bluuebunny/crossref_metadata_2025 huggingface dataset:
Dialogue Exhibitions: Putting Transformative Learning Theory into Practice
Authors: Cohen Orna , Heinecke Andreas
Published: March 2018

Exhibitions in museums, science centers, and other socio‐cultural locations can play a key role in shifting patterns in interpersonal relationships and understanding between “us” and “them.” This objective of changing attitudes and shifting perspectives can be accomplished with exhibitions designed with a clear methodology based on the Theory of Transformative Learning (Mezirow 1978, 1991, 2000). How can museum educators ensure that learners internalize attitude changes and perspective shifts, and what evidence can be shown that these learning objectives have actually been met? In this article, we explain the Theory of Transformative Learning and how it is applied to exhibitions to facilitate exactly these objectives.
Should school‐based physical therapists be more targeted in their interventions for children with disabilities?
Authors: Knox Virginia
Published: March 2018

This commentary is on the original article by McCoy et al. on pages 1140–1148 of this issue.
Effects of empagliflozin on cardiorespiratory fitness and significant interaction of loop diuretics
Authors: Carbone Salvatore , Canada Justin M. , Billingsley Hayley E. , Kadariya Dinesh , Dixon Dave L. , Trankle Cory R. , Buckley Leo F. , Markley Roshanak , Vo Chau , Medina de Chazal Horacio , Christopher Sanah , Buzzetti Raffaella , Van Tassell Benjamin W. , Abbate Antonio
Published: March 2018

The effects of empagliflozin on cardiorespiratory fitness in patients with type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) are unknown. In this pilot study we determined the effects of empagliflozin 10 mg/d for 4 weeks on peak oxygen consumption (VO2) in 15 patients with T2DM and HFrEF. As an exploratory analysis, we assessed whether there was an interaction of the effects of empagliflozin on peak VO2 of loop diuretics. Empagliflozin reduced body weight (−1.7 kg; P = .031), but did not change peak VO2 (from 14.5 mL kg−1 min−1 [12.6‐17.8] to 15.8 [12.5‐17.4] mL kg−1 min−1; P = .95). However, patients using loop diuretics (N = 9) demonstrated an improvement, whereas those without loop diuretics (N = 6) experienced a decrease in peak VO2 (+0.9 [0.1‐1.4] vs −0.9 [−2.1 to −0.3] mL kg−1 min−1; P = .001), and peak VO2 changes correlated with the baseline daily dose of diuretics (R = +0.83; P < .001). Empagliflozin did not improve peak VO2 in patients with T2DM and HFrEF. However, as a result of exploratory analysis, patients concomitantly treated with loop diuretics experienced a significant improvement in peak VO2.
Effect of once weekly dulaglutide by baseline beta‐cell function in people with type 2 diabetes in the AWARD programme
Authors: Mathieu Chantal , Del Prato Stefano , Botros Fady T. , Thieu Vivian T. , Pavo Imre , Jia Nan , Haupt Axel , Karanikas Chrisanthi A. , García‐Pérez Luis‐Emilio
Published: March 2018

Glucagon‐like peptide‐1 receptor agonists lower blood glucose in type 2 diabetes (T2D) partially through glucose‐dependent stimulation of insulin secretion. The aim of this study was to investigate whether beta‐cell function (as measured by HOMA2‐%B) at baseline affects the glycaemic response to dulaglutide. Dulaglutide‐treated patients from AWARD‐1, AWARD‐3 and AWARD‐6 clinical studies were categorised based on their homeostatic model assessment of beta‐cell function (HOMA2‐%B) tertiles. Changes in glycaemic measures in response to treatment with once‐weekly dulaglutide were evaluated in each HOMA2‐%B tertile. Patients with low HOMA2‐%B had higher baseline glycated haemoglobin (HbA1c), fasting and postprandial blood glucose, and longer duration of diabetes (P < .001, all) (mean low, middle and high tertiles with dulaglutide 1.5 mg: HOMAB‐2%B, 31%, 58%, 109%; HbA1c, 8.7%, 7.7%, 7.3%, respectively). At 26 weeks, the low tertile experienced larger reductions in HbA1c compared to the high tertile with dulaglutide 1.5 mg (mean; −1.55% vs. −0.98% [−16.94 vs. −10.71 mmol/mol]). Differences between low and high tertiles disappeared when adjusted for baseline HbA1c (LSM; −1.00 vs. −1.18% [−10.93 vs. −12.90 mmol/mol]). Greater decreases in fasting blood glucose and greater increases in fasting C‐peptide were observed in the low tertile. Similar increases in HOMA2‐%B were observed in all tertiles. Dulaglutide demonstrated clinically relevant HbA1c reduction irrespective of estimated baseline beta‐cell function.
An adaptive bivariate kernel smoothing method for determining instars of Austrosimulium tillyardianum (Diptera: Simuliidae) larvae
Authors: Cen Guan‐Jun , Gao Xu‐Yuan , Long Xiu‐Zhen , Zeng Xian‐Ru , Liu Ji‐Min , Wei De‐Wei , Yu Yong‐Hao
Published: March 2018

1. In insects, instar determination is generally based on the frequency distribution of sclerotised body part measurements. Commonly used univariate methods, such as histograms and univariate kernel smoothing, are not sufficient to reflect the distribution of the measurements, because development of sclerotised body parts is multidimensional.

2. This study used an adaptive bivariate kernel smoothing method, based on 10 pairs of separating variables, to differentiate instars of Austrosimulium tillyardianum (Diptera: Simuliidae) larvae in two‐dimensional space. A variable bandwidth matrix was used and separation lines between instars were defined.

Using the Crosby growth ratio, Brooks' rule and the new standard recently proposed, larvae were separated into nine instars. It was found that, using the bivariate kernel smoothing method, the clustering accuracy and determination of separation lines as instar class limits were higher than those associated with the univariate kernel smoothing method. With the exceptions of the paired separating variables, head capsule length and antennal segment 3 length (AS3L), the mean probabilities of correct classifications was > 85%. The pair of separating variables that yielded the greatest classification accuracy comprised mandible length (ML) and AS3L, which had mean probabilities of 0.8984. The clustering accuracy was higher for early‐ and late‐instar larvae, but lower for instars 6 and 7.

The adaptive bivariate kernel smoothing method was better than univariate methods for instar determination, especially in the detection of divisions between instars and identification of a larval instar.
Investing in early public works: financial risks and returns in English and Welsh turnpikes, 1820–82
Authors: Bogart Dan
Published: March 2018

Private and local investors provided much of the capital to improve England's infrastructure during its industrialization. This study investigates the financial returns to investors in turnpike road trusts. It draws on parliamentary reports which provide comprehensive data on finances, including payments to bondholders. One key finding is that turnpike trusts paid their bondholders a return above the yield on government bonds before 1850. Afterwards turnpike interest payments declined, yet they still yielded competitive returns. Another key finding is that the risks were modest. Returns to holding individual turnpike bonds varied, with most paying 4 to 5 per cent and some paying zero. The latter were not the majority and in many cases interest payments resumed within a few years. Diversified portfolios of turnpike bonds enjoyed lower risks, and outperformed portfolios with railway and canal securities traded on the London exchange before 1850. Overall, the results contribute to a better understanding of the risks and returns associated with investing in early public works.
The state‐of‐the‐art in digital technology‐based assessment
Authors: O'Leary Michael , Scully Darina , Karakolidis Anastasios , Pitsia Vasiliki
Published: March 2018

The role of digital technology in assessment has received a great deal of attention in recent years. Naturally, technology offers many practical benefits, such as increased efficiency with regard to the design, implementation and scoring of existing assessments. More importantly, it also has the potential to have profound, transformative effects on the field of assessment by facilitating the integration of formative activities with accountability requirements and broadening the range of abilities and the scope of constructs that can be assessed. This article provides an overview of the current state‐of‐the‐art in digital technology‐based assessment, with particular reference to advances in the automated scoring of constructed responses, the assessment of complex 21st century skills in large‐scale assessments and innovations involving high fidelity virtual reality simulations. Key challenges with respect to each are highlighted before the extent to which digital technology is truly transforming assessment is considered.
Impact of white blood cells on thrombotic risk in patients with optimized platelet count in essential thrombocythemia
Authors: Buxhofer‐Ausch Veronika , Steurer Michael , Sormann Siegfried , Schloegl Ernst , Schimetta Wolfgang , Gisslinger Bettina , Schalling Martin , Krauth Maria Theresa , Thiele Jürgen , Ruckser Reinhard , Gastl Günther , Gisslinger Heinz
Published: March 2018

Objectives

Risk of thrombosis is significantly enhanced by both elevated platelet (PLT) and white blood cell (WBC) counts according to a retrospective analysis of a large anagrelide registry in thrombocythemic MPN patients. We were interested in the impact of elevated WBC counts on thrombosis risk in patients where PLT counts were reduced below the calculated cutoff of 574.5 G/L by treatment with anagrelide.

Methods

Cox regression analysis and Kaplan‐Meier plot were applied on all patients in the registry with optimized PLT counts.

Results

Using the calculated cutoff of 9.66 G/L for WBC, Cox regression analysis revealed a clear influence of elevated WBC counts on the occurrence of a major thrombotic event (P = .012). A Kaplan‐Meier plot revealed a markedly shorter time to a major thrombotic event for patients with WBC counts above the cutoff (P = .001).

Conclusions

These data suggest that additional correction of elevated WBC counts is mandatory in patients with optimally managed PLT counts to reduce thrombotic risk. This study is the first investigation in a prospectively observed large patient cohort which was treated homogenously allowing for evaluation of single parameters for an effect on thrombophilia.
Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking
Authors: Blackwell Kim T. , Salinas Armando G. , Tewatia Parul , English Brad , Hellgren Kotaleski Jeanette , Lovinger David M.
Published: March 2018

