bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between Islamic work ethic and workplace outcome
Authors: Mohammad Jihad , Quoquab Farzana , Idris Fazli , Al-Jabari Mohammed , Hussin Nazimah , Wishah Raed
Published: June 2018

Purpose

The purpose of this paper is to examine the relationship between Islamic work ethic (IWE) and employees’ attitude and behaviour in term of perceived organisational justice, psychological ownership (PSY), and employees’ performance in the Islamic financial institutions in Malaysia.

Design/methodology/approach

This study used a sample of 301 employees of Islamic financial institutions and employed structural equation modelling-partial least square technique in order to analyse the data.

Findings

The findings demonstrated that IWE has both direct and indirect effects on attitudinal as well as behavioural outcomes.

Practical implications

Managers who want to enhance their employees’ attitude and behaviour are strongly advised to give proper attention to the concept work ethic. Moreover, they need to conduct training programs to instil these values and to emphasise its crucial role in enhancing the effectiveness and efficiency of the organisation.

Originality/value

This study contributes to the body of knowledge on IWE by: testing its ability to predict employees’ performance, their perception of organisational justice, and their feeling of PSY, and examining the mediating effect of perceived organisational justice and PSY between IWE and employees’ performance.
Accountability breeds response-ability
Authors: Tariq Hussain , Weng Qingxiong (Derek)
Published: June 2018

Purpose

The purpose of this paper is to investigate the link between perceived subordinate performance and abusive supervision. From the perspective of moral exclusion theory, the authors examine cooperative goal interdependence and competitive goal interdependence as key boundary conditions to hypothesize and demonstrate the direct negative relationship between low-performing subordinates and abusive supervision. Within the moral exclusion framework, supervisors may strategically abuse low performers when cooperative goal interdependence is high, or competitive goal interdependence is low. Moreover, this study explores the impact of abusive supervision on subordinate’s objective performance.

Design/methodology/approach

This research employs two independent studies to examine the antecedents and consequences of abusive supervision based on respondents from a Fortune 500 company located in Anhui province of People’s Republic of China (PRC). Study 1 uses a time lagged, single source survey while Study 2 employs multi-source, multi-wave data. The results support the integrated model.

Findings

Across the two studies, the results showed that the direct negative relationship between perceived subordinate performance and abusive supervision was found to be stronger when cooperative goal interdependence was high and when competitive goal interdependence was low. Study 2 also revealed the negative impact of abusive supervision on subordinate’s objective performance and that the conditional indirect effect of subordinate’s perceived performance on objective performance via abusive supervision was contingent on the extent of cooperative and competitive goal interdependence.

Originality/value

The results clearly demonstrate that supervisors are likely to turn to abusive supervision in response to poor performing subordinates but that the tendency to use abuse as an instrumental strategy for improving subordinate performance is dependent on the nature of goal interdependence between the supervisor and subordinates’ goals. The research also shows that although supervisors may turn to abusive supervision under certain goal interdependence conditions, it is not an effective strategy for actually improving subordinate objective performance. In fact, it has the opposite effect.
Foreign direct investment in the G-20: to what extent do institutions matter?
Authors: Tomelin Jurema , Amal Mohamed , Hein Nelson , Carpes Dani Andreia
Published: June 2018

Purpose

This study aims to identify to what extent the economic factor effect is more salient in shaping inward foreign direct investment (IFDI) than are institutional factors in G-20 inflow patterns.

Design/methodology/approach

Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method was applied using the World Bank Governance and Development Indicators, followed by a panel data technique over the period 2005-2015 to estimate the connections between the different dimensions of economics, institutions and IFDI in the G-20.

Findings

Results showed that countries with better economic performance contrasting with the governance indicators are more effective at attracting IFDI. However, the correlation between FDI intensity and governance indicators has been found relatively weak, which may suggest a more controversial role of institutions as determinants of IFDI.

Research limitations/implications

This quantitative approach uses a country-level set of variables; therefore, the authors suggest the development of more firm-level analysis of the impact of institutions. Also, the limitation of the TOPSIS method itself is based on heuristic assumptions.

Practical implications

The main findings point to a relatively low impact of institutions on IFDI. The authors suggest that the global financial crisis has changed the rationale of decision-making by multinational companies.

Originality/value

The originality of the present study was to apply a multi criteria decision-making technique on FDI’s analysis combined with institutional data.
Applying a Bayesian weighted surveillance approach to detect chronic wasting disease in white‐tailed deer
Authors: Jennelle Christopher S. , Walsh Daniel P. , Samuel Michael D. , Osnas Erik E. , Rolley Robert , Langenberg Julia , Powers Jenny G. , Monello Ryan J. , Demarest E. David , Gubler Rolf , Heisey Dennis M.
Published: June 2018

Surveillance is critical for early detection of emerging and re‐emerging infectious diseases. Weighted surveillance leverages heterogeneity in infection risk to increase sampling efficiency.

Here, we apply a Bayesian approach to estimate weights for 16 surveillance classes of white‐tailed deer in Wisconsin, USA, relative to hunter‐harvested yearling males. We used these weights to conduct a surveillance programme for detecting chronic wasting disease (CWD) in white‐tailed deer at Shenandoah National Park (SHEN) in Virginia, USA.

