bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalized privacy in open data sharing scenarios
Authors: Sánchez David , Viejo Alexandre
Published: April 2017

Purpose

The purpose of this paper is to propose a privacy-preserving paradigm for open data sharing based on the following foundations: subjects have unique privacy requirements; personal data are usually published incrementally in different sources; and privacy has a time-dependent element.

Design/methodology/approach

This study first discusses the privacy threats related to open data sharing. Next, these threats are tackled by proposing a new privacy-preserving paradigm. The main challenges related to the enforcement of the paradigm are discussed, and some suitable solutions are identified.

Findings

Classic privacy-preserving mechanisms are ineffective against observers constantly monitoring and aggregating pieces of personal data released through the internet. Moreover, these methods do not consider individual privacy needs.

Research limitations/implications

This study characterizes the challenges to the tackled by a new paradigm and identifies some promising works, but further research proposing specific technical solutions is suggested.

Practical implications

This work provides a natural solution to dynamic and heterogeneous open data sharing scenarios that require user-controlled personalized privacy protection.

Social implications

There is an increasing social understanding of the privacy threats that the uncontrolled collection and exploitation of personal data may produce. The new paradigm allows subjects to be aware of the risks inherent to their data and to control their release.

Originality/value

Contrary to classic data protection mechanisms, the new proposal centers privacy protection on the individuals, and considers the privacy risks through the whole life cycle of the data release.
A study of facility management operation strategy in shopping malls
Authors: Chotipanich Sarich , Issarasak Sittiporn
Published: April 2017

Purpose

This paper is a continuing exploration into facilities management (FM) strategy through the arrangement of its decision choices. The purpose of this paper is to identify the existence of FM operation strategy and to add empirical evidence to this subject to the field of FM and property management. Its main objectives are to gain insights into the arrangement of the FM strategic choices in operation and its relationship with business strategy.

Design/methodology/approach

The study investigated the configurations of operational approaches and activities that should reflect strategic decisions. The investigation was undertaken through a study of four reputed shopping malls located in Bangkok. The relevant data were collected through semi-structured interviews with the key FM persons of each case study, plus archival document searches, and observations of operational processes. Subsequently, the data were examined in a cross-case analysis to identify the key patterns of relationships between the FM operational arrangements and the business strategy of the mall.

Findings

This study found that the functional scheme of FM adopted in operations was deliberately related to the needs of business strategy and the operations of the given shopping mall. A range of strategic choices for FM operations was also found. Certain choices are shared among the case studies, while their arrangements varied according to the particular business strategy and context.

Research limitations/implications

The number of case studies was rather limited, while the results were predominantly involved with a single type of facility.

Originality/value

The study identified the pattern of strategic choices entailed in the FM operations in shopping malls. The findings add to the understanding on FM strategy by widening the perspectives about the strategic choices of FM operations and how they are connected with the business strategy and operation model of retail estate. It adds empirical evidence and case studies regarding FM operations and its strategic features.
Preparation of water-resistant adhesives from soy flour with less water-soluble components for wood bonding
Authors: Gui Chengsheng , Zhu J. , Liu Xq , Zhang Zhongtao
Published: April 2017

Purpose

The purpose of this paper is to prepare a water-resistant adhesive (SA) from soy flour (SF) with less water-soluble components.

Design/methodology/approach

Defatted SF was suspended and stirred in water. Then, the pH of dispersion was adjusted to a predetermined value (i.e. 8, 9 or 10) by the addition of 2M sodium hydroxide (NaOH) solution. After stirring at a predetermined temperature (25°C, 35°C, 45°C) for different time (1 h, 2 h, 3 h), the 2M hydrochloric acid (HCl) solution was added in a dropwise manner into the dispersion until the pH value was adjusted to 4.5. Then, the dispersion was centrifuged at 6,000 rpm for 2 min. The obtained precipitate with less water-soluble components was used as an adhesive (SA) directly.

Findings

SA had a wet strength of 1.02 MPa when used for the fabrication of poplar plywood. Polyvinyl alcohol (PVA) solution was applied to improve the tack of SAs to wood surface and the viscosities of SAs were decreased from 10,200 cP to 4,100 cP at room temperature after the PVA addition. The soy proteins in SAs were not denatured to a large extent according to the differential scanning calorimetry and light microscopy. The remained multilevel structures of soy protein played a positive contribution to the water resistance of SAs, and the bond lines of cured SAs were much more stable than those of the cured SF and soy protein concentrate (SPC).

Research limitations/implications

The fluidity and solid content of soy adhesives is much lower than formaldehyde adhesives. Further investigations are needed to improve the fluidity of soy adhesives with high solid contents.

