bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Secretory Immunoglobulins Enhance Norovirus Infection
Authors: Turula Holly , Bragazzi-Cunha Juliana , Ramakrishnan Sadeesh , Wilke Carol , Gonzalez-Hernandez Mariam , Pry Alexandra , Fava Julianne , Svoboda Sophia , Shah Yatrik , Corthesy Blaise , Moore Bethany , Wobus Christiane E.
Published: January 2018

Secretory immunoglobulins (SIg) are a first line of mucosal defense by the host. They are secreted into the gut lumen via the polymeric immunoglobulin receptor (pIgR) where they bind to antigen and are transported back across the FAE via M cells. Noroviruses are highly prevalent, enteric pathogens that cause significant morbidity, mortality and economic losses worldwide. Murine norovirus (MNV) exploits microfold (M) cells to cross the lymphoid follicle-associated epithelium (FAE) and infect the underlying population of immune cells. However, whether natural, innate SIg can protect against norovirus infection remains unknown. To investigate the role of natural SIg during murine norovirus pathogenesis, we used pIgR-deficient animals, which lack SIg in the intestinal lumen. Contrary to other enteric pathogens, acute MNV replication was significantly reduced in the gastrointestinal tract of pIgR-deficient animals compared to controls, despite increased numbers of dendritic cells, macrophages, and B cells in the Peyer’s patch, established MNV target cell types. Also, natural SIg did not alter MNV FAE binding or FAE crossing into the lymphoid follicle. Instead, further analysis revealed enhanced baseline levels of the antiviral molecules interferon gamma (IFNɣ) and inducible nitric oxide synthase (iNOS) in the small intestine of naive pIgR-deficient animals compared to controls. Removing the microbiota equalized IFNɣ and iNOS transcript levels as well as MNV viral loads in germ-free pIgR KO mice compared to germ-free controls. These data are consistent with a model whereby SIg sensing reduces pro-inflammatory, antiviral molecules, which facilitates intestinal homeostasis but thereby promotes MNV infection. In conclusion, these findings demonstrate that natural SIg are not protective during norovirus infection in mice and represent another example of indirect modulation of enteric virus pathogenesis by the microbiota.
Vagus Nerve Stimulation Promotes Gastric Emptying by Increasing Pyloric Opening Measured with Magnetic Resonance Imaging
Authors: Lu Kun-Han , Cao Jiayue , Oleson Steven , Ward Matthew P , Powley Terry L , Liu Zhongming
Published: January 2018

Background

Vagus nerve stimulation (VNS) is an emerging electroceutical therapy for remedying gastric disorders that are poorly managed by pharmacological treatments and/or dietary changes. Such therapy seems promising since the vagovagal neurocircuitry controlling the enteric nervous system strongly influences gastric functions.

Methods

Here, the modulatory effects of left cervical VNS on gastric emptying in rats was quantified using a 1) feeding protocol in which the animal voluntarily consumed a post-fast, gadolinium-labeled meal and 2) newly developed, robust, sensitive and non-invasive imaging strategy to measure antral motility, pyloric activity and gastric emptying based on contrast-enhanced magnetic resonance imaging (MRI) and computer-assisted image processing pipelines.

Key Results

VNS significantly accelerated gastric emptying (control vs. VNS: 24.9±3.5% vs. 40.7±3.9% of meal emptied per 4hrs, p<0.05). This effect resulted from a greater relaxation of the pyloric sphincter (control vs. VNS: 1.4±0.2 vs. 2.5±0.5 mm2cross-sectional area of lumen, p<0.05), without notable changes in antral contraction amplitude (control vs. VNS: 30.6±3.0% vs. 32.5±3.0% occlusion), peristaltic velocity (control vs. VNS: 0.67±0.03 vs. 0.67±0.03 mm/s), or frequency (control vs. VNS: 6.3±0.1 vs. 6.4±0.2 cpm). The degree to which VNS relaxed the pylorus positively correlated with gastric emptying rate (r = 0.5465, p<0.01).

Conclusions & Inferences

The MRI protocol employed in this study is expected to enable advanced preclinical studies to understand stomach pathophysiology and its therapeutics. Results from this study suggest an electroceutical treatment approach for gastric emptying disorders using cervical VNS to control the degree of pyloric sphincter relaxation.

Key Points

Vagus nerve stimulation is emerging as a new electroceutical therapy for treating gastric disorders. However, its underlying mechanism(s) and therapeutic effect(s) remain incompletely understood.

Vagus nerve stimulation significantly accelerated gastric emptying by promoting the relaxation of the pyloric sphincter.

