bluuebunny/crossref_metadata_2025 huggingface dataset:
International consensus statement on the peri‐operative management of anaemia and iron deficiency
Authors: Muñoz M. , Acheson A. G. , Auerbach M. , Besser M. , Habler O. , Kehlet H. , Liumbruno G. M. , Lasocki S. , Meybohm P. , Rao Baikady R. , Richards T. , Shander A. , So‐Osman C. , Spahn D. R. , Klein A. A.
Published: December 2016

Despite current recommendations on the management of pre‐operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best‐practice and evidence‐based statements to advise on patient care with respect to anaemia and iron deficiency in the peri‐operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow‐up. We urge anaesthetists and peri‐operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.
Histological and clinical evaluation of the hard palate mucous membrane graft for treatment of lower eyelid retraction
Authors: Larsen Sofie D.H. , Heegaard Steffen , Toft Peter B.
Published: December 2016

Purpose

To evaluate the histological appearances of the epithelial cells and the clinical effect of the hard palate mucous membrane (HPM) graft for the treatment of lower eyelid retraction (LER).

Methods

This was a follow‐up study involving 15 patients, with a total of 16 eyes operated. Five patients had LER as a result of Graves' ophthalmopathy and/or inferior rectus recession, six patients because of wearing an eye prosthesis, two patients because of previous tumour excision, one patient because of proptosis due to sphenoid wing meningioma and one patient because of previous lower eyelid blepharoplasty. Three imprint biopsies were taken from each patient, one from the tarsal conjunctiva in the healthy eye, one from the graft in the operated eye and one from unoperated hard palate. The inferior scleral show was measured on pre‐ and postoperative photographs and related to the horizontal corneal diameter.

Results

Median follow‐up time was 21.2 [range 4.5–87.9] months. Imprints from the graft and the hard palate showed equally large epithelial cells; imprints from conjunctiva showed small epithelial cells. The mean (±SD) scleral show was 0.12 ± 0.09 cornea diameter before surgery and 0.0003 ± 0.08 cornea diameter at invited follow‐up (p < 0.001, paired t‐test). Corrected for direction of gaze, the mean improvement in scleral show was 0.12 ± 0.08 cornea diameter. Thirteen of 14 patients were satisfied with the final result.

Conclusion

A HPM graft for LER maintains its native epithelial morphology and gives a lasting improvement in most patients.
Prediction of serum theophylline concentrations and cytochrome P450 1A2 activity by analyzing urinary metabolites in preterm infants
Authors: Sohn Jin A , Kim Han‐Suk , Oh Jaeseong , Cho Joo‐Youn , Yu Kyung‐Sang , Lee Juyoung , Shin Seung Han , Lee Jin A , Choi Chang Won , Kim Ee‐Kyung , Kim Beyong Il , Park Eun Ae
Published: December 2016

Aims

The purpose of this study was to explore clinical markers reflecting developmental changes in drug clearance by preterm infants.

Methods

Preterm infants administered aminophylline or theophylline to treat apnoea of prematurity were enrolled in this study. Trough and one of 2 h, 4 h or 6 h post‐dose blood samples and urine samples were collected during steady state, to determine the concentrations of theophylline and its targeted metabolites. CYP1A2*1C and CYP1A2*1F genotypes were analyzed. Total, renal and nonrenal clearances of theophylline were calculated, and cytochrome P450 1A2 (CYP1A2) activity was obtained from the ratio of 1‐methyluric acid and 3‐methylxanthine to theophylline in urine. Multiple linear regression analysis was performed to evaluate the relationships between theophylline clearance and the clinical characteristics of preterm infants.

Results

A total of 152 samples from 104 preterm infants were analyzed. A strong association between the serum trough and urine theophylline concentrations was found (P < 0.001). Total, renal and nonrenal clearances of theophylline were 0.50 ± 0.29 ml kg−1 min−1, 0.16 ± 0.06 ml kg−1 min−1 and 0.34 ± 0.28 ml kg−1 min−1, respectively. CYP1A2 activity correlated positively with the postnatal age and postmenstrual age. However, CYP1A2 genotype was not associated with CYP1A2 activity, which was significantly associated with nonrenal clearance. CYP1A2 activity, postnatal age , weight and 24‐h urine output were significantly associated with total theophylline clearance.

Conclusions

CYP1A2 activity can be monitored using noninvasive random urine samples, and it can be used to assess developmental changes in theophylline clearance by preterm infants.
Anticholinergic Exposure in a Cohort of Adults Aged 80 years and Over
Authors: Wauters Maarten , Klamer Therese , Elseviers Monique , Vaes Bert , Dalleur Olivia , Degryse Jan , Durán Carlos , Christiaens Thierry , Azermai Majda , Vander Stichele Robert
Published: December 2016