Originality/value

Novel water-resistant soy adhesives were provided.
Comparative study of rapid and conventional tooling for plastics injection molding
Authors: Mendible Gabriel Antonio , Rulander Jack A. , Johnston Stephen P.
Published: April 2017

Purpose

This study aims to evaluate the performance of injection molding inserts produced via rapid and conventional manufacturing techniques considering the mechanical and thermal performance of the tools as well as the resulting molded part quality.

Design/methodology/approach

Three insert materials and manufacturing techniques were evaluated, jetted photopolymer (PolyJet) 3D printing using digital ABS, direct metal laser sintering (DMLS) using bronze and machining using stainless steel. Molding trials were performed, and the insert surface temperature, longevity and part properties were evaluated. Complementary information was acquired using computer simulation.

Findings

Similar behavior and part quality were observed in machined and DMLS inserts. The latter were used for 500 cycles without any signs of failure. PolyJet inserts had increased cycle time and slower rate of cooling which increased shrinkage and crystallinity in the molded parts. PolyJet inserts could be produced quickly at a lower cost than machined or DMLS inserts.

Research limitations/implications

Cooling within the insert was not studied; inserts were cooled indirectly by the mold plates behind them. Subsequent studies will incorporate cooling lines directly into the inserts.

Originality/value

Little research has been done to understand the thermal behavior of inserts manufactured via rapid tooling techniques. This study provides a direct comparison between rapid tooling techniques, which is supported by simulation results and analysis of the actual molding properties.
Plate auto-level system for fused deposition modelling (FDM) 3D printers
Authors: Soriano Heras Enrique , Blaya Haro Fernando , de Agustín del Burgo José María , Islán Marcos Manuel Enrique
Published: April 2017

Purpose

The purpose of this paper is to present a solution for the levelling plate of fused deposition modelling (FDM) additive manufacturing (AM) systems. This automatic levelling system is presented as an evolution of actual systems, which uses a new ultrasound sensing system.

Design/methodology/approach

After obtaining a prototype, different tests were conducted for getting a system which solves the level plate problem and can be mounted in any FDM AM machine. Several benchmark models were obtained and compared with current equipment concepts for the validity of the product.

Findings

All tests were performed with high accuracy, enabling the production of geometries that could not have been achieved without this novel system.

Practical implications

This development will enable experienced users to set aside the problems of calibration and focus on the purpose of this type of machines, making prototypes.

Originality/value

A system architecture has been developed and integrated into an open hardware AM system, allowing real-time adjustment of the plate during each layer, thus eliminating the need of levelling the plate, allowing to achieve easier printing, and without increasing the cost significantly.
Selection of additive manufacturing processes
Authors: Wang Yuanbin , Blache Robert , Xu Xun
Published: April 2017

Purpose

This study aims to review the existing methods for additive manufacturing (AM) process selection and evaluate their suitability for design for additive manufacturing (DfAM). AM has experienced a rapid development in recent years. New technologies, machines and service bureaus are being brought into the market at an exciting rate. While user’s choices are in abundance, finding the right choice can be a non-trivial task.

Design/methodology/approach

AM process selection methods are reviewed based on decision theory. The authors also examine how the user’s preferences and AM process performances are considered and approximated into mathematical models. The pros and cons and the limitations of these methods are discussed, and a new approach has been proposed to support the iterating process of DfAM.

Findings

All current studies follow a sequential decision process and focus on an “a priori” articulation of preferences approach. This kind of method has limitations for the user in the early design stage to implement the DfAM process. An “a posteriori” articulation of preferences approach is proposed to support DfAM and an iterative design process.

Originality/value

This paper reviews AM process selection methods in a new perspective. The users need to be aware of the underlying assumptions in these methods. The limitations of these methods for DfAM are discussed, and a new approach for AM process selection is proposed.
The challenge of building support for human resource programs
Authors: Maurer Rick
Published: April 2017

Purpose

The purpose of this paper is to provide human resource (HR) leaders with a practical, straightforward approach to the challenge of building support (and reducing resistance). Building support for new programs is difficult in many organizations, and the cost of failed change is large. HR is not immune to these pitfalls. The primary reason that projects fail is resistance. Resistance itself is not the problem. But, how leaders look at and work with resistance is a significant problem.

Design/methodology/approach

This approach is based on some 20 years of practice working with leaders on ways to build support for change. The author has helped leaders apply this approach in HR departments, as well as many other departments within organizations. This approach has been applied in aerospace, healthcare, large city library systems and telecommunications, to name a few.

Findings

The key finding is not that this approach is so wonderful, but that the mindset of the leader(s) is the key. When a leader or a leadership team believes that people and their thoughts and feelings actually matter, and that the department is best-served by respecting the people who work with and for them, then building support for change has a good chance of succeeding. The approach described here works well with leaders who want to engage others with dignity and respect.

Practical implications

This paper is meant to be practical. In fact, it invites readers to consider a change they are considering as they read the paper. By the end of the paper, readers should begin to see ways to apply these ideas immediately. Many people apply these ideas without further education or consultant assistance.

