bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol consumption and tobacco smoking among community‐dwelling older Australian men: The Concord Health and Ageing in Men Project
Authors: Ilomäki Jenni , Gnjidic Danijela , Le Couteur David G , Bell J Simon , Blyth Fiona M , Handelsman David J , Cumming Robert G , Seibel Markus J , Waite Louise M , Naganathan Vasi , Hilmer Sarah N
Published: June 2013

Aim

To describe the prevalence and correlates of alcohol consumption and tobacco smoking among older Australian men.

Method

Self‐reported alcohol and tobacco use was assessed among a random sample of community‐dwelling men aged ≥70 years living in Sydney (n = 1705) from 2005 to 2007. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with alcohol and tobacco use.

Results

The prevalence of heavy/excessive drinking was 19.2%, daily drinking 33.7%, and binge drinking 14.1%. Daily drinking was associated with chronic pain (OR = 1.38, 95% CI: 1.07–1.78). Binge drinking was associated with anxiety (OR = 1.93, 95% CI: 1.05–3.54) and being widowed (OR = 1.74, 95% CI: 1.11–2.73). Six per cent of men were current smokers and 56.7% were former smokers. Former smoking was associated with polypharmacy (OR = 1.47, 95% CI: 1.14–1.91) and each additional comorbid condition (OR = 1.11, 95% CI: 1.03–1.19).

Conclusions

Nearly one‐fifth of older men drank heavily or excessively. This highlights the need for public health initiatives to reduce alcohol consumption in older people.
From “Queue Jumpers” to “Absolute Scum of the Earth”: Refugee and Organised Criminal Deviance in Australian Asylum Policy
Authors: Cameron Matthew
Published: June 2013

The arrival of asylum seekers by boat in Australia is no longer represented as a threat by the Australian government because of characteristics of asylum seekers themselves, but is instead predominantly represented as threatening because of the involvement of transnational organised crime in the form of people smugglers. This progression, which is demonstrated by comparison of the approach of the Howard coalition government with that of the Rudd and Gillard Labor governments, is best understood by reference to conventional understandings of organised crime and irregular migration, and critical accounts of both phenomena. Understood in this way, organised crime and people‐smuggling discourses serve to externalise the asylum seeker “problem” and maintain punitive policies, inhibiting the development of effective regional responses to the issue.
The Strategic Nature of Compliance: An Empirical Evaluation of Law Implementation in the Central Monitoring System of the European Union
Authors: König Thomas , Mäder Lars
Published: June 2013

This compliance study models correct and timely implementation of policies in a multilevel system as a strategic game between a central monitoring agency and multiple implementers and evaluates statistically the empirical implications of this model. We test whether compliance is determined by the anticipated enforcement decision of the monitoring agency and whether this agency is responsive to the probability of enforcement success and the potential sanctioning costs produced by noncomplying implementers. Compared to other monitoring systems, the centralized monitoring system of the European Union (EU) is praised for exemplary effectiveness, but our findings reveal that the monitoring agency refrains from enforcing compliance when the probability of success is low, and the sanctioning costs are high. This results in a compliance deficit, even though the selective enforcement activities of the monitoring agency are almost always successful before court.
Up‐dosing with bilastine results in improved effectiveness in cold contact urticaria
Authors: Krause K. , Spohr A. , Zuberbier T. , Church M. K. , Maurer M.
Published: June 2013

Background

Cold contact urticaria (CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro‐inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up‐dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge.

Methods

Twenty patients with CCU were included in this randomized, crossover, double‐blind, placebo‐controlled 12‐week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14‐day washout periods. The primary readout was change in critical temperature thresholds (CTT). Secondary readouts were changes in pruritus, levels of histamine IL‐6, IL‐8 and TNF‐α collected by skin microdialysis and safety and tolerability of bilastine.

Results

Bilastine 20 mg was highly effective (P < 0.0001) in reducing CTT. Up‐dosing to 80 mg significantly (P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL‐6 and IL‐8 assessed 1–3 h after cold challenge were significantly (P < 0.05) decreased following up‐dosing with 80 mg bilastine. Bilastine treat‐ment was well tolerated without evidence of increased sedation with dose escala‐tion.

Conclusions

Bilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up‐dosing was without sedation and supports urticaria treatment guidelines.
Generation and functional analysis of human TNF‐α/iNOS‐producing dendritic cells (Tip‐DC)
Authors: Wilsmann‐Theis D. , Koch S. , Mindnich C. , Bonness S. , Schnautz S. , von Bubnoff D. , Bieber T.
Published: June 2013

Background

A unique type of CD11cpos dendritic cells (DC) is abundant in inflamed tissue, for example, in chronic inflammatory skin diseases. Due to their remarkable production of tumor necrosis factor (TNF)‐α and inducible NO synthase (iNOS), these cells have been referred to as TNF and iNOS‐producing DC (Tip‐DC). While Tip‐DC have been mainly characterized in murine models of infection, functional data about their human counterpart are lacking.

Objectives

We sought to generate human Tip‐DC in vitro und thus provide a new model for the investigation of their phenotype and function.

Methods

We generated human Tip‐DC from monocytic precursor cells of healthy individuals, atopic and psoriatic patients using human serum. Resting and stimulated cells were analyzed by flow cytometry, real‐time PCR, and by ELISA. INOS activity was measured by fluorometric detection of NO.

