananaRiver nearFairbanks. Humpback whitefish dispersed from the wetland complex ofMintoFlats inJune, moved upstream through lateAugust, arrived at the spawning areas in earlySeptember and began moving downstream in earlyOctober. In 2009, spatially segregated movements were observed when approximately 40% of the radio‐tagged humpback whitefish moved to theTananaRiver, suggesting that humpback whitefish inMintoFlats are comprised of mixed spawning stocks. These study results provide a complete account of humpback whitefish movements and their associated spawning habitats, which will allow for better‐informed management strategies.
Cerebrospinal fluid biomarkers of neurodegeneration in patients with juvenile and classic myotonic dystrophy type 1
Authors: Peric S. , Mandic‐Stojmenovic G. , Markovic I. , Stefanova E. , Ilic V. , Parojcic A. , Misirlic‐Dencic S. , Ostojic M. , Rakocevic‐Stojanovic V. , Kostic V.
Published: July 2013

Background and purpose

The aim of the present study was to analyze cerebrospinal fluid (CSF) levels of total tau (T‐tau), phosphorylated tau (P‐tau) and the 42‐amino‐acid form of β‐amyloid (Aβ42) in patients with myotonic dystrophy type 1 (DM1), and their possible correlations with cognitive and behavioral manifestations in these patients.

Methods

Lumbar puncture was performed in 74 patients with DM1 [27 with the childhood/juvenile form (jDM1) and 47 with the adult form (aDM1) of the disease] and 26 control subjects who were subjected to orthopedic surgery. Sandwich ELISA was used for measuring the levels of T‐tau, P‐tau and Aβ42.

Results

The CSF level of Aβ42 was at its lowest in patients with jDM1 and at its highest in controls (P < 0.05). A tendency of T‐tau and P‐tau to increase was greater in aDM1 patients than in jDM1 patients and controls (P > 0.05). In both jDM1 and aDM1 patients, significant correlations were found between Aβ42 and T‐tau (rho = 0.81 and rho = 0.67, respectively, P < 0.01), as well as between Aβ42 and P‐tau (rho = 0.87 and rho = 0.67, respectively, P < 0.01). The Aβ42/P‐tau ratio decreased with age in aDM1 patients (rho = −0.30, P < 0.05). Only the level of Aβ42 in the CSF of jDM1 patients was correlated with the size of the CTG expansion (rho = −0.53, P < 0.05). Only a few correlations were observed between levels of biomarkers and neuropsychological testing.

Conclusion

The CSF level of Aβ42 was decreased in patients with jDM1, whilst the Aβ42/P‐tau ratio was decreased in aDM1 patients. Positive correlations between Aβ42, T‐tau and P‐tau were observed in both forms of disease. Further studies with larger cohorts of DM1 patients are necessary.
The unique N‐terminal region of SRMS regulates enzymatic activity and phosphorylation of its novel substrate docking protein 1
Authors: Goel Raghuveera K. , Miah Sayem , Black Kristin , Kalra Natasha , Dai Chenlu , Lukong Kiven E.
Published: July 2013

SRMS (Src‐related tyrosine kinase lacking C‐terminal regulatory tyrosine and N‐terminal myristoylation sites) belongs to a family of nonreceptor tyrosine kinases, which also includes breast tumour kinase and Fyn‐related kinase. SRMS, similar to breast tumour kinase and Fyn‐related kinase, harbours a Src homology 3 and Src homology 2, as well as a protein kinase domain. However, unlike breast tumour kinase and Fyn‐related kinase, SRMS lacks a C‐terminal regulatory tail but distinctively possesses an extended N‐terminal region. Both breast tumour kinase and Fyn‐related kinase play opposing roles in cell proliferation and signalling. SRMS, however, is an understudied member of this family. Although cloned in 1994, information on the biochemical, cellular and physiological roles of SRMS remains unreported. The present study is the first to explore the expression pattern of SRMS in breast cancers, its enzymatic activity and autoregulatory elements, and the characterization of docking protein 1 as its first bonafide substrate. We found that, similar to breast tumour kinase, SRMS is highly expressed in most breast cancers compared to normal mammary cell lines and tissues. We generated a series of SRMS point and deletion mutants and assessed enzymatic activity, subcellular localization and substrate recognition. We report for the first time that ectopically‐expressed SRMS is constitutively active and that its N‐terminal region regulates the enzymatic activity of the protein. Finally, we present evidence indicating that docking protein 1 is a direct substrate of SRMS. Our data demonstrate that, unlike members of the Src family, the enzymatic activity of SRMS is regulated by the intramolecular interactions involving the N‐terminus of the enzyme and that docking protein 1 is a bona fide substrate of SRMS.