Originality/value

Resistance remains a bad word in organizations. (Organization development is a notable exception to that generality.) Leaders often give lip service to engagement and take part in high-involvement activities but fail to follow through. The author attempts to make the work as easy to access as possible, while avoiding simplistic thinking, to give leaders low-risk ways to begin to increase their respect for people (and their resistance). Leaders who try out more respectful ways to engage people are likely to up the ante and experiment with deeper ways of making contact with others.
Dispersion beyond miles: configuration and performance in virtual teams
Authors: Prasad Ambika , DeRosa Darleen , Beyerlein Michael
Published: April 2017

Purpose

The purpose of this paper is to understand different aspects of structural dispersion in virtual teams (VTs). The study measures five types of dispersion, their impact on VT performance and the moderating effect of electronic communication.

Design/methodology/approach

The authors collected data from 44 globally distributed VTs representing 403 members. The authors used details of the members’ locations to measure five elements of dispersion for each team: spatial, time-zone, number of locations, extent of numerical balance across locations and extent of isolated members for a team. The authors used two items to assess effective electronic communication and measured team performance on four items from three sources – members, leaders and third-party stakeholders.

Findings

Using regression, the authors found that the number of sites, degree of team balance and isolation had a negative impact on team performance. Spatial and temporal dispersion did not impact performance. Effective electronic communication moderated the relationship of team performance with team balance and the number of sites.

Research limitations/implications

Study presents novel findings on the role of team configuration in VTs. Limitations: the study provides pointers to the likelihood of a non-linear relationship between spatial distance and performance; however, the scope of the paper does not permit an examination of this model. Future research can study this relationship. Second, the study does not examine how team configuration impacts the team processes that discount performance. Finally, the study treats each index of dispersion as independent of the others. The analysis does not study the interplay between and among the indices.

Practical implications

The findings provide clear indicators for managers and researchers of VTs on the issues associated with the location and configuration of the teams. Managers, while designing and managing dispersed members are now informed of the impact of the number of sites and the sub-group dynamics. The study underscores the importance of effective electronic communication in managing dispersion.

Social implications

The study presents how faultiness based on location of VT sub-groups (as represented in the configuration of a team) can hamper performance. Literature suggests that this faultiness can also extend to social identities (based on gender, culture, etc.). The indicators provided by this study in this respect provide a topical focus for research because diverse dispersed teams are becoming more prevalent.

Originality/value

The study is the first empirical exploration of dispersion in VTs beyond the traditionally acknowledged dimensions of spatial distance and time-zones. It is a timely response to the recent trends in literature. Additionally, the study derives data from a unique data set of global VTs, thus making findings easily generalizable.
Emergence of team engagement under time pressure: role of team leader and team climate
Authors: Sharma Anshu , Bhatnagar Jyotsna
Published: April 2017

Purpose

This paper aims to identify the determinants of team engagement emerging as a collective team-level phenomenon under time pressure context. The paper particularly explores how teams working under time pressure conditions use their social resources to develop into highly engaged teams.

Design/methodology/approach

The paper develops a conceptual framework along with related propositions by integrating diverse literature from the field of team processes, leadership and engagement. The arguments are theoretically embedded into the job demands-resources (JD-R) model to explain the emergence of team engagement under time pressure conditions.

Findings

The suggested conceptual model based on the JD-R model reveal that teams working under time pressure conditions view it as a challenging job demand and, hence, use their social resources as a coping mechanism, thereby developing into highly engaged teams. However, the paper finds that for team engagement to emerge under time pressure, teams require two important determinants. These two main determinants are team leader engaging behaviors and team climate. Engaging team leader’s behaviors include four sub-components: emotional agility, use of humor, efficient delegation and quality of feedback. Team climate constitute three sub-components: open communication, fun at work and compassion within the team. Only teams which have a strong team climate and team leaders’ engaging behaviors tend to have high team engagement under time pressure contexts.

Research limitations/implications

The paper offers implications for both HR and line managers in team-based organizations to promote factors that enhance team engagement, for teams to perform under time pressure situations.

Originality/value

The paper identifies determinants of team engagement under time pressure context and further adds to the understanding of team processes by theoretically exploring how time pressure as a job demand can be channeled in a positive manner for promoting team engagement by using teams’ social resources: team leader’s engaging behaviors and team climate.
The impact of within-team variance on transactive memory system development and team performance
Authors: King Kylie Goodell
Published: April 2017

Purpose

The purpose of this paper is to describe the dispersion models, where within-team variance is the outcome of interest, and propose the application of these models to the measurement of the transactive memory system (TMS). As teams become increasingly prominent in educational contexts and within organizations, it is important to evaluate how various measures of individual and team attributes relate to team performance. One measure that has been evaluated by a number of previous empirical studies is TMSs.

