bluuebunny/crossref_metadata_2025 huggingface dataset:
Refugee health
Authors: Mehrotra Anushka
Published: July 2015

Working with refugees and asylum seekers can be a challenging, yet rewarding, part of a GP's workload. They can be a vulnerable group, with complex medical and social needs that can be difficult to deal with in a 10-minute consultation. Since a GP is often their first point of contact in the community, having a better understanding of the common issues and how to manage these can have a great impact on the lives of refugees.
Effect of Ramadan fasting in Saudi Arabia on serum bone profile and immunoglobulins
Authors: Bahijri Suhard M. , Ajabnoor Ghada M. , Borai Anwar , Al-Aama Jumana Y. , Chrousos George P.
Published: July 2015

Background:

Each year Muslims fast from dawn to sunset for 1 month (Ramadan). In Saudi Arabia, the sleep–wake cycle during Ramadan is severely disturbed and is associated with abolition of the circadian cortisol rhythm, exposing Saudis to continuously increased cortisol levels, which may influence the immune response. In addition to cortisol, sleep and fasting affect the secretion of parathyroid hormone (PTH) and hence bone metabolism.

Methods:

Our objective was to investigate the effect of Ramadan type fasting on secretory patterns of PTH, markers of bone metabolism, and serum immunoglobulins. Blood samples from healthy young volunteers were collected at 9 a.m. and 9 p.m. (± 1 hour) before (Shaban) and 2 weeks into Ramadan. Calcium, phosphorus, magnesium, albumin, alkaline phosphatase, 25-OH vitamin D, intact PTH (iPTH), and immunoglobulin (Ig) A, M and G were measured.

Results:

During Ramadan, evening-adjusted calcium was higher ( p = 0.036) and phosphate lower ( p < 0.001) than the corresponding morning value. Moreover, the Ramadan mean morning phosphate was higher and the evening level lower was than Shabaan values ( p = 0.010 and p <0.001, respectively), while mean iPTH level was decreased compared with the morning value ( p = 0.001), and the evening mean during Shabaan ( p = 0.029). Mean IgG concentration was significantly lower during Ramadan ( p = 0.003 and p = 0.021 for morning and evening, respectively).

Conclusions:

Changes in dietary practices during Ramadan modulated PTH secretion to a pattern which might be beneficial to bone health. Combined effects of fasting and disturbed sleep led to a noted decrease in IgG level. Therefore, a possible beneficial effect of fasting on bone turnover is combined with decreased immune response.
Exploring the Relationship Between Professional Commitment and Job Satisfaction Among Nurses
Authors: Hsu Hsiu-Chin , Wang Pao-Yu , Lin Li-Hui , Shih Whei-Mei , Lin Mei-Hsiang
Published: July 2015

This cross-sectional study explored the relationship between professional commitment and job satisfaction among nurses. A total of 132 registered nurses were recruited from a hospital in northern Taiwan. A self-reported structured questionnaire was used to collect data. Findings revealed significant differences among nurses in willingness to make an effort and their marital status, appraisal in continuing their careers, job level, and goals and values related to working shifts. Significant differences were found between inner satisfaction and work sector and marital status. Nurses’ professional commitment was strongly related to job satisfaction; aspects of professional commitment explained 32% of the variance in job satisfaction. Study results may inform health care institutions about the importance of nurses’ job satisfaction and professional commitment so hospital administration can improve these aspects of organizational environment.
Boriding kinetics and mechanical behaviour of AISI O1 steel
Authors: Elias-Espinosa M. , Ortiz-Domínguez M. , Keddam M. , Gómez-Vargas O. A. , Arenas-Flores A. , Barrientos-Hernández F. R. , West A. R. , Sinclair D. C.
Published: July 2015

In this work, American Iron and Steel Institute (AISI) O1 steel was pack borided in the temperature range of 1123–1273 K for treatment times between 2 and 8 hours. A kinetic model was proposed for estimating the boron diffusion coefficients through the Fe2B layers. As a result, the boron activation energy for the AISI O1 steel was estimated as 197·2 kJ mol− 1. This value of energy was compared to the literature data. In addtion, to extend the validity of the present model, two additional boriding conditions were done. The Fe2B layers grown on AISI O1 steel were characterised by use of the following experimental techniques: scanning electron microscopy, X-ray diffraction analysis and Daimler-Benz Rockwell-C indentation technique. Finally, the scratch and pin on disc tests for wear resistance were respectively performed using an LG Motion Ltd and a CSM tribometer under dry sliding conditions.
Novel whole blood assay for phenotyping platelet reactivity in mice identifies ICAM-1 as a mediator of platelet-monocyte interaction
Authors: Armstrong Paul C. J , Kirkby Nicholas S. , Chan Melissa V. , Finsterbusch Michaela , Hogg Nancy , Nourshargh Sussan , Warner Timothy D.
Published: July 2015

