bluuebunny/crossref_metadata_2025 huggingface dataset:
In search of miracles: pilgrimage to the miraculous places
Authors: Liutikas Darius
Published: July 2015

Purpose

– The purpose of this paper is to discuss various aspects of the development of the places of apparitions and miraculous images, motives and behavioral characteristics of pilgrims coming to the miraculous places of the Virgin Mary in Lithuania.

Design/methodology/approach

– The paper reviews literature about miraculous events and presents miraculous places in Lithuania (apparition places of the Virgin Mary and sites of miraculous images). Various classifications are applied. Pilgrims
'
motivation and behavioral aspects are analyzed based on the quantitative survey.

Findings

– The research showed that the main motives of religious pilgrims visiting miraculous places were asking for God’s grace, health, expressing gratitude to Jesus or Virgin Mary as well as spiritual quest and renewal. These places attract pilgrims who want to solve different problems in their life or to recover from illnesses. Religious pilgrimage has different forms and rituals, and constitutes different models of the specific behavior. During the journey, pilgrims perform various religious practices such as praying, singing hymns, kissing the relics, etc. The grouping of devotional rituals performed during the pilgrimage and at the destination place is presented.

Originality/value

– The paper is important to the researchers of pilgrimage and religious tourism. For the first time, miraculous places of Lithuania are analyzed in the broader international context. Classifications of the miraculous sites indicate various aspects of the development of these places. Motives and behavioral characteristics of pilgrims enable to better understand the multidimensional reality of religious pilgrimage.
Religious tourism and religious tolerance: insights from pilgrimage sites in India
Authors: Shinde Kiran A
Published: July 2015

Purpose

– This paper aims to explore the ways in which religious tourism in India fosters religious tolerance.

Design/methodology/approach

– The paper uses a conceptual apparatus derived from the basic structure of religious tourism comprising motivation, journey and destination, to understand various aspects of tolerance. Tolerance, with the implicit meaning of diversity and pluralism, is examined at two levels – intra-religion and inter-religion – using field investigations from three Hindu pilgrimage sites, namely, Vrindavan, Tuljapur, Shegaon and review of one Muslim site called Ajmer Sharif. These sites exhibit a range of combinations, sectarian traditions within Hindu and their interactions with others, including Muslims and foreigners.

Findings

– Each of the sites provides different sets of opportunities for the “others” to get exposed to religious and cultural aspects. It is found that tolerance within the Hindu sects and with non-Hindus from other religious faiths is a function of their engagement with cultural performances and participation in the religious tourism economy in a pilgrimage site.

Originality/value

– On a broader level, this paper argues that conceptualising tolerance within a social and cultural sphere helps in a better understanding of tolerance and identifying areas within religious tourism where it can be promoted. A conscious effort to promote tolerance through religious tourism will add value to religious tourism and help it thrive.
Soil acidification exerts a greater control on soil respiration than soil nitrogen availability in grasslands subjected to long‐term nitrogen enrichment
Authors: Chen Dima , Li Jianjun , Lan Zhichun , Hu Shuijin , Bai Yongfei
Published: July 2015

Terrestrial ecosystems worldwide are receiving increasing amounts of biologically reactive nitrogen (N) as a consequence of anthropogenic activities. This intended or unintended fertilization can have a wide‐range of impacts on biotic communities and hence on soil respiration.

Reduction in below‐ground carbon (C) allocation induced by high N availability has been assumed to be a major mechanism determining the effects of N enrichment on soil respiration. In addition to increasing available N, however, N enrichment causes soil acidification, which may also affect root and microbial activities. The relative importance of increased N availability vs. soil acidification on soil respiration in natural ecosystems experiencing N enrichment is unclear.

We conducted a 12‐year N enrichment experiment and a 4‐year complementary acid addition experiment in a semi‐arid Inner Mongolian grassland. We found that N enrichment had contrasting effects on root and microbial respiration. N enrichment significantly increased root biomass, root N content and specific root respiration, thereby promoting root respiration. In contrast, N enrichment significantly suppressed microbial respiration likely by reducing total microbial biomass and changing the microbial community composition.

The effect on root activities was due to both soil acidity and increased available N, while the effect on microbes primarily stemmed from soil acidity, which was further confirmed by results from the acid addition experiment. Our results indicate that soil acidification exerts a greater control than soil N availability on soil respiration in grasslands experiencing long‐term N enrichment.

These findings suggest that N‐induced soil acidification should be included in predicting terrestrial ecosystem C balance under future N deposition scenarios.
A comparison of clearfelling and gradual thinning of plantations for the restoration of insect herbivores and woodland plants
Authors: Atkinson Beth , Bailey Sallie , Vaughan Ian P. , Memmott Jane
Published: July 2015

Testing restoration methods is essential for the development of restoration ecology as a science. It is also important to monitor a range of taxa, not just plants which have been the traditional focus of restoration ecology. Here, we compare the effects on ground flora and leaf‐miners, of two restoration practices used when restoring conifer plantations.

Two methods of restoration were investigated: clearfelling of plantations and the gradual thinning of conifers over time. Unrestored plantations and native broadleaved woodlands were also surveyed, these representing the starting point of restoration and the reference community, respectively. The study sites consist of two forest types (acidic Quercus woodland and mesotrophic Fraxinus woodland) enabling us to compare the two restoration methods in different habitat types. We use a well‐replicated, large‐scale study system consisting of 32 woodland plots, each 2 ha in size.