Anticholinergics are frequently prescribed for older adults and can lead to adverse drug events. The novel MARANTE (Muscarinic Acetylcholinergic Receptor ANTagonist Exposure) scale measures the anticholinergic exposure by incorporating potency and dosages of each medication into its calculations. The aims were to assess prevalence and intensity of the anticholinergic exposure in a longitudinal cohort study of community‐dwelling patients aged 80 years and over (n = 503) and to study the impact on mortality and hospitalization. Chronic medication use at baseline (November 2008–September 2009) was entered and codified with the Anatomical Therapeutic Chemical classification. Time‐to‐event analysis until first hospitalization or death was performed at 18 months after inclusion, using Kaplan–Meier curves. Cox regression was performed to control for covariates. Mean age was 84 years (range 80–102), and mean number of medications was 5 (range 0–16). Prevalence of anticholinergic use was 31.8%, with 9% taking ≥2 anticholinergics (range 0–4). Main indications for anticholinergics were depression, pain and gastric dysfunction. Female gender, the level of multi‐morbidity and the number of medications were associated with anticholinergic use. Mortality and hospitalization rate were 8.9% and 31.0%, respectively. After adjustment for the level of multi‐morbidity and medication intake, multi‐variable analysis showed increased risks of mortality (HR 2.3, 95% CI: 1.07–4.78) and hospitalization (HR 1.7; 95% CI: 1.13–2.59) in those with high anticholinergic exposure. The longitudinal study among Belgian community‐dwelling oldest old demonstrated great anticholinergic exposure, which was associated with increased risk of mortality and hospitalization after 18 months.
An investigation of mental imagery in bipolar disorder: Exploring “the mind's eye”
Authors: Di Simplicio Martina , Renner Fritz , Blackwell Simon E , Mitchell Heather , Stratford Hannah J , Watson Peter , Myers Nick , Nobre Anna C , Lau‐Zhu Alex , Holmes Emily A
Published: December 2016

Objectives

Mental imagery abnormalities occur across psychopathologies and are hypothesized to drive emotional difficulties in bipolar disorder (BD). A comprehensive assessment of mental imagery in BD is lacking. We aimed to test whether (i) mental imagery abnormalities (abnormalities in cognitive stages and subjective domains) occur in BD relative to non‐clinical controls; and (ii) to determine the specificity of any abnormalities in BD relative to depression and anxiety disorders.

Methods

Participants included 54 subjects in the BD group (depressed/euthymic; n=27 in each subgroup), subjects with unipolar depression (n=26), subjects with anxiety disorders (n=25), and non‐clinical controls (n=27) matched for age, gender, ethnicity, education, and premorbid IQ. Experimental tasks assessed cognitive (non‐emotional) measures of mental imagery (cognitive stages). Questionnaires, experimental tasks, and a phenomenological interview assessed subjective domains including spontaneous imagery use, interpretation bias, and emotional mental imagery.

Results

(i) Compared to non‐clinical controls, the BD combined group reported a greater impact of intrusive prospective imagery in daily life, more vivid and “real” negative images (prospective imagery task), and higher self‐involvement (picture‐word task). The BD combined group showed no clear abnormalities in cognitive stages of mental imagery. (ii) When depressed individuals with BD were compared to the depressed or anxious clinical control groups, no significant differences remained—across all groups, imagery differences were associated with affective lability and anxiety.

Conclusions

Compared to non‐clinical controls, BD is characterized by abnormalities in aspects of emotional mental imagery within the context of otherwise normal cognitive aspects. When matched for depression and anxiety, these abnormalities are not specific to BD—rather, imagery may reflect a transdiagnostic marker of emotional psychopathology.
Association of adipocyte enhancer‐binding protein 1 with Alzheimer's disease pathology in human hippocampi
Authors: Shijo Masahiro , Honda Hiroyuki , Suzuki Satoshi O. , Hamasaki Hideomi , Hokama Masaaki , Abolhassani Nona , Nakabeppu Yusaku , Ninomiya Toshiharu , Kitazono Takanari , Iwaki Toru
Published: December 2016

Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF‐κB pathway in macrophages and regulates adipogenesis in preadipocytes. Up‐regulation of AEBP1 in the hippocampi of patients with Alzheimer's disease (AD) has been revealed by microarray analyses of autopsied brains from the Japanese general population (the Hisayama study). In this study, we compared the expression patterns of AEBP1 in normal and AD brains, including in the hippocampus, using immunohistochemistry. The subjects were 24 AD cases and 52 non‐AD cases. Brain specimens were immunostained with antibodies against AEBP1, tau protein, amyloid β protein, NF‐κB, GFAP and Iba‐1. In normal brains, AEBP1 immunoreactivity mainly localized to the perikarya of hippocampal pyramidal neurons, and its expression was elevated in the pyramidal neurons and some astrocytes in AD hippocampi. Although AEBP1 immunoreactivity was almost absent in neurons containing neurofibrillary tangles, AEBP1 was highly expressed in neurons with pretangles and in the tau‐immunopositive, dystrophic neurites of senile plaques. Nuclear localization of NF‐κB was also observed in certain AEBP1‐positive neurons in AD cases. Comparison of AD and non‐AD cases suggested a positive correlation between the expression level of AEBP1 and the degree of amyloid β pathology. These findings imply that AEBP1 protein has a role in the progression of AD pathology.
Putting physical environments in their place: The next chapter?
Authors: Gregory Kenneth J.
Published: December 2016

The content of two books by Kenneth Gregory on the nature of physical geography, published in 1985 and 2000 provides a basis from which to consider changing priorities and, in the light of recent developments, to speculate about what additional chapter might be appropriate in 2016. It is suggested that physical environment, always a part of physical geography, characterized using techniques recently available, could be the subject for such a further chapter. This is already being anticipated by enhancements of existing techniques, by utilization of new methods, and by application of novel integrating concepts. A general integrated, holistic model that is more place located is required, and should be formulated so that it can be adapted for specific places and characterized in ways to indicate sensitivity, stressors, or risk factors. This model with cultural overlay needs to be positioned in space and time to focus on how it has arisen. Such a model could provide the basis for enquiries about whether it is optimal, how it could be improved, sustainably restored, and designed. It could be used for analyzing potential results of climate change and would put physical environment in its place within physical geography.

