Increasing estrus expression in the lactating dairy cow.

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 F2α 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 PGF2α. 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 PGF2α is administered to induce luteolysis.

Commissioning for COPD care: a new, recordable metric that supports the patient interest.

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.

Interoperable atlases of the human brain.

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.

Pregnancy outcomes after change in dose delivery of prostaglandin F2α and time of gonadotropin-releasing hormone injection in a 5-day timed artificial insemination program in lactating dairy cows.

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.

Ovulation timing and conception risk after automated activity monitoring in lactating dairy cows.

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.

Use of mortality within 30 days of a COPD hospitalisation as a measure of COPD care in UK hospitals.

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.

Decision-making for ecosystem-based management: evaluating options for a krill fishery with an ecosystem dynamics model.

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.

Short communication: Change in dose delivery of prostaglandin F2α in a 5-day timed artificial insemination program in lactating dairy cows.

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.

Clinical features associated with ADB-BUTINACA exposure in patients attending emergency departments in England.

OBJECTIVE: Synthetic cannabinoid receptor agonists (SCRA) are commonly encountered new psychoactive substances. Here we report the recent detection of ADB-BUTINACA in samples from patients attending United Kingdom emergency departments with toxicity after suspected drug misuse and describe the associated clinical features. METHODS: Consenting adults (≥16 y) presenting to participating hospitals with toxicity after suspected drug misuse have been included in the Identification Of Novel psychoActive substances (IONA) study since March 2015. Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. RESULTS: By December 2021, analytical data were available for 1279 IONA participants and ADB-BUTINACA was detected in at least one sample from 10 (9 males, age range 16-51 median 45 years), all presenting since February 2021. Smoking 'spice' was reported by four patients, two had ingested edible "cannabis" gums and four reported heroin use (2 intravenous, 1 smoked, 1 route not known). Co-use of pregabalin (oral) and crack cocaine (smoked) were also reported. In 3 cases ADB-BUTINACA was the only substance detected, while in seven other substances of misuse were also detected including other SCRA, opioids, benzodiazepines cocaine and pregabalin. Clinical features reported in these 2 groups respectively included reduced level of consciousness (3/3, 6/7), agitation (0/3, 4/7), tachycardia (0/3, 3/7), seizures (1/3, 1/7), hallucinations (1/3, 1/7), hypotension (1/3, 1/7). Metabolic acidosis (1/3, 0/7) and respiratory acidosis (1/3, 0/7), All 10 patients recovered with supportive care, including intubation and ventilation for one case. The median length of hospital stay was 19 h (range 2.6-131 h). CONCLUSIONS: ADB-BUTINACA has recently emerged as a drug of misuse in England. Clinical features of toxicity are consistent with those of other SCRA and include reduced level of consciousness, respiratory and/or metabolic acidosis, seizures, confusion and hallucinations.

Synthetic cannabinoid receptor agonists: classification and nomenclature.