There were 179 plant species identified in the plots. Clearfelled plots had greater overall ground flora species richness than other management regimes (thinned, unrestored plantation and native woodland), but the richness of woodland plant species did not differ between clearfelled, thinned, native woodland and unrestored plantation plots.

More than 10 000 leaf‐miners comprising 122 species were collected. Increased plant species richness was associated with increased leaf‐miner species richness under all management regimes except clearfelled plots.

Forest type did not affect the response to restoration method; that is, there was no interaction between management regime and forest type for any of the variables measured.

Synthesis and applications. Our results suggest that both the clearfelling and gradual thinning approaches to plantation restoration maintain woodland ground flora species. Either method can be used without detriment to woodland ground flora species richness. However, these methods differed in their effects on the leaf‐miner–plant species richness relationship. If increasing invertebrate herbivore species richness is a concern, the gradual thinning approach is more appropriate.
Taxonomic review of the genusLymantria(Lepidoptera:Erebidae:Lymantriinae) inKorea
Authors: Lee Kwang‐Su , Kang Tae Hwa , Jeong Ji Woong , Ryu Dong Pyo , Lee Heung‐Sik
Published: July 2015

A taxonomic review of theKoreanLymantria Hübner, 1819 was conducted. A total of nine species of five subgenera with two unrecorded species are listed:Lymantria(Porthetria)dispar Linnaeus 1758,L. (P.)xylina Swinhoe 1903,L. (Lymantria)monacha(Linnaeus 1758),L. (L.)minomonis Matsumura 1933 (new toKorea),L. (L.)similis monachoidesSchintlimeister 2004 (new toKorea),L. (L.)lucescens(Butler 1881),L. (Nyctria)mathura Moore 1865,L. (Collentria)fumida Butler 1877, andL. (Spinotria)bantaizana Matsumura 1933.Lymantria(Lymantria)minomonisandL. (L.)similis monachoidesare newly added to theKorean fauna.Lymantria(L.)minomoniswas found only onBogildo Island ofJeollanam‐do in the southern part ofKorea, andL. (L.)similis monachoideswas collected in centralKorea.Lymantria(Porthetria)xylinaandL. (Collentria)fumidawere not examined in this study, and it is considered that the previous records were due to misidentification or they are only distributed in the northern part of theKoreanPeninsula. We provide diagnoses of two unrecorded species and adult habitus and genitalia photos of theKoreanLymantriaspecies.
Influences of food sources on reproduction and aggregation pheromone production of Riptortus pedestris (Hemiptera: Alydidae) in its adult stage
Authors: Lim Eugene , Kim Junheon , Cho Kwang‐Sik , Yun Jae Gill , Park Chung Gyoo
Published: July 2015

The dietary importance of sweet persimmon fruit (SPF) was determined in adult bean bug, Riptortus pedestris, by investigating the effect of feeding SPF and soybean seeds and peanut on longevity, weight change, fecundity and ability for pheromone production in the bean bug. Adult female R. pedestris fed on SPF had significantly shorter lifespans than those fed on soybean, while in males there was no significant difference. Males and females fed on SPF were significantly lighter than those fed on soybean seeds. Females fed on SPF did not lay eggs at all, but those fed on soybean laid 155.8 eggs, and those fed on soybean seed complemented with peanut seed laid 120.8 eggs in 50 days. The amount of pheromone components (E)‐2‐hexenyl (E)‐2‐hexenoate and (E)‐2‐hexenyl (Z)‐2‐hexenoate produced by male R. pedestris fed on SPF was significantly less than that produced by males fed on soybean. Other pheromone components, tetradecyl isobutyrate and octadecyl isobutyrate, were not produced by adult males fed on SPF. This difference was apparent at one week after emergence and was more at three weeks after emergence. In the present study, we demonstrated that SPF had adverse effect on female survivorship, reproduction of female adults and production of the aggregation pheromone by adult males, compared to soybean food. These results suggested that SPF is unsuitable for adult R. pedestris. Management of nearby vegetation of fruit orchards may play an important role in reducing damage by adult R. pedestris.
The face of conservation responding to a dynamically changing world
Authors: WIEDERHOLT Ruscena , TRAINOR Anne M. , MICHEL Nicole , SHIREY Patrick D. , SWAISGOOD Ronald R. , TALLAMY Doug , COOK‐PATTON Susan C.
Published: July 2015

In its 40‐year history, the science of conservation has faced unprecedented challenges in terms of environmental damage and rapid global change, and environmental problems are only increasing as greater demands are placed on limited natural resources. Conservation science has been adapting to keep pace with these changes. Here, we highlight contemporary and emerging trends and innovations in conservation science that we believe represent the most effective responses to biodiversity threats. We focus on specific areas where conservation science has had to adjust its approach to address emerging threats to biodiversity, including habitat destruction and degradation, climate change, declining populations and invasive species. We also document changes in attitudes, norms and practices among conservation scientists. A key component to success is engaging and maintaining public support for conservation, which can be facilitated through the use of technology. These recent trends in conservation and management are innovative and will assist in optimizing conservation strategies, increasing our leverage with the general public and tackling our current environmental challenges.
Yolk‐sac larval development of the substrate‐brooding cichlid Archocentrus nigrofasciatus in relation to temperature
Authors: VLAHOS Nikolaos , VASILOPOULOS Michael , MENTE Eleni , HOTOS George , KATSELIS George , VIDALIS Kosmas
Published: July 2015