Generally, for surveillance, risk of infection increased with age and was greater in males. Clinical suspect deer had the highest risk, with weight estimates of 33.33 and 9.09 for community‐reported and hunter‐reported suspect deer, respectively. Fawns had the lowest risk with an estimated weight of 0.001.

We used surveillance weights for Wisconsin deer to determine sampling effort required to detect a CWD‐positive case in SHEN if prevalence in yearling males ≥0.025. The sampling required to detect CWD was 37–91 adult deer, depending on the adult male:female ratio in the surveillance stream. We collected rectal biopsies from 49 female and 21 male adult deer, and 10 additional samples from vehicle‐killed deer. CWD was not detected and we concluded with 95% probability that prevalence in the reference population (yearling males) was between 0.0% and 3.6%.

Synthesis and applications. Our approach allows managers to estimate relative surveillance weights for different host classes and quantify limits of disease detection in real time when only a sample of animals from a population can be tested, resulting in considerable cost savings for agencies performing wildlife disease detection surveillance. Additionally, it provides a rigorous means of estimating prevalence limits when a disease/pathogen is not detected in a sample set. It is therefore applicable to other wildlife, domestic animal and human disease systems, which can be characterized by surveillance classes with heterogeneous probability of infection. This methodology is also extendable to other disciplines such as invasive species, environmental toxicology, and generally, any ecological question seeking to efficiently use scarce financial and human resources to maximize the detection probability of a rare event.
Consumer‐mediated indirect interaction with a native plant lowers the fitness of an invasive competitor
Authors: Bogdziewicz Michał , Lichti Nathanael I. , Zwolak Rafał
Published: June 2018

Seed dispersal is a primary driver, via propagule pressure, of biological invasions. In animal‐dispersed plants, theory predicts that indirect ecological interactions at the neighbourhood scale may determine landscape‐scale patterns of seed dispersal and predation, and thus invasion.

Indirect interactions in seed dispersal may arise between two plant species if shared seed dispersal agents adjust their foraging decisions to the relative frequencies of co‐occurring seeds. We used seed‐tracking experiments and empirically parameterized simulations to test the hypothesis that an indirect interaction between two plant species, mediated by scatterhoarding rodents that both consume and disperse seeds, affects recruitment of an invasive tree. We predicted that acorns of Quercus rubra (invasive in Central Europe) would experience higher caching (and therefore survival) rates when they co‐occurred with native Quercus petraea than when they occurred in isolation, that Q. petraea acorns would survive at lower rates with Q. rubra relative to isolation, and that this interaction would facilitate Q. rubra seedling recruitment in Q. petraea forests.

Contrary to expectations, the presence of Q. petraea reduced caching of Q. rubra acorns, and co‐occurrence with Q. rubra increased caching of Q. petraea. Thus, a rodent‐mediated indirect interaction may be slowing rather than facilitating the Q. rubra invasion. However, our simulations indicate that the magnitude of this indirect interaction will change nonlinearly as Q. rubra becomes more dominant on the landscape, and that the pace of invasion will accelerate as the alien species is released from the rodent‐mediated effect of Q. petraea.

Synthesis. The presence of native Quercus petraea decreases recruitment rates of Quercus rubra, and consequently, slows down the invasion process. The strong dependence of pairwise interactions on the presence of a third‐party species emphasizes the role of indirect interactions in the invasion processes.
Modified Constraint‐Induced Movement Therapy is a feasible and potentially useful addition to the Community Rehabilitation tool kit after stroke: A pilot randomised control trial
Authors: Baldwin Cathryn R. , Harry Amy J. , Power Lynda J. , Pope Katherine L. , Harding Katherine E.
Published: June 2018

Background/aim

The National Stroke Foundation recommends that Occupational Therapists use Constraint‐Induced Movement Therapy (CIMT) with stroke survivors that experience an upper limb deficit. CIMT involves constraining the unaffected upper limb coupled with intensive therapy. The aim of this study was to evaluate the feasibility and effectiveness of a modified, low intensity version of CIMT (mCIMT) provided within usual resources of an Australian community rehabilitation setting.

Methods

A pilot randomised control trial (n = 19) was conducted with stroke survivors referred for community rehabilitation. Participants were randomly assigned to either mCIMT or usual care. Both groups received six one‐hour outpatient Occupational Therapy sessions (focussed on upper limb rehabilitation) over a two‐week period. The intervention group (mCIMT) were asked to wear a constraint device on their unaffected hand for 90% of their waking hours and were provided with a home exercise program based on CIMT principles. Participants were included if they had some active upper limb movement, no significant cognitive deficits and sufficient balance. Outcome measures included upper limb function (WMFT) and participation (MAL) evaluated at baseline, immediately following the two‐week intervention period and at four‐week follow‐up.

Results

Only a very small proportion of patients met the eligibility criteria. There were no differences between groups, with the exception of a small increase in reported upper extremity use in functional tasks at post‐intervention assessment when compared to the usual care group.

