bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing healthcare professional knowledge, attitudes, and practices on hypertension management. Announcing a new World Hypertension League resource
Authors: Campbell Norm R. C. , Dashdorj Naranjargal , Baatarsuren Uurtsaikh , Myanganbayar Maral , Dashtseren Myagmartseren , Unurjargal Tsolmon , Zhang Xin‐Hua , Veiga Eugenia Velludo , Beheiry Hind Mamoun , Mohan Sailesh , Almustafa Bader , Niebylski Mark , Lackland Daniel
Published: September 2017

To assist hypertension control programs and specifically the development of training and education programs on hypertension for healthcare professionals, the World Hypertension League has developed a resource to assess knowledge, attitudes, and practices on hypertension management. The resource assesses: (1) the importance of hypertension as a clinical and public health risk; (2) education in national or international hypertension recommendations; (3) lifestyle causes of hypertension; (4) measurement of blood pressure, screening, and diagnosis of hypertension; (5) lifestyle therapy counseling; (6) cardiovascular risk assessment; (7) antihypertensive drug therapy; and (8) adherence to therapy. In addition, the resource assesses the attitudes and practices of healthcare professionals for task sharing/shifting, use of care algorithms, and use of registries with performance reporting functions. The resource is designed to help support the Global Hearts Alliance to provide standardized and enhanced hypertension control globally.
A diphenyldiselenide derivative induces autophagy via JNK in HTB‐54 lung cancer cells
Authors: Díaz Marta , González Roncesvalles , Plano Daniel , Palop Juan Antonio , Sanmartín Carmen , Encío Ignacio
Published: September 2017

Symmetric aromatic diselenides are potential anticancer agents with strong cytotoxic activity. In this study, the in vitro anticancer activities of a novel series of diarylseleno derivatives from the diphenyldiselenide (DPDS) scaffold were evaluated. Most of the compounds exhibited high efficacy for inducing cytotoxicity against different human cancer cell lines. DPDS 2, the compound with the lowest mean GI50 value, induced both caspase‐dependent apoptosis and arrest at the G0/G1 phase in acute lymphoblastic leucemia CCRF‐CEM cells. Consistent with this, PARP cleavage; enhanced caspase‐2, ‐3, ‐8 and ‐9 activity; reduced CDK4 expression and increased levels of p53 were detected in these cells upon DPDS 2 treatment. Mutated p53 expressed in CCRF‐CEM cells retains its transactivating activity. Therefore, increased levels of p21CIP1 and BAX proteins were also detected. On the other hand, DPDS 6, the compound with the highest selectivity index for cancer cells, resulted in G2/M cell cycle arrest and caspase‐independent cell death in p53 deficient HTB‐54 lung cancer cells. Autophagy inhibitors 3‐methyladenine, wortmannin and chloroquine inhibited DPDS 6‐induced cell death. Consistent with autophagy, increased LC3‐II and decreased SQSTM1/p62 levels were detected in HTB‐54 cells in response to DPDS 6. Induction of JNK phosphorylation and a reduction in phospho‐p38 MAPK were also detected. Moreover, the JNK inhibitor SP600125‐protected HTB‐54 cells from DPDS 6‐induced cell death indicating that JNK activation is involved in DPDS 6‐induced autophagy. These results highlight the anticancer effects of these derivatives and warrant future studies examining their clinical potential.
Betacellulin regulates the proliferation and differentiation of retinal progenitor cells in vitro
Authors: Zhang Dandan , Shen Bingqiao , Zhang Yi , Ni Ni , Wang Yuyao , Fan Xianqun , Sun Hao , Gu Ping
Published: September 2017

Retinal progenitor cells (RPCs) hold great potential for the treatment of retinal degenerative diseases. However, their proliferation capacity and differentiation potential towards specific retinal neurons are limited, which limit their future clinical applications. Thus, it is important to improve the RPCs’ ability to proliferate and differentiate. Currently, epidermal growth factor (EGF) is commonly used to stimulate RPC growth in vitro. In this study, we find that betacellulin (BTC), a member of the EGF family, plays important roles in the proliferation and differentiation of RPCs. Our results showed that BTC can significantly promote the proliferation of RPCs more efficiently than EGF. EGF stimulated RPC proliferation through the EGFR/ErbB2‐Erk pathway, while BTC stimulated RPC proliferation more powerfully through the EGFR/ErbB2/ErbB4‐Akt/Erk pathway. Meanwhile, under differentiated conditions, the BTC‐pre‐treated RPCs were preferentially differentiated into retinal neurons, including photoreceptors, one of the most important types of cells for retinal cell replacement therapy, compared to the EGF‐pre‐treated RPCs. In addition, knockdown of endogenous BTC expression can also obviously promote RPC differentiation into retinal neuronal cells. This data demonstrate that BTC plays important roles in promoting RPC proliferation and differentiation into retinal neurons. This study may provide new insights into the study of RPC proliferation and differentiation and make a step towards the application of RPCs in the treatment of retinal degenerative diseases.
Role of IL‐18 in atopic asthma is determined by balance of IL‐18/IL‐18BP/IL‐18R
Authors: Zhang Huiyun , Wang Junling , Wang Ling , Xie Hua , Chen Liping , He Shaoheng
Published: September 2017