Key Points

Low-volume, high-throughput whole blood aggregometry will facilitate future mouse platelet function research. Application of this approach identifies ICAM-1 as a novel mediator of platelet-monocyte interaction through fibrinogen binding.
RETRACTED ARTICLE: Mechanistic attributes of S100A7 (psoriasin) in resistance of anoikis resulting tumor progression in squamous cell carcinoma of the oral cavity
Authors: Dey Kaushik Kumar , Sarkar Siddik , Pal Ipsita , Das Subhasis , Dey Goutam , Bharti Rashmi , Banik Payel , Roy Joygopal , Maity Sukumar , kulavi Indranil , Mandal Mahitosh
Published: July 2015

Background

Squamous cell carcinoma of the oral cavity (SCCOC) is the dominant origin of cancer associated mortality. Previous findings by our study reported that acquisition of anoikis resistance has a significant role in tumor progression of oral cavity. Several genes were over-expressed in anoikis-resistant cells under detached conditions which we confirmed earlier by microarray. Normal oral squamous epithelia grow adherent to a basement membrane, and when detached from the extracellular matrix, undergoes programmed cell death. The acquisition of anoikis-resistance is crucial phenomena in oral tumor advancement. In the current study, we have identified S100A7 expression as contributing factor for anoikis resistance and tumorigenicity in human oral cancer cells. Further, we have explored that elevated S100A7 expression in anoikis-sensitive oral keratinocytes and cancer cells reshape them more resistant to anoikis and apoptosis inducers via activation of cellular intrinsic and extrinsic avenue.

Methods

A subset of human cancer cell lines TU167, JMAR, JMARC39, JMARC42 and MDA-MB-468 were utilized for the generation of resistant stable cell lines. Further, immunohistochemistry, western blot and immunoprecipitation, assays of apoptosis, soft agar assay, orthotopic animal model and signaling elucidation were performed to establish our hypothesis.

Results

S100A7 gene is found to be responsible for anoikis resistance and tumorigenicity in human oral cancer cells. We have observed up-regulation of S100A7 in anoikis resistant cell lines, orthotropic model and patients samples with head and neck cancer. It is also noticed that secretion of S100A7 protein in conditioned medium by anoikis resistant head & neck cancer cell and in saliva of head and neck cancer patients. Up-regulation of S100A7 expression has triggered enhanced tumorigenicity and anchorage-independent growth of cancer cells through Akt phosphorylation leading to development of aniokis resistance in head and neck cancer cells.

Conclusions

These data have led us to conclude that S100A7 is the major contributing factor in mediating anoikis-resistance of oral cancer cells and local tumor progression, and S100A7 might be useful as diagnostic marker for early detection of primary and recurrent squamous cell cancer.
From genes to genomes in the clinic
Authors: Veltman Joris A. , Lupski James R.
Published: July 2015

Editorial summary

Next-generation sequencing is revolutionizing medical genetics and in the near future will pervade all medical fields. To maximize the potential clinical utility of this approach, global data sharing and phenotyping are needed, and the role of the geneticist in the interpretation of variation is vital.
Next-generation sequencing to guide cancer therapy
Authors: Gagan Jeffrey , Van Allen Eliezer M.
Published: July 2015

As a result of multiple technological and practical advances, high-throughput sequencing, known more commonly as “next-generation” sequencing (NGS), can now be incorporated into standard clinical practice. Whereas early protocols relied on samples that were harvested outside of typical clinical pathology workflows, standard formalin-fixed, paraffin-embedded specimens can more regularly be used as starting materials for NGS. Furthermore, protocols for the analysis and interpretation of NGS data, as well as knowledge bases, are being amassed, allowing clinicians to act more easily on genomic information at the point of care for patients. In parallel, new therapies that target somatically mutated genes identified through clinical NGS are gaining US Food and Drug Administration (FDA) approval, and novel clinical trial designs are emerging in which genetic identifiers are given equal weight to histology. For clinical oncology providers, understanding the potential and the limitations of DNA sequencing will be crucial for providing genomically driven care in this era of precision medicine.
Global genetic carrier testing: a vision for the future
Authors: Beaudet Arthur L.
Published: July 2015

Editorial summary

Expanded genetic carrier testing is changing clinical practice. Current experience highlights the need for rigorous curation of tens of thousands of variants as to their pathogenicity and phenotypic effects. There is an urgent need for strategies to present a range of options to families to enable them to make informed decisions. The potential exists to avoid the great majority of serious inherited, but not de novo, single-gene disabilities.
Hypoxia accelerates vascular repair of endothelial colony-forming cells on ischemic injury via STAT3-BCL3 axis
Authors: Lee Sang Hun , Lee Jun Hee , Han Yong-Seok , Ryu Jung Min , Yoon Yeo Min , Han Ho Jae
Published: July 2015

Introduction

Endothelial colony-forming cells (ECFCs) significantly improve tissue repair by providing regeneration potential within injured cardiovascular tissue. However, ECFC transplantation into ischemic tissue exhibits limited therapeutic efficacy due to poor engraftment in vivo. We established an adequate ex vivo expansion protocol and identified novel modulators that enhance functional bioactivities of ECFCs.

Methods

To augment the regenerative potential of ECFCs, functional bioactivities of hypoxia-preconditioned ECFCs (hypo-ECFCs) were examined.