Conclusions

Modified CIMT can be applied to a typical Australian community rehabilitation setting, to treat upper limb deficits in stroke survivors. The resources used for mCIMT largely equalled usual care, with no differences in outcomes, suggesting that the intervention is feasible and potentially beneficial. However, there were very few stroke survivors who met participation criteria, indicating that demand for the intervention is limited.
Dynamics of transparent exopolymer particle production and aggregation during viral infection of the coccolithophore, Emiliania huxleyi
Authors: Nissimov Jozef I. , Vandzura Rebecca , Johns Christopher T. , Natale Frank , Haramaty Liti , Bidle Kay D.
Published: June 2018

Emiliania huxleyi produces calcium carbonate (CaCO3) coccoliths and transparent exopolymer particles (TEP), sticky, acidic carbohydrates that facilitate aggregation. E. huxleyi's extensive oceanic blooms are often terminated by coccolithoviruses (EhVs) with the transport of cellular debris and associated particulate organic carbon (POC) to depth being facilitated by TEP‐bound ‘marine snow’ aggregates. The dynamics of TEP production and particle aggregation in response to EhV infection are poorly understood. Using flow cytometry, spectrophotometry and FlowCam visualization of alcian blue (AB)‐stained aggregates, we assessed TEP production and the size spectrum of aggregates for E. huxleyi possessing different degrees of calcification and cellular CaCO3:POC mass ratios, when challenged with two EhVs (EhV207 and EhV99B1). FlowCam imaging also qualitatively assessed the relative amount of AB‐stainable TEP (i.e., blue:red ratio of each particle). We show significant increases in TEP during early phase EhV207‐infection (∼ 24 h) of calcifying strains and a shift towards large aggregates following EhV99B1‐infection. We also observed the formation of large aggregates with low blue:red ratios, suggesting that other exopolymer substances contribute towards aggregation. Our findings show the potential for virus infection and the associated response of their hosts to impact carbon flux dynamics and provide incentive to explore these dynamics in natural populations.
Microbial life under ice: Metagenome diversity and in situ activity of Verrucomicrobia in seasonally ice‐covered Lakes
Authors: Tran Patricia , Ramachandran Arthi , Khawasik Ola , Beisner Beatrix E. , Rautio Milla , Huot Yannick , Walsh David A.
Published: June 2018

Northern lakes are ice‐covered for a large part of the year, yet our understanding of microbial diversity and activity during winter lags behind that of the ice‐free period. In this study, we investigated under‐ice diversity and metabolism of Verrucomicrobia in seasonally ice‐covered lakes in temperate and boreal regions of Quebec, Canada using 16S rRNA sequencing, metagenomics and metatranscriptomics. Verrucomicrobia, particularly the V1, V3 and V4 subdivisions, were abundant during ice‐covered periods. A diversity of Verrucomicrobia genomes were reconstructed from Quebec lake metagenomes. Several genomes were associated with the ice‐covered period and were represented in winter metatranscriptomes, supporting the notion that Verrucomicrobia are metabolically active under ice. Verrucomicrobia transcriptome analysis revealed a range of metabolisms potentially occurring under ice, including carbohydrate degradation, glycolate utilization, scavenging of chlorophyll degradation products, and urea use. Genes for aerobic sulfur and hydrogen oxidation were expressed, suggesting chemolithotrophy may be an adaptation to conditions where labile carbon may be limited. The expression of genes for flagella biosynthesis and chemotaxis was detected, suggesting Verrucomicrobia may be actively sensing and responding to winter nutrient pulses, such as phytoplankton blooms. These results increase our understanding on the diversity and metabolic processes occurring under ice in northern lakes ecosystems.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd
Transient uterine contractions as a potential pathology mimic on premenopausal pelvic MRI and the role of routine repeat T2 sagittal images to improve observer confidence
Authors: Lam John YM , Voyvodic Frank , Jenkins Melissa , Knox Steven
Published: June 2018

Introduction

Pelvic MRI has an increasingly important role in the evaluation of non‐malignant uterine pathology including uterine leiomyomas, adenomyosis and endometriosis. Normal physiological myometrial junctional zone transient contractions can also be identified on MRI and have the potential to act as pathology mimics. This study aims to evaluate both the incidence of visible physiological contractions in premenopausal female pelvic MRI and also to support the routine acquisition of a repeat T2 sagittal sequence to differentiate transient physiological contractions from true underlying pathology and therefore improve observer confidence.

Methods

A total of 279 female patients of child‐bearing age who had undergone a pelvic MRI over a 16 month period met the inclusion criteria. All patients underwent a standard examination protocol on the same hardware. This included performing two separate T2‐weighted sagittal sequences as part of the protocol firstly as the initial and then as the final series for the examination. The sagittal series were reviewed separately by four readers and conclusions made for each case with regards to the presence of identifiable contractions on one or both series and their potential to act as pathology mimics.

Results

Of the 279 cases, there were 34 cases (12.2%) that were found to have transient junctional zone contractions acting as pathology mimics, resembling either leiomyomata or adenomyosis.

Conclusions

Standard MRI sequences need to be able to distinguish normal transient physiological uterine contractions from true pathology to avoid diagnostic error. The routine utility of a repeat T2‐weighted sagittal sequence performed at the conclusion of a patient's examination was shown to improve reader confidence in distinguishing transient contractions from true uterine pathology while adding minimal time penalty to the overall examination. It is therefore advocated that all premenopausal female pelvic MRI cases have a T2 sagittal series as the initial and then the final series as part of a routine protocol.
The HEART Pathway Randomized Controlled Trial One‐year Outcomes
Authors: Stopyra Jason P. , Riley Robert F. , Hiestand Brian C. , Russell Gregory B. , Hoekstra James W. , Lefebvre Cedric W. , Nicks Bret A. , Cline David M. , Askew Kim L. , Elliott Stephanie B. , Herrington David M. , Burke Gregory L. , Miller Chadwick D. , Mahler Simon A.
Published: June 2018

Objective

The objective was to determine the impact of the HEART Pathway on health care utilization and safety outcomes at 1 year in patients with acute chest pain.

