bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple metachronous rare primary malignant tumors: A case report
Authors: Ying Xiaozhen , Zhang Heying , Chen Bizheng , Wu He , Bao Liming , Qian Shi , Ying Xihui
Published: August 2019

Multiple primary malignant tumors (MPMTs) are rarely seen among the patients with malignant neoplasms. Moreover, the existence of five MPMTs in the same patient is an extremely rare phenomenon. In this case, a 42‐year‐old male patient developed five metachronous MPMTs within 16 years and the duration between each malignant tumor shortened with the progression of the disease. Multidisciplinary treatments were used on this patient and he fought against the cancers until the end of his life. Our report provides us with a new awareness of MPMTs, which should be considered when we come across with cancer patients who develop various unexplainable symptoms after the diagnosis of the first neoplasm.
Pharmacogenetics of opioids: a narrative review
Authors: Kumar S. , Kundra P. , Ramsamy K. , Surendiran A.
Published: August 2019

Advances in the field of pharmacogenomics have resulted in the discovery of some important single‐nucleotide polymorphisms which are found to be associated with opioid dose variability. This, to a large extent, explains genetic variability in the analgesic dose of opioids. These polymorphisms are found in various areas relevant to pain perception, including the nociceptive and antinociceptive pathways, drug receptors, drug‐metabolising enzymes and drug efflux molecules. An in‐depth knowledge of single‐nucleotide polymorphisms can help clinicians to address interindividual variability in opioid dosing and requirements. In the era of precision medicine, these genetic markers can also help us to design prognostic tools to accurately predict the analgesic dose of opioids.
Lymphopaenia in the diagnosis of paediatric appendicitis: a false sense of security?
Authors: Greer Douglas , Bennett Peter , Wagstaff Benjamin , Croaker David
Published: August 2019

Background

Appendicitis is a common indication for emergent surgery in children; however, it is a small proportion of presentations with abdominal pain. As viral illness is a common differential diagnosis, lymphopaenia is used by some as a predictor against appendicitis. Furthermore, neutrophil–lymphocyte ratio (NLR) has been found to predict appendicitis. We aimed to verify if lymphopaenia predicted against appendicitis in children.

Methods

Retrospective review was conducted for all patients aged 15 years and under presenting with abdominal pain to our institution in 2017, and data including age, white cell count, neutrophil and lymphocyte count, NLR, C‐reactive protein and diagnosis of appendicitis were recorded. Statistical analysis was performed using Stata©. Receiver operating characteristic curves for various tests were formed and areas under curve (AUC) compared using regression, P < 0.05 was considered significant.

Results

A total of 1263 patients were presented, of whom 546 had their blood performed and were included, 86 had appendicitis and 460 did not. Neutrophilia was the best predictor for appendicitis (AUC = 0.86), significantly higher than NLR (0.81), P < 0.05. Lymphopaenia was a poor negative predictor of appendicitis (AUC = 0.46), and while isolated lymphopaenia was more predictive (AUC = 0.23) this was inferior to the positive prediction of neutrophilia, P < 0.05.

Conclusion

The value of isolated lymphopaenia to predict against appendicitis is largely accounted for inherently normal neutrophils, independently lymphopaenia has little value. NLR, while predictive, is a weaker predictor than neutrophilia.
Impacts of USAID and development assistance toward counterterrorism efforts: Empirical evidence in context of Pakistan
Authors: Shahzad Umer , Farooq Muhammad Umar , Qin Fengming
Published: August 2019

This article studies whether the pursuit of foreign aid for counterterrorism purposes militarizes or mitigates terrorism. It focuses on the USAID and official development assistance (ODA) flows to Pakistan, which recently has experienced an increase due to the presence of deadliest terrorist organizations. By using the time series data from 1985 to 2016, the paper investigated the foreign aid and terrorism nexus for pre‐9/11 and post‐9/11 periods. The empirical estimations of autoregressive distributed lag bound testing approach reported that an increase in military expenditures fuels terrorism in post‐9/11 period and the ODA helps to control terrorism from the country. On the contrary, USAID reported insignificant response toward terrorist attacks in pre‐ and post‐9/11 periods, suggesting that the foreign aid from the United States has no significant impact on counterterrorism policies for Pakistan. The outcomes of the current study can be utilized in policymaking of counterterrorism and to explore the nexus between foreign aid, terrorism, and military expenditures. The paper concludes that the concerns about the use of foreign aid as counterterrorism tool are warranted, but that actual manifestations are nuanced.
Longitudinal exposure of English primary care patients to pharmacogenomic drugs: An analysis to inform design of pre‐emptive pharmacogenomic testing
Authors: Kimpton James E. , Carey Iain M. , Threapleton Christopher J.D. , Robinson Alexandra , Harris Tess , Cook Derek G. , DeWilde Stephen , Baker Emma H.
Published: August 2019

Aims

To investigate the longitudinal exposure of English primary care patients to pharmacogenomic drugs to inform design of pre‐emptive testing.

Methods

Sixty‐three drugs were identified with dosing guidelines based on variants of 19 pharmacogenes in the Pharmacogenomics Knowledgebase on 01 September 2018. Prescribing of these pharmacogenomic drugs between 1993 and 2017 was summarised for a sample of 648 141 English patients aged 50–99 years on 01 January 2013, registered with Clinical Practice Research Datalink practices during 2011–12. Exposure of patients to pharmacogenomic drugs retrospectively (2, 10, 20 y) and prospectively (5 y) was described.