Positionner les environnements physiques au bon endroit : est‐ce le prochain chapitre ?

Kenneth Gregory a fait paraître, en 1985 et 2000, deux ouvrages portant sur la géographie physique, lesquels forment une assise sur laquelle on peut aborder le changement des priorités et, à la lumière de l'évolution récente, spéculer sur le prochain chapitre pouvant convenir en 2016. Il est proposé que l'environnement physique, en tant que composante de la géographie physique qui est décrite à l'aide de techniques mises au point récemment, pourrait faire l'objet d'un nouveau chapitre. Ceci est déjà envisagé grâce aux améliorations apportées aux techniques existantes, à l'utilisation de nouvelles méthodes et au déploiement de nouveaux concepts intégrateurs. Il est nécessaire de concevoir un modèle général, intégré et holistique qui soit davantage axé sur le lieu afin d'être adaptable à des lieux particuliers et de montrer les facteurs de sensibilité, de stress, ou de risque. Ce modèle est doté d'une couche culturelle et doit se positionner dans l'espace et le temps afin de mettre l'accent sur son émergence. Un tel modèle servirait d'assise aux études visant à établir s'il est optimal et comment il peut être amélioré, durablement restauré et conçu. Il pourrait être utilisé dans l'optique d'analyser les répercussions possibles des changements climatiques et permettrait de positionner l'environnement physique au bon endroit au sein de la géographie physique.
New 3‐alkylpyridine marine alkaloid analogues as promising antitumor agents against the CD44+/high/CD24−/low subset of triple‐negative breast cancer cell line
Authors: de Lima Aline Brito , Barbosa Camila de Souza , Gonçalves Alessandra Mirtes Marques Neves , Santos Fabio Vieira dos , Viana Gustavo Henrique Ribeiro , Varotti Fernando de Pilla , Silva Luciana Maria
Published: December 2016

Triple‐negative breast cancer (TNBC) is one of the most aggressive cancers in women. Additionally, presence of residual cancer stem cells (CSC) in TNBC has challenged the efficacy of chemotherapy. Thus, the development of new molecules with potential action against CSC is fundamental. In this study, six synthetic analogues of theonelladin C, a 3‐alkylpyridine marine alkaloid, were tested for cytotoxic activity against human TNBC cell line (BT‐549) and tumorspheres derived from BT‐549. Cytotoxicity assay was performed by sulforhodamine B (SRB). BT‐549 and tumorspheres were examined for CD44+/high/CD24−/low markers, indicative of CSC profile, by flow cytometry. Clonogenic assay was performed to verify inhibiting growth of tumorspheres by the synthetic analogues. Cell death by apoptosis was investigated employing annexin V assay. SRB assay on BT‐549 cells revealed that compounds 1c and 2c were the most active of the series, with IC50 values of 18.66 and 9.8 μm, respectively. Compounds 1c and 2c were able to reduce both CSC‐like population (CD44+/high/CD24−/low) and non‐CSC population (CD44+/high/CD24+/high) in tumorsphere model. Clonogenic and annexin V assays confirmed the ability of 1c and 2c to induce growth inhibition and apoptosis in BT‐549 cells and tumorspheres. These preliminary data indicate that these compounds are a promising class for development of anticancer agents.
Prognostic impact of the length of the longitudinal resection margin in colon cancer
Authors: Lee S. Y. , Kim C. H. , Kim Y. J. , Kim H. R.
Published: December 2016

Aim

Although several guidelines recommend a longitudinal resection margin (LRM) of at least 5 cm, the impact of the LRM on survival is still unknown. The study assessed the prognostic significance of the LRM in patients with colon cancer.

Method

We retrospectively reviewed 1343 primary colon cancer patients without distant metastasis who underwent curative resection between January 2004 and December 2012. Patients were classified into three groups: LRM < 3 cm (n = 186), LRM ≥ 3 and <5 cm (n = 376) and LRM ≥5 cm (n = 781). Clinicopathological characteristics and the oncological outcome in the three groups were compared.

Results

The median LRM length was 5.0 cm (range 0.5–26.0 cm). With increasing LRM, the number of retrieved lymph nodes (LNs) tended to increase (19.5 ± 12.0, 22.1 ± 12.8 and 30.0 ± 16.2; P < 0.001). After a median follow‐up period of 45 (1–128) months, 3‐year disease‐free survival (DFS) (89.2%, 89.0% and 87.0%; P = 0.629) and 5‐year overall survival (OS) (89.0%, 92.1% and 91.8%; P = 0.679) were not significantly different between the three groups. When confounders were adjusted, LRM was not significantly associated with either DFS or OS, but the number of retrieved LNs (< 12) was an independent risk factor for both DFS (hazard ratio 1.748, 95% confidence interval 1.048–2.917) and OS (hazard ratio 1.929, 95% confidence interval 1.046–3.559).

