bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative and oncological outcomes of radical prostatectomy for high‐risk prostate cancer in the UK: an analysis of surgeon‐reported data
Authors: Aning Jonathan J. , Reilly Gavin S. , Fowler Sarah , Challacombe Ben , McGrath John S. , Sooriakumaran Prasanna ,   on behalf of the BAUS Section of Oncology
Published: January 2019

Objectives

To analyse the perioperative and oncological outcomes of all radical prostatectomies (RPs) performed for high‐risk prostate cancer in the British Association of Urological Surgeons (BAUS) national registry from 2014 to 2015.

Patients and Methods

We identified and analysed outcomes of all RPs performed for high‐risk prostate cancer (clinical stage >T2 and/or biopsy Gleason grade >7 and/or preoperative prostate‐specific antigen level ≥20 ng/mL) in the national registry for 2014 and 2015. Surgeon reporting of data was mandated during this period. Institution and individual surgeon volume–outcome relationships were assessed.

Results

In total, 3671/13 947 (26.3%) patients underwent RP for high‐risk prostate cancer over the 2‐year period. Robot‐assisted RP was the most prevalent approach (60.7%). In all, 39% of men received an extended pelvic lymph node dissection (LND), but over one‐third (33.8%) had no LND. Minimally invasive techniques were associated with a significantly shorter length of stay. The reported rates of Clavien–Dindo ≥III complications within the dataset were low (2.0%), regardless of surgical modality or surgeon volume. No statistically significant surgeon volume–outcome relationships were identified when surgeon volume was stratified into tertiles.

Conclusion

RP for high‐risk prostate cancer in the UK appears safe, regardless of modality used or surgeon volume. No clear evidence that surgeon volume impacts on early perioperative outcomes was seen. Quality assurance of the surgeon‐reported BAUS dataset is now required to drive quality improvement in national practice.
A within‐subject clinical trial on the conversion of mandibular two‐implant to three‐implant overdenture: Patient‐centered outcomes and willingness to pay
Authors: Emami Elham , Alesawy Aminah , de Grandmont Pierre , Cerutti‐Kopplin Daiane , Kodama Naoki , Menassa Mélanie , Rompré Pierre , Durand Robert
Published: January 2019

Objectives

To examine the impact of adding a third midline implant with stud attachment to a mandibular two‐implant overdenture on patient‐oriented outcomes.

Methods

In this pre–post design clinical trial, following the standard procedures, mandibular two‐implant overdentures of 17 edentulous individuals (61.9 ± 6.6 years) were converted to three‐implant overdentures by adding a stud attachment to an unloaded midline implant. Patient‐oriented outcomes included patient expectations and satisfaction with implant overdenture as well as willingness to pay the cost of conversion. Data were collected at baseline and at the 6‐week follow‐up using visual analog and binary scales as well as open‐ended questions. Statistical analysis included descriptive statistics, Spearman's correlation, Fisher exact test, Mann–Whitney U test, and the exact sign test.

Results

After connecting the third midline implant to the mandibular two‐implant overdenture, there was a statistically significant decrease in the anteroposterior movement (p = 0.005) as evaluated by clinicians. Moreover, study participants reported an increase in perceived stability of the overdenture (95% CI; 0.68–1.00, p = 0.002) and in their ability to speak (95% CI; 0.63–1.00, p = 0.008). The addition of a third implant met the expectations of 94% of patients in regard to lower denture stability, 100% for retention, and 82.4% for comfort. The mandibular three‐implant overdenture increased patient general satisfaction over a short period of time, but this improvement was not statistically significant. About 80% of patients would recommend this type of prosthesis to their peers but only 47% of them would agree to pay a large increase in the cost of treatment compared to a two‐implant overdenture.

Conclusions

The addition of a midline third implant to an existing mandibular two‐implant overdenture resulted in several improved patient‐reported outcomes.
Association study of cell cycle proteins and human papillomavirus in laryngeal cancer in Chinese population
Authors: Cui Lifang , Qu Congling , Liu Honggang
Published: January 2019

Objective

To investigate the role of human papillomavirus (HPV) in laryngeal squamous cell carcinoma (LSCC) and analyse the relationship between HPV and the expression of cell cycle‐related proteins.

Design

The study consisted of LSCC between 2005 and 2011 in Tongren Hospital. Clinical data such as age, sex, smoking/alcohol consumption, and TNM stage were collected. HPV DNA and cell cycle‐related proteins were assessed in terms of clinical features.

Setting

Single‐centre study.

Participants

A total of 332 LSCC patients were included in the study.

Main outcome measures

The presence of genotype‐specific HPV DNA was evaluated using PCR‐RDB in formalin‐fixed paraffin‐embedded tissues. All samples were also evaluated for p16INK4A, p21WAF1/CIP1, P53, Cyclin D1, and Ki67 immunohistochemical staining by tissue microarray.

Results

HPV DNA was detected in 45 of 332 (13.55%) patients with LSCC, with HPV‐16 being the predominant genotype. The presence of HPV‐16 DNA was significantly associated with basaloid squamous cell carcinoma and cystic lymph node metastasis (P < 0.05). Of the 332 patients, 36 (10.84%) were scored as p16INK4A positivity and they were more likely to be female (P < 0.05). Cyclin D1‐positivity and p21WAF1/CIP1‐positivity were observed in 60.24% (200/332) and 40.66% (135/332), respectively. In 114 cases (34.33%), LSCCs had moderate‐ to ‐strong p53 accumulation, which was correlated with TNM stage (P < 0.05). HPV‐16 DNA was correlated with p16INK4A and manifested a higher Ki‐67 labelling index and p21WAF1/CIP1 expression than HPV‐16‐negative tumours (P < 0.05). No relationship was observed between Cyclin D1or P53 expression and HPV‐16 infection (P > 0.05).