MRI offers high spatial and temporal resolution to non-invasively characterize gastric motility and physiology in preclinical animal models.
Genetically encoded ratiometric indicators for potassium ion
Authors: Shen Yi , Wu Sheng-Yi , Rancic Vladimir , Qian Yong , Miyashita Shin-Ichiro , Ballanyi Klaus , Campbell Robert E. , Dong Min
Published: January 2018

Potassium ion (K+) homeostasis and dynamics play critical roles in regulating various biological activities, and the ability to monitor K+spatial-temporal dynamics is critical to understanding these biological functions. Here we report the design and characterization of a Förster resonance energy transfer (FRET)-based genetically encoded K+indicator, KIRIN1, constructed by inserting a bacterial cytosolic K+binding protein (Kbp) between a fluorescent protein (FP) FRET pair, mCerulean3 and cp173Venus. Binding of K+induces a conformational change in Kbp, resulting in an increase in FRET efficiency. KIRIN1 was able to detect K+at physiologically relevant concentrationsin vitroand is highly selective toward K+over Na+. We further demonstrated that KIRIN1 allowed real-time imaging of pharmacologically induced depletion of cytosolic K+in live cells, and KIRIN1 also enabled optical tracing of K+efflux and reuptake in neurons upon glutamate stimulation in cultured primary neurons. These results demonstrate that KIRIN1 is a valuable tool to detect K+in vitroand in live cells.
The gender difference in leadership effectiveness and its Sino-US comparison
Authors: Yan Shimei , Wu Yike , Zhang Gang
Published: January 2018

Purpose

There are mainly two viewpoints on women’s leadership effectiveness compared with that of men – the questioning view and the admiring view, two points of view that are not in agreement. Based on that, this study aims to find the gender difference in leadership effectiveness.

Design/methodology/approach

This study uses carefully matched male and female presidents (223 pairs) of Chinese listed companies and male and female chief executive officers (141 pairs) of American listed companies as samples. Analysis of variance was conducted to analyze the indicator data of the leadership effectiveness.

Findings

The findings show that women’s leadership effectiveness is not significantly inferior to that of men, and that women’s leadership effectiveness compared to that of men in the Chinese cultural context is not inferior to that in the American cultural context. The findings do not support the questioning view of women’s leadership effectiveness.

Originality/value

This study first uses the carefully matched (female/male leaders) data of Chinese listed companies and American listed companies as samples to find which viewpoint (the questioning view and the admiring view) is supported or is not supported.
A comprehensive rubric for instructional design in e-learning
Authors: Debattista Martin
Published: January 2018

Purpose

The recognition of practice in online instruction is still subject to interpretation and different approaches as a result of the rapid changes in technology and its effect on society. The purpose of this paper is to address these differences through a synthesis that can be easily accessed and consulted by educators in the field of e-learning.

Design/methodology/approach

This paper reviews different examples of rubrics and instruments in higher education to propose a more comprehensive rubric that constitutes a synthesis of how some institutions in HE approach best practice in this field.

Findings

The proposed comprehensive rubric emanating from the synthesis of different approaches supports the development, remixing, sharing and integration of online modules and courses by providing a single reference point with as wide a range as possible of potential pedagogical tools, facilities and approaches to e-learning.

Research limitations/implications

It is not within the scope of this paper to review quality assurance processes and administrative components, but to propose a rubric for course design and self-review of faculty and higher education institutions for a better alignment with what is regarded as current standard best practice.

Practical implications

Instructional designers in e-learning have a new comprehensive rubric that can consult at design stage.

Originality/value

Different approaches towards what is called “good practice” are brought together and analysed to provide a synthesis and a single source that can be consulted by practitioners in the field of e-learning.
The Ombudsman Act 1980: redressing administrative grievances in Bangladesh
Authors: Karim Sheikh Mohammad Towhidul
Published: January 2018

Purpose

It is recognized worldwide that an ombudsman system makes the public administration more transparent and accountable to the public. This paper aims to examine the provisions of the Ombudsman Act 1980, as well as the position, role and necessity of the Office of the Ombudsman in Bangladesh. It also evaluates how the ombudsman institution can act as a gateway for citizens of Bangladesh to resolve complaints against the maladministration of public administration in the country.

Design/methodology/approach

The study is basically qualitative in nature where both primary and secondary sources have been used. As well, a combination of analytical methods and current legislative methods, together with future legislative techniques, was used in the study.

Findings

This study finds that the ombudsman is a vital institution for Bangladesh to eliminate maladministration, nepotism and abuse of human rights, as well as abuse of the power of the public administration. Going forward, Bangladesh needs to amend the existing Ombudsman Act 1980 and then take proper steps to firmly establish the Ombudsman Office to ensure and increase public confidence, operational effectiveness and good governance and human rights throughout the country.

Research limitations/implications

The main implication of this study is that it will play an important role for the development of the rule of law and human rights in Bangladesh. This study will make its readers and particularly the citizens of Bangladesh aware of the importance of the “Office of the Ombudsman” in Bangladesh and the existing loopholes in the current Ombudsman Act 1980. This research also provides a new avenue for scholars to contribute their knowledge and wisdom toward nation-building by further researching the Office of the Ombudsman in Bangladesh. In this way, scholars in this field can share their experiences of the role of the ombudsman to a wider audience.