Results

During 2011–12, 58% of patients were prescribed at least 1 pharmacogenomic drug, increasing to 80% over the previous 20 years. Multiple exposure was common, with 47% patients prescribed ≥2 pharmacogenomic drugs and 7% prescribed ≥5 pharmacogenomic drugs over the next 5 years. The likelihood of exposure to pharmacogenomic drugs increased with age, with 89% patients ≥70 years prescribed at least 1 pharmacogenomic drug over the previous 20 years. Even among those aged 50–59 years, 71% were prescribed at least 1 pharmacogenomic drug over the previous 20 years. The pharmacogenomic drugs prescribed to the most patients were for pain relief, gastroprotection, psychiatric and cardiovascular conditions. Three pharmacogenes (CYP2D6, CYP2C19 and SLCO1B1) accounted for >95% pharmacogenomic drugs prescribed.

Conclusions

In primary care patients, exposure to pharmacogenomic drugs is extremely common, multiplicitous and has commenced by relatively early adulthood. A small number of pharmacogenes account for the majority of drugs prescribed. These findings could inform design of pre‐emptive pharmacogenomic testing for implementation in primary care.
CD4+ count‐dependent concentration–effect relationship of rituximab in rheumatoid arthritis
Authors: Bensalem Amina , Mulleman Denis , Thibault Gilles , Azzopardi Nicolas , Goupille Philippe , Paintaud Gilles , Ternant David
Published: August 2019

Aims

Rituximab is approved in rheumatoid arthritis (RA). A substantial decrease in CD4+ count was observed in responders after a single cycle of treatment. This study aimed to describe and quantifying the influence of CD4+ count depletion on the concentration–response relationship of rituximab in RA patients.

Methods

In this retrospective monocentric observational study, 52 patients were assessed. Repeated measurements of rituximab concentrations (pharmacokinetics), CD4+ counts (biomarker) and disease activity score in 28 joints (DAS28, clinical response) were made. Rituximab pharmacokinetics was described using a 2‐compartment model, and CD4+ cell counts and DAS28 measurements were described using indirect turnover and direct Emax pharmacokinetic–pharmacodynamic models, respectively. Delay between rituximab concentrations and responses was accounted for by including biophase compartments.

Results

Elimination half‐life of rituximab was 18 days. The pharmacokinetic–pharmacodynamic model showed that DAS28 response to rituximab was partly associated with CD4+ cell depletion. At 6 months, a deeper DAS28 decrease was observed in patients when CD4+ cell count is decreased: median [interquartile range] of DAS28 was 3.7 [2.9–4.4] and 4.5 [3.7–5.3] in patients with and without CD4+ decrease, respectively.

Conclusions

This is the first study to quantify the relationship between rituximab concentrations, CD4+ count and DAS28 in RA patients. This model showed that approximately 75% of patients had CD4+ count decrease, and that the clinical improvement is 2‐fold higher in patients with CD4+ cells decrease than in others.
The somatic integration definition of the beginning of life
Authors: Brown Mark T.
Published: August 2019

The somatic integration definition of life is familiar from the debate on the determination of death, with some bioethicists arguing that it supports brain death while others argue that some brain‐dead bodies exhibit sufficient somatic integration for biological life. I argue that on either interpretation, the somatic integration definition of life implies that neither the preimplantation embryo nor the postimplantation embryo meet the somatic integration threshold condition for organismal human life. The earliest point at which a somatic integration determination of life could be made would be the beginning of the fetal stage, 9 weeks postfertilization. Bioethical implications are considered, specifically with respect to the moral status of the postimplantation embryo in embryo research and abortion.
Design, synthesis, and in vitro antitumor activity of a transferrin receptor‐targeted peptide–doxorubicin conjugate
Authors: Li Songtao , Zhao Hongling , Fan Yanfang , Zhao Guiqin , Wang Ruxing , Wen Fuyu , Wang Jianping , Wang Xiaohui , Wang Yu , Gao Yang
Published: August 2019

In this study, a peptide–drug conjugate was designed and synthesized by connecting a transferrin receptor (TfR)‐targeted binding peptide analog BP9a (CAHLHNRS) with doxorubicin (DOX) through N‐succinimidyl‐3‐maleimidopropionate (SMP) as the cross‐linker. Confocal laser scanning microscopy results indicated that free DOX mainly accumulated in the nuclei of both TfR overexpressed HepG2 hepatoma cells and L‐O2 normal liver cells expressing low level of TfR; most of the BP9a‐DOX conjugate displayed cytoplasmic location, and its cellular uptake by HepG2 cells was obviously reduced by TfR blockage test. Nevertheless, the cellular uptake of this conjugate by L‐O2 cells was much less than that of free DOX. Meanwhile, the BP9a‐DOX conjugate exhibited lower in vitro antiproliferative activity against HepG2 cells than free DOX, but its cytotoxic effect on L‐O2 cells was decreased compared with that of free DOX. These results suggest that BP9a could be applied as a potential TfR‐targeted peptide vector for selective drug delivery.
Preschool Self‐Regulation and Preacademic Skills as Mediators of the Long‐Term Impacts of an Early Intervention
Authors: McCoy Dana C. , Gonzalez Kathryn , Jones Stephanie
Published: August 2019