Conclusion

HPV DNA was detected in 13.55% patients with LSCC, with HPV‐16 being the predominant genotype and it was correlated with p16INK4A and manifested a higher Ki‐67 labelling index and p21WAF1/CIP1 expression than HPV‐16‐negative tumours.
Characteristics of Single Pivotal Trials Supporting Regulatory Approvals of Novel Non‐orphan, Non‐oncology Drugs in the European Union and United States from 2012−2016
Authors: Morant Anne Vinther , Jagalski Vivien , Vestergaard Henrik Tang
Published: January 2019

For regulatory approval of a new medicine, the gold standard for demonstration of efficacy has traditionally been a minimum of two positive, adequate, and well‐controlled clinical trials. Nevertheless, drugs to treat cancer and rare diseases are usually approved based on a single and often uncontrolled pivotal trial. In contrast, little is known about single pivotal trial approvals for non‐orphan, non‐oncology drugs. Between 2012 and 2016, 23 novel therapeutic drugs were approved by the US Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA) for 27 non‐orphan, non‐oncology indications each based on a single pivotal trial. Although there was considerable variation in the nature and strength of the efficacy evidence supporting these drug approvals, the majority (85%) of the pivotal trials were randomized and controlled. For all superiority trials, the primary outcome was met with a statistical significance of P ≤ 0.005. Most approvals were supported by additional efficacy data from nonpivotal studies.
Estimating Promotion Effects Using Big Data: A Partially Profiled LASSO Model with Endogeneity Correction*
Authors: Sun Luping , Zheng Xiaona , Jin Ying , Jiang Minghua , Wang Hansheng
Published: January 2019

Retailers are interested in understanding which price promotions are profitable and which are not. However, simultaneously estimating the promotion effects of a large number of products on retailer sales and profits is technically challenging for both researchers and practitioners. To address this challenge, this study proposes a Partially Profiled Least Absolute Shrinkage and Selection Operator (Partially Profiled LASSO) model, which can estimate ultra‐high‐dimensional regression relationships at a low computational cost and control for the endogeneity of promotion depth. The model can flexibly incorporate the time‐varying promotion effects and the cross‐over effects among the promotions of different products. We conduct an empirical study using data provided by a large retailer over a 5‐month period. Our model efficiently identifies products with promotion effects and the promotion effects are significantly associated with certain promotion, product, and category characteristics. The results also show that our model with cross‐over effects outperforms the benchmark models that are widely used to handle the high‐dimensional predictor matrix (e.g., the standard LASSO and principal component regression methods). This article contributes to the related literature on price promotion and marketing analytics in data‐rich environments, and provides implications for retailers to make more informed promotion strategies.
Niches within a niche: ecological differentiation of subterranean amphipods across Europe's interstitial waters
Authors: Fišer Cene , Delić Teo , Luštrik Roman , Zagmajster Maja , Altermatt Florian
Published: January 2019

Species that successfully colonized subterranean environments are subject to two opposing selection processes. Stringent abiotic factors select for convergent adaptations, such as loss of eyes and pigments, while interspecific competition drives between‐species divergence. Subterranean species can resolve opposing selection by adaptation to physically different microhabitats. Yet, species frequently co‐occur in physically homogeneous subterranean habitats, like interstitial. These co‐occurrences in such a narrow ecological context can be explained either by equalizing mechanisms, in which neither of the co‐occurring species has a competitive advantage, or by more complex niche models that include species’ differentiation along a trophic niche axis. We tested these hypotheses using the amphipod genus Niphargus. We analysed Europe‐wide co‐occurrence records of Niphargus species from interstitial habitats, split into six independent large‐scale regions. Firstly, we addressed whether species’ pairwise co‐occurrences are random using a probabilistic model. Secondly, we tested whether species cluster into distinct functional–morphological groups and whether ecologically or phylogenetically distinct species are more likely to co‐occur. We found that 68% of species co‐occurrences were not different from random expectation, indicating that most species had access to most sites within each region. The remaining 32% co‐occurred either significantly more or less often than expected by chance. Cluster analysis of functional morphological characters showed that interstitial species belong to two feeding types, micro‐ and macrofeeders, likely representing two peaks of the interstitial adaptive landscape, and hinting that niche divergence, as a mechanism allowing coexistence, is favoured. Finally, we found that the number of co‐occurrences increases with increasing differentiation of functional morphology, but not phylogenetic differences. We conclude that ecological differentiation may be important in shaping such interstitial communities.
Evaluation of dental students’ knowledge and patient care towards HIV/AIDS individuals
Authors: Lorosa Adair H. , Pereira Claudia M. , Hussne Renata P. , Silva‐Boghossian Carina M.
Published: January 2019

Purpose

The aim was to evaluate the knowledge of the students of dental students regarding patients care towards HIV positive individuals.