Methods

Adult emergency department (ED) patients with chest pain (N = 282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, ED providers used the HEART score and troponin measures (0 and 3 hours) to risk stratify patients. Usual care was based on American College of Cardiology/American Heart Association guidelines. Major adverse cardiac events (MACE—cardiac death, myocardial infarction [MI], or coronary revascularization), objective testing (stress testing or coronary angiography), and cardiac hospitalizations and ED visits were assessed at 1 year. Randomization arm outcomes were compared using Fisher's exact tests.

Results

A total of 282 patients were enrolled, with 141 randomized to each arm. MACE at 1 year occurred in 10.6% (30/282): 9.9% in the HEART Pathway arm (14/141; 10 MIs, four revascularizations without MI) versus 11.3% in usual care (16/141; one cardiac death, 13 MIs, two revascularizations without MI; p = 0.85). Among low‐risk HEART Pathway patients, 0% (0/66) had MACE, with a negative predictive value (NPV) of 100% (95% confidence interval = 93%–100%). Objective testing through 1 year occurred in 63.1% (89/141) of HEART Pathway patients compared to 71.6% (101/141) in usual care (p = 0.16). Nonindex cardiac‐related hospitalizations and ED visits occurred in 14.9% (21/141) and 21.3% (30/141) of patients in the HEART Pathway versus 10.6% (15/141) and 16.3% (23/141) in usual care (p = 0.37, p = 0.36).

Conclusions

The HEART Pathway had a 100% NPV for 1‐year safety outcomes (MACE) without increasing downstream hospitalizations or ED visits. Reduction in 1‐year objective testing was not significant.
Cigarette consumption and biomarkers of nicotine exposure during pregnancy and postpartum
Authors: Taghavi Taraneh , Arger Christopher A. , Heil Sarah H. , Higgins Stephen T. , Tyndale Rachel F.
Published: June 2018

Background and Aims

Smokers can regulate their nicotine intake by altering the number of cigarettes smoked per day (CPD) and their smoking intensity. The current study aimed to compare the utility of self‐reported CPD, total nicotine equivalents (TNE) and urinary cotinine to estimate nicotine intake during pregnancy.

Design

Longitudinal smoking behavior and biomarker data were collected at early pregnancy, late pregnancy and at postpartum as part of a smoking cessation trial to examine voucher‐based incentives for decreasing smoking.

Setting

Obstetric practices in Burlington, Vermont, United States.

Participants

A subset of participants (n = 47) from the parent trial, recruited between December 2006 and June 2012, who provided a urine sample at each assessment during early pregnancy, late pregnancy and postpartum.

Measurements

Smoking was assessed using self‐reported CPD, TNE, TNE/CPD and urinary cotinine.

Findings

Pregnant smokers reported smoking 10.4 CPD at early pregnancy, 7.2 CPD at late pregnancy (a 31% reduction at late pregnancy, P = 0.001) and 8.6 CPD at postpartum (a 19% increase from late pregnancy, P = 0.08). TNE exposure was 41% (P = 0.07) and 48% (P = 0.03) lower at early and late pregnancy, respectively, compared to postpartum. TNE/CPD was on average 167% higher at late pregnancy compared to early pregnancy (P = 0.01) and remained high at postpartum, where it was 111% higher compared to early pregnancy (P = 0.007). Uriniary cotinine underestimated nicotine intake by 55% during early pregnancy and by 65% during late pregnancy compared to postpartum (Pinteraction < 0.001); the underestimation was greater in slower (Pinteraction < 0.001) versus faster (Pinteraction = 0.04) nicotine metabolizers.

Conclusions

Neither cigarettes smoked per day (CPD) nor cotinine provides an accurate estimate of nicotine exposure during pregnancy. CPD underestimates nicotine intake substantially due to under‐reporting and/or higher intensity of smoking, while cotinine underestimates nicotine intake markedly due to accelerated nicotine (and cotinine) metabolism during pregnancy.
After how many drinks does someone experience acute consequences—determining thresholds for binge drinking based on two event‐level studies
Authors: Labhart Florian , Livingston Michael , Engels Rutger , Kuntsche Emmanuel
Published: June 2018

Background and Aims

The threshold of 4+/5+ drinks per occasion has been used for decades in alcohol research to distinguish between non‐risky versus risky episodic drinking. However, no study has assessed the validity of this threshold using event‐level data. This study aimed to determine the optimal thresholds for the detection of five acute alcohol‐related consequences (hangover, blackout, risky sex, fights and injury) using data from two event‐level studies.

Design

An event‐level study to assess the ability to use the number of drinks consumed to discriminate between nights with and without consequences using the area under the receiver operating characteristic (AUROC) curve. Optimal thresholds were determined using the Youden Index based on sensitivity and specificity. Separate thresholds were estimated for gender and age groups (16–17 versus 18–25).

Setting

Lausanne and Zurich, Switzerland.