This study explores children's early academic and self‐regulatory skills as potential pathways through which a preschool enrichment program—the Chicago School Readiness Project (CSRP)—may contribute to low‐income children's long‐term outcomes (N = 466; Mage at baseline = 4.10 years). We find that CSRP's impact on high school grades may be partially explained by early gains in vocabulary and math skills. Although impacts on high school executive function (EF) were more equivocal, our results suggest that early improvements in math skills attributable to the intervention may, in turn, predict long‐term gains in EF skills. These results complement the existing literature on preschool fade out, while also shedding light on the cross‐domain relations between academic and self‐regulatory skills.
Psychological services for food allergy: The unmet need for patients and families in the United Kingdom
Authors: Knibb Rebecca , Halsey Mary , James Polly , du Toit George , Young Judith
Published: August 2019

Research over the past 20 years has demonstrated the significant impact food allergy can have on quality of life and mental health of patients and their families, yet there is a paucity of psychological services to support families in coping with this condition. This paper provides a short overview of the psychological impact of food allergy, followed by a discussion of the use of paediatric psychological services for long‐term conditions. To our knowledge, few paediatric allergy clinics in the UK have funding for dedicated clinical psychology services. Two such services are based at Southampton General Hospital and the Evelina London Children's Hospital. This paper includes descriptions of these services and how they are currently being used by patients and families. This is followed by an allergy clinician's perspective on the use of psychological services. Recommendations are made for allergy services to work with hospital psychology services to develop, integrate and deliver psychological services for all patients with allergy and their families who are in need. Future research also needs to focus on the efficacy of psychological therapies and group interventions in food allergy.
Practitioner insights as a means of setting a context for conservation
Authors: Sanders Michele Jeanette , Miller Laura , Bhagwat Shonil A. , van der Grient Jesse Marije Anne , Rogers Alex David
Published: August 2019

A key obstacle to conservation success is the tendency of conservation professionals to tackle each challenge individually rather than collectively and in context. We sought to prioritize barriers to conservation previously described in the conservation literature. We undertook an online survey of 154 practitioners from over 70 countries to ascertain the most important barriers to conservation they faced. We used statistical analyses to identify the key impediments to conservation success and to examine whether these were affected by organizational attributes. Twenty‐one barriers were identified. The importance ascribed to those was influenced by continent of operation and organization size, but not by organization age or autonomy (from larger parent organizations). We found the most important barriers to consider when undertaking conservation action were wider issues (e.g., population growth, consumerism, favoring development, and industrial‐scale activity), operating environment (e.g., lack of political will, ineffective law enforcement, weak governments, corruption, safety and security), community attributes (e.g., dynamics, conflicts, and education levels), and the way conservation is undertaken (overconfidence, lack of funding, and externally set agendas). However, we advise against applying a one‐size‐fits‐all approach. We propose that conservationists account for the complex socioecological systems they operate in if they are to achieve success.
909. CYMBIDIUM SICHUANICUM
Authors: Cribb Phillip , Schuiteman André , Want Terry
Published: August 2019

Cymbidium sichuanicum is illustrated and its habitat is described. Distinctions from related species are discussed, and suggestions for its cultivation are given.
911. COELOGYNE KALIANA
Authors: Cribb Phillip , Schuiteman André , Want Terry
Published: August 2019

Coelogyne kaliana from Malaysia is illustrated and the history of its collection and habitat are described. Distinctions from related species are discussed, and suggestions for its cultivation are given.
912. PETROCOSMEA THERMOPUNCTA
Authors: Shaw Julian M. H.
Published: August 2019

Petrocosmea thermopuncta, a probable hybrid species from Yunnan, is described and illustrated. Formerly known in cultivation as P. grandiflora, this taxon is named thermopuncta (hotspot) with reference to the dark spot in the corolla tube and its growing in a biodiversity hotspot, (though of uncertain geographical provenance).
Impact of dietary protein on postprandial glycaemic control and insulin requirements in Type 1 diabetes: a systematic review
Authors: Paterson M. A. , King B. R. , Smart C. E. M. , Smith T. , Rafferty J. , Lopez P. E.
Published: August 2019

Aim

Postprandial hyperglycaemia is a challenge for people living with Type 1 diabetes. In addition to carbohydrate, dietary protein has been shown to contribute to postprandial glycaemic excursions with recommendations to consider protein when calculating mealtime insulin doses. The aim of this review is to identify and synthesize evidence about the glycaemic impact of dietary protein and insulin requirements for individuals with Type 1 diabetes.

Methods

A systematic literature search of relevant biomedical databases was performed to identify research on the glycaemic impact of dietary protein when consumed alone, and in combination with other macronutrients in individuals with Type 1 diabetes.

Results

The review included 14 published studies dated from 1992 to 2018, and included studies that researched the impact of protein alone (n = 2) and protein in a mixed meal (n = 12). When protein was consumed alone a glycaemic effect was not seen until ≥ 75 g. In a carbohydrate‐containing meal ≥ 12.5 g of protein impacted the postprandial glucose. Inclusion of fat in a high‐protein meal enhanced the glycaemic response and further increased insulin requirements. The timing of the glycaemic effect from dietary protein ranged from 90 to 240 min. Studies indicate that the postprandial glycaemic response and insulin requirements for protein are different when protein is consumed alone or with carbohydrate and/or fat.