Methods

Two hundred and eighty‐three dental students (pre‐clinical, n = 45; clinical, n = 238) answered an electronic questionnaire, approaching biosafety procedures, oral manifestations of AIDS and knowledge of HIV infection. Data were present as an average from findings from students of nine different semesters, grouping them by pre‐clinical (1‐4) and clinical (5‐9) semesters, from two different university campuses. Furthermore, data were analysed using the t test and chi‐square test.

Results

Students’ mean age was 24 years. Amongst 14 oral manifestations questioned, Kaposi sarcoma, oral candidiasis, necrotizing ulcerative gingivitis and herpes simplex were more associated with HIV. Over 90% of the respondents would be concerned about becoming infected with HIV after a needle stick injury and were willing to be tested for HIV; know that HIV/AIDS patients can contaminate dental care professionals, that needle perforation can transmit HIV, and that medical professionals are more prone to cross‐contamination. Regarding the use of physical barrier, almost all participants use disposable mask, goggles, cap and procedure gloves with all patients; the use of disposable lab coat and two pairs of gloves were the least used with all patients.

Conclusions

Participating students have good knowledge on biosafety in the management of HIV/AIDS patients, as well as on the most commonly associated oral manifestations. However, there is a need for improvement on some topics related to HIV/AIDS, especially regarding less known oral lesions, and HIV diagnostic tests.
Increased intrinsic connectivity for structural atrophy and functional maintenance after acute ischaemic stroke
Authors: Yang Y. , Chen Y. , Chen K. , Wei D. , Li P. , Zeng W. , Pei J. , Mao H. , Jia J. , Zhang Z.
Published: January 2019

Background and purpose

Significant clinical recovery has commonly been observed in ischaemic stroke patients with irreversible brain structural damage. However, brain mechanisms that help to maintain clinical function remain unclear.

Methods

Sixty‐two patients with acute ischaemic stroke underwent longitudinal clinical assessments and magnetic resonance scanning. The clinical recovery trajectory was evaluated using a hierarchical linear model and intrinsic connectivity was analysed with a seed‐based approach to examine its changing pattern based on the regional volume changes calculated using voxel‐wise analysis.

Results

It was observed that clinical outcome measures improved mainly in the short‐term period (baseline versus 3 weeks) and then remained stable. Grey matter volume was reduced significantly in the bilateral caudate over the entire 3‐year long‐term period. Significant intrinsic connectivity increases were observed in the caudate–middle cingulum over the short‐term period and in the caudate–precuneus and caudate–calcarine over the long‐term period. Finally, it was found that increased caudate–calcarine connectivity was associated with reduced right caudate volume, and a positive correlation was found between increased caudate–middle cingulum connectivity and the amount of modified Rankin score changes.

Conclusions

The increased intrinsic connectivity found in this study tends to be a compensatory mechanism for post‐stroke structural damage, associated with clinical recovery. The study helps in understanding the significance of enhanced intrinsic connectivity in post‐stroke long‐term assessment and rehabilitation.
Self‐organizing hair peg‐like structures from dissociated skin progenitor cells: New insights for human hair follicle organoid engineering and Turing patterning in an asymmetric morphogenetic field
Authors: Weber Erin L. , Woolley Thomas E. , Yeh Chao‐Yuan , Ou Kuang‐Ling , Maini Philip K. , Chuong Cheng‐Ming
Published: January 2019

Human skin progenitor cells will form new hair follicles, although at a low efficiency, when injected into nude mouse skin. To better study and improve upon this regenerative process, we developed an in vitro system to analyse the morphogenetic cell behaviour in detail and modulate physical‐chemical parameters to more effectively generate hair primordia. In this three‐dimensional culture, dissociated human neonatal foreskin keratinocytes self‐assembled into a planar epidermal layer while fetal scalp dermal cells coalesced into stripes, then large clusters, and finally small clusters resembling dermal condensations. At sites of dermal clustering, subjacent epidermal cells protruded to form hair peg‐like structures, molecularly resembling hair pegs within the sequence of follicular development. The hair peg‐like structures emerged in a coordinated, formative wave, moving from periphery to centre, suggesting that the droplet culture constitutes a microcosm with an asymmetric morphogenetic field. In vivo, hair follicle populations also form in a progressive wave, implying the summation of local periodic patterning events with an asymmetric global influence. To further understand this global patterning process, we developed a mathematical simulation using Turing activator‐inhibitor principles in an asymmetric morphogenetic field. Together, our culture system provides a suitable platform to (a) analyse the self‐assembly behaviour of hair progenitor cells into periodically arranged hair primordia and (b) identify parameters that impact the formation of hair primordia in an asymmetric morphogenetic field. This understanding will enhance our future ability to successfully engineer human hair follicle organoids.
Access and barriers to oral health care for dependent elderly people living in rest homes
Authors: Gopalakrishnan Anoop , Kahu Ella , Jones Linda , Brunton Paul
Published: January 2019

Aim

To report New Zealand rest home (rest home is the New Zealand term for residential aged care facilities where dependent, institutionalised, elderly people reside.) managers’ opinions on access and barriers to oral health care for rest home residents.

Methods

An exploratory study using qualitative descriptive methods. Eleven rest home managers in a region of New Zealand were interviewed about admission assessments for new residents, oral health care, availability of dental facilities, staff training in oral hygiene, residents’ nutritional needs and oral hygiene aids.