Participants

Three hundred and sixty‐nine participants aged 16–25 years.

Measurements

On 3554 weekend nights, participants reported total number of alcoholic drinks consumed the previous night and acute consequences (hangover, blackout, risky sex, fights and injury)

Findings

Hangover was the most frequently reported consequence and injury the least for both genders. Throughout age groups and studies, optimal thresholds for any consequence, and for hangover only, were equal to 4+/5+ (40+/50+ g alcohol) while those for blackouts, risky sex, fights and injuries were up to three drinks higher. Adolescents tended to experience consequences more often and at slightly lower drinking levels than did adults. For all consequences but injuries, the optimal thresholds were one to two drinks lower for women than for men.

Conclusions

Event‐level data collection techniques appear particularly suitable to estimate thresholds at which acute alcohol‐related consequences occur. Binge drinking thresholds of 4+/5+ (women/men) drinks, equivalent to 40+/50+ g pure alcohol, predict the occurrence of consequences accurately in general but are too low to predict severe acute alcohol‐related consequences.
Mast cells—Good guys with a bad image?
Authors: Meyer Nicole , Zenclussen Ana Claudia
Published: June 2018

Mast cells (MCs) are most known because of their prominent role in allergy. In the last years, however, it has become clear that they have pleiotropic functions and a high adaptability to the milieu. This review focuses on negative and positive roles of MCs within the body with particular emphasis on their participation in reproductive processes.
Recent trends in the management of pelvic organ prolapse in Australia and New Zealand
Authors: Miller Brendan J. , Seman Elvis I. , O'Shea Robert T. , Hakendorf Paul H. , Nguyen Tran T.T.
Published: June 2018

Objective

To compare current practice in the management of female pelvic organ prolapse in Australia and New Zealand with that in 2007, and assess the impact on practice of the withdrawal of Prolift® and Prosima® mesh kits in 2015.

Materials and Methods

In early 2015, two invitations to participate in a survey, including a link to Surveymonkey, were emailed to 2506 Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) trainees and fellows. The online survey closely resembled a printed survey that was posted to RANZCOG trainees and fellows in 2007 and had additional questions relating to the impact of withdrawal of Prolift® and Prosima® products.

Results

Four‐hundred‐and‐three doctors participated, giving a response rate of 16%. Native tissue repair was the procedure of choice for primary and recurrent prolapse of the anterior and posterior vaginal wall. An implant was used to treat 45% of anterior recurrences and 25% of posterior recurrences. Vaginal hysterectomy and repair were the procedures of choice for uterovaginal prolapse. Sacrospinous hysteropexy was the uterine preservation procedure of choice, preferred by 41%. For post‐hysterectomy vault prolapse, sacrospinous colpopexy and vaginal repair was preferred by 65% of respondents. Between 2007 and 2015, there was a substantial decrease in respondents’ usage of implants across all indications except for midurethral slings and sacrocolpo/hysteropexy. Forty‐two percent of respondents changed their practice as a result of Prolift® and Prosima® being withdrawn.

Conclusion

There is a trend toward increasing use of various native tissue prolapse repair procedures and midurethral slings, and less utilisation of transvaginal mesh for prolapse.
LAMP‐1 gene is overexpressed in high grade glioma
Authors: Sarafian Victoria S. , Koev Ilian , Mehterov Nikolay , Kazakova Maria , Dangalov Krassimir
Published: June 2018

High‐grade gliomas (HGG) are the most frequent brain tumors in adults. Glioblastoma multiforme (GBM) is their most aggressive form resistant to therapy. It was shown that inhibition of autophagy reduced GBM development and autophagy interfering agents are regarded as a new strategy to fight glioma cells. The lysosome‐associated membrane proteins (LAMPs) display differential expression particularly in cancer. There are few data on their expression and especially on their molecular profile. The aim of the present study is to investigate the expression of LAMP‐1 and LAMP‐2 genes and proteins in HGG. Newly diagnosed patients with HGG and healthy controls were examined by immunohistochemistry and qPCR for both protein and mRNA levels of LAMP‐1 and LAMP‐2. The transcriptional activity of LAMP‐1 in HGG was significantly higher compared to normal brain and to LAMP‐2. The two glycoproteins were detected in the cytosol of tumor cells with varying intensity, LAMP‐1 showing again enhanced expression. In conclusion, novel data on LAMP‐1 overexpression in HGG are presented suggesting involvement of this gene and protein in cell adhesion and tumor progression. These findings might help the elucidation of the complex biological role of the multifunctional LAMPs proteins and to predict novel therapeutic targets in lysosomes.
High incidence of autoimmune gastritis in patients misdiagnosed with two or more failures of H. pylori eradication
Authors: Furuta T. , Baba S. , Yamade M. , Uotani T. , Kagami T. , Suzuki T. , Tani S. , Hamaya Y. , Iwaizumi M. , Osawa S. , Sugimoto K.
Published: June 2018

Background

Although autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure.

Aims

We investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history.

Methods

A total of 404 consecutive patients who visited the H. pylori‐specific out‐patient unit of our hospital from June 2015 to June 2017 were enrolled. Of these, 137 were treatment‐naive, 47 had failed treatment once (single failure), and 220 had failed treatment twice or more (multiple failures) by 13C‐UBT. Gastroscopy was performed in all patients. Culture tests of gastric mucosal samples were performed for H. pylori and other bacteria positive for urease activity. Anti‐parietal cell antibody (APCA) was measured. Patients with severe atrophy in the gastric corpus and positivity for APCA were diagnosed as having AIG.