Conclusions

This systematic review provides evidence that dietary protein contributes to postprandial glycaemic excursions and insulin requirements. These insights have important implications for the education of people with Type 1 diabetes and highlights the need for more effective insulin dosing strategies for mixed macronutrient meals.
Prevalence and characteristics of renal artery fibromuscular dysplasia in hypertensive women below 50 years old
Authors: Di Monaco Silvia , Lengelé Jean‐Philippe , Heenaye Sheik , Danse Etienne , Hammer Frank , Lopez‐Sublet Marilucy , Toubiana Laurent , Rabbia Franco , Persu Alexandre
Published: August 2019

Background

Renal fibromuscular dysplasia (FMD) is typically diagnosed in young hypertensive women. The 2014 European FMD Consensus recommended screening in all hypertensive women <30 yo. However, the prevalence of renal FMD in young/middle‐aged hypertensive women remains unclear. The aim of this work was to assess the prevalence and characteristics of renal FMD in hypertensive women ≤50 yo.

Methods

We retrospectively included all consecutive women aged ≤50 years referred to our Hypertension Unit from 2014 to 2017 and collected standardized information on patient characteristics and screening modalities.

Results

Of 1083 incident hypertensive patients, 157 patients fitted with inclusion criteria. The prevalence of renal FMD varied between 3.2% in the whole sample and 7.5% in patients explored by CTA and/or MRA (n = 67). In the subgroup of patients ≤30 yo (n = 32), the corresponding figures were 3.1% and 5.6%. The yearly prevalence of FMD tended to increase over time, in parallel with increased use of CTA/MRA as a first‐line imaging modality. Out of 5 patients with renal FMD, 2 were revascularized and 1 had extra‐renal FMD.

Conclusions

The prevalence of renal FMD in young/middle‐aged hypertensive women is probably one order of magnitude higher than previously assumed, in the range of 3%‐8%, depending on imaging modalities. While the diagnosis of FMD does not influence short‐term management in all patients, it may allow close monitoring and prevention of complications of the disease over time. This analysis provides the rationale for a prospective, multicentre study aiming at determining the cost‐effectiveness of systematic screening for renal FMD.
Microglia cytoarchitecture in the brain of adenosine A2A receptor knockout mice: Brain region and sex specificities
Authors: Simões-Henriques Carla , Mateus‐Pinheiro Miguel , Gaspar Rita , Pinheiro Helena , Mendes Duarte Joana , Baptista Filipa I. , Canas Paula M. , Fontes-Ribeiro Carlos Alberto , Cunha Rodrigo A. , Ambrósio António F. , Gomes Catarina A.
Published: August 2019

Microglia cells exert a critical role in brain development, mainly supported by their immune functions, which predicts an impact on the genesis of psychiatric disorders. In fact, microglia stress during gestation is, for instance, associated with chronic anxiety and cognitive deficits accompanied by long‐lasting, region‐ and sex‐specific changes in microglia morphology. We recently reported that the pattern of microglia morphologic plasticity, which is sex‐determined, impacts on anxious‐like behaviour and cognition. We also reported that the pharmacologic blockade of adenosine A2A receptors (A2AR) is able to reshape microglia morphology, in a sex‐specific manner and with behavioural sequelae. In order to better understand the role of A2AR in the sex differentiation of microglia, we now compared their morphology in wild‐type and A2AR knockout male and female C57BL/6 mice in two cardinal brain regions implicated in anxiety‐like behaviour and cognition, the prefrontal cortex (PFC) and the dorsal hippocampus (dHIP). We report interregional differences between PFC and dHIP in a sex‐specific manner: while males presented more complex microglia in the dHIP, microglia from females had a more complex morphology in the PFC. Surprisingly, the genetic deletion of A2AR did not alter these sex differences, but promoted the exclusive remodelling (increase in complexity) in PFC microglia from females. These findings further support the existence of a heterogeneous microglial network, distinct between sexes and brain regions, and help characterizing the role of A2AR in the sex‐ and brain region‐specific morphologic differentiation of microglia.
Pathological responses to single‐pulse electrical stimuli in epilepsy: The role of feedforward inhibition
Authors: Hebbink Jurgen , Huiskamp Geertjan , van Gils Stephan A. , Leijten Frans S. S. , Meijer Hil G. E.
Published: August 2019

Delineation of epileptogenic cortex in focal epilepsy patients may profit from single‐pulse electrical stimulation during intracranialEEGrecordings. Single‐pulse electrical stimulation evokes early and delayed responses. Early responses represent connectivity. Delayed responses are a biomarker for epileptogenic cortex, but up till now, the precise mechanism generating delayed responses remains elusive. We used a data‐driven modelling approach to study early and delayed responses. We hypothesized that delayed responses represent indirect responses triggered by early response activity and investigated this for 11 patients. Using two coupled neural masses, we modelled early and delayed responses by combining simulations and bifurcation analysis. An important feature of the model is the inclusion of feedforward inhibitory connections. The waveform of early responses can be explained by feedforward inhibition. Delayed responses can be viewed as second‐order responses in the early response network which appear when input to a neural mass falls below a threshold forcing it temporarily to a spiking state. The combination of the threshold with noisy background input explains the typical stochastic appearance of delayed responses. The intrinsic excitability of a neural mass and the strength of its input influence the probability at which delayed responses to occur. Our work gives a theoretical basis for the use of delayed responses as a biomarker for the epileptogenic zone, confirming earlier clinical observations. The combination of early responses revealing effective connectivity, and delayed responses showing intrinsic excitability, makes single‐pulse electrical stimulation an interesting tool to obtain data for computational models of epilepsy surgery.
Does Parkinson's disease increase the risk of cardiovascular events? A systematic review and meta‐analysis
Authors: Alves M. , Caldeira D. , Ferro J. M. , Ferreira J. J.
Published: August 2019