Results

Interviews with managers indicated that rest homes have no policies for the provision of oral health care and only arrange dental check‐ups or treatment when requested by residents or family. Barriers to accessing care include making appointments, availability of staff and transport particularly for bedridden patients. Staff receive basic oral hygiene training only and face resistance to oral hygiene from some residents. No homes had a dental chair at their premises. All rest homes stocked oral hygiene aids such as toothbrushes and toothpastes. Electric toothbrushes were not generally promoted with cost being a key factor.

Conclusion

While rest home managers were aware of the importance of good oral health, there are barriers to care. Finance is a challenge as dental care is not publicly funded and many residents rely on a limited income. Recommendations include policy changes to better fund oral health, specific oral health training for rest home staff, provision of mobile dental services to rest homes and the inclusion of gerodontology in the dental school curriculum.
Spirits of Yokokurayama: shrine of the Japanese trilobites
Authors: Stocker Christopher , Williams Mark , Oji Tatsuo , Tanaka Gengo , Komatsu Toshifumi , Wallis Simon
Published: January 2019

‘We are such stuff as dreams are made on, and our little life is rounded with a sleep’. So sleep the trilobites of Yokokurayama, a sacred mountain hidden within the beautiful landscape of Japan’s Shikoku’s island. And though Prospero may have been speaking to his daughter and her fiancé (in William Shakespeare’s The Tempest), he might well have been contemplating the magnificent trilobite fossils of Yokokurayama. Japan may be better known for its sweeping volcanic landscapes, majestic castles, Shinto shrines and bullet trains, but it is also home to important collections of Silurian and Devonian trilobites.
Ichnoentomology: insect traces in soils, palaeosols and other substrates
Authors: Genise Jorge F.
Published: January 2019

Ichnology is the science that studies traces, mostly trace fossils, which are defined as morphologically recurrent structures (nests, burrows, trackways) resulting from the life activity of an individual organism modifying the substrate. Leonardo da Vinci was probably the first ichnologist. He mentioned the existence of traces of worms in rocks. Trace fossils reflect how extinct animals behaved. They are as parts of a time machine that allow us to almost see how extinct animals made their nests, fed, reproduced and walked. Moreover, they allow us to reconstruct palaeoenvironments and the evolutionary history of many taxa. Ichnology was originally developed by geologists; traces first caught our attention in rocks (palaeoichnology) and then in extant environments (neoichnology). For many years ichnology was only studied in marine or lacustrine environments, whereas terrestrial ichnology has been developed over the last few decades. Insect traces are the most common in terrestrial environments, such as palaeosols, but they are also common in plant remains, bones, and in some subaquatic substrates. Ichnoentomology deals with insect traces in soils, palaeosols and other substrates.
Death of chondrocytes in Kashin‐Beck disease: Apoptosis, necrosis or necroptosis?
Authors: Zhang Ying , He Ying , Zhang Dan , Zhang Meng , Wang Mengying , Zhang Ying , Ma Tianyou , Chen Jinghong
Published: January 2019

The purpose of this paper was to investigate chondrocyte distribution and death in the cartilage in Kashin‐Beck disease (KBD). Apoptotic chondrocytes were detected by TUNEL assay. Ultrastructural changes were examined by transmission electron microscope (TEM). Biochemical markers associated with apoptosis (eg, caspase‐3) and necroptosis (eg, RIP3) were investigated by immunohistochemistry. In KBD cartilage chondrocyte death was characterized by paler staining of the cells. Multiple chondral cell clusters surrounded the areas lacking cells in the deep zone. The per cent of TUNEL‐positive and RIP3‐positive chondrocytes were higher in the middle zones of KBD samples; however, there was some positive staining for TUNEL but negative staining for caspase‐3. Immunohistochemistry failed to detect significant differences in caspase‐3 levels in KBD children compared to controls, suggesting that beside apoptosis necroptosis dominates as a cell death mechanism in the middle zone of cartilage from KBD children. To clarify further the presence of chondrocyte necroptosis in KBD, we performed TUNEL, caspase‐3 and RIP3 staining in a rat KBD model which is based upon T‐2 toxin treatment under selenium‐deficient conditions. Apoptosis and necroptosis co‐existed in the middle zone in this rat KBD model. Ultrastructural analysis of chondrocyte from deep cartilage revealed abnormal cells with numerous morphological changes, such as plasma membrane breakdown, generalized swelling of the cytoplasm and loss of identifiable organelles. Chondrocyte death by necrosis in the deep zone of cartilages in KBD may be a result of exposure to T‐2 toxin from bone marrow or bloodstream under selenium‐deficient nutrition status in KBD endemic areas. Chondrocyte death plays a key role in either the initiation or the progression of KBD pathogenesis.
Recent trends for the employment of jumbo squid (Dosidicus gigas) by‐products as a source of bioactive compounds with nutritional, functional and preservative applications: a review
Authors: Ezquerra‐Brauer Josafat Marina , Aubourg Santiago P.
Published: January 2019