Results

A total of 43 patients were diagnosed as having AIG, of whom two were treatment‐naive (1.5%, 2/137), 1 failed eradication once (2.1% 1/47), and 40 failed treatment at least twice (18.2%, 40/220). The incidence of AIG was significantly higher in the multiple failure group than in the single failure or treatment‐naive groups. Urease‐positive bacteria, such as Klebsiella pneumoniae and alpha‐streptococcus, were identified in 33 of the 35 AIG patients who underwent culture testing.

Conclusion

AIG patients were often misdiagnosed as refractory to eradication therapy, probably because achlorhydria in AIG might allow urease‐positive bacteria other than H. pylori to colonise the stomach, causing positive 13C‐UBT results.
The Production of Thin‐Walled Jointless Gold Beads from the Maykop Culture Megalithic Tomb of the Early Bronze Age at Tsarskaya in the North Caucasus: Results of Analytical and Experimental Research
Authors: Trifonov V. A. , Shishlina N. I. , Loboda A. Yu. , Kolobylina N. N. , Tereschenko E. Yu. , Yatsishina E. B.
Published: June 2018

This study, the first of this kind, reconstructs the technicalchaîne operatoireof thin‐walled jointless gold bead production in the Maykop culture on the basis of trace‐wear analysis, experimental research and comparative analysis, using gold beads from the Early Bronze Age dolmen (c. 3200–2900bc) in kurgan 2 at Tsarskaya (discovered in 1898). The results of the study demonstrate that such beads were produced from a perforated disc‐shaped blank by pressure (with intermittent annealing) within a hemispherical depression in a shaping block (presumably made from stone or bone) and subsequent abrasive treatment of the surface. Most probably, this technique was a regional expression of Near Eastern jewellery traditions that emerged within the urbanized centres of Upper Mesopotamia in the early fourth millenniumbcand spread out, through the Caucasus, into the southern boundaries of the Eurasian steppe.
Self‐ownership, relational dignity, and organ sales
Authors: Hershenov David
Published: June 2018

Material property has traditionally been conceived of as separable from its owner and thus alienable in an exchange. So it seems that you could sell your watch or even your kidney because it can be removed from your wrist or abdomen and transferred to another. However, if we are each identical to a living human animal, self‐ownership is impossible for self‐separation is impossible. We thus cannot sell our parts if we don't own the whole that they compose. It would be incoherent to own all of your body's parts but not the whole body; and it would be arbitrary to own some but not all of your removable parts. These metaphysical obstacles to organ sales do not apply to the selling of the organs of the deceased. The human being goes out of existence at death and is not identical to the body's remains. Any objections to selling the organs of the deceased must instead be due to dignity rather than metaphysical or conceptual considerations. But the remains lack the intrinsic dignity of the human being, instead possessing, at best, relational dignity. Relational dignity would not provide sufficient reason to prohibit life‐saving sales.
Physical Activity Classification with Dynamic Discriminative Methods
Authors: Ray Evan L. , Sasaki Jeffer E. , Freedson Patty S. , Staudenmayer John
Published: June 2018

A person's physical activity has important health implications, so it is important to be able to measure aspects of physical activity objectively. One approach to doing that is to use data from an accelerometer to classify physical activity according to activity type (e.g., lying down, sitting, standing, or walking) or intensity (e.g., sedentary, light, moderate, or vigorous). This can be formulated as a labeled classification problem, where the model relates a feature vector summarizing the accelerometer signal in a window of time to the activity type or intensity in that window. These data exhibit two key characteristics: (1) the activity classes in different time windows are not independent, and (2) the accelerometer features have moderately high dimension and follow complex distributions. Through a simulation study and applications to three datasets, we demonstrate that a model's classification performance is related to how it addresses these aspects of the data. Dynamic methods that account for temporal dependence achieve better performance than static methods that do not. Generative methods that explicitly model the distribution of the accelerometer signal features do not perform as well as methods that take a discriminative approach to establishing the relationship between the accelerometer signal and the activity class. Specifically, Conditional Random Fields consistently have better performance than commonly employed methods that ignore temporal dependence or attempt to model the accelerometer features.
Phase III randomized study of the proposed adalimumab biosimilar GP2017 in psoriasis: impact of multiple switches
Authors: Blauvelt A. , Lacour J.-P. , Fowler J.F. , Weinberg J.M. , Gospodinov D. , Schuck E. , Jauch-Lembach J. , Balfour A. , Leonardi C.L.
Published: June 2018

Background

Adalimumab is used to treat several inflammatory diseases, including plaque psoriasis. GP2017 is a proposed adalimumab biosimilar.

Objectives

To assess the impact of multiple switches between GP2017 and reference adalimumab (ref-ADMB) following the demonstration of equivalent efficacy and similar safety and immunogenicity, in adult patients with active, clinically stable, moderate-to-severe plaque psoriasis.