Design/methodology/approach

In past studies of TMS and in most teams research, team-level data are collected and correlated with performance, or individual-level data are collected, aggregated to the team-level data and then correlated with performance. While this is appropriate in situations where data are isomorphic or similar across levels of measurement, there are often important differences among within-team responses that lead to a discrepancy between the sum of individual attributes and a team-level measure.

Findings

Preliminary results demonstrate that within-team variance in reported levels of TMS has an inverse relationship with team performance.

Research limitations/implications

Future research should further evaluate the ability for dispersion models of TMS to predict team performance, especially in organizational settings with professional rather than student teams.

Originality/value

This paper provides a new approach to measuring TMS and relating TMS to team performance.
Estimating melanin location in the pigmented skin lesions by hue–saturation–lightness color space values of dermoscopic images
Authors: Sakai Hiroshi , Ando Yoshimi , Ikinaga Kuniko , Tanaka Masaru
Published: April 2017

The depth of melanin in the skin can be estimated roughly by observation of the color exhibited on dermoscopy. Currently, there are no objective methods to estimate it. The aim of the present study was to clarify the relationship between the depth of melanin in the skin and the color variation exhibited, and to objectively estimate the 3‐D location of melanin in the pigmented skin lesions from dermoscopic images. Representative colors in dermoscopic images of acral compound nevus, Spitz nevus and blue nevus were evaluated by the subjectively perceived color on dermoscopy and objective values in hue–saturation–lightness color space values. Brown colors due to small quantities of superficial melanin in the skin had high saturation and low lightness values, whereas black colors due to large quantities of superficial melanin had low saturation and low lightness values. On the other hand, colors due to melanin in the dermis were perceived as blue–gray on dermoscopy, but extracted colors showed gray–brown hue and intermediate saturation and high lightness values. In all cases, extracted representative colors of pigmented skin lesions had similar hue values within the red–orange range. Objective estimation of the 3‐D location of melanin in the pigmented skin lesions is possible by the saturation and lightness values of the colors extracted from dermoscopic images. Subjectively perceived colors of melanin, especially in the dermis, can be modified by the surrounding environment effect and blue color perception.
Effects of Helicobacter pylori treatment on rosacea: A single‐arm clinical trial study
Authors: Saleh Parviz , Naghavi‐Behzad Mohammad , Herizchi Hamdieh , Mokhtari Fatemeh , Mirza‐Aghazadeh‐Attari Mohammad , Piri Reza
Published: April 2017

Rosacea is a chronic dermatological disease. Helicobacter pylori has been discussed as one of its causative factors. In this clinical trial study, we attempted to evaluate the effect of H. pylori standard eradication protocol on the rosacea clinical course. In this single‐arm clinical trial, patients ascertained to have H. pylori infection based on serological studies were assessed to examine existence of rosacea. Patients with concurrent rosacea and H. pylori infection were included in the study and underwent standard H. pylori eradication therapy. Rosacea was evaluated using the Duluth rosacea grading score at the beginning, 2 months later and at the end of the trial (day 180). Of 872 patients positive for H. pylori, 167 patients (19.15%) manifested the clinical features of rosacea. The patients with concurrent rosacea were younger (P < 0.001) and with a female sex predominance (P = 0.03) when compared with rosacea‐free patients. Of 167 patients, 150 received H. pylori eradication therapy, demonstrating a 92% (138/150) cure rate. The rosacea Duluth score grading on day 0, 60 and 180 among 138 patients significantly decreased in most of the criteria except for telangiectasias (P = 0.712), phymatous changes (P = 0.535) and the existence of peripheral involvement (P = 0.431). The present study concluded that H. pylori eradication leads to improvement of rosacea.
Soil aggregation and associated microbial communities modify the impact of agricultural management on carbon content
Authors: Trivedi Pankaj , Delgado‐Baquerizo Manuel , Jeffries Thomas C. , Trivedi Chanda , Anderson Ian C. , Lai Kaitao , McNee Matthew , Flower Kenneth , Pal Singh Bhupinder , Minkey David , Singh Brajesh K.
Published: April 2017

Soil carbon (C) stabilisation is known to depend in part on its distribution in structural aggregates, and upon soil microbial activity within the aggregates. However, the mechanisms and relative contributions of different microbial groups to C turnover in different aggregates under various management practices remain unclear. The aim of this study was to determine the role of soil aggregation and their associated microbial communities in driving the responses of soil organic matter (SOM) to multiple management practices. Our results demonstrate that higher amounts of C inputs coupled with greater soil aggregation in residue retention management practices has positive effects on soil C content. Our results provide evidence that different aggregate size classes support distinct microbial habitats which supports the colonisation of different microbial communities. Most importantly our results indicate that the effects of management practices on soil C is modulated by soil aggregate sizes and their associated microbial community and are more pronounced in macro‐aggregate compared with micro‐aggregate sizes. Based on our findings we recommend that differential response of management practices and microbial control on the C turnover in macro‐aggregates and micro‐aggregate should be explicitly considered when accounting for management impacts on soil C turnover.
Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases
Authors: Elbert N. J. , van Meel E. R. , den Dekker H. T. , de Jong N. W. , Nijsten T. E. C. , Jaddoe V. W. V. , de Jongste J. C. , Pasmans S. G. M. A. , Duijts L.
Published: April 2017

Background

Breastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease‐related modification of the exposure or modified by maternal history of allergy, eczema, or asthma.

Methods

This study among 5828 children was performed in a population‐based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2‐4 months, 4‐6 months, and ≥6 months) and exclusiveness (nonexclusive vs exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant allergic sensitization and food‐allergic sensitization were measured by skin prick tests, and physician‐diagnosed inhalant and food allergy by a postal questionnaire. Data on parental‐reported eczema were available from birth until age 10 years.

Results

We observed no association of breastfeeding with any allergic sensitization, physician‐diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (P‐value for trend <.05). Nonexclusively breastfed children had an overall increased risk of eczema (adjusted odds ratio [95% confidence interval]: 1.11 [1.01, 1.23]), compared with children exclusively breastfed for 4 months. Risk period‐specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross‐lagged modeling showed no consistent results for disease‐related modification of the exposure. Results were not modified by maternal history of allergy, eczema, or asthma (lowest P‐value for interaction=.13).

Conclusion

Shorter duration or nonexclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician‐diagnosed allergy at age 10 years.
Clinicopathologic features and immunohistochemical spectrum of 11 cases of epithelioid malignant peripheral nerve sheath tumors, including INI1/SMARCB1 results and BRAF V600E analysis
Authors: Rekhi Bharat , Kosemehmetoglu Kemal , Tezel Gaye Guler , Dervisoglu Sergulen
Published: April 2017

Epithelioid malignant peripheral nerve sheath tumor (MPNST) is a rare, relatively less chemosensitive sarcoma. We report clinicopathologic features of 11 epithelioid MPNSTs, including rare forms, along with INI1 immunostaining and BRAF V600E mutation results. BRAF V600E mutation was tested by Real‐time polymerase chain reaction (PCR) technique. Eleven tumors occurred in six men and five women (M:F ratio = 0.85:1) within an age range of 5–73 years (average = 44), mostly in lower limbs (five), followed by upper limbs (four). Tumor size (n = 6), varied from 3.1 to 15 cm (average = 8.3). Histopathologically, most tumors were multilobular, characterized by epithelioid to round‐shaped, malignant cells, along with spindle cells (three cases), “rhabdoid‐like” cells (seven cases) and pleomorphic giant cells (single case). By immunohistochemistry, tumor cells were positive for S100 protein (11/11) (100%), EMA (3/7) (42.8%), pan CK(2/7) (28.5%), and HMB45 (1/11) (9%), while these were negative for Melan A (0/11) and INI1 (3/11), including a single tumor, displaying HMB45 positivity. BRAF V600E mutation was positive in 1/8 cases, that lacked melanocytic marker expression. All patients (n = 5) were treated by surgical resection. During follow‐up (n = 8, median duration = 23 months), four patients developed tumor recurrences and four developed metastasis, mostly to lymph nodes (3). Finally, four patients were alive with disease, two were alive with no evidence of disease, and two patients died of disease. Epithelioid MPNSTs have a diverse histopathologic spectrum. Loss of INI1 is useful, including in identifying rare forms of epithelioid MPNST, displaying melanocytic differentiation. Most tumors are treated by surgical resection. Loss of INI1 and the presence of BRAF V600E mutation in some cases raises future possibility of exploring targeted therapy in those, rare epithelioid MPNSTs.
Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease
Authors: Bye W. A. , Jairath V. , Travis S. P. L.
Published: April 2017

Background

Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut‐specific immunosuppression.

Aim

To review the safety of vedolizumab and summarise post‐marketing data to assess if any safety concerns that differ from registration trials have emerged.

Method

A systematic bibliographic search identified six registration trials and nine cohort studies.

Results

Integrated data from registration trials included 2830 vedolizumab‐exposed patients (4811 person‐years exposure [PYs]) and 513 placebo patients. This reported lower exposure‐adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6‐67.3) and serious adverse events (20.0/100 PYs; 95% CI: 18.5‐21.5) compared to placebo (82.9/100 PYs; 95% CI: 68.3‐97.5) and (28.3/100 PYs 95% CI: 20.6‐35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab‐exposed patients (7.4/100 PYs; 95% CI: 6.6‐8.3) compared to placebo (6.7 PYs; 95% CI: 3.2‐10.1). Six post‐marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited.