Conclusion

LRM was not associated with oncological outcome, but care should be taken to obtain an adequate number of LNs for better survival.
Anastomotic stenosis after coloanal, colorectal and ileoanal anastomosis: what is the best management?
Authors: Kraenzler A. , Maggiori L. , Pittet O. , Alyami M. S. , Prost à la Denise J. , Panis Y.
Published: December 2016

Aim

To assess the results of treatment for colorectal (CRA), coloanal (CAA) or ileal pouch–anal (IPAA) anastomotic stenosis (AS).

Method

All patients operated on for AS from 1995 to 2014 were included. Success was defined as the absence of an additional surgical procedure for AS during 12 months after the last procedure and the absence of a stoma at the end of follow‐up.

Results

Fifty consecutive patients presenting with AS after CRA (n = 16, 32%), CAA (n = 18, 36%) or IPAA (n = 16, 32%), performed for colorectal cancer (n = 28, 56%), familial adenomatous polyposis (n = 5, 10%), inflammatory bowel disease (n = 8, 16%), diverticulitis (n = 4, 8%), benign colorectal neoplasia (n = 3, 6%) or other (n = 2, 4%) underwent a total of 99 procedures including digital (n = 14, 14%), instrumental (n = 38, 38%) or endoscopic dilatation (n = 5, 5%), transanal AS stricturoplasty (n = 9, 10%), transanal circular stapler resection (n = 11, 11%) or transabdominal redo‐anastomosis (n = 22, 22%). Overall the per‐procedure success rate was 53% (52/99). Success rates were 36% (5/14) for digital dilatation, 40% (15/38) for instrumental dilatation, 20% (1/5) for endoscopic dilatation, 64% (7/11) for circular stapler resection, 89% (8/9) for stricturoplasty and 73% (16/22) for transabdominal redo‐anastomosis. After a mean follow‐up of 46 months, 42/50 (84%) patients had treatment that was considered successful. Multivariate analysis identified redo‐anastomosis [OR = 5.1 (95% CI: 1.4–18.7), P = 0.003] as the only independent prognostic factor for success.

Conclusion

AS should be managed according to a step‐up strategy. Conservative procedures are associated with acceptable success rates. If these fail, transabdominal redo‐anastomosis is associated with the highest probability of success.
Microvascular proliferation of brain metastases mimics glioblastomas in squash cytology
Authors: Gi T. , Sato Y. , Tokumitsu T. , Yamashita A. , Moriguchi‐Goto S. , Takeshima H. , Sato S. , Asada Y.
Published: December 2016

Objective

Although microvascular proliferation is a key feature in the diagnosis of high‐grade glioma, the characteristics of metastatic tumour vessels in smear preparations have not been documented. In this study, the vascular changes in metastatic brain tumours, using squash cytology to examine the vascular patterns in brain metastases, were reviewed.

Methods

One hundred and forty‐three squash smears of brain tissue, including 25 normal or reactive tissue, 23 malignant lymphomas, 8 grade I glioma (pilocytic astrocytoma), 23 grade II glioma (diffuse astrocytoma and oligodendroglioma), 42 grade IV glioma (glioblastoma), and 22 metastasis, were assessed. Two vascular patterns were assessed: thick and branching, and glomeruloid. The vessel density, nuclear layer and the number of vessel branches were compared. Furthermore, tumour vessels of brain metastases were analysed by histology and for immunohistochemical expression of CD34, α‐smooth muscle actin (SMA) and high‐molecular‐weight caldesmon (h‐CD).

Results

Among 22 metastatic tumours, thick and branching vessels were found in 17 (77%) and glomeruloid vessels in 13 (59%). These incidences of microvascular proliferation patterns were similar to those of glioblastomas or pilocytic astrocytomas. Vessel density, nuclear layer and vessel wall branches were significantly higher in metastatic tumours than malignant lymphomas, grade II gliomas or normal brain tissues. Glomeruloid vessels consisted of CD34‐positive cells and α‐SMA‐positive cells, and α‐SMA‐positive cells had a low h‐CD expression. These immunohistochemical patterns were similar to those of high‐grade gliomas.

Conclusions

The vascular features of metastatic brain tumours are similar to those of glioblastomas, suggesting that these microvascular proliferations contribute to the progression of metastatic tumours.
Using regional patterns for predicting local temporal change: a test by natural experiment in the Great Lakes bioregion, Ontario, Canada
Authors: Desrochers Rachelle E. , Currie David J. , Kerr Jeremy T.
Published: December 2016

Aim

It has been found that species richness can be a peaked function of natural area, meaning that conversion of natural cover can increase species numbers. Here, we test whether regional richness–environment relationships can predict local change in species richness.

Location

The greater park ecosystem of Thousand Islands National Park (TINPecosystem), Ontario, Canada.

Methods

We evaluated change in bird richness in 85 100‐km2sites, censused from 1981 to 1985 and from 2001 to 2005. We related change in richness over 20 years to change in natural land cover for sites having initially less or greater than half natural area to determine whether richness changes in the direction predicted. We also assessed the extent to which local effects (site‐level extinction and colonization based on species‐specific habitat amount and neighbourhood occupancy by conspecifics) affected the predictability of species richness response to environmental change.