Results

Tip‐DC closely resembled their in vivo counterparts by expressing CD11c, CD86, and CD40 while lacking CD1a, CD1c, or CD207/Langerin. Bacterial stimulation of Tip‐DC from healthy donors, atopic dermatitis, or psoriasis patients resulted in a similar increase in iNOS activity and TNF‐α production. In kinetic experiments, TNF‐α, a putative activator of Tip‐DC, could not induce NOS2. Upon bacterial stimulation, TNFA, IL6, IL12B, and IL23A mRNA appeared in a first wave, while IL12A and NOS2 mRNA were up‐regulated later on but not blocked by anti‐TNF‐α agents, implying a biphasic pro‐inflammatory response.

Conclusions

We developed a new model for the study of human Tip‐DC and provide the first evidence of their pro‐inflammatory capacity.
Retinoic acids up‐regulate functional eosinophil‐driving receptor CCR3
Authors: Ueki S. , Nishikawa J. , Yamauchi Y. , Konno Y. , Tamaki M. , Itoga M. , Kobayashi Y. , Takeda M. , Moritoki Y. , Ito W. , Chihara J.
Published: June 2013

Eotaxins and their receptor CCR3 have a definitive role for tissue accumulation of eosinophils both under homeostatic and pathologic conditions. However, physiological stimuli that can up‐regulate CCR3 in blood‐derived human eosinophils have not been recognized. As a prior gene microarray study revealed up‐regulation of CCR3 in eosinophils stimulated with retinoic acids (RAs), the expression of functional CCR3 was examined. We found that 9‐cis RA and all‐trans RA (ATRA) significantly induced surface CCR3 expression regardless of the presence of IL‐3 or IL‐5. Pharmacological manipulations with receptor‐specific agonists and antagonists indicated that retinoic acid receptor‐α activation is critical for CCR3 up‐regulation. RA‐induced CCR3 was associated with its functional capacity, in terms of the calcium mobilization and chemotactic response to eotaxin‐1 (CCL11). Our study suggests an important role of vitamin A derivatives in the tissue accumulation of eosinophils.
Does Flow Experience Lead to Risk? How and for Whom
Authors: Schüler Julia , Nakamura Jeanne
Published: June 2013

Background: Previous research has focused on the positive consequences of flow, an intrinsically rewarding state of deep absorption. In contrast, the present research links flow to impaired risk awareness and to risky behaviour. We expected flow to enhance self‐efficacy beliefs, which in turn were hypothesised to result in low risk awareness and risky behaviour in sports. In addition, we predicted that individuals' level of experience in the activity would moderate the expected effects. Methods: One study with kayakers (Study 1) and two studies with rock climbers (Studies 2 and 3) were conducted. Kayakers completed a survey while still on the river; climbers responded during and upon completion of a climb. Results: In all studies flow was related to risk awareness. Study 2 additionally showed its association with risky behaviour. Studies 2 and 3 revealed that these relationships were mediated by self‐efficacy. The mediations were moderated by level of experience (Study 3). Conclusions: The results indicated that inexperienced but not experienced participants respond to self‐efficacy beliefs evoked by flow with impaired risk awareness and with risky behaviour. Theoretical implications for flow and risk research as well as practical implications for risk prevention are discussed.
Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients
Authors: Abdel Jalil Mariam H. , Hawwa Ahmed F. , McKiernan Patrick J. , Shields Michael D. , McElnay James C.
Published: June 2013

Aims

To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter‐patient pharmacokinetic variability within children following liver transplantation.

Methods

The present study retrospectively examined tacrolimus whole blood pre‐dose concentrations (n = 628) of 43 children during their first year post‐liver transplantation. Population pharmacokinetic analysis was performed using the non‐linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates.

Results

The final model identified time post‐transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation:
urn:x-wiley:03065251:media:bcp12174:bcp12174-math-5001
where TVCL is the typical value for apparent clearance, TPT is time post‐transplantation in days and the CYP3A5 is 1 where *1 allele is present and 0 otherwise. The population estimate and inter‐individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h−1 kg−1 (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%.

Conclusion

Tacrolimus apparent clearance was influenced by time post‐transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time‐related changes in tacrolimus clearance.
Protocatechuic Acid Induces Angiogenesis through PI3K‐Akt‐eNOS‐VEGF Signalling Pathway
Authors: Kang Zechun , Zhu Haibo , Jiang Wanglin , Zhang Shuping
Published: June 2013