The striatum, the input structure of the basal ganglia, is a major site of learning and memory for goal‐directed actions and habit formation. Spiny projection neurons of the striatum integrate cortical, thalamic, and nigral inputs to learn associations, with cortico‐striatal synaptic plasticity as a learning mechanism. Signaling molecules implicated in synaptic plasticity are altered in alcohol withdrawal, which may contribute to overly strong learning and increased alcohol seeking and consumption. To understand how interactions among signaling molecules produce synaptic plasticity, we implemented a mechanistic model of signaling pathways activated by dopamine D1 receptors, acetylcholine receptors, and glutamate. We use our novel, computationally efficient simulator, NeuroRD, to simulate stochastic interactions both within and between dendritic spines. Dopamine release during theta burst and 20‐Hz stimulation was extrapolated from fast‐scan cyclic voltammetry data collected in mouse striatal slices. Our results show that the combined activity of several key plasticity molecules correctly predicts the occurrence of either LTP, LTD, or no plasticity for numerous experimental protocols. To investigate spatial interactions, we stimulate two spines, either adjacent or separated on a 20‐μm dendritic segment. Our results show that molecules underlying LTP exhibit spatial specificity, whereas 2‐arachidonoylglycerol exhibits a spatially diffuse elevation. We also implement changes in NMDA receptors, adenylyl cyclase, and G protein signaling that have been measured following chronic alcohol treatment. Simulations under these conditions suggest that the molecular changes can predict changes in synaptic plasticity, thereby accounting for some aspects of alcohol use disorder.
A silent eligibility trace enables dopamine‐dependent synaptic plasticity for reinforcement learning in the mouse striatum
Authors: Shindou Tomomi , Shindou Mayumi , Watanabe Sakurako , Wickens Jeffery
Published: March 2018

Dopamine‐dependent synaptic plasticity is a candidate mechanism for reinforcement learning. A silent eligibility trace – initiated by synaptic activity and transformed into synaptic strengthening by later action of dopamine – has been hypothesized to explain the retroactive effect of dopamine in reinforcing past behaviour. We tested this hypothesis by measuring time‐dependent modulation of synaptic plasticity by dopamine in adult mouse striatum, using whole‐cell recordings. Presynaptic activity followed by postsynaptic action potentials (pre–post) caused spike‐timing‐dependent long‐term depression in D1‐expressing neurons, but not in D2 neurons, and not if postsynaptic activity followed presynaptic activity. Subsequent experiments focused on D1 neurons. Applying a dopamine D1 receptor agonist during induction of pre–post plasticity caused long‐term potentiation. This long‐term potentiation was hidden by long‐term depression occurring concurrently and was unmasked when long‐term depression blocked an L‐type calcium channel antagonist. Long‐term potentiation was blocked by a Ca2+‐permeable AMPA receptor antagonist but not by an NMDA antagonist or an L‐type calcium channel antagonist. Pre–post stimulation caused transient elevation of rectification – a marker for expression of Ca2+‐permeable AMPA receptors – for 2–4‐s after stimulation. To test for an eligibility trace, dopamine was uncaged at specific time points before and after pre‐ and postsynaptic conjunction of activity. Dopamine caused potentiation selectively at synapses that were active 2‐s before dopamine release, but not at earlier or later times. Our results provide direct evidence for a silent eligibility trace in the synapses of striatal neurons. This dopamine‐timing‐dependent plasticity may play a central role in reinforcement learning.
Canalisation in the wild: effects of developmental conditions on physiological traits are inversely linked to their association with fitness
Authors: Boonekamp Jelle J. , Mulder Ellis , Verhulst Simon
Published: March 2018

Ecological conditions affect fitness, but mechanisms causing such effects are not well known, while evolved responses to environmental variation may depend on the underlying mechanisms. Consequences of environmental conditions vary strongly between traits, but a framework to interpret such variation is lacking. We propose that variation in trait response may be explained by differential canalisation, with traits with larger fitness effects showing weaker responses to environmental perturbations due to preferential resource allocation to such traits. We tested the canalisation hypothesis using brood size manipulation in wild jackdaw nestlings in which we measured eight physiological traits (mainly oxidative stress markers), and two feather traits. For each trait, we estimated manipulation response and association with fitness (over‐winter survival). As predicted, a strong negative correlation emerged between manipulation response and association with fitness (r =−0.76). We discuss the consequences of differential trait canalisation for the study of mechanisms mediating environmental effects on fitness.
Calcium plus magnesium indicates digestibility: the significance of the second major axis of plant chemical variation for ecological processes
Authors: Mládková Pavla , Mládek Jan , Hejduk Stanislav , Hejcman Michal , Pakeman Robin J.
Published: March 2018

Plant variation in nutrient concentrations encompasses two major axes. The first is connected to nitrogen (N) and phosphorus (P), reflects growth rate and has been designated as the leaf economics spectrum (LES) while the second follows the gradient in calcium (Ca) and magnesium (Mg) and mirrors cell structural differences. Here, we tested in grasslands whether the sum Ca + Mg concentrations is a better indicator of digestibility than LES constituents. Structural equation modelling revealed that the total effect size of N (0.30) on digestibility was much lower than that of Ca + Mg (0.58). The N effect originated predominantly from sampling date (biomass ageing), while the Ca + Mg effect largely from phylogenetic composition (proportion of monocots). Thus, plant variation in partially substitutable divalent cations seems to play a significant role in biomass digestion by ruminants. This finding contests, together with litter decomposition studies, the prominent role of the LES for understanding both fundamental ecological processes.
Hypertension and the acute phase of intracerebral haemorrhage: more evidence of the ‘silent killer’
Authors: Arboix A.
Published: March 2018

Click here to view the accompanying paper in this volume.
Risk score prediction model for dementia in patients with type 2 diabetes
Authors: Li C.‐I. , Li T.‐C. , Liu C.‐S. , Liao L.‐N. , Lin W.‐Y. , Lin C.‐H. , Yang S.‐Y. , Chiang J.‐H. , Lin C.‐C.
Published: March 2018

Background and purpose

No study has established a prediction dementia model in the Asian populations. This study aimed to develop a prediction model for dementia in Chinese type 2 diabetes patients.