Results

Local effects predicted bird richness changes through time far better than natural area change (adjustedr2 = 0.56 vs. adjustedr2 = 0.13). Species richness did not consistently respond to change in natural area in the directions predicted by the broader spatial richness–environment relationship, tending to increase with decrease in natural area regardless of the initial amount of natural area. The observed natural area changes (+0.7 km2to −4.4 km2) were small relative to the changes in richness (+60 species to −37 species), likely impacting our ability to detect a response.

Main conclusions

The importance of local effects observed here in determining site‐level species presence and consequently species richness has implications for species monitoring and the use of species richness as a measure of the avian response to land cover modification in Ontario. Detecting richness responses to environmental changes may often be challenged by low ‘signal‐to‐noise’ ratios and highlights the benefits of long‐term species monitoring.
Covered versus uncovered metal stents for malignant gastric outlet obstruction: Systematic review and meta‐analysis
Authors: Hamada Tsuyoshi , Hakuta Ryunosuke , Takahara Naminatsu , Sasaki Takashi , Nakai Yousuke , Isayama Hiroyuki , Koike Kazuhiko
Published: December 2016

Background and Aim

Self‐expandable metal stents (SEMS) are used for non‐resectable malignant gastric outlet obstruction (GOO). Studies of covered versus uncovered SEMS have yielded inconsistent results as a result of heterogeneity in design and patient population. We carried out a meta‐analysis to compare covered and uncovered gastroduodenal SEMS.

Methods

Using MEDLINE, Embase, and the Cochrane database, we identified 1624 patients from 13 prospective and retrospective studies that evaluated covered and uncovered SEMS for malignant GOO and were published until October 2016. We pooled data on SEMS dysfunction, technical and clinical success, and adverse events using the fixed‐effect or random‐effects model.

Results

Compared with uncovered SEMS, covered SEMS did not show any significant difference in stent dysfunction risk (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.79–1.32). A subgroup analysis of five randomized trials suggested a trend toward a lower dysfunction risk in covered SEMS (RR, 0.63; 95% CI, 0.45–0.88). Covered SEMS were associated with a lower occlusion risk (RR, 0.44; 95% CI, 0.28–0.68), but with a higher migration risk (RR, 4.28; 95% CI, 2.89–6.34). Technical and clinical success rates were comparable between the groups. Overall adverse events tended to be more frequent in covered SEMS (RR, 1.75; 95% CI, 1.09–2.83).

Conclusions

Outcomes of covered and uncovered gastroduodenal SEMS were comparable, although the lower dysfunction rate of covered SEMS observed in the analysis of randomized trials needs further investigation. Antimigration mechanisms for covered SEMS and identification of patients who can achieve longer patency from uncovered SEMS would help improve the outcomes of gastroduodenal SEMS.
Mass‐Independent and Mass‐Dependent Ca Isotopic Compositions of Thirteen Geological Reference Materials Measured by Thermal Ionisation Mass Spectrometry
Authors: He Yongsheng , Wang Yang , Zhu Chuanwei , Huang Shichun , Li Shuguang
Published: December 2016

We report mass‐independent and mass‐dependent Ca isotopic compositions for thirteen geological reference materials, including carbonates (NIST SRM 915a and 915b), Atlantic seawater as well as ten rock reference materials ranging from peridotite to sandstone, using traditional ε and δ values relative to NIST SRM 915a, respectively. Isotope ratio determinations were conducted by independent unspiked and 43Ca‐48Ca double‐spiked measurements using a customised Triton Plus TIMS. The mean of twelve measurement results gave ε40/44Ca values within ± 1.1, except for GSP‐2 that had ε40/44Ca = 4.04 ± 0.15 (2SE). Significant radiogenic 40Ca enrichment was evident in some high K/Ca samples. At an uncertainty level of ± 0.6, all reference materials had the same ε43/44Ca and ε48/44Ca values. We suggest the use of δ44/42Ca to report mass‐dependent Ca isotopic compositions. The precision under intermediate measurement conditions for δ44/42Ca over eight months in our laboratory was ± 0.03‰ (with n ≥ 8 repeat measurements). Measured igneous reference materials gave δ44/42Ca values ranging from 0.27‰ to 0.54‰. Significant Ca isotope fractionation may occur during magmatic and metasomatism processes. Studied reference materials with higher (Dyn/Ybn) tend to have lower δ44/42Ca, implying a potential role of garnet in producing magmas with low δ44/42Ca. Sandstone GBW07106 had a δ44/42Ca value of 0.22‰, lower than all igneous rocks studied so far.
Effects of Airflow Induced by Rainfall on Shallow Groundwater Table Fluctuations
Authors: Zang Yong Ge , Sun Dong Mei , Feng Ping , Semprich Stephan
Published: December 2016