In this study, we sought to elucidate whether protocatechuic acid contributes to induce angiogenesis as well as its mechanisms. To this end, we examined the role of protocatechuic acid on human brain microvascular endothelial cell line (HBMEC) proliferation, invasion and tube formation in in vitro. For the study of mechanisms involved, the phosphoinositide 3 kinase (PI3K)‐Akt inhibitor LY294002, the endothelial nitric oxide synthase (eNOS) inhibitor L‐NAME, vascular endothelial growth factor (VEGF), antagonist sFlt‐1 and VEGF receptor blocker SU‐1498 were used. Proliferation of HBMEC was tested by MTT. Scratch adhesion test was used to assess the ability of invasion. A Matrigel tube formation assay was performed to test capillary tube formation ability. PI3K‐Akt‐eNOS‐VEGF pathway activation in HBMEC was tested by Western blot. Our data suggested that protocatechuic acid induces angiogenesis in vitro by increasing proliferation, invasion and tube formation. VEGF expression was increasing by protocatechuic acid and counteracted by VEGF antagonist sFlt‐1, LY294002 and L‐NAME in HBMEC. Tube formation was increased by protocatechuic acid and counteracted by VEGF receptor blocker‐SU1498, LY294002 and L‐NAME. These data suggest that protocatechuic acid may be a candidate therapy for stroke recovery by promoting angiogenesis via a programmed PI3K/Akt/eNOS/VEGF signalling axis.
Exploring the use of Web 2.0 technology to promote moral and psychosocial development: Can YouTube work?
Authors: Koh Caroline
Published: June 2013

This paper explores the use of the video sharing site, YouTube, as a platform for enhancing moral and psychosocial development through increased awareness of moral values and models of moral behavior. The research involved a qualitative design whereby video snippets illustrating moral issues were identified from YouTube. These video snippets were analyzed in terms of their viewership, the moral dilemma and the levels of moral judgment that they presented. The comments made by viewers in response to the video contents were then captured and their contents analyzed for evidence of moral reasoning and ego (psychosocial) development. The findings showed that the video sharing websites such as YouTube offered opportunities for moral issues to be featured, shared and discussed at a global level, as well as moral judgments and ego development to be made evident through viewers' comments. From an educational viewpoint, it also paves the way for the use of appropriate video footage for promoting moral values and moral development.
Impact of gait analysis on correction of excessive hip internal rotation in ambulatory children with cerebral palsy: a randomized controlled trial
Authors: Wren Tishya A L , Lening Christopher , Rethlefsen Susan A , Kay Robert M
Published: June 2013

Aim

The aim of this study was to determine if gait analysis improves correction of excessive hip internal rotation in ambulatory children with spastic cerebral palsy (CP).

Method

Children undergoing orthopedic surgery were randomized to receive or not receive a preoperative gait analysis report. This secondary analysis included all participants whose gait report recommended external femoral derotation osteotomy (FDRO). One‐year postoperative, and pre‐ to postoperative change in femoral anteversion, mean hip rotation in stance, and mean foot progression in stance were compared between groups and in subgroups based on whether the recommendation for FDRO was followed.

Results

Outcomes did not differ between the group which received a gait report (n=39; 19 males, 20 females; mean age 10y 4mo [SD 3y]; hemiplegia, 3; di/triplegia, 28; quadriplegia, 8; Gross Motor Function Classification System [GMFCS]: level I, 5; level II, 12; level III 19; level IV, 3) and the control group (n=26; 14 males, 12 females; mean age 9y 5mo [SD 2y 10mo]; hemiplegia, 1; di/triplegia, 21; quadriplegia, 4; GMFCS: level I, 4; level II, 1; level III, 9; level IV, 2; all p values >0.29), but improved more in the gait report subgroup in which the FDRO recommendation was followed (seven limbs; change in anteversion −32.9°, hip rotation −25.5°, foot progression −36.2°) than in the control group (anteversion −12.2°, hip rotation −7.6°, foot progression −12.4°; all p values ≤0.02) and the gait report subgroup in which FDRO was not performed (32 limbs; anteversion −1.0°, hip rotation 0.5°, foot progression −8.0°; all p values ≤0.003). Postoperative measures became normal only in the gait report subgroup in which the recommended FDRO was performed.

Interpretation

Gait analysis can improve outcomes when its recommendations are incorporated in the treatment plan.
The Unintended Consequences of Italy's Labour Laws: How Extensive Labour Regulation Distorts the Italian Economy
Authors: Melchiorre Matthew , Rocca Emilio
Published: June 2013

Simple solutions to complex problems often have unintended and undesirable consequences. An example is Italy's approach to combating unemployment. Rigid laws designed to protect the employed perversely discourage businesses from hiring and people from working. They also encourage precarious temporary employment among young people, informal work, and under‐the‐table deals that compromise worker benefits. The numbers of Italy's unemployed and of those outside the workforce are much higher than official estimates suggest. Italy's employment protection legislation – arguably the most restrictive in Europe – creates that which it seeks to prevent: the insecurity of unemployment.
A Novel Echocardiographic Predictor of Atrial Fibrillation Recurrence: L‐Wave
Authors: Ari Hasan , Ari Selma , Akkaya Mehmet , Yasar Sarigul O. , Emlek Nadir , Aydin Cihan , Çetinkaya Seçkin , Bozat Tahsin , Melek Mehmet
Published: June 2013