In order to conserve and culture the cichlid fish Archocentrus nigrofasciatus, more information about its reproductive biology and its larval behavior and morphogenesis is necessary. Currently, temperatures ranging from 21 to 27 °C are used in ornamental aquaculture hatcheries. Lower temperatures are preferred to reduce the costs of water heating, and 23 °C is usually the selected temperature. However, there is limited information on culturing protocols for ornamental species and most of the information generated on this topic remains scarce. Thus, the present study examines the morphological development of Archocentrus nigrofasciatus during the yolk‐sac period up to the age of 100 h post‐hatching in relation to 2 temperature regimes used in ornamental aquaculture: a temperature of 27 °C (thermal optimum) and a decreased temperature of 23 °C (thermal tolerance). The results of this study suggest that the 27 °C temperature generates intense morphological changes in yolk‐sac development in a shorter period. This has advantages as it reduces the time of yolk‐sac larval development, and, thus, minimizes the transition phase to exogenous feeding and maximizes the efficiency at which yolk is converted into body tissues. The present paper provides necessary information to produce freshwater ornamental fish with better practices so as to increase larval survival and capitalize on time for growth.
The provision of convenience and variety by the market
Authors: Bronnenberg Bart J.
Published: July 2015

Consumers commonly face purchasing costs, for example, travel or wait time, that are fixed to quantity but increase with variety. This article investigates the impact of such costs on the demand and supply of variety. Purchasing costs limit demand for variety like prices limit demand for quantity. When demand for variety is low, manufacturers generally invest substantially in lowering purchasing costs, to attract consumers. In the monopolistic competition free‐entry equilibrium, providing convenience increases the demand for variety, but its costs reduce supply. The desirability of nonprice competition in convenience and its implications for variety and market concentration are discussed.
Patent pools, litigation, and innovation
Authors: Choi Jay Pil , Gerlach Heiko
Published: July 2015

This article analyzes patent pools and their effects on litigation incentives, overall royalty rates, and social welfare when patent rights are probabilistic and can be invalidated in court. With probabilistic patents, the license fees reflect the strength of the patents. We show that patent pools of complementary patents can be used to discourage infringement by depriving potential licensees of the ability to selectively challenge patents and making them committed to a proposition of all‐or‐nothing in patent litigation. If patents are sufficiently weak, patent pools with complementary patents reduce social welfare as they charge higher licensing fees and chill subsequent innovation incentives.
Building new plants or entering by acquisition? Firm heterogeneity and entry barriers in the U.S. cement industry
Authors: Perez‐Saiz Hector
Published: July 2015

I estimate a model of entry for the cement industry that considers two options of expansion: building a plant or acquiring an incumbent. The model takes into account that there is a transfer of the buyer firm‐level characteristics to the acquired plants, which affects profits from the acquisition. Estimates show that a less‐permissive Reagan–Bush administration's merger policy would decrease the number of acquired plants by 71%, greenfield entry would increase by 9.2% and consumer surplus would decrease by 23.5%. Results suggest that regulators should be concerned about policies that negatively affect the efficient reallocation of assets between incumbents and entrants.
Controlling opportunism in vertical contracting when production precedes sales
Authors: Montez João
Published: July 2015

In a make‐to‐stock vertical contracting setting with private contracts, when retailers do not observe each other's stocks before choosing their prices, an opportunism problem always exist in contract equilibria but public market‐wide Resale Price Maintenance (RPM) can restore monopoly power. However other widely used tools which do not fall under antitrust scrutiny and require only private bilateral contracts, such as buyback contracts, also allow the producer to fully exercise his monopoly power. We conclude that a more lenient policy toward RPM is unlikely to affect the producer's ability to control opportunism.
Intrapartum assessment of caput succedaneum by transperineal ultrasound: a two‐centre pilot study
Authors: Hassan Wassim A. , Eggebo Torbjorn M. , Salvesen Kjell A. , Lindtjorn Elsa , Lees Christoph
Published: July 2015

Digital assessments of caput succedaneum are subjective; however, caput succedaneum can also be expressed as ultrasound measured skin–skull distance (SSD). In this study, we aimed to compare the clinical and ultrasound assessment of caput succedaneum (caput) in nulliparous women in the first stage of labour. Furthermore, we aimed to investigate the repeatability of ultrasound measurements. We observed a significant but low correlation between clinical and ultrasound assessments (Kappa value 0.29; P < 0.01). Interobserver repeatability for SSD showed an intraclass correlation coefficient of 0.96 (95% CI, 0.93–0.98). The mean difference for the caput measurements was −0.4 mm (95% CI, −0.85 to 0.05), and limits of agreement were −3.44 to 2.64 mm. We conclude that ultrasound measured SSD is an objective expression of caput with significant correlation with clinical assessment.
Sperm DNA fragmentation abnormalities in men from couples with a history of recurrent miscarriage
Authors: Leach Mikaela , Aitken Robert J. , Sacks Gavin
Published: July 2015

Background

Previous studies have described an association between sperm with DNA damage and a history of recurrent miscarriage (RM), although it is not clear whether there is benefit in screening for sperm DNA fragmentation and to what extent DNA fragmentation impacts upon RM.

Aims

To identify what proportion of couples experiencing RM are affected by DNA fragmentation abnormalities.

Materials and Methods

In this retrospective study, between 2008 and 2013, couples with a history of recurrent miscarriage (≥3 first trimester miscarriages) were investigated comprehensively for known causes (karyotype, uterine, antiphospholipid syndrome, thrombophilia) and also by semen analysis, including DNA fragmentation [sperm chromatin structure analysis (SCSA)]. Statistical analysis was performed on SPSS software with significance taken as P < 0.05.

Results

There were 108 couples with a median sperm DNA fragmentation index (DFI) of 9.50%. Normal levels were found in 70.5% of men (DFI < 15%), 23% had high levels (DFI 15–30%), and 6.5% had very high levels (DFI > 30%). Couples with otherwise unexplained recurrent miscarriage had significantly higher DFI than those with other causes identified on routine screening (P = 0.012).

Conclusions

In couples experiencing RM, 30% (32/108) of men had sperm with high levels of DNA fragmentation (DFI > 15%). This may be a contributing factor to the clinical syndrome of RM, and future clinical trials of therapies for these couples are warranted.
Engagement, Disengagement, or Exit: A Theory of Equilibrium Associations
Authors: Penn Elizabeth Maggie
Published: July 2015

This article considers the possibility of mutually beneficial communication among groups when any group may choose to unilaterally join or exit an alliance. My main concern is the trade‐off groups face between the informational benefits of associating with others in a large society versus the costs imposed by power sharing and preference diversity. When these costs are sufficiently high, groups may prefer exit to association. The results of this article characterize the associations of groups that can be sustained in equilibrium, and within those associations, the types of groups that choose to meaningfully communicate with others. The results demonstrate that there can be benefits or costs associated with the inclusion of preference extremists in a diverse society, whether or not those extremists choose to actively communicate with outgroups. The results also speak to institutional mechanisms for fostering communication across diverse groups.
Topical dexamethasone γ‐cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema
Authors: Ohira Akihiro , Hara Katsunori , Jóhannesson Gauti , Tanito Masaki , Ásgrímsdóttir Gudrún Marta , Lund Sigrún H. , Loftsson Thorsteinn , Stefánsson Einar
Published: July 2015

Purpose

To compare in a randomized, controlled trial topical 1.5% dexamethasone γ‐cyclodextrin nanoparticle eye drops (DexNP) with posterior subtenon injection of triamcinolone acetonide in diabetic macular oedema (DME).

Methods

In this prospective, randomized, controlled trial, 22 eyes of 22 consecutive patients with DME were randomized to (i) topical treatment with DexNP ×3/day (4 weeks), ×2/day (4 weeks) and ×1/day (4 weeks) or (ii) one posterior subtenon injection of 20 mg triamcinolone acetonide. Study visits were at baseline and 4, 8, 12 and 16 weeks.

Results

The logMAR (Snellen) visual acuity (mean ± SD) improved significantly with DexNP from 0.41 ± 0.3 (Snellen 0.39) to 0.32 ± 0.25 (0.48) and 0.30 ± 0.26 (0.50) at 4 and 8 weeks, respectively. One‐third of the DexNP group improved more than 0.3 logMAR units. For triamcinolone, logMAR changed significantly from 0.42 ± 0.28 (0.38) at baseline to 0.32 ± 0.29 (0.48) at 4w and 0.33 ± 0.37 (0.47) at 12w. The central macular thickness (CMT) decreased significantly with DexNP from 483 ± 141 μm to 384 ± 142 μm at 4w and 342 ± 114 μm at 8w. For triamcinolone, CMT decreased significantly at all time‐points: 494 ± 94 μm, 388 ± 120, 388 ± 145, 390 ± 136 and 411 ± 104 μm at 0, 4, 8, 12 and 16 weeks, respectively. There was a modest increase in intraocular pressure (IOP) at all time‐points with DexNP while no increase was seen with triamcinolone. Serum cortisol was affected by both treatments.

Conclusion

Topical DexNP significantly improve visual acuity and decrease macular thickness in patients with DME. The effect is similar to that from subtenon triamcinolone. A modest increase in IOP was seen with the nanoparticle eye drops, but IOP normalized after the discontinuation of treatment.
Economic burden of hepatitis C in Egypt: the future impact of highly effective therapies
Authors: Estes C. , Abdel‐Kareem M. , Abdel‐Razek W. , Abdel‐Sameea E. , Abuzeid M. , Gomaa A. , Osman W. , Razavi H. , Zaghla H. , Waked I.
Published: July 2015

Background

The prevalence of hepatitis C virus (HCV) infection in Egypt is the highest in the world, yet the total economic burden has not been quantified. Improved understanding of costs and the impact of treatment strategies will provide for better allocation of resources to reduce HCV disease and economic burden.

Aim

A modelling approach was used to quantify the current HCV‐infected population, future disease progression and associated costs in Egypt.