Results

Phosphorylations of the JAK2/STAT3 pathway and clonogenic proliferation were enhanced by short-term ECFC culturing under hypoxia, whereas siRNA-targeting of STAT3 significantly reduced these activities. Expression of BCL3, a target molecule of STAT3, was increased in hypo-ECFCs. Moreover, siRNA inhibition of BCL3 markedly reduced survival of ECFCs during hypoxic stress in vitro and ischemic stress in vivo. In a hindlimb ischemia model of ischemia, hypo-ECFC transplantation enhanced blood flow ratio, capillary density, transplanted cell proliferation and survival, and angiogenic cytokine secretion at ischemic sites.

Conclusions

Hypoxia preconditioning facilitates functional bioactivities of ECFCs by mediating regulation of the STAT3-BCL3 axis. Thus, a hypoxic preconditioned ex vivo expansion protocol triggers expansion and functional bioactivities of ECFCs via modulation of the hypoxia-induced STAT3-BCL3 axis, suggesting that hypo-ECFCs offer a therapeutic strategy for accelerated neovasculogenesis in ischemic diseases.
Determination of hydrogen cyanide concentration in mainstream smoke of tobacco products by polarography
Authors: Mahernia Shabnam , Amanlou Arash , kiaee Gita , Amanlou Massoud
Published: July 2015

Background

There has been a worldwide concern for the health risks of cigarette smoking and hydrogen cyanide (HCN) considered as one of the hazardous tobacco compounds which is needed to be determined in order to reduce the dose related to smoke disease risk.

In this study, we prepare the experimental procedure to entrap the HCN from mainstream smoke of different brands of Tehran cigarette, through simulating human inhalation and determine its concentration applying polarography.

Results

The HCN level of the 50 commonly consumed tobacco products (47 cigarettes and 3 cigars) obtained from local store is ranged between 17.56 ± 1.02 and 1553.98 ± 0.56 μg per stick, this acquired amount is more than FDA approval (10 μg per stick), so the harmful effects of smoking is indicative.

Conclusions

The comparative study of the results shows that the price and the weight of each product do not indicate HCN level. As can be seen, R2 value which is a statistical measure of how close the data are to the fitted regression line is low (R2 < 0.2). So it should not be deceived by names such as ultra light or infinite gravity to suck, because this names or the price haven’t effect on the amount of HCN and its destructive effects.
The sulfidation process of sterling silver in different corrosive environments: impact of the process on the surface films formed and consequences for the conservation-restoration community
Authors: Storme Patrick , Schalm Olivier , Wiesinger Rita
Published: July 2015

Background

Precious objects made of silver and/or its alloys tarnish and become black when exposed to ambient atmospheres containing moisture and ppb-amounts of H2S. Such objects usually contain small but variable amounts of copper as alloying constituent and this affects the corrosion process due to a preferential oxidation of copper. However the visual appearance of the formed tarnishing layers on different types of silver alloys is very similar. Therefore, conservators-restorers are confronted with the problem that in some cases certain cleaning techniques are very effective while in other similar cases the removal of tarnishing layers is unsatisfactory. Since cleaning experiments are not allowed on genuine objects, many investigations use artificially corroded dummies instead. In order to evaluate the representativity and reproducibility of this often used methodology, differences in morphology, microstructure and composition of the sulfide layers on sterling silver generated by different sulfidation methods were analysed.

Results

Sterling silver samples were artificially aged in five different environments. The samples exposed to uncontrolled ambient air at different locations (e.g. residential and laboratory environments) showed different corrosion rates and corrosion colours. Three accelerated ageing methods were executed in a gaseous or liquid environment under controlled conditions. These tests showed different results in morphology, microstructure, composition, thickness and the interface between bulk and corrosion layer. A first accelerated sulfidation procedure in a Na2S solution alternated with exposure to air, resulted in a fast corrosion rate and an even corrosion layer formation with several S-species. A second series of sulfidation in a controlled gas environment of H2S and SO2 developed a thin but uneven corrosion layer, mainly consisting of oxides. A third corrosion methodology used was based on the thioacetamide method. This resulted in an even and relative thick corrosion layer, comparable to the Na2S/aeration sulfidation system. However, the interface between the corrosion layer and the bulk is importantly different, showing severe voids.

Conclusions

The corrosion layers generated by five different experimental sulfidation series on identical prepared sterling silver coupons were clearly different from each other. Analyses demonstrated that the composition and microstructure of the corrosion layers were strongly dependent on the sulfidation method used and copper was found to be an important element present in all sulfide layers analysed. Therefore, artificially corroded sterling silver is not necessarily representative for naturally tarnished historical objects and the extrapolation of the cleaning results obtained on dummies to historical objects must be performed with care.
Stock assessment and management implications of an endemic fish, Oxygymnocypris stewartii, in the Yarlung Zangbo River in Tibet, China
Authors: Huo Bin , Ma Bao Shan , Xie Cong Xin , Duan You Jian , Yang Xue Feng , Huang Hai Ping
Published: July 2015

Background

Oxygymnocypris stewartiiis an endemic species only inhabiting the middle and upper reaches of the Yarlung Zangbo River and its tributaries at altitudes above 3600 m in the Qinghai-Tibet Plateau and has suffered a continuous decline of population size owing to anthropogenic disturbance. However, little is known about the stock status of this species and how to protect it. In this study, we evaluated the population status ofO. stewartiiand investigated two management policies including the minimum age limits and seasonal closure in the Yarlung Zangbo River.