Only 50%–60% of total seafood catch is used for human consumption, seafood processing being considered as one of the main sources of by‐products. Among marine species, jumbo squid (JS; Dosidicus gigas) represents the most important squid fishery, showing an increasing economic interest in many countries. As for any other marine species, the regular cleaning, dressing and processing produce high quantities of by‐products (skin, head, fins, viscera, tentacles, unclaimed mantle, etc.) that are rich in many nutrients (proteins, lipids, minerals, vitamins, enzymes, biopolymers, etc.). This review compiles information about extraction and employment of JS by‐products with the aim of enhancing their economic value and reduce environmental drawbacks. A special emphasis is given to the relevance in developing methods susceptible to transform by‐products into useful and profitable products susceptible to be applied in several industries such as food, medicine, agrochemical or pharmaceutical. Future possible trends for widening this profitable use are mentioned.
Effects of germination on tocopherol, secoisolarlciresinol diglucoside, cyanogenic glycosides and antioxidant activities in flaxseed (Linum usitatissimum L.)
Authors: Li Xiang , Li Jingyan , Dong Shan , Li Yufei , Wei Liping , Zhao Caicai , Li Junyi , Liu Xuebo , Wang Yutang
Published: January 2019

The changes in chemical composition and antioxidant activities of brown and golden flaxseeds (Linum usitatissimum L.) during 5‐day germination were investigated. Flaxseeds germinated in a dark and closed incubator at the temperature of 25 °C. With noticeable reduction in fat content, germinated flaxseeds were determined higher percentage of linolenic acid. The total phenolic content and antioxidant activities increased with germination time. The highest amount of secoisolarlciresinol diglucoside (SDG) was found in 2‐day germinated brown and golden flaxseeds, which increased 1.04‐fold and 1.09‐fold, respectively, and germinated flaxseed oil was found rich in SDG. Intriguingly, germination increased the α‐tocopherol content from 0 to 4.58 mg per 100 g and 0 to 7.83 mg per 100 g in brown and golden flaxseeds while γ‐tocopherol decreased. Germination process also reduced the total content of cyanogenic glucosides, the content of linustatin, neolinustatin and lotaustralin decreased significantly, but caused an increase in the content of linamarin. Therefore, germination can be utilised as an effective method to improve the nutritional value of flaxseed.
An innovative nurse‐led cystoscopy clinic in Denmark
Authors: Quallich Susanne , Frey Anders , Østergren Peter Busch , Madsen Søren Sorensen
Published: January 2019

The need for serial surveillance cystoscopy after a diagnosis of bladder cancer and long wait times led to the development of a nurse‐led cystoscopy in The University Hospital of Southwestern Denmark, in Esbjerg, Denmark. This paper discusses the background, development and success of these training programme in Esbjerg, Denmark. Four nurses have participated in a structured in‐house training programme that started in 2014. In the last 4 years these four nurses have successfully performed 1024 cystoscopies. To date, there have not been any poor outcomes, in terms of missed diagnosis or procedure complications. This programme has offered a way to improve satisfaction of the residents and staff urologists while successfully and safely meeting the needs of the community.
Modulating antibody‐dependent cellular cytotoxicity of epidermal growth factor receptor‐specific heavy‐chain antibodies through hinge engineering
Authors: D'Eall Calvin , Pon Robert A , Rossotti Martin A , Krahn Natalie , Spearman Maureen , Callaghan Deborah , van Faassen Henk , Hussack Greg , Stetefeld Jörg , Butler Michael , Durocher Yves , Zhang Jianbing , Henry Kevin A , Tanha Jamshid
Published: January 2019

Human IgG1 and IgG3 antibodies (Abs) can mediate Ab‐dependent cellular cytotoxicity (ADCC), and engineering of the Ab Fc (point mutation; defucosylation) has been shown to affect ADCC by modulating affinity for FcRγIIIa. In the absence of a CH1 domain, many camelid heavy‐chain Abs (HCAbs) naturally bear very long and flexible hinge regions connecting their VHH and CH2 domains. To better understand the influence of hinge length and structure on HCAb ADCC, we produced a series of hinge‐engineered epidermal growth factor receptor (EGFR)‐specific chimeric camelid VHH‐human Fc Abs and characterized their affinities for recombinant EGFR and FcRγIIIa, their binding to EGFR‐positive tumor cells, and their ability to elicit ADCC. In the case of one chimeric HCAb (EG2‐hFc), we found that variants bearing longer hinges (IgG3 or camelid hinge regions) showed dramatically improved ADCC in comparison with a variant bearing the human IgG1 hinge, in similar fashion to a variant with reduced CH2 fucosylation. Conversely, an EG2‐hFc variant bearing a truncated human IgG1 upper hinge region failed to elicit ADCC. However, there was no consistent association between hinge length and ADCC for four similarly engineered chimeric HCAbs directed against distinct EGFR epitopes. These findings demonstrate that the ADCC of some HCAbs can be modulated simply by varying the length of the Ab hinge. Although this effect appears to be heavily epitope‐dependent, this strategy may be useful to consider during the design of VHH‐based therapeutic Abs for cancer.
Recognising and managing dying patients in the acute hospital setting: can we do better?
Authors: Gunasekaran Bharathy , Scott Caroline , Ducharlet Kathryn , Marco David , Mitchell Imogen , Weil Jennifer
Published: January 2019

Healthcare professionals have limited formal end‐of‐life care training despite the large proportion of hospital deaths. A retrospective review of 201 acute hospital deaths revealed 166 (82.6%) had documentation to suggest the patient was dying but this was performed late with a median time between documentation and death of 0.84 days. Furthermore, 132 (66%) patients received an intervention in the final 48 h of life. This highlights the need to improve the recognition and management of dying patients in acute hospitals.
Management of frail older people with acute illness
Authors: Mudge Alison M. , Hubbard Ruth E.
Published: January 2019