Methods

The retrospective cohort study included 27 540 Chinese type 2 diabetes patients (aged 50–94 years) enrolled in the Taiwan National Diabetes Care Management Program. Participants were randomly allocated into derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression models were used to identify risk factors for dementia in the derivation set. Steps proposed by the Framingham Heart Study were used to establish a prediction model with a scoring system.

Results

The average follow‐up was 8.09 years, with a total of 853 incident dementia cases in the derivation set. The dementia risk score summed up the individual scores (from 0 to 20). The areas under the curve of 3‐, 5‐ and 10‐year dementia risks were 0.82, 0.79 and 0.76 in the derivation set and 0.84, 0.80 and 0.75 in the validation set, respectively.

Conclusions

The proposed score system is the first dementia risk prediction model for Chinese type 2 diabetes patients in Taiwan.
Association of serum Cystatin C with neuromyelitis optica spectrum disorders
Authors: Shu Y. , Zhang L. , Chang Y. , Li R. , Sun X. , Li J. , Wu H. , Yang Y. , Peng L. , Lu Z. , Kermode A. G. , Qiu W.
Published: March 2018

Background and purpose

The relationship between Cystatin C (CysC) and neuromyelitis optica spectrum disorders (NMOSD) is unknown.

Methods

Serum CysC levels were measured in 105 Chinese patients with NMOSD (53 in relapse, 52 in remission) and 109 healthy controls (HCs). The association of CysC with NMOSD and its clinical and magnetic resonance imaging parameters were evaluated.

Results

Cystatin C levels were significantly lower in patients with relapsing NMOSD than in those in remission (P < 0.001) or HCs (P < 0.05). CysC levels in NMOSD remission were higher than in HCs (P = 0.002). CysC levels were positively associated with age and negatively associated with brain lesion numbers in relapsing NMOSD (r = −0.252, P = 0.069).

Conclusion

Our results indicate a reduced serum level of CysC in patients with relapsing NMOSD and an increased level in remission. Further studies on the role of CysC in NMOSD are warranted.
Depression comorbidity in epileptic rats is related to brain glucose hypometabolism and hypersynchronicity in the metabolic network architecture
Authors: Zanirati Gabriele , Azevedo Pamella Nunes , Venturin Gianina Teribele , Greggio Samuel , Alcará Allan Marinho , Zimmer Eduardo R. , Feltes Paula Kopschina , DaCosta Jaderson Costa
Published: March 2018

Objective

Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy syndromes in the world. Depression is an important comorbidity of epilepsy, which has been reported in patients with TLE and in different experimental models of epilepsy. However, there is no established consensus on which brain regions are associated with the manifestation of depression in epilepsy. Here, we investigated the alterations in cerebral glucose metabolism and the metabolic network in the pilocarpine‐induced rat model of epilepsy and correlated it with depressive behavior during the chronic phase of epilepsy.

Methods

Fluorodeoxyglucose (18F‐FDG) was used to investigate the cerebral metabolism, and a cross‐correlation matrix was used to examine the metabolic network in chronically epileptic rats using micro–positron emission tomography (microPET) imaging. An experimental model of epilepsy was induced by pilocarpine injection (320 mg/kg, ip). Forced swim test (FST), sucrose preference test (SPT), and eating‐related depression test (ERDT) were used to evaluate depression‐like behavior.

Results

Our results show an association between epilepsy and depression comorbidity based on changes in both cerebral glucose metabolism and the functional metabolic network. In addition, we have identified a significant correlation between brain glucose hypometabolism and depressive‐like behavior in chronically epileptic rats. Furthermore, we found that the epileptic depressed group presents a hypersynchronous brain metabolic network in relation to the epileptic nondepressed group.

Significance

This study revealed relevant alterations in glucose metabolism and the metabolic network among the brain regions of interest for both epilepsy and depression pathologies. Thus it seems that depression in epileptic animals is associated with a more diffuse hypometabolism and altered metabolic network architecture and plays an important role in chronic epilepsy.
Comparison of visual lameness scores to gait asymmetry in racing Thoroughbreds during trot in‐hand
Authors: Pfau T. , Sepulveda Caviedes M. F. , McCarthy R. , Cheetham L. , Forbes B. , Rhodin M.
Published: March 2018