Results

Estimates of the total mortality rate were 0.35 year−1for females and 0.65 year−1for males. The natural mortality rates were estimated as 0.10 and 0.22 year−1for females and 0.12 and 0.29 year−1for males using two empirical methods. TheO. stewartiipopulation may be in near full exploitation under the current harvesting strategy in the Yarlung Zangbo River, with a high chance of recruitment failure in the future. Although both minimum age limits and seasonal closure could be effective measures to conserve theO. stewartiistock, it was proposed that a seasonal closure was implemented each year from September to December according to the complexity of the application and the effects on the income of local fishermen and on the biological invasion.

Conclusions

The stock ofO. stewartiimay be in near full exploitation under the current harvesting strategy, with a high chance of recruitment failure in the future. Our results indicated that the imposition of the seasonal closure from September to December might be the effective measure to conserve theO. stewartiipopulation.
The evaluation of a scoring system in airway management after oral cancer surgery
Authors: Lee Ho-Jin , Kim Jin-Wook , Choi So-Young , Kim Chin-Soo , Kwon Tae-Geon , Paeng Jun-Youg
Published: July 2015

Background

The purpose of this retrospective study was to investigate the usefulness of tracheostomy scoring system in the decision of postoperative airway management in oral cancer patients.

Materials and methods

A total of 104 patients were reviewed in this retrospective study, who underwent radical resection with or without neck dissection and free flap reconstruction due to oral cancer. The patients were classified into three groups according to the timing of the extubation; extubated groups (n = 51), overnight intubation group (n = 45), and tracheostomy group (n = 8). Cameron’s score was used to evaluate the relation between the state of the patient’s airway and the type of the operation.

Results

Tracheostomy was performed in eight patients (8/104, 7.7 %). A total of 22 patients (21.2 %) had more than 5 points of which 17 patients (77.3 %) did not have a tracheostomy and any postoperative emergency airway problems. The tracheostomy scores were significantly different among the three groups. Hospital stay showed a significant correlation with the tracheostomy score.

Conclusions

The scoring system did not quite agree with the airway management of the authors’ clinic; however, it can be one of the clinical factors predicting the degree of the postoperative airway obstruction and surgical aggressiveness for recovery. The further studies are needed for clinically more reliable scoring systems.
Neutrophils rapidly transit inflamed lymphatic vessel endothelium via integrin-dependent proteolysis and lipoxin-induced junctional retraction
Authors: Rigby David A , Ferguson David J P , Johnson Louise A , Jackson David G
Published: July 2015

Neutrophils are the first leukocyte population to be recruited from the circulation following tissue injury or infection, where they play key roles in host defense. However, recent evidence indicates recruited neutrophils can also enter lymph and shape adaptive immune responses downstream in draining lymph nodes. At present, the cellular mechanisms regulating neutrophil entry to lymphatic vessels and migration to lymph nodes are largely unknown. Here, we have investigated these events in an in vivo mouse Mycobacteriumbovis bacillus Calmette-Guérin vaccination model, ex vivo mouse dermal explants, and in vitro Transwell system comprising monolayers of primary human dermal lymphatic endothelial cells. We demonstrate that neutrophils are reliant on endothelial activation for adhesion, initially via E-selectin and subsequently, by integrin-mediated binding to ICAM-1 and VCAM-1, combined with CXCL8-dependent chemotaxis. Moreover, we reveal that integrin-mediated neutrophil adhesion plays a pivotal role in subsequent transmigration by focusing the action of matrix metalloproteinases and the 15-lipoxygenase-1-derived chemorepellent 12(S)-hydroxyeicosatetraenoic acid at neutrophil:endothelial contact sites to induce transient endothelial junctional retraction and rapid, selective neutrophil trafficking. These findings reveal an unexpectedly intimate collaboration between neutrophils and the lymphatic vessel endothelium, in which these phagocytic leukocytes act as pathfinders for their own transit during inflammation.
Intravenous immunoglobulin skews macrophages to an anti-inflammatory, IL-10-producing activation state
Authors: Kozicky Lisa K , Zhao Zheng Yu , Menzies Susan C , Fidanza Mario , Reid Gregor S D , Wilhelmsen Kevin , Hellman Judith , Hotte Naomi , Madsen Karen L , Sly Laura M
Published: July 2015