It is recognized that IL‐18 is related to development of asthma, but role of IL‐18 in asthma remains controversial and confusing. This is largely due to lack of information on expression of IL‐18 binding protein (BP) and IL‐18 receptor (R) in asthma. In this study, we found that plasma levels of IL‐18 and IL‐18BP were elevated in asthma. The ratio between plasma concentrations of IL‐18 and IL‐18BP was 1:12.8 in asthma patients. We demonstrated that 13‐fold more monocytes, 17.5‐fold more neutrophils and 4.1‐fold more B cells express IL‐18BP than IL‐18 in asthmatic blood, suggesting that there is excessive amount of IL‐18BP to abolish actions of IL‐18 in asthma. We also discovered that more IL‐18R+ monocytes, neutrophils and B cells are located in asthmatic blood. Once injected, IL‐18 eliminated IL‐18R+ monocytes in blood, but up‐regulated expression of IL‐18R in lung macrophages of OVA‐sensitized mice. Our data clearly indicate that the role of IL‐18 in asthma is very likely to be determined by balance of IL‐18/IL‐18BP/IL‐18R expression in inflammatory cells. Therefore, IL‐18R blocking or IL‐18BP activity enhancing therapies may be useful for treatment of asthma.
Language growth in children with heterogeneous language disorders: a population study
Authors: Norbury Courtenay Frazier , Vamvakas George , Gooch Debbie , Baird Gillian , Charman Tony , Simonoff Emily , Pickles Andrew
Published: September 2017

Background

Language development has been characterised by significant individual stability from school entry. However, the extent to which trajectories of language growth vary in children with language disorder as a function of co‐occurring developmental challenges is a question of theoretical import, with implications for service provision.

Methods

SCALES employed a population‐based survey design with sample weighting procedures to estimate growth in core language skills over the first three years of school. A stratified sample (n = 529) received comprehensive assessment of language, nonverbal IQ, and social, emotional and behavioural difficulties at 5–6 years of age and 95% of the sample (n = 499) were assessed again at ages 7–8. Language growth was measured using both raw and standard scores in children with typical development, children with language disorder of unknown origin, and children with language disorders associated with a known clinical condition and/or intellectual disability.

Results

Overall, language was stable at the individual level (estimated ICC = 0.95) over the first three years of school. Linear mixed effects models highlighted steady growth in language raw scores across all three groups, including those with multiple developmental challenges. There was little evidence, however, that children with language disorders were narrowing the gap with peers (z‐scores). Adjusted models indicated that while nonverbal ability, socioeconomic status and social, emotional and behavioural deficits predicted initial language score (intercept), none predicted language growth (slope).

Conclusions

These findings corroborate previous studies suggesting stable language trajectories after ages 5–6 years, but add considerably to previous work by demonstrating similar developmental patterns in children with additional nonverbal cognitive deficits, social, emotional, and behavioural challenges, social disadvantage or clinical diagnoses.
A single‐session growth mindset intervention for adolescent anxiety and depression: 9‐month outcomes of a randomized trial
Authors: Schleider Jessica , Weisz John
Published: September 2017

Background

Single‐session interventions (SSIs) show promise in the prevention and treatment of youth psychopathology, carrying potential to improve the scalability and accessibility of youth psychological services. However, existing SSIs have conferred greater benefits for youths with anxiety, compared to depression or comorbid problems, and their effects have generally waned over time – particularly for follow‐ups exceeding 3 months.

Method

To help address these discrepancies, we tested whether a novel SSI teaching growth mindset of personality (the belief that personality is malleable) could reduce depression and anxiety and strengthen perceived control in high‐risk adolescents (N = 96, ages 12–15). At baseline, youths were randomized to receive a 30‐min, computer‐guided growth mindset intervention or a supportive‐therapy control. Youths and parents reported youth anxiety and depressive symptoms, and youths reported their levels of perceived control, at baseline and across a 9‐month follow‐up period.

Results

Compared to the control program, the mindset intervention led to significantly greater improvements in parent‐reported youth depression (d = .60) and anxiety (d = .28), youth‐reported youth depression (d = .32), and youth‐reported perceived behavioral control (d = .29) by 9‐month follow‐up. Intervention effects were nonsignificant for youth‐reported anxiety, although 9‐month effect sizes reached the small‐to‐medium range (d = .33). Intervention group youths also experienced more rapid improvements in parent‐reported depression, youth‐reported depression, and perceived behavioral control across the follow‐up period, compared to control group youths.

Conclusions

Findings suggest a promising, scalable SSI for reducing internalizing distress in high‐risk adolescents. Clinical Trial Registration Number: NCT03132298.
Practitioner Review: Treatment of chronic insomnia in children and adolescents with neurodevelopmental disabilities
Authors: Bruni Oliviero , Angriman Marco , Calisti Fabrizio , Comandini Alessandro , Esposito Giovanna , Cortese Samuele , Ferri Raffaele
Published: September 2017

Background

Sleep disturbances, in particular insomnia, represent a common problem in children with neurodevelopmental disabilities (NDDs). Currently, there are no approved medications for insomnia in children by the US Food and Drug Administration or European Medicines Agency and therefore they are prescribed off‐label. We critically reviewed pediatric literature on drugs as well as nonpharmacological (behavioral) interventions used for sleep disturbances in children with NDDs.

