bluuebunny/crossref_metadata_2025 huggingface dataset:
Why the ‘last drinking occasion’ approach to measuring alcohol consumption should be avoided
Authors: Østhus Ståle , Brunborg Geir Scott
Published: June 2015

Introduction and Aims

There has been debate about which type of measurement instrument gives the best alcohol consumption estimates. This study used alcohol consumption data for a simulated population to compare the last drinking occasion (LDO) method against the true alcohol consumption. The LDO method requires respondents to indicate the quantity consumed at the LDO, and this information is used to calculate population estimates.

Design and Methods

We simulated three hypothetical distributions of alcohol consumption, each with different underlying drinking patterns and each representing an idealised example of the distribution of alcohol consumption in Norway, Russia and France under specified conditions. We investigated the level of agreement between LDO consumption and the within‐person average consumption, and the expected bias that arises when parameters of interest such as means, percentiles, exceedance proportions, differences in group means, correlation and regression coefficients, attributable fractions, and estimated disease risk functions, are calculated from LDO consumption.

Results

Severe bias was found when LDO consumption was used to calculate common parameters of interest in alcohol and health research. The bias is caused by poor agreement between consumption at the LDO and the within‐person ‘true’ or average consumption. The asymptotically expected bias is particularly problematic because it is unpredictable in terms of direction and magnitude, it varies across groups and populations, and it is probably impossible to adjust for.

Discussion and Conclusion

Future data collections should avoid relying on the LDO method as a measure of typical alcohol consumption, despite its ease of administration. [Østhus S, Brunborg GS. Why the ‘last drinking occasion’ approach to measuring alcohol consumption should be avoided. Drug Alcohol Rev 2015;34:549–58]
Alcohol outlet density and violence: A geographically weighted regression approach
Authors: Cameron Michael P. , Cochrane William , Gordon Craig , Livingston Michael
Published: June 2015

Introduction and Aims

We investigate the relationship between outlet density (of different types) and violence (as measured by police activity) across the North Island of New Zealand, specifically looking at whether the relationships vary spatially.

Design and Methods

We use New Zealand data at the census area unit (approximately suburb) level, on police‐attended violent incidents and outlet density (by type of outlet), controlling for population density and local social deprivation. We employed geographically weighted regression to obtain both global average and locally specific estimates of the relationships between alcohol outlet density and violence.

Result

We find that bar and night club density, and licensed club density (e.g. sports clubs) have statistically significant and positive relationships with violence, with an additional bar or night club is associated with nearly 5.3 additional violent events per year, and an additional licensed club associated with 0.8 additional violent events per year. These relationships do not show significant spatial variation. In contrast, the effects of off‐licence density and restaurant/café density do exhibit significant spatial variation. However, the non‐varying effects of bar and night club density are larger than the locally specific effects of other outlet types.

Discussion and Conclusion

The relationships between outlet density and violence vary significantly across space for off‐licences and restaurants/cafés. These results suggest that in order to minimise alcohol‐related harms, such as violence, locally specific policy interventions are likely to be necessary. [Cameron MP, Cochrane W, Gordon C, Livingston M. Alcohol outlet density and violence: A geographically weighted regression approach. Drug Alcohol Rev 2016;35:280–288]
Intermittent dosing of rapamycin maintains antiepileptogenic effects in a mouse model of tuberous sclerosis complex
Authors: Rensing Nicholas , Han Lirong , Wong Michael
Published: June 2015

Objective

Inhibitors of the mechanistic target of rapamycin (mTOR) pathway have antiepileptogenic effects in preventing epilepsy and pathologic and molecular mechanisms of epileptogenesis in mouse models of tuberous sclerosis complex (TSC). However, long‐term treatment with mTOR inhibitors may be required to maintain efficacy and potentially has chronic side effects, such as immunosuppression. Attempts to minimize drug exposure will facilitate translational efforts to develop mTOR inhibitors as antiepileptogenic agents for patients with TSC. In this study, we tested intermittent dosing paradigms of mTOR inhibitors for antiepileptogenic properties in a TSC mouse model.

Methods

Western blot analysis of phosphorylation of S6 protein was used to assess the dose‐ and time‐dependence of mTOR inhibition by rapamycin in control mice and conditional knockout mice with inactivation of the Tsc1 gene in glial fibrillary acidic protein (GFAP)–expressing cells (Tsc1GFAPCKO mice). Based on the Western blot studies, different dosing paradigms of rapamycin starting at postnatal day 21 were tested for their ability to prevent epilepsy or pathologic abnormalities in Tsc1GFAPCKO mice: 4 days of rapamycin only (4–∞), 4 days on–24 days off (4–24), and 4 days on–10 days off (4–10).

Results

mTOR activity was inhibited by rapamycin in a dose‐dependent fashion and recovered to baseline by about 10 days after the last rapamycin dose. The 4–10 and 4–24 dosing paradigms almost completely prevented epilepsy and the 4–10 paradigm inhibited glial proliferation and megalencephaly in Tsc1GFAPCKO mice.

Significance

Intermittent dosing of rapamycin, with drug holidays of more than 3 weeks, maintains significant antiepileptogenic properties in mouse models of TSC. These findings have important translational applications in developing mTOR inhibitors as antiepileptogenic agents in TSC patients by minimizing drug exposure and potential side effects.
Rapid brief feedback intracerebral stimulation based on real‐time desynchronization detection preceding seizures stops the generation of convulsive paroxysms
Authors: Salam Muhammad T. , Kassiri Hossein , Genov Roman , Perez Velazquez Jose L.
Published: June 2015

Objective

To investigate the abortion of seizure generation using “minimal” intervention in hippocampi using two rat models of human temporal lobe epilepsy.

