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Using an activity monitoring system (AMS) equipped with an accelerometer, 2 experiments were conducted to test the hypotheses that (1) enhancing progesterone before inducing luteolysis or (2) exposing cows to estradiol cypionate (ECP) or testosterone propionate (TP) after luteolysis would increase occurrence and intensity of estrus. Our goal was to determine if more cows could be detected in estrus by an AMS compared with other estrus-detection aids. In experiment 1, cows (n=154) were fitted with both an AMS collar and a pressure-sensitive, rump-mounted device (HeatWatch; HW) and assigned to 3 treatments: (1) no CL + progesterone insert (CIDR) for 5d, (2) CL only, or (3) CL + 2 CIDR inserts for 5d to achieve a range in concentrations of progesterone. Prostaglandin F 2α was administered to all cows upon CIDR insert removal or its equivalent. Progesterone concentration up to 72h posttreatment was greatest in CL + 2 CIDR, followed by CL only, and no CL + CIDR cows. Estrus occurred 14 to 28h earlier in no CL + CIDR compared with CL-bearing cows. Estrus intensity was greater for CL + 2 CIDR than for CL-only cows. The AMS and HW detected 70 and 59% of cows defined to be in estrus, respectively. In experiment 2, cows (n=203) were equipped with both an AMS and a friction-activated, rump-mounted patch (Estrotect patch) and assigned to receive 1mg of ECP, 2mg of TP, or control 24h after PGF 2α . Concentrations of estradiol 24 and 48h after treatment were greater in ECP cows compared with controls. Estrus expression detected by AMS or patches in cows defined to be in estrus tended to be greater or was greater for ECP compared with controls, respectively. Compared with controls and in response to TP or ECP, estrus occurred 8 to 18h earlier and was of greater intensity for ECP cows, respectively. The AMS and patches determined 73 and 76% of cows defined to be in estrus, respectively. Of cows exposed to the AMS, HW, or patches, 70, 61, and 75%, respectively, were detected in estrus and more than 93% of these subsequently ovulated. In contrast, of the residual cows not detected in estrus, 62 to 77% ovulated in the absence of detected estrus. Only ECP was successful in inducing more expression and intensity of estrus, and proportions of cows detected in estrus exceeded 80%. Given the large proportion of cows equipped with AMS collars ovulating in the absence of estrus, further research is warranted to determine if more pregnancies can be achieved by inseminating those cows not detected in estrus at an appropriate time when PGF 2α is administered to induce luteolysis., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.

Neuroscience and molecular biology have been generating large datasets over the past years that are reshaping how research is being conducted. In their wake, open data sharing has been singled out as a major challenge for the future of research. We conducted a comparative study of citations of data publications in both fields, showing that the average publication tagged with a data-related term by the NCBI MeSH (Medical Subject Headings) curators achieves a significantly larger citation impact than the average in either field. We introduce a new metric, the data article citation index (DAC-index), to identify the most prolific authors among those data-related publications. The study is fully reproducible from an executable Rmd (R Markdown) script together with all the citation datasets. We hope these results can encourage authors to more openly publish their data.

We hypothesized that GnRH would increase pregnancy risk (PR) in a split-time AI program for cows in which estrus was not detected. A total of 1,236 suckled beef cows at 12 locations in 3 states (Colorado, Kansas, and North Dakota) were enrolled. Before applying the fixed-time AI program, BCS was assessed. Cows were treated on d -7 with a progesterone insert concurrent with 100 μg GnRH and on d 0 with 25 mg PGF plus removal of the insert. Estrus-detection patches were affixed to cows at insert removal. Estrus was defined to have occurred when an estrus-detection patch was >50% colored (activated). Cows in estrus by 65 h ( = 758; 61.3% of all cows) were randomly allocated to 2 treatments: 1) 100 μg GnRH and early + GnRH (E+G; = 373) or 2) AI only at 65 h (early - no GnRH [E-G]; = 385). The remaining cows were randomly allocated to 2 treatments: 1) 5(L+G; = 252) or 2) AI only at 84 h (late no GnRH [L-G]; = 226). Pregnancy was determined 35 d after AI via transrectal ultrasound. Pregnancy risk did not differ ( = 0.68) between E+G and E-G cows (61.9 vs. 60.4%, respectively). Conversely, for cows inseminated at 84 h, PR was greater ( = 0.01) in cows that received GnRH (L+G) compared with their herd mates not receiving GnRH (L- G; 41.7 vs. 30.8%, respectively). Of those cows not detected in estrus by 65 h, 42.1% were detected by 84 h, for a total expression of estrus by all cows of 77.6%. Administration of GnRH increased ( < 0.01) PR in cows not detected in estrus by 84 h (+GnRH = 33.4% [ = 146] vs. no GnRH = 15.0% [ = 128]) but had no effect in cows expressing estrus by 84 h (+GnRH = 65.3% [ = 103] vs. no GnRH = 61.7% [ = 97]). Neither estrus expression by 65 or 84 h nor PR was influenced by BCS, parity, or days postpartum at AI. Cows had greater PR when they had been detected in estrus before AI, and PR was improved by administration of GnRH at 65 h after insert removal in cows that were not detected in estrus and inseminated at 84 h.

A multilocation study examined pregnancy risk (PR) after delaying AI in suckled beef cows from 60 to 75 h when estrus had not been detected by 60 h in response to a 7-d CO-Synch + progesterone insert (CIDR) timed AI (TAI) program (d -7: CIDR insert concurrent with an injection of GnRH; d 0: PGF injection and removal of CIDR insert; and GnRH injection at TAI [60 or 75 h after CIDR removal]). A total of 1,611 suckled beef cows at 15 locations in 9 states (CO, IL, KS, MN, MS, MT, ND, SD, and VA) were enrolled. Before applying the fixed-time AI program, BCS was assessed, and blood samples were collected. Estrus was defined to have occurred when an estrus detection patch was >50% colored (activated). Pregnancy was determined 35 d after AI via transrectal ultrasound. Cows ( = 746) detected in estrus by 60 h (46.3%) after CIDR removal were inseminated and treated with GnRH at AI (Control). Remaining nonestrous cows were allocated within location to 3 treatments on the basis of parity and days postpartum: 1) GnRH injection and AI at 60 h (early-early = EE; = 292), 2) GnRH injection at 60 h and AI at 75 h (early-delayed = ED; = 282), or 3) GnRH injection and AI at 75 h (delayed-delayed = DD; = 291). Control cows had a greater ( < 0.01) PR (64.2%) than other treatments (EE = 41.7%, ED = 52.8%, DD = 50.0%). Use of estrus detection patches to delay AI in cows not in estrus by 60 h after CIDR insert removal (ED and DD treatments) increased ( < 0.05) PR to TAI when compared with cows in the EE treatment. More ( < 0.001) cows that showed estrus by 60 h conceived to AI at 60 h than those not showing estrus (64.2% vs. 48.1%). Approximately half (49.2%) of the cows not in estrus by 60 h had activated patches by 75 h, resulting in a greater ( < 0.05) PR than their nonestrous herd mates in the EE (46.1% vs. 34.5%), ED (64.2% vs. 39.2%), and DD (64.8% vs. 31.5%) treatments, respectively. Overall, cows showing estrus by 75 h (72.7%) had greater ( < 0.001) PR to AI (61.3% vs. 37.9%) than cows not showing estrus. Use of estrus detection patches to allow for a delayed AI in cows not in estrus by 60 h after removal of the CIDR insert improved PR to TAI by optimizing the timing of the AI in those cows.

Context: Recreational use of Synthetic Cannabinoid Receptors Agonists (SCRAs) has become increasingly common in many countries and may cause severe toxic effects., Objective: To describe the clinical features of toxicity in seven men after analytically confirmed exposure to MDMB-CHMICA, a recently described indole-based SCRA., Materials and Methods: Clinical information and biological samples (blood, urine) were collected from patients with severe toxicity after suspected use of novel psychoactive substances. Samples were analyzed by data-independent liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Case Reports: All seven cases were men who presented to hospitals in England between July and October 2015; six reported smoking "legal high" products. In all cases, MDMB-CHMICA was identified in blood samples taken on admission to hospital. Other substances were identified in four cases (methadone 1, methiopropamine 1, other SCRAs 2). Clinical features in all seven cases and in the three exposed to MDMB-CHIMICA alone included acidosis (7/7 and 3/3) which was respiratory (3/7 and 3/3), metabolic (3/7 and 0/3) or mixed (1/7, 0/3), reduced level of consciousness (6/7 and 3/3), mydriasis (5/7 and 3/3), tachycardia (5/7 and 2/3), bradycardia (2/7 and 1/3), tonic-clonic convulsions (2/7 and 1/3) and agitation (3/7 and 1/3). Recovery occurred within 24 h in all cases except one male also exposed to methiopropamine., Conclusions: Analytically confirmed exposure to MDMB-CHMICA was associated with acidosis (often of respiratory origin), reduced level of consciousness, mydriasis, heart rate disturbances and convulsions.

Protected areas are widely considered essential for biodiversity conservation. However, few global studies have demonstrated that protection benefits a broad range of species. Here, using a new global biodiversity database with unprecedented geographic and taxonomic coverage, we compare four biodiversity measures at sites sampled in multiple land uses inside and outside protected areas. Globally, species richness is 10.6% higher and abundance 14.5% higher in samples taken inside protected areas compared with samples taken outside, but neither rarefaction-based richness nor endemicity differ significantly. Importantly, we show that the positive effects of protection are mostly attributable to differences in land use between protected and unprotected sites. Nonetheless, even within some human-dominated land uses, species richness and abundance are higher in protected sites. Our results reinforce the global importance of protected areas but suggest that protection does not consistently benefit species with small ranges or increase the variety of ecological niches.

Land use and related pressures have reduced local terrestrial biodiversity, but it is unclear how the magnitude of change relates to the recently proposed planetary boundary ("safe limit"). We estimate that land use and related pressures have already reduced local biodiversity intactness--the average proportion of natural biodiversity remaining in local ecosystems--beyond its recently proposed planetary boundary across 58.1% of the world's land surface, where 71.4% of the human population live. Biodiversity intactness within most biomes (especially grassland biomes), most biodiversity hotspots, and even some wilderness areas is inferred to be beyond the boundary. Such widespread transgression of safe limits suggests that biodiversity loss, if unchecked, will undermine efforts toward long-term sustainable development., (Copyright © 2016, American Association for the Advancement of Science.)

Context: Toxicity from the use of synthetic cannabinoid receptor agonists (SCRAs) has been encountered increasingly frequent in many countries., Objective: To characterise presentation rates, demographic profiles and reported clinical features for users of SCRAs referred by health professionals in the United Kingdom to the National Poisons Information Service (NPIS), to compare reported toxicity between commonly used branded products, and to examine the impact of legal control measures on enquiry numbers., Methods: NPIS telephone enquiry records were searched for SCRA-related terms for the 8-year period 1st January 2007 to 31st December 2014, consolidating multiple enquiries about the same case into a single record. Demographic data, reported exposure details, clinical features and poisoning severity were analysed, excluding cases where SCRA exposure was unlikely., Results: Enquiries to the NPIS were made concerning 510 individuals relating to probable SCRA use, with annual numbers increasing year on year. Most patients were male (80.8%) and <25 years old (65.1%). Common clinical features reported in the 433 (84.9%) patients reporting SCRA use without other substances included tachycardia (n = 73, 16.9%), reduced level of consciousness (n = 70, 16.2%), agitation or aggression (n = 45, 10.4%), vomiting (n = 30, 6.9%), dizziness (n = 26, 6.0%), confusion (n= 21, 4.8%), mydriasis (n = 20, 4.6%) and hallucinations (n = 20, 4.6%). The Maximum Poisoning Severity Score (PSS) indicated severe toxicity in 36 cases (8.3%). Legal control of "second generation" SCRAs did not affect the rate of growth in enquiry numbers or the proportion with severe toxicity. The three most commonly reported products were "Black Mamba" (n= 88, 20.3%), "Pandora's Box" (n= 65, 15.0%) and "Clockwork Orange" (n= 27, 6.2%). Neurological and general features were recorded more often with "Clockwork Orange" than for "Black Mamba" and "Pandora's Box", but moderate or severe toxicity was significantly less common after reported use of this product., Conclusions: Enquiries about SCRA-related toxicity have become increasingly frequent in the UK in spite of legal controls and commonly involve younger males. Differences in the patterns of toxicity associated with different branded preparations may occur, although further work with larger patient numbers is needed to confirm this.

Background: Healthcare metrics have been used to drive improvement in outcome and delivery in UK hospital stroke and cardiac care. This model is attractive for chronic obstructive pulmonary disease (COPD) care because of disease frequency and the burden it places on primary, secondary and integrated care services., Methods: Using 'hospital episode statistics' (UK 'coding'), we examined hospital 'bed days/1000 population' in 150 UK Primary Care Trusts (PCTs) during 2006-07 and 2007-08. Data were adjusted for COPD prevalence. We looked at year-on-year consistency and factors which influenced variation., Results: There were 248 996 COPD admissions during 2006-08. 'Bed days/1000 PCT population' was consistent between years (r = 0.87; P < 0.001). There was a >2-fold difference in bed days between the best and worst performing PCTs which was primarily a consequence of variation in emergency admission rate (P < 0.001) and proportion of emergency admissions due to COPD (P < 0.001) and to only a lesser extent length of hospital stay (P < 0.001)., Conclusions: Bed days/1000 population appears a useful annual metric of COPD care quality. Good COPD care keeps patients active and out of hospital and requires co-ordinated action from both hospital and community services, with an important role for integrated care. This metric demonstrates that current care is highly variable and offers a measurable target to commission against., (© The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Expression of estrus after PG and before fixed-time AI has been reported to change the uterine environment, increase accessory sperm numbers, fertilization rates, and overall embryo survival. Thus, expression of estrus can strongly impact overall pregnancy success. Because of variation in percentage of beef females detected in estrus and number of animals per study, it can be difficult to detect a significant effect of estrus on pregnancy success. Thus, a meta-analysis was conducted using data from 10,116 beef females in 22 studies that utilized variations of the 5 most common fixed-time AI protocols (CO-Synch, 7-day CO-Synch+CIDR, 5-day CIDR, PG 6-day CIDR, and the 14-day CIDR protocols) to examine the effect of detection in standing estrus on subsequent fixed-time AI pregnancy success. A random-effects model was used to combine the studies/herds. The overall model indicated a positive effect of estrus on conception rates with cows detected in estrus before fixed-time AI having a 27% greater (P<0.05; 95% CI=22-32%) conception rate compared with those not detected in estrus. Next we determined factors that influenced expression of estrus. Data were available on 547 cows synchronized with a CIDR based fixed-time AI protocols and observed for estrus before AI during 2-4 breeding seasons. Analysis of these cows indicated that days postpartum (P=0.22) did not impact estrous expression. In contrast, BCS influenced estrous expression (P=0.04) with cows in a BCS of ≤4 (51±5%) having decreased expression of estrus compared to cows with a BCS>4 (≥70±4%). Initiation of estrous cycles before the breeding season also influenced estrous expression (P=0.03), with anestrous cows having greater expression of estrus compared with estrus-cycling cows (78±5% vs. 70±5%, respectively). In conclusion, among all currently recommended fixed-time AI protocols, cows detected in estrus before fixed-time AI had improved conception rates, with BCS and estrus-cycling status having the greatest influence on expression of estrus., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Context: Synthetic cannabinoids (SCs) such as "Spice", "K2", etc. are widely available via the internet despite increasing legal restrictions. Currently, the prevalence of use is typically low in the general community (<1%) although it is higher among students and some niche groups subject to drug testing. Early evidence suggests that adverse outcomes associated with the use of SCs may be more prevalent and severe than those arising from cannabis consumption., Objectives: To identify systematically the scientific reports of adverse events associated with the consumption of SCs in the medical literature and poison centre data., Method: We searched online databases (Medline, PsycInfo, Embase, Google Scholar and Pubmed) and manually searched reference lists up to December 2014. To be eligible for inclusion, data had to be from hospital, emergency department, drug rehabilitation services or poison centre records of adverse events involving SCs and included both self-reported and/or analytically confirmed consumption., Results: From 256 reports, we identified 106 eligible studies including 37 conference abstracts on about 4000 cases involving at least 26 deaths. Major complications include cardiovascular events (myocardial infarction, ischemic stroke and emboli), acute kidney injury (AKI), generalized tonic-clonic seizures, psychiatric presentations (including first episode psychosis, paranoia, self-harm/suicide ideation) and hyperemesis. However, most presentations were not serious, typically involved young males with tachycardia (≈ 37-77%), agitation (≈ 16-41%) and nausea (≈ 13-94%) requiring only symptomatic care with a length of stay of less than 8 hours., Conclusions: SCs most frequently result in tachycardia, agitation and nausea. These symptoms typically resolve with symptomatic care, including intravenous fluids, benzodiazepines and anti-emetics, and may not require inpatient care. Severe adverse events (stroke, seizure, myocardial infarction, rhabdomyolysis, AKI, psychosis and hyperemesis) and associated deaths manifest less commonly. Precise estimates of their incidence are difficult to calculate due to the lack of widely available, rapid laboratory confirmation, the variety of SC compounds and the unknown number of exposed individuals. Long-term consequences of SCs use are currently unknown.