Practical implications

The study will facilitate policymakers and the government to enact an effective new law or to amend the existing law relating to the ombudsman.

Originality/value

The paper sets out the proposed amendment to the Ombudsman Act 1980. Hence, it will be of interest to policymakers, government, organizations of civil society and those developing countries that have not taken steps toward forming an ombudsman institution.
Reform in the Indian real estate sector: an analysis
Authors: Basanta Kumar Basanta Kumar , Chawla Neelam , Mohanty Brajaraj
Published: January 2018

Purpose

This paper aims to discuss the essential features, merits and drawbacks of the recently enacted Indian Real Estate Act, 2016, an economic reform measure pertaining to the real estate sector (RES). This paper analyses the impact of the Act and Union Budget 2016 on the inflow of foreign d irect investment (FDI) in India, and examines its ramifications on the world economy.

Design/methodology/approach

The study is based on secondary data sources, including consumer forum reports, investigative reports from national agencies, court decisions, government websites, real estate companies and industry associations. A sample survey on the implications of the Act has been conducted using Facebook and and through personal interaction with various stakeholders.

Findings

The Indian RES was unregulated prior to the passage of the Act, which has several provisions aimed at protecting the interest of consumers by tightening fraudulent practices of promoters/developers. Stakeholders are hopeful, but there is some apprehension. The government’s budgetary and fiscal support for infrastructure development has had an impact on the FDI inflow.

Practical implications

The Act is new, so there is not enough data to judge its real impact on the economy. However, it has started showing evidence of impact through a recent judgment by the Supreme Court of India punishing a promoter.

Originality/value

Regulating the Indian RES is a challenging task, but the new regulations are likely to provide confidence to foreign investors who may see India as a safety net for investment. This paper is timely and may help move things in this direction.
Implied expense theory in financial reporting: a steady-state approach
Authors: Laitinen Erkki Kalervo
Published: January 2018

Purpose

The purpose of this study is to use a steady-state model structure to investigate earnings management (EM) theoretically in the context of different expense theories. Empirically, the objective is to apply the theoretical model to investigate the implicit choice of expense theories for reporting expenses. The study aims to present a new approach to analyze EM.

Design/methodology/approach

The study makes use of ten-year time-series data originally from 1,015 Finnish public and private firms to estimate the parameters of the steady-state model, and to investigate which expense theories the firms implicitly follow in financial reporting. The parameters are estimated using the restricted least squares regression method. The final sample included data from 631 firms fulfilling restrictions for the consistency of estimates.

Findings

The paper provides empirical insights about expense theories that Finnish firms implicitly follow in financial reporting. Evidence shows that the reporting of expenses mainly follows the units-of-revenue and the rate-of-return theories. Only a small number of firms follow the interest expense theory.

Research limitations/implications

The study is based on a steady-state approach, and therefore, the research results may lack generalizability as only 62% of the original sample firms obtained consistent estimates. Therefore, researchers are encouraged to use more general models for further theoretical and empirical work.

Practical implications

The paper includes implications for a new approach to EM. It also gives implications how to analyze different expense theories in the context of EM both theoretically and empirically.

Originality/value

This paper develops a new approach to investigate EM.
The effect of political-economic reform on the quality of financial reporting in Egypt
Authors: Makhaiel Nargis Kaisar Boles , Sherer Michael Leslie Joseph
Published: January 2018

Purpose

This paper aims to study the influence of political-economic reform and especially privatisation on the quality of financial reporting of the Egyptian companies.

Design/methodology/approach

The paper analyses data from official documents and 34 interviews with company executives, financial analysts, external auditors and Stock Exchange regulators to inform our understanding of the relationship between changes in the Egyptian environment and the quality of financial reporting.

Findings

The findings of the research suggest that the recent Egyptian political-economic reform, resulting in privatisation has significant influence on negative accounting practices and hence on lowering the quality of financial reporting through its effect on: departure from uniform accounting system and public accounting regulations; issuing new stock exchange regulative rules; reviving the role of Stock Exchange; and increasing competition within Stock Exchange regarding raising funds.

Originality/value

This paper contributes to the literature by identifying the effect of socio-cultural factors on motivating executives to 7 exercise negative accounting practices and hence producing low-quality financial reports (FRs) and by highlighting the fact that accounting practices cannot be generalised worldwide due to the absence of universal socio-cultural factors which shape these practices. This paper employs new institutional sociology theory and contributes to that theory by acknowledging the active interplay between institutional context and economic environment.
Condition monitoring based on modified CUSUM and EWMA control charts
Authors: Lampreia Suzana Paula Gomes Fernando da Silva , Requeijo José Fernando Gomes , Dias José António Mendonça , Vairinhos Valter Martins , Barbosa Patrícia Isabel Soares
Published: January 2018

Purpose

The application of condition-based maintenance on selected equipment can allow online monitoring using fixed, half-fixed or portable sensors. The collected data not always allow a straightforward interpretation and many false alarms can happen. The paper aims to discuss these issues.