Structured digital abstract

SRMS physically interacts with Dok-1 by pull down (View Interaction: 1, 2)

Dok-1 physically interacts with SRMS by anti bait coimmunoprecipitation (View Interaction: 1, 2, 3)

SRMS phosphorylates Dok-1 by protein kinase assay (View interaction)

Dok-1 physically interacts with SRMS by anti tag coimmunoprecipitation (View interaction)
Mechanisms of impaired differentiation in rhabdomyosarcoma
Authors: Keller Charles , Guttridge Denis C.
Published: July 2013

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, with presumed skeletal muscle origins, because of its myogenic phenotype. RMS is composed of two main subtypes, embryonal RMS (eRMS) and alveolar RMS (aRMS). Whereas eRMS histologically resembles embryonic skeletal muscle, the aRMS subtype is more aggressive and has a poorer prognosis. In addition, whereas the genetic profile of eRMS is not well established, aRMS is commonly associated with distinct chromosome translocations that fuse domains of the transcription factors Pax3 and Pax7 to the forkhead family member FOXO1A. Both eRMS and aRMS tumor cells express myogenic markers such as MyoD, but their ability to complete differentiation is impaired. How this impairment occurs is the subject of this review, which will focus on several themes, including signaling pathways that converge on Pax–forkhead gene targets, alterations in MyoD function, epigenetic modifications of myogenic promoters, and microRNAs whose expression patterns in RMS alter key regulatory circuits to help maintain tumor cells in an opportunistically less differentiated state.
A large proportion ofNorthAmerican net ecosystem production is offset by emissions from harvested products, river/stream evasion, and biomass burning
Authors: Turner David P. , Jacobson Andrew R. , Ritts William D. , Wang Weile L. , Nemani Ramakrishna
Published: July 2013

Diagnostic carbon cycle models produce estimates of net ecosystem production (NEP, the balance of net primary production and heterotrophic respiration) by integrating information from (i) satellite‐based observations of land surface vegetation characteristics; (ii) distributed meteorological data; and (iii) eddy covariance flux tower observations of net ecosystem exchange (NEE) (used in model parameterization). However, a full bottom‐up accounting ofNEE(the vertical carbon flux) that is suitable for integration with atmosphere‐based inversion modeling also includes emissions from decomposition/respiration of harvested forest and agricultural products,CO2evasion from streams and rivers, and biomass burning. Here, we produce a daily time stepNEEfor North America for the year 2004 that includesNEPas well as the additional emissions. ThisNEEproduct was run in the forward mode through the CarbonTracker inversion setup to evaluate its consistency withCO2concentration observations. The year 2004 was climatologically favorable forNEPoverNorthAmerica and the continental total was estimated at 1730 ± 370 TgC yr−1(a carbon sink). Harvested product emissions (316 ± 80 TgC yr−1), river/stream evasion (158 ± 50 TgC yr−1), and fire emissions (142 ± 45 TgC yr−1) counteracted a large proportion (35%) of theNEPsink. Geographic areas with strong carbon sinks included MidwestUScroplands, and forested regions of theNortheast,Southeast, andPacificNorthwest. The forward mode run with CarbonTracker produced good agreement between observed and simulated wintertimeCO2concentrations aggregated over eight measurement sites aroundNorthAmerica, but overestimates of summertime concentrations that suggested an underestimation of summertime carbon uptake. As terrestrialNEPis the dominant offset to fossil fuel emission overNorthAmerica, a good understanding of its spatial and temporal variation – as well as the fate of the carbon it sequesters ─ is needed for a comprehensive view of the carbon cycle.
Climate effects on amphibian distributions depend on phylogenetic resolution and the biogeographical history of taxa
Authors: Duarte L. D. S. , Both C. , Debastiani V. J. , Carlucci M. B. , Gonçalves L. O. , Cappelatti L. , Seger G. D. S. , Bastazini V. A. G. , Brum F. T. , Salengue E. V. , Bernardo‐Silva J. S.
Published: July 2013

Aim

Disentangling the effects of climate and historical factors on biodiversity distribution remains a challenge for biogeographers. Here, we provide an analytical framework to discriminate the contributions of contemporary climate and the biogeographical history of taxa to the geographical distributions of phylogenetic lineages. Furthermore, we evaluate the constraint that the biogeographical history of clades exerts on the association between climate and clade distribution, i.e. the historical legacy of climatic effects. As a case study, we analysed the distributions of amphibian lineages across the Americas.

Location

The Americas.

Methods

We tallied the number of amphibian species per genus in each of 262 ecoregions. Each ecoregion was described by the composition of phylogenetic lineages using phylogenetic fuzzy weighting. The composition of amphibian genera and phylogenetic clades represented the distributions of shallow and deep phylogenetic nodes, respectively. We characterized each ecoregion by the biogeographical history of amphibian taxa and its current climate, whose influences on shallow and deep phylogenetic nodes were analysed using variation partitioning analysis.

Results

The association between climate and the distributions of deep phylogenetic nodes showed a strong historical legacy, although the distribution of amphibian genera was mostly associated with climate. Hyloidea were associated with a Gondwanan origin and higher annual mean temperatures, whereas other clades (e.g. Caudata) were related to a Laurasian origin and higher temperature seasonality. Microhylidae were related to occurrence in the Early Jurassic in Gondwana and recent occurrence in the Neotropics.

Main conclusions

Biogeographical patterns can be thought of as the net outcome of evolutionary, historical and ecological processes. Although temperature is likely to affect the ecology of amphibians, the effects of climate on the distributions of deep phylogenetic nodes were strongly constrained by the biogeographical history of clades. Nevertheless, local, climatically driven processes are likely to influence the distributions of shallow phylogenetic nodes. The historical biogeography of clades might help to explain the interplay between evolutionary and environmental processes in determining assembly patterns found elsewhere.
Climate‐change‐driven deterioration of the condition of floodplain forest and the future for the avifauna
Authors: Mac Nally Ralph , Lada Hania , Cunningham Shaun C. , Thomson James R. , Fleishman Erica
Published: July 2013

Aim

We used models of remotely sensed estimates of forest‐stand condition (degree of die‐back) with models of avian responses to stand condition to determine how the avifauna responded to a 13‐year drought, and how the avifauna might respond to a predicted much warmer and drier climate in the next 60 years.

Location

Floodplain forests of the southern Murray–Darling Basin, Australia.

Methods

We selected 45 2‐ha locations that spanned the full range of stand condition and conducted bird surveys and rapid assessments of breeding, which involved repeated measurements over the breeding season. These values were modelled as functions of stand condition and several other on‐site predictors. We made hindcast estimates of the proportions of forest in different stand‐condition classes. We developed a trajectory of change in these proportions under the regionally downscaled estimates of climate change under the A1F1 IPCC emission scenario, which were linked with patterns of change in drier, hotter extant forests. The hindcast and projected values were coupled with the results of the statistical models for the avifauna to provide future projections for the avifauna.

Results

Three avifaunal variables (measures of abundance, effective species richness and total breeding score summed for all species) were strongly related to stand condition. Hindcast estimates based on the assumption of original good condition suggested that the response variables had declined by > 25% since 1750. Projected declines in the response variables from 2009 to 2070 were > 29%, while differences between 1750 and 2070 were > 58%.

Conclusions

Stand condition strongly influences birds, so that reliable estimates of avifaunal change can be made by using remotely sensed estimates of stand condition. Given probable changes in forest condition under climate change, we project that the prospects for these avifauna are dire under the A1F1 or more extreme emission scenarios.
Domain separation and characterization of PriC, a replication restart primosome factor in Escherichia coli
Authors: Aramaki Takahiko , Abe Yoshito , Ohkuri Takatoshi , Mishima Tomonori , Yamashita Shoji , Katayama Tsutomu , Ueda Tadashi
Published: July 2013

In Escherichia coli the oriC‐independent primosome plays an essential role in replication restart after dissociation of the replication DNA–protein complex by DNA damage. Primosome is thought to form via two pathways: one PriA dependent and the other PriA independent. PriC is a key protein in the replication restart of the PriA‐independent pathway. In this study, we determined that PriC was divided into two domains. Then, we obtained information that: (i) the C‐terminal domain preferentially binds to single‐stranded DNA (ssDNA); (ii) the binding of PriC to ssDNA depends on salt concentration; and (iii) the binding site size of PriC is approximately 7–9 nucleotides. The protease digestion of PriC suggested that a possible DNA‐binding site is the N‐terminus of the C‐terminal domain where basic amino acid residues are concentrated. Interestingly, α‐helical induction of the C‐terminal domain of PriC occurred after the addition of DNAs. Also, we examined the role of heptad repeat of leucine or valine residues in the C‐terminal domain and PriC oligomerization. This study describes the structure and function analysis of PriC which forms the primosome complex in replication restart.
The relationship between neutrophil‐to‐lymphocyte ratio and vascular calcification in end‐stage renal disease patients
Authors: Turkmen Kultigin , Ozcicek Fatih , Ozcicek Adalet , Akbas Emin Murat , Erdur Fatih Mehmet , Tonbul Halil Zeki
Published: July 2013