An investigation of groundwater table fluctuations induced by rainfall should consider interactions between the liquid and gas phases in soils. In this study, a water‐air two‐phase flow model was initially verified by simulating an infiltration experiment. It was then employed to model the interactions between liquid and gas phases regarding actions of airflow on the groundwater table and the fluctuations of the phreatic level and water level in the well induced by rainfall. The effects of airflo7w caused by rainfall on phreatic level fluctuations were also studied quantitatively by comparing the results obtained using the proposed model with those obtained from a water single‐phase flow model. The simulation results show that in addition to actual recharge, compressed airflow in unsaturated zones causes the phreatic level to increase, but the rise in the phreatic level is lower than that in the pore‐air pressure head in unsaturated zones due to the mitigation of capillary fringe. The existence of airflow enhances the phreatic level rise during and after rainfall. In addition, the water level in the well, pushed by the phreatic level fluctuations, varies similarly to the phreatic level, but it experiences somewhat delayed and slightly attenuated. The Lisse effect precisely reflects the phreatic level fluctuations before actual recharge. Furthermore, the fluctuations in the phreatic level and water level in the well and the contributions of airflow to phreatic level fluctuations are affected by many factors: rain intensity, initial moisture, overlying aquitard, groundwater table depths, and screen depths of the well.
Hypermethylation of ATP‐binding cassette B1 (ABCB1) multidrug resistance 1 (MDR1) is associated with cisplatin resistance in the A549 lung adenocarcinoma cell line
Authors: Li Angui , Song Jianfei , Lai Qi , Liu Bangqing , Wang Haiyong , Xu Yinhui , Feng Xiaoyan , Sun Xiaolin , Du Zhenzong
Published: December 2016

Development of multiple drug resistance has been attributed to the overexpression of the ATP‐binding cassette B1 (ABCB1) gene. In this study, the major purpose was to assess the expression and methylation levels of ABCB1 in human lung adenocarcinoma and to reveal the relationship between these processes and acquisition of cisplatin (DDP) resistance in the human cancer cell line A549. Methylation and expression levels of the ABCB1 gene ABCB1 in clinical human lung tissue were assessed using bisulphite sequencing, reverse transcription real‐time PCR (RT2‐PCR) and Western blot methods. Cell viability, DDP resistance and apoptosis of A549 cells were evaluated using the Cell Counting Kit‐8 and fluorescence‐activated cell sorter analysis. Our results showed that the onset of resistance to the cisplatin analogue, DDP, was associated with hypermethylation of the ABCB1 gene. Expression of the ABCB1 gene was enhanced at both mRNA and protein levels. Treatment with 5‐Aza‐C contributed to the hypomethylation of the ABCB1 gene and decreased ABCB1 protein expression in A549 cells. In conclusion, this in vitro and human tissue study of lung adenocarcinoma cells demonstrated that hypermethylation of the ABCB1 gene correlated with increased gene expression and was associated with the acquisition of resistance to the cisplatin analogue, DDP in human lung adenocarcinoma cells. Taken together, our study highlighted the connection between increased ABCB1 methylation level and upregulated expression of the gene in lung cancer. Moreover, the abnormally high expression of ABCB1 in A549 cells contributed to the development of the DDP resistance.
Factors influencing suicidal ideation among Chinese patients with stomach cancer: qualitative study
Authors: Zhang X.K. , Procter N.G. , Xu Q. , Chen X.Y. , Lou F.L.
Published: December 2016

Aim

The aim of this qualitative descriptive study was to explore the influencing factors of suicidal ideation in Chinese patients diagnosed with stomach cancer.

Introduction

More recently, links have been made between suicide and cancer. For inpatients with cancer, nurses are at the front line to cope with suicidal issues in clinical settings.

Method

This study was part of a larger study that investigated psychological strains and related factors associated with suicidal ideation. Thirty‐two patients with stomach cancer participated in a face‐to‐face interview. Thematic analysis was used to analyse the qualitative data.

Findings

Four themes were identified as protective factors against suicidal ideation: suicidal denial and fears of stigmatization; positive coping skills; family connectedness; and desire to live well and longer.

Discussion

Consistent with previous research, these four protective factors may encourage participants to think more positively about life and cancer.

Conclusion

Our findings suggest four protective factors for targeted suicide prevention, which may play an important role in future suicide‐prevention programmes for Chinese patients diagnosed with stomach cancer.

Implications for nursing

Nurses may help reduce patients' risk for suicidal ideation more effectively by discussing beliefs, family and meaning in life perspectives, as well as offering health education about positive coping skills.

Implications for healthy policy

Clinical nurses, hospitals and the government should work collaboratively with each other. It is suggested that Chinese national guidelines for working with the high‐risk suicide populations should be considered within a future mental health working plan.
Bilateral social security agreements and pensions portability: A study of four migrant corridors between EU and non‐EU countries
Authors: Holzmann Robert
Published: December 2016

The article summarizes four corridor studies on bilateral social security agreements (BSSAs) between four European Union (EU) members that were undertaken to assess their working and the establishment of benefit portability. BSSAs between migrant‐sending and migrant‐receiving countries are seen as the most important instrument to establish portability of social security benefits for internationally mobile workers. Yet, only about 23 per cent of international migrants profit from BSSAs and their functioning has been little analyzed and even less assessed. The four corridors studied (Austria‐Turkey, Germany‐Turkey, Belgium‐Morocco, and France‐Morocco) were selected to allow for comparison of both similarities and differences in experiences. The evaluation of these corridors’ BSSAs was undertaken against a methodological framework and three selected criteria: fairness for individuals, fiscal fairness for countries, and bureaucratic effectiveness for countries and migrant workers. The results for pension portability suggest that the investigated BSSAs work and overall deliver reasonably well on individual fairness. The results on fiscal fairness are clouded by conceptual and empirical gaps. Bureaucratic effectiveness would profit from information and communication technology‐based exchanges on both corridors once available.
The digital nudge in social security administration
Authors: Gregor Shirley , Lee‐Archer Brian
Published: December 2016