Design/methodology/approach

Statistical techniques can be used to perform early failure detection. With the application of Cumulative Sum (CUSUM) Modified Charts and the Exponentially Weighted Moving Average (EWMA) Charts, special causes of variation can be detected online and during the equipment functioning. Before applying these methods, it is important to check data for independence. When the independence condition is not verified, data should be modeled with an ARIMA (p, d, q) model. Parameters estimation is obtained using the Shewhart Traditional Charts.

Findings

With data monitoring and statistical methods, it is possible to detect any system or equipment failure trend, so that we can act at the right time to avoid catastrophic failures.

Originality/value

In this work, an electro pump condition is monitored. Through this process, an anomaly and four stages of aggravation are forced, and the CUSUM and EWMA modified control charts are applied to test an online equipment monitoring. When the detection occurs, the methodology will have rules to define the degree of intervention.
Part 2
Authors: Ganguly Debojyoti , Mondal Chanchal , Roy Choudhury Asim Kumar
Published: January 2018

Purpose

The purpose of this study is to optimize single-bath dyeing process of wool and silk blend, to achieve uniform colour strength for both the fibre after the dyeing process. Due to different absorption characteristics of wool and silk, two-stage dyeing is preferred in the industry. If the fibres are dyed together, the wool fibre becomes darker and the silk fibre becomes lighter after the dyeing process. Solid dyeing effect can be achieved using a single-bath dyeing process.

Design/methodology/approach

The dye-acceptor sites in the wool fibre are first blocked using one commercial syntan Mesitol HWS. Then, the syntan-treated wool and silk fibres (80:20 blend ratios) are dyed with Telon Navy AMF dyes in the presence of sodium sulphate. To explore the influence of Syntan, sodium sulphate and the experimental conditions on the dyeing process and to optimize the process, central composite design (CCD) of four factors and three levels was tested.

Findings

The design process is optimized using four independent variables: Mesitol HWS concentration, sodium sulphate concentration, pH of dyebath and temperature of dyeing. Three levels of Mesitol HWS concentration (5, 10 and 15 per cent), sodium sulphate concentration (10, 20 and 30 per cent), pH (2.5, 4 and 5.5) and temperature of dyeing (70, 80 and 900°C) were selected for this study. These variables are optimized using response surface regression equation of the ratio of K/S wool and K/S silk. The predicted equation matched well with the experimental data.

Originality/value

This paper proposes the use of one-bath dyeing process of wool and silk blend fabric to reduce the dyeing time, process step and to save water.
Purification and characterisation of milk‐clotting and caseinolytic activities of pepsin isolated from adult sheep abomasa
Authors: Slamani Rosa , Labadi Redouane , Brahim Errahmani Mohamed , Bellal Mohand Mouloud
Published: January 2018

Ovine pepsin was isolated and assessed for its milk‐clotting properties and caseinolytic activity in comparison with commercial chymosin. Ovine pepsin showed similar responses to variations in pH, temperature and CaCl2 concentration of milk compared with chymosin, although its pH sensitivity was higher. SDS‐PAGE electrophoretic analysis of the casein fractions treated with ovine pepsin showed that alpha‐casein was more susceptible to proteolysis than beta‐casein, in contrast to chymosin. Curd‐firming properties of skim milk gels obtained with ovine pepsin and chymosin were evaluated by Gelograph under the same conditions. Curd produced using ovine pepsin was less firm than that made with chymosin.
Effects of seed mixture sowing with transgenic Bt rice and its parental line on the population dynamics of target stemborers and leafrollers, and non‐target planthoppers
Authors: Li Zhuo , Li Li‐Kun , Liu Bin , Wang Long , Parajulee Megha N. , Chen Fa‐Jun
Published: January 2018

The widespread planting of insect‐resistant crops has caused a dramatic shift in agricultural landscapes, thus raising concerns about the potential impacts on both target and non‐target pests. In this study, we examined the potential effects of intra‐specific seed mixture sowing with transgenic Bt rice (Bt) and its parental non‐transgenic line (Nt) (100% Bt rice [Bt100], 5% Nt+95% Bt [Nt05Bt95], 10% Nt+90% Bt [Nt10Bt90], 20% Nt+80% Bt [Nt20Bt80], 40% Nt+60% Bt [Nt40Bt60] and 100% Nt rice [Nt100]) on target and non‐target pests in a 2‐year field trial in southern China. The occurrence of target pests, Sesamia inferens, Chilo suppressalis and Cnaphalocrocis medinalis, decreased with the increased ratio of Bt rice, and the mixture ratios with more than 90% Bt rice (Bt100 and Nt05Bt95) significantly increased the pest suppression efficiency, with the lowest occurrences of non‐target planthoppers, Nilaparvata lugens and Sogatella furcifera in Nt100 and Nt05Bt95. Furthermore, there were no significant differences in 1000‐grain dry weight and grain dry weight per 100 plants between Bt100 and Nt05Bt95. Seed mixture sowing of Bt rice with ≤10% (especially 5%) of its parent line was sufficient to overcome potential compliance issues that exist with the use of block or structured refuge to provide most effective control of both target and non‐target pests without compromising the grain yield. It is also expected that the strategy of seed mixture sowing with transgenic Bt rice and the non‐transgenic parental line would provide rice yield stability while decreasing the insecticide use frequency in rice production.
Methotrexate might reduce ischemic stroke in patients with rheumatoid arthritis: a population‐based retrospective cohort study
Authors: Tam Hong‐Wei , Chen Chyong‐Mei , Leong Pui‐Ying , Chen Chao‐Hsi , Li Yuan‐Chao , Wang Yu‐Hsun , Lin Li‐Chi , Chiou Jeng‐Yuan , Wei James Cheng‐Chung
Published: January 2018