Methods

PubMed, Ovid (including PsycINFO, Ovid MEDLINE®, and Embase), and Web of Knowledge databases were searched through February 12, 2017, with no language restrictions. Two authors independently and blindly performed the screening.

Results

Good sleep practices and behavioral interventions, supported by moderate‐to‐low level evidence, are the first recommended treatments for pediatric insomnia but they are often challenging to implement. Antihistamine agents, such as hydroxyzine or diphenhydramine, are the most widely prescribed sedatives in the pediatric practice but evidence supporting their use is still limited. An increasing body of evidence supports melatonin as the safest choice for children with NDDs. Benzodiazepines are not recommended in children and should only be used for transient insomnia, especially if daytime anxiety is present. Only few studies have been carried out in children's and adolescents’ zolpidem, zaleplon, and eszopiclone, with contrasting results. Limited evidence supports the use of alpha‐agonists such as clonidine to improve sleep onset latency, especially in attention deficit/hyperactivity disorder subjects. Tricyclic antidepressants, used in adults with insomnia, are not recommended in children because of their safety profile. Trazodone and mirtazapine hold promise but require further studies.

Conclusions

Here, we provided a tentative guide for the use of drugs for insomnia in children with NDDs. Well‐controlled studies employing both objective polysomnography and subjective sleep measures are needed to determine the efficacy, effectiveness, and safety of the currently prescribed pediatric sleep medicines in children with NDDs.
Production‐level risk factors for syncytial hepatitis in farmed tilapia (Oreochromis niloticus L)
Authors: Kabuusu R M , Aire A T , Stroup D F , Macpherson C N L , Ferguson H W
Published: September 2017

Syncytial hepatitis (SHT) is an emerging viral disease of tilapia characterized by significant morbidity and mortality. This study aimed to establish the production‐level risk factors associated with presence and severity of SHT. Production factors were analysed during multiple outbreaks of SHT that occurred between 2011 and 2013 on a single tilapia farm in Ecuador and compared with the year 2010 before the SHT outbreaks. Relative risks, t tests, modified Poisson and forward stepwise linear regression analyses were performed using EPIINFO™. Compared to other strains, Chitralada had an elevated risk of SHT [RR = 2.1 (95%CI 1.8–2.4)]. Excessive mortality associated with the presence (and severity) of SHT increased by 611 (365), 6,814 (5,768) and 388 (340) deaths per 100,000 fry when stocking density, dissolved oxygen and pond production cycles were raised by 1 fish/m2, 1 mg/L and 1 cycle, respectively. Excessive mortality associated with the presence (and severity) of SHT decreased by 337 (258) and 1,354 (1,025) deaths per 100,000 when stocking weight and water temperature increased by 1 g and 1°C, respectively. Time (season and stocking year) was not significantly associated with SHT. This study shows that some production factors increase the risk incidence and severity of SHTon a farm.
Response of Caligus rogercresseyi (Boxshall & Bravo, 2000) to treatment with Hydrogen Peroxide: Recovery of parasites, fish infestation and egg viability under experimental conditions
Authors: Marín S L , González M P , Madariaga S T , Mancilla M , Mancilla J
Published: September 2017

Hydrogen peroxide (HP) is used to remove C. rogercresseyi from fish but little is known about its effect on this species. This study determined EC50 and concentration immobilizing 100% of specimens, capacity of parasites exposed to HP to recover and infest fish, and effect on survival into the copepodid stage. EC50 and concentration immobilizing 100% of specimens were estimated by exposing parasites for 20 min to 11 concentrations and evaluating effect at 1 and 24 h post‐exposure. Capacity to recover and infest fish, and survival into copepodid were evaluated by exposing parasites and eggs to HP for 20 min. Recovery and fish infestation were evaluated at 25 and 24 h post‐exposure, respectively. Eggs were grown until control reached the copepodid stage and survival calculated. EC50 was 709.8 ppm.100% immobilization was obtained at 825 ppm. Male and female recover 0.5 and 1 h post‐exposure, respectively. Percentage of parasites exposed and not exposed to HP that were recovered on fish was not significantly different. Survival to copepodid was lower in those exposed to HP. HP effect is greater on copepodids, but 100% of the mobile stages are immobilized under 825 ppm causing detachment from fish and potentially driven away, reducing infestation risk.
Antibiotic susceptibility and molecular characterization of Aeromonas hydrophila from grass carp
Authors: Yang Ying , Miao Pengfei , Li Hua , Tan Shuwen , Yu Haiyi , Yu Hui
Published: September 2017

Aeromonas hydrophila is the leading cause of fish borne outbreaks and also represents a major threat to human health worldwide. This bacterium harbors many virulence factors such as aerolysin, elastase, and lipase genes. The extensive use of antibiotics is a contributing factor to the increasing incidence of antimicrobial‐resistant A. hydrophila. In the current study, we aimed to determine the incidence and features of A. hydrophila in grass carp in south China. We found 63 (31.5%) A. hydrophila isolates through investigation of 200 samples from five provinces in south China. All isolates were analyzed for virulence genes by polymerase chain reaction (PCR), antibiotic susceptibility analysis was carried out using the disk diffusion method, and molecular typing was performed using enterobacterial repetitive intergenic consensus sequence PCR (ERIC‐PCR). The results showed that the positive for aerolysin, elastase, hemolysin, and lipase gene were 71.43, 46.03, 0.00, and 55.56%, respectively. Antimicrobial susceptibility results indicated that most strains were resistant to ampicillin (95.24%), tetracycline (88.89%), and streptomycin (79.37%). A lot of multiple antibiotic resistance were found. The isolates were grouped into five clusters by ERIC‐PCR and shown the genetic diversity. Thus, our findings demonstrated the presence of A. hydrophila from grass carp, provided insights into the dissemination of antibiotic‐resistant strains, and improved our knowledge of microbiological risk assessment in this bacteria.