The concept of nudge theory, from the fields of behavioural science, political theory and behavioural economics, has sparked government initiatives yielding significant public value. A nudge is a method for predictably altering behaviour without restricting consumer choice options or significantly changing incentives. Nudges work by leveraging default human behaviour such as the tendency to take the path of least resistance when exercising choice. Government agencies have run many successful trials with simple textual nudges designed to positively influence behaviours such as tax compliance, voter registration and student attrition. This article develops the concept of the digital nudge in social security administration. The digital nudge leverages predictive analytics technology within a digital government framework to support a social investment policy approach. Based on a literature review of nudges within a digital government context, the article identifies examples of innovation within social security administration where nudges are contributing to better social outcomes. At the same time, concerns regarding ethics and privacy are identified as nudges are applied at the individual rather than the population level. The use of data and personal information to drive the nudge process has to be managed in such a way that individual rights are protected. This requirement has to be reconciled with the broader interests of society in achieving affordable outcomes, the parameters of which are determined through the political process.
Coordinating social programmes: Analysis of scenarios and implementation approaches based on the ISSA Guidelines on ICT
Authors: Ruggia‐Frick Raúl
Published: December 2016

The development of social security policies and programmes raises the need for their coordination to enhance effectiveness as well as to prevent the fragmentation of social policies, programmes and services. Although there are expected benefits, implementing coordinated programmes poses significant technical challenges, which increase the complexities and costs of projects and hinder the achievement of such initiatives. Some of the main difficulties are related to system and information integration (Interoperability) as well as the ability to enforce data security and privacy regulations. To help meet such challenges, the International Social Security Association (ISSA) has developed Guidelines on Information and Communication Technology to support the integrated ICT‐based implementation of social programmes. This article reviews existing scenarios, discusses the benefits and challenges of coordinated approaches, and offers models to show how to implement such types of systems while applying the ISSA Guidelines.
Introduction: Pursuing excellence in social security administration
Authors: McKinnon Roddy
Published: December 2016

This 2016 special issue addresses the topic of excellence in social security administration. For the International Social Security Association, “excellence” is most usually associated with ensuring that the technical processes and administrative procedures that underpin the delivery of social security benefits and services are high‐performing, well‐governed and sustainable. But it also refers to the covered population’s perceptions of the quality and adequacy of the services and benefits provided. The academic literature on “social security” is immense, but the larger part of this published research addresses questions of social security theory and policy. The critical, analytical literature on social security administration, including that which marries theoretical analysis with the empirical evidence of administrative performance, is thus smaller. A major aim of this special issue is to make a contribution to redressing this imbalance. This is done not only to support and stimulate research that draws equally on empirical evidence and the theoretical literature, but in a very practical sense to better take into account and provide responses to the increasingly complex operational challenges facing social security administrations
Comparison of Left Atrial Bipolar Voltage and Scar Using Multielectrode Fast Automated Mapping versus Point‐by‐Point Contact Electroanatomic Mapping in Patients With Atrial Fibrillation Undergoing Repeat Ablation
Authors: LIANG JACKSON J. , ELAFROS MELISSA A. , MUSER DANIELE , PATHAK RAJEEV K. , SANTANGELI PASQUALE , SUPPLE GREGORY E. , SCHALLER ROBERT D. , FRANKEL DAVID S. , DIXIT SANJAY
Published: December 2016

Voltage Differences With Multielectrode Mapping

Introduction

Bipolar voltage criteria to delineate left atrial (LA) scar have been derived using point‐by‐point (PBP) contact electroanatomical mapping. It remains unclear how PBP‐derived LA scar correlates with multielectrode fast automated mapping (ME‐FAM) derived scar. We aimed to correlate scar and bipolar voltages from LA maps created using PBP versus ME‐FAM.

Methods and Results

In consecutive patients undergoing repeat AF ablation, 2 separate LA maps were created using PBP and ME‐FAM during sinus rhythm before ablation. Contiguous areas in the LA with a bipolar voltage cutoff of ≤0.2 mV represented dense scar; LA scar percentage was calculated for each map. Each LA shell was divided into 9 regions and each region further subdivided into 4 quadrants for additional analysis; mean voltages of all points obtained using PBP versus ME‐FAM in each region were compared. Forty maps (20 PBP: mean 228.5 ± 95.6 points; 20 ME‐FAM: 923.0 ± 382.6 points) were created in 20 patients. Mapping time with ME‐FAM was shorter compared with PBP (13.3 ± 5.3 vs. 34.4 ± 13.1 minutes; P < 0.001). Mean LA scar percentage was higher with PBP compared with ME‐FAM (15.5 ± 17.1% vs. 12.8 ± 17.6%; P = 0.04). Mean PBP voltage distribution was lower (compared with ME‐FAM) in the septum (0.95 ± 0.73 vs. 1.46 ± 0.99 mV; P = 0.009), posterior wall (0.84 ± 0.42 vs. 1.40 ± 0.83 mV; P = 0.0008), roof (0.78 ± 0.80 vs. 1.39 ± 1.09 mV; P = 0.0003), and right PV–LA junction (0.34 ± 0.25 vs. 0.59 ± 0.50 mV; P = 0.01) regions, while voltages were similar in all other LA regions (all P > 0.05).