Aim

To investigate the effects of hydroxychloroquine, sulfasalazine and methotrexate on ischemic stroke in patients with rheumatoid arthritis (RA).

Methods

This population‐based retrospective cohort study included 7904 RA patients and 15 808 non‐RA patients between 2000 and 2010. All of the participants were sampled from the National Health Insurance Research Database (NHIRD) of Taiwan. Using univariate analyses, these two groups of patients were compared to evaluate the differences in disease‐modifying anti‐rheumatic drugs usage and demographic variables. Cox proportional hazard models and Schoenfeld residuals test were performed to estimate the hazard ratios for ischemic stroke and proportional hazard assumptions of these drugs, respectively.

Results

The mean age of participants was about 53 years old, and about 70% of RA patients were women. The hazard ratio for ischemic stroke was 1.21 (95% CI: 1.10–1.34; P < 0.01) in the case group compared with the control group, and this significant difference persisted throughout the 10‐year period. With respect to RA patients, while hydroxychloroquine showed an insignificant protective effect on ischemic stroke, sulfasalazine and methotrexate were found out to have inconsistent effects during these 10 years. The proportional hazard assumption test of methotrexate at > 0.5 defined daily dose (8.75 mg/week) was violated at a significant level after adjustment (P = 0.0002).

Conclusions

At a dosage of > 0.5 defined daily dose, short‐term methotrexate might decrease ischemic stroke risk in RA patients, while hydroxychloroquine and sulfasalazine were neutral.
Do women with complex alcohol and other drug use histories want women‐only residential treatment?
Authors: Neale Joanne , Tompkins Charlotte N. E. , Marshall Alison D. , Treloar Carla , Strang John
Published: January 2018

Background

Women‐only addiction services tend to be provided on a poorly evidenced assumption that women want single‐sex treatment. We draw upon women's expectations and experiences of women‐only residential rehabilitation to stimulate debate on this issue.

Methods

Semi‐structured interviews were undertaken with 19 women aged 25–44 years [currently in treatment (n = 9), successfully completed treatment (n = 5), left treatment prematurely (n = 5)]. All had histories of physical or sexual abuse, and relapses linked to relationships with men. Interviews were audio‐recorded, transcribed verbatim, coded and analysed inductively following Iterative Categorization.

Findings

Women reported routinely that they had been concerned, anxious or scared about entering women‐only treatment. They attributed these feelings to previous poor relationships with women, being more accustomed to male company and negative experiences of other women‐only residential settings. Few women said that they had wanted women‐only treatment, although many became more positive after entering the women‐only service. Once in treatment, women often explained that they felt safe, supported, relaxed, understood and able to open up and develop relationships with other female residents. However, they also described tensions, conflicts, mistrust and social distancing that undermined their treatment experiences.

Conclusions

Women who have complex histories of alcohol and other drug use do not necessarily want or perceive benefit in women‐only residential treatment.
Between Indigenous Paramountcy and Democracy: How Differentiated Citizenship and the UN Declaration on the Rights of Indigenous Peoples Could Help Fijian Self‐determination
Authors: O'Sullivan Dominic
Published: January 2018

Contemporary Fijian politics is shaped by a colonial legacy of extraordinary complexity and political tension. Since gaining independence from Great Britain in 1970, Fiji's history has been distinguished by incoherent and inconsistent accounts of political power. These concern the political rights belonging to indigenous peoples as first occupants vis‐à‐vis the claims to political recognition by the descendants of Indian indentured labourers. The relative power between the indigenous aristocracy and commoners is a further complicating variable. Following three coups (1987 and 2006) and a putsch (2000), indigenous paramount authority has been positioned against various forms of democracy and military oversight of the political process. However, none of these political arrangements has enhanced indigenous self‐determination. This article argues that indigenous self‐determination is more likely to be realised through a form of differentiated liberal citizenship consistent with the United Nations’ Declaration on the Rights of Indigenous Peoples. This reasonably requires the extension of the Declaration's provisions to indigenous Fijians, who, as a recent majority indigenous population, are constrained by colonial legacy in a similar manner to the minority indigenous populations for whose benefit the Declaration was primarily adopted.
Long‐term uveal melanoma survivors: measuring their quality of life
Authors: Frenkel Shahar , Rosenne Hadas , Briscoe Daniel , Hendler Karen , Bereket Ronen , Molcho Michal , Pe'er Jacob
Published: January 2018

Purpose

Patients with uveal melanoma (UM) undergo lifelong follow‐up as metastases can occur more than 20 years after diagnosis. Little is known about the quality of life (QoL) of UM survivors over such an extended period. To investigate their QoL, we used various estimating factors.