Methods

Direct healthcare costs were calculated from a nationally representative hospital and a disability adjusted life year (DALY) template was used with monetary value assigned to lost life years. Three scenarios were considered: (i) Historical treatment scenario: 50% SVR; 65 000 treated annually, (ii) Current treatment scenario: 90% sustained virologic response (SVR); 65 000 treated annually, (iii) Increased treatment scenario: 90% SVR; 325 000 treated annually by 2018.

Results

Cumulative DALYs (2015–2030) under Scenario 1 were estimated at 7.88 million and cumulative costs estimated at $89.07 billion. Annual DALYs increased 16% during 2015–2030 while annual costs more than doubled. Scenario 2 reduced cumulative DALYs and costs by 7% and 4%, respectively. Under Scenario 3, total costs declined 73% to $1047 million during 2015–2030. As compared to Scenario 1, cumulative DALYs and costs decreased 37% and 35%, respectively.

Conclusions

This is the first estimate of the total economic burden of HCV in Egypt. Extraordinary measures are necessary to substantially reduce HCV disease and cost burden. With newer therapies, strategies to reduce disease burden are feasible and cost‐effective.
Randomised clinical trial: a dose‐ranging study of vonoprazan, a novel potassium‐competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis
Authors: Ashida K. , Sakurai Y. , Nishimura A. , Kudou K. , Hiramatsu N. , Umegaki E. , Iwakiri K. , Chiba T.
Published: July 2015

Background

The potassium‐competitive acid blocker vonoprazan (VPZ) has potent acid‐inhibitory effects and may offer clinical advantages over conventional therapy for acid‐related disorders.

Aim

To investigate the efficacy and safety of VPZ in patients with erosive oesophagitis (EO).

Methods

In this multicentre, randomised, double‐blind, parallel‐group, dose‐ranging study, patients ≥20 years with endoscopically confirmed EO [Los Angeles (LA) grades A−D] received VPZ 5, 10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary endpoint was the proportion of healed EO subjects as shown by endoscopy at week 4.

Results

A total of 732 subjects received VPZ or LPZ. The proportion of healed EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non‐inferior to LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and 87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of adverse events was similar across the groups.

Conclusions

Vonoprazan was effective and non‐inferior to LPZ in healing EO. VPZ 20 mg or higher was highly efficacious for severe EO (LA grades C/D). VPZ was associated with no safety concern during this 8‐week study, while there was a dose‐dependent increase in serum gastrin. Once‐daily VPZ 20 mg is the recommended clinical dose for treating EO.
Messenger RNA encoding constitutively active Toll-like receptor 4 enhances effector functions of human T cells
Authors: Pato A , Eisenberg G , Machlenkin A , Margalit A , Cafri G , Frankenburg S , Merims S , Peretz T , Lotem M , Gross G
Published: July 2015

Adoptive T cell therapy of cancer employs a large number of ex-vivo-propagated T cells which recognize their targets either by virtue of their endogenous T cell receptor (TCR) or via genetic reprogramming. However, both cell-extrinsic and intrinsic mechanisms often diminish the in-vivo potency of these therapeutic T cells, limiting their clinical efficacy and broader use. Direct activation of human T cells by Toll-like receptor (TLR) ligands induces T cell survival and proliferation, boosts the production of proinflammatory cytokines and augments resistance to regulatory T cell (Treg) suppression. Removal of the TLR ligand-binding region results in constitutive signalling triggered by the remaining cytosolic Toll/interleukin-1 receptor (TIR) domain. The use of such TIR domains therefore offers an ideal means for equipping anti-tumour T cells with the arsenal of functional attributes required for improving current clinical protocols. Here we show that constitutively active (ca)TLR-4 can be expressed efficiently in human T cells using mRNA electroporation. The mere expression of caTLR-4 mRNA in polyclonal CD8 and CD4 T cells induced the production of interferon (IFN)-γ, triggered the surface expression of CD25, CD69 and 4-1BB and up-regulated a panel of cytokines and chemokines. In tumour-infiltrating lymphocytes prepared from melanoma patients, caTLR-4 induced robust IFN-γ secretion in all samples tested. Furthermore, caTLR-4 enhanced the anti-melanoma cytolytic activity of tumour-infiltrating lymphocytes and augmented the secretion of IFN-γ, tumour necrosis factor (TNF)-α and granulocyte–macrophage colony-stimulating factor (GM-CSF) for at least 4 days post-transfection. Our results demonstrate that caTLR-4 is capable of exerting multiple T cell-enhancing effects and can potentially be used as a genetic adjuvant in adoptive cell therapy.
Effect of subconjunctival glucose on retinal ganglion cell survival in experimental retinal ischaemia and contrast sensitivity in human glaucoma
Authors: Shibeeb O'Sam , Chidlow Glyn , Han Guoge , Wood John PM , Casson Robert J
Published: July 2015

Purpose

This study aims to evaluate the effect of subconjunctival glucose on the retinal ganglion cells (RGCs) in experimental retinal ischaemia and contrast sensitivity in humans with primary open‐angle glaucoma (POAG).