Two experiments were conducted to determine the effect of administering PGF at the initiation of the 7-d CO-Synch+controlled internal drug release (CIDR) fixed-timed AI (TAI) protocol on pregnancy rates of suckled beef cows and replacement heifers. Within location, cows were stratified by days postpartum (DPP), BCS, and parity (Exp. 1; = 1,551) and heifers were stratified by BCS (Exp. 2; = 999) and randomly assigned to 1 of 2 treatments: 1) CO-Synch+CIDR (100-μg injection of GnRH at CIDR insertion [d -10] with a 25-mg injection of PGF at CIDR removal [d -3] followed by injection of GnRH and TAI on d 0) or 2) PG-CO-Synch+CIDR (a 25-mg injection of PGF on d -10 of the CO-Synch+CIDR protocol). Follicle diameter and corpus luteum (CL) development were assessed on d -10 and -3, and pregnancy status was determined on d 30 to 35. Blood was collected on d -20, -10, -3, and 0 relative to TAI to determine concentrations of progesterone (P4). In Exp. 1, TAI pregnancy rates did not differ ( = 0.667) between treatments and were affected by BCS ( = 0.003) and DPP ( = 0.006). Concentrations of P4 were greater ( < 0.0001) on d -3 for CO-Synch+CIDR than for PG-CO-Synch+CIDR (4.1 ± 0.2 and 3.4 ± 0.2 ng/mL, respectively). Follicle diameter on d -3 differed ( = 0.05) between PG-CO-Synch+CIDR (13.4 ± 0.3 mm) and CO-Synch+CIDR (12.5 ± 0.3 mm) treatments. Cows with P4 > 2.5 ng/mL on d -10 had greater ( = 0.024) pregnancy rate to TAI (56.5%) compared with cows with 2.5 ng/mL < P4 > 1 (43.0%), whereas cows with P4 < 1 ng/mL were intermediate (51.6%). Cows with a CL on d -10 had greater ( = 0.012) pregnancy rates to TAI than cows without a CL (66.3 vs. 39.4%, respectively). In Exp. 2, TAI pregnancy rates did not differ ( = 0.316) between treatments. Concentrations of P4 differed ( < 0.0001) on d -3 with greater concentrations of P4 for CO-Synch+CIDR than for PG-CO-Synch+CIDR (3.75 ± 0.20 ng/mL and 3.60 ± 0.21 ng/mL, respectively). Follicle diameter was similar ( = 0.749) between treatments on d -10 and -3. Regardless of treatment, cyclic status tended ( = 0.062) to improve pregnancy rates to TAI (55 vs. 45%, for cycling and noncycling heifers, respectively). We concluded that addition of PGF to the 7-d CO-Synch+CIDR protocol decreased concentrations of P4 in cows and heifers and increased follicle diameter at CIDR removal in cows but failed to increase TAI pregnancy rates.

Caffeine is the most widely used neurostimulant in the world. There is considerable debate on its effect on immune cells as it has been shown to antagonize adenosine receptors (ARs), which mediate an anti-inflammatory switch in activated immune cells. A second target is phosphodiesterase, where it acts as an inhibitor. If the primary effect of caffeine on mononuclear phagocytes were to antagonize ARs we would expect cells exposed to caffeine to have a prolonged proinflammatory response. The aim of this study was to investigate the effects and mechanism of action of caffeine in mononuclear phagocytes. Human mononuclear phagocytes were separated from whole blood and pretreated with protein kinase A inhibitor (PKA) and then exposed to micromolar physiological concentrations of caffeine. Phagocytosis and phagocytosis exhaustion were quantified using flow cytometry. Treatments were analyzed and compared to controls, using a beta regression controlling for factors of age, gender, caffeine intake, and exercise. We found that caffeine suppresses phagocytosis at micromolar physiological concentrations. This suppression was prevented when mononuclear phagocytes were pretreated with PKA inhibitor, suggesting that caffeine's phagocytic suppression may be due to its function as a phosphodiesterase inhibitor, pushing cells towards an anti-inflammatory response. Additionally, these effects are altered by regular caffeine intake and fitness level, emphasizing that tolerance and immune robustness are important factors in mononuclear phagocyte activation. These results demonstrate that caffeine may be acting as a phosphodiesterase inhibitor and suppressing phagocytosis in mononuclear phagocytes by promoting an anti-inflammatory response.

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies., Paperclip: VIDEO ABSTRACT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Rapid and effective administration of antidotes by emergency medical responders is needed to improve the survival of patients severely poisoned after deliberate release of chemical weapons, but intravenous access is difficult to obtain while wearing personal protective equipment and in casualties with circulatory collapse. To test the hypothesis that rapid and substantial bioavailability of the antidotes HI-6 oxime and dicobalt edetate can be achieved via the intraosseous (IO) route, plasma concentration-time profiles of these antidotes were compared after administration by the intravenous and IO routes in a minipig animal model., Methods: 12 male Göttingen minipigs were randomly allocated to receive 7.14 mg/kg of HI-6 (by rapid bolus) then 4.28 mg/kg of dicobalt edetate (over 1 min) via the intravenous or IO route. Plasma concentrations of each antidote were measured over 360 min following administration and plasma concentration-time profiles plotted for each drug by each route., Results: Peak HI-6 and cobalt concentrations occurred within 2 min of administration by both the intravenous and IO routes. Mean areas under the concentration-time curves (SD) to the end of the experiment (area under the concentration-time curve, AUC (0-t)) for cobalt were 430 (47, intravenous) and 445 (40, IO) μg-min/mL (mean difference 15, 95% CI -41 to 70, p=0.568) and for HI-6 were 2739 (1038, intravenous) and 2772 (1629, IO) μg-min/mL (mean difference 0.33, 95% CI -1724 to 1790, p=0.97). Increases in heart rate (by 50 beats/min intravenous and 27 beats/min IO) and BP, (by 67/58 mm Hg intravenous and 78/59 mm Hg IO), were observed after dicobalt edetate, consistent with the known adverse effects of this antidote., Discussion: This study demonstrates rapid and similar systemic bioavailability of HI-6 and dicobalt edetate when given by the IO and intravenous routes. IO delivery of these antidotes is appropriate in the acute management of patients with organophosphate and cyanide intoxication when the intravenous route is impractical., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Target identification for tractography studies requires solid anatomical knowledge validated by an extensive literature review across species for each seed structure to be studied. Manual literature review to identify targets for a given seed region is tedious and potentially subjective. Therefore, complementary approaches would be useful. We propose to use text-mining models to automatically suggest potential targets from the neuroscientific literature, full-text articles and abstracts, so that they can be used for anatomical connection studies and more specifically for tractography. We applied text-mining models to three structures: two well-studied structures, since validated deep brain stimulation targets, the internal globus pallidus and the subthalamic nucleus and, the nucleus accumbens, an exploratory target for treating psychiatric disorders. We performed a systematic review of the literature to document the projections of the three selected structures and compared it with the targets proposed by text-mining models, both in rat and primate (including human). We ran probabilistic tractography on the nucleus accumbens and compared the output with the results of the text-mining models and literature review. Overall, text-mining the literature could find three times as many targets as two man-weeks of curation could. The overall efficiency of the text-mining against literature review in our study was 98% recall (at 36% precision), meaning that over all the targets for the three selected seeds, only one target has been missed by text-mining. We demonstrate that connectivity for a structure of interest can be extracted from a very large amount of publications and abstracts. We believe this tool will be useful in helping the neuroscience community to facilitate connectivity studies of particular brain regions. The text mining tools used for the study are part of the HBP Neuroinformatics Platform, publicly available at http://connectivity-brainer.rhcloud.com/.