Diastolic dysfunction leads to atrial fibrillation (AF) by increasing left atrial pressure and also increases recurrence rate after cardioversion. So, L‐wave, which is associated with severe diastolic dysfunction, could predict recurrent AF after cardioversion. The aim of this study was to investigate predictive value of L‐wave for AF recurrence at first month after electrical cardioversion. A total of 127 patients with persistent AF were evaluated for this study and finally 73 patients were included according to the study criteria. Echocardiographic examinations were performed for all patients before and at 24th hour after electrical cardioversion. Heart rates and rhythms were followed with electrocardiography monitor and 12‐lead ECG at first week and first month. Seventy patients achieved sinus rhythm (SR) after cardioversion and 3 patients who did not go into SR excluded from the study. Patients were divided into 2 groups according to having (group 1) or not having (group 2) L‐wave on echocardiography. Twenty‐two patients (6 men, 16 women) had L‐wave and 48 patients (19 men, 29 women) did not have L‐wave. Duration of AF was longer in group 1 as compared to group 2 (P = 0.03). Mean heart rate was lower in group 1 than in group 2 (P < 0.001). Duration of AF and presence of L‐wave were significant parameters for AF recurrence in univariate analysis, however, presence of L‐wave was the only significant parameter for AF recurrence in multivariate analysis. Ten patients in group 1 (45.5%) and 7 patients (14.6%) in group 2 (P = 0.005) had AF recurrence at the end of first month after cardioversion. L‐wave did predict AF recurrence with 59% sensitivity, 77% specificity, 45% positive predictive value, and 85% negative predictive value at 1 month. Echocardiographic L‐wave could predict the AF recurrence.
An Echocardiographic Presentation of a Massive, Reverse Flow Caused by an Electrical Failure of the Left Ventricular Assist Device. The Continuous Flow Device Dysfunction
Authors: Paluszkiewicz Lech , Morshuis Michiel , Gummert Jan
Published: June 2013

Mini‐Abstract

We present a case of a 57‐year‐old patient, 32 months after continuous flow, left ventricular assist device implantation. He was admitted on emergency basis after he noticed a temporary pump stop. The echocardiographic examination revealed a massive reverse flow during diastole from the aorta into the left ventricle through outflow graft. The echocardiographic presentation of a pump stop depends on the cause of dysfunction. In cases of device thrombosis, the quantity of reverse flow depends on the size of the thrombus. In our case, device chamber was clot‐free and the volume of reverse flow is high. The device was successfully replaced.
Stress Cardiomyopathy with an “Inverse” Takotsubo Pattern in a Patient with Acute Aneurysmal Subarachnoid Hemorrhage
Authors: Waller Christine J. , Vandenberg Byron , Hasan David , Kumar Avinash B.
Published: June 2013

Background

Subarachnoid hemorrhage (SAH) induced myocardial dysfunction (often labeled neurogenic stunned myocardium) encompasses a spectrum of clinical presentations ranging from an isolated elevation of cardiac enzymes to cardiogenic shock.

Objective

We describe a case of stress cardiomyopathy in a patient following acute aneurysmal subarachnoid hemorrhage that showed an “inverse” or reverse takotsubo pattern on echocardiography.

Case Report

The patient was a 46‐year‐old female who presented with acute cardiogenic shock following acute subarachnoid hemorrhage necessitating aggressive cardiorespiratory in the ICU. Her admission echo showed a depressed left ventricular ejection fraction of 25%. The basal 2/3 of the left ventricle (LV) was severely hypokinetic and the apical 1/3 of the LV was hypercontractile, i.e. the reverse or inverse takotsubo pattern of regional wall motion abnormality. With ongoing aggressive support her cardiovascular function steadily improved and on day 6 her follow up echo showed LV ejection fraction increased to 60–65% with resolution of the previous regional wall motion abnormality. The patient was discharged to a neuro‐rehabilitation facility on day 16.

The “inverse” or “reverse” takotsubo pattern of regional wall motion abnormalities, i.e. with preserved apical LV contractility and hypokinesis of the basal walls of the LV is more common in patients following acute SAH.
Cardiac Tamponade with only Left Heart Collapse in a Child with Severe Pulmonary Artery Hypertension
Authors: Varghese Mithun J. , Kothari Shyam S.
Published: June 2013

Mini‐Abstract

A 5‐year‐old child presented with severe hypotension and respiratory distress. Echocardiography demonstrated severe pulmonary arterial hypertension, pericardial effusion, and left ventricular (but not right atrial/right ventricular) collapse. Definite but transient hemodynamic improvement occurred with pericardiocentesi, but the patient succumbed to severe pulmonary artery hypertension and heart failure.
Reproducibility and Optimization of Analysis Parameters of Tissue Doppler–Derived Strain and Strain Rate Measurements for Very Low Birth Weight Infants
Authors: Helfer Sven , Schmitz Lothar , Bührer Christoph , Czernik Christoph
Published: June 2013

Aims

To assess the effects of region of interest (ROI) size and strain length (SL) on the quality of analysis and to determine the feasibility and reproducibility of tissue Doppler–derived cardiac strain (S) and strain rate (SR) measurements for preterm infants <1500 g birth weight.

Methods and Results

The beat‐to‐beat variation (BBV) for different combinations of ROI width (RW), ROI length (RL), and SL was determined from 60 good quality images of left and right free walls and the interventricular septum. We examined the impact of RW, RL, and SL on BBV and estimated inter‐ and intra‐operator variability. BBV was smallest for RW = 2 mm. Raising SL (even at the cost of RL) led to a decrease in BBV. Several combinations provided a low BBV without significant difference. Coefficients of variation for intra‐ and inter‐operator variability ranged from 15.1% to 65.2%. Both were lower for systolic than for diastolic values.