Background and purpose

The impact of Parkinson's disease (PD) on the risk of cardiovascular disease is poorly known. The aim was to systematically review observational studies evaluating the association between PD and cardiovascular events.

Methods

MEDLINE through PubMed, the Web of Science and Cochrane Central Register of Controlled Trials with conference proceedings were searched from inception to 4 July 2019. Two reviewers independently selected studies comparing cardiovascular events between Parkinson's disease and control groups. Ischaemic stroke, myocardial infarction and cardiovascular mortality were the outcomes of interest. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were derived by random effects meta‐analysis. Heterogeneity was assessed using the I2 test. The study protocol was registered at PROSPERO: CRD42017076527.

Results

Eleven studies were included: nine cohort studies and two case–control studies. PD was associated with a significantly increased risk of stroke (nine studies: OR 1.66, 95% CI 1.19, 2.34; I2 = 50%). No significant differences were detected regarding myocardial infarction risks (eight studies: OR 1.15, 95% CI 0.72, 1.83; I2 = 76%) nor cardiovascular mortality risks (seven studies: OR 1.11, 95% CI 0.85, 1.45; I2 = 47%) in PD patients.

Conclusions

The best evidence available showed an association between PD and increased risk of stroke. The risk of myocardial infarction and cardiovascular mortality was not different in PD and non‐PD individuals.
Epilepsy in systemic lupus erythematosus: prevalence and risk factors
Authors: Hopia L. , Andersson M. , Svenungsson E. , Khademi M. , Piehl F. , Tomson T.
Published: August 2019

Background and purpose

The aim was to study the prevalence of epilepsy in a hospital‐based systemic lupus erythematosus (SLE) cohort and to investigate the relationship between epilepsy and other manifestations of neuropsychiatric SLE (NPSLE).

Methods

The study population consisted of 440 SLE patients recruited from 1998 to 2012. An epilepsy‐screening questionnaire was sent to all patients, where those screening positive were invited to a neurological examination with documentation of NPSLE symptoms according to the American College of Rheumatology nomenclature. Occurrences of autoantibodies (double stranded DNAantibody, antinuclear antibody, lupus anticoagulant, Sjögren's syndrome A, Sjögren's syndrome B) and the antiphospholipid syndrome (APS) were tabulated.

Results

Out of 440 patients, 14% were dead and 2.7% were lost to follow‐up. The questionnaire was sent to 368 patients; 312 (85%) responded. Of these, 131 (42%) screened positive. Epilepsy was confirmed in 36 (11.5%), of whom 30 (83%) had focal onset. Ten (3.2%) patients had isolated or provoked seizures. Manifestations of NPSLE occurred in 50%. The rates of cerebrovascular disease and psychosis were elevated two‐ and three‐fold in NPSLE patients with epilepsy versus NPSLE patients without epilepsy, respectively (P = 0.001 and P = 0.0006). APS was more common in patients with epilepsy compared to epilepsy‐free SLE patients with or without NPSLE (P = 0.02). In 50% of patients with epilepsy, no other etiology than SLE was detected.

Conclusions

A high prevalence of epilepsy in SLE patients is reported, with association to concurrent cerebrovascular disease, APS and psychosis. Our findings support the notion of a multifactorial background for epilepsy in SLE including both vascular disease and features consistent with autoimmunity.
A multimodal conversational coach for active ageing based on sentient computing and m‐health
Authors: Griol David , Molina José Manuel , Sanchis Araceli
Published: August 2019

As life expectancy increases, it has become more necessary to find ways to support healthy ageing. A number of active ageing initiatives are being developed nowadays to foster healthy habits in the population. This paper presents our contribution to these initiatives in the form of a multimodal conversational coach that acts as a coach for physical activities. The agent can be developed as an Android app running on smartphones and coupled with cheap widely available sport sensors in order to provide meaningful coaching. It can be employed to prepare exercise sessions, provide feedback during the sessions, and discuss the results after the exercise. It incorporates an affective component that informs dynamic user models to produce adaptive interaction strategies.
Toc‐Tum mini‐games: An educational game accessible for deaf culture based on virtual reality
Authors: Chaves Edilson M. , Braga Paulo Bruno de A. , Montenegro Yuri Fontenelle L. , Rodrigues Vitória B. , Munguba Marilene C. , de Albuquerque Victor Hugo C.
Published: August 2019