Our objective was to assess the effects of progesterone before initiating an estrus- or ovulation-synchronization program in addition to the influence of parity, BCS, and days postpartum on resulting pregnancy rates per AI. Experimental data were combined from 73 herd-year studies consisting of more than 8,500 suckled beef cows exposed to variants of the CO-Synch program. Blood was harvested from samples collected at 10 and 0 d before the onset of CO-Synch, and progesterone concentrations of the samples were determined. The progesterone environment preceding synchronization was assessed in 3 ways on the basis of progesterone concentrations measured in the 2 defined blood samples. All binomial logistic regression models used procedure GLIMMIX in SAS and included the fixed effects of program duration, inclusion of progesterone via an intravaginal insert, parity, days postpartum at AI, BCS, and appropriate interactions. In addition, model 1 included 3 categories of progesterone concentrations (low [<1 ng/mL], medium [1.00 to 3.99 ng/mL], and high [≥4.00 ng/mL] concentrations) at 10 and 0 d before synchronization and their interaction. Model 2 included 4 categories defining the stage of the estrous cycle (late diestrus, early diestrus, and proestrus-estrus-metestrus) or anestrus, at which cows started the synchronization program. Model 3 defined cows as cycling or noncycling at the onset of the program. Significant effects of progesterone supplementation, which hormone was used to initiate the timed AI program, parity, BCS, days postpartum, and progesterone status assessed in 3 ways were consistent in nearly all models. Progesterone status at the onset of synchronization was not important to pregnancy outcomes in multiparous cows, whereas pregnancy rate per AI was suppressed in primiparous cows that began in a low-progesterone environment (proestrus, estrus, metestrus, or anestrus). A significant 3-way interaction of parity, BCS, and days postpartum in 2 models reinforced the importance of these factors to AI pregnancy outcomes. Ancillary analyses identified the significant effects of cycling status and BCS as well as days postpartum on luteolytic response to PGF(2α). Pregnancy loss of 2.7% to 4.2% was detected to occur between a positive pregnancy diagnosis at 35 d post-AI and later stages of pregnancy. We concluded that progesterone status at the onset of the synchronization program is critical to pregnancy outcomes in primiparous but not multiparous cows.

Human activities, especially conversion and degradation of habitats, are causing global biodiversity declines. How local ecological assemblages are responding is less clear--a concern given their importance for many ecosystem functions and services. We analysed a terrestrial assemblage database of unprecedented geographic and taxonomic coverage to quantify local biodiversity responses to land use and related changes. Here we show that in the worst-affected habitats, these pressures reduce within-sample species richness by an average of 76.5%, total abundance by 39.5% and rarefaction-based richness by 40.3%. We estimate that, globally, these pressures have already slightly reduced average within-sample richness (by 13.6%), total abundance (10.7%) and rarefaction-based richness (8.1%), with changes showing marked spatial variation. Rapid further losses are predicted under a business-as-usual land-use scenario; within-sample richness is projected to fall by a further 3.4% globally by 2100, with losses concentrated in biodiverse but economically poor countries. Strong mitigation can deliver much more positive biodiversity changes (up to a 1.9% average increase) that are less strongly related to countries' socioeconomic status.

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - http://www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.

Objective: To characterise the patterns of presentation and clinical features of toxicity following reported recreational use of benzofuran compounds ((2-aminopropyl)-2,3-dihydrobenzofurans) in the UK, as reported to the National Poisons Information Service (NPIS), and to compare clinical features of toxicity with those after reported mephedrone use., Methods: NPIS patient-specific telephone enquiries and user sessions for TOXBASE(®), the NPIS online information database, related to (2-aminopropyl)-2,3-dihydrobenzofurans and associated synonyms were reviewed from March 2009 to August 2013. These data were compared with those of mephedrone, the recreational substance most frequently reported to NPIS, collected over the same period., Results: There were 63 telephone enquiries concerning 66 patients and 806 TOXBASE(®) user sessions regarding benzofuran compounds during the period of study. The first telephone enquiry was made in July 2010 and the highest numbers of enquiries were received in August 2010 (33 calls, 112 TOXBASE(®) sessions). Patients were predominantly male (82%) with a median age of 29 years; 9 reported co-ingestion of other substances. Comparing the 57 patients who reported ingesting benzofuran compounds alone with 315 patients ingesting mephedrone alone, benzofurans were more often associated with stimulant features, including tachycardia, hypertension, mydriasis, palpitation, fever, increased sweating, and tremor, (72% vs. 38%, odds ratio [OR] 4.2, 95% confidence interval [CI] 2.27-7.85, P < 0.0001) and mental health disturbances (58% vs. 38%, OR 2.3, 95% CI 1.29-4.07, P = 0.006). Other features reported after benzofuran compound ingestion included gastrointestinal symptoms (16%), reduced level of consciousness (9%), chest pain (7%), and creatinine kinase elevation (5%)., Conclusions: Reported ingestion of benzofuran compounds is associated with similar toxic effects to those of amphetamines and cathinones. Mental health disturbances and stimulant features were reported more frequently following reported ingestion of benzofuran compounds than after ingestion of mephedrone.