Chronic inflammation was found to be correlated with coronary (CAC) and thoracic peri‐aortic calcification (TAC) in end‐stage renal disease (ESRD) patients. Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in cardiac and noncardiac disorders. Data regarding NLR and its association with TAC and CAC are lacking. We aimed to determine the relationship between NLR and vascular calcification in ESRD patients. This was a cross‐sectional study involving 56 ESRD patients (22 females, 34 males; mean age, 49.9 ± 14.2 years) receiving peritoneal dialysis or hemodialysis for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. TAC and CAC scores were measured by using an electrocardiogram‐gated 64‐multidetector computed tomography. NLR was calculated as the ratio of the neutrophils and lymphocytes. There was a statistically significant correlation between NLR, TACS and CACS in ESRD patients (r = 0.43, P = 0.001 and r = 0.30, P = 0.02, respectively). The stepwise linear regression analysis revealed that age, as well as NLR were independent predictors of TACS. However, increased age was the only independent predictor of CACS according to linear regression analysis. Simple calculation of NLR can predict vascular calcification in ESRD patients.
Late‐moulting Black‐necked Grebes Podiceps nigricollis show greater body mass in the face of failing food supply
Authors: Fox Anthony D. , Ramo Cristina , Varo Nico , Sánchez Marta I. , Amat Juan A. , Green Andy J.
Published: July 2013

From August to December, thousands of Black‐necked Grebes Podiceps nigricollis concentrate during the flightless moult period in salt ponds in the Odiel Marshes, southern Spain, where they feed on the brine shrimp Artemia parthenogenetica. We predicted that because Black‐necked Grebes moulted in a food‐rich, predator‐free environment, there would be no net loss of body mass caused by the use of fat stored to meet energy needs during remigial feather replacement (as is the case for some other diving waterbirds). However, because the food resource disappears in winter, we predicted that grebes moulting later in the season would put on more body mass prior to moult because of the increasing risk of an Artemia population crash before the moult period is completed. Body mass determinations of thousands of birds captured during 2000–2010 showed that grebes in active wing‐moult showed greater mass with date of capture. Early‐moulting grebes were significantly lighter at all stages than late‐moulting birds. Grebes captured with new feathers post‐moult were significantly lighter than those in moult. This is the first study to support the hypothesis that individual waterbirds adopt different strategies in body mass accumulation according to timing of moult: early‐season grebes were able to acquire an excess of energy over expenditure and accumulate fat stores while moulting. Delayed moulters acquired greater fat stores in advance of moult to contribute to energy expenditure for feather replacement and retained extra stores later, most likely as a bet hedge against the increasing probability of failing food supply and higher thermoregulatory demands late in the season. An alternative hypothesis, that mass change is affected by a trophically transmitted cestode using brine shrimps as an intermediate host and Black‐necked Grebes as final host, was not supported by the data.
Revascularization of immature permanent teeth with apical periodontitis
Authors: Moreno‐Hidalgo M. C. , Caleza‐Jimenez C. , Mendoza‐Mendoza A. , Iglesias‐Linares A.
Published: July 2013

The aim of this minireview was to identify and review the scientific evidence regarding regenerative endodontic protocols claiming to revascularize permanent immature teeth with apical periodontitis. The literature was identified using the PubMed/MEDLINE, Scopus, Scirus, EMBASE and Cochrane databases up to February 2013. Studies were selected independently by two different researchers (kappa index: 0.88), based on established inclusion/exclusion criteria. The methodological quality of the reviewed papers was classified as high, medium or low (HQ, MQ, LQ). The search strategy identified 285 titles. Nine studies, both human and animal based, were selected after application of the criteria (LQ:5; MQ:4). In most of these studies (seven of nine), the revascularization protocol included a triple antibiotic combination as canal disinfectant for a period of 1–4 weeks after blood clot formation (LQ:5; MQ:4), although there is no clear consensus about the treatment protocol. Two studies reported tooth discoloration after the revascularization process (LQ:2), and only three (LQ:1; MQ:2) reported a success rate of 54.9% in dogs and 73.6% and 80% in humans, respectively.

Revascularization of immature permanent teeth with apical periodontitis is possible and preferable to apexification. Nevertheless, there is a widespread lack of randomized clinical trials and blinded measures. In addition, the small sample sizes that are common in these studies as well as the generally low quality of the analysed publications require the results to be viewed with caution. There is a high risk of bias, with a low quality of available information, for developing clinical guidelines for regenerative endodontic protocols; rigorous randomized clinical trials are therefore needed.
Reduction in Enteroccocus faecalis counts – a comparison between rotary and reciprocating systems
Authors: Ferrer‐Luque C. M. , Bejarano I. , Ruiz‐Linares M. , Baca P.
Published: July 2013

Aim

To compare the chemomechanical reduction and regrowth of Enterococcus faecalis between rotary and reciprocating systems in root canal preparation.