Intravenous Ig is used to treat autoimmune or autoinflammatory disorders, but the mechanism by which it exerts its immunosuppressive activity is not understood completely. To examine the impact of intravenous Ig on macrophages, we compared cytokine production by LPS-activated macrophages in the presence and absence of intravenous Ig. Intravenous Ig treatment induced robust production of IL-10 in response to LPS, relative to LPS stimulation alone, and reduced production of proinflammatory cytokines. This anti-inflammatory, intravenous Ig-induced activation was sustained for 24 h but could only be induced if intravenous Ig were provided within 1 h of LPS stimulation. Intravenous Ig activation led to enhanced and prolonged activation of MAPKs, Erk1/2, p38, and Erk5, and inhibition of each reduced intravenous Ig-induced IL-10 production and suppression of IL-12/23p40. IL-10 production occurred rapidly in response to intravenous Ig + LPS and was sufficient to reduce proinflammatory IL-12/23p40 production in response to LPS. IL-10 induction and reduced IL-12/23p40 production were transcriptionally regulated. IL-10 played a direct role in reducing proinflammatory cytokine production by macrophages treated with intravenous Ig + LPS, as macrophages from mice deficient in the IL-10R β chain or in IL-10 were compromised in their ability to reduce proinflammatory cytokine production. Finally, intraperitoneal injection of intravenous Ig or intravenous Ig + LPS into mice activated macrophages to produce high levels of IL-10 during subsequent or concurrent LPS challenge, respectively. These findings identify IL-10 as a key anti-inflammatory mediator produced by intravenous Ig-treated macrophages and provide insight into a novel mechanism by which intravenous Ig may dampen down inflammatory responses in patients with autoimmune or autoinflammatory diseases.
Rapid externalization of 27-kDa heat shock protein (HSP27) and atypical cell death in neutrophils treated with the sphingolipid analog drug FTY720
Authors: Skrzeczyńska-Moncznik Joanna , Bzowska Małgorzata , Nogieć Anna , Sroka Agnieszka , Zarebski Mirosław , Vallières Luc , Guzik Krzysztof
Published: July 2015

The sphingolipid analog fingolimod is known to induce apoptosis of tumor cells and lymphocytes. Its effect on neutrophils has not been investigated so far. Here, we describe a fingolimod-induced atypical cell death mechanism in human neutrophils, characterized by rapid translocation of heat shock protein 27 to the cell surface, extensive cell swelling and vacuolization, atypical chromatin staining and nuclear morphology, and phosphorylation of mixed lineage kinase domain-like protein. Fingolimod also induces typical apoptotic features, including rapid externalization of phosphatidylserine and activation of caspase-8. Fingolimod-induced neutrophil death is independent of sphingosine-1-phosphate receptors and positively regulated by protein phosphatase A. Externalization of phosphatidylserine and heat shock protein 27 can be partially inhibited by inhibitors of caspase-8 [Z-Ile-Glu(O-Me)-Thr-Asp(O-Me)-fluoromethyl ketone], receptor-interacting protein kinase 1 (necrostatin-1), receptor-interacting protein kinase 3 (necrosulfonamide), and heat shock protein 90 [geldanamycin and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin]. Furthermore, NADPH oxidase 1 inhibition with diphenyleneiodonium chloride protects neutrophils against fingolimod-mediated cell death. Overall, these observations suggest that fingolimod acts through a mechanism involving the necrosome signaling complex and the oxidative stress machinery.
Hepatic CD206-positive macrophages express amphiregulin to promote the immunosuppressive activity of regulatory T cells in HBV infection
Authors: Dai Kai , Huang Ling , Sun Xiaomei , Yang Lihua , Gong Zuojiong
Published: July 2015

Hepatitis B virus is a major cause of chronic liver inflammation worldwide. Innate and adaptive immune responses work together to restrain or eliminate hepatitis B virus in the liver. Compromised or failed adaptive immune response results in persistent virus replication and spread. How to promote antiviral immunity is a research focus for hepatitis B virus prevention and therapy. In this study, we investigated the role of macrophages in the regulation of antiviral immunity. We found that F4/80+CD206+CD80lo/+ macrophages were a particular hepatic macrophage subset that expressed amphiregulin in our mouse hepatitis B virus infection model. CD206+ macrophage-derived amphiregulin promoted the immunosuppressive activity of intrahepatic regulatory T cells, demonstrated by higher expression of CTLA-4, ICOS, and CD39, as well as stronger inhibition of antiviral function of CD8+ T cells. Amphiregulin-neutralizing antibody diminished the effect of CD206+ macrophages on regulatory T cells. In addition, we found that CD206+ macrophage-derived amphiregulin activated mammalian target of rapamycin signaling in regulatory T cells, and this mammalian target of rapamycin activation was essential for promotion of regulatory T cell activity by CD206+ macrophages. Adoptive transfer of CD206+ macrophages into hepatitis B virus-infected mice increased cytoplasmic hepatitis B virus DNA in hepatocytes and also increased serum hepatitis B surface antigen. The antiviral activity of CD8+ T cells was decreased after macrophage transfer. Therefore, our research indicated that amphiregulin produced by CD206+ macrophages plays an important role in modulating regulatory T cell function and subsequently restrains the antiviral activity of CD8+ T cells. Our study offers new insights into the immunomodulation in hepatitis B virus infection.
Recent findings on the role of natural killer cells in the pathogenesis of systemic lupus erythematosus
Authors: Spada Roberto , Rojas José M , Barber Domingo F
Published: July 2015