Methods

The recording or stimulation electrodes were implanted into both hippocampi (CA1 area). Using the kainic acid (chronic: experiment duration 24 days) and the 4‐aminopyridine (acute: experiment duration 2 h) models of paroxysms in rats, a real‐time feedback stimulation paradigm was implemented, which triggered a short periodic electrical stimulus (5 Hz for 5 s) upon detecting a seizure precursor. Our seizure precursor detection algorithm relied on the monitoring of the real‐time phase synchronization analysis, and detected/anticipated electrographic seizures as early as a few seconds to a few minutes before the behavioral and electrographic seizure onset, with a very low false‐positive rate of the detection.

Results

The baseline mean seizure frequencies were 5.39 seizures per day (chronic) and 13.2 seizures per hour (acute). The phase synchrony analysis detected 88% (434 of 494) of seizures with a mean false alarm of 0.67 per day (chronic) and 83% (86 of 104) of seizures with a mean false alarm of 0.47 per hour (acute). The feedback stimulation reduced the seizure frequencies to 0.41 seizures per day (chronic) and 2.4 seizures per hour (acute). Overall, the feedback stimulation paradigm reduced seizure frequency by a minimum of 80% to a maximum of 100% in 10 rats, with 83% of the animals rendered seizure‐free.

Significance

This approach represents a simple and efficient manner for stopping seizure development. Because of the short on‐demand stimuli, few or no associated side effects are expected in clinical application in patients with epilepsy. Abnormal synchrony patterns are common features in epilepsy and other neurologic and psychiatric syndromes; therefore, this type of feedback stimulation paradigm could be a novel therapeutic modality for use in various neurologic and psychiatric disorders.
A review of research into second intention equine wound healing using manuka honey: Current recommendations and future applications
Authors: Dart A. J. , Bischofberger A. S. , Dart C. M. , Jeffcott L. B.
Published: June 2015

In addition to the generic properties of honey, manuka honey has a nonperoxide antimicrobial activity largely attributed to methylglyoxal. Commercially, manuka honey is graded against a standard antiseptic, phenol, to provide a measure of antimicrobial activity referred to as the unique manuka factor (UMF). The higher the UMF, the greater the antimicrobial activity. However, more recently, there is evidence that manuka honey can also modulate the initial inflammatory response through activation of toll‐like receptor 4 on monocytes to enhance production of cytokines important in tissue repair and regeneration. Recent studies investigating the effects of manuka honey on second intention healing of lower limb wounds in horses have shown that wounds treated with UMF 20 manuka honey retracted less and healed faster than untreated wounds. Using this wound healing model, the primary effects of manuka honey appeared to be associated with the modulation of the initial inflammatory reaction rather than its antimicrobial effects. Based on the current knowledge, treatment with manuka honey should be instituted as soon as possible after injury. Where bacterial contamination is substantial, manuka honey with a UMF ≥15 should be used. While bandages will improve the contact between the honey and the wound and may be indicated in the early stages of wound healing, prolonged bandaging may lead to the production of excessive granulation tissue. If topical treatment without a bandage is to be used, more honey is not necessarily better. Using a thin film combined with regular application, contact times may be optimised. Application 2–3 times daily to open wounds may improve efficacy. Manuka honey should be applied for at least 21 days after wounding but there may be beneficial effects if it is applied until wound healing is almost complete.
Epithelial deletion of podoplanin is dispensable for re‐epithelialization of skin wounds
Authors: Baars Sebastian , Bauer Christine , Szabowski Sibylle , Hartenstein Bettina , Angel Peter
Published: June 2015

The mucin‐like transmembrane protein podoplanin (PDPN) is prominently represented in tumor‐associated gene expression signatures of numerous types of cancer including squamous cell carcinoma, and gain‐of‐function and knockdown approaches in tissue culture strongly suggested an important role of PDPN in cell proliferation, migration and adhesion. PDPN is absent during epidermal homeostasis but is highly expressed in basal keratinocytes during cutaneous wound healing. Enhanced motility of immortalized keratinocytes upon ectopic PDPN overexpression argues for wound healing defects upon podoplanin deficiency in keratinocytes; however, in vivo data that unequivocally define the impact of PDPN by functional studies in a physiologically relevant system are still missing. Here, we have applied an in vivo loss‐of‐function approach by generating a novel transgenic mouse line with keratinocyte‐specific podoplanin deficiency. Performing cutaneous full‐thickness excisional wounds to examine re‐epithelialization capacity, unexpectedly, no defects were observed in wound healing properties of mutant mice. Similarly, PDPN‐deficient primary keratinocytes showed no impairment in migration, adhesion or proliferation. Thus, PDPN function is not rate‐limiting for re‐epithelialization but may be functionally compensated by an as yet unknown protein. Our data also call for in vivo functional studies on PDPN in settings of skin tumor development and progression to clarify PDPN's role in skin pathology.
CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin‐10 production predominantly by regulatory B cells
Authors: Fjelbye Jonas , Antvorskov Julie C. , Buschard Karsten , Issazadeh‐Navikas Shohreh , Engkilde Kåre
Published: June 2015

Conflicting observations have been reported concerning the role of CD1d‐dependent natural killer T (NKT) cells in contact hypersensitivity (CHS), supporting either a disease‐promoting or downregulatory function. We studied the role of NKT cells in CHS by comparing the immune response in CD1d knockout (CD1d KO) and wild‐type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0.5% DNCB (w/v) on the ears fifteen days later. We demonstrate that CD1d KO mice, as compared with Wt littermates, have more pronounced infiltration of mononuclear cells in the skin (29.1% increase; P < 0.001), lower frequencies of interleukin‐10+ B cells (Bregs) in the spleen (53.2% decrease; P < 0.05) and peritoneal cavity (80.8% decrease; P < 0.05) and increased production of interferon‐γ (3‐fold; P < 0.05) after DNCB sensitisation and challenge, which suggests an important regulatory and protective role of CD1d‐dependent NKT cells in CHS in our model, at least in part via regulation of IL‐10 producing Bregs.
Food consumption rates of piscivorous brown trout (Salmo trutta) foraging on contrasting coregonid prey
Authors: Jensen H. , Kahilainen K. K. , Vinni M. , Gjelland K. Ø. , Malinen T. , Harrod C. , Amundsen P.‐A.
Published: June 2015

Knowledge of predator–prey dynamics is essential to understand ecosystem functioning. Quantification of such interactions is important for fisheries management, in particular in the case of stocking programmes. Here, food consumption rates (FCR) were quantified for wild and stocked piscivorous brown trout,Salmo truttaL., in three subarctic lakes with contrasting coregonid (Coregonusspp.) prey communities, using the Wisconsin and the Elliott–Hurley bioenergetic models.FCRwas highest for stocked brown trout in lakes with the lowest predator densities, and lowest for wild brown trout. AlthoughFCRestimate may vary somewhat depending on the specific model used, such tools are imperative for the proper impact assessment of brown trout stocking programmes and for the provision of advice on optimal stocking densities.
Upstream and downstream responses of fish assemblages to an eastern Amazonian hydroelectric dam
Authors: Sá‐Oliveira Júlio C. , Hawes Joseph E. , Isaac‐Nahum Victoria J. , Peres Carlos A.
Published: June 2015

Major hydroelectric dams are proliferating in tropical regions such as Amazonia, where extensive new hydropower developments are planned despite potentially severe ecological and social impacts. The status of freshwater biota in the vicinity of existing dams could be valuable to predict the effects of such developments, but detailed ecological monitoring before and after dam construction is frequently lacking.

In the absence of these data, we used a space‐for‐time replacement to compare a key component of the aquatic biota at upstream and downstream sites, with the latter more closely resembling river channel conditions prior to the dam. We assessed the fish assemblages upstream and downstream of the Coaracy Nunes Dam in Amapá, Brazil, the first ecological study at this site since this dam was constructed 42 years earlier. We used gillnets during eight bimonthly field campaigns, covering both wet and dry seasons, and sampled the ichthyofauna (1819 individuals, 81 species) at four sites: Downstream Channel, Reservoir, Upstream Lake and Upstream Channel.

We found clear negative impacts on the abundance, biomass, species richness, alpha diversity and species dominance upstream of the dam. The physical subdivision of the river channel and the upstream channel conversion from lentic to lotic habitats were strongly associated with differences in the composition and structure of fish communities. Notable changes include an increased contribution of small‐bodied fish in the reservoir and an absence of long‐distance migrants upstream of the dam.

Downstream channel habitats, in particular, retained their fish diversity with high conservation value typical of eastern Amazonia, yet these areas now face the threat of new hydropower development farther downstream. The long‐term impacts on aquatic biodiversity highlighted in this study are especially relevant in the face of burgeoning new hydroelectricity development plans for rivers across lowland Amazonia.
Safety and efficacy of long‐term tolvaptan therapy for decompensated liver cirrhosis
Authors: Kogiso Tomomi , Tokushige Katsutoshi , Hashimoto Etsuko , Ikarashi Yuichi , Kodama Kazuhisa , Taniai Makiko , Torii Nobuyuki , Shiratori Keiko
Published: June 2015

Aim

Recently, the short‐term efficacy of the vasopressin V2 receptor antagonist tolvaptan for the treatment of ascites in cirrhosis was reported. However, the long‐term effects remain unknown. Here, we report the clinical features of decompensated cirrhosis treated using long‐term tolvaptan therapy, and evaluate its safety and efficacy.

Methods

Fifty‐five cirrhotic patients hospitalized due to ascites, despite receiving appropriate diuretic treatment, were treated with tolvaptan. We excluded 35 patients due to liver transplant (20.0%), death (28.6%), poor general status (14.3%), improved ascites (5.7%) or other reasons (31.4%). In 20 cases treated with tolvaptan for 6 months, total body water (TBW) and extracellular fluids (ECW) were measured using bioelectric impedance analysis (BIA) with an InBody720.

Results

The median age of the 20 patients was 64 years (range, 48–90), and 60% were male. The etiology of cirrhosis included hepatitis C (45%), alcohol‐induced (20%) and other (35%). The percentage of patients with Child–Pugh class A, B and C was 0%, 40% and 60%, respectively. Biochemical findings revealed that serum creatinine levels and estimated glomerular filtration rate were not affected during 6 months of treatment with tolvaptan, and there was no renal disturbance. The median serum sodium levels were increased from 138 to 139 mEq/L, but serious adverse events related to renal and liver function were not observed. Data also revealed that long‐term treatment reduced the BIA‐estimated ECW/TBW ratio.