Methods

A cohort of patients diagnosed and treated for UM with regularly scheduled follow‐up visits was asked to fill in a European Organization for Research and Treatment of Cancer (EORTC) questionnaire comprised of the EORTC QLQ‐C30 and EORTC QLQ‐OPT30 modules. An additional open question examined other changes in the patients’ lifestyle since diagnosis. Independent demographic and medical data were collected from patient records.

Results

Two hundred and thirty‐two of 294 patients agreed to complete the questionnaire. General QoL correlated highly with the eye‐related QoL. Statistically significant higher QoL was associated with tumours not involving the ciliary body, and with better best‐corrected visual acuity (BCVA). A subgroup of 39% of the patients reported severe disability affecting eye‐related tasks. Thirty‐three per cent were highly concerned about various aspects of their future health. Patients who underwent enucleation reported lower eye‐related QoL and described problems related to body image in response to the open question.

Conclusion

General QoL of UM patients is only slightly affected by their malignancy. However, body image and psychosocial adjustment are major issues involved in evaluating QoL. Continuous long‐term psychosocial treatment is needed from the time of diagnosis in a subgroup of patients suffering from eye‐related disabilities.
The association of interferon‐gamma, interleukin‐4 and interleukin‐17 single‐nucleotide polymorphisms with susceptibility to tuberculosis
Authors: Mansouri Fatemeh , Heydarzadeh Rasoul , Yousefi Saber
Published: January 2018

Susceptibility to tuberculosis and progression of the disease depend on interactions between the bacterial agent, host immune system, and environmental and genetic factors. In this case‐controlled study, we aimed to determine the role of single‐nucleotide polymorphisms of interferon‐gamma, interleukin‐4 and interleukin‐17 in susceptibility to tuberculosis. Genomic DNA was extracted from peripheral blood samples of patients and controls. The association of single‐nucleotide polymorphisms in interleukin‐4 (−590C/T), interleukin‐17 (−152A/G) and interferon‐gamma (+874T/A) was investigated by polymerase chain reaction (PCR)‐restriction fragment length polymorphism and amplification refractory mutation system‐PCR. A total of 76 tuberculosis patients and 119 healthy individuals were included in this study. The interferon‐gamma (+874T/A) TA genotype was significantly associated with susceptibility to tuberculosis in patients compared to controls (OR = 1.76; 95%CI = 0.84–3.71; p = 0.007), while the interferon‐gamma (+874T/A) TT genotype (OR = 0.51; 95%CI = 0.19–1.36; p = 0.007) had protective effects against tuberculosis and was related to a low risk of tuberculosis development. The difference between allelic and genotypic frequencies of interleukin‐4 (−590C/T) between patients and controls was not significant (p = 0.46). Multivariate logistic regression analysis revealed that the interleukin‐17 (−152A/G) AG genotype (OR = 2.27; 95%CI = 1.19–4.34; p = 0.03) and AA genotype (OR = 1.03; 95%CI = 0.43–2.44; p = 0.03) were significantly different between patients and controls. In conclusion, single‐nucleotide mutations in different cytokine genes may have protective effects or increase the risk of tuberculosis.
The impact of parallel regulatory–health technology assessment scientific advice on clinical development. Assessing the uptake of regulatory and health technology assessment recommendations
Authors: Tafuri Giovanni , Lucas Inês , Estevão Steve , Moseley Jane , d'Andon Anne , Bruehl Hannah , Gajraj Elangovan , Garcia Sonia , Hedberg Niklas , Massari Marco , Molina Andrea , Obach Mercè , Osipenko Leeza , Petavy Frank , Petschulies Marco , Pontes Caridad , Russo Pierluigi , Schiel Anja , Van de Casteele Marc , Zebedin‐Brandl Eva‐Maria , Rasi Guido , Vamvakas Spiros
Published: January 2018

Aims

The parallel regulatory–health technology assessment scientific advice (PSA) procedure allows manufacturers to receive simultaneous feedback from both EU regulators and health technology assessment (HTA) bodies on development plans for new medicines. The primary objective of the present study is to investigate whether PSA is integrated in the clinical development programmes for which advice was sought.

Methods

Contents of PSA provided by regulators and HTA bodies for each procedure between 2010 and 2015 were analysed. The development of all clinical studies for which PSA had been sought was tracked using three different databases. The rate of uptake of the advice provided by regulators and HTA bodies was assessed on two key variables: comparator/s and primary endpoint.

Results

In terms of uptake of comparator recommendations at the time of PSA in the actual development, our analysis showed that manufacturers implemented comparators to address both the needs of regulators and of at least one HTA body in 12 of 21 studies. For primary endpoints, in all included studies manufacturers addressed both the needs of the regulators and at least one HTA body.

Conclusions

One of the key findings of this analysis is that manufacturers tend to implement changes to the development programme based on both regulatory and HTA advice with regards to the choice of primary endpoint and comparator. It also confirms the challenging choice of the study comparator, for which manufacturers seem to be more inclined to satisfy the regulatory advice. Continuous research efforts in this area are of paramount importance from a public health perspective.
An update on adjunctive treatment options for bipolar disorder
Authors: Dean Olivia M , Gliddon Emma , Van Rheenen Tamsyn E , Giorlando Francesco , Davidson Sandra K , Kaur Manreena , Ngo Trung T , Williams Lana J
Published: January 2018

Objectives

Bipolar disorder is a complex illness often requiring combinations of therapies to successfully treat symptoms. In recent years, there have been significant advancements in a number of therapies for bipolar disorder. It is therefore timely to provide an overview of current adjunctive therapeutic options to help treating clinicians to inform their patients and work towards optimal outcomes.

Methods

Publications were identified from PubMed searches on bipolar disorder and pharmacotherapy, nutraceuticals, hormone therapy, psychoeducation, interpersonal and social rhythm therapy, cognitive remediation, mindfulness, e‐Health and brain stimulation techniques. Relevant articles in these areas were selected for further review. This paper provides a narrative review of adjunctive treatment options and is not a systematic review of the literature.

Results

A number of pharmacotherapeutic, psychological and neuromodulation treatment options are available. These have varying efficacy but all have shown benefit to people with bipolar disorder. Due to the complex nature of treating the disorder, combination treatments are often required. Adjunctive treatments to traditional pharmacological and psychological therapies are proving useful in closing the gap between initial symptom remission and full functional recovery.

Conclusions

Given that response to monotherapy is often inadequate, combination regimens for bipolar disorder are typical. Correspondingly, psychiatric research is working towards a better understanding of the disorder's underlying biology. Therefore, treatment options are changing and adjunctive therapies are being increasingly recognized as providing significant tools to improve patient outcomes. Towards this end, this paper provides an overview of novel treatments that may improve clinical outcomes for people with bipolar disorder.
Relational autonomy, care, and Jehovah's Witnesses in Germany
Authors: Rajtar Małgorzata
Published: January 2018

Drawing from an ethics of care, relational approaches to autonomy have recently emerged in bioethics. Unlike individual autonomy with its emphasis on patients’ rights, choice, and self‐determination which has been the hallmark of bioethics consistent with the ideology of individualism in neoliberal democracies in Western countries, relational autonomy highlights the relatedness, interdependency, and social embeddedness of patients. By examining the mediating role that male Hospital Liaison Committee members in Germany play in facilitating care that supports Jehovah's Witnesses’ refusal of blood transfusions, this article moves beyond ‘dyadic relations’ and contexts of caregiving. It also contributes to a deeper understanding of care and relational conceptualizations of Witness patients’ autonomy globally.
Fragile lives with fragile rights: Justice for babies born at the limit of viability
Authors: Hendriks Manya J. , Lantos John D.
Published: January 2018

There is an inconsistency in the ways that doctors make clinical decisions regarding the treatment of babies born extremely prematurely. Many experts now recommend that clinical decisions about the treatment of such babies be individualized and consider many different factors. Nevertheless, many policies and practices throughout Europe and North America still appear to base decisions on gestational age alone or on gestational age as the primary factor that determines whether doctors recommend or even offer life‐sustaining neonatal intensive care treatment. These policies are well intentioned. They aim to guide doctors and parents to make decisions that are best for the baby. That is an ethically appropriate goal. But in relying so heavily on gestational age, such policies may actually do the babies a disservice by denying some babies treatment that might be beneficial and lead to intact survival. In this paper, we argue that such policies are unjust to premature babies and ought to be abolished. In their place, we propose individualized treatment decisions for premature babies. This would treat premature babies as we treat all other patients, with clinical decisions based on an individualized estimation of likelihood that treatment would be beneficial.
Screening for mental health problems in a Norwegian preschool population. A validation of the ages and stages questionnaire: Social‐emotional (ASQ:SE)
Authors: Stensen Kenneth , Stenseng Frode , Lydersen Stian , de Wolff Marianne Suzanne , Wallander Jan , Drugli May Britt
Published: January 2018

Background

Early detection of mental health problems in childhood is important. However, studies on screening instruments for preschool children are rare. The aim of this study was to validate the Ages and Stages Questionnaire: Social‐Emotional (ASQ:SE) with teacher reports and examine its screening accuracy in a preschool population.