Systemic lupus erythematosus is a chronic, multifactorial autoimmune disease of complex etiology, characterized by loss of tolerance to nuclear autoantigens, expansion of autoreactive T and B cell clones, polyclonal B cell activation that gives rise to hypergammaglobulinemia, and increased autoantibody production, as well as immune complex deposition and multiorgan tissue inflammation. As disease progresses, immune cells, mainly T cells and macrophages, infiltrate affected organs and amplify the local inflammatory response. Natural killer cells are large, granular lymphocytes that are an important link between the innate and adaptive immune systems; variations in their activity correlate with several autoimmune diseases. To date, the literature has disregarded natural killer cells as relevant modulators in systemic lupus erythematosus pathogenesis, as these cells are few in number and show a dysfunctional phenotype in patients with active systemic lupus erythematosus. This review focuses on research that could help define the role of natural killer cells in systemic lupus erythematosus and their function in regulating this autoimmune disorder in nonlymphoid organs.
A Practical Solution for Dyspareunia in Breast Cancer Survivors: A Randomized Controlled Trial
Authors: Goetsch Martha F. , Lim Jeong Y. , Caughey Aaron B.
Published: July 2015

Purpose

Dyspareunia is common in breast cancer survivors because of low estrogen. This study explored whether dyspareunia is introital pain, preventable with analgesic liquid.

Patients and Methods

In a randomized, controlled, double-blind trial, estrogen-deficient breast cancer survivors with severe penetrative dyspareunia applied either saline or 4% aqueous lidocaine to the vulvar vestibule for 3 minutes before vaginal penetration. After a 1-month blinded trial of patient-assessed twice-per-week tampon insertion or intercourse, all patients received lidocaine for 2 months in an open-label trial. The primary outcome was patient-related assessment of penetration pain on a scale of zero to 10. Secondary outcomes were sexual distress (Female Sexual Distress Scale), sexual function (Sexual Function Questionnaire), and resumption of intercourse. Comparisons were made with the Mann-Whitney U and Wilcoxon signed rank test with significance set at P < .05.

Results

In all, 46 patients, screened to exclude those with pelvic muscle and organ pain, uniformly had clinical evidence of severe vulvovaginal atrophy, dyspareunia (median pain score, 8 of 10; interquartile range [IQR], 7 to 9), increased sexual distress scores (median, 30.5; IQR, 23 to 37; abnormal, > 11), and abnormal sexual function. Users of lidocaine reported less pain during intercourse in the blinded phase (median score of 1.0 compared with saline score of 5.3; P = .007). After open-label lidocaine use, 37 (90%) of 41 reported comfortable penetration. Sexual distress decreased (median score, 14; IQR, 3 to 20; P < .001), and sexual function improved in all but one domain. Of 20 prior abstainers from intercourse who completed the study, 17 (85%) had resumed comfortable penetrative intimacy. No partners reported penile numbness.

Conclusion

Breast cancer survivors with menopausal dyspareunia can have comfortable intercourse after applying liquid lidocaine compresses to the vulvar vestibule before penetration.
Cross Talk Between GH-Regulated Transcription Factors HNF6 and CUX2 in Adult Mouse Liver
Authors: Conforto Tara L. , Steinhardt George F. , Waxman David J.
Published: July 2015

Hepatocyte-enriched nuclear factor (HNF)6 and CUX2 are GH and STAT5-regulated homeobox transcription factors. CUX2 shows female-specific expression and contributes to liver sex differences by repressing many male-biased genes and inducing many female-biased genes, whereas HNF6 is expressed at similar levels in male and female liver. In cell-based transfection studies, CUX2 inhibited HNF6 transcriptional regulation of the sex-specific gene promoters CYP2C11 and CYP2C12, blocking HNF6 repression of CYP2C11 and HNF6 activation of CYP2C12. These inhibitory actions of CUX2 can be explained by competition for HNF6 DNA binding, as demonstrated by in vitro EMSA analysis and validated in vivo by global analysis of the HNF6 cistrome. Approximately 40 000 HNF6-binding sites were identified in mouse liver chromatin, including several thousand sites showing significant sex differences in HNF6 binding. These sex-biased HNF6-binding sites showed strong enrichment for correspondingly sex-biased DNase hypersensitive sites and for proximity to genes showing local sex-biased chromatin marks and a corresponding sex-biased expression. Further, approximately 90% of the genome-wide binding sites for CUX2 were also bound by HNF6. These HNF6/CUX2 common binding sites were enriched for genomic regions more accessible in male than in female mouse liver chromatin and showed strongest enrichment for male-biased genes, suggesting CUX2 displacement of HNF6 as a mechanism to explain the observed CUX2 repression of male-biased genes in female liver. HNF6 binding was sex independent at a majority of its binding sites, and HNF6 peaks were frequently associated with cobinding by multiple other liver transcription factors, consistent with HNF6 playing a global regulatory role in both male and female liver.
Net Neutrality, Business Models, and Internet Interconnection
Authors: Choi Jay Pil , Jeon Doh-Shin , Kim Byung-Cheol
Published: July 2015