We demonstrated that 50mg of PGF₂α on d 6 successfully induced luteolysis in lactating dairy cows enrolled in a traditional 5-d Ovsynch-72 program [GnRH injection 5 d before (d 0; GnRH-1) and 56 (p.m. on d 7; GnRH-2) or 72 h (d 8; GnRH-2) after a 25-mg injection of PGF₂α (d 5 and 6 after GnRH injection); timed artificial insemination (AI) on d 8]. Our current objective was to determine pregnancy outcomes in lactating dairy cows after a 50-mg injection of PGF₂α on d 6 or a 25-mg injection of PGF₂α on d 5 and 6 in a 5-d Ovsynch program. Cows in herd 1 diagnosed not pregnant between 30 and 36 d since last AI were enrolled to receive either a 50-mg injection of PGF₂α on d 6 (1 × 50; n=134) or a 25-mg injection of PGF₂α on d 5 and 6 (2 × 25; n=139) after GnRH-1 (d 0), with GnRH-2 at 72 h after PGF₂α injection (d 5), concurrent with timed AI (d 8). Cows in herd 2 diagnosed not pregnant between 34 and 40 d were treated similarly: even-tagged cows received the 2 × 25 (n=422) treatment, and odd-tagged cows received the 1 × 50 (n=450) treatment, except that GnRH-2 was administered at 56 h. Blood collected from cows in herd 1 at d 0, 5, 6, and 8 was assayed for progesterone. Luteolysis was defined to occur when progesterone concentration was ≥1 ng/mL on d 5, and 72 h later (d 8) was either <0.5 ng/mL or <1 ng/mL. Progesterone concentrations did not differ between treatments on pretreatment d 0 and 5, but were greater in 1 × 50 than 2 × 25 cows on d 6 (4.7 ± 0.2 vs. 1.1 ± 0.2 ng/mL) and d 8 (0.43 ± 0.04 vs. 0.19 ± 0.04 ng/mL), respectively. Luteolysis was greater in the 2 × 25 versus 1 × 50 treatment when the cut point was 0.5 ng/mL, whereas no difference was detected when the cut point was <1 ng/mL on d 8. Lack of complete luteolysis was greater in cows classified as early cycle on d 0 or having a new corpus luteum after d 0 because progesterone concentration was greater on d 5 and 6 than for cows classified as late cycle on d 0 or cows having low progesterone on d 0 and 5. Pregnancy per AI at 30 to 40 d did not differ between 2 × 25 and 1 × 50 cows having luteolysis by d 8 or in all cows (37.2 vs. 33.3%) in herd 1, respectively, but differed in herd 2 (24.7 vs. 19.5%; no treatment by herd interaction). We conclude that incomplete luteolysis by d 8 was greater in 1 × 50 cows using a cut point of <0.5 ng/mL at AI. The difference in pregnancy outcome in herd 2 may have resulted from insufficient time for complete luteolysis before GnRH-2 at 56 h compared with GnRH-2 at 72 h (at AI) in herd 1., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Photodynamic therapy (PDT) is a binary therapy using a drug and high-energy light source. PDT is approved for several premalignant and malignant conditions. Recent in-vitro and animal data suggest that enhanced tumor-specific cytotoxicity can be achieved with far less collateral damage to normal surrounding tissues if PDT is administered continuously at a lower dose rate for extended periods of time. Based on these promising preclinical data, we conducted a Phase I clinical trial of continuous low-irradiance photodynamic therapy (CLIPT) using 630 nm laser energy and intravenously administered porforin sodium as the photosensitizer. We determined the maximum tolerated dose (MTD) of CLIPT on skin and tumor response in subjects with cutaneous and subcutaneous metastatic nodules who had failed radiation and surgery., Methods: Patients with cutaneous and/or subcutaneous metastatic nodules that had failed radiation and surgery were offered enrollment into the trial. The initial study design planned for sequential cohorts of six subjects to be treated at increasing laser intensity, starting at 100 J/cm(2) administered continuously over 24 h (10(-2) dose rate compared with standard PDT). Dose-limiting toxicity was defined as partial or full-thickness necrosis of the surrounding tumor-free, previously irradiated skin. The MTD was defined as the highest laser energy at which ≤33% of subjects experienced the dose-limiting toxicity. Subjects received intravenous porfirmer sodium 0.8 mg/kg 48 h before commencing CLIPT. Response rates and quality of life measures were assessed., Results: Nine subjects were enrolled with chest wall progression of breast cancer following mastectomy. All had failed prior surgery and electron-beam radiation therapy. The initial two subjects were treated at 100 J/cm(2) and developed partial thickness skin necrosis. Dose reduction was therefore instituted, and the next cohort was treated at 50 J/cm(2). None of the subsequent seven subjects suffered partial or full thickness necrosis, thus establishing the MTD at 50 J/cm(2) over 24 h (0.5 mW irradiance). Six of the nine subjects (67%) had either a complete or partial clinical response. Of note, two subjects had significant regression of tumor nodules distant from the treatment field. Of the eight subjects whose terminal deoxynucleotidyl transferase dUTP nick end labeling assay results were available, 8 (100%) demonstrated histologic response to treatment as evidenced by either tumor apoptosis or regression. Quality of life measures were improved following treatment-particularly bleeding and pain from the tumor nodules., Conclusions: The MTD of CLIPT was established at 50 J/cm(2) administered continuously over 24 h. These preliminary data suggest CLIPT may be an effective, low-morbidity therapeutic modality in the treatment of cutaneous and subcutaneous metastases of breast cancer following mastectomy. Further evaluation in a larger cohort is warranted to better assess efficacy and optimize the intervention., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In 2010, the international community, under the auspices of the Convention on Biological Diversity, agreed on 20 biodiversity-related "Aichi Targets" to be achieved within a decade. We provide a comprehensive mid-term assessment of progress toward these global targets using 55 indicator data sets. We projected indicator trends to 2020 using an adaptive statistical framework that incorporated the specific properties of individual time series. On current trajectories, results suggest that despite accelerating policy and management responses to the biodiversity crisis, the impacts of these efforts are unlikely to be reflected in improved trends in the state of biodiversity by 2020. We highlight areas of societal endeavor requiring additional efforts to achieve the Aichi Targets, and provide a baseline against which to assess future progress., (Copyright © 2014, American Association for the Advancement of Science.)

Habitat loss and degradation, driven largely by agricultural expansion and intensification, present the greatest immediate threat to biodiversity. Tropical forests harbour among the highest levels of terrestrial species diversity and are likely to experience rapid land-use change in the coming decades. Synthetic analyses of observed responses of species are useful for quantifying how land use affects biodiversity and for predicting outcomes under land-use scenarios. Previous applications of this approach have typically focused on individual taxonomic groups, analysing the average response of the whole community to changes in land use. Here, we incorporate quantitative remotely sensed data about habitats in, to our knowledge, the first worldwide synthetic analysis of how individual species in four major taxonomic groups--invertebrates, 'herptiles' (reptiles and amphibians), mammals and birds--respond to multiple human pressures in tropical and sub-tropical forests. We show significant independent impacts of land use, human vegetation offtake, forest cover and human population density on both occurrence and abundance of species, highlighting the value of analysing multiple explanatory variables simultaneously. Responses differ among the four groups considered, and--within birds and mammals--between habitat specialists and habitat generalists and between narrow-ranged and wide-ranged species.

The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Diagnosing acute pancreatitis in the dog can be challenging. The aim of this study was to determine the concentrations of pancreas-specific lipase immunoreactivity (cPLI), and the activities of amylase and lipase, in the peritoneal fluid from a population of dogs diagnosed with acute pancreatitis based on clinical signs, ultrasonographic findings and serum cPLI concentrations. In a prospective study, cPLI concentrations, and amylase and lipase activities, were measured in the peritoneal fluid of 14 dogs with pancreatitis and 19 dogs with non-pancreatic disease. The sensitivity and specificity of peritoneal fluid cPLI concentration (cut-off value 500 µg/L) were 100.0% (95% confidence interval, CI, 80.7-100.0%) and 94.7% (95% CI 76.7-99.7%), respectively. The sensitivity and specificity of peritoneal fluid amylase (cut-off value 1050 U/L) and lipase activities (cut-off value 500 U/L) were 71.4% (95% CI 44.5-90.2%) and 84.2% (95% CI 62.8-95.8%) for amylase activity, and 92.9% (95% CI 69.5-99.6%) and 94.7% (95% CI 76.7-99.7%) for lipase activity, respectively. In conclusion, peritoneal fluid cPLI concentration was highly sensitive as a complementary diagnostic tool in a group of dogs with suspected acute pancreatitis. Peritoneal fluid lipase activity was not as sensitive as cPLI concentration, but may also support a diagnosis of acute pancreatitis in dogs., (Published by Elsevier Ltd.)

Novel psychoactive substances (NPS) can cause significant acute toxicity but usually little is known about their toxicity when they enter the recreational drug scene. Current data sources include online user forums, user questionnaires, case reports/series, and deaths; however, these are limited by their focus on sub-populations and generally include severe cases and specific geographical areas. Approximately 54% of countries have at least one poisons information service (in 2012 there were 274 worldwide) providing advice to healthcare professionals and/or the public on poisoning. They provide advice on recreational drug and NPS toxicity. In 2012, 2.5% of telephone enquiries to the UK National Poisons Information Service and 2.4% of enquiries to US poisons centres related to recreational drugs. Data are collected at population level and can be used to complement other data sources with clinical details on acute NPS toxicity and geographical/time patterns of toxicity. Like other acute NPS toxicity data, poisons centre data should be interpreted within their limitations, notably the absence of analytical confirmation and reliance on secondary reporting of clinical features. This manuscript demonstrates the breadth and depth of poisons information service data in the literature with a focus on mephedrone and synthetic cannabinoid-receptor agonists. In our opinion it would be possible to develop a more robust and systematic reporting system using a network of poisons information services both within and across countries that would be complimentary to other datasets on acute NPS toxicity and allow more accurate data triangulation., (Copyright © 2014 John Wiley & Sons, Ltd.)

Using 1 market-available activity monitor, 3 experiments were conducted in dairy cows to determine timing of ovulation, compare within-herd conception risk of cows inseminated based on activity monitors versus timed artificial insemination (AI), and determine conception risk of cows inseminated at various intervals after achieving an activity threshold. In experiment 1, ovaries were scanned every 3h by transrectal ultrasonography to determine the time of ovulation beginning 14 ± 0.5 h after the achieved activity threshold (n=132) or first standing event (n=59), or both (n=59). Progesterone at the first ovarian scan (0.1 ± 0.01 ng/mL) and ovarian structures [1 or 2 preovulatory-sized follicles (16.5 ± 0.2 mm)] confirmed that 88.6% of cows identified by activity were in estrus. The remaining 15 cows (11.4%) with a corpus luteum and elevated progesterone concentration (5.3 ± 0.5 ng/mL) were classified as false positives. The average interval from first standing event to ovulation (n=59) differed slightly from the interval after the achieved threshold (26.4 ± 0.7 vs. 24.6 ± 0.7 h, respectively). In 97 cows fitted with activity monitors, that interval was 25.7 ± 0.4 h. In experiment 2, the conception risk in 394 cows in 1 herd fitted with activity monitors was compared with that of 413 cows submitted to a timed AI program through 3 AI services. Days to first AI were reduced in cows fitted with activity monitors, and conception risk after activity threshold was less than that for timed AI at first service because of differing days in milk at first AI. Both median and mean days to pregnancy, however, were reduced in activity-group cows by 10 and 24 d, respectively, compared with timed AI cows. In experiment 3, 4,019 cows in 19 herds were inseminated after achieving the activity threshold. Conception risk was determined for cows inseminated at various intervals after the achieved activity threshold. A curvilinear conception risk curve peaked at 47.9% for primiparous cows inseminated between 13 and 16 h, whereas conception risk in multiparous cows was steady at 34% through 12 h and decreased thereafter. These experiments demonstrate that time of ovulation after activity threshold closely resembles the time of ovulation after first standing estrus. Time of insemination up to 12h after the activity threshold produced similar conception risks for multiparous cows, whereas intervals shorter than 13 and greater than 16 h in primiparous cows seemed to compromise their conception risk. Although conception risk may not be improved at individual inseminations after achieving an activity threshold, the rate of achieving pregnancy is hastened. Activity monitors can accurately predict ovulation and time of AI., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