Conclusion

Long‐term tolvaptan treatment was a safe and effective treatment for decompensated cirrhosis.
A double-tuned 1H/23Na resonator allows 1H-guided 23Na-MRI in ischemic stroke patients in one session
Authors: Neumaier-Probst Eva , Konstandin Simon , Ssozi Judith , Groden Christoph , Hennerici Michael , Schad Lothar R. , Fatar Marc
Published: June 2015

Background

Established imaging methods are still not confident in the determination of stroke onset. Sodium imaging in animal models and lately in humans implicates that the sodium signal intensity within the ischemic lesion increases in a time-dependent fashion. Sodium imaging usually requires a time-consuming change of resonators or magnetic resonance imaging systems. To avoid this, we used a double-tuned 1H/23Na birdcage head coil in combination with a protocol minimizing T1- and T2*-weighting effects for measurement of sodium intensity in acute stroke patients.

Methods

Multinuclear 1H/23Na data sets were obtained from 16 stroke patients [75 ± 9.9 (standard deviation) years old] 4-130 h after symptom onset. The protocol was acquired on a clinical 3T magnetic resonance imaging site using a double-tuned 1H/23Na birdcage head coil. Sodium signal intensity within the lesion and homologous contralateral side was measured and compared.

Results

With an acquisition time of the complete magnetic resonance imaging protocol of 22 min, a nonlinear sodium signal intensity increase within the lesion over time after stroke onset was acknowledged. Onset time within six-hours showed an increase of only 8% or less, whereas onset time beyond 8.5 h demonstrated increases of 36% or more reaching a maximum of 170% > 120 h. In addition, some patients showed a difference in sodium signal intensity compared with diffusion weighted imaging lesion.

Conclusions

The use of a double-tuned 1H/23Na birdcage head coil in a clinical setting ‘allowed sodium intensity measurements’ in a justifiable time also for acute stroke patients, and heterogenous sodium signal intensity in the diffusion weighted imaging lesion might represent differences in tissue damage or repair.
Dynamic Changes of Intramural Hematoma in Patients with Acute Spontaneous Internal Carotid Artery Dissection
Authors: Heldner Mirjam R. , Nedelcheva Mila , Yan Xin , Slotboom Johannes , Mathier Etienne , Hulliger Justine , Verma Rajeev K. , Sturzenegger Matthias , Jung Simon , Bernasconi Corrado , Arnold Marcel , Wiest Roland , Fischer Urs
Published: June 2015

Background

We prospectively investigated temporal and spatial evolution of intramural hematomas in patients with acute spontaneous internal carotid artery dissection using repeated magnetic resonance imaging over six-months. Aim The aim of the present study was to assess dynamic changes of intramural hematoma in patients with acute spontaneous internal carotid artery dissection at multiple follow-up time-points with T1w, PD/T2w, and magnetic resonance angiography.

Methods

We performed serial multiparametric magnetic resonance imaging in 10 patients with spontaneous internal carotid artery dissection on admission, at days 1, 3, 7–14 and at months 1·5, 3, and 6. We calculated the volume and extension of the hyperintense intramural hematoma using T1w and PD/T2w fat suppressed sequences and assessed the degree of stenosis due to the hematoma using magnetic resonance angiography.

Results

Mean interval from symptom onset to first magnetic resonance imaging was two-days (SD 2·7). Two patients presented with ischemic stroke, three with transient ischemic attacks, and five with pain and local symptoms only. Nine patients had a transient increase of the intramural hematoma volume, mainly up to day 10 after symptom onset. Fifty percent had a transient increase in the degree of the internal carotid artery stenosis on MRA, one resulting in a temporary occlusion. Lesions older than one-week were predominantly characterized by a shift from iso- to hyperintese signal on T2w images. At three-month follow-up, intramural hematoma was no longer detectable in 80% of patients and had completely resolved in all patients after six-months.

Conclusions

Spatial and temporal dynamics of intramural hematomas after spontaneous internal carotid artery dissection showed an early volume increase with concomitant progression of the internal carotid artery stenosis in 5 of 10 patients. Although spontaneous internal carotid artery dissection overall carries a good prognosis with spontaneous hematoma resorption in all our patients, early follow-up imaging may be considered, especially in case of new clinical symptoms.
Prognostic importance of weight change on short-term functional outcome in acute ischemic stroke
Authors: Kim Yerim , Kim Chi Kyung , Jung Seunguk , Ko Sang-Bae , Lee Seung-Hoon , Yoon Byung-Woo
Published: June 2015

Background

Controversy exists regarding the question of whether weight change decreases or increases the risk of mortality.

Aim

The aim of this study was to evaluate the prognostic importance of weight change on short-term outcomes in acute ischemic stroke patients.

Methods

A total of 654 patients with acute ischemic stroke were enrolled in this study from March 2010 to May 2013. We assessed the weight change of each participant between admission and discharge from the Department of Neurology. Weight change was defined as change ≥0.05 kg/baseline body mass index unit. We evaluated the short-term outcomes using a modified Rankin Scale at three-months after the onset of a stroke.