Human hearing is an important sense, which complements the other senses, and is essential for children to begin to acquire basic concepts of the world; however, in severe cases of disability, children become marginalized from these benefits. An example of this is with music, a deaf individual is to be able to perceive it. With this in mind, we developed a novel medical expert system based on virtual reality, called Toc‐Tum mini‐games, applying basic concepts of music in an accessible way to the deaf culture. The intelligent proposed system is validated in two different tests: (a) with the target audience to evaluate the interest in the game and (b) with professionals knowledgeable in the field of music or who have had contact with the deaf, evaluate the impact of the game teaching music to the deaf. The tests with the target audience showed that the methods of interaction allowed the children to understand most of the stages and that they were animated during the test days. Regarding the professionals, they were interested in the possibility of using the proposed system in question, even if some modifications in the design had to be made. The results showed that the Toc‐Tum mini‐games is an intelligent tool capable of introducing music in a playful and manageable way using a virtual environment.
Shifting perceptions of rapid temperature changes’ effects on marine fisheries, 1945–2017
Authors: McClenachan Loren , Grabowski Jonathan H. , Marra Madison , McKeon C. Seabird , Neal Benjamin P. , Record Nicholas R. , Scyphers Steven B.
Published: August 2019

Climate‐driven warming has both social and ecological effects on marine fisheries. While recent changes due to anthropogenic global warming have been documented, similar basin‐wide changes have occurred in the past due to natural temperature fluctuations. Here, we document the effects of rapidly changing water temperatures along the United States’ east coast using observations from fisheries newspapers during a warming phase (1945–1951) and subsequent cooling phase (1952–1960) of the Atlantic Multidecadal Oscillation, which we compared to similar recent observations of warming waters (1998–2017). Historical warming and cooling events affected the abundance of species targeted by fishing, the prevalence of novel and invasive species, and physical access to targeted species. Fishing communities viewed historical cooling waters twice as negatively as they did warming waters (72% vs. 35% of observations). Colder waters were associated with a decrease in fishing opportunity due to storminess, while warming waters were associated with the potential for new fisheries. In contrast, recent warming waters were viewed as strongly negative by fishing communities (72% of observations), associated with disease, reductions in abundances of target species, and shifts in distributions across jurisdictional lines. This increasing perception that warming negatively affects local fisheries may be due to an overall reduction of opportunity in fisheries over the past half century, an awareness of the relative severity of warming today, larger changes in American culture, or a combination of these factors. Negative perceptions of recent warming waters’ effects on fisheries suggest that fishing communities are currently finding the prospect of climate adaptation difficult.
Fish assemblage composition within the floodplain habitat mosaic of a tropical lake (Tonle Sap, Cambodia)
Authors: Pool Thomas , Elliott Vittoria , Holtgrieve Gordon , Arias Mauricio , Altman Irit , Kaufman Leslie , McCann Kevin , Fraser Evan D. G. , Tudesque Loïc , Chevalier Mathieu , Grenouillet Gael , Chea Ratha , Lek Sovan , McMeans Bailey , Cooperman Michael , Phen Chheng , Hannah Lee , Miller Ben , Guo Chuanbo , Nam So
Published: August 2019

Understanding how habitat heterogeneity is linked to biodiversity patterns within flood–pulse catchments is needed for their effective conservation. To study those communities, researchers have begun to explore how local environmental factors influence species composition patterns at relatively fine scales within complex habitat mosaics. However, a robust description of the link between communities’ composition and their floodplain habitat characteristics remains poorly articulated.

In the Tonle Sap Lake (TSL) of Cambodia, we evaluated whether mesohabitat‐scale (1–5 km) factors throughout the floodplain structured the fish assemblage temporally and spatially. First, we determined whether TSL fish assemblage changed seasonally and, if so, what assemblage components were driving that change. Second, we determined whether environmental factors structured fish composition across floodplain mesohabitat patches during the wet season. Third, we evaluated whether dominant species displayed affinities for specific areas within the floodplain during the wet season, potentially identifying critical mesohabitat patches for the fish assemblage.

Fish were collected from nine sites along an elevational gradient traversing the floodplain every 3 months from March 2014 through January 2015. Correspondence analysis and analysis of variance were used to assess seasonal variation in the species composition. Canonical correspondence analysis and a mantel test were then used to identify the significance of environmental factors structuring the fish assemblage.

Fish assemblages changed across seasons; in particular, migratory species occurrence decreased during the dry season. During the wet season, the fish assemblage was structured spatially by mesohabitat‐scale factors such as vegetation and water quality. Furthermore, the flooded forest mesohabitat directly adjacent to the permanent lake displayed particularly high species richness and abundance. However, a majority of TSL species appeared to be highly mobile, occurring across multiple floodplain mesohabitats.

We concluded that fish assemblage structure and floodplain mesohabitat use within TSL may depend strongly upon the maintenance of the natural flow regime. Since the flow regime will probably be modified by upstream dam development, trade‐offs will emerge between the cycle of fishing on which local residents depend, and the hydropower and agricultural benefits of damming the Mekong River system.
Passive acoustic monitoring shows no effect of anthropogenic noise on acoustic communication in the invasive round goby (Neogobius melanostomus)
Authors: Higgs Dennis M. , Humphrey Sarah R.
Published: August 2019

Passive acoustic monitoring (PAM) can be a powerful tool to survey populations of soniferous species in natural settings. Using PAM allows monitoring of behaviour and activity unobtrusively to get a more accurate assessment of behavioural responses than traditional techniques. The use of PAM can also be beneficial for behaviourally cryptic species or other taxa that might be missed by more traditional sampling methods.