Regular monitoring of movement asymmetry with inertial measurement units (IMUs) to aid in the diagnosis of the underlying cause of a lameness is feasible. Normal ranges for specific groups of horses may be required, with consideration of expert veterinary opinions for both asymmetry screening and lameness assessment. The aim of this study was to determine movement asymmetry values compared with expert lameness scores to enable screening for lameness in Thoroughbreds in race training.IMUgait assessment during in‐hand trot‐up was performed in 25 racehorses undergoing routine gait analysis or lameness examination at the Singapore Turf Club. Video recordings were graded numerically (0–5) for lameness by six experienced racehorse veterinarians. Inter‐observer agreement and consistency were determined. Median lameness scores were used to calculate sensitivity and specificity for head, withers and pelvic movement asymmetry. Guideline values for aligning movement asymmetry values with expert opinions about forelimb and hindlimb lameness were determined from receiver operating characteristics (ROC). Inter‐observer agreement was poor to fair, inter‐observer consistency was good (intraclass correlation coefficient: 0.667 for forelimbs and 0.617 for hindlimbs).ROCs indicated higher discriminative power for hindlimb lameness using pelvic asymmetry (90% sensitivity, 93% specificity) compared with forelimb lameness using head asymmetry (69% sensitivity, 89% specificity) or withers asymmetry (44% sensitivity, 89% specificity). When compared to expert lameness scores from videos of a limited number of Thoroughbred racehorses, preliminary guideline values for movement asymmetry screening for forelimb lameness (>|14.5 mm|) and hindlimb lameness (>|7.5 mm|) are higher than previously reported clinical thresholds of >|7 mm| for head movement and >|4 mm| for pelvic movement asymmetry.
Behavioural assessment of pain in 66 horses, with and without a bit
Authors: Cook W. R. , Kibler M.
Published: March 2018

Horses can be ridden with or without a bit. Comparing the behaviour of the same horse in different modes constituted a ‘natural experiment’. Sixty‐nine behaviours in 66 bitted horses were identified as induced by bit‐related pain and recognised as forms of stereotypic behaviour. A prototype questionnaire for the ridden horse was based on 6 years of feedback from riders who had switched from a bitted to a bit‐free bridle. From a template of 69 behavioural signs of pain derived from answers to the questionnaire, the number of pain signals shown by each horse, first when bitted and then bit‐free, was counted and compared. After mostly multiple years of bit usage, the time horses had been bit‐free ranged from 1 to 1095 days (median 35). The number of pain signals exhibited by each horse when bitted ranged from 5 to 51 (median 23); when bit‐free from 0 to 16 (median 2). The number of pain signals for the total population when bitted was 1575 and bit‐free 208; an 87% reduction. Percentage reduction of each of 69 pain signals when bit‐free, ranged from 43 to 100 (median 87). The term ‘bit lameness’ was proposed to describe a syndrome of lameness caused by the bit. Bit pain had a negative effect on proprioception, i.e. balance, posture, coordination and movement. Only one horse showed no reduction in pain signals when bit‐free. The welfare of 65 of 66 horses was enhanced by removing the bit; reducing negative emotions (pain) and increasing the potential to experience positive emotions (pleasure). Grading welfare on the Five Domains Model, it was judged that – when bitted – the population exhibited ‘marked to severe welfare compromise and no enhancement’ and – when bit‐free – ‘low welfare compromise and mid‐level enhancement.’ The bit‐free data were consistent with the ‘one‐welfare’ criteria of minimising risk and preventing avoidable suffering.
Clinical findings and prognosis of interference injuries to the palmar aspect of the forelimbs in Standardbred racehorses: A study on 74 cases
Authors: Dabbene I. , Bullone M. , Pagliara E. , Gasparini M. , Riccio B. , Bertuglia A.
Published: March 2018

Background

Information on interference injuries in racehorses is lacking.

Objective

To describe clinical findings and prognosis of palmar forelimb interference injuries in Standardbreds.

Study design

Retrospective cohort study.

Methods

Records of 74 racehorses sustaining palmar forelimb interference injuries were studied; 7 occurred during training and 67 during racing. The number of starts before injury, hind shoeing status, gait penalties and racing speeds in cases occurring during racing were compared with negative controls (67 age, sex and speed category matched horses) from the same races. The number of starts and racing speed in 30 racing days preceding recruitment were compared with those following recruitment (negative controls) or return to racing (cases). Clinical aspects and outcome in interference‐induced superficial digital flexor (SDF) tendonitis were compared with 77 horses with overstrain‐induced SDF tendonitis.

Results

In 89% of cases, there was SDF tendonitis and this was associated with a longer time to return to racing (6 months vs. 1 months; P<0.001). The presence of gait penalties (odds ratio (OR) 11.13; 95% CI 3.74, 41.64; P<0.001) and unshod hind feet (OR = 6.26, 95% CI 2.26, 19.62; P<0.001) increased risk of interference injuries. After recruitment/return to racing, horses with interference injuries participated in a lower number of races (24 startsperracing day, interquartile range [IQR] 20–32) compared with controls (49, IQR 43–55, P<0.0001). Interference‐induced tendonitis cases (n = 58) had a shorter time to return to racing (245 ± 137 days) than overstrain‐induced tendonitis cases (331 ± 118 days, P<0.001).

Main limitations

Data were collected retrospectively; time of ultrasonographic assessment varied and health status of the racing controls is unknown.