We hypothesized that pregnancy outcomes may be improved by inducing luteal regression, ovulation, or both (i.e., altering progesterone status) before initiating a timed-artificial insemination (TAI) program in suckled beef cows. This hypothesis was tested in two experiments in which cows were treated with either PGF2α (PG) or PG + GnRH before initiating a TAI program to increase the proportion of cows starting the program in a theoretical marginal (<1 ng/mL; experiment 1) or elevated (≥1 ng/mL; experiment 2) progesterone environment, respectively. The control was a standard CO-Synch + controlled internal drug release (CIDR) program employed in suckled beef cows (100 μg GnRH intramuscularly [IM] [GnRH-1] and insertion of a progesterone-impregnated intravaginal CIDR insert on study Day -10, 25 mg PG and CIDR insert removal on study Day -3, and 100 μg GnRH IM [GnRH-2] and TAI on study Day 0). In both experiments, blood was collected before each injection for later progesterone analyses. In experiment 1, cows at nine locations (n = 1537) were assigned to either: (1) control or (2) PrePG (same as control with a PG injection on study Day -13). The PrePG cows had larger (P < 0.05) follicles on study Day -10 and more (P < 0.05) ovulated after GnRH-1 compared with control cows (60.6% vs. 36.5%), but pregnancy per TAI was not altered (55.5% vs. 52.2%, respectively). In experiment 2, cows (n = 803) at four locations were assigned to: (1) control or (2) PrePGG (same as control with PG injection on study Day -20 and GnRH injection on study Day -17). Although pregnancy per TAI did not differ between control and PrePGG cows (44.0% vs. 44.4%, respectively), cows with body condition score greater than 5.0 or 77 or more days postpartum at TAI were more (P < 0.05) likely to become pregnant than thinner cows or those with fewer days postpartum. Presynchronized cows in both experiments were more (P < 0.05) likely than controls to have luteolysis after initial PG injections and reduced (P < 0.05) serum progesterone; moreover, treatments altered the proportion of cows and pregnancy per TAI of cows in various progesterone categories before the onset of the TAI protocol. In combined data from both experiments, cows classified as anestrous before the study but with elevated progesterone on Day -10 had increased (P < 0.05) pregnancy outcomes compared with anestrous cows with low progesterone concentrations. Progesterone concentration had no effect on pregnancy outcome of cycling cows. In summary, luteal regression and ovulation were enhanced and progesterone concentrations were altered by presynchronization treatments before the 7-day CO-Synch + CIDR program, but pregnancy per TAI was not improved., (Copyright © 2014 Elsevier Inc. All rights reserved.)

'Wasp-waist' systems are dominated by a mid trophic-level species that is thought to exert top-down control on its food and bottom-up control on its predators. Sardines, anchovy, and Antarctic krill are suggested examples, and here we use locusts to explore whether the wasp-waist concept also applies on land. These examples also display the traits of mobile aggregations and dietary diversity, which help to reduce the foraging footprint from their large, localised biomasses. This suggests that top-down control on their food operates at local aggregation scales and not at wider scales suggested by the original definition of wasp-waist. With this modification, the wasp-waist framework can cross-fertilise marine and terrestrial approaches, revealing how seemingly disparate but economically important systems operate., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To characterise the patterns of presentation, clinical effects and possible harms of acute toxicity following recreational use of alpha methyltryptamine (AMT) in the United Kingdom, as reported by health professionals to the National Poisons Information Service (NPIS) and to compare clinical effects with those reported after mephedrone use., Methods: NPIS telephone enquiries and TOXBASE user sessions, the NPIS online information database, related to AMT were reviewed from March 2009 to September 2013. Telephone enquiry data were compared with those for mephedrone, the recreational substance most frequently reported to the NPIS, collected over the same period., Results: There were 63 telephone enquiries regarding AMT during the period of study, with no telephone enquiries in 2009 or 2010, 19 in 2011, 35 in 2012 and 9 in 2013 (up to September). Most patients were male (68%) with a median age of 20 years. The route of exposure was ingestion in 55, insufflation in 4 and unknown in 4 cases. Excluding those reporting co-exposures, clinical effects recorded more frequently in AMT (n = 55) compared with those of mephedrone (n = 488) users including acute mental health disturbances (66% vs. 32%; Odds Ratio [OR], 4.00; 95% Confidence Intervals [CI], 2.22-7.19), stimulant effects (66% vs. 40%; OR, 2.82; 95% CI 1.57-5.06) and seizures (14% vs. 2%; OR, 9.35; 95% CI 3.26-24.18)., Conclusions: Although still infrequent, toxicity following reported exposure to AMT has been encountered in the United Kingdom since January 2011. Stimulant features, acute mental health disturbances and seizures are more frequently reported than in those presenting following reported use of mephedrone.

Objective: To report the demographic and clinical characteristics of cases of methoxetamine toxicity reported to The National Poisons Information Service (NPIS) by healthcare professionals. To assess the pattern of enquiries from health professionals to the UK NPIS related to methoxetamine, including the period of the making of the UK first Temporary Class Drug Order (TCDO)., Methods: All telephone enquiries to and user sessions for TOXBASE, the NPIS on-line information resource, related to methoxetamine (and synonyms 'MXE', 'mket' and '2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone') were reviewed from 1 April 2010 to 1 August 2012. Data were compared for the 3 months before and after the TCDO., Results: There were 47 telephone enquiries and 298 TOXBASE sessions regarding methoxetamine during the period of study. Comparing the 3 months before and after the TCDO, TOXBASE sessions for methoxetamine fell by 79% (from 151 to 32) and telephone enquiries by 80% (from 15 to 3). Clinical features reported by enquirers were consistent with case reports of analytically confirmed methoxetamine toxicity and typical toxidromes were of stimulant (36%), reduced consciousness (17%), dissociative (11%) and cerebellar (6.4%) types, but also particularly featured acute disturbances in mental heath (43%)., Conclusions: Structured NPIS data may reveal trends in drugs of abuse use and toxicity when interpreted within their limitations. Since April 2012, there have been fewer enquiries to NPIS from clinicians, indicating reduced presentations with suspected methoxetamine toxicity to healthcare services. It is unclear if this is related to the TCDO made on 5 April 2012.

Mortality rate has been proposed as a metric of hospital chronic obstructive pulmonary disease (COPD) care in light of variation seen in national COPD audits. Using Hospital Episode Statistics (hospital 'coding') we examined 30-day mortality after COPD hospitalisation in 150 UK hospitals during 2006-2007 and 2007-2008. Mean and median 30-day mortalities were similar each year but the coefficient of variation was >20% and hospitals could change from a low or high quartile to the median by chance. We could not detect any reasons for hospitals being at the extremes. 30-day mortality after COPD hospitalisation is a complex variable and unlikely to be useful as a primary annual COPD metric.