To quantify seasonality of reproduction in an aquatic invasive species and to assess possible interactions between both abiotic and biotic noise and acoustic ecology, we deployed multiple hydrophones to fully characterise the acoustic behaviour of round goby (Neogobius melanostomus), a highly invasive species. We also aimed to quantify levels of anthropogenic noise around the goby communities. We tested correlations of round goby calling rates with overall noise levels and the presence of boat traffic as direct tests of the hypothesised role of noise on natural acoustic behaviour of fish.

Round goby showed a clear diel patterning of calling behaviour, with the highest activity during the night and ceasing at midday; supporting the importance of acoustic—as opposed to visual—signalling for mate attraction. Calls also allowed us to pinpoint spawning areas for possible remediation. We saw no correlation between measures of background noise and calling behaviour or presence of boats and calling, suggesting that increased levels of noise have no effect on the natural calling behaviour of this species.

Passive acoustic monitoring of round goby calling behaviour is a promising technique for those interested in remediation of this highly invasive species, as it can be difficult to quantify population levels by more conventional means. The lack of noise effects we see suggests that noise from recreational boats does not disrupt signalling in this species with limited hearing range, although more investigation is needed to ascertain whether noise could be a stressor in other contexts.
Intratumoral heterogeneity in programmed death‐ligand 1 immunoreactivity is associated with variation in non‐small cell lung carcinoma histotype
Authors: Naso Julia R , Wang Gang , Pender Alexandra , Wong Selina K , Zhu Jingyao , Ho Cheryl , Ionescu Diana N , Zhou Chen
Published: August 2019

Aims

Accurate assessment of programmed death‐ligand 1 (PD‐L1) levels in non‐small cell lung carcinoma (NSCLC) samples is complicated by intratumoral heterogeneity. We aimed to: (i) establish whether intratumoral PD‐L1 variation is associated with differences in local histotype; (ii) identify histotypes associated with a tendency for there to be higher or lower PD‐L1 scores; and (iii) estimate the frequency of clinically significant discordance in PD‐L1 levels between intratumoral histotype areas.

Methods and results

We reviewed 166 NSCLC resection specimens clinically tested for PD‐L1 with the 22C3 pharmDx assay. Multiple histotypes were present in 55% (68/123) of non‐mucinous adenocarcinoma samples. Solid histotypes had significantly higher PD‐L1 levels than other histotypes, both when samples were grouped by predominant histotype, and when histotype areas within a tumour were compared (P < 0.02). Lepidic areas had significantly lower PD‐L1 levels than other histotype areas within the same tumour (P < 0.02). Discordance between intratumoral histotype areas at a clinically relevant threshold (PD‐L1 tumour proportion score of 1% or 50%) was present in 32% (22/68) of non‐mucinous adenocarcinoma specimens with multiple histotype areas. The lepidic histotype was most frequently involved in discordance.

Conclusions

Intratumoral heterogeneity in PD‐L1 is associated with variation in histotype. Over‐representation of solid areas may increase the PD‐L1 score assigned to a tumour, whereas over‐representation of lepidic areas may decrease the PD‐L1 score. Evaluation of how histotype representation impacts on the predictive value of PD‐L1 testing is warranted.
Why does impression management positively influence interview ratings? The mediating role of competence and warmth
Authors: Amaral Amanda A. , Powell Deborah M. , Ho Jordan L.
Published: August 2019

Though interviews assess job applicants' skills and abilities, they can be influenced by extraneous factors, including impression management (IM) tactics. Interviewees’ self‐promotion and ingratiation IM tactics predict higher interview ratings; however, researchers have yet to determine why these tactics work. We assessed whether two fundamental dimensions of social perception, competence and warmth, mediate the relationship between IM tactics and interview ratings. We hypothesized that interviewee competence mediates the relationship between self‐promotion and interview ratings, and interviewee warmth mediates the relationship between ingratiation and interview ratings. Using real employment interviews, we found that competence mediates the relationship between self‐promotion and interview ratings, but warmth did not mediate the relationship between ingratiation and interview ratings in the way we expected.
Variants of consumption‐wealth ratios and predictability of U.S. government bond risk premia
Authors: Çepni Oğuzhan , Gupta Rangan , Wohar Mark E.
Published: August 2019

This paper compares the ability of alternative consumption‐wealth ratios, based on constant parameter (cay), Markov‐switching (cay
MS), and time‐varying parameter (cay
TVP) cointegration estimation of the consumption function, for predicting in‐ and out‐of‐sample movements of quarterly excess returns of U.S. government bonds over 1953:Q2 to 2015:Q3. Our findings show that after controlling for standard financial and macroeconomic factors, cay outperforms the cay
MS and cay
TVP in predicting the path of excess returns on bonds.
DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild‐type NSCLC cells to AZD9291
Authors: Li Yang‐ling , Ding Ke , Hu Xiu , Wu Lin‐wen , Zhou Dong‐mei , Rao Ming‐jun , Lin Neng‐ming , Zhang Chong
Published: August 2019