Conclusion

Tissue Doppler imaging–derived S and SR measurements are feasible in very low birth weight infants. Reproducibility is comparable to older infants for systolic S and SR. For optimal analysis quality, SL and RW should be high while RL should be small (though inside segment size). Best results were obtained with RW = 2 mm, RL = 1 mm, and SL = 6 mm.
Sharing the Blame? Local Electoral Accountability and Centralized School Finance in California
Authors: Joanis Marcelin
Published: June 2013

Although local electoral accountability should be stronger when responsibilities are clearly assigned to local governments, the involvement of higher tiers of government is often associated with policies specifically designed to improve local accountability. This article investigates the impact of centralization on local electoral accountability in the context of California's school finance system. Results show that voters are responsive to differences in dropout rates and pupil–teacher ratios, at least in some contexts, and that local electoral accountability is affected by a district's degree of centralization. Dropout rate regressions reveal that the No Child Left Behind Act of 2001 appears to have sharpened local electoral accountability.
Plant neighbours mediate bird predation effects on arthropod abundance and herbivory
Authors: GIFFARD BRICE , BARBARO LUC , JACTEL HERVÉ , CORCKET EMMANUEL
Published: June 2013

Tritrophic interactions among plants, herbivores and predators are expected to be influenced by the surrounding vegetation. Neighbouring plants can influence focal plant colonisation by herbivorous insects and the foraging behaviour of natural enemies, such as insectivorous birds.

The aim of the experiment was to disentangle the interactive effects of neighbouring plants and avian predation on arthropod abundance and insect leaf damage in oak tree seedlings, using exclusion cages and vegetation removal.

The presence or removal of surrounding herbaceous vegetation differentially mediated top‐down effects of insectivorous birds on distinct arthropod guilds and herbivore damage in seedlings. Avian predation reduced sawfly larval abundance regardless of the presence of plant neighbours; lepidopteran larval abundance only when plant neighbours were removed; and spider abundance only when plant neighbours were left intact. The removal of plant neighbours increased prey accessibility for foraging insectivorous birds and decreased chewer damage on seedlings. The density of concealed‐feeder insects (leaf miners) increased with plant neighbour removal and when seedlings were less damaged by chewer guild, suggesting intraguild competition.

These results highlight the strong indirect effects of neighbouring vegetation on tritrophic interactions involving a focal plant species, its associated herbivores and the upper trophic level of predators.
unc5c haploinsufficient phenotype: striking similarities with the dcc haploinsufficiency model
Authors: Auger Meagan L. , Schmidt Ewoud R. E. , Manitt Colleen , Dal‐Bo Greg , Pasterkamp R. Jeroen , Flores Cecilia
Published: June 2013

DCC and UNC5 homologs (UNC5H) are guidance cue receptors highly expressed by mesocorticolimbic dopamine neurons. We have shown that dcc heterozygous mice exhibit increased dopamine, but not norepinephrine, innervation and function in medial prefrontal cortex. Concomitantly, dcc heterozygotes show blunted mesolimbic dopamine release and behavioral responses to stimulant drugs. These changes appear only in adulthood. Recently, we found an adolescent emergence of UNC5H expression by dopamine neurons and co‐expression of DCC and UNC5H by single dopamine cells. Here, we demonstrate selective expression of unc5 homolog c mRNA by dopamine neurons in adulthood. We show that unc5c haploinsufficiency results in diminished amphetamine‐induced locomotion in male and female mice. This phenotype is identical to that produced by dcc haploinsufficiency and is observed after adolescence. Notably, and similar to dcc haploinsufficiency, unc5c haploinsufficiency leads to dramatic increases in tyrosine hydroxylase expression in the medial prefrontal cortex, but not in the nucleus accumbens. In contrast, medial prefrontal cortex dopamine‐β‐hydroxylase expression is not altered. We confirmed that UNC5C protein is reduced in the ventral tegmental area of unc5c heterozygous mice, but that DCC expression in this region remains unchanged. UNC5C receptors may also play a role in dopamine function and influence sensitivity to behavioral effects of stimulant drugs of abuse, at least upon first exposure. The striking similarities between the dcc and the unc5c haploinsufficient phenotypes raise the possibility that functions mediated by DCC/UNC5C complexes may be at play.
Genetic variation in adaptive traits and seed transfer zones for Pseudoroegneria spicata (bluebunch wheatgrass) in the northwestern United States
Authors: Bradley St. Clair John , Kilkenny Francis F. , Johnson Richard C. , Shaw Nancy L. , Weaver George
Published: June 2013

A genecological approach was used to explore genetic variation in adaptive traits in Pseudoroegneria spicata, a key restoration grass, in the intermountain western United States. Common garden experiments were established at three contrasting sites with seedlings from two maternal parents from each of 114 populations along with five commercial releases commonly used in restoration. Traits associated with size, flowering phenology, and leaf width varied considerably among populations and were moderately correlated with the climates of the seed sources. Pseudoroegneria spicata populations from warm, arid source environments were smaller with earlier phenology and had relatively narrow leaves than those from mild climates with cool summers, warm winters, low seasonal temperature differentials, high precipitation, and low aridity. Later phenology was generally associated with populations from colder climates. Releases were larger and more fecund than most of the native ecotypes, but were similar to native populations near their source of origin. Differences among native populations associated with source climates that are logical for survival, growth, and reproduction indicate that genetic variation across the landscape is adaptive and should be considered during restoration. Results were used to delineate seed transfer zones and population movement guidelines to ensure adapted plant materials for restoration activities.
Gene flow and demographic history of leopards (Panthera pardus) in the central Indian highlands
Authors: Dutta Trishna , Sharma Sandeep , Maldonado Jesús E. , Wood Thomas C. , Panwar Hemendra S. , Seidensticker John
Published: June 2013