Conclusions

SDF tendonitis is common with palmar forelimb interference injuries in Standardbreds and increases time to return to racing. Interference‐induced SDF tendonitis has a better prognosis than overstrain‐induced tendonitis.
A review of the mechanisms of action of dimethylfumarate in the treatment of psoriasis
Authors: Brück Jürgen , Dringen Ralf , Amasuno Adriana , Pau‐Charles Ignasi , Ghoreschi Kamran
Published: March 2018

Fumaric acid esters (FAEs) such as dimethylfumarate (DMF) are used for the treatment of adults with moderate‐to‐severe psoriasis. The mode of action of FAEs is complex. Here, we provide a comprehensive review of the literature to describe the molecular mechanisms by which DMF and its active metabolite monomethylfumarate (MMF) exert their anti‐inflammatory and immune modulatory effects. MMF can bind to the hydroxy‐carboxylic acid receptor 2 (HCA2) on the cell surface and both DMF and MMF react with intracellular glutathione following cell penetration. DMF and to some extent also MMF modulate the activity of certain cellular signalling proteins such as the nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2), nuclear factor kappa B (Nf‐κB) and the cellular concentration of cyclic adenosine monophosphate. Some studies show that DMF can also affect the hypoxia‐inducible factor 1‐alpha (HIF‐1α). These actions seem to be responsible for i) the downregulation of inflammatory cytokines and ii) an overall shift from a proinflammatory Th1/Th17 response to an anti‐inflammatory/regulatory Th2 response. Both steps are necessary for the amelioration of psoriatic inflammation, although additional mechanisms have been proposed. There is a growing body of evidence to support the notion that DMF/MMF may also exert effects on granulocytes and non‐immune cell lineages including keratinocytes and endothelial cells. A better understanding of the multiple molecular mechanisms involved in the cellular action of FAEs will help to adapt and further improve the use of such small molecules for the treatment of psoriasis and other chronic inflammatory diseases.
Maternal care exerts disease‐modifying effects on genetic absence epilepsy and comorbid depression
Authors: Sarkisova K. Y. , Gabova A. V.
Published: March 2018

WAG/Rij rats, a genetic animal model of absence epilepsy with comorbidity of depression, exhibit behavioral depression‐like symptoms and spontaneous generalized spike‐wave discharges (SWDs) in the EEG at the age of 6 to 8 months. The aim of the present study was to test the hypothesis that maternal care is an environmental factor which, along with genetic predisposition, may contribute to the expression of absence seizures and depression‐like comorbidity later in life. To achieve this, a cross‐fostering procedure was used. EEG and behavior in the forced swimming test were analyzed in WAG/Rij and Wistar offspring reared by their own mothers (non‐cross‐fostered), foster mothers of the same strain (in‐fostered) or another strain (cross‐fostered) at the age of 7 to 8 months. Maternal care and forced swimming test behavior were assessed in the dams. WAG/Rij mothers showed depression‐like behavior and reduced maternal care irrespective of litter size and litter composition (own or foster pups) compared with Wistar dams. WAG/Rij offspring reared by Wistar dams with a high level of maternal care exhibited less and shorter SWDs and reduced depression‐like comorbidity in adulthood compared with age‐matched WAG/Rij offspring reared by their own or foster WAG/Rij mothers with a low level of maternal care. Moreover, rearing by Wistar mothers delayed the onset of absence epilepsy in WAG/Rij rats. Adoption by WAG/Rij dams did not change EEG and behavior in Wistar rats. Our study demonstrates that improvement of early care‐giving environment can be used as a disease‐modifying treatment to counteract epileptogenesis and behavioral comorbidities in genetic absence epilepsy.
Social participation and the onset of hypertension among the middle‐aged and older population: Evidence from the China Health and Retirement Longitudinal Study
Authors: Tu Raoping , Inoue Yosuke , Yazawa Aki , Hao Xiaoning , Cai Guoxi , Li Yueping , Lin Xiuquan , He Fei , Yamamoto Taro
Published: March 2018

Aim

While previous studies have examined the association between health‐related behaviors and hypertension, comparatively little attention has been paid to the role of social participation (i.e. participating in community organizations). The aim of the present study was to investigate the longitudinal association between social participation and hypertension among the middle‐aged and older population (aged ≥45 years) in China where the prevalence of hypertension has been increasing rapidly in the past few decades.

Methods

Data came from the China Health and Retirement Longitudinal Study waves 2011 and 2013. Information was obtained from 5483 participants on blood pressure, social participation and covariates. A sex‐stratified Poisson regression model with a robust variance estimator was used to examine the associations.

Results

During the period between 2011 and 2013, 20.6% of men and 17.2% of women developed hypertension. A Poisson regression model showed that participating in community organizations once a week or more frequently was inversely associated with the onset of hypertension in women (incidence rate ratio 0.80, 95% confidence interval 0.67–0.95, P = 0.012). Among men, no such association was found.

Conclusion

The present study suggests that promoting social participation might help mitigate the disease burden associated with hypertension in China, particularly among women. Geriatr Gerontol Int 2018; 18: 1093–1099.
Awareness of atrial fibrillation in Japan: A large‐scale, nationwide Internet survey of 50 000 Japanese adults
Authors: Akiyama Hisanao , Hasegawa Yasuhiro
Published: March 2018

Aim

Atrial fibrillation (AF) is the most common underlying cause of cardiogenic cerebral embolism. To prevent cardiogenic cerebral embolism, it is important to determine the level of awareness of AF in Japan.

Methods

We used survey monitor attribute data to sample 172 824 Japanese adults aged ≥50 years from all 47 Japanese prefectures. Next, we carried out an Internet survey to determine these individuals’ level of awareness of AF.