DYRK1A is considered a potential cancer therapeutic target, but the role of DYRK1A in NSCLC oncogenesis and treatment requires further investigation. In our study, high DYRK1A expression was observed in tumour samples from patients with lung cancer compared with normal lung tissues, and the high levels of DYRK1A were related to a reduced survival time in patients with lung cancer. Meanwhile, the DYRK1A inhibitor harmine could suppress the proliferation of NSCLC cells compared to that of the control. As DYRK1A suppression might be effective in treating NSCLC, we next explored the possible specific molecular mechanisms that were involved. We showed that DYRK1A suppression by siRNA could suppress the levels of EGFR and Met in NSCLC cells. Furthermore, DYRK1A siRNA could inhibit the expression and nuclear translocation of STAT3. Meanwhile, harmine could also regulate the STAT3/EGFR/Met signalling pathway in human NSCLC cells. AZD9291 is effective to treat NSCLC patients with EGFR‐sensitivity mutation and T790 M resistance mutation, but the clinical efficacy in patients with wild‐type EGFR remains modest. We showed that DYRK1A repression could enhance the anti‐cancer effect of AZD9291 by inducing apoptosis and suppressing cell proliferation in EGFR wild‐type NSCLC cells. In addition, harmine could enhance the anti‐NSCLC activity of AZD9291 by modulating STAT3 pathway. Finally, harmine could enhance the anti‐cancer activity of AZD9291 in primary NSCLC cells. Collectively, targeting DYRK1A might be an attractive target for AZD9291 sensitization in EGFR wild‐type NSCLC patients.
Kin recognition and co‐operative foraging inDrosophila melanogasterlarvae
Authors: Khodaei Lucas , Long Tristan A. F.
Published: August 2019

A long‐standing goal for biologists and social scientists is to understand the factors that lead to the evolution and maintenance of co‐operative behaviour between conspecifics. To that end, the fruit fly,Drosophila melanogaster, is becoming an increasingly popular model species to study sociality; however, most of the research to date has focused on adult behaviours. In this study, we set out to examine group‐feeding behaviour by larvae and to determine whether the degree of relatedness between individuals mediates the expression co‐operation. In a series of assays, we manipulated the average degree of relatedness in groups of third‐instar larvae that were faced with resource scarcity, and measured the size, frequency and composition of feeding clusters, as well as the fitness benefits associated with co‐operation. Our results suggest that larvalD. melanogasterare capable of kin recognition (something that has not been previously described in this species), as clusters were more numerous, larger and involved more larvae, when more closely related kin were present in the social environment. These findings are discussed in the context of the correlated fitness‐associated benefits of co‐operation, the potential mechanisms by which individuals may recognize kin, and how that kinship may play an important role in facilitating the manifestation of this co‐operative behaviour.
The effects of (E)‐2‐hexenal on morphological, physiological, and biochemical indices of postharvest disease Penicillium cyclopium spores
Authors: Ma Shuang , Zhang Jihong , Chen Shaoyang , Zeng Li
Published: August 2019

The study investigated the effects of (E)‐2‐hexenal on morphology and function of Penicillium cyclopium spores, and these conidia were treated with (E)‐2‐hexenal at various concentrations. (E)‐2‐hexenal at 8× minimum fungicidal concentration (8× MFC, 2560 μl/L) severely damaged conidia membranes through scanning electron microscopy, which resulted in the changes in membrane permeability parameters including the release of intracellular adenosine triphosphate content, loss of 260 nm‐absorbing materials, and the decrease of extracellular pH, the increase in extracellular conductivity, and membrane leakage as determined by propidium iodide staining. (E)‐2‐hexenal (≤2 × MFC, 640 μl/L) always induced superoxide dismutase and catalase enzyme activities in P. cyclopium conidia. These results suggest that (E)‐2‐hexenal damages fungal spore membranes, and inhibit spore germination in a dose‐dependent manner, causing a series of changes in membrane permeability parameters, which serves as the inhibitory mechanism of (E)‐2‐hexenal against P. cyclopium.

Practical applications

(E)‐2‐hexenal treatment significantly resulted in serious detrimental damages in the morphology and function in P. cyclopium spores. The work presented (E)‐2‐hexenal could control fungal pathogens through disruption of cell membrane integrity and membrane permeability. The results revealed that (E)‐2‐hexenal can be used as a new anti‐fungal agent against P. cyclopium.
Portrayals of Minorities and Women in Super Bowl Advertising
Authors: Taylor Charles R. , Mafael Alexander , Raithel Sascha , Anthony Carissa M. , Stewart David W.
Published: August 2019

Portrayals of women and minorities advertising have long been of interest to advertising scholars. While research has found that the overall representation of these groups has increased, some stereotypes persist, and so do questions about the quality and prominence of portrayals. This study examines portrayals of minorities and women in Super Bowl advertising, the main “pop culture” showcase for US advertising. A content analysis of 10 years of Super Bowl ads is conducted and a multinomial logit regression model is employed to delve deeper into the content analysis results. Findings show that while the overall representation of women and various minority groups is strong, a deeper analysis shows that these groups are seldom depicted as primary characters by themselves and that some subtle stereotypes persist. We also find that ads featuring female principal characters are more likely to feature home settings, sexual appeals, emotional messages, and music as a major element and that it is less likely for female (vs. male) celebrities to be used. Minority principal characters are more likely to be celebrities and be included in ads with music or for technical products but are less likely to be included in ads featuring corporate social responsibility messages.
How to handle hypertriglyceridaemia in acute pancreatitis – Still a vote for conservatives?
Authors: Eriksson Mats , Angelin Bo
Published: August 2019

Click here to view the Original article by Berberich et al.