We analyze the effect of net neutrality regulation in a two-sided market framework when content is heterogeneous in its sensitivity to delivery quality. We characterize the equilibrium in a neutral network constrained to offer the same quality vis-à-vis a nonneutral network where Internet service providers are allowed to engage in second-degree price discrimination with a menu of quality-price pairs. We find that the merit of net neutrality regulation depends crucially on content providers' business models. More generally, our analysis can be considered a contribution to the literature on second-degree price discrimination in two-sided platform markets. (JEL D42, D43, D85, L51, L86, L88)
Evolution of Impatience: The Example of the Farmer-Sheriff Game
Authors: Levine David K. , Modica Salvatore , Weinschelbaum Federico , Zurita Felipe
Published: July 2015

The literature on the evolution of impatience, focusing on one-person decision problems, often finds that evolutionary forces favor the more patient individuals. This paper shows that in games where equilibrium involves threat of punishment there are forces generating an evolutionary advantage to the impatient. In particular, it offers a two-population example where evolutionary forces favor impatience in one group while favoring patience in the other. Moreover, efficiency may also favor impatient individuals. In our example, it is efficient for one population to evolve impatience and for the other to develop patience. Yet, evolutionary forces move the opposite direction. (JEL C73, C78)
Referrals: Peer Screening and Enforcement in a Consumer Credit Field Experiment
Authors: Bryan Gharad , Karlan Dean , Zinman Jonathan
Published: July 2015

Empirical evidence on peer intermediation lags behind both theory and practice in which lenders use peers to mitigate adverse selection and moral hazard. Using a referral incentive under individual liability, we develop a two-stage field experiment that permits separate identification of peer screening and enforcement. Our key contribution is to allow for borrower heterogeneity in both ex ante repayment type and ex post susceptibility to social pressure. Our method allows identification of selection on repayment likelihood, selection on susceptibility to social pressure, and loan enforcement. Implementing our method in South Africa we find no evidence of screening but large enforcement effects. (JEL D14, D82, G21, O12, O16)
Selling Cookies
Authors: Bergemann Dirk , Bonatti Alessandro
Published: July 2015

We propose a model of data provision and data pricing. A single data provider controls a large database that contains information about the match value between individual consumers and individual firms (advertisers). Advertisers seek to tailor their spending to the individual match value. The data provider prices queries about individual consumers' characteristics (cookies). We determine the equilibrium data acquisition and pricing policies. Advertisers choose positive and/or negative targeting policies. The optimal query price influences the composition of the targeted set. The price of data decreases with the reach of the database and increases with the fragmentation of data sales. (JEL C78, D83, L11, L82, M37)
Adult attention-deficit/hyperactivity disorder: Associations between subtype and lifetime substance use – a clinical study.
Authors: Liebrenz Michael , Gamma Alex , Ivanov Iliyan , Buadze Anna , Eich Dominique
Published: July 2015

ADHD is the one of the most prevalent childhood disorders and has been associated with impairments persisting into adulthood. Specifically, childhood ADHD is an independent clinical risk factor for the development of later substance use disorders (SUD). Moreover, adults who meet diagnostic criteria for ADHD have shown high rates of comorbid SUDs. Few studies, however, have reported on the relationship between ADHD subtypes and SUD in adult samples. The purpose of this study was to characterize a clinical sample of adults with ADHD and to identify possible associations between ADHD subtypes, lifetime substance use, and if ADHD subtypes may be preferentially associated with specific substances of abuse. We recruited 413 adult ADHD patients, performed an evaluation of their ADHD and conducted an interview on their use of psychotropic substances. Complete data was obtained for 349 patients. Lifetime substance abuse or dependence was 26% and occasional use was 57% in this sample. The inattentive subtype was significantly less likely to abuse or be dependent on cocaine than the combined subtype. Our findings underscore the high rate of comorbidity between substance use and ADHD in adults. The more frequent abuse/dependence of cocaine by adult patients with hyperactive-impulsive symptoms should be kept in mind when treating this patient group.
What’s in a Name? Exploring the Nomenclature of Science Communication in the UK
Authors: Illingworth Sam , Redfern James , Millington Steve , Gray Sam
Published: July 2015

This study, via a consideration of the literature, and a survey of science communicators, presents concise and workable definitions for science outreach, public engagement, widening participation, and knowledge exchange, in a UK context.  

Sixty-six per cent of participants agreed that their definitions of outreach, public engagement, and widening participation aligned with those of their colleagues, whilst 64% felt that their personal definitions matched those of their institute. However, closer inspection of the open-ended questions found the respondents often differed in the use of the nomenclature. In particular, the respondents found it difficult to define knowledge exchange in this context.
The Multicommodity-Ring Location Routing Problem
Authors: Gianessi Paolo , Alfandari Laurent , Létocart Lucas , Wolfler Calvo Roberto
Published: July 2015

The multicommodity-ring location routing problem (MRLRP) studied in this paper is an NP-hard minimization problem arising in city logistics. The aim is to locate a set of urban distribution centers (UDCs) and to connect them via a ring in which massive flows of goods will circulate. Goods are transported from gates located outside the city to a UDC, and either join a second UDC through the ring before being delivered in electric vans to the final customers or are delivered directly to the customers from the first UDC. The reverse trip with pickup and transportation to the gates is also possible. A delivery service path starts at a particular UDC, then visits a subset of customers and ends at the same UDC, another UDC, or a self-service parking lot (SPL). A pickup route can start from an SPL or a UDC and ends at a UDC. The objective is to minimize the sum of the installation costs of the ring, flow transportation costs, and routing costs. The MRLRP belongs to the class of location-routing problems (LRP). We model it with a set-partitioning-like representation of delivery and pickup trips and arc-flow elements to describe goods transportation in the ring and between the ring and the gates. We present three approaches to solving the MRLRP: an exact method for small-size instances, a matheuristic for instances of a larger size, and a hybrid approach that applies the exact method to the columns output by the matheuristic. Numerical results are provided for an exhaustive set of instances, obtained by extending benchmark instances of the capacitated LRP with additional MRLRP features.
Understanding antipsychotic-induced weight gain and other metabolic issues
Authors: Richards Denis Ben , Bressington Daniel
Published: July 2015

Second-generation antipsychotic medications are recommended as first-line treatments for people experiencing psychosis, but many of these drugs are closely associated with metabolic changes that significantly contribute towards poor physical health and increased mortality rates. Current evidence suggests that considerable variations exist among this group of drugs with respect to their independent effects on metabolism—some of these discrepancies probably relate to their differing effects on neurotransmitters. This article explores some of the more commonly accepted hypotheses for the reasons antipsychotics contribute towards metabolic disorders and discusses the potential implications for practice.
Why do men self-harm? A literature review
Authors: Souter Gary
Published: July 2015

This critical review developed and analysed two key strands. One strand examined the reasons why men self-harm; the other examined effective ways to educate staff about self-harm. These strands were interweaved to develop an in-depth and informative review to help educate and inform staff who work with and support men who self-harm. A systematic search strategy was conducted to find primary research articles for analysis and evaluation. Three key themes emerged: interpersonal relationships; attitudes and educating staff. This review recommends that staff should be encouraged to change their behaviour and view themselves and their relationships differently. This can have a positive impact on developing and maintaining therapeutic relationships.
Self-management, compassion and recovery: The Tidal Model in mental health practice
Authors: Ramage David , Ellis Steve , Marks-Maran Di
Published: July 2015

This article explores compassion-based mental health therapy through the use of the Tidal Model. A literature review is presented on compassion-focused therapy in general and the Tidal Model in particular, including a critical examination of evaluation studies that have been undertaken into the Tidal Model. The article concludes with a case example of the Tidal Model of mental health practiced for one resident in a independent mental health hospital in the north of England.
Examining access for women in alcohol misuse treatment
Authors: Fernandez Jeff
Published: July 2015

This article examines how services develop to meet their aims of equality in an increasingly diverse, multicultural UK. It focuses on women and the clinical areas of alcohol misuse. the ratio for women presenting themselves to services has always been outnumbered by males, in the ratio 4:1. There are some anecdotal reasons for this, such as that women might have a fear of social services being involved, or a fear that children will be taken off them (if the woman with alcohol dependency has children). Therefore, females may not present to services to seek help for their dependency, which then has the potential to become ‘hidden’ from substance misuse services. This article looks at how services can be open and accommodate women in substance misuse services and meet their recovery needs. It looks at the clinical field of alcohol and looks at the approach the primary care alcohol service in Islington has used to see how it has adapted its service to accommodate this. It looks to see whether the service can treat women as well as men, and improve on the current ratio in favour of males presenting to services. This article argues that the field of alcohol provision can accommodate and treat women successfully to become alcohol-free.
Estimation of Values below the Limit of Detection of a Contemporary Sensitive Troponin I Assay Improves Diagnosis of Acute Myocardial Infarction
Authors: Boeckel Jes-Niels , Palapies Lars , Zeller Tanja , Reis Sophia M , von Jeinsen Beatrice , Tzikas Stergios , Bickel Christoph , Baldus Stephan , Blankenberg Stefan , Münzel Thomas , Zeiher Andreas M , Lackner Karl J , Keller Till
Published: July 2015

BACKGROUND

The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI.

METHODS

Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. Data on cs-cTnI was available in 1786 patients. As a comparator the hs-cTnI version of the assay was used. To reconstruct quantities below the LoD of the cs-cTnI assay, a gamma regression approach incorporating the GRACE (Global Registry of Acute Coronary Events) score variables was used.

RESULTS

Censoring of cs-cTnI data below the LoD yielded weaker diagnostic information [area under the curve (AUC), 0.781; 95% CI, 0.731–0.831] regarding AMI compared to the hs-cTnI assay (AUC, 0.949; CI, 0.936–0.961). Use of our model to estimate cs-cTnI values below the LoD showed an AUC improvement to 0.921 (CI, 0.902–0.940). The cs-cTnI LoD concentration had a negative predictive value (NPV) of 0.950. An estimated concentration that was to be undercut by 25% of patients presenting with suspected AMI was associated with an improvement of the NPV to 0.979.

CONCLUSIONS

Estimation of values below the LoD of a cs-cTnI assay with this new approach improves the diagnostic performance in evaluation of patients with suspected AMI.