Results

We obtained valid responses from 53 128 respondents. There were 13 119 respondents (27.5%) spanning all age groups who had never heard the term AF (no prior knowledge), just 1791 respondents (3.8%) who knew AF well and 27 351 respondents (57.3%) who knew the name of the condition, but did not understand the disease or its treatment. No prior knowledge was highest in Kochi Prefecture (36.0%) and lowest in Yamanashi Prefecture. Knowing AF well was highest in Kyoto Prefecture (5.1%) and lowest in Tottori Prefecture, and knowing only the name was highest in Aomori Prefecture (63.0%). Factors contributing significantly to having “no prior knowledge” of AF included younger age, male sex and smaller population size (rural region), but not the numbers of arrhythmia or stroke specialists.

Conclusions

Currently, 3.8% of Japanese adults had high awareness of AF, and we find this value very low. We also noted age‐, sex‐ and region‐related differences in awareness level. We believe that awareness initiatives that take into account age‐ and sex‐related differences and prioritize prefectures with lower awareness of AF will be important for preventing cardiogenic cerebral embolism in the future. Geriatr Gerontol Int 2018; 18: 1100–1107.
A Rapid Acid Digestion Technique for the Simultaneous Determination of Bromine and Iodine in Fifty‐Three Chinese Soils and Sediments by ICP‐MS
Authors: He Tao , Xie Junyi , Hu Zhaochu , Liu Ting , Zhang Wen , Chen Haihong , Liu Yongsheng , Zong Keqing , Li Ming
Published: March 2018

Bromine and iodine are important tracers for geochemical and environmental studies. In this study, a rapid acid digestion (HNO3 + HF) with ammonia dilution for the simultaneous determination of bromine and iodine in soils and sediments using ICP‐MS was developed. The recoveries of Br and I were controlled by the synergic effect of temperature and time. It took only 15 min at 140 °C for the complete recovery of Br and I in sediment (GSD‐2) and soil (GSS‐24) reference materials, which is a process that needs 2–6 h at 90 °C. A serious loss of Br and I was found at a higher digestion temperature of 190 °C. A 5% v/v NH4OH dilution effectively eliminated the memory effects and stabilised the signals of Br and I. Moreover, ammonia dilution also avoided the corrosiveness of HF on the sample introduction system and torch of ICP‐MS. Tellurium is a more suitable internal standard element than In in the ammonia medium. To avoid the adsorption of residues of dissolution on Te, addition of Te should be carried out after centrifuging the solution. The developed method was successfully applied to determine Br and I in fifty‐three Chinese soil and sediment reference materials. This simple method shows great potential for the rapid determination of Br and I in large batches of geological and environmental samples commonly analysed for mineral exploration and environmental geochemistry studies.
The twin faces of public sector design
Authors: Clarke Amanda , Craft Jonathan
Published: March 2018

Design thinking has become a popular approach for governments around the world seeking to address complex governance challenges. It offers novel techniques and speaks to broader questions of who governs, how they govern, and the limits of rational instrumentalism in policy making. Juxtaposing design thinking with an older tradition of policy design, this article offers the first critical analysis of the application of design thinking to policy making. It argues that design thinking does not sufficiently account for the political and organizational contexts of policy work. Design thinking also errs in universally privileging one particular policy style over others, and fails to account for the reality of policy mixes. Despite these deficiencies, it is argued that design thinking can inform and enrich governance by helping policy designers produce more adaptable designs, better appreciate the behavioral dynamics of public sector design, and leverage networked approaches to social problem solving.
Contribution of basal and aerial tillers to sward growth in intermittently stocked elephant grass
Authors: Pereira Lilian Elgalise Techio , Paiva Adenilson José , Geremia Eliana Vera , Da Silva Sila Carneiro
Published: March 2018

Elephant grass (Pennisetum purpureum Schumach. cv. Napier) is characterized by high dry matter production and a high contribution of aerial tillers to the tiller population. However, grazing management strategies that favor an increase in aerial tillers, such as long regrowth periods, particularly when associated with severe grazing, can result in a decrease in sward growth, as they are subject to a high level of intraclonal competition. We evaluated the contribution of basal and aerial tillers to sward growth in Napier elephant grass to comprehend how strategies of intermittent stocking management interfere with the relative contribution of each tiller class. Treatments corresponded to combinations of two post‐grazing heights (35 and 45 cm) and two pre‐grazing conditions (95% and maximum canopy light interception during regrowth—LI95% and LIMax, respectively) and were allocated to experimental units (850 m2 paddocks) according to a 2 × 2 factorial arrangement in a randomized complete block design with four replicates from January 2011 to April 2012. Basal tillers were the main contributors to sward growth in elephant grass. In this way, although the production of aerial tillers is an important adaptive response of this forage grass species, grazing management strategies that maximize aerial tillering do not result in greater leaf growth or minimize stem growth rates. The frequency of defoliation was the main modulator of plant responses related to light competition, and the higher leaf growth associated with lower stem growth rates were obtained with the LI95% pre‐grazing target. Severe grazing (35 cm) associated with LI95% is the grazing management strategy recommended to maximize leaf and sward growth rates in Napier elephant grass subjected to rotational stocking.
Demystifying Fisher Information: What Observation Data Reveal about Our Models
Authors: Schenk Judith , Poeter Eileen , Navidi William
Published: March 2018