Methods

First, we measured the intravitreal concentration of glucose at various time points after a subconjunctival injection of 100 μl of 50% glucose to Sprague‐Dawley rats. Next, treatment and control groups received 50% subconjunctival glucose and iso‐osmotic (8%) saline, respectively, 1 h prior to a unilateral ischaemic retinal injury; 7 days later, the damage profiles were compared using RGC and axon counts. Subsequently, we conducted a double‐blind, crossover, pilot clinical study in seven eyes of five pseudophakic subjects with severe POAG. Subjects received either 0.3 mL of 50% glucose subconjunctivally or iso‐osmotic (8%) saline, then vice versa after a 2–3 week ‘wash‐out’ period; change in contrast sensitivity from baseline was the primary outcome.

Results

Subconjunctival glucose preserved approximately 60% of Brn3a‐positive RGCs in all retinal zones compared with an 80% loss in control retinas, and rescued approximately 40% of the axonal loss. In the human trial, the contrast sensitivity at 12 cycles/degree was 0.24 log units greater than baseline (95% confidence interval 0.12–0.36; P < 0.001).

Conclusions

Subconjunctival glucose partially protects RGC somata and axons against an ischaemic insult and temporarily recovers contrast sensitivity in patients with severe POAG. Although an unlikely therapeutic strategy for POAG, the findings motivate further bioenergetic‐based research in glaucoma and other optic nerve and retinal diseases, where energy failure may be part of the pathogenesis.
Alpha‐mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function
Authors: Borgwardt L. , Danielsen E.R. , Thomsen C. , Månsson J.E. , Taouatas N. , Thuesen A.M. , Olsen K.J. , Fogh J. , Dali C.I. , Lund A.M.
Published: July 2015

Alpha‐mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The understanding of the central nervous system (CNS) pathology is limited. This study is the first describing the CNS pathology and the correlation between the CNS pathology and intellectual disabilities in human AM. Thirty‐four patients, aged 6–35 years, with AM were included. Data from 13 healthy controls were included in the analysis of the magnetic resonance spectroscopy (MRS). Measurements of CNS neurodegeneration biomarkers in cerebrospinal fluid (CSF), CSF‐oligosaccharides, and performance of cerebral magnetic resonance imaging (MRI) and MRS were carried out. On MRI, 5 of 10 patients had occipital white matter (WM) signal abnormalities, and 6 of 10 patients had age‐inappropriate myelination. MRS demonstrated significantly elevated mannose complex in gray matter and WM. We found elevated concentrations of tau‐protein, glial fibrillary acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF samples, respectively. A negative correlation between CSF‐biomarkers and cognitive function and CSF‐oligosaccharides and cognitive function was found. The combination of MRS/MRI changes, elevated concentrations of CSF‐biomarkers and CSF‐oligosaccharides suggests gliosis and reduced myelination, as part of the CNS pathology in AM. Our data demonstrate early neuropathological changes, which may be taken into consideration when planning initiation of treatment.
MicroRNA dysregulation in rhabdomyosarcoma: a new player enters the game
Authors: Li Zheng , Yu Xin , Shen Jianxiong , Liu Yang , Chan Matthew T. V. , Wu William K. K.
Published: July 2015

Rhabdomyosarcoma (RMS) is the most common of the soft tissue sarcomas with resultant high morbidity, frequently occuring in paediatric patients and young adults. While the molecular basis of RMS has received considerable attention, exact mechanisms underlying its development and metastasis remain unclear. MicroRNAs (miRNAs) are endogenously expressed small non‐coding RNAs that negatively regulate gene expression via translational inhibition or mRNA degradation. Deregulated expression of miRNA has been implicated in initiation, progression, and metastasis of RMS. miRNAs have emerged as key regulators of several physiological and pathophysiological processes and have opened new avenues for diagnosis and treatment of RMS. This review summarizes deregulation and functional roles of miRNAs in RMS and their potential applications for diagnosis, prognosis and treatment of this malignancy. As a rapidly evolving field in basic and translational medicine, it is hopeful that miRNA research will ultimately improve management of RMS.
Neurological symptoms in essential thrombocythemia: impact of JAK2V617F mutation and response to therapy
Authors: Aroldi Andrea , Cecchetti Caterina , Colombo Arianna , Cattaneo Leonardo , Pioltelli Pietro Enrico , Pogliani Enrico Maria , Elli Elena Maria
Published: July 2015

Patients with essential thrombocythemia (ET) often suffer from neurological symptoms (NS) not ever resulting from previous thrombotic cerebral events (TCE). We reported NS occurred in 282 patients, in order to identify the factors influencing ET‐related NS in the absence of TCE, and the response to therapy. Overall, 116 of 282 patients (41%) presented NS; 101 of them (87%) reported subjective transient and fluctuating NS, without concurrent TCE, which we defined as ET‐related NS, by frequency: cephalalgia, chronic paresthesias, dizziness or hypotension, visual disturbances, and tinnitus. In univariate analysis, ET‐related NS resulted more frequently in young people (P = 0.017) and in females (P = 0.025). We found a higher prevalence of JAK2V617F mutation in ET‐related NS patients (P = 0.021). In multivariate analysis, gender (P = 0.024) and JAK2V617F mutation (P = 0.041) remained significantly associated with the development of ET‐related NS, with a risk of about four times higher for JAK2V617F‐mutated patients (OR = 3.75). Ninety‐seven of 101 patients with ET‐related NS received an antiplatelet (AP) agent at the time of NS, whereas only selected high‐risk ET‐related NS patients were treated with a cytoreductive drug, according to the published guidelines and similarly to patients without NS. We observed that only 32 of 97 (33%) patients with ET‐related NS achieved a complete response after AP treatment. Among the 65 non‐responder patients, 36 (55.4%) improved NS after the introduction of cytoreductive therapy; therefore, the addition of cytoreductive treatment should be considered in this setting.
Mitochondrial abnormalities in the myofibrillar myopathies
Authors: Jackson S. , Schaefer J. , Meinhardt M. , Reichmann H.
Published: July 2015