Methodology

Seventy‐six single‐rooted human mandibular premolars were selected and standardized to 15 mm in length. Root canals were enlarged up to a size 25 K‐file and irrigated with distilled water and then were infected with E. faecalis for 4 weeks. The specimens were divided into 3 groups (n = 24) for instrumentation with Mtwo, Twisted File and WaveOne. Each group was further divided into two subgroups (n = 12) according to the irrigant used: distilled water or 5.25% sodium hypochlorite (NaOCl). Before and after rotary preparation, microbiological samples were collected using three sterilized paper points, and efficacy was expressed as reduction in percentage. The proportion of grown samples for 60 days was evaluated using nonparametric Kaplan–Meier survival analysis. Differences amongst groups were tested using the log‐rank test at a significance level of 0.05.

Results

In the main root canal, the percentage reduction in the distilled water and 5.25% NaOCl groups ranged from 95.9% to 100%, with no significant differences amongst the three systems (P > 0.05). The bacterial regrowth in NaOCl groups revealed that Mtwo had the lowest number of samples regrown at 60 days, giving statistically significant differences with respect to Twisted File (P = 0.029) and WaveOne (P = 0.005).

Conclusions

Reciprocating and rotary systems resulted in similar percentage reduction in E. faecalis when using either distilled water or 5.25% NaOCl solution. Over time, the Mtwo system was more effective regarding disinfection.
An evaluation of the periapical status of teeth with necrotic pulps using periapical radiography and cone‐beam computed tomography
Authors: Abella F. , Patel S. , Durán‐Sindreu F. , Mercadé M. , Bueno R. , Roig M.
Published: July 2013

Aim

To evaluate the presence or absence of periapical (PA) radiolucencies on individual roots of teeth with necrotic pulps, as assessed with digital PA radiographs and cone‐beam computed tomography (CBCT).

Methodology

Digital PA radiographs and CBCT scans were taken from 161 endodontically untreated teeth (from 155 patients) diagnosed with non‐vital pulps (pulp necrosis with normal PA tissue, symptomatic apical periodontitis, asymptomatic apical periodontitis, acute apical abscess and chronic apical abscess). Images were assessed by two calibrated endodontists to analyse the radiographic PA status of the teeth. A consensus was reached in the event of any disagreement. The data were analysed using a McNemar's test, and significance was set at P ≤ 0.05.

Results

Three hundred and forty paired images of roots were assessed with both digital PA radiographs and CBCT images. Fifteen additional roots were identified with CBCT. PA radiolucencies were present in 132 (38.8%) roots when assessed with PA radiographs, and in 196 (57.6%) roots when assessed with CBCT. This difference was statistically significant (P < 0.05). In teeth diagnosed with pulp necrosis, symptomatic apical periodontitis or acute apical abscess, CBCT images revealed a statistically larger number of PA radiolucencies than did PA radiographs (P < 0.05). No statistical differences were observed between PA radiographs and CBCT in teeth classified with asymptomatic apical periodontitis (P = 0.31) or chronic apical abscess (P = 1).

Conclusions

Unlike PA radiographs, CBCT revealed a higher prevalence of PA radiolucencies when endodontically untreated teeth with non‐vital pulps were examined.
Genomic organization and reproductive regulation of a large lipid transfer protein in the varroa mite, Varroa destructor (Anderson & Trueman)
Authors: Cabrera A. R. , Shirk P. D. , Duehl A. J. , Donohue K. V. , Grozinger C. M. , Evans J. D. , Teal P. E. A.
Published: July 2013

The complete genomic region and corresponding transcript of the most abundant protein in phoretic varroa mites, Varroa destructor (Anderson & Trueman), were sequenced and have homology with acarine hemelipoglycoproteins and the large lipid transfer protein (LLTP) super family. The genomic sequence of VdLLTP included 14 introns and the mature transcript coded for a predicted polypeptide of 1575 amino acid residues. VdLLTP shared a minimum of 25% sequence identity with acarine LLTPs. Phylogenetic assessment showed VdLLTP was most closely related to Metaseiulus occidentalis vitellogenin and LLTP proteins of ticks; however, no heme binding by VdLLTP was detected. Analysis of lipids associated with VdLLTP showed that it was a carrier for free and esterified C12‐C22 fatty acids from triglycerides, diacylglycerides and monoacylglycerides. Additionally, cholesterol and β‐sitosterol were found as cholesterol esters linked to common fatty acids. Transcript levels of VdLLTP were 42 and 310 times higher in phoretic female mites when compared with males and quiescent deutonymphs, respectively. Coincident with initiation of the reproductive phase, VdLLTP transcript levels declined to a third of those in phoretic female mites. VdLLTP functions as an important lipid transporter and should provide a significant RNA interference target for assessing the control of varroa mites.
Cytochrome P450‐encoding genes from the Heliconius genome as candidates for cyanogenesis
Authors: Chauhan R. , Jones R. , Wilkinson P. , Pauchet Y. , ffrench‐Constant R. H.
Published: July 2013