Results

Among the 654 patients, 35.2% were included in the weight-change group. Weight loss occurred in 24.6% of the participants during the hospital stay following the stroke, which lasted an average of nine-days. Compared with the weight-stable group, the pronounced weight-loss group had a higher risk of unfavorable outcomes (odds ratio 2.43; 95% confidence interval 1.12-5.25).

Conclusions

Short-term weight loss after stroke appears to be more common than we expected, and our results suggest that it is associated with unfavorable functional outcomes. Therefore, clinical nutrition should be considered as a component of medical treatment and weight loss should be monitored as an indicator of malnutrition.
Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue following Stroke Practice Guidelines, Update 2015
Authors: Eskes Gail A. , Lanctôt Krista L. , Herrmann Nathan , Lindsay Patrice , Bayley Mark , Bouvier Laurie , Dawson Deirdre , Egi Sandra , Gilchrist Elizabeth , Green Theresa , Gubitz Gord , Hill Michael D. , Hopper Tammy , Khan Aisha , King Andrea , Kirton Adam , Moorhouse Paige , Smith Eric E. , Green Janet , Foley Norine , Salter Katherine , Swartz Richard H.
Published: June 2015

Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals, and the evidence suggests one-third or more will experience vascular-cognitive impairment, and/or intractable fatigue, either alone or in combination. The 2015 update of the Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Module guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. The three consequences of stroke that are the focus of the this guideline (poststroke depression, vascular cognitive impairment, and fatigue) have high incidence rates and significant impact on the lives of people who have had a stroke, impede recovery, and result in worse long-term outcomes. Significant practice variations and gaps in the research evidence have been reported for initial screening and in-depth assessment of stroke patients for these conditions. Also of concern, an increased number of family members and informal caregivers may also experience depressive symptoms in the poststroke recovery phase which further impact patient recovery. These factors emphasize the need for a system of care that ensures screening occurs as a standard and consistent component of clinical practice across settings as stroke patients transition from acute care to active rehabilitation and reintegration into their community. Additionally, building system capacity to ensure access to appropriate specialists for treatment and ongoing management of stroke survivors with these conditions is another great challenge.
Influence of the Strain on Dielectric and Ferroelectric Properties of 0.5BaZr0.2Ti0.8O3–0.5Ba0.7Ca0.3TiO3
Authors: Xu Xijun , Yuan Guoliang , Xu Bo , Yin Jiang , Liu Junming , Liu Zhiguo
Published: June 2015

0.5BaZr0.2Ti0.8O3‐0.5Ba0.7Ca0.3TiO3 ceramic and its epitaxial films on (0 0 1) SrTiO3 substrate were prepared to compare their dielectric and ferroelectric properties. The ceramic has a high dielectric permittivity, a weak dielectric relaxation, a low ferroelectric Curie temperature (TC) of 60°C and a fast polarization relaxation. The films show much lower dielectric permittivities and mild dielectric relaxations. Furthermore, the TC of film with 40, 100, and 200 nm thickness is 155°C, 110°C, and 60°C, respectively, because the epitaxial strain decreases with the film thickness increasing. The higher the TC is, the more stable the room‐temperature polarization is.
Calibrating the molecular clock beyond cytochrome b: assessing the evolutionary rate of COI in birds
Authors: Lavinia Pablo D. , Kerr Kevin C. R. , Tubaro Pablo L. , Hebert Paul D. N. , Lijtmaer Darío A.
Published: June 2015

Estimating the age of species or their component lineages based on sequence data is crucial for many studies in avian evolutionary biology. Although calibrations of the molecular clock in birds have been performed almost exclusively using cytochrome b (cyt b), they are commonly extrapolated to other mitochondrial genes. The existence of a large, standardized cytochrome c oxidase subunit I (COI) library generated as a result of the DNA barcoding initiative provides the opportunity to obtain a calibration for this mitochondrial gene in birds. In this study we compare the evolutionary rate of COI relative to cyt b across ten different avian orders. We obtained divergence estimates for both genes from nearly 300 phylogenetically independent pairs of species through the analysis of almost 5000 public sequences. For each pair of species we calculated the difference in divergence between COI and cyt b. Our results indicate that COI evolves on average 14% slower than cyt b, but also reveal considerable variation both among and within avian orders, precluding the use of this value as a standard adjustment for the COI molecular clock for birds. Our findings suggest that this variation is partially explained by a clear negative relationship between the difference in divergence in these genes and the age of species. Distances for cyt b are higher than those for COI for closely related species, but the values become similar as the divergence between the species increases. This appears to be the result of a stronger pattern of negative time‐dependency in the rate of cyt b than in that of COI, a difference that could be related to lower functional constraints on a small number of sites in cyt b that allow it to initially accumulate mutations more rapidly than COI.
Associations of Angiotensin‐Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta‐Analysis
Authors: Gong Feng‐Feng , Hu Cai‐Yun , Lu Shan‐Shan , Qian Zhen‐Zhong , Feng Fang , Wu Yi‐Le , Yang Hui‐Yun , Sun Ye‐Huan
Published: June 2015