Frailty status is intrinsically related to every aspect of older patients’ hospital journeys: the way in which they present to hospital, their health status at admission, vulnerability to complications in hospital and rate of recovery after an acute insult. In younger people, hospitalisation is usually the result of a serious illness or injury, such as sepsis or major trauma. Management can be underpinned by evidence‐based algorithms relating to the precipitating insult and recovery usually follows a predictable trajectory. In older people who are frail, on the other hand, admission to hospital may be triggered by an illness that may seem minor, such as a viral infection, which causes a geriatric syndrome. A fall or delirium with no major precipitant should be considered an indicator of frailty. Promptly recognising the acute illness and the increased risk for hospital‐associated complications is essential for providing safe systems of care for frail older people. Early consideration of health assets and engagement of families and community services can have an important role in successful recovery during and beyond the hospital stay. Effective decision‐making about clinical interventions can benefit from explicit assessment of frailty status and consideration of patient priorities.
The impact of international migration on the public pension system: The case of Portugal
Authors: Alves José , Craveiro Daniela , Garcia Maria Teresa Medeiros , Albuquerque Paula
Published: January 2019

This article analyses the impact of replacement migration on the financial sustainability of the old‐age pension system in Portugal, a country with one of the largest ageing populations in Europe. We do this using demographic forecasts and prospective exercises for the evolution of the Portuguese economy. During the 2015–2060 period, our results evidence the positive impacts of international migration on old‐age pension system financial balances, reaching over 3 per cent of GDP after 2045. Moreover, even when taking into considering the low dynamics for the Portuguese economy, replacement migration is an important input to improve pension system financial sustainability.
Synthesis of highly pure and dense 0.9(KNbO3)‐0.1(BaNi1/2Nb1/2O3‐δ) ceramic with superior magnetic properties
Authors: Tiwari Rajender Prasad , Hashmi Syed Zimad Husain , Sharma Raghav , Khan Saif Ahmad , Birajdar Balaji
Published: January 2019

Residual NiO phase is generally detected in 0.9(KNbO3)–0.1(BaNi1/2Nb1/2O3‐δ) (KBNNO) synthesized using NiO as a nickel precursor by solid‐state reaction. In this work, NiO phase is found to exist in the form of the residual NiO particles with a size of 100‐200 nm using energy dispersive X‐ray elemental mapping. These NiO residual particles are eliminated by using nickel acetate as a nickel precursor and a 100% perovskite phase KBNNO is successfully synthesized at as low as 600°C temperature. Furthermore, using the two‐step sintering technique, 100% relative density is achieved in this material. The nickel acetate–based KBNNO shows a robust ferromagnetism with the saturation magnetization of 11.42 memu/g and the remanent magnetization of 3.89 memu/g which is 38 times higher than that of previously reported value in NiO‐based KBNNO. Thus, a highly pure and fully dense KBNNO ceramic with superior magnetic properties is obtained using nickel acetate and by the two‐step sintering method. This is a key step forward in the processing of KBNNO and is likely to have a significant impact on other physical properties of this newly invented and promising photovoltaic perovskite material.
Training young adults with intellectual disability to read critically on the internet
Authors: Delgado Pablo , Ávila Vicenta , Fajardo Inmaculada , Salmerón Ladislao
Published: January 2019

Background

Young people with intellectual disability (ID) are becoming frequent Internet users, but they present difficulties selecting reliable Internet sources.

Methods

The present authors tested an instructional programme aimed at increasing skills to evaluate information from the Internet of 33 young adult students with intellectual disability enrolled in special needs education (19.4 years). The programme was composed of different web pages that provided conflicting views on a controversial topic. Students participated in small group discussions supported with Wh‐question graphic organizers and contrasting cases during seven sessions.

Results

Differences between pre‐ and post‐tests indicated that the programme is effective in increasing students’ ability to select trustworthy web pages, and to use source characteristics to justify such selection by means of supervised instruction.

Conclusion

Promoting Internet use in a safe way might increase the opportunities of young people with intellectual disability to make choices and self‐determined decisions about their life (Handbook of research‐based practices for educating students with intellectual disability, 2016, New York, NY: Taylor & Francis).
Phenotypic plasticity in breeding plumage signals in both sexes of a migratory bird: responses to breeding conditions
Authors: Moreno Juan , Cantarero Alejandro , Plaza Mireia , López‐Arrabé Jimena
Published: January 2019

Adaptive phenotypic plasticity may respond to present ambient conditions. Sexual and social signals in both sexes may express phenotype performance. Plumage signals that change discontinuously allow relating discrete variation to previous performance. Both sexes of the pied flycatcher Ficedula hypoleuca present white patches on the wings and on the forehead, which constitute sexual and social signals. Forehead patches are moulted together with body plumage in Africa, while wing patches are partly moulted in Africa and partly in the breeding area soon after breeding. We studied individual inter‐year changes (corrected for regression to the mean) in the size of forehead and wing patches of both sexes in seven years for females or six years for males in two nearby study areas in central Spain. We found that initial signal extent strongly delimits the possible subsequent changes negatively. There is a negative association of male age with forehead patch changes. Cold and rainy springs are associated in females with decreases in both patch areas and vice versa, while no association with climate is observed in male wing patch changes. Cold pre‐breeding conditions predict positive changes in female wing and male forehead patches. Breeding success is positively associated with forehead patch changes in females. Late‐breeding males experience more positive changes in forehead patch size than early‐breeding males. Some of these trends can be explained by variable costs of breeding in certain conditions for subsequent signal production and/or maintenance, while absence of trends in some cases may be explained by sex differences in costs of breeding and interactions with phenotypic quality of breeders.
Electrophysiological characteristics of the earliest activation site in idiopathic right ventricular outflow tract arrhythmias under mini‐electrode mapping
Authors: Liu Menghui , Jiang Jingzhou , Su Chen , Li Jie , Chen Xumiao , Ma Yuedong , Feng Chong , Liu Jun , Dong Yugang , Tang Anli , He Jiangui , Wang Lichun
Published: January 2019

Introduction

Right ventricular outflow tract ventricular arrhythmias (RVOT VAs) often originate in the voltage‐transitional zone. The target electrogram could be compromised by the architecture of the roving catheter. Mini‐electrodes could improve the mapping resolution, especially in low‐voltage areas. The aim was to assess the electrophysiological characteristics of the earliest activation site (EAS) of RVOT VAs during mapping using mini‐electrodes.

Methods and Results

Twenty‐seven patients with RVOT‐type VAs were mapped using Orion mini‐electrodes and the Rhythmia mapping system. Bipolar and unipolar electrograms were analyzed and compared with conventional ablation catheter recordings. Twenty‐five patients (25 of 27) were successfully mapped and ablated at the RVOT. At the EAS, all 25 (100%) patients exhibited local sharp potentials (spiky potential) at the VAs, and 88% (22 of 25) individuals showed reverse late potentials in adjacent sinus beats on the bipolar mini‐electrode recordings. Related unipolar electrograms manifested 20% “q‐plateau‐QS,” 76% “gross QS,” and 4% “late QS” patterns related to spiky potential voltages and advanced times. Compared with electrograms recorded by ablation catheter, bipolar mini‐electrode recordings exhibited significantly shorter spiky potential durations (P = 0.001) and a significantly increased incidence of the reverse late potentials (P = 0.041). Unipolar mini‐electrode recordings had a lower incidence ratio of “late QS” patterns (P = 0.039).

Conclusion

Compared with ablation catheter mapping, mini‐electrodes improved the mapping resolution of the EAS of RVOT VAs and exhibited shorter spiky potential durations and reduced incidence of “later QS” unipolar patterns.
Deficiency of TPPP2, a factor linked to oligoasthenozoospermia, causes subfertility in male mice
Authors: Zhu Feng , Yan Peipei , Zhang Jingjing , Cui Yiqiang , Zheng Meimei , Cheng Yiwei , Guo Yueshuai , Yang Xiaoyu , Guo Xuejiang , Zhu Hui
Published: January 2019

Oligoasthenozoospermia is a major cause of male infertility; however, its etiology and pathogenesis are unclear and may be associated with specific gene abnormalities. This study focused on Tppp2 (tubulin polymerization promoting protein family member 2), whose encoded protein localizes in elongating spermatids at stages IV‐VIII of the seminiferous epithelial cycle in testis and in mature sperm in the epididymis. In human and mouse sperm, in vitro inhibition of TPPP2 caused significantly decreased motility and ATP content. Studies on Tppp2 knockout (KO) mice demonstrated that deletion of TPPP2 resulted in male subfertility with a significantly decreased sperm count and motility. In Tppp2−/− mice, increased irregular mitochondria lacking lamellar cristae, abnormal expression of electron transfer chain molecules, lower ATP levels, decreased mitochondrial membrane potential and increased apoptotic index were observed in sperm, which could be the potential causes for its oligoasthenozoospermia phenotype. Moreover, we identified a potential TPPP2‐interactive protein, eEf1b (eukaryotic translation elongation factor 1 beta), which plays an important role in protein translation extension. Thus, TPPP2 is probably a potential pathogenic factor in oligoasthenozoospermia. Deficiency of TPPP2 might affect the translation of specific proteins, altering the structure and function of sperm mitochondria, and resulting in decreased sperm count, motility and fertility.
Endoplasmic reticulum aminopeptidase 1 polymorphism Ile276Met is associated with atopic dermatitis and affects the generation of an HLA‐C associated antigenic epitope in vitro
Authors: Niepiekło‐Miniewska W. , Mpakali A. , Stratikos E. , Matusiak Ł. , Narbutt J. , Lesiak A. , Kuna P. , Wilczyńska K. , Nowak I. , Wiśniewski A. , Zwolińska K. , Ponińska J. , Płoski R. , Szepietowski J.C. , Kuśnierczyk P.
Published: January 2019

Background

Atopic dermatitis (AD) is a common inflammatory skin disease of complex aetiology, with interactions between susceptibility genes and environmental factors. We have previously described a protective effect of the KIR2DS1 gene encoding the natural killer cell receptor, whose ligands are HLA‐C molecules. Here, we found an association of HLA‐C*05:01 allele with AD. KIR‐HLA‐C interactions are affected by peptides presented by HLA‐C. The generation of these peptides is strongly influenced by endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2). Expression and activity of ERAP molecules depend on the polymorphisms of their genes.

Objective

Possible associations of several single nucleotide polymorphisms (SNPs) in the ERAP1 and ERAP2 genes with susceptibility to AD.