Conclusions

In AF patients undergoing repeat ablation, bipolar voltage is greater in certain LA segments with ME‐FAM compared with PBP mapping.
The X‐linked juvenile retinoschisis protein retinoschisin is a novel regulator of mitogen‐activated protein kinase signalling and apoptosis in the retina
Authors: Plössl Karolina , Weber Bernhard H.F. , Friedrich Ulrike
Published: December 2016

X‐linked juvenile retinoschisis (XLRS) is a hereditary retinal dystrophy in young males, caused by mutations in the RS1 gene. The function of the encoded protein, termed retinoschisin, and the molecular mechanisms underlying XLRS pathogenesis are still unresolved, although a direct interaction partner of the secreted retinoschisin, the retinal Na/K‐ATPase, was recently identified. Earlier gene expression studies in retinoschisin‐deficient (Rs1h−/Y) mice provided a first indication of pathological up‐regulation of mitogen‐activated protein (MAP) kinase signalling in disease pathogenesis. To further investigate the role for retinoschisin in MAP kinase regulation, we exposed Y‐79 cells and murine Rs1h−/Y retinae to recombinant retinoschisin and the XLRS‐associated mutant RS1‐C59S. Although normal retinoschisin stably bound to retinal cells, RS1‐C59S exhibited a strongly reduced binding affinity. Simultaneously, exposure to normal retinoschisin significantly reduced phosphorylation of C‐RAF and MAP kinases ERK1/2 in Y‐79 cells and murine Rs1h−/Y retinae. Expression of MAP kinase target genes C‐FOS and EGR1 was also down‐regulated in both model systems. Finally, retinoschisin treatment decreased pro‐apoptotic BAX‐2 transcript levels in Y‐79 cells and Rs1h−/Y retinae. Upon retinoschisin treatment, these cells showed increased resistance against apoptosis, reflected by decreased caspase‐3 activity (in Y‐79 cells) and increased photoreceptor survival (in Rs1h−/Y retinal explants). RS1‐C59S did not influence C‐RAF or ERK1/2 activation, C‐FOS or EGR1 expression, or apoptosis. Our data imply that retinoschisin is a novel regulator of MAP kinase signalling and exerts an anti‐apoptotic effect on retinal cells. We therefore discuss that disturbances of MAP kinase signalling by retinoschisin deficiency could be an initial step in XLRS pathogenesis.
Shockwaves prevent from heart failure after acute myocardial ischaemia via RNA/protein complexes
Authors: Tepeköylü Can , Primessnig Uwe , Pölzl Leo , Graber Michael , Lobenwein Daniela , Nägele Felix , Kirchmair Elke , Pechriggl Elisabeth , Grimm Michael , Holfeld Johannes
Published: December 2016

Shock wave treatment (SWT) was shown to induce regeneration of ischaemic myocardium via Toll‐like receptor 3 (TLR3). The antimicrobial peptide LL37 gets released by mechanical stress and is known to form complexes with nucleic acids thus activating Toll‐like receptors. We suggested that SWT in the acute setting prevents from the development of heart failure via RNA/protein release. Myocardial infarction in mice was induced followed by subsequent SWT. Heart function was assessed 4 weeks later via transthoracic echocardiography and pressure–volume measurements. Human umbilical vein endothelial cells (HUVECs) were treated with SWT in the presence of RNase and proteinase and analysed for proliferation, tube formation and LL37 expression. RNA release and uptake after SWT was evaluated. We found significantly improved cardiac function after SWT. SWT resulted in significantly higher numbers of capillaries and arterioles and less left ventricular fibrosis. Supernatants of treated cells activated TLR3 reporter cells. Analysis of the supernatant revealed increased RNA levels. The effect could not be abolished by pre‐treatment of the supernatant with RNase, but only by a sequential digestion with proteinase and RNase hinting strongly towards the involvement of RNA/protein complexes. Indeed, LL37 expression as well as cellular RNA uptake were significantly increased after SWT. We show for the first time that SWT prevents from left ventricular remodelling and cardiac dysfunction via RNA/protein complex release and subsequent induction of angiogenesis. It might therefore develop a potent regenerative treatment alternative for ischaemic heart disease.
The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder
Authors: Gevaert Thomas , Ridder Dirk De , Vanstreels Els , Daelemans Dirk , Everaerts Wouter , Aa Frank Van Der , Pintelon Isabel , Timmermans Jean‐Pierre , Roskams Tania , Steiner Clara , Neuhaus Jochen
Published: December 2016

The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT+ ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody‐related issues and interspecies differences in this matter. Fresh samples were obtained from human, rat, mouse and guinea pig cystectomies and processed for single/double immunohistochemistry/immunofluorescence. Specific antibodies against KIT, mast cell tryptase (MCT), anoctamin‐1 (ANO1) and vimentin were used to characterize the cell types expressing KIT. Gut (jejunum) tissue was used as an external antibody control. Our results revealed KIT expression on mast cells but not on ICC in human, rat, mouse and guinea pig bladder. Parallel immunohistochemistry showed KIT expression on ICC in human, rat, mouse and guinea pig gut, which confirmed the selectivity of the KIT antibody clones. In conclusion, we have shown that KIT+ cells in human, rat, mouse and guinea pig bladder are mast cells and not ICC. The present report is important as it opposes the idea that KIT+ ICC are present in bladder. In this perspective, functional concepts of KIT+ ICC being involved in sensory and/or motor aspects of bladder physiology should be revised.