Gene flow is a critical ecological process that must be maintained in order to counteract the detrimental effects of genetic drift in subdivided populations, with conservation benefits ranging from promoting the persistence of small populations to spreading adaptive traits in changing environments. We evaluated historical and contemporary gene flow and effective population sizes of leopards in a landscape in central India using noninvasive sampling. Despite the dramatic changes in land‐use patterns in this landscape through recent times, we did not detect any signs that the leopard populations have been through a genetic bottleneck, and they appear to have maintained migration–drift equilibrium. We found that historical levels of gene flow (mean mh = 0.07) were significantly higher than contemporary levels (mean mc = 0.03), and populations with large effective population sizes (Satpura and Kanha Tiger Reserves) are the larger exporters of migrants at both timescales. The greatest decline in historical versus contemporary gene flow is between pairs of reserves that are currently not connected by forest corridors (i.e., Melghat‐Pench mh − mc = 0.063; and Kanha‐Satpura mh − mc = 0.054). We attribute this reduction in gene flow to accelerated fragmentation and habitat alteration in the landscape over the past few centuries, and suggest protection of forest corridors to maintain gene flow in this landscape.
Effect of orally administered sodium bicarbonate on caecal pH
Authors: Taylor E. A. , Beard W. L. , Douthit T. , Pohlman L.
Published: June 2013

Reasons for performing study

Caecal acidosis is a central event in the metabolic cascade that occurs following grain overload. Buffering the caecal acidosis by enterally administered sodium bicarbonate (NaHCO3) may be beneficial to affected horses.

Objectives

To determine the effect and duration of enterally administered NaHCO3on caecal pHin healthy horses.

Study design

Experimental study using horses with caecal cannulas.

Methods

Nine horses had been previously fitted with a caecal cannula. Six horses received 1.0 g/kg bwt NaHCO3and 3 control horses were given 3 l of water via nasogastric tube. Clinical parameters, water consumption, venous blood gases, caecal pH, faecal pHand faecal water content were measured at 6 h intervals over a 36 h study period.

Results

Horses that received enterally administered NaHCO3had significantly increased caecal pHthat lasted the duration of the study. Treated horses increased their water intake, and developed metabolic alkalaemia, significantly increased plasma sodium concentrations and significantly decreased plasma potassium concentrations.

Conclusions

Enterally administered NaHCO3may be beneficial in buffering caecal acidosis.
The treatment and diagnosis of temporomandibular disorders using high‐tech devices
Authors: Dodes John E
Published: June 2013

Background

Temporomandibular disorder (TMD) is a collective term that embraces a number of clinical problems involving the masticatory muscles, jaw joint, associated structures or a combination of these structures. There are a number of devices currently utilised by dentists that claim to diagnose, treat, cure or ameliorate the symptoms of TMD.

Objective

To critically evaluate the evidence of safety and effectiveness for commonly used electronic diagnostic and treatment devices for TMD.

Methods

PubMed and the authors' extensive library were searched for studies evaluating the safety and/or effectiveness of electronic diagnostic and treatment devices for TMD. Only controlled studies involving human subjects were included.

Results

Thirty‐six articles were reviewed. The quality of the articles varied with the most rigorous studies presenting negative conclusions concerning the usefulness of high‐tech devices for the treatment and diagnosis of temporomandibular disorder.

Conclusion

The scientific literature does not support the use of electronic diagnostic and treatment devices for TMD.
Engineering RNA‐binding proteins for biology
Authors: Chen Yu , Varani Gabriele
Published: June 2013

RNA‐binding proteins play essential roles in the regulation of gene expression. Many have modular structures and combine relatively few common domains in various arrangements to recognize RNA sequences and/or structures. Recent progress in engineering the specificity of the PUF class RNA‐binding proteins has shown that RNA‐binding domains may be combined with various effector or functional domains to regulate the metabolism of targeted RNAs. Designer RNA‐binding proteins with tailored sequence specificity will provide valuable tools for biochemical research as well as potential therapeutic applications. In this review, we discuss the suitability of various RNA‐binding domains for engineering RNA‐binding specificity, based on the structural basis for their recognition. We also compare various protein engineering and design methods applied to RNA‐binding proteins, and discuss future applications of these proteins.
The impacts of climate change and human activities on biogeochemical cycles on the Qinghai‐Tibetan Plateau
Authors: Chen Huai , Zhu Qiuan , Peng Changhui , Wu Ning , Wang Yanfen , Fang Xiuqing , Gao Yongheng , Zhu Dan , Yang Gang , Tian Jianqing , Kang Xiaoming , Piao Shilong , Ouyang Hua , Xiang Wenhua , Luo Zhibin , Jiang Hong , Song Xingzhang , Zhang Yao , Yu Guirui , Zhao Xinquan , Gong Peng , Yao Tandong , Wu Jianghua
Published: June 2013