Conclusions

Post‐marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post‐operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those pre‐disposed to infection, malignancy or the elderly.
The risk of gastric cancer in patients with gastric intestinal metaplasia in 5‐year follow‐up
Authors: Pittayanon R. , Rerknimitr R. , Klaikaew N. , Sanpavat A. , Chaithongrat S. , Mahachai V. , Kullavanijaya P. , Barkun A.
Published: April 2017

Background

Gastric intestinal metaplasia (GIM) is the premalignant stage of gastric cancer; however, consensus on its management has not been established.

Aim

To determine the risk factors for gastric cancer in a population of patients with GIM to guide the appropriate clinical recommendations in a low prevalence area for gastric cancer.

Methods

This was a retrospective cohort study. Ninety‐one patients with GIM diagnosed between 2004 and 2014 were recruited for surveillance EGD every 6‐12 months until a diagnosis of gastric cancer or completion of the planned 5‐year follow‐up duration. Possible risk factors for gastric cancer were assessed.

Results

At initial presentation, 81 of the 91 patients (89%) had complete GIM, whereas the remaining 11% had a study entry diagnosis of incomplete GIM. No cancer developed amongst patients with complete GIM. In contrast, five of the 10 patients exhibiting incomplete GIM (50%) progressed to high‐grade dysplasia (n=2) or cancer (n=3). Male gender (P=.027), and incomplete GIM (P=.001) were associated with high‐risk histology (dysplasia or cancer) by study end. A trend suggested a possible association with smoking (P=.08).

Conclusion

Male patients and those with incomplete GIM are at greatest risk of developing dysplasia or early gastric cancer. Further studies in determining optimal surveillance intervals and impact on cancer incidence and mortality are still required.
Configuring climate responsibility in the city: carbon footprints and climate justice in Hong Kong
Authors: Fuller Sara
Published: April 2017

Climate action is increasingly marked by the responsibilisation of individuals. In this context, carbon footprints have gained traction as a means of both quantifying individual responsibility for climate change and for motivating individual action through changes in behaviour. However, these mechanisms raise questions for climate justice in terms of how such moral and political responsibility is configured and distributed within the city. Drawing on a case study of Hong Kong, this paper explores the ways in which carbon footprinting configures responsibility for climate action by juxtaposing carbon footprints and the associated techniques of quantification alongside a discussion of the everyday practices of residents in a low‐income neighbourhood. It argues that carbon footprints offer important opportunities for measuring the impacts of carbon‐intensive activities and generating discussions about the allocation of responsibility for addressing climate change. However, it also demonstrates that individual carbon footprints ignore the uneven nature of carbon emissions in cities as well as obscuring important questions about the roles and responsibilities of other actors. In conclusion, the paper calls for an approach centred on common but differentiated responsibilities for carbon production and consumption to enable a more nuanced configuration of climate justice in the city.
Safety, pharmacokinetics and pharmacological effects of the selective androgen receptor modulator, GSK2881078, in healthy men and postmenopausal women
Authors: Clark Richard V. , Walker Ann C. , Andrews Susan , Turnbull Philip , Wald Jeffrey A. , Magee Mindy H.
Published: April 2017

Aim

Selective androgen receptor modulators (SARMs) induce anabolic effects on muscle without the adverse effects of androgenic steroids. In this first‐in‐human study, we report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of the SARM GSK2881078.

Methods

In Part A, healthy young men (n = 10) received a single dose of study drug (0 mg, 0.05 mg, 0.1 mg, 0.2 mg GSK2881078 or matching‐placebo). In Part B, repeat‐dose cohorts in men (n = 65) were 0.05 mg, 0.2 mg then 0.08 mg, 0.24 mg, 0.48 mg, 0.75 mg, or placebo; in women (n = 24) they were 0.24 mg, 0.35 mg, or placebo (7 days for 0.5 mg, 14 days for other doses).

Results

PK analysis showed dose‐proportional increases in exposure and a long >100‐h half‐life. No significant effects on vital signs, electrocardiograms, cardiac telemetry or standard clinical laboratory studies were observed. A dose–response effect was observed on lowering both high‐density lipoprotein and sex hormone‐binding globulin. In females at 0.35 mg, differences from placebo were −0.518 (95% confidence interval: –0.703, −0.334) mmol l–1 and −39.1 (−48.5, −29.7) nmol l–1, respectively. Women showed greater sensitivity to these parameters at lower doses than men. Drug‐related adverse events (AEs) were mild. One woman developed a drug rash and was withdrawn. Two men had elevated creatine phosphokinase after physical exertion during follow‐up. A serious AE occurred in a subject on placebo.

Conclusions

These data demonstrate pharmacodynamic effects with acceptable tolerability and support further clinical evaluation of this SARM.
Prescribing Safety Assessment 2016: Delivery of a national prescribing assessment to 7343 UK final‐year medical students
Authors: Maxwell Simon R. J. , Coleman Jamie J. , Bollington Lynne , Taylor Celia , Webb David J.
Published: April 2017

Aims

Newly graduated doctors write a large proportion of prescriptions in UK hospitals but recent studies have shown that they frequently make prescribing errors. The prescribing safety assessment (PSA) has been developed as an assessment of competence in relation to prescribing and supervising the use of medicines. This report describes the delivery of the PSA to all UK final‐year medical students in 2016 (PSA2016).