Practical applications

Investigating the prevalence of Aeromonas hydrophilia isolates from grass carp could improved for assuring this microbial safety on food. In this study, antibiotic susceptibility, virulence genes, and molecular subtyping were selected to comprehensive analyze A. hydrophilia isolates. As grass carp are common and popular fish choices in China, therefore the continuous monitoring of this pathogens are vital to ensure the safety.
Clinical profile of hepatitis C virus infection in a developing country: India
Authors: Mahajan Ramit , Midha Vandana , Goyal Omesh , Mehta Varun , Narang Vikram , Kaur Kirandeep , Singh Arshdeep , Singh Dharmatma , Bhanot Rishu , Sood Ajit
Published: September 2017

Background and Aim

The epidemiology and clinical profile of hepatitis C virus (HCV) varies worldwide, and data from developing countries are sparse. The aim of the present study was to assess the clinical profile of HCV infection in a developing country in South‐East Asia (India).

Methods

This observational study assessed patient demographics, viral characteristics, risk factors for virus acquisition, and disease characteristics in HCV patients diagnosed between January 2004 and December 2015.

Results

Of 8035 patients who were diagnosed with HCV infection, a majority were men (68.3%), middle aged (52.2%), and from low (34%) to middle (46%) socioeconomic status and rural population (69.8%). Eighty‐two percent had identifiable risk factors, the most common being history of dental treatment (52%) and therapeutic injections with reusable syringes/needles (45%). Household contacts of index patients had high prevalence of HCV (15.3%). Common genotypes were genotype 3 (70.4%) and genotype 1 (19.3%). Although a majority of patients were either asymptomatic (54.8%) or had non‐specific symptoms (6.7%) at presentation, a significant proportion (9.3%) had advanced liver disease. Presentation with cirrhosis (38.8%) was associated with male gender, higher age at time of virus detection, rural residence, alcohol or opium intake, and coinfections with hepatitis B virus or human immunodeficiency virus.

Conclusions

Hepatitis C virus infection in northern India is seen more commonly in men, the middle aged and people from rural background and low to middle socioeconomic status. The common possible risk factors are dental treatment and exposure to reused syringes and needles. Although the most common presentation is incidental detection, a large number of patients present with advanced liver disease.
Indicators in Social Life Cycle Assessment: A Review of Frameworks, Theories, and Empirical Experience
Authors: Kühnen Michael , Hahn Rüdiger
Published: September 2017

Industrial ecology (IE) and life cycle sustainability assessment (LCSA) are increasingly important in research, regulation, and corporate practice. However, the assessment of the social pillar is still at a developmental stage, because social life cycle assessment (SLCA) is fragmented and lacks a foundation on empirical experience. A critical reason is the absence of general standardized indicators that clearly reflect and measure businesses’ social impact along product life cycles and supply chains. Therefore, we systematically review trends, coherences, inconsistencies, and gaps in research on SLCA indicators across industry sectors. Overall, we find that researchers address a broad variety of sectors, but only few sectors receive sufficient empirical attention to draw reasonable conclusions while the field is additionally still largely an a‐theoretical one. Furthermore, researchers overlook important social core issues as they concentrate heavily on worker‐ and health‐related indicators. Therefore, we synthetize the most important indicators used in research as a step toward standardization (including critical challenges in applying these indicators and recommendations for their future development), highlight important trends and gaps (e.g., the focus on worker‐ and health‐related indicators and the a‐theoretical nature of the SLCA literature), and emphasize critical shortcomings in the SLCA field organized along the key phases of design, implementation, and evolution through which performance measurement approaches such as SLCA typically progress in their development and maturation. With this, we contribute to the maturation and establishment of the social pillar of LCSA and IE.
DJ‐1 deficiency impairs autophagy and reduces alpha‐synuclein phagocytosis by microglia
Authors: Nash Yuval , Schmukler Eran , Trudler Dorit , Pinkas‐Kramarski Ronit , Frenkel Dan
Published: September 2017

Parkinson's disease (PD) is a progressive neurodegenerative disorder, of which 1% of the hereditary cases are linked to mutations in DJ‐1, an oxidative stress sensor. The pathological hallmark of PD is intercellular inclusions termed Lewy Bodies, composed mainly of α‐Synuclein (α‐Syn) protein. Recent findings have shown that α‐Syn can be transmitted from cell to cell, suggesting an important role of microglia, as the main scavenger cells of the brain, in clearing α‐Syn. We previously reported that the knock down (KD) of DJ‐1 in microglia increased cells’ neurotoxicity to dopaminergic neurons. Here, we discovered that α‐Syn significantly induced elevated secretion of the proinflammatory cytokines IL‐6 and IL‐1β and a significant dose‐dependent elevation in the production of nitric oxide in DJ‐1 KD microglia, compared to control microglia. We further investigated the ability of DJ‐1 KD microglia to uptake and degrade soluble α‐Syn, and discovered that DJ‐1 KD reduces cell‐surface lipid raft expression in microglia and impairs their ability to uptake soluble α‐Syn. Autophagy is an important mechanism for degradation of intracellular proteins and organelles. We discovered that DJ‐1 KD microglia exhibit an impaired autophagy‐dependent degradation of p62 and LC3 proteins, and that manipulation of autophagy had less effect on α‐Syn uptake and clearance in DJ‐1 KD microglia, compared to control microglia. Further studies of the link between DJ‐1, α‐Syn uptake and autophagy may provide useful insights into the role of microglia in the etiology of the PD.

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Molecular basis of oral squamous cell carcinoma in young patients: Is it any different from older patients?
Authors: dos Santos Costa Sara Ferreira , Brennan Peter A. , Gomez Ricardo Santiago , Fregnani Eduardo Rodrigues , Santos‐Silva Alan Roger , Martins Manoela Domingues , de Castro‐Junior Gilberto , Rahimi Siavash , Fonseca Felipe Paiva
Published: September 2017

Oral squamous cell carcinoma (OSCC) is the commonest subtype of oral cancer, mainly affecting older patients. It used to be a rare disease among individuals younger than 40 years, but recently increased incidences in this age group are being reported worldwide. The pathogenesis of OSCC affecting young patients remains controversial, and the well‐known etiological factors for oral cancer, tobacco, and alcohol use are believed to play a minor role in the carcinogenesis of the neoplasm, suggesting that the etiology and the molecular basis of OSCC may differ between younger and older patients. Although several molecular markers and chromosomal abnormalities have been demonstrated to differ between both groups, most of the studies have failed to find significant differences. Moreover, divergent results have also been obtained regarding the presence of high‐risk human papillomavirus infection in OSCC of young patients. Given these contradictory results and the limited methodological approaches of the majority of the studies, the exact difference between both age groups remains to be fully established. In this review, we evaluate the available data to establish the current evidence that might support the hypothesis that the molecular basis of OSCC in young patients (especially those under 40 years) differ from the older patients.
Turning the Sword: How NPD Teams Cope with Front‐End Tensions
Authors: Andriopoulos Constantine , Gotsi Manto , Lewis Marianne W. , Ingram Amy E.
Published: September 2017

Front‐end new product development (NPD) is fraught with tensions that fuel and inhibit innovation. According to paradox theory, tensions pose a double‐edged sword, sparking learning and creativity or anxiety and counterproductive responses. NPD teams' shared understandings—how they think about (cognition) and approach (motivation) tensions—turn the sword. Existing literature examines innovation tensions and their management. Yet scholars call for deeper dives, seeking research that unpacks cognitive and motivational drivers underlying how NPD teams cope with tensions. This paper responds, presenting a four‐year inductive study of five NPD consultancies. Across cases, findings explicate the roles of paradoxical cognitive frames and regulatory motivational focus. Across firms, the front‐end NPD teams framed tensions paradoxically. Three frames—guided freefall, benevolent dictatorship, and cohesive diversity—helped teams develop shared understandings of tensions as paradoxical, posing competing yet interdependent demands. Teams varied, however, in their regulatory focus, influencing how they applied the frames to approach tensions. In the most innovative case, teams applied a promotion focus, energized to explore tensions in search of more creative alternatives and synergies. In less innovative cases, teams applied a prevention focus, motivated to avoid risk and loss. Together, paradoxical frames and regulatory focus shaped teams' coping behaviors and resulting innovation. Resulting theory posits the interplay among cognitive, motivational, and behavioral drivers of innovation. Results offer three contributions. First, this study extends understanding of antecedents to team innovation and front‐end NPD. Second, findings deepen insights into team cognition and paradoxical frames. Last, the theoretical framework explicates how cognitive‐motivational interactions enable coping behaviors that foster innovation. The conclusion poses managerial and research implications. Building from paradox theory this study suggests means to foster shared paradoxical frames and promotion focus in NPD teams. Further, study limitations highlight opportunities to extend its generalizability and elaborate underlying drivers of innovation.

Practitioner Points

Paradoxical frames and a promotion focus help teams at the front end of NPD cope with tensions and fuel virtuous cycles of innovation.

Training front‐end NPD leaders and team members in paradoxical thinking will help them frame competing demands as synergistic and tap into the energizing potential of tensions.

Positive messaging about NPD tensions that emphasizes gain, risk, and movement over cautiousness and vigilance, aids adoption of a promotion focus—motivation that helps further mobilize front‐end innovation.
Safety of Back‐Transfer to Local Hospitals During an Acute Care Hospitalization
Authors: Nelson Leah F. , Harland Karisa K. , Shane Dan M. , Ahmed Azeemuddin , Mohr Nicholas M.
Published: September 2017

Purpose

This paper investigates patient outcomes including length of stay (LOS), cost of hospitalization, bounce‐back rates, transition to hospice care, and mortality, following back‐transfer.

Methods

This study was an observational case‐control study of adults hospitalized in Iowa between 2005 and 2013 to identify back‐transferred patients. Back‐transfer was defined as the transfer of rural patients near the end of their acute hospitalization in a comprehensive medical center back to a local community hospital for the completion of their medical care. Demographic, geographic, rurality, procedural, and disease information was compared between case and control groups, then propensity score (PS) matching was performed to create comparable groups to perform analyses.

Findings

Over the 9‐year period, 1,056,773 patients meeting inclusion criteria were admitted, of which 430 (0.04%) were back‐transferred. After PS matching, LOS was 60% (95% CI: 0.50‐0.71) higher and costs were 42% (95% CI: 0.33‐0.50) higher in the back‐transferred group. Back‐transferred cases had 8.34 (95% CI: 3.66‐19.0) times the odds of hospice transition and 2.17 (95% CI: 1.37‐3.46) the odds of mortality compared to controls. Four percent of back‐transfers “failed” with the patient being returned to the larger hospital before discharge.

Conclusions

Back‐transfer is a rare occurrence, and it is associated with longer LOS, higher hospitalization cost, higher mortality, more hospice transfers, and occasional bounce‐backs to comprehensive medical centers. Future work should focus more on prospective indications for transfer, the role of end‐of‐life care, financial impact, and identifying patient populations for whom back‐transfer is safest.
Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate
Authors: Lelkes Zoltán , Abdurakhmanova Shamsiiat , Porkka‐Heiskanen Tarja
Published: September 2017

The cholinergic basal forebrain contributes to cortical activation and receives rich innervations from the ascending activating system. It is involved in the mediation of the arousing actions of noradrenaline and histamine. Glutamatergic stimulation in the basal forebrain results in cortical acetylcholine release and suppression of sleep. However, it is not known to what extent the cholinergic versus non‐cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate. To clarify this question, we administered N‐methyl‐D‐aspartate (NMDA), a glutamate agonist, into the basal forebrain in intact rats and after destruction of the cholinergic cells in the basal forebrain with 192 immunoglobulin (Ig)G‐saporin. In eight Han–Wistar rats with implanted electroencephalogram/electromyogram (EEG/EMG) electrodes and guide cannulas for microdialysis probes, 0.23 μg 192 IgG‐saporin was administered into the basal forebrain, while the eight control animals received artificial cerebrospinal fluid. Two weeks later, a microdialysis probe targeted into the basal forebrain was perfused with cerebrospinal fluid on the baseline day and for 3 h with 0.3 mmNMDA on the subsequent day. Sleep–wake activity was recorded for 24 h on both days. NMDA exhibited a robust arousing effect in both the intact and the lesioned rats. Wakefulness was increased and both non‐REM and REM sleep were decreased significantly during the 3‐h NMDA perfusion. Destruction of the basal forebrain cholinergic neurones did not abolish the wake‐enhancing action of NMDA. Thus, the cholinergic basal forebrain structures are not essential for the mediation of the arousing action of glutamate.
Gaining insights into in situ behaviour of an endangered seahorse using action cameras
Authors: Claassens L. , Hodgson A. N.
Published: September 2017

Observation bias is an Achilles heel of behavioural research, particularly during underwater in situ assessments. The advent of small, affordable underwater action cameras has helped to overcome this problem and were used to investigate the behaviour of the endangered Knysna seahorse (Hippocampus capensis) within a South African residential marina estate during the austral summer. Four GoPro® cameras were deployed over three time periods, October to December 2015, December 2015 to January 2016 and January to March 2016, and at different times of the day (morning, midday, afternoon) to ascertain whether: (1) cameras can be used to investigate seahorse behaviour, (2) seahorse behaviour changes throughout the day, (3) behaviour can be used to assess the impact of an external stressor (boat noise) on H. capensis. Thirty‐six hours from a total of 161 h (23%) recorded contained seahorse footage. Seahorses were significantly more visible during the morning and spent >80% of their time hunting. Courting behaviour took place exclusively during the morning and aggression was noted between males only. Boat noise increased during the December holiday period and a significant decrease in seahorse visibility, time spent feeding, and courting events were noted during this time. This suggests that noise has an adverse impact on the behaviour of H. capensis. This study confirms the efficacy of using small action cameras in seahorse behavioural research.
Environmental DNA metabarcoding: Transforming how we survey animal and plant communities
Authors: Deiner Kristy , Bik Holly M. , Mächler Elvira , Seymour Mathew , Lacoursière‐Roussel Anaïs , Altermatt Florian , Creer Simon , Bista Iliana , Lodge David M. , de Vere Natasha , Pfrender Michael E. , Bernatchez Louis
Published: September 2017

The genomic revolution has fundamentally changed how we survey biodiversity on earth. High‐throughput sequencing (“HTS”) platforms now enable the rapid sequencing of DNA from diverse kinds of environmental samples (termed “environmental DNA” or “eDNA”). Coupling HTS with our ability to associate sequences from eDNA with a taxonomic name is called “eDNA metabarcoding” and offers a powerful molecular tool capable of noninvasively surveying species richness from many ecosystems. Here, we review the use of eDNA metabarcoding for surveying animal and plant richness, and the challenges in using eDNA approaches to estimate relative abundance. We highlight eDNA applications in freshwater, marine and terrestrial environments, and in this broad context, we distill what is known about the ability of different eDNA sample types to approximate richness in space and across time. We provide guiding questions for study design and discuss the eDNA metabarcoding workflow with a focus on primers and library preparation methods. We additionally discuss important criteria for consideration of bioinformatic filtering of data sets, with recommendations for increasing transparency. Finally, looking to the future, we discuss emerging applications of eDNA metabarcoding in ecology, conservation, invasion biology, biomonitoring, and how eDNA metabarcoding can empower citizen science and biodiversity education.
Effects of zoochory on the spatial genetic structure of plant populations
Authors: Gelmi‐Candusso Tiziana A. , Heymann Eckhard W. , Heer Katrin
Published: September 2017

Spatial genetic structure (SGS) of plants results from the nonrandom distribution of related individuals.SGSprovides information on gene flow and spatial patterns of genetic diversity within populations. Seed dispersal creates the spatial template for plant distribution. Thus, in zoochorous plants, dispersal mode and disperser behaviour might have a strong impact onSGS. However, many studies only report the taxonomic group of seed dispersers, without further details. The recent increase in studies onSGSprovides the opportunity to review findings and test for the influence of dispersal mode, taxonomic affiliation of dispersers and their behaviour. We compared the proportions of studies withSGSamong groups and tested for differences in strength ofSGSusingSpstatistics. The presence ofSGSdiffered among taxonomic groups, with reduced presence in plants dispersed by birds. Strength ofSGSwas instead significantly influenced by the behaviour of seed dispersal vectors, with higherSGSin plant species dispersed by animals with behavioural traits that result in short seed dispersal distances. We observed high variance in the strength ofSGSin plants dispersed by animals that actively or passively accumulate seeds. Additionally, we foundSGSwas also affected by pollination and marker type used. Our study highlights the importance of vector behaviour onSGSeven in the presence of variance created by other factors. Thus, more detailed information on the behaviour of seed dispersers would contribute to better understand which factors shape the spatial scale of gene flow in animal‐dispersed plant species.
Mutual independence of alkaline‐ and calcium‐mediated signalling in Aspergillus fumigatus refutes the existence of a conserved druggable signalling nexus
Authors: Loss Omar , Bertuzzi Margherita , Yan Yu , Fedorova Natalie , McCann Bethany L. , Armstrong‐James Darius , Espeso Eduardo A. , Read Nick D. , Nierman William C. , Bignell Elaine M.
Published: September 2017

Functional coupling of calcium‐ and alkaline responsive signalling occurs in multiple fungi to afford efficient cation homeostasis. Host microenvironments exert alkaline stress and potentially toxic concentrations of Ca2+, such that highly conserved regulators of both calcium‐ (Crz) and pH‐ (PacC/Rim101) responsive signalling are crucial for fungal pathogenicity. Drugs targeting calcineurin are potent antifungal agents but also perturb human immunity thereby negating their use as anti‐infectives, abrogation of alkaline signalling has, therefore, been postulated as an adjunctive antifungal strategy. We examined the interdependency of pH‐ and calcium‐mediated signalling in Aspergillus fumigatus and found that calcium chelation severely impedes hyphal growth indicating a critical requirement for this ion independently of ambient pH. Transcriptomic responses to alkaline pH or calcium excess exhibited minimal similarity. Mutants lacking calcineurin, or its client CrzA, displayed normal alkaline tolerance and nuclear translocation of CrzA was unaffected by ambient pH. Expression of a highly conserved, alkaline‐regulated, sodium ATPase was tolerant of genetic or chemical perturbations of calcium‐mediated signalling, but abolished in null mutants of the pH‐responsive transcription factor PacC, and PacC proteolytic processing occurred normally during calcium excess. Taken together our data demonstrate that in A. fumigatus the regulatory hierarchy governing alkaline tolerance circumvents calcineurin signalling.
The ribokinases of Arabidopsis thaliana and Saccharomyces cerevisiae are required for ribose recycling from nucleotide catabolism, which in plants is not essential to survive prolonged dark stress
Authors: Schroeder Rebekka Y. , Zhu Anting , Eubel Holger , Dahncke Kathleen , Witte Claus‐Peter
Published: September 2017

Nucleotide catabolism in Arabidopsis thaliana and Saccharomyces cerevisiae leads to the release of ribose, which requires phosphorylation to ribose‐5‐phosphate mediated by ribokinase (RBSK). We aimed to characterize RBSK in plants and yeast, to quantify the contribution of plant nucleotide catabolism to the ribose pool, and to investigate whether ribose carbon contributes to dark stress survival of plants.

We performed a phylogenetic analysis and determined the kinetic constants of plant‐expressed Arabidopsis and yeast RBSKs. Using mass spectrometry, several metabolites were quantified in AtRBSK mutants and double mutants with genes of nucleoside catabolism. Additionally, the dark stress performance of several nucleotide metabolism mutants and rbsk was compared.

The plant PfkB family of sugar kinases forms nine major clades likely representing distinct biochemical functions, one of them RBSK. Nucleotide catabolism is the dominant ribose source in plant metabolism and is highly induced by dark stress. However, rbsk cannot be discerned from the wild type in dark stress. Interestingly, the accumulation of guanosine in a guanosine deaminase mutant strongly enhances dark stress symptoms.