Methods

A total of 1428 children, aged 18 months – 5 years, attending child‐care centers were recruited in Norway. Their teachers completed a survey including the ASQ:SE and the Caregiver‐Teacher Report Form (C‐TRF). The Spearman's correlation was calculated for the convergence between the ASQ:SE and the C‐TRF and the screening accuracy of the ASQ:SE was assessed using receiver operating characteristic (ROC) analysis with the criterion of a score at or above the 90th percentile for the C‐TRF total problem score.

Results

The Spearman's correlation between the total scores for the ASQ:SE and the C‐TRF were from .49 to .72. The ROC analyses demonstrated that the ASQ:SE had a promising ability to classify children at risk based on the C‐TRF criterion with AUC ranging from .87 to .96 for the different forms. The ASQ:SE generally demonstrated high specificity across all forms and some forms (from age 30 months upwards) produced both high sensitivity and high specificity using the selected cutoff values.

Conclusions

The ASQ:SE could serve as a good starting point for screening for social‐emotional problems among children in child‐care centers. The 30‐ to 60‐month ASQ:SE forms exhibit promising psychometric properties and may prove useful for early detection. The 18‐ to 24‐month ASQ:SE forms demonstrate more limited efficacy in detecting children at risk.
RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer
Authors: Xiao Chao , Wang Yupeng , Zheng Miao , Chen Jian , Song Guohe , Zhou Zhijie , Zhou Chongzhi , Sun Xing , Zhong Lin , Ding Erxun , Zhang Yi , Yang Liu , Wu Gang , Xu Shifeng , Zhang Hong , Wang Xiaoliang
Published: January 2018

Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. The present study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6‐knockdown cells. Transfection with RBBP6 shRNA improved the levels of G2‐M phase arrest, which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, the tumor growth rate of nude mice in the RBBP6‐knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer.
Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer
Authors: Ide Hisamitsu , Lu Yan , Noguchi Takahiro , Muto Satoru , Okada Hiroshi , Kawato Suguru , Horie Shigeo
Published: January 2018

Intratumoral androgen biosynthesis has been recognized as an essential factor of castration‐resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1‐month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC‐MS/MS assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose‐dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1‐month oral administration of curcumin, Aldo‐Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin's natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer.
Development and validation of the Cholinergic Urticaria Quality‐of‐Life Questionnaire (CholU‐QoL)
Authors: Ruft J. , Asady A. , Staubach P. , Casale T. , Sussmann G. , Zuberbier T. , Maurer M. , Weller K. , Altrichter S.
Published: January 2018

Background

Cholinergic urticaria (CholU), a common form of chronic inducible urticaria, is characterized by itchy weals that occur in response to physical exercise or passive warming. CholU patients frequently exhibit a high burden of disease. As of yet, no specific instrument is available to assess their disease‐related quality‐of‐life (QoL) impairment.

Objective

The aim of this study was to develop and validate the first disease‐specific QoL instrument for CholU patients, the Cholinergic Urticaria Quality‐of‐Life Questionnaire (CholU‐QoL).

Methods

Using a combined approach of the literature search, semistructured patient interviews and expert opinion, we developed 96 potential CholU‐QoL items. Subsequent item selection was performed by means of impact analysis complemented by an expert review for face validity. The resulting final CholU‐QoL was then tested for levels of validity, reliability and influence factors in 88 CholU patients. In parallel, an US American‐Canadian English version of the CholU‐QoL was developed.

Results

The final 28‐item CholU‐QoL was found to have a 5‐domain structure (“symptoms,” “functional life,” “social interaction,” “therapy,” “emotions”) with excellent internal consistency. The CholU‐QoL also showed a valid total score, and good levels of convergent validity, known‐groups validity, as well as test‐retest reliability. Multiple regression analysis found no significant drivers of the CholU‐QoL total score.

Conclusions and Clinical Relevance

The CholU‐QoL is the first disease‐specific QoL instrument for CholU and also the first specific QoL measure in the field of chronic inducible urticarias. It may serve as a valuable tool for clinical trials and improve routine patient management.
“I Choose to be Here”: Tensions between Autonomy and Precarity in Craft Market Vendors’ Work
Authors: Kovesi Caroline , Kern Leslie
Published: January 2018

Outdoor markets have emerged as key nodes in cities’ attempts to revitalize downtown areas through culture and consumption. However, few studies have investigated urban markets as sites of labor, or explored work conditions from the perspective of vendors themselves. As self–employed creative workers in a seasonal industry, artisan vendors experience various forms of economic insecurity related to precarity inherent to their line of work. This article investigates the experiences of artisan craft vendors in Ottawa's popular ByWard Market. Through interviews with vendors, we explore themes such as artisan identity, relationships in the market, and economic and labor conditions. We argue that although precarity seems to be inherent in the vendors’ work conditions, it does not undermine their identities as artisans, in part because of the strong value attached to autonomous, creative work. This attachment may, however, hinder artisan vendors’ abilities to organize for structural changes that would mitigate their economic precarity.