Introduction: The emergence of novel psychoactive substances has changed the epidemiology of drugs used recreationally throughout Europe and have posed significant challenges for clinicians, researchers and regulators. Synthetic cannabinoid receptor agonists have made up a large proportion of these novel psychoactive substances. Developed for legitimate scientific research, synthetic cannabinoid receptor agonists are potent agonists at CB1 and CB2 receptors and there have been many case reports of severe or fatal toxicity following their recreational use. At least 180 analytically confirmed compounds belonging to this group of drugs have been reported in Europe as of January 2019. Synthetic cannabinoid receptor agonists have a complex molecular structure, consisting of four pharmacophore components termed the 'core', 'tail', 'linker' and 'linked' groups. This structural complexity offers multiple opportunities for chemical modification to evade drug control legislation based on chemical structure, and this explains the large numbers of individual products that have been detected.Objectives: To discuss the chemical structure of synthetic cannabinoid receptor agonists and to describe the different nomenclature used to identify individual compounds thereby increasing understanding of their chemical heterogenicity and the potential relevance of their molecular structure to the risk of toxicity.Methods: The European Database on New Drugs (EDND) and EMCDDA-Europol annual implementation reports (2010-2017) was searched for compounds with known agonist activity at CB1 and/or CB2 receptors. Information on the different names and chemical structures of each compound was extracted and analysed for patterns. PUBMED, Google Scholar and MEDLINE databases were searched, in addition to non-peer reviewed sources, for data on structure, structure-activity relationships and nomenclatures for each compound.Nomenclature of synthetic cannabinoid receptor agonists: The structural complexity of synthetic cannabinoid receptor agonists presents challenges for nomenclature. There are several nomenclature systems in use.Colloquial and clandestine names: Non-scientific names (e.g. AKB-48, 2NEI, XLR-11) have been used to refer to specific compounds and most have probably been invented by vendors, presumably for the purpose of successful marketing of recreational products, however such names do not convey useful information about structure.Systematic chemical names: Each compound has a systematic chemical name that describes its exact structure; however, it is complex, unwieldy, inaccessible to non-chemists and not suitable for routine communication or clinical use.Serial names: Represent iterative designations assigned to compounds produced as a series in a laboratory (e.g. 'WIN-', 'HU-', 'CP-', 'JWH-' and 'AM-'). This nomenclature does not provide structural information or reflect structural similarities between compounds.Systematic abbreviated names: Succinctly describe each compound utilising structural pharmacophores. The chemical motif in each pharmacophore group is assigned a unique code-letter and assembled into a name with the format of 'Linked Group - TailCoreLinker'. Frequently encountered groups include indole and indazole cores, amino-acid-like like groups, most notably methyl-3,3-dimethylbutanoate (MDMB), methanone linker groups and pentyl, 5-fluoropentyl and 4-fluorobenzyl tails. There has been inconsistent usage of this nomenclature, likely due to a lack of consensus and identification of code-letters for several chemical motifs.Emerging compounds and practices: Tricyclic carbazole and γ-carbolinone core analogues have been identified and may represent the next significant structural analogues to emerge onto the recreational market. There is a need to establish basic pharmacological and toxicological data for these analogues.Conclusions: There is a need for international consensus on the nomenclature used to name synthetic cannabinoid receptor agonists to ensure precise and effective communication between professional groups in the clinic and for the purposes of research and regulation, especially with the emergence of analogues of existing compounds and novel structural motifs. A well-defined nomenclature system also supports quick and accurate communication of the structure-activity of these compounds, potentially highlighting compounds that carry a significant risk of toxicity.

Effect of the UK Psychoactive Substances Act 2016 on episodes of toxicity related to new psychoactive substances as reported to the National Poisons Information Service. A time series analysis.

BACKGROUND: There have been recent increases in use of new psychoactive substances (NPS) associated with acute health harms including hospital presentations due to toxicity and increasing numbers of deaths. In response, the UK Government enacted generic legislation on 26th May 2016 (the Psychoactive Substances Act) making it an offence to produce, possess with intent to supply, supply, import or export, or possess within a custodial setting a psychoactive substance. We studied the impact of this Act on monthly frequency of enquiries made by health professionals to the UK National Poisons Information Service (NPIS) about NPS. We also studied five commonly used 'conventional' drugs of misuse that had been controlled prior to January 2009. METHOD: Anonymised clinical enquiries to the NPIS and accesses to the poisons information database TOXBASE were reviewed retrospectively from January 2009 to December 2018 to ascertain the trends in reported toxicity for NPS, cocaine, heroin, cannabis, amphetamines and MDMA. Data were analysed using interrupted time series analysis with the date of the PSA used as an independent predictor. RESULTS: Over the period of study there were 3,866 NPIS telephone enquiries and 79,271 TOXBASE user accesses made by UK health professionals concerning NPS. There were increases in monthly TOXBASE accesses (t = 7.408, P < 0.0001) and telephone enquiries (t = 4.74, P < 0.001) over the pre-specified period January 2009 to May 2016. Comparing the period after the PSA with that before, there were significant reductions in TOXBASE accesses (t = -3.327, P < 0.001) and telephone enquiries (t = -6.97, P < 0.001), although reductions started before May 2016. There were no significant changes for the five conventional drugs. There were significant reductions in telephone enquiries (t = -3.418, P < 0.001) and non-significant reductions in TