bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical significance of perineural invasion in patients with de novo metastatic prostate cancer
Authors: Zhao J. , Chen J. , Zhang M. , Tang X. , Sun G. , Zhu S. , Liu J. , Zhang H. , Zhang X. , Yin X. , Zhao P. , Zhu X. , Ni Y. , Dai J. , Shen P. , Chen N. , Zeng H.
Published: January 2019

Background

The clinical value of perineural invasion (PNI) in patients with localized prostate cancer (PCa) is widely explored. However, its role in metastatic PCa (mPCa) remains unknown.

Objectives

We aim to investigate the clinical significance of PNI in patients with mPCa.

Materials and methods

Data of 515 mPCa patients between 2012 and 2018 were retrospectively studied. PNI and its intensity were identified by prostate biopsy. The prognostic value of PNI was evaluated by Kaplan–Meier curves and Cox proportional‐hazards model.

Results

Perineural invasion was detected in 170/515 (33.0%) cases. Among them 73/170 (42.9%) and 97/170 (57.1%) harbored unifocal PNI (uni‐PNI) and multifocal PNI (multi‐PNI), respectively. Compared to patients without PNI, those with PNI had statistically shorter castration‐resistant PCa‐free survival (CFS) and numerically shorter overall survival (OS) (mCFS: 15.4‐ vs. 18.5‐Mo, p = 0.015; mOS: 63.8‐ vs. 71.4‐Mo, p = 0.108). Patients harboring multi‐PNI were associated with poorer clinical outcomes than those with uni‐PNI (mCFS: 12.4‐ vs. 18.0‐Mo, p = 0.040; mOS: 39.7‐Mo vs. NR, p = 0.018) or those without PNI (mCFS: 12.4‐ vs. 18.5‐Mo, p = 0.002; mOS: 39.7‐ vs. 71.4‐Mo, p = 0.002). Totally, neither uni‐PNI nor multi‐PNI was an independent risk factor impacting survival outcomes in multivariate analyses. While remarkably, for patients with favorable/intermediate‐risk mPCa, multi‐PNI was an independent adverse prognosticator for both CFS and OS (CFS: HR: 1.705, 95% CI: 1.029–2.825, p = 0.038; OS: HR: 3.294, 95% CI: 1.464–7.413, p = 0.004).

Discussion and Conclusion

This study filled the blank of the clinical significance of PNI in mPCa. We found that multi‐PNI could distinguish men with relatively poor prognosis from patients initially regarded as with favorable survival outcomes by other prognosticators, and thus, avoid disease underestimation in this group of patients. Our finding would help physicians have a deeper understanding of the heterogeneity of mPCa and make better individualized therapeutic strategy.
Living with tinnitus and the health care journey: An interpretative phenomenological analysis
Authors: Marks Elizabeth , Smith Paula , McKenna Laurence
Published: January 2019

Objectives

Tinnitus is a very common experience, and although usually mild, in a significant proportion of people, it is intrusive, persistent, and disabling. This paper explores the lived experience of chronic disabling tinnitus, with the aim of understanding how distress and chronicity occur, and what might help to reduce this.

Design

Nine individuals were interviewed 6 months after completing mindfulness‐based cognitive therapy (MBCT) as part of a randomized controlled trial. The results reported here focus on their experiences of tinnitus before receiving MBCT.

Methods

Data were collected through semi‐structured, face‐to‐face interviews with a clinical psychologist, and an interpretative phenomenological analysis approach was used.

Results

Two supraordinate themes emerged. ‘Living with tinnitus’ describes a range of significant and profound life changes that result from the condition. Tinnitus can be a life‐altering condition affecting thoughts, emotions, attention, behaviour, and the social world. ‘The health care journey’ shows how chronic distress was intensified by unhelpful health communications and alleviated by helpful consultations.

Conclusions

Tinnitus is a biopsychosocial condition, and associated distress is affected by cognitive, behavioural, attentional, and social factors. The individuals’ initial reactions to tinnitus interact with the responses of others, including health care professionals. The burden of tinnitus could be reduced by developing early interventions that offer clear, helpful, and realistic information about tinnitus and appropriate treatments.

Statement of contribution

What is already known on this subject?

Tinnitus is the experience of an internal sound without an external sound source.

It can be troubling, disabling, and chronic and usually has no clear medical cause or medical treatment, but psychological interventions are promising.

Cognitive, behavioural, and attentional factors play a role in distress and therapeutic outcome.

Clinical encounters are improved by aligning patient and clinician and sharing decision‐making.

What does this study add?

It is the first in‐depth study exploring how tinnitus distress and health care systems interact.

It shows how a biopsychosocial approach to tinnitus may reduce tinnitus burden more effectively than a biomedical, diagnostic‐focused approach.

It indicates how effective early health care information could be used to reduce chronic tinnitus distress.
Effects of developmental stress on animal phenotype and performance: a quantitative review
Authors: Eyck Harrison J.F. , Buchanan Katherine L. , Crino Ondi L. , Jessop Tim S.
Published: January 2019

Developmental stressors are increasingly recognised for their pervasive influence on the ecology and evolution of animals. In particular, many studies have focused on how developmental stress can give rise to variation in adult behaviour, physiology, and performance. However, there remains a poor understanding of whether general patterns exist in the effects and magnitude of phenotypic responses across taxonomic groups. Furthermore, given the extensive phenotypic variation that arises from developmental stressors, it remains important to ascertain how multiple processes may explain these responses. We compiled data from 111 studies to examine and quantify the effect of developmental stress on animal phenotype and performance from juveniles to adulthood, including studies from birds, reptiles, fish, mammals, insects, arachnids, and amphibians. Using meta‐analytic approaches, we show that across all studies there is, on average, a moderate to large negative effect of developmental stress exposure (posterior mean effect: |d| = −0.51) on animal phenotype or performance. Additionally, we demonstrate that interactive effects of timing of stressor onset and the duration of exposure to stressors best explained variation in developmental stress responses. Animals exposed to stressors earlier in development had more‐positive responses than those with later onset, whereas longer duration of exposure to a stressor caused responses to be stronger in magnitude. However, the high amount of heterogeneity in our results, and the low degree of variance explained by fixed effects in both the meta‐analysis (R2= 0.034) and top‐ranked meta‐regression model (R2= 0.02), indicate that phenotypic responses to developmental stressors are likely highly idiosyncratic in nature and difficult to predict. Despite this, our analyses address a critical knowledge gap in understanding what effect developmental stress has on phenotypic variation in animals. Additionally, our results highlight important environmental and proximate factors that may influence phenotypic responses to developmental stressors.
Intravenous immune globulin affects cytokine production in T lymphocytes and monocytesjmacrophages
Authors: Andersson J , Skansén-Saphir U , Sparrelid E , Andersson U
Published: January 2019

Immune globulin for intravenous use (IVIG) has been used in many inflammatory conditions due to its immunomodulatory potential. The effector mechanisms are incompletely understood. This study dealt with the effects of IVIG on cytokine production in vitro. Cytokine synthesis was identified at the single-cell level using cytokine-specific MAb and indirect immunocytochemical techniques. Peripheral blood mononuclear cells (PBMC) were stimulated for 96 h by immobilized anti-CD3 MAb or by a combination of a protein kinase C activator (PMA) and a calcium ionophore (ionomycin). The addition of IVIG (6 mg/ml) caused a marked inhibition of proliferation and blast transformation despite unaffected cell survival. Anti-CD3-stimulatcd cultures containing IVIG exhibited a significant inhibition of production of T-cell derived lymphokines IL-2, IL-10, TNF-β, IFN-1 and TNF-α (made by both monocytes and T cells), while synthesis of the monokinc IL-8 was significantly increased. The expression of IL-2 receptors was significantly suppressed. Similar but transient inhibition of most T-cell products (IL-2, IL-3, IL-4, IL-5, IL-10, TNF-β and GM-CSF) was noted in the PMA/ionomycin-containing cultures. In contrast, no effects were found on IFN-γ or TNF-α production. The supcrantigen streptococcal pyrogenic exotoxin-A (SPE-A) induced vigorous cell activation and extensive cytokine synthesis. IVIG was added either at the beginning or 24 h after the initiation of cultures in order to elucidate the importance of direct toxinneutralization. Addition of IVIG from the beginning of cultures induced a strong reduction of blast transformation and an almost complete inhibition of lymphokinc production, in particular of IFN-γ and TNF-β. Supplementation with IVIG 24 h after initiation of cultures also led to a significant decrease in lymphokine synthesis. Monokine production (IL-1α, IL-1β, IL-lra, IL-6 and IL-8) was either unaffected or even increased. These two facts argue against direct antigen-neutralization as being the only mechanism at work. However, in IVIG-exposed PBMC stimulated with LPS, IL-6 production was significantly r,educed. A significant upregulation of IL-lra was noticed in unstimulated PBMC cultured with IVIG. The results in all the experiments did not indicate a cytotoxic effect by IVIG on cell survival and the production of certain cytokines were unaffected. Instead, the authors believe that the results suggest a previously little examined functional link where the humoral immune response may have direct immunoregulatory effects on the cellular immune system.
Intravenous immune globulin therapy of lupus nephritis: use of pathogenic anti-DNA-reactive IgG
Authors: Silvestris F , D'Amore O , Cafforio P , Savino L , Dammacco F
Published: January 2019

The authors have recently shown that antibodies with anti-idiotype (Id) specificity to pathogenic Ids of lupus nephritis may occasionally occur in several intravenous immune globulin (IVIG) preparations because they are present in healthy donors and the healthy relatives of SLE patients. In the present study, the authors purified these anti-Ids and treated two SLE patients with nephritis in parallel with conventional high-dose IVIG management with a commercial preparation (IVIG 6) in three controls for two months. Because pathogenic Ids of anti-DNA molecules, such as both 8·l2 and F4 Ids. show a cationic mobility in isoclectrie focusing, a commercial preparation of IVIG (11) was absorbed on a Sepharose column coupled with DC-305-39 myeloma protein, namely a 8·l2+ and F4+ cationic IgG. Infusion of the eluate (EL-11) induced a prompt resolution of proteinuria levels and an evident decrease of serum levels of anti-DNA antibodies in both patients, whereas in the three controls, proteinuria and anti-DNA antibodies were scarcely reduced. In addition, plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α were also significantly influenced by both treatments. The mean values of both cytokines increased significantly after 1 h and then progressively declined over the next 48 h. It was of interest, however, that the increased TNF-α in the two EL-11-treated patients was significantly lower than in the three controls. The data suggest that reduction of active lupus nephritis by enriched specific anti-Id molecules is the result of two (or perhaps more) mechanisms: suppression of pathogenic idiotypes at the cellular level and improvement in the mesangium of the secretion of antiinflammatory cytokines, such as IL-6. whose defective function is related to the autoimmune disorder.
Composite cardiovascular risk factor target achievement and its predictors in US adults with diabetes: The Diabetes Collaborative Registry
Authors: Fan Wenjun , Song Yang , Inzucchi Silvio E. , Sperling Laurence , Cannon Christopher P. , Arnold Suzanne V. , Kosiborod Mikhail , Wong Nathan D.
Published: January 2019

Aim

To investigate multiple risk factor target attainment in adults with diabetes mellitus (DM) for atherosclerotic cardiovascular disease (ASCVD) prevention and the predictors of such attainment in a contemporary DM registry.

Methods

In the US Diabetes Collaborative Registry we identified patients who were at target for glycated haemoglobin (HbA1c; < 53 mmol/mol (7%) or < 64 mmol/mol (8%) if with ASCVD), LDL cholesterol (< 2.6 mmol/L (100 mg/dL) or < 1.8 mmol/L (70 mg/dL) 1.8 if with ASCVD) and blood pressure (BP; <140/90 mmHg and < 130/80 mmHg as an alternate), and who had non‐smoking status, by sex, race and history of ASCVD. Multiple logistic regression was used to examine predictors of target attainment.

Results

In 74 393 patients with DM who had available data (mean age 69.0 years, 41.0% women), overall target attainment for HbA1c, BP, LDL cholesterol and non‐smoking status was 73.6%, 69.0% (40.3% for BP <130/80 mmHg), 48.6% and 85.2%, respectively. Only 21.6% (13.0% with BP <130/80 mmHg) were at target for all four measures, and the proportions were higher in men (23.6%) versus women (18.6%) and in white people (22.5%) versus African‐American people (14.7%) and people of other races (20.8%; P < 0.01). A total of 62.4% were on a moderate‐/high‐intensity statin. Age (≥65 years: odds ratio [OR] 1.9, 95% confidence interval [CI] 1.7‐2.0; and 55‐64 years: OR 1.3, 95% CI 1.2‐1.4 vs. <55 years), male sex (OR 1.3, 95% CI 1.3‐1.4), white race (OR 1.4, 95% CI 1.3‐1.5), middle or high income (ORs 1.1, 95% CI 1.1‐1.2 or 1.4, 95% CI 1.4‐1.5, respectively) were associated, and depression (OR 0.9, 95% CI 0.8‐1.0) was inversely associated with meeting all four targets (all P = 0.01 to P < 0.001).

Conclusions

In our US registry of patients with DM, only one in five patients were achieving comprehensive risk factor control. Multifactorial interventions will be necessary to optimize ASCVD risk factor control.
Dapagliflozin and cardiovascular mortality and disease outcomes in a population with type 2 diabetes similar to that of the DECLARE‐TIMI 58 trial: A nationwide observational study
Authors: Norhammar Anna , Bodegård Johan , Nyström Thomas , Thuresson Marcus , Nathanson David , Eriksson Jan W.
Published: January 2019

Aims

To investigate cardiovascular (CV) safety and event rates for dapagliflozin versus other glucose‐lowering drugs (GLDs) in a real‐world type 2 diabetes population after applying the main inclusion criteria and outcomes from the DECLARE‐TIMI 58 study.

Methods

Patients with new initiation of dapagliflozin and/or other GLDs were identified in Swedish nationwide healthcare registries for the period 2013 to 2016. Patients were included if they met the main DECLARE‐TIMI 58 inclusion criteria: age ≥40 years and established CV disease or presence of multiple‐risk factors, e.g. men aged ≥55 years and women aged ≥60 years with hypertension or dyslipidaemia. Propensity scores for the likelihood of dapagliflozin initiation were calculated, then 1:3 matching was carried out. DECLARE‐TIMI 58 outcomes were hospitalization for heart failure (HHF) or CV‐specific mortality, and major adverse CV events (MACE; CV‐specific mortality, myocardial infarction, or stroke). Cox survival models were used to estimate hazard ratios (HRs).

Results

After matching, a total of 28 408 new‐users of dapagliflozin and/or other GLDs were identified, forming the population for the present study (henceforth referred to as the DECLARE‐like cohort. The mean age of this cohort was 66 years, and 34% had established CV disease. Dapagliflozin was associated with 21% lower risk of HHF or CV mortality versus other GLDs (HR 0.79, 95% confidence interval [CI] 0.69‐0.92) and had no significant association with MACE (HR 0.90, 95% CI 0.79‐1.03). HHF and CV mortality risks, separately, were lower at HR 0.79 (95% CI 0.67‐0.93) and HR 0.75 (95% CI 0.57‐0.97), respectively. Non‐significant associations were seen for myocardial infarction and stroke: HR 0.91 (95% CI 0.74‐1.11) and HR 1.06 (95% CI 0.87‐1.30), respectively.

Conclusion

In a real‐world population similar to those included in the DECLARE‐TIMI 58 study, dapagliflozin was safe with regard to CV outcomes and resulted in lower event rates of HHF and CV mortality versus other GLDs.
Knitting patterns of biodiversity, range size and body size in aquatic beetle faunas: significant relationships but slightly divergent drivers
Authors: Heino Jani , Alahuhta Janne
Published: January 2019

1. Ecogeographical rules refer to recurring patterns in nature, including the latitudinal diversity gradient (LDG), Rapoport's rule and Bergmann's rule, amongst others. In the present study, the existence of these rules was examined for diving beetles (Coleoptera: Dytiscidae), a family of aquatic predatory beetles.

2. Assemblage‐level data were analysed for diving beetles, focusing on species richness, local contribution to beta diversity (LCBD), mean range size and mean body size across the biogeographical provinces of Northern Europe. First, each of these variables was correlated with latitude, and then variation in each variable was modelled using actual environmental variables in boosted regression tree analysis.

3. Species richness was found to decrease with latitude, LCBD increased with latitude, mean range size did not show a significant relationship with latitude, and mean body size decreased with latitude. The latter finding was in contrast to Bergmann's rule. The actual environmental variables best predicting variation in these four response variables varied among the models, although they generally included temperature‐related and land use variables as the most influential ones.

4. The results obtained in the present study suggest that diving beetles conformed to the LDG, did not follow Rapoport's rule, and showed a reversed latitudinal gradient in the context of Bergmann's rule. In addition, species‐poor provinces harboured ecologically most unique faunas, suggesting that species richness and LCBD are complementary measures of biodiversity.

5. Even though general support was not found for most of the ecogeographical rules examined, the findings of the present study are interesting because they suggest that aquatic ectothermic invertebrates may show patterns different from those originally described for terrestrial endothermic vertebrates.
Responses of an endangered brown bear population to climate change based on predictable food resource and shelter alterations
Authors: Penteriani Vincenzo , Zarzo‐Arias Alejandra , Novo‐Fernández Alís , Bombieri Giulia , López‐Sánchez Carlos A.
Published: January 2019

The survival of an increasing number of species is threatened by climate change: 20%–30% of plants and animals seem to be at risk of range shift or extinction if global warming reaches levels projected to occur by the end of this century. Plant range shifts may determine whether animal species that rely on plant availability for food and shelter will be affected by new patterns of plant occupancy and availability. Brown bears in temperate forested habitats mostly forage on plants and it may be expected that climate change will affect the viability of the endangered populations of southern Europe. Here, we assess the potential impact of climate change on seven plants that represent the main food resources and shelter for the endangered population of brown bears in the Cantabrian Mountains (Spain). Our simulations suggest that the geographic range of these plants might be altered under future climate warming, with most bear resources reducing their range. As a consequence, this brown bear population is expected to decline drastically in the next 50 years. Range shifts of brown bear are also expected to displace individuals from mountainous areas towards more humanized ones, where we can expect an increase in conflicts and bear mortality rates. Additional negative effects might include: (a) a tendency to a more carnivorous diet, which would increase conflicts with cattle farmers; (b) limited fat storage before hibernation due to the reduction of oak forests; (c) increased intraspecific competition with other acorn consumers, that is, wild ungulates and free‐ranging livestock; and (d) larger displacements between seasons to find main trophic resources. The magnitude of the changes projected by our models emphasizes that conservation practices focused only on bears may not be appropriate and thus we need more dynamic conservation planning aimed at reducing the impact of climate change in forested landscapes.
Bioaccessibility and antioxidant activity of phenolic compounds in cooked pulses
Authors: Lafarga Tomás , Villaró Silvia , Bobo Gloria , Simó Joan , Aguiló‐Aguayo Ingrid
Published: January 2019

The aim of this study was to evaluate the bioaccessibility of polyphenols and antioxidant activity in cooked pulses and to study the effect of cooking on their total phenolic content (TPC) and antioxidant capacity. Cooked faba beans showed the highest TPC, followed by soybeans and lentils or peas. TPC ranged from 10.4 ± 0.2 to 52.9 ± 0.3 mg/100 g and was positively correlated with antioxidant activity. Cooking resulted in increased TPC and antioxidant activity of the methanolic extracts, caused by cell disruption and improved extraction of polyphenols. Although polyphenols were lost in the cooking water, boiled legumes had more polyphenols than those resulting cooking broths. In vitro gastrointestinal digestion resulted in increased TPC and antioxidant capacity of the extracts. Soybeans showed the highest amount of bioaccessible polyphenols. The release of phenolics from cooked legumes was mainly achieved during the intestinal phase. Literature data may underestimate the TPC and antioxidant capacity of pulses.
Degradation of anti‐nutritional factors and reduction of immunoreactivity of tempeh by co‐fermentation with Rhizopus oligosporus RT‐3 and Actinomucor elegans DCY‐1
Authors: Huang Lu , Wang Chenxi , Zhang Yongzhu , Chen Xiaohong , Huang Zhihai , Xing Guangliang , Dong Mingsheng
Published: January 2019

The effects of solid‐state fermentation with four filamentous fungi (Rhizopus oligosporus, Actinomucor elegans, Neurospora crassa and Rhizopus oryzae) and their combination on the degradation of protein allergens and anti‐nutritional factors (ANFs) of tempeh were evaluated. Glycinin, β‐conglycinin, trypsin inhibitor and flatulence‐causing oligosaccharides were significantly hydrolysed by all assayed strains but the level of reduction of ANFs depended on the strain. ELISA was conducted to evaluate IgE immunoreactivity using sera from soy sensitive individuals. Results revealed that co‐fermentation of R. oligosporus and A. elegans resulted in the highest reduction in IgE immunoreactivity for all sera used and showed greatest degradations on α’, α, β, acidic subunits (100% hydrolysed) and extensive hydrolysis of flatulence‐causing oligosaccharides. Tempeh fermented with R. oligosporus and A. elegans displayed high level of soluble protein and peptide (<10 kD) content. Co‐fermentation of R. oligosporus and A. elegans was proved to be effective in producing hypoallergenic tempeh.
Effects of incorporating roasted lupin (Lupinus angustifolius) flour on the physicochemical and sensory attributes of beef sausage
Authors: Leonard William , Hutchings Scott C. , Warner Robyn D. , Fang Zhongxiang
Published: January 2019

The effects of incorporating lupin flour on the physicochemical and sensory characteristics of beef sausages were explored. Lupin (Lupinus angustifolius) flour was roasted, then hydrated to match the moisture content of beef meat. The beef sausage samples were manufactured for six treatments by replacing beef with hydrated lupin flour from 0% to 36% (w/w). Proximate analysis revealed that carbohydrate (dietary fibre) level was increased from 9.62% to 19.31%, whereas fat content was decreased from 11.62% to 7.91%. Inclusion of lupin flour increased the meat emulsion stability (fluid released decreased from 9.35% to 1.53%) and decreased cooking loss from 22.70% to 14.30%. Softer texture and greater adhesiveness were observed in lupin‐incorporated formulations. Sensory evaluation indicated no significant difference between control and 12% lupin‐enriched beef sausage formulation in appearance, aroma, flavour and overall liking, suggesting lupin flour can be added to beef sausage at this level without compromising consumer acceptance.
In vitro antioxidant activity and phenolic profiles of tropical fruit by‐products
Authors: Nguyen Nhat Minh Phuong , Le Thien Trung , Vissenaekens Hanne , Gonzales Gerard Bryan , Van Camp John , Smagghe Guy , Raes Katleen
Published: January 2019

Peel and seeds of red‐skinned passion fruit, mango, longan, rambutan, white‐flesh and red‐flesh dragon fruit were screened for their in vitro antioxidant activity, and determination of a detailed profile of phenolic compounds. Rambutan peel and mango seed extracts exhibited the highest total phenolic content and antioxidant activities (DPPH, ABTS and FRAP values). By using UPLC‐QTOF‐MS/MS analysis, the profiles of soluble and bound phenolics in the fruit by‐products were obtained. Ellagic acid, geraniin, quercetin hexoside, gallic and galloyshikimic acid were predominant in rambutan peel, whereas, mangiferin, ellagic acid and galloy(di)glucoside were the major phenolic compounds in mango seed. Main phenolic compounds in longan peel were ellagic acid, galloyldiglucoside, and gallic acid, while in dragon fruit peel this was isorhamnetin glycoside, isorhamnetin glucorhamoside. Meanwhile, rutin and quercetin hexoside were predominant in passion fruit peel. These findings contribute significantly to the database of phenolic profiles of by‐products of tropical fruits.
Free radical scavenging activities of phytochemical mixtures and aqueous methanolic extracts recovered from processed coffee leaves
Authors: Chen Xiumin , Kitts David D. , Ji Dayi , Ding Jian
Published: January 2019

It is well known that the choice of extraction solvents greatly affects both phytochemical composition and related bioactivity of plant extract. Herein, we show that coffee leaf extracts derived from 80% methanol have no effect on basal nitric oxide production in Raw 264.7 cells, whereas, a different result was observed with a previous hot water extract. Phytochemical mixtures formulated to contain equivalent amounts of CQAs, mangiferin and rutin know to present in coffee leaves showed a relatively low (3.5–18.5%, TPC; 17.6–31.6%, ABTS; 7.9–13.6%, DPPH; and 8.5–29.7%, ORAC) contribution to antioxidant activities when compared to the coffee leaf extracts. We conclude that the solvent polarity is particularly important to the unique phytochemical mixture recovered, which in turn governs the bioactivity. This study also demonstrated that other phytochemicals in coffee leaves that were not measured in this study are important in assessing total antioxidant activity of this potential plant beverage.
The march of governance and the actualities of failure: the case of economic development twenty years on
Authors: Jones Martin
Published: January 2019

Twenty years ago, Bob Jessop (1998) published a defining piece on the “rise of governance” and the “risks of failure”, using the example of economic development to frame concerns with the state of capitalism at that time. This charted the rise of governance, outlined key governance practices, and offered preliminary reflections on the nature, forms, and logic of governance failure ‒ given that whilst there are already extensive literatures on market failure and state failure, governance failure required focused concern and thematic analysis. This paper, 20 years post‐Jessop on governance rise and risks, tells the tale of how governance in Britain (and England specifically) has marched on and, building on Jessop, has indeed failed, repeatedly and spectacularly. The paper reveals Jessop's governance dilemmas in action and specifically how the contradictions and crises tendencies of capitalism have both necessitated the use of, and been played out in and through, geographical space. The paper reveals an economic governance landscape of unresolved crises and contradictions, which is linked to problems of state rationality and legitimation, exhibited by the Brexit debacle in Britain.
Is risperidone effective in reducing challenging behaviours in individuals with intellectual disabilities after 1 year or longer use? A placebo‐controlled, randomised, double‐blind discontinuation study
Authors: Ramerman L. , de Kuijper G. , Scheers T. , Vink M. , Vrijmoeth P. , Hoekstra P. J.
Published: January 2019

Background

Many people with intellectual disabilities use risperidone long term for the management of challenging behaviours, despite its limited proof of effectiveness and its clear association with adverse events. Therefore, this study aimed to investigate the effectiveness of ongoing treatment with risperidone in reducing challenging behaviours versus controlled discontinuation on behaviour and health parameters.

Method

This was a placebo‐controlled, double‐blind, randomised discontinuation trial of risperidone. In the discontinuation group, risperidone was gradually replaced by a placebo over 14 weeks, while the control group maintained their existing dosage. Eight weeks after discontinuation, behaviour (as measured by the ‘Aberrant Behavior Checklist’) and health parameters (dyskinesia, akathisia, parkinsonism, weight, waist circumference, sedation and laboratory outcomes) were compared in both groups.

Results

A total of 25 participants were included in the trial, of which 11 were randomised into the discontinuation group and 14 were randomised into the continued treatment group. In the discontinuation group, 82% completely withdrew from risperidone. There was no significant change in irritability, compared with the continuation group, although there was a Group*Time effects on stereotypical behaviour in favour of the continuation group. Significant Group*Time effects were also found for weight, waist, body mass index, prolactin levels and testosterone levels, with beneficial effects for the discontinuation group.

Conclusion

Discontinuation of long‐term risperidone for reducing challenging behaviours is possible, without an increase in irritability. Discontinuation of risperidone may have beneficial effects on weight, waist circumference, prolactin levels and testosterone levels. The study suffered from difficulties in achieving the required sample size, which affected study power and generalizability.
Differences in Social Isolation and Its Relationship to Health by Rurality
Authors: Henning‐Smith Carrie , Moscovice Ira , Kozhimannil Katy
Published: January 2019

Purpose

Social isolation is an urgent threat to public health. Meanwhile, health outcomes across multiple measures are worse in rural areas, where distance to neighbors is often greater and opportunities for social interaction may be scarcer. Still, very little research examines rural‐urban differences in social isolation. This study addresses that gap by examining differences in social isolation by rurality among US older adults.

Methods

Using Wave 2 of the National Social Life, Health, and Aging Project data (n = 2,439), we measured differences between urban and rural (micropolitan or noncore) residents across multiple dimensions of social isolation. We also conducted multivariable analysis to assess the associations between rurality, sociodemographic characteristics, and loneliness, overall and by rurality. Finally, we conducted multivariable analysis to assess the association between social isolation and self‐rated health, adjusting for rurality.

Findings

Compared to urban residents, rural residents had more social relationships and micropolitan rural residents were more likely to be able to rely on family members (95.8% vs 91.3%, P < .05). Micropolitan rural residents reported lower rates of loneliness than urban residents after adjusting for sociodemographic and health characteristics (b = –0.32, P < .05), whereas noncore rural, non‐Hispanic black residents had a greater likelihood of reporting loneliness (b = 4.33, P < .001).

Conclusions

Overall, noncore and micropolitan rural residents reported less social isolation and more social relationships than urban residents. However, there were differences by race and ethnicity among rural residents in perceived loneliness. Policies and programs to address social isolation should be tailored by geography and should account for within‐rural differences in risk factors.
Evaluation of alternative pond production systems for raising largemouth bass, Micropterus salmoides
Authors: Quintero Herbert , Roy Luke A. , Park Jeonghwan , Kelly Anita M. , Heikes David
Published: January 2019

This study evaluated three different pond‐based production systems for raising largemouth bass, Micropterus salmoides, for the food fish market, using nine 0.04‐ha ponds. Treatments included traditional ponds (TP), intensively aerated ponds (IAP), and split‐pond systems (SPS). TP and SPS ponds were aerated at 9.3 kW/ha, while IAP was aerated at 18.6 kW/ha. TP was stocked at 7,500 fish per ha (three replicates per treatment), and the other two production systems (SPS, IAP) were stocked with 12,500 fish per ha. Feed‐habituated advanced fingerlings (128 ± 47.6 g mean individual weight) were cultured for 157 days. Fish were fed a formulated diet (42% protein, 16% lipid) four times a day, feeding with a maximum allowance of 3% of total body weight and readjusted to the initial body weight biweekly. Fish raised in the SPS displayed a significantly lower specific growth rate, lower individual final weight, and lower weight gain, but the biomass gained was significantly higher than TP but not IAP. Final biomass gained was 50% higher in the SPS and IAP than in the TP. Survival rate and feed conversion ratio were not significantly different among treatments and ranged from 71 to 79% and 1.64 to 2.14, respectively.
From fish‐processing waste to feed additives for crayfish
Authors: Rodriguez Yamila Eliana , Sacristán Hernán Javier , Laitano María Victoria , López‐Greco Laura Susana , Fernández‐Gimenez Analía V.
Published: January 2019

This research studied the in vitro compatibility of Cherax quadricarinatus digestive proteases and crude enzyme extracts recovered from fish‐processing waste to evaluate their potential use as feed additives to increase digestion efficiency in decapod crustaceans. The sources of exogenous enzymes were: Pleoticus muelleri (Pm), Artemesia longinaris (Al), and Illex argentinus (Ia). The midgut glands of early (7.2 ± 0.34 g) and advanced juveniles (13.8 ± 1.49 g) of C. quadricarinatus were used for all the assays. The compatibility and synergy between crayfish and exogenous enzymes were evaluated through sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) electrophoresis and the hydrolysis of azocasein and four different meals. SDS–PAGE gels demonstrated that crayfish bands remained active when their enzymes were combined with the enzymes from Pm and Ia. An apparent enzymatic synergism was found when Pm and crayfish proteases were incubated together at pH 6 and 8 with azocasein (p ˂ 0.05). The ability to hydrolyze the different feed ingredients varied among the enzyme combinations assayed. Our findings suggest that fish waste has potential as a source of proteases, adding value to these processing residues and promoting a zero‐waste industry. Enzymes obtained from Pm and Ia are suitable to be used as food additives for crayfish. The results should be validated through feeding trials.
Testing an hypothesis of hybrid zone movement for toads in France
Authors: van Riemsdijk Isolde , Butlin Roger K. , Wielstra Ben , Arntzen Jan W.
Published: January 2019

Hybrid zone movement may result in substantial unidirectional introgression of selectively neutral material from the local to the advancing species, leaving a genetic footprint. This genetic footprint is represented by a trail of asymmetric tails and displaced cline centres in the wake of the moving hybrid zone. A peak of admixture linkage disequilibrium is predicted to exist ahead of the centre of the moving hybrid zone. We test these predictions of the movement hypothesis in a hybrid zone between common (Bufo bufo) and spined toads (B. spinosus), using 31 nuclear and one mtDNA SNPs along a transect in the northwest of France. Average effective selection inBufohybrids is low and clines vary in shape and centre. A weak pattern of asymmetric introgression is inferred from cline discordance of seven nuclear markers. The dominant direction of gene flow is fromB. spinosustoB. bufoand is in support of southward movement of the hybrid zone. Conversely, a peak of admixture linkage disequilibrium north of the hybrid zone suggests northward movement. These contrasting results can be explained by reproductive isolation of theB. spinosusandB. bufogene pools at the southern (B. spinosus) side of the hybrid zone. The joint occurrence of asymmetric introgression and admixture linkage disequilibrium can also be explained by the combination of low dispersal and random genetic drift due to low effective population sizes.
Autopsy report of a late delayed radiation injury after a period of 45 years
Authors: Tanikawa Satoshi , Kato Yasutaka , Tanino Mishie , Terasaka Shunsuke , Kurokawa Yasuo , Arai Nobutaka , Nagashima Kazuo , Tanaka Shinya
Published: January 2019

For delayed radiation injury, image analysis has considerably advanced, but neuropathological findings are still required to establish diagnosis. A patient who had received radiation therapy for pineal germinoma at age 14 developed neurological and psychiatric abnormalities after 15 years as a late delayed radiation injury. Autopsy at age 59 revealed diffuse changes in the white matter consisting in order of severity of myelin pallor, demyelination, and necrosis which were characterized by a lack of glial reaction. The cerebral cortex was relatively well preserved. As delayed radiation injuries, hyalinous changes in the vascular wall, angiomatous lesions and, fresh and old petechial hemorrhages were found. Moreover, vascular changes associated with arteriosclerosis were also present. Furthermore, a focal glial nodule was detected which was considered to be a new radiation‐induced neoplasia. These findings suggest that late delayed radiation injury may slowly develop over 30 years and may involve damage to neuroglial stem cell compensation. It is also evident that arteriosclerotic changes and newly induced neoplasia may develop in delayed radiation injury cases.
Metabolic reprogramming in the pathogenesis of glioma: Update
Authors: Masui Kenta , Onizuka Hiromi , Cavenee Webster K. , Mischel Paul S. , Shibata Noriyuki
Published: January 2019

Cancer is a genetic disease that is currently classified not only by its tissue and cell type of origin but increasingly by its molecular composition. Increasingly, tumor classification and subtyping is being performed based upon the oncogene gains, tumor suppressor losses, and associated epigenetic and transcriptional features. However, cancers, including brain tumors, are also characterized by profound alterations in cellular metabolism. At present, even though signature mutations in known metabolic enzymes are recognized as being important, the metabolic landscape of tumors is not currently incorporated into tumor diagnostic categories. Here we describe a set of recent discoveries on metabolic reprogramming driven by mutations in the genes for the isocitrate dehydrogenase (IDH) and receptor tyrosine kinase (RTK) pathways, which are the most commonly observed aberrations in diffuse gliomas. We highlight the importance of oncometabolites to dynamically shift the epigenetic landscape in IDH‐mutant gliomas, and c‐Myc and mechanistic target of rapamycin (mTOR) complexes in RTK‐mutated gliomas to adapt to the microenvironment through metabolic reprogramming. These signify the integration of the genetic mutations with metabolic reprogramming and epigenetic shifts in diffuse gliomas, shedding new light onto potential patient subsets, coupled with information to guide the development of new therapeutic opportunities against the deadly types of brain tumors.
Increasing compliance of safe medication administration in pediatric anesthesia by use of a standardized checklist
Authors: Kanjia Megha Karkera , Adler Adam C. , Buck David , Varughese Anna M.
Published: January 2019

Background

Medication errors pose a significant risk perioperatively. In the perioperative environment, common medication administration processes are not typically performed. Given the common administration of potentially harmful medications and the potential for medication errors, patient risk is substantial. Specifically, intravenous acetaminophen has been used more frequently in the perioperative period which yielded an increase in medication administration errors reported.

Aims

This project was initiated by Cincinnati Children's Hospital after an increase in perioperative acetaminophen dosing errors was reported. After mapping the administration process of perioperative acetaminophen, we sought to reduce medication errors by the use of a safety checklist. Acetaminophen was used as a surrogate for other perioperative medications in this quality improvement project.

Methods

Use of a failure mode effects analysis assisted the team in understanding the failures of the process of safe medication administration. Subsequently, key drivers of this process were designed to include accurate understanding and documentation of medication history, consistent communication between perioperative caregivers, and an efficient checklist process. A multidisciplinary team conducted a series of tests to modify key drivers. Data were collected by utilizing data from a paper checklist, prior to the electronic medical record change that was prompted by this study. A total of 633 checklists and electronic medical records were analyzed during a 6‐month period; data were analyzed using control charts and statistical process control methods.

Results/Analysis

The percentage of compliance with the safe administration checklist for acetaminophen in the preoperative period increased to 97%. Use of the paper checklist likely prompted the appropriate increase in compliance with safe administration. Additionally, provider‐specific feedback produced a significant increase in compliance with the use of the checklist.

Conclusion

Application of quality improvement methods, specifically a safety checklist, were utilized to improve the safe administration of acetaminophen during the perioperative period. Increasing reliability of accurate delivery and administration of medication to patients are crucial in optimizing patient safety. Use of a medication safety checklist may be beneficial in reducing potential administration errors, specifically for high‐risk medications.
Filtering performance in visual working memory is improved by reducing early spatial attention to the distractors
Authors: Allon Ayala S. , Luria Roy
Published: January 2019

We investigated the underlying processes that enable improving filtering irrelevant items from entering visual working memory (WM). To this end, participants performed a bilateral change‐detection task in which either targets or targets along with distractors (i.e., the filtering condition) appeared in the memory array while ERPs were recorded. In the cue‐present condition, we provided a spatial cue coupled with a temporal cue regarding where and when the distractors would appear. On some of the filtering trials, after the offset of the memory array, task‐irrelevant probes were briefly flashed either at the locations of the targets or at the locations of the distractors. This enabled measuring whether reactivating the filtering settings resulted in reducing spatial attentional resources to the distractors, allocating additional spatial attentional resources to the targets, or both, as was measured by the P1/N1 amplitude. Results revealed that, relative to the cue‐absent condition, in the cue‐present condition the P1/N1 amplitude was reduced for probes at the distractors and was similar for probes at the targets. In addition, the reduction in the P1/N1 amplitude was accompanied by a reduced filtering cost in accuracy performance in the cue‐present condition relative to the cue‐absent condition. These findings suggest that reactivating the distractor filtering settings improved filtering performance in visual WM by reducing the allocation of spatial attention to the distractors already at early processing stages, and not by allocating additional spatial attentional resources to the targets.
Potential of Citizen Science for Enhancing Infrastructure Monitoring Data and Decision‐Support Models for Local Communities
Authors: Gharaibeh Nasir , Oti Isaac , Meyer Michelle , Hendricks Marccus , Van Zandt Shannon
Published: January 2019

Citizen science is a process by which volunteer members of the public, who commonly lack advanced training in science, engage in scientific activities (e.g., data collection) that might otherwise be beyond the reach of professional researchers or practitioners. The purpose of this article is to discuss how citizen‐science projects coordinated by interdisciplinary teams of engineers and social scientists can potentially enhance infrastructure monitoring data and decision‐support models for local communities. The article provides an interdisciplinary definition of infrastructure data quality that extends beyond accuracy to include currency, timeliness, completeness, and equitability. We argue that with this expanded definition of data quality, citizen science can be a viable method for enhancing the quality of infrastructure monitoring data, and ultimately the credibility of risk analysis and decision‐support models that use these data. The article concludes with a set of questions to aid in producing high‐quality infrastructure monitoring data by volunteer citizen scientists.
Measuring fiscal spillovers in EMU and beyond: A Global VAR approach
Authors: Belke Ansgar H. , Osowski Thomas U.
Published: January 2019

This paper identifies and measures fiscal spillovers in the EU countries empirically using a global vector autoregression (GVAR) model. Our aim was to look at the sign and the absolute values of fiscal spillovers in a countrywise perspective and at the time profile (impulse response) of the impacts of fiscal shocks. We find moderate spillover effects of fiscal policy shocks originating in Germany and France. However, there is significant variation regarding the magnitude of the spillovers on individual destination countries and country clusters. Furthermore, we find some evidence that German or French fiscal spillovers are stronger on EMU than on non‐EMU countries.
Understanding low interest rates: evidence from Japan, Euro Area, United States and United Kingdom
Authors: Gehringer Agnieszka , Mayer Thomas
Published: January 2019

The paper investigates the factors determining long‐term interest rates. Our estimation results for major industrialized economies suggest that central banks have actually had a key influence on the level of long‐term interest rates. We thus show that 1) the customary neoclassical model of interest rate determination, on which central banks tend to rely, is neither rooted in the institutional setup of the credit markets nor supported by the data, and that 2) the Austrian explanation incorporated in the model of Wicksell–Mises–Hayek of the credit and business cycle fits better the economic reality. As central bank policy makers might lack the necessary knowledge and foresight to set market rates to levels consistent with economic fundamentals, there is a high chance of misalignments of market rates. The correction of misalignments could lead to severe economic disruptions.