With a pace of about twice the observed rate of global warming, the temperature on the Qinghai‐Tibetan Plateau (Earth's ‘third pole’) has increased by 0.2 °C per decade over the past 50 years, which results in significant permafrost thawing and glacier retreat. Our review suggested that warming enhanced net primary production and soil respiration, decreased methane (CH4) emissions from wetlands and increased CH4 consumption of meadows, but might increase CH4 emissions from lakes. Warming‐induced permafrost thawing and glaciers melting would also result in substantial emission of old carbon dioxide (CO2) and CH4. Nitrous oxide (N2O) emission was not stimulated by warming itself, but might be slightly enhanced by wetting. However, there are many uncertainties in such biogeochemical cycles under climate change. Human activities (e.g. grazing, land cover changes) further modified the biogeochemical cycles and amplified such uncertainties on the plateau. If the projected warming and wetting continues, the future biogeochemical cycles will be more complicated. So facing research in this field is an ongoing challenge of integrating field observations with process‐based ecosystem models to predict the impacts of future climate change and human activities at various temporal and spatial scales. To reduce the uncertainties and to improve the precision of the predictions of the impacts of climate change and human activities on biogeochemical cycles, efforts should focus on conducting more field observation studies, integrating data within improved models, and developing new knowledge about coupling among carbon, nitrogen, and phosphorus biogeochemical cycles as well as about the role of microbes in these cycles.
Predicting species‐specific responses of fungi to climatic variation using historical records
Authors: Diez Jeffrey M. , James Timothy Y. , McMunn Marshall , Ibáñez Inés
Published: June 2013

Although striking changes have been documented in plant and animal phenology over the past century, less is known about how the fungal kingdom's phenology has been changing. A few recent studies have documented changes in fungal fruiting in Europe in the last few decades, but the geographic and taxonomic extent of these changes, the mechanisms behind these changes, and their relationships to climate are not well understood. Here, we analyzed herbarium data of 274 species of fungi from Michigan to test the hypotheses that fruiting times of fungi depend on annual climate and that responses depend on taxonomic and functional groups. We show that the fungal community overall fruits later in warmer and drier years, which has led to a shift toward later fruiting dates for autumn‐fruiting species, consistent with existing evidence. However, we also show that these effects are highly variable among species and are partly explained by basic life‐history characteristics. Resulting differences in climate sensitivities are expected to affect community structure as climate changes. This study provides a unique picture of the climate dependence of fungal phenology in North America and an approach for quantifying how individual species and broader fungal communities will respond to ongoing climate change.
Changes in the timing of hay cutting in Germany do not keep pace with climate warming
Authors: Bock Anna , Sparks Tim H. , Estrella Nicole , Menzel Annette
Published: June 2013

A unique long‐term phenological data set of over 110 000 records of 1st cutting dates for haymaking across Germany, spanning the years 1951–2011 was examined. In addition, we analyzed a long‐term data set in the beginning of flowering of meadow foxtail (Alopecurus pratensis) covering the last 20 years. We tested whether hay‐cutting dates (based on a human decision when to cut) showed trends, temperature relationships and spatial distribution similar to the development of this grassland species, and if these trends could be related to climate change. The timing of 1st hay cut was strongly influenced (P < 0.001) by altitude, latitude and longitude, revealing in particular an east‐west gradient. Over the past 60 years, there have been changes in the timing of hay cutting, with the majority of German federal states having significant (P < 0.05) advances of approximately 1 day per decade. Overall, the response to mean March–May temperature was highly significant (−2.87 days °C−1; P < 0.001). However, in the last 20 years, no federal state experienced a significant advance and two were even significantly delayed. The temperature response in this post‐1991 period became less or non‐significant for most of the federal states. We suggest that differences in agricultural land use and unequal uptakes of Agri‐Environment Schemes (AES, which encourage later cutting) were likely to be responsible for the regional differences, while the general increase in AES appears to have confounded the overall trend in hay cutting in the last 20 years. Trends over time and responses to temperature were small relative to those associated with the phenology of meadow foxtail. The advance in phenology of this species is greater than the advance in hay cutting, implying that hay cutting may not be keeping pace with a changing climate, which may have a positive effect on grassland ecology.
Forecasting range expansion into ecological traps: climate‐mediated shifts in sea turtle nesting beaches and human development
Authors: Pike David A.
Published: June 2013

Some species are adapting to changing environments by expanding their geographic ranges. Understanding whether range shifts will be accompanied by increased exposure to other threats is crucial to predicting when and where new populations could successfully establish. If species overlap to a greater extent with human development under climate change, this could form ecological traps which are attractive to dispersing individuals, but the use of which substantially reduces fitness. Until recently, the core nesting range for the Critically Endangered Kemp's ridley sea turtle (Lepidochelys kempii) was ca. 1000 km of sparsely populated coastline in Tamaulipas, Mexico. Over the past twenty‐five years, this species has expanded its range into populated areas of coastal Florida (>1500 km outside the historical range), where nesting now occurs annually. Suitable Kemp's ridley nesting habitat has persisted for at least 140 000 years in the western Gulf of Mexico, and climate change models predict further nesting range expansion into the eastern Gulf of Mexico and northern Atlantic Ocean. Range expansion is 6–12% more likely to occur along uninhabited stretches of coastline than are current nesting beaches, suggesting that novel nesting areas will not be associated with high levels of anthropogenic disturbance. Although the high breeding‐site fidelity of some migratory species could limit adaptation to climate change, rapid population recovery following effective conservation measures may enhance opportunities for range expansion. Anticipating the interactive effects of past or contemporary conservation measures, climate change, and future human activities will help focus long‐term conservation strategies.
Toll‐like receptors 3, 4 and 9 in hepatocellular carcinoma: Relationship with clinicopathological characteristics and prognosis
Authors: Eiró Noemí , Altadill Antonio , Juárez Luis M. , Rodríguez Manuel , González Luis O. , Atienza Sara , Bermúdez Sandra , Fernandez‐Garcia Belen , Fresno‐Forcelledo Manuel F. , Rodrigo Luis , Vizoso Francisco J.
Published: June 2013

Aim

Hepatocellular carcinoma (HCC) is in the 10 leading cancer types, being difficult to detect as most of patients who develop this tumor have no symptoms other than those related to their long‐standing liver disease. The liver is constantly exposed to bacterial products, viral infection, alcohol or other products, which may be the cause of chronic liver damage, and thus an increasing risk for HCC. Toll‐like receptors (TLR) have gained an extraordinary interest in cancer research due to their role in several biological processes such as innate immune responses, the induction of adaptive immune responses, regulation of inflammation, would healing and carcinogenesis. Therefore, the aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in HCC.

Methods

The expression levels of TLR3, TLR4 and TLR9 were analyzed in tumors from 30 patients with HCC. The analysis was performed by immunohistochemistry. Results were correlated with various clinicopathological findings and with overall survival.

Results

TLR3 was significantly high in large tumors (>4 cm in diameter) compared with small tumors (P < 0.05). Our results demonstrated that patients whose tumors showed both TLR4 and TLR9 positive immunostaining had poor prognosis. In addition, TLR9 expression by fibroblast‐like cells was significantly associated with a shortened overall survival (P = 0.015).

Conclusion

The results demonstrated an association between TLR3, TLR4 and TLR9 expression and tumor aggressiveness and poor prognosis in HCC.
The willingness of informal caregivers to assist their care‐recipient to use Home Medicines Review
Authors: Carter Stephen R. , Moles Rebekah , White Lesley , Chen Timothy F.
Published: June 2013

Objectives

Informal caregivers experience daily hassles – a form of persistent stress, as a consequence of caregiving. This study aimed to develop and test a new theoretical model of health information‐seeking behaviour, the Knowledge Hassles Information Seeking Model (KHISM). KHISM hypothesized that the knowledge hassles of caregivers – daily stressors experienced while dealing with tasks which require knowledge about the safety and effectiveness of the care‐recipients' medicines – would influence caregivers' willingness to assist their care‐recipient to use an Australian medication management service, Home Medicines Review (HMR).

Methods

A cross‐sectional postal survey was conducted among 2350 members of Carers (NSW, Australia). Respondents were included in the study if they were involved in medication‐related tasks for their care‐recipient and were not paid as caregivers. Also, their care‐recipient needed to be taking more than five medicines daily or more than 12 doses daily and had not yet experienced HMR. Structural equation modelling was used to test the model.

Results

A total of 324 useable surveys were returned yielding a response rate of 14%. Respondents were quite willing to assist their care‐recipient to use HMR (willingness). The model predicted 51% of the variation in willingness. Knowledge hassles increased positive outcome expectancy (β = 0.40, P < 0.05) and indirectly increased willingness.

Conclusions

The more caregivers experience hassles with medication knowledge, the more they perceive HMR to be a helpful information source and the more willing they are to use it. Targeted marketing centred on HMR as an information source may increase caregivers' demand for HMR. Further exploration of the phenomenon of knowledge hassles is warranted.
C. S. Lewis: The Question of Multiple Incarnations
Authors: Brazier Paul
Published: June 2013

Formulated by Aquinas, commented on by post‐Copernican philosophers and theologians, analysed in depth by C.S. Lewis, and deliberated by some contemporary writers, the question of multiple incarnations either within humanity or amongst extra‐terrestrial sentient species is all too intermittently examined: ‘Can the Christ be incarnated more than once in our reality, or somewhere else in the universe, or another reality?’ In this paper, we examine the debate and the conclusions: that is, Lewis’s position within his philosophical theology and his analogical narratives; also, some contemporary philosophers of religion and theologians (Karl Rahner, with Christopher L. Fisher and David Fergusson; Sjoerd L. Bonting and William B. Drees; E.L. Mascall and Brian Hebblethwaite; Oliver Crisp and Keith Ward). How do they relate to Aquinas’s handling of the question and how do they compare with Lewis’s approach based on a theology of the imagination (grounded in Augustine and Alice Meynell)? Can Lewis resolve the argument? Could alien species have witnessed wholly different acts, equally unique, costly to God, and necessary to the process of salvation? Any answer or explanation relates to the function and purpose of the incarnation: the Fall, original sin—therefore, how we define the boundaries, limits, of atonement.