Myofibrillar myopathies are a genetically diverse group of skeletal muscle disorders, with distinctive muscle histopathology. Causative mutations have been identified in the genes MYOT, LDB3, DES, CRYAB, FLNC, BAG3, DNAJB6, FHL1, PLEC and TTN, which encode proteins which either reside in the Z‐disc or associate with the Z‐disc. Mitochondrial abnormalities have been described in muscle from patients with a myofibrillar myopathy. We reviewed the literature to determine the extent of mitochondrial dysfunction in each of the myofibrillar myopathy subtypes. Abnormal mitochondrial distribution is a frequent finding in each of the subtypes, but a high frequency of COX‐negative or ragged red fibres, a characteristic finding in some of the conventional mitochondrial myopathies, is a rare finding. Few in vitro studies of mitochondrial function have been performed in affected patients.
Generic lamotrigine versus brand‐name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard
Authors: Ting Tricia Y. , Jiang Wenlei , Lionberger Robert , Wong Jessica , Jones Jace W. , Kane Maureen A. , Krumholz Allan , Temple Robert , Polli James E.
Published: July 2015

Objective

To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand‐name drug pharmacokinetic (PK) performance in “generic‐brittle” patients with epilepsy under clinical use conditions.

Methods

This randomized, double‐blind, multiple‐dose, steady‐state, fully replicated bioequivalence study compared generic lamotrigine to brand‐name Lamictal in “generic‐brittle” patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2‐week treatment period yielded two 12‐h PK profiles for brand‐name and generic forms for each patient. Steady‐state area under the curve (AUC), peak plasma concentration (Cmax), and minimum plasma concentration (Cmin) data were subjected to conventional average bioequivalence (ABE) analysis, reference‐scaled ABE analysis, and within‐subject variability (WSV) comparisons. In addition, generic‐versus‐brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events.

Results

Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady‐state AUC, Cmax, and Cmin for generic‐versus‐brand were 97.2–101.6%, 98.8–104.5%, and 93.4–101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic‐versus‐brand were similar but not identical, in part because brand‐versus‐brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical.

Significance

Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand‐to‐generic switching. Bioequivalence results in “generic‐brittle” patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.
Ca‐channel blocker‐induced gingival overgrowth that improved with non‐surgical therapy during visiting care: a case report
Authors: Kato Tomotaka , Takiuchi Hiroya , Yamaguchi Masahiro , Naito Toru
Published: July 2015

Objectives

To present a case of gingival overgrowth during visiting care.

Background

Ca‐channel blocker‐induced gingival overgrowth is a well‐known adverse event. However, only limited information on the treatment of calcium‐channel blocker‐induced gingival overgrowth during visiting care has been reported.

Clinical report

The patient was an 88‐year‐old female living in a nursing home since dementia. She had been taking a calcium‐channel blocker and observed gingival overgrowth. Initial therapy was performed and changed the antihypertensive medication from a calcium‐channel blocker to an angiotensin converting enzyme inhibitor. After initial therapy, the gingival overgrowth improved significantly. In addition, the defecation rate was improved.

Conclusion

This case indicated that periodontal therapy is useful even for dementia patients during visiting dental care.
Urban Employment in Small Businesses and the Level of Economic Development: Evidence from Chinese Cities
Authors: Moreno‐Monroy Ana I. , Yu Shu , Euse Victoria
Published: July 2015

Based on a panel of Chinese cities over the period 2004–2009, we analyze the relationship between the level of economic development and the share of urban employment in small businesses. We find that this relationship can be described by an inverted U‐shape. In cities with lower levels of economic development, the restructure of the state sector along with a booming service industry is associated with a higher share of employment in small businesses. On the other hand, in cities with higher levels of economic development, a more vibrant manufacturing sector is related to a lower share of employment in small businesses.
Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts
Authors: Kitamura Hodaka , Ozono Eiko , Iwanaga Ritsuko , Bradford Andrew P. , Okuno Junko , Shimizu Emi , Kurayoshi Kenta , Kugawa Kazuyuki , Toh Hiroyuki , Ohtani Kiyoshi
Published: July 2015

The transcription factor E2F is the principal target of the tumor suppressor pRB. E2F plays crucial roles not only in cell proliferation by activating growth‐related genes but also in tumor suppression by activating pro‐apoptotic and growth‐suppressive genes. We previously reported that, in human normal fibroblasts, the tumor suppressor genes ARF, p27Kip1 and TAp73 are activated by deregulated E2F activity induced by forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. In contrast, growth‐related E2F targets are activated by both E2F activities, underscoring the roles of deregulated E2F in tumor suppression in the context of dysfunctional pRB. In this study, to further understand the roles of deregulated E2F, we explored new targets that are specifically activated by deregulated E2F using DNA microarray. The analysis identified nine novel targets (BIM, RASSF1, PPP1R13B, JMY, MOAP1, RBM38, ABTB1, RBBP4 and RBBP7), many of which are involved in the p53 and RB tumor suppressor pathways. Among these genes, the BIM gene was shown to be activated via atypical E2F‐responsive promoter elements and to contribute to E2F1‐mediated apoptosis. Our results underscore crucial roles of deregulated E2F in growth suppression to counteract loss of pRB function.
Relationship between Polyamines and Other Cold‐induced Response Mechanisms in Different Cereal Species
Authors: Gondor O. K. , Szalai G. , Kovács V. , Janda T. , Pál M.
Published: July 2015