There have been numerous studies concerning the associations of angiotensin‐converting enzyme (ACE) gene insertion/deletion (I/D), angiotensin II receptor 1 (AT1R) gene A1166C, and endothelial nitric oxide synthase (eNOS) gene 4b/a polymorphisms with risk of pregnancy hypertensive disorders (PHDs). However, the results are inconsistent. A total of 83 eligible studies (10,354/18,446 cases/controls) were included in this meta‐analysis. Pooled odds ratios with corresponding 95% confidence intervals were used to calculate these associations. The effects of ethnicity and types of PHDs were also considered. Results showed significant associations between the ACE gene polymorphism and PHDs in all of the populations except that in Africa. The associations also existed in AT1R, eNOS gene polymorphism and PHDs in part of the gene models in the overall population. These results indicated the ACE gene polymorphism was associated with an increased risk of PHDs, whereas the eNOS and AT1R gene polymorphism only have increased susceptibility to PHDs in part of the gene models.
Whole Brain Volume Measured from 1.5T versus 3T MRI in Healthy Subjects and Patients with Multiple Sclerosis
Authors: Chu Renxin , Tauhid Shahamat , Glanz Bonnie I. , Healy Brian C. , Kim Gloria , Oommen Vinit V. , Khalid Fariha , Neema Mohit , Bakshi Rohit
Published: June 2015

BACKGROUND

Whole brain atrophy is a putative outcome measure in monitoring relapsing‐remitting multiple sclerosis (RRMS). With the ongoing MRI transformation from 1.5T to 3T, there is an unmet need to calibrate this change. We evaluated brain parenchymal volumes (BPVs) from 1.5T versus 3T in MS and normal controls (NC).

METHODS

We studied MS [n = 26, age (mean, range) 43 (21‐55), 22 (85%) RRMS, Expanded Disability Status Scale (EDSS) 1.98 (0‐6.5), timed 25 foot walk (T25FW) 5.95 (3.2‐33.0 seconds)] and NC [n = 9, age 45 (31‐53)]. Subjects underwent 1.5T (Phillips) and 3T (GE) 3‐dimensional T1‐weighted scans to derive normalized BPV from an automated SIENAX pipeline. Neuropsychological testing was according to consensus panel recommendations.

RESULTS

BPV‐1.5T was higher than BPV‐3T [mean (95% CI) + 45.7 mL (+35.3, +56.1), P < .00001], most likely due to improved tissue‐CSF contrast at 3T. BPV‐3T showed a larger volume decrease and larger effect size in detecting brain atrophy in MS versus NC [−74.5 mL (−126.5, −22.5), P = .006, d = .92] when compared to BPV‐1.5T [−51.3.1 mL (−99.8, −2.8), P = .04, d = .67]. Correlations between BPV‐1.5T and EDSS (r = −.43, P = .027) and BPV‐3T and EDSS (r = −.49, P = .011) and between BPV‐1.5T and T25FW (r = −.46, P = .018) and BPV‐3T and T25FW (r = −.56, P = .003) slightly favored 3T. BPV‐cognition correlations were significant (P < .05) for 6 of 11 subscales to a similar degree at 1.5T (r range = .44‐.58) and 3T (r range = .43‐.53).

CONCLUSIONS

Field strength may impact whole brain volume measurements in patients with MS though the differences are not too divergent between 1.5T and 3T.
A new likelihood ratio metric for the psychomotor vigilance test and its sensitivity to sleep loss
Authors: Basner Mathias , Mcguire Sarah , Goel Namni , Rao Hengyi , Dinges David F.
Published: June 2015

The Psychomotor Vigilance Test (PVT) is a widely used assay of behavioural alertness sensitive to the effects of sleep loss and circadian misalignment. However, there is currently no accepted PVT composite outcome metric that captures response slowing, attentional lapses and compensatory premature reactions observed typically in sleep‐deprived subjects. We developed a novel likelihood ratio metric (LRM) based on relative frequency distributions in 50 categories of reaction times (RT) and false starts in alert and sleep‐deprived subjects (acute total sleep deprivation: n = 31 subjects). The LRM had the largest effect size both in a 33‐h total sleep deprivation protocol [1.96; 95% confidence interval (CI): 1.61–2.44; followed by response speed 1/RT, effect size 1.93, 95% CI: 1.55–2.65] and in a chronic partial sleep restriction protocol (1.22; 95% CI: 0.96–1.59; followed by response speed 1/RT, effect size 1.21, 95% CI: 0.94–1.59; 5 nights at 4 h sleep per night; n = 43 subjects). LRM scores correlated highly with response speed (R2 = 0.986), and less well with five other common PVT outcome metrics (R2 = 0.111–0.886). In conclusion, the new LRM is a sensitive PVT outcome metric with high statistical power that takes subtle sleep loss‐related changes in the distribution of reaction times (including false starts) into account, is not prone to outliers, does not require baseline data and can be calculated and interpreted easily. Congruence between LRM and PVT response speed and their similar effect size rankings support the use of response speed as the primary, most sensitive and most parsimonious standard PVT outcome metric for determining neurobehavioural deficits from sleep loss.
LTP3 contributes to disease susceptibility in Arabidopsis by enhancing abscisic acid (ABA) biosynthesis
Authors: Gao Shan , Guo Wenya , Feng Wen , Liu Liang , Song Xiaorui , Chen Jian , Hou Wei , Zhu Hongxia , Tang Saijun , Hu Jian
Published: June 2015