We hypothesized that 50mg of prostaglandin F2α (PG) on d 6 would induce luteolysis in a traditional 5-d Ovsynch-72 program [GnRH 5 d before (d 0) and 72 h after (d 8) 25-mg PG doses (d 5 and 6 after GnRH); timed artificial insemination (AI) on d 8]. Experiment 1 monitored luteal regression of original and GnRH-induced luteal tissue (corpus luteum, CL) by transrectal ultrasonography and blood serum concentrations of progesterone after both 25-mg doses of PG (d 5 and 6; control; n=31) or a single 50-mg dose of PG on d 6 (n=30). Estrous cycles were presynchronized (GnRH 7d before 25 mg of PG); 11 d later, cows were enrolled in a 5-d Ovsynch-72 program (62 to 71 d in milk) and treatments were administered. Blood was sampled for progesterone analysis and luteal structures were measured on d 0 (original CL) and d 5 through 9 to monitor original and new GnRH-induced CL. Control PG reduced luteal tissue area of original CL on d 6 and 7 compared with PG administered only on d 6, but no difference between treatments was detected by d 9. In contrast, no differences were detected in luteal tissue area of the induced CL on d 5 through 9. Serum progesterone on d 5 through 9 differed only on d 6 for control and the 50-mg dose. Luteolysis occurred in all 31 controls, but luteolytic failure occurred in 2 of 30 cows receiving 50mg, in which no CL were present on d 0 but 1 or 3 new CL were present on d 5 in these 2 cows. Pregnancy outcome 32 d after AI was 14 of 30 (40%) compared with 15 of 30 (50%) for control versus 50-mg dose, respectively. Experiment 2 monitored luteolysis in nonpregnant repeat-service cows subsequently treated with the same 2 treatments as in experiment 1. Serum progesterone in 63 cows (serum progesterone ≥1 ng/mL on d 5) on d 5, 6, and 8 differed only on d 6 for control and the 50-mg dose. Luteolysis occurred in 32 of 34 controls and in 29 of 29 cows treated with 50mg. Pregnancy outcome 32 d after AI was 17 of 33 (52%) compared with 13 of 29 (45%) for control versus 50-mg dose, respectively. We concluded that the single 50-mg dose was equivalent to the control based on actual luteal tissue regression and decreased progesterone., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Antarctic krill is a cold water species, an increasingly important fishery resource and a major prey item for many fish, birds and mammals in the Southern Ocean. The fishery and the summer foraging sites of many of these predators are concentrated between 0° and 90°W. Parts of this quadrant have experienced recent localised sea surface warming of up to 0.2°C per decade, and projections suggest that further widespread warming of 0.27° to 1.08°C will occur by the late 21(st) century. We assessed the potential influence of this projected warming on Antarctic krill habitat with a statistical model that links growth to temperature and chlorophyll concentration. The results divide the quadrant into two zones: a band around the Antarctic Circumpolar Current in which habitat quality is particularly vulnerable to warming, and a southern area which is relatively insensitive. Our analysis suggests that the direct effects of warming could reduce the area of growth habitat by up to 20%. The reduction in growth habitat within the range of predators, such as Antarctic fur seals, that forage from breeding sites on South Georgia could be up to 55%, and the habitat's ability to support Antarctic krill biomass production within this range could be reduced by up to 68%. Sensitivity analysis suggests that the effects of a 50% change in summer chlorophyll concentration could be more significant than the direct effects of warming. A reduction in primary production could lead to further habitat degradation but, even if chlorophyll increased by 50%, projected warming would still cause some degradation of the habitat accessible to predators. While there is considerable uncertainty in these projections, they suggest that future climate change could have a significant negative effect on Antarctic krill growth habitat and, consequently, on Southern Ocean biodiversity and ecosystem services.

Brain activity generates extracellular voltage fluctuations recorded as local field potentials (LFPs). It is known that the relevant microvariables, the ionic currents across membranes, jointly generate the macrovariables, the extracellular voltage, but neither the detailed biophysical knowledge nor the required computational power have been available to model these processes. We simulated the LFP in a model of the rodent neocortical column composed of >12,000 reconstructed, multicompartmental, and spiking cortical layer 4 and 5 pyramidal neurons and basket cells, including five million dendritic and somatic compartments with voltage- and ion-dependent currents, realistic connectivity, and probabilistic AMPA, NMDA, and GABA synapses. We found that, depending on a number of factors, the LFP reflects local and cross-layer processing. Active currents dominate the generation of LFPs, not synaptic ones. Spike-related currents impact the LFP not only at higher frequencies but below 50 Hz. This work calls for re-evaluating the genesis of LFPs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Context: 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a N-methoxybenzyl-substituted phenethylamine with potent serotoninergic effects. We describe seven cases of analytically confirmed toxicity due to the recreational use of 25I-NBOMe in the United Kingdom., Case Series: Seven patients, all young adult males, presented to hospitals in the northeast of England with clinical toxicity after recreational drug use in January 2013. Clinical features included tachycardia (n = 7), hypertension (4), agitation (6), aggression, visual and auditory hallucinations (6), seizures (3), hyperpyrexia (3), clonus (2), elevated white cell count (2), elevated creatine kinase (7), metabolic acidosis (3), and acute kidney injury (1). LC-MS/MS analysis identified 25I-NBOMe as the main active substance in the plasma of all seven cases., Conclusions: Severe clinical toxicity may occur following recreational use of 25I-NBOMe, with stimulant and serotoninergic features predominating. Clinicians should be alert to this substance, in view of its emergence in Europe as well as in the United States.

Decision-makers charged with implementing ecosystem-based management (EBM) rely on scientists to predict the consequences of decisions relating to multiple, potentially conflicting, objectives. Such predictions are inherently uncertain, and this can be a barrier to decision-making. The Convention on the Conservation of Antarctic Marine Living Resources requires managers of Southern Ocean fisheries to sustain the productivity of target stocks, the health and resilience of the ecosystem, and the performance of the fisheries themselves. The managers of the Antarctic krill fishery in the Scotia Sea and southern Drake Passage have requested advice on candidate management measures consisting of a regional catch limit and options for subdividing this among smaller areas. We developed a spatially resolved model that simulates krill-predator-fishery interactions and reproduces a plausible representation of past dynamics. We worked with experts and stakeholders to identify (1) key uncertainties affecting our ability to predict ecosystem state; (2) illustrative reference points that represent the management objectives; and (3) a clear and simple way of conveying our results to decision-makers. We developed four scenarios that bracket the key uncertainties and evaluated candidate management measures in each of these scenarios using multiple stochastic simulations. The model emphasizes uncertainty and simulates multiple ecosystem components relating to diverse objectives. We summarize the potentially complex results as estimates of the risk that each illustrative objective will not be achieved (i.e., of the state being outside the range specified by the reference point). This approach allows direct comparisons between objectives. It also demonstrates that a candid appraisal of uncertainty, in the form of risk estimates, can be an aid, rather than a barrier, to understanding and using ecosystem model predictions. Management measures that reduce coastal fishing, relative to oceanic fishing, apparently reduce risks to both the fishery and the ecosystem. However, alternative reference points could alter the perceived risks, so further stakeholder involvement is needed to identify risk metrics that appropriately represent their objectives.

The hybrid approach to palliation of hypoplastic left heart syndrome using pulmonary artery bands, a patent ductus arteriosus (PDA) stent, and atrial septostomy has been well described. One potential complication of hybrid stage 1 palliation is the development of neointimal formation and in-stent stenosis (ISS). This study aimed to identify predictors of ISS development. Patients who underwent hybrid stage 1 palliation between 2002 and 2010 were included in the study. The clinical information included oxygen saturation, weight, vital signs, and medications. Echocardiographic data included ventricular function, degree of tricuspid regurgitation, and velocity through the PDA stent and pulmonary artery bands. Hemodynamic data from interstage catheterizations were similarly noted. Patients who developed clinically significant ISS requiring either transcatheter intervention or early stage 2 repair were compared with those who did not. Of the 66 patients included in the study, 40 were boys (61 %). The median age at hybrid palliation was 7 days (range, 1-93 days), and the median initial weight was 3.2 kg (range, 1.4-5 kg). In 13 patients (20 %), ISS developed. The mean initial weight was significantly greater in the ISS group (3.5 ± 0.5 vs. 3.0 ± 0.6 kg) (p = 0.03). The mean oxygen saturations did not differ significantly between the no-ISS group (82.2 % ± 5.7 %) and the ISS group (81.4 % ± 2.0 %) (p = 0.31). The mean PDA velocities were higher in the ISS group (2.7 ± 0.4 m/s) and increased at a faster rate than in the no-ISS group at (2.4 ± 0.4 m/s) (p = 0.01). The degree of tricuspid regurgitation, ventricular function, and pulmonary artery band gradients shown by echocardiography were similar in the two groups. The development of ISS after hybrid stage 1 palliation can lead to interstage interventions or earlier comprehensive stage 2 repair. Patients with greater initial weight and a lower stent-to-weight ratio are more likely to develop ISS. The cause of ISS is complex, and additional investigation of its etiology currently is ongoing.