Cytochrome P450s are important both in the metabolism of xenobiotics and the production of compounds such as cyanogenic glucosides, which insects use in their defence. In the present study, we use transcriptomic and genomic information to isolate and name P450‐encoding genes from the butterfly Heliconius melpomene. We classify each of the putative genes into its appropriate superfamily and compare the distribution of P450s across sequenced insects. We also identify homologues of two P450s known to be involved in cyanogenesis in the six‐spot Burnet moth, Zygaena filipendulae. Classification of Heliconius P450s should be an important step in the dissection of their role in the exploitation of their host plant, the passion vine Passiflora.
Pharmaceutical supply chain networks with outsourcing under price and quality competition
Authors: Nagurney Anna , Li Dong , Nagurney Ladimer S.
Published: July 2013

In this paper, we present a pharmaceutical supply chain network model with outsourcing under price and quality competition, in both equilibrium and dynamic versions. We consider a pharmaceutical firm that is engaged in determining the optimal pharmaceutical flows associated with its supply chain network activities in the form of manufacturing and distribution. In addition to multimarket demand satisfaction, the pharmaceutical firm seeks to minimize its total cost, with the associated function also capturing the firm's weighted disrepute cost caused by possible quality issues associated with the contractors. Simultaneously, the contractors, who compete with one another noncooperatively in prices in the manner of Bertrand, and in quality, seek to secure manufacturing and distribution of the pharmaceutical product from the pharmaceutical firm. This game theory model allows for the determination of the optimal pharmaceutical product flows associated with the supply chain in‐house and outsourcing network activities and provides the pharmaceutical firm with its optimal make‐or‐buy decisions and the optimal contractor selections. We state the governing equilibrium conditions and derive the equivalent variational inequality formulation. We then propose dynamic adjustment processes for the evolution of the product flows, the quality levels, and the prices, along with stability analysis results. The algorithm yields a discretization of the continuous‐time adjustment processes. We present convergence results and compute solutions to numerical examples to illustrate the generality and applicability of the framework.
A taxonomical analysis, current methods and objectives on location‐routing problems
Authors: Lopes Rui Borges , Ferreira Carlos , Santos Beatriz Sousa , Barreto Sérgio
Published: July 2013

Location‐routing is a branch of locational analysis that takes into account distribution aspects. This paper proposes a taxonomy, with two levels, for location‐routing problems. The first level focuses on the structural characteristics of the problems. The second level branches into the different algorithmic approaches and objective perspectives. An introduction to the previously defined problems is presented, categorising the papers in the literature (a total of 149 references) according to the proposed classification. Moreover, an overview of the most significant aspects of the different solution methods and main objectives, with special emphasis on multi‐objective approaches, is provided. Some data providing a better insight into the publication progress are also included. Finally, several promising research directions are identified.
MIP‐and‐refine matheuristic for smart grid energy management
Authors: Fischetti Matteo , Sartor Giorgio , Zanette Arrigo
Published: July 2013

In the past years, we have witnessed an increasing interest in smart buildings, in particular for optimal energy management, renewable energy sources, and smart appliances. In this paper, we investigate the problem of scheduling smart appliance operation in a given time horizon with a set of energy sources and accumulators. Appliance operation is modeled in terms of uninterruptible sequential phases with a given power demand, with the goal of minimizing the energy bill fulfilling duration, energy, and user preference constraints. A mixed‐integer linear programming (MIP) model and greedy heuristic algorithm are given, which are used in a synergic way. We show how a general purpose (off‐the‐shelf) MIP‐refining procedure can be effectively used for improving, in short computing time, the quality of the solutions provided by the initial greedy heuristic. Computational results confirm the viability of the overall approach, in terms of both solution quality and speed.
The biogeographic history of ruminant faunas determines the phylogenetic structure of their assemblages at different scales
Authors: Cantalapiedra Juan L. , Fernández Manuel Hernández , Morales Jorge
Published: July 2013

Phylogenetic community structure may help us understand how macroecological and macroevolutionary processes shape assemblages at large geographical scales. In this paper, we test hypotheses linking the formation of large‐scale assemblages, evolutionary processes and macroecology. To provide new insight into ruminant biogeography and evolution, phylogenetic community structure metrics were calculated for faunal assemblages at four hierarchical levels. Phylogenetic relatedness indices (net relatedness index and nearest taxon index) were determined for 59 ruminant assemblages at the landscape scale and scale of their respective climate domains (continuous biome stretches). Species pools at the global and biogeographic realm levels were used to construct null observation models. Significantly, assemblages were selected if they were distributed across biogeographic realms and represented all the world's biomes. Non‐random patterns were also tested for biogeographic realms within the global ruminant species pool. By examining ruminant assemblages at different scales we were able to observe that ruminant faunas show a distribution mainly limited within the boundaries of their biogeographic realms. However, the diversification of some clades was found to be restricted to extremely arid domains in the Sahara and Arabia. The random patterns featured by other extreme climate domains could reflect phylogenetically heterogeneous filling by less biome‐restricted lineages outside Africa.
Sleepiness in Spanish nursing staff – influence of chronotype and care unit in circadian rhythm impairment: research protocol
Authors: Moreno‐Casbas María Teresa , Ruzafa‐Martinez Maria , Rol Maria Angeles , Madrid Juan Antonio , Serrano Pinto Antonio , González‐María Esther , Fuentelsaz‐Gallego Carmen ,   The SYCE Network
Published: July 2013

Aims

To determine how prevalent circadian rhythm impairments are in nurses working in medical, surgical and intensive care units in five Spanish hospitals and how the quality of night‐time sleeping and sleepiness affect the nurses′ morning and evening chronotypes.

Background

Shift work is a recognized work pattern for nurses in all countries. Given the important role that nurses play in hospital care, it is vital to establish what repercussions this has on the nurses′ working schedules and how any disturbance in circadian rhythm affects patient safety.

Design

A multicentre, observational, descriptive and cross‐sectional study in seven hospitals in the Spanish National Health System.

Method

A stratified sample of 1,300 nurses is being collected in three types of units: medical, surgical and intensive care. The 3‐year study started in January 2012 and will continue until December 2014, with no exclusion criteria. The Kronowise® will be used to monitor the nurses' circadian rhythms, by recording their activity, position and wrist temperature. We will also use three questionnaires to evaluate sleep quality, daytime drowsiness and chronotype: (a) Pittsburg Sleep Quality Index; (b) Epworth Daytime Sleepiness Scale; and (c) Morning and Evening Questionnaire. Data will be collected from each hospital and statistical analysis will be carried out using the SPSS 19.0.

Discussion

The study findings will show the current state of the nurses' circadian rhythms and how shift work can affect them and their job performance. Funding for this 3‐year study was granted in December 2011 by the Spanish Health Research Fund (PI 11/00646, Health Ministry). This project is also funded by the Instituto de Salud Carlos III (RETICEF, RD12/0043/0011, RD12/0043/0006).
Control in chronic condition self‐care management: how it occurs in the health worker–client relationship and implications for client empowerment
Authors: Lawn Sharon , Delany Toni , Sweet Linda , Battersby Malcolm , C. Skinner Timothy
Published: July 2013

Aim

To examine health worker–client interactions during care planning to understand processes that foster client empowerment and disempowerment.

Background

It is unclear how health worker–client exchanges and information sharing through chronic condition care planning currently operate in primary health care. Moreover, it is unclear how control in these exchanges either enhances collaborative decision‐making, partnership and client empowerment, or works to create client disempowerment and dependency on workers and health services.

Design

Critical discourse analysis of qualitative data from ethnographic observations and audio‐taped worker–client consultations.

Method

Multidisciplinary teams in two Australian community‐based primary healthcare sites participated. This included nurses, general practitioners and allied health workers and their clients who had a chronic condition care plan. Nineteen worker–client consultations were observed/recorded in 2011.

Results

Control was expressed through multiple processes inherent in the worker role and in their interactions with clients. When workers exercised disproportionate control and clients relinquished their own control, client disempowerment and dependency were evident. Clients' attempts to gain control and workers' attempts to relinquish control alleviated clients' disempowerment and dependency. However, structural features of information sharing systems and workers' care planning behaviours diminished such efforts.

Conclusion

Worker awareness of their communication style and the power of their role must improve for client chronic condition self‐care management to be achieved. Training on the impacts of control in worker communication and systems where they work must be provided if unbeneficial forms of client dependency are to be overcome and true self‐care management is to be realized.
The relationship between goal orientation and career striving in young adolescents
Authors: Creed Peter , Buys Nick , Tilbury Clare , Crawford Meegan
Published: July 2013

We surveyed 280 students (61% girls; M = 15.3 years) and, in the context of goal setting theory and self‐regulation, tested a cross‐sectional model in which goal orientation (learning, performance–prove, performance–avoid) was viewed as an antecedent to self‐efficacy and outcome expectations, self‐efficacy and outcome expectations were tested as antecedents to goal setting, and goal setting tested as an antecedent to career‐striving behaviors (exploration, planning). After controlling for educational achievement, learning orientation was directly, positively, associated with self‐efficacy and outcome expectations, and indirectly associated with career aspirations, career exploration, and planning; and performance–avoid orientation was negatively associated with self‐efficacy. The study demonstrated that goal orientation is an important variable to consider when examining career development in adolescents.
Predictors of fear of crime: general fear versus perceived risk
Authors: Chadee Derek , Ng Ying Nikita K.
Published: July 2013

Much of the literature on fear of crime (FOC) has focused on the role of risk perceptions in understanding FOC, with little consideration given to psychological factors not directly related to crime, but that can impact the levels of FOC. This study introduces general fear (GF) as an explanatory factor in understanding FOC. A proportional random sample of 1,197 respondents was obtained from 406 enumeration districts across Trinidad. The results revealed GF as the strongest predictor of FOC across ethnicity, sex, age, area of residence, and victim status. Explanations and areas for further investigation are offered.
Mesenchymal stem cells in acute lung injury: are they ready for translational medicine?
Authors: Xu Feng , Hu Yue , Zhou Jiebai , Wang Xiangdong
Published: July 2013

Acute lung injury (ALI) is a severe clinical condition responsible for high mortality and the development of multiple organ dysfunctions, because of the lack of specific and effective therapies for ALI. Increasing evidence from pre‐clinical studies supports preventive and therapeutic effects of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in ALI/ARDS (acute respiratory distress syndrome). Therapeutic effects of MSCs were noticed in various delivery approaches (systemic, local, or other locations), multiple origins (bone marrow or other tissues), or different schedules of administrations (before or after the challenges). MSCs could reduce the over‐production of inflammatory mediators, leucocyte infiltration, tissue injury and pulmonary failure, and produce a number of benefit factors through interaction with other cells in the process of lung tissue repair. Thus, it is necessary to establish guidelines, standard operating procedures and evaluation criteria for translating MSC‐based therapies into clinical application for patients with ALI.
Gene variants associated with antisocial behaviour: a latent variable approach
Authors: Bentley Mary Jane , Lin Haiqun , Fernandez Thomas V. , Lee Maria , Yrigollen Carolyn M. , Pakstis Andrew J. , Katsovich Liliya , Olds David L. , Grigorenko Elena L. , Leckman James F.
Published: July 2013

Objective

The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years.

Methods

Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15‐year follow‐up of a randomized trial of a prenatal and infancy nurse‐home visitation programme in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed.

Results

Eight single‐nucleotide polymorphisms (SNPs) from eight genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all eight genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid and cholinergic signalling as well as stress response pathways in mediating susceptibility to antisocial behaviour.

Conclusions

This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential ‘co‐action’ of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the aetiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a ‘shared’ variance across genetic risk alleles associated with complex neuropsychiatric dimensional phenotypes using relatively small numbers of well‐characterized research participants.
Treatment of psoriasis with non‐registered fumaric acid esters in The Netherlands: a nationwide survey among Dutch dermatologists
Authors: Fallah Arani S. , Balak D.M.W. , Neumann H.A.M. , Kuipers M.V. , Thio H.B.
Published: July 2013

Background

Psoriasis vulgaris is a T‐cell mediated disease that affects 2–3% of the worldwide white‐skinned population. Fumaric acid esters are mentioned as an effective therapy for moderate‐to‐severe psoriasis vulgaris in adult patients in the new guidelines for psoriasis treatment.

Objectives

To obtain an insight into the use of fumaric acid esters by Dutch dermatologists in the Netherlands.

Methods

This was a cross‐sectional postal survey. An anonymous survey was posted to all Dutch dermatologists. In this survey, data were collected on the extent of fumaric acid esters use, the reasons for use, the reasons for non‐ or limited use of fumaric acid esters, the perception of fumaric acid esters as a mono‐therapy with regards to the effectiveness, the safety, the adverse events and the overall satisfaction of fumaric acid esters as a mono‐therapy.

Results

Sixty‐three per cent of the 300 responders indicated to prescribe fumaric acid esters for the treatment of psoriasis. About 37% of the dermatologists indicated (almost) never to prescribe it. Biologicals were considered as the most effective therapy. Fumaric acid esters were regarded as the safest therapy. They were generally well‐tolerated by the patients similar to that for methotrexate according to the respondents.

Conclusion

A large proportion of the dermatologists in our survey indicated to prescribe fumaric acid esters. It is considered to be effective, safe and without adverse events profile that is favourable in the practice, also as compared with other systemic therapies such as methotrexate and biologicals.
Testing probabilistic adaptive real‐time flood forecasting models
Authors: Smith P.J. , Beven K.J. , Leedal D. , Weerts A.H. , Young P.C.
Published: July 2013

Operational flood forecasting has become a complex and multifaceted task, increasingly being treated in probabilistic ways to allow for the inherent uncertainties in the forecasting process. This paper reviews recent applications of data‐based mechanistic (DBM) models within the operationalUK NationalFloodForecastingSystem. The position ofDBMmodels in the forecasting chain is considered along with their offline calibration and validation. The online adaptive implementation with assimilation of water level information as used for forecasting is outlined. Two example applications based uponUKlocations where severe flooding has occurred, theRiverEden atCarlisle andRiverSevern atShrewsbury, are presented.