Although nucleotide catabolism contributes to carbon mobilization upon darkness and is the dominant source of ribose, the contribution appears to be of minor importance for dark stress survival.
Effects of pre‐surgical nasoalveolar moulding on maxillary arch and nasal form in unilateral cleft lip and palate before lip surgery
Authors: Fuchigami T. , Kimura N. , Kibe T. , Tezuka M. , Amir M. S. , Suga H. , Takemoto Y. , Hashiguchi M. , Maeda‐Iino A. , Nakamura N.
Published: September 2017

Structured Abstract

Objectives

To investigate the effects of pre‐surgical nasoalveolar moulding (PNAM) on the maxillary arch and nasal form in patients with unilateral cleft lip and palate (UCLP).

Setting and Sample Population

This is a retrospective case series study. The subjects were infants with complete UCLP who were treated with PNAM (n = 18) at Kagoshima University Medical and Dental Hospital (Japan) between 2006 and 2013.

Material and Methods

Maxillary dental casts and facial photographs were taken at the time of the first visit and immediately prior to lip surgery to evaluate the maxillary arch and nasal form changes. The dental casts were scanned with a laser scanner, and changes in the 3‐Dimensional coordinates of anatomical landmarks and alveolar cleft width were analysed. Moreover, we investigated the correlation between the changes in the maxillary alveolar arch and nasal form.

Results

Regarding the maxillary alveolar arch form, the anterior points of the major segment had moved significantly to the cleft side just prior to the time of lip repair, and the alveolar cleft width was significantly decreased. For nasal form, the inclination and displacement of the columella were significantly improved. The improvement of columella inclination was moderately correlated with the posterior movement of the anterior points of the major segment.

Conclusions

These findings indicate that PNAM for infants with UCLP enhanced symmetry in the maxillary alveolar arch and nasolabial form. In addition, the posterior movement of the anterior points of the maxillary alveolar arch was correlated with the improvement of columella deformation.
Low‐gluten, nontransgenic wheat engineered with CRISPR/Cas9
Authors: Sánchez‐León Susana , Gil‐Humanes Javier , Ozuna Carmen V. , Giménez María J. , Sousa Carolina , Voytas Daniel F. , Barro Francisco
Published: September 2017

Coeliac disease is an autoimmune disorder triggered in genetically predisposed individuals by the ingestion of gluten proteins from wheat, barley and rye. The α‐gliadin gene family of wheat contains four highly stimulatory peptides, of which the 33‐mer is the main immunodominant peptide in patients with coeliac. We designed two sgRNAs to target a conserved region adjacent to the coding sequence for the 33‐mer in the α‐gliadin genes. Twenty‐one mutant lines were generated, all showing strong reduction in α‐gliadins. Up to 35 different genes were mutated in one of the lines of the 45 different genes identified in the wild type, while immunoreactivity was reduced by 85%. Transgene‐free lines were identified, and no off‐target mutations have been detected in any of the potential targets. The low‐gluten, transgene‐free wheat lines described here could be used to produce low‐gluten foodstuff and serve as source material to introgress this trait into elite wheat varieties.
Generalized Additive Models with Principal Component Analysis: An Application to Time Series of Respiratory Disease and Air Pollution Data
Authors: Souza Juliana B. , Reisen Valdério A. , Franco Glaura C. , Ispány Márton , Bondon Pascal , Santos Jane Meri
Published: September 2017

Environmental epidemiological studies of the health effects of air pollution frequently utilize the generalized additive model (GAM) as the standard statistical methodology, considering the ambient air pollutants as explanatory covariates. Although exposure to air pollutants is multi-dimensional, the majority of these studies consider only a single pollutant as a covariate in the GAM model. This model restriction may be because the pollutant variables do not only have serial dependence but also interdependence between themselves. In an attempt to convey a more realistic model, we propose here the hybrid generalized additive model–principal component analysis–vector auto-regressive (GAM–PCA–VAR) model, which is a combination of PCA and GAMs along with a VAR process. The PCA is used to eliminate the multicollinearity between the pollutants whereas the VAR model is used to handle the serial correlation of the data to produce white noise processes as covariates in the GAM. Some theoretical and simulation results of the methodology proposed are discussed, with special attention to the effect of time correlation of the covariates on the PCA and, consequently, on the estimates of the parameters in the GAM and on the relative risk, which is a commonly used statistical quantity to measure the effect of the covariates, especially the pollutants, on population health. As a main motivation to the methodology, a real data set is analysed with the aim of quantifying the association between respiratory disease and air pollution concentrations, especially particulate matter PM10, sulphur dioxide, nitrogen dioxide, carbon monoxide and ozone. The empirical results show that the GAM–PCA–VAR model can remove the auto-correlations from the principal components. In addition, this method produces estimates of the relative risk, for each pollutant, which are not affected by the serial correlation in the data. This, in general, leads to more pronounced values of the estimated risk compared with the standard GAM model, indicating, for this study, an increase of almost 5.4% in the risk of PM10, which is one of the most important pollutants which is usually associated with adverse effects on human health.
How Important Are Scale Effects for Growth When Knowledge Is a Public Good?
Authors: Sánchez‐Losada Fernando
Published: September 2017

In this paper, by proposing an R&D accumulation law for an economy with an expanding number of firms, I seek to reconcile the following three facts: the positive relationship between the fraction of income allocated to R&D expenditure and growth; the positive relationship between the number of firms and total factor productivity growth; and knowledge as a non‐rival and non‐excludable good. There are scale effects because of the public nature of knowledge, but the economy also grows in the absence of population growth. I find that population growth explains one‐fifth of market income growth but only one‐sixteenth of efficient income growth.