Methods

This 51-week double-blinded, phase III study randomly assigned patients to GP2017 (n = 231) or ref-ADMB (n = 234) 80 mg subcutaneously at week 0, then 40 mg biweekly from week 1. At week 17, patients were rerandomized to switch (n = 126) or continue (n = 253) treatment. The primary end point was patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16, with equivalence confirmed if the 95% confidence interval (CI) for the difference in PASI 75 between treatments was ± 18%. The key secondary end point was the change from baseline to week 16 in continuous PASI. Other end points were PASI over time; PASI 50, 75, 90 and100; pharmacokinetics; safety; tolerability and immunogenicity for the switched and continued treatment groups.

Results

Equivalent efficacy between GP2017 and ref-ADMB was confirmed for the primary (66·8% and 65·0%, respectively; 95% CI −7·46 to 11·15) and key secondary end points (−60·7% and −61·5%, respectively; 95% CI –3·15 to 4·84). PASI improved over time and was similar between treatment groups at week 16, and the switched and continued groups from weeks 17 to 51. There were no relevant safety or immunogenicity differences between GP2017 and ref-ADMB at week 16, or the switched and continued groups from weeks 17 to 51. No hypersensitivity to adalimumab was reported upon switching.

Conclusions

Following the demonstration of GP2017 biosimilarity to ref-ADMB, switching up to four times between GP2017 and ref-ADMB had no detectable impact on efficacy, safety or immunogenicity.
Role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer
Authors: Shinke Go , Yamada Daisaku , Eguchi Hidetoshi , Iwagami Yoshifumi , Asaoka Tadafumi , Noda Takehiro , Wada Hiroshi , Kawamoto Koichi , Gotoh Kunihito , Kobayashi Shogo , Takeda Yutaka , Tanemura Masahiro , Mori Masaki , Doki Yuichiro
Published: June 2018

Current therapies for pancreatic ductal cancer (PDAC) do not sufficiently control distant metastasis. Thus, new therapeutic targets are urgently needed. Numerous studies have suggested that the epithelial‐mesenchymal transition (EMT) is pivotal for metastasis of carcinomas. The fact that the EMT is reversible suggests the possibility that it is induced by an epigenetic mechanism. In this study, we aimed to investigate the role of histone deacetylase 1 (HDAC1), which is an epigenetic mechanism on distant metastasis of PDAC. We investigated the HDAC1 expression in 103 resected PDAC specimens obtained from patients who were treated with/without preoperative therapy using immunohistochemistry. To validate the findings in the clinical samples, we evaluated the HDAC1 activity, the EMT‐associated genes and the migration/invasion ability in vitro, and performed an HDAC1 inhibitor assay. The high expression of HDAC1 in clinical samples was significantly associated with poor progression‐free survival, especially distant metastasis‐free survival. In vitro, HDAC1 inhibitors decreased the invasion ability and reversed the EMT change; the only factor to show a concomitant decrease was the expression of SNAIL. We confirmed that the HDAC1 expression was associated with the SNAIL expression in clinical samples. Moreover, the resistant cells and parental cells did not show any significant differences in the expression of HDAC1; this was consistent with the finding that preoperative therapy did not alter the HDAC1 expression in clinical samples. The targeting of HDAC1, which could suppress metastasis by inhibiting the EMT, is a promising treatment option for PDAC.
Fumarate hydratase inactivation in hereditary leiomyomatosis and renal cell cancer is synthetic lethal with ferroptosis induction
Authors: Kerins Michael J. , Milligan John , Wohlschlegel James A. , Ooi Aikseng
Published: June 2018

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome characterized by inactivation of the Krebs cycle enzyme fumarate hydratase (FH). HLRCC patients are at high risk of developing kidney cancer of type 2 papillary morphology that is refractory to current radiotherapy, immunotherapy and chemotherapy. Hence, an effective therapy for this deadly form of cancer is urgently needed. Here, we show that FH inactivation (FH−/−) proves synthetic lethal with inducers of ferroptosis, an iron‐dependent and nonapoptotic form of cell death. Specifically, we identified gene signatures for compound sensitivities based on drug responses for 9 different drug classes against the NCI‐60 cell lines. These signatures predicted that ferroptosis inducers would be selectively toxic to FH−/− cell line UOK262. Preferential cell death against UOK262‐FH−/− was confirmed with 4 different ferroptosis inducers. Mechanistically, the FH−/− sensitivity to ferroptosis is attributed to dysfunctional GPX4, the primary cellular defender against ferroptosis. We identified that C93 of GPX4 is readily post‐translationally modified by fumarates that accumulate in conditions of FH−/−, and that C93 modification represses GPX4 activity. Induction of ferroptosis in FH‐inactivated tumors represents an opportunity for synthetic lethality in cancer.
Family Turbulence and Child Internalizing and Externalizing Behaviors: Moderation of Effects by Race
Authors: Womack Sean R. , Taraban Lindsay , Shaw Daniel S. , Wilson Melvin N. , Dishion Thomas J.
Published: June 2018

This study examined the impact of residential instability and family structure transitions on the development of internalizing and externalizing problems from age 2 through 10.5. Child's race was examined as a moderator. Caregiver reports of internalizing and externalizing behaviors were obtained on 665 children at ages 5 and 10.5. Early‐childhood residential and family structure transitions predicted elevated internalizing and externalizing problems at ages 5 and 10.5, but only for Caucasian children. These findings suggest that residential and family structure instability during early childhood independently contribute to children's later emotional and behavioral development, but vary as a function of the child's race. Community organizations (e.g., Women, Infant, and Children) can connect turbulent families with resources to attenuate effects of residential and family structure instability.
Immunotherapy with oral administration of humanized anti-CD3 monoclonal antibody: a novel gut-immune system-based therapy for metaflammation and NASH
Authors: Ilan Y , Shailubhai K , Sanyal A
Published: June 2018

The immune system plays a role in the pathogenesis of non-alcoholic steatohepatitis (NASH) underlying hepatocyte injury and fibrosis progression at all disease stages. Oral administration of anti-CD3 monoclonal antibody (mAb) has been shown in preclinical studies to be an effective method for systemic immune modulation and alleviates immune-mediated disorders without T cell depletion. In the present review, we summarize the concept of the oral administration of humanized anti-CD3 mAb in patients with NASH and discuss the potential of this treatment to address the current requirements of treatments for NASH. Recently published preclinical and clinical data on oral administration of anti CD3 are discussed. Human trials have shown that the oral administration of anti-CD3 in healthy volunteers, patients with chronic hepatitis C virus (HCV) infection and patients with NASH and type 2 diabetes is safe and well tolerated, as well as biologically active. Oral anti-CD3 induces regulatory T cells, suppresses the chronic inflammatory state associated with NASH and exerts a beneficial effect on clinically relevant parameters. Foralumab is a fully human anti-CD3 mAb that has recently been shown to exert a potent anti-inflammatory effect in humanized mice. It is being developed for treatment of NASH and primary biliary cholangitis (PBC). Oral administration of anti CD3 may provide an effective therapy for patients with NASH.
Long‐term follow‐up of a large prospective cohort of patients with nonfunctioning pituitary adenomas: The outcome of a conservative management policy
Authors: Levy Miles J. , Robertson Iain J , Khalk Naima , Vitello Sabrina , Reddy Narendra , Bhake Ragini , Howlett Trevor A.
Published: June 2018

Objective

To assess the clinical outcome of a strategy of conservative monitoring of patients with nonfunctioning pituitary adenomas (NFPA) after pituitary surgery and in patients without surgery.

Design

Retrospective study of outcomes, using a clinical information system.

Patients

An unselected, clinical series of patients seen in a single centre between 1989 and 2015.

Measurements

Review of clinical information system data to obtain details and dates of surgery, radiotherapy, pituitary imaging and outcomes.

Results

We identified 190 cases of NFPA. Trans‐sphenoidal surgery (TSS) had been performed as primary therapy in 132 cases (all macro‐adenomas). At a mean 7.6‐years follow‐up after TSS without immediate pituitary radiotherapy, recurrence occurred in 10.7% of cases with no visible postoperative residual adenoma, 38.8% with intrasellar and 66.7% with extrasellar residuum. Recurrence was defined as growth of residual tumour requiring intervention. On survival analysis, at 10 years, recurrence‐free survival was 75% in patients with no residual tumour and 40% with intrasellar residuum. Recurrence occurred in 12.5% of 24 patients who had received postop radiotherapy. Patients were monitored conservatively without initial surgery in 65 patients. After a mean of 5‐year monitoring, only 20% required intervention during follow‐up (18.5% TSS) and 30.8% died of nonpituitary causes during follow‐up.

Conclusion

This study suggests that a conservative approach may be safe and appropriate in patients with NFPA if followed up with appropriate imaging surveillance, whether postoperative or without primary surgery.
Introduction of a colorectal cancer screening programme: results from a single‐centre study
Authors: Vermeer N. C. A. , Bahadoer R. R. , Bastiaannet E. , Holman F. A. , Meershoek‐Klein Kranenbarg E. , Liefers G. J. , van de Velde C. J. H. , Peeters K. C. M. J.
Published: June 2018

Aim

In 2014, a national colorectal cancer (CRC) screening programme was launched in the Netherlands. It is difficult to assess for the individual patients with CRC whether the oncological benefits of surgery will outweigh the morbidity of the procedure, especially in early lesions. This study compares patient and tumour characteristics between screen‐detected and nonscreen‐detected patients. Also, we present an overview of treatment options and clinical dilemmas when treating patients with early‐stage colorectal disease.

Method

Between January 2014 and December 2016, all patients with nonmalignant polyps or CRC who were referred to the Department of Surgery of the Leiden University Medical Centre in the Netherlands were included. Baseline characteristics, type of treatment and short‐term outcomes of patients with screen‐detected and nonscreen‐detected colorectal tumours were compared.

Results

A total of 426 patients were included, of whom 240 (56.3%) were identified by screening. Nonscreen‐detected patients more often had comorbidity (P = 0.03), the primary tumour was more often located in the rectum (P = 0.001) and there was a higher rate of metastatic disease (P < 0.001). Of 354 surgically treated patients, postoperative adverse events did not significantly differ between the two groups (P = 0.38). Of 46 patients with T1 CRC in the endoscopic resection specimen, 23 underwent surgical resection of whom only 30.4% had residual invasive disease at colectomy.

Conclusion

Despite differences in comorbidity, stage and surgical outcome of patients with screen‐detected tumours compared to nonscreen‐detected tumours were not significantly different. Considering its limited oncological benefits as well as the rate of adverse events, surgery for nonmalignant polyps and T1 CRC should be considered carefully.