Information theory is the basis for understanding how information is transmitted as observations. Observation data can be used to compare uncertainty on parameter estimates and predictions between models. Jacobian Information (JI) is quantified as the determinant of the weighted Jacobian (sensitivity) matrix. Fisher Information (FI) is quantified as the determinant of the weighted FI matrix. FI measures the relative disorder of a model (entropy) in a set of models. One‐dimensional models are used to demonstrate the relationship between JI and FI, and the resulting uncertainty on estimated parameter values and model predictions for increasing model complexity, different model structures, different boundary conditions, and over‐fitted models. Greater model complexity results in increased JI accompanied by an increase in parameter and prediction uncertainty. FI generally increases with increasing model complexity unless model error is large. Models with lower FI have a higher level of disorder (increase in entropy) which results in greater uncertainty of parameter estimates and model predictions. A constant‐head boundary constrains the heads in the area near the boundary, reducing sensitivity of simulated equivalents to estimated parameters. JI and FI are lower for this boundary condition as compared to a constant‐outflow boundary in which the heads in the area of the boundary can adjust freely. Complex, over‐fitted models, in which the structure of the model is not supported by the observation dataset, result in lower JI and FI because there is insufficient information to estimate all parameters in the model.
Proposed information outreach programme in primary and secondary health care of Punjab, Pakistan
Authors: Naeem Salman B. , Bhatti Rubina
Published: March 2018

The study reported is part of Dr. Naeem's doctoral research, supervised by Professor Bhatti, with the objective to propose an information outreach programme for health care professionals working in rural areas of the Punjab province, Pakistan. A cross‐sectional survey was conducted involving 517 practitioners from across different health care facilities in the area. The goals of the outreach programme are identified on the basis of the findings regarding practitioners’ current usage and awareness of, as well as attitude and self‐efficacy towards using health information resources. The identification of these goals and their related activities, including logistical, promotional and educational, results in a model of the required inputs and investments to achieve both the short term, intermediate and long term results of the programme.

F.J.
Hepatic granulomas: a 17‐year single tertiary centre experience
Authors: Gaspar Rui , Andrade Patricia , Silva Marco , Peixoto Armando , Lopes Joanne , Carneiro Fatima , Liberal Rodrigo , Macedo Guilherme
Published: March 2018

Aims

Hepatic granulomas have an estimated prevalence of 5% in liver biopsies, with a wide range of aetiologies globally. Our aim was to assess the clinical relevance, presenting features and underlying aetiology in a non‐transplant, tertiary referral centre from a western country.

Methods and results

This was a retrospective, single‐centre review of clinical, laboratory and histological data including all adult patients for whom a liver biopsy was performed from January 1998 to December 2014. A total of 297 cases with hepatic granulomas were found in 9374 biopsies, but 57 were excluded from analysis either because they were lipogranulomas or the biopsy/aetiological work‐up had not been performed at our institution. Overall, the most common aetiology was tuberculosis (35.8%), followed by primary biliary cholangitis (PBC) – 15.0%. In 30 patients (12.5%) granulomas were classified as idiopathic. From 1998 to June 2006 there were 147 granulomas in 5304 biopsies (2.8%), a frequency that did not change significantly compared to the period from July 2006 to December 2014 (93 granulomas in 4070 biopsies, 2.3%, P > 0.05). However, for the majority of cases (61.9%) there was a shift in granuloma aetiology during the former time‐period that infectious diseases were responsible, whereas in the latter, autoimmune liver diseases (43%) were the main aetiology. In addition, while three cases of drug‐induced granulomas were found from 1998 to June 2006, we report two cases in the second time‐period.

Conclusions

Hepatic granulomas can result from various infectious and non‐infectious diseases. During recent years, an epidemiological shift regarding granuloma aetiology was observed, from systemic infectious diseases to non‐infectious, mainly immune‐mediated primary liver disorders. With an appropriate work‐up the aetiology can be identified in the vast majority of cases (~90%), rendering its histological identification and characterisation essential, as disease‐specific therapies are becoming available.
Current issues with luminal subtype classification in terms of prediction of benefit from endocrine therapy in early breast cancer
Authors: Alfarsi Lutfi , Johnston Simon , Liu Dong‐Xu , Rakha Emad , Green Andrew R
Published: March 2018

Endocrine therapy for oestrogen receptor‐positive (ER+) breast cancer (BC) is arguably the most successful targeted cancer therapy to date. Nevertheless, resistance to endocrine therapy still occurs in a significant proportion of patients, limiting its clinical utility. ER+ or luminal BC, which represents approximately three‐quarters of all breast malignancies, are biologically heterogeneous, with no distinct, clinically defined subclasses able to predict the benefit of endocrine therapy in early settings. To improve patient outcomes there is a clear need for improved understanding of the biology of the luminal BC, with subsequent translation into more effective methods of diagnosis to identify potential predictive biomarkers for endocrine therapy. This review summarises current knowledge of factors predictive of benefit of endocrine therapy and discusses why molecular classification systems of BC have yet to be translated into the clinic.