Methods

The PSA is a 2‐hour online assessment comprising eight sections which cover various aspects of prescribing defined within the outcomes of undergraduate education identified by the UK General Medical Council. Students sat one of four PSA ‘papers’, which had been standard‐set using a modified Angoff process.

Results

A total of 7343 final‐year medical students in all 31 UK medical schools sat the PSA. The overall pass rate was 95% with the pass rates for the individual papers ranging from 93 to 97%. The PSA was re‐sat by 261 students who had failed and 80% of those candidates passed. The internal consistency (Cronbach's alpha) of the four papers ranged from 0.74 to 0.77 (standard error of measurement 4.13–4.24%). There was a statistically significant variation in performance between medical school cohorts (F = 32.6,P < 0.001) and a strongly positive correlation in performance for individual schools between PSA2015 and PSA2016 (r = 0.79, 95% CI 0.61–0.90;P < 0.01).

Conclusions

PSA2016 demonstrated the feasibility of delivering a standardized national prescribing assessment online. The vast majority of UK final‐year medical students were able to meet a prespecified standard of prescribing competence.
Targeting anti‐apoptotic BCL2 family proteins in haematological malignancies – from pathogenesis to treatment
Authors: Vogler Meike , Walter Harriet S. , Dyer Martin J. S.
Published: April 2017

The B‐cell lymphoma 2 (BCL2) family of proteins comprise key regulators of apoptosis and are implicated in the pathogenesis of many malignancies, including lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to tumour cells or render them more sensitive to chemotherapy. Inhibition of the anti‐apoptotic functions of BCL2 proteins using structure‐based design to produce specific inhibitors of protein–protein interactions has been achieved for BCL2, MCL1 and BCL‐XL (also termed BCL2L1), providing an armamentarium of new targeted therapies called BH3‐mimetics. The first BCL2‐specific inhibitor, venetoclax, has shown extraordinary single agent activity in chronic lymphocytic leukaemia (CLL), with surprisingly little toxicity given the expression of BCL2 in normal tissues. Despite success in CLL, where sensitivity to BCL2 inhibition is seen in nearly all cases, key questions have not yet been addressed. For example, responses to venetoclax in other B‐cell and myeloid malignancies are heterogeneous, highlighting the need to identify biomarkers that correlate with response and, secondly, to identify/develop other specific compounds that synergise with BCL2 inhibition. In this review, we summarise the biology of BCL2 proteins, the mechanism of action of BH3‐mimetics and the status of their clinical development in haematological malignancies.
The Lateglacial to early Holocene tephrochronological record from Lake Hämelsee, Germany: a key site within the European tephra framework
Authors: Jones Gwydion , Lane Christine S. , Brauer Achim , Davies Siwan M. , de Bruijn Renée , Engels Stefan , Haliuc Aritina , Hoek Wim Z. , Merkt Josef , Sachse Dirk , Turner Falko , Wagner‐Cremer Friederike
Published: April 2017

Here we present the results of a detailed cryptotephra investigation through the Lateglacial to early Holocene transition, from a new sediment core record obtained from Lake Hämelsee, Germany. Two tephra horizons, the Laacher See Tephra (Eifel Volcanic Field) and the Saksunarvatn Ash (Iceland), have been previously described in this partially varved sediment record, indicating the potential of the location as an important Lateglacial tephrochronological site in northwest Europe. We have identified three further tephra horizons, which we correlate to: the c. 12.1 ka BP Vedde Ash (Iceland), the c. 11 ka BP Ulmener Maar tephra (Eifel Volcanic Field) and the c. 10.8 ka BP Askja‐S tephra (Iceland). Three additional cryptotephra deposits have been found (locally named HÄM_T1616, HÄM_T1470 and HÄM_T1456‐1455), which cannot be correlated to any known eruption at present. Geochemical analysis of the deposits suggests that these cryptotephras most likely have an Icelandic origin. Our discoveries provide age constraints for the new sediment records from Lake Hämelsee and enable direct stratigraphical correlations to be made with other tephra‐bearing sites across Europe. The new tephrostratigraphical record, within a partially varved Lateglacial sediment record, highlights the importance of Lake Hämelsee as a key site within the European tephra lattice.
Recent progress in the understanding of relaxin family peptides and their receptors
Authors: Summers R J
Published: April 2017

Linked Articles

This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc
Predictive mechanisms linking brain opioids to chronic pain vulnerability and resilience
Authors: Jones Anthony Kenneth Peter , Brown Christopher Andrew
Published: April 2017