Several plant lipid transfer proteins (LTPs) act positively in plant disease resistance. Here, we show that LTP3 (At5g59320), a pathogen and abscisic acid (ABA)‐induced gene, negatively regulates plant immunity in Arabidopsis. The overexpression of LTP3 (LTP3‐OX) led to an enhanced susceptibility to virulent bacteria and compromised resistance to avirulent bacteria. On infection of LTP3‐OX plants with Pseudomonas syringae pv. tomato, genes involved in ABA biosynthesis, NCED3 and AAO3, were highly induced, whereas salicylic acid (SA)‐related genes, ICS1 and PR1, were down‐regulated. Accordingly, in LTP3‐OX plants, we observed increased ABA levels and decreased SA levels relative to the wild‐type. We also showed that the LTP3 overexpression‐mediated enhanced susceptibility was partially dependent on AAO3. Interestingly, loss of function of LTP3 (ltp3‐1) did not affect ABA pathways, but resulted in PR1 gene induction and elevated SA levels, suggesting that LTP3 can negatively regulate SA in an ABA‐independent manner. However, a double mutant consisting of ltp3‐1 and silent LTP4 (ltp3/ltp4) showed reduced susceptibility to Pseudomonas and down‐regulation of ABA biosynthesis genes, suggesting that LTP3 acts in a redundant manner with its closest homologue LTP4 by modulating the ABA pathway. Taken together, our data show that LTP3 is a novel negative regulator of plant immunity which acts through the manipulation of the ABA–SA balance.
Motifs in the assembly of food web networks
Authors: Baiser Benjamin , Elhesha Rasha , Kahveci Tamer
Published: June 2015

The assembly of local communities from regional pools is a multifaceted process that involves the confluence of interactions and environmental conditions at the local scale and biogeographic and evolutionary history at the regional scale. Understanding the relative influence of these factors on community structure has remained a challenge and mechanisms driving community assembly are often inferred from patterns of taxonomic, functional, and phylogenetic diversity. Moreover, community assembly is often viewed through the lens of competition and rarely includes trophic interactions or entire food webs. Here, we use motifs – subgraphs of nodes (e.g. species) and links (e.g. predation) whose abundance within a network deviates significantly as compared to a random network topology – to explore the assembly of food web networks found in the leaves of the northern pitcher plantSarracenia purpurea. We compared counts of three‐node motifs across a hierarchy of scales to a suite of null models to determine if motifs are over‐, under‐, or randomly represented. We then assessed if the pattern of representation of a motif in a given network matched that of the network it was assembled from. We found that motif representation in over 70% of site networks matched the continental network they were assembled from and over 75% of local networks matched the site networks they were assembled from for the majority of null models. This suggests that the same processes are shaping networks across scales. To generalize our results and effectively use a motif perspective to study community assembly, a theoretical framework detailing potential mechanisms for all possible combinations of motif representation is necessary.
A trade off in the absolute magnitudes of seed and microsite limitations and their effects on population regulation
Authors: García‐Meza Diego , Martorell Carlos
Published: June 2015

Microsite limitation (ML) occurs when the number of suitable sites for development determines population size. Seed limitation (SL) arises when seeds cannot occupy all microsites. Both limitations have been measured on relative scales, but absolute values would allow analyzing the relationship between them and their contributions to population regulation. A tradeoff is expected because small‐seeded species are prolific and thus could have low SL, whereas large seeds perform better under different conditions, lowering ML. We assessed whether there is such tradeoff, and if it is mediated by seed size. We measured the absolute magnitudes of limitations through seed addition experiments, and tested whether they determine population density in 14 herbs with different seed sizes in a semiarid grassland. All species were limited by microsites and seeds. The tradeoff occurred only during germination, but was seemingly not mediated by seed size. Annual species were more limited by microsites than perennials, which suffered more SL. Population densities were smaller for species with greater ML measured over the life cycle, but marginally so when ML was measured during germination. SL only reduced annual‐plant density. These negative correlations indicate that our measurements correspond to actual limitations. Microsites limited populations depending on the process analyzed (germination, survival and whole life‐cycle) and the life history of species, suggesting that an integral approach to ML is required rather than focusing only on germination. Comparing annuals and perennials, we found that the strongest limitation is the main determinant of population size. The tradeoff was consistent with seed size and competition–colonization tradeoff, but our results were inconclusive. The SL–ML tradeoff seems to arise from still‐unidentified evolutionary constraints, and may contribute to the maintenance of species diversity, preventing any single species from becoming dominant and excluding its neighbors.
Community Factors in Differential Responses of Child Protective Services
Authors: McCallum Karen , Cheng An‐Lin
Published: June 2015

Objective

In response to criticisms of the traditional investigative model of child protective services (CPS) as adversarial, a Differential Response Model has emerged, with investigative and noninvestigative alternative response (AR) paths. The purpose of this study was to identify relationships of county‐level community variables to response paths.

Design and Sample

Secondary analysis used data from the National Child Abuse and Neglect Data System linked to county‐level variables from the American Community Survey. The final dataset included 62,499 cases and 98 counties from five states.

Measures

Multilevel modeling was used to analyze the binary outcome variable of CPS response path (AR, non‐AR). Predictor variables included indicators at child, county, and state levels.

Results

County‐level variables (housing vacancy, child poverty, unemployment, and households with public assistance) were significant predictors (p < .05) of CPS response path and accounted for 12.30% of variability in the final three‐level model. Individual variables (report source, maltreatment type, child age, race, and number of children in the report) were also significant predictors.