To find a connection between polyamines and various protective effectors involved in the development of cold tolerance, eight different cereal genotypes, including wheat, barley and oat species, were investigated during the acclimation phase to low temperature. Exposure to low temperature induced different changes in the levels of polyamines, and other signalling molecules, such as salicylic acid and abscisic acid, and of other protective compounds, namely flavonols, sugars and antioxidant enzyme activity, and in the lipid composition of certain membrane factions. The most remarkable differences were observed in the oat varieties compared to the other cereal genotypes, which was manifested in the lack of spermidine accumulation and of decrease in trans‐Δ3‐hexadecanoic acid content, in lower initial and not cold‐inducible abscisic acid content and guaiacol peroxidase activity after cold treatment. Correlation analysis revealed that spermidine shows strong positive relationship with flavonols, abscisic acid and ascorbate peroxidase, while was in negative relationship with trans‐Δ3‐hexadecanoic acid. These results suggest that spermidine may have a crucial role in the cold acclimation signalling processes in cereals.
Microwave Dielectric Properties of LiKSm2(MoO4)4 Ceramics with Ultralow Sintering Temperatures
Authors: Zhai Xiao‐Liu , Zheng Xu , Xi Hai‐Hong , Li Wen‐Bo , Han Jun , Zhou Di
Published: July 2015

In this work, a novel low‐temperature firing microwave dielectric ceramic LiKSm2(MoO4)4 was prepared via solid‐state reaction method. Ceramic samples with relative densities about 94.6% were obtained at sintering temperature 640°C–680°C. The best microwave dielectric properties was obtained in ceramic sample sintered at 620°C with a permittivity about 11.5, a Q × f value about 39 000 GHz and a temperature coefficient of frequency about −15.9 ppm/°C. According to XRD patterns and backscattered electron micrograph, combined with Energy Dispersive Spectra analysis, of cofired samples with 30 wt% aluminum sintered at 620°C/4 h, the LiKSm2(MoO4)4 ceramic was found to be chemically compatible with Al but react seriously with Ag, forming AgSmMo2O8 phase, at its sintering temperature.
Melter Feed Reactions at T ≤ 700°C for Nuclear Waste Vitrification
Authors: Xu Kai , Hrma Pavel , Rice Jarrett , Riley Brian J. , Schweiger Michael J. , Crum Jarrod V.
Published: July 2015

To understand feed‐to‐glass conversion for the vitrification of nuclear waste, we investigated batch reactions and phase transitions in a simulated nuclear waste glass melter feed heated at 5 K/min up to 700°C using optical microscopy, scanning electron microscopy with energy‐dispersive X‐ray spectroscopy, and X‐ray diffraction. To determine the content and composition of leachable phases, we performed leaching tests; the leachates were analyzed by inductively coupled plasma atomic emission spectroscopy. By 400°C, gibbsite and sodium borates lost water and converted to amorphous phase, whereas other metallic hydroxides dehydrated to oxides. Between 400°C and 700°C, carbonates decomposed before 500°C; amorphous aluminum oxide and calcium oxide reacted with the sodium borate and formed the more durable amorphous borate phase along with intermediate crystalline products; above 500°C, quartz began to dissolve, and hematite started to convert to trevorite.
Preliminary insight into the periostin leverage during periodontal tissue healing
Authors: Padial‐Molina Miguel , Volk Sarah L. , Rios Hector F.
Published: July 2015

Background

Tissue repair and regeneration is assisted by the efficient coordination of cell and extracellular matrix interactions mediated by matricellular molecules such as periostin. Given its high expression around the teeth, the periodontal organ represents an ideal system to capture the protein dynamics during wound healing.

Methods

An observational prospective case–control study was designed to characterize periostin changes over time after periodontal surgery in tissue, oral fluids and serum by histological, protein and mRNA analyses.

Results

Histological analysis showed lower periostin with a diffuse local distribution pattern in disease patients. Levels of periostin in gingival crevicular fluid (GCF) increased over time for both groups, more noticeably in the periodontitis subjects. A transient and subtle change in circulating periostin levels was also noticed. The mRNA periostin levels contrasted with the protein levels and may indicate the underlying post‐transcriptional regulatory process during chronic inflammation. Levels of known periodontal disease biomarkers such as IL‐β, IL1‐α, TNF‐α, MIP‐1α and CRP served as tissue stability markers and complemented the clinical parameters recorded.

Conclusion

The transient local increase in GCF periostin after eliminating the local etiology in periodontally affected sites suggests its importance in the maturation and stability of the connective tissue. The decreasing levels observed as the tissue healed highlight its spatial/temporal significance.