Methods

Peripheral blood DNA isolation from 318 patients and 549 controls. PCR‐SSO or PCR‐SSP for HLA‐C typing; TaqMan Genotyping Assay for ERAP typing.

Results

Only one SNP in the ERAP1 gene, rs26618T>C, causing the amino acid change Ile276Met, had an association with AD. To gain insight on the functional role of this SNP, we produced recombinant variants differing only at position 276 (Ile or Met) and tested their aminopeptidase activity against a N‐terminally extended precursor LIVDRPVTLV of the HLA‐C*05:01 epitope IVDRPVTLV. Both ERAP1 variants were able to efficiently generate the epitope, although the 276Ile allotype was able to do this about 50% faster. Furthermore, both variants were quite inefficient in further degradation of the mature epitope. Finally, we found that the effect of 276Met on susceptibility to AD was seen only in KIR2DS1‐negative individuals, not protected by this KIR.

Conclusion

Associations of HLA‐C*05:01 allele and rs26618T>C (Ile276Met) ERAP1 polymorphism with AD, and a significant difference between these two ERAP1 variants in their ability to generate an epitope for the HLA‐C*05:01 molecule was found.
Understanding FEV1 for the purpose of cystic fibrosis registry comparisons: Does bias in annual review FEV1 affect between‐centre comparison within the UK? An analysis of registry data
Authors: Hoo Zhe Hui , Campbell Michael J. , Walters Stephen J. , Wildman Martin J.
Published: January 2019

Rationale, aims, and objective

We previously demonstrated that annual review %FEV1 underestimates lung health of adults with CF compared with %FEV1 captured during periods of clinical stability. This has implications in the comparisons against registries with encounter‐based FEV1, such as the United States. It is uncertain whether this bias affects between‐centre comparison within the United Kingdom. Previous funnel plot analyses have identified variation in annual review %FEV1 according to centre size; hence, we investigated whether paired differences between annual review and best %FEV1 also vary according to centre size.

Methods

This registry analysis included 18 adult CF centres in the United Kingdom with ≥80% completeness for best FEV1 data in 2014. Mean discrepancy between annual review and best %FEV1 is a surrogate for the extent by which annual review %FEV1 underestimates lung health, and was plotted against centre size. A local polynomial regression (LOESS) curve was used to explore the relationship between the two variables. An appropriate model is fitted based on the LOESS curve to determine the strength of relationship between discrepancies in %FEV1 and centre size.

Results

There is an inverted U‐shaped relationship between mean discrepancies in %FEV1 and centre size. A regression of the paired mean difference in %FEV1 against centre size showed a significant improvement in the goodness of fit for a quadratic model (R2 = 23.8% for a quadratic model compared with 0.4% for a linear one; P = 0.048 for the quadratic term).

Conclusions

Annual review %FEV1 underestimated lung health of adults from small and large centres in the United Kingdom to a greater extent compared with medium‐sized centres. A plot of %FEV1 against centre size (eg, funnel plot comparison) would be affected by systematic bias in annual review %FEV1. Therefore, annual review %FEV1 is an unreliable metric to compare health outcomes of adult CF centres within the United Kingdom.
Subcutaneous thermal sensor microchip validation in vervet monkeys (Chlorocebus pygerythrus) during normothermic and hypothermic situations
Authors: Navarro‐Serra Ana , Sanz‐Cabañes Héctor
Published: January 2019

Background

Internal temperature data are essential for clinical evaluation in veterinary medicine. During the last decade, new thermometry devices have been developed. Identification microchips with a temperature sensor offer double utility to clinicians by satisfying animal identification regulations and providing a non‐invasive method for temperature measurement.

Methods

During this study, 26 healthy vervet monkeys (Chlorocebus pygerythrus) were implanted with a subcutaneous temperature transponding microchip. For each monkey, internal temperature measurements from the microchip and from an anaesthetic monitor (rectal sensor) were recorded every 5 minutes during an anaesthetic procedure.

Results

In this study, there were 83 paired samples obtained under normothermic conditions and another 72 paired samples obtained under hypothermic conditions, with interclass correlation coefficients of 0.79 and 0.69, respectively, between the two temperature measurement approaches.

Conclusion

Measurements obtained using the examined microchip thermal sensor exhibited good and excellent correlation with rectal temperature measurements under hypothermic and normothermic conditions, respectively.
How Collective Engagement Creates Competitive Advantage for Organizations: A Business‐Level Model of Shared Vision, Competitive Intensity, and Service Performance
Authors: Eldor Liat
Published: January 2019

We argue that collective engagement can serve as a unique value‐creation capacity at the business level by linking shared vision and service performance. We also propose that competitive intensity will be a market indicator by which management can enhance the effect of shared vision on collective engagement, and indirectly strengthen service performance (through collective engagement). Furthermore, we argue that this distinctive value‐creation capability, embedded in collective engagement, generates competitive advantage; specifically, one that competing organizations will struggle to replicate. We examine our moderated‐mediation model by using a three‐time‐point method derived from five different sources in 198 retail‐service branches. Our findings indicate that collective engagement, fueled by shared organizational vision, improves service performance. Furthermore, as this conditional indirect effect of shared vision on service quality and customer satisfaction was solely generated through collective engagement rather than other mechanisms (i.e., commitment and involvement), it creates a competitive advantage for engagement‐oriented organizations.