Objective: To determine the prevalence of hypocobalaminemia or methylmalonic acidemia (or both) in dogs with chronic gastrointestinal disease., Sample: Serum samples from 56 dogs with chronic gastrointestinal disease and 43 control dogs., Procedures: Serum cobalamin and methylmalonic acid (MMA) concentrations were measured in all samples and compared between groups. A correlation between serum cobalamin and MMA concentrations and the canine chronic enteropathy clinical activity index was evaluated via the Spearman rank correlation., Results: 20 of 56 (36%) dogs with gastrointestinal disease had hypocobalaminemia. Serum cobalamin concentrations were significantly lower in dogs with gastrointestinal disease than in control dogs. Five of 56 (9%) dogs with chronic gastrointestinal disease and 5 of 20 (25%) hypocobalaminemic dogs had increased MMA concentrations. There was a significant negative correlation (Spearman r = -0.450) between serum cobalamin and MMA concentrations in dogs with gastrointestinal disease. No correlation was found between the canine chronic enteropathy clinical activity index and serum cobalamin or MMA concentrations., Conclusions and Clinical Relevance: These data indicated the prevalence of hypocobalaminemia in dogs with chronic gastrointestinal disease was 20 of 56 (36%). Five of 20 (25%) hypocobalaminemic dogs had increased serum MMA concentrations, which indicated that although hypocobalaminemia was common in these dogs, it did not always appear to be associated with a deficiency of cobalamin on a cellular level. Hypocobalaminemia is a risk factor for negative outcome in dogs with chronic gastrointestinal disease and should be considered in every patient with corresponding clinical signs.

Injecting drug users are the principal at risk group for blood borne viruses. The aim was to assess the feasibility of screening substance misusers for blood borne viruses, and to offer appropriate vaccinations/referral to hepatology services. This was a nurse led prospective 6-month study based at a large Substance Misuse Service in south east England. Of the 196 consecutive individuals assessed, 81 were eligible for HBV immunization of whom only 33.3% completed a vaccination course. Prevalence of positive serological markers were: anti-HBc 14.4%, HBsAg 1.5%, and HCV antibody 37.9%. Compared to men, women were more likely to accept blood borne virus testing (83.3% vs. 62.3%), have ever injected (89.6% vs. 76.3%), overdose (54.2% vs. 23.6%), be anti-HBc positive (27.5% vs. 8.8%), drink alcohol above national recommended guidelines (41.7% vs. 25.7%), and have a positive HCV serology (55% vs. 30.4%) (P ≤ 0.05 for all). Of the 73 individuals identified with a positive HBsAg and or HCV antibody, only 14 (19.1%) were known to hepatology services and 8 (20%) of those eligible subsequently accepted a specialist referral. In conclusion, serological markers for blood borne viruses remain high in substance misusers (anti-HBc 14.4%, HCV antibody 37.9%), with women more likely to be positive. Overall, only 33.3% and 20%, respectively, complete HBV vaccination and accept a hepatology referral. A multidisciplinary approach is paramount to address both the blood borne viruses and the substance misuse and realignment of hepatitis services to Substance Misuse Services may offer such a strategy., (Copyright © 2012 Wiley Periodicals, Inc.)

It is well-established that synapse formation involves highly selective chemospecific mechanisms, but how neuron arbors are positioned before synapse formation remains unclear. Using 3D reconstructions of 298 neocortical cells of different types (including nest basket, small basket, large basket, bitufted, pyramidal, and Martinotti cells), we constructed a structural model of a cortical microcircuit, in which cells of different types were independently and randomly placed. We compared the positions of physical appositions resulting from the incidental overlap of axonal and dendritic arbors in the model (statistical structural connectivity) with the positions of putative functional synapses (functional synaptic connectivity) in 90 synaptic connections reconstructed from cortical slice preparations. Overall, we found that statistical connectivity predicted an average of 74 ± 2.7% (mean ± SEM) synapse location distributions for nine types of cortical connections. This finding suggests that chemospecific attractive and repulsive mechanisms generally do not result in pairwise-specific connectivity. In some cases, however, the predicted distributions do not match precisely, indicating that chemospecific steering and aligning of the arbors may occur for some types of connections. This finding suggests that random alignment of axonal and dendritic arbors provides a sufficient foundation for specific functional connectivity to emerge in local neural microcircuits.

The morphology of neocortical pyramidal neurons is not only highly characteristic but also displays an intrinsic diversity that renders each neuron morphologically unique. We investigated the significance of this intrinsic morphological diversity in in silico networks composed of thick-tufted layer 5 (TTL5) pyramidal neurons, by comparing the in silico and in vitro properties of TTL5 synaptic connections. The synaptic locations of in silico connections were determined by placing 3D reconstructed TTL5 neurons randomly in a volume equivalent to that of layer 5 in the juvenile rat somatosensory cortex and using a 'collision-detection' algorithm to identify the incidental loci of axo-dendritic overlap. The activation time of the modelled synapses and their biophysical properties were characterized based on experimental measurements. We found that the anatomical loci of synapses and the physiological properties of the somatically recorded EPSPs closely matched those recorded experimentally without the need for any fine-tuning. Furthermore, perturbations to both the physiological or anatomical parameters of the model did not alter the average physiological properties of the population of modelled synaptic connections. This microcircuit-level robust behaviour was due to the intrinsic diversity of the morphology of pyramidal neurons in the microcircuit. We conclude that synaptic transmission in a network of TTL5 neurons is highly invariant across microcircuits suggesting that intrinsic diversity is a mechanism to ensure the same average synaptic properties in different animals of the same species. Finally, we show that the average physiological properties of the TTL5 microcircuit are surprisingly robust to anatomical and physiological perturbations also partly due to the intrinsic diversity of pyramidal neuron morphology.

The electrical diversity of neurons arises from the expression of different combinations of ion channels. The gene expression rules governing these combinations are not known. We examined the expression of twenty-six ion channel genes in a broad range of single neocortical neuron cell types. Using expression data from a subset of twenty-six ion channel genes in ten different neocortical neuronal types, classified according to their electrophysiological properties, morphologies and anatomical positions, we first developed an incremental Support Vector Machine (iSVM) model that prioritizes the predictive value of single and combinations of genes for the rest of the expression pattern. With this approach we could predict the expression patterns for the ten neuronal types with an average 10-fold cross validation accuracy of 87% and for a further fourteen neuronal types not used in building the model, with an average accuracy of 75%. The expression of the genes for HCN4, Kv2.2, Kv3.2 and Caβ3 were found to be particularly strong predictors of ion channel gene combinations, while expression of the Kv1.4 and Kv3.3 genes has no predictive value. Using a logic gate analysis, we then extracted a spectrum of observed combinatorial gene expression rules of twenty ion channels in different neocortical neurons. We also show that when applied to a completely random and independent data, the model could not extract any rules and that it is only possible to extract them if the data has consistent expression patterns. This novel strategy can be used for predictive reverse engineering combinatorial expression rules from single-cell data and could help identify candidate transcription regulatory processes.

Ion channels are membrane proteins that selectively conduct ions across the cell membrane. The flux of ions through ion channels drives electrical and biochemical processes in cells and plays a critical role in shaping the electrical properties of neurons. During the past three decades, extensive research has been carried out to characterize the molecular, structural, and biophysical properties of ion channels. This research has begun to elucidate the role of ion channels in neuronal function and has subsequently led to the development of computational models of ion channel function. Although there have been substantial efforts to consolidate these findings into easily accessible and coherent online resources, a single comprehensive resource is still lacking. The success of these initiatives has been hindered by the sheer diversity of approaches and the variety in data formats. Here, we present "Channelpedia" (http://channelpedia.net), which is designed to store information related to ion channels and models and is characterized by an efficient information management framework. Composed of a combination of a database and a wiki-like discussion platform Channelpedia allows researchers to collaborate and synthesize ion channel information from literature. Equipped to automatically update references, Channelpedia integrates and highlights recent publications with relevant information in the database. It is web based, freely accessible and currently contains 187 annotated ion channels with 45 Hodgkin-Huxley models.