Chronic pain is a major global healthcare problem that is currently inadequately treated. In addition, the current use of opioids for treatment has reached far beyond the paucity of evidence for long‐term benefits relative to risks. Benefit–risk models for opioid and non‐opioid treatments would benefit from a rational, mechanism‐based understanding of neuroplastic and neurochemical contributions to chronic pain. Here, we evaluate the findings and limitations of representative research investigating brain neuroplasticity and neurochemistry in chronic pain. In sum, the mechanisms of pain‐related neuroplasticity in the brain remain poorly understood because neuroimaging studies have been largely descriptive. We argue that definition is needed of optimal (pain‐resilient) and suboptimal (pain‐vulnerable) functioning of the endogenous opioid system in order to identify neurochemical contributions to aberrant neuroplasticity in chronic pain. We outline the potential benefits of computational approaches that utilize evolutionary and statistical optimality principles, illustrating this approach with mechanistic hypotheses on opioid function. In particular, we discuss the role of predictive mechanisms in perceptual and associative plasticity and evidence for their modulation by endogenous opioids. Future research should attempt to utilize formal computational models to provide evidence for the clinical validity of this approach, thereby providing a rational basis for future treatment and, ideally, prevention.

Linked Articles

This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc
Documenting and harnessing the biological potential of molecules in Distributed Drug Discovery (D3) virtual catalogs
Authors: Abraham Milata M. , Denton Ryan E. , Harper Richard W. , Scott William L. , O'Donnell Martin J. , Durrant Jacob D.
Published: April 2017

Virtual molecular catalogs have limited utility if member compounds are (i) difficult to synthesize or (ii) unlikely to have biological activity. The Distributed Drug Discovery (D3) program addresses the synthesis challenge by providing scientists with a free virtual D3 catalog of 73,024 easy‐to‐synthesizeN‐acyl unnatural α‐amino acids, their methyl esters, and primary amides. The remaining challenge is to document and exploit the bioactivity potential of these compounds. In the current work, a search process is described that retrospectively identifies all virtual D3 compounds classified as bioactive hits in PubChem‐cataloged experimental assays. The results provide insight into the broad range of drug‐target classes amenable to inhibition and/or agonism by D3‐accessible molecules. To encourage computer‐aided drug discovery centered on these compounds, a publicly available virtual database of D3 molecules prepared for use with popular computer docking programs is also presented.
How to manage chronic urticaria ‘beyond’ guidelines: a practical algorithm
Authors: Rutkowski K. , Grattan C. E. H.
Published: April 2017

Chronic urticaria (CU) is a disease characterized by pruritic weals, angio‐oedema or both occurring for at least 6 weeks. It encompasses spontaneous and inducible urticarias. The national and international guidelines outline the principles of treatment. Omalizumab, an anti‐immunoglobulin E monoclonal antibody, has transformed the management of many severe and treatment‐refractory patients. However, current UK guidance on its use does not address the needs of those with less severe disease, inducible urticarias, idiopathic histaminergic angio‐oedema without weals as a presentation of CU and omalizumab non‐responders. Our algorithm and a summary of the evidence to support its principles offers guidance and a more systematic targeted approach to using a range of ‘off‐label’ agents for specific phenotypes of CU. It will be of use when guideline‐recommended mast cell mediator antagonists fail to control symptoms and/or using omalizumab is ineffective, not practical or unfunded.
Development, validation and testing of a skin sampling method for assessment of metal exposure
Authors: Erfani Behnaz , Midander Klara , Lidén Carola , Julander Anneli
Published: April 2017

Background

Nickel, cobalt and chromium are frequent skin sensitizers. Skin exposure results in eczema in sensitized individuals, the risk being related to the skin dose.

Objectives

To develop a self‐sampling method for quantification of skin exposure to metals, to validate the method, and to assess its feasibility.

Methods

Defined metal doses (0.01–5 µg) were applied to the fingers of 5 participants. Skin areas (2 cm2) were sampled with 1% HNO3, either as 0.1 ml on a swab, or as 0.5 ml on a wipe. Furthermore, 17 participants performed self‐sampling by swab after 2 h of leisure activity. Samples were extracted in 1% HNO3 and analysed by inductively coupled plasma mass spectrometry.

Results

The sampling efficiency by swab was 46%, as compared with 93% for acid wipe sampling, for all tested doses. Most metal from the skin dose was detected in the first swab (33–43%). Despite lower sampling efficiency by swab, skin doses of metals following 2 h of leisure activity without hand washing were quantified in all participants, and ranged from 0.0016 to 0.15 µg/cm2, from 0.00014 to −0.0020 µg/cm2 and from 0.00048 to −0.027 µg/cm2 for nickel, cobalt, and chromium, respectively.

Conclusions

The results indicate a future potential of skin sampling by swab to detect and monitor metals on skin by self‐sampling. This will contribute to better knowledge of metal skin exposure among dermatitis patients, workers, and the general population.