Conclusion

County‐level community variables have significant relationships with CPS response paths and impact how CPS units respond to new referrals. Research is needed to apply advanced multilevel analytic procedures to more accurately model nested relationships.
“Nobody Wants to Be an Outsider”: From Diversity Management to Diversity Engagement
Authors: Howarth Caroline , Andreouli Eleni
Published: June 2015

This article develops an analysis of diversity in two ways. We start with a theoretical discussion of the ways in which diversity has been approached within psychology, showing the competing arguments that have been developed that connect diversity, community, and multiculturalism. We show that not only are there psychological consequences to contemporary experiences of increased diversity but also that fundamental psychological capacities—such as self‐consciousness, identity, and dialogue—actually stem from the experience of diversity. This has important implications for diversity management policies. The second part of the article gives an empirical illustration of how diversity is experienced in schools across England drawing on 13 interviews with senior staff and 11 focus groups with pupils aged between 12 and 14 years old. We discuss three themes related to experiences of diversity: (1) from difference to diversity, (2) real and imagined mobility across communities, and (3) collaborative practices, projects, and knowledge. What the empirical examples show is that critically engaging with diversity can be a more productive project than practices which construct diversity in terms of distinct groups that need respect and tolerance. Hence we argue approaches that promote engaging with diversity rather than traditional diversity management are more in line with foundational psychological insights as well as empirical research findings.
Functional capacity in idiopathic pulmonary fibrosis: Looking beyond the lungs
Authors: Holland Anne E.
Published: June 2015

See article, page 953
Do Trade Agreements Stimulate International Trade Differently? Evidence from 296 Trade Agreements
Authors: Kohl Tristan , Brakman Steven , Garretsen Harry
Published: June 2015

In a seminal article, Rose (2004) found that the assumed positive impact of the WTO on international trade was questionable. This finding has been scrutinised and modified in subsequent research, using different data sets, econometric methods and separating the WTO from other forms of trade agreements. A key characteristic of the subsequent literature is the rather simplistic way in which trade agreements are treated whereby all trade agreements are lumped together. Trade agreements come, however, in many different forms and shapes. This study addresses these differences in trade agreements. Using a unique database of 296 trade agreements, we distinguish 17 trade‐related policy domains and indicate whether the agreements contain legally enforceable commitments. This extensive and novel taxonomy of trade agreements enables us to allow for the possible heterogeneity of the impact of trade agreements on international trade. Using a gravity model, we find that trade agreement heterogeneity indeed matters for international trade and that countries experience significant trade increases due to comprehensive trade agreements even if not all participants are in the WTO.
Evaluation of systemic absorption and renal effects of topical ophthalmic flurbiprofen and diclofenac in healthy cats
Authors: Lanuza Rick , Rankin Amy J. , KuKanich Butch , Meekins Jessica M.
Published: June 2015

Objective

To investigate systemic absorption and renal effects of topically applied ophthalmic flurbiprofen and diclofenac in healthy cats.

Animals studied

Twelve domestic shorthair cats.

Procedures

Cats were randomly assigned to two treatment groups (n = 6) and administered one drop (approximately 40 μL) of either flurbiprofen 0.03% or diclofenac 0.1% in both eyes four times daily (6 am, 12 pm, 6 pm, and 12 am) for 14 days. Blood samples were collected on days 0, 4, 8, 14, 16, and 17 and analyzed by liquid chromatography and mass spectrometry for flurbiprofen and diclofenac plasma concentrations. A complete blood count (CBC), serum chemistry, and urinalysis were analyzed at the beginning of the study (Day 0) and at the end of topical drug administration (Day 15).

Results

Both drugs demonstrated systemic absorption. Flurbiprofen was detected (mean ± SD) at day 4 (237 ± 65 ng/mL), day 8 (396 ± 91 ng/mL), day 14 (423 ± 56 ng/mL), day 16 (350 ± 66 ng/mL), and day 17 (270 ± 62 ng/mL), and diclofenac was detected (mean ± SD) at day 4 (130 ± 44 ng/mL), day 8 (131 ± 25 ng/mL), day 14 (150 ± 36 mg/mL), and sporadically on day 16. Flurbiprofen plasma concentration decreased slowly over 48 h after the last dose. No clinically significant abnormalities were noted in the serum blood urea nitrogen, creatinine, or urine specific gravity at the end of topical drug administration compared to the beginning of the study.

Conclusions

Flurbiprofen and diclofenac were systemically absorbed after topical administration four times daily to both eyes of healthy cats. Flurbiprofen reached higher plasma concentrations compared to diclofenac.
Convection-Enhanced Intravitreous Drug Delivery in Human Eye
Authors: Narasimhan Arunn , Sundarraj C.
Published: June 2015

Two-dimensional computational model has been developed for simulation of convection-assisted drug transport during intravitreal drug delivery for vitrectomized human eye. The convection current in vitreous humor was induced by laser heating. The model drug fluorescein was placed initially in different positions inside the vitreous. The transport of drug, taking the natural convection flow into account, was numerically solved using appropriate conservation equations. For a simulation period of 60 min, the convection-assisted diffusion increased the average drug mass fraction in the retinal target region by 5.7 times compared to the pure diffusion model, in case of central depot. Even for low diffusivity high molecular weight compounds, the convection in vitreous proved useful in enhancing the transport across vitreous. The study showed that inducing convection in vitreous could be potentially used for drug delivery in eye. Also laser heating could be explored as an option to enhance the delivery of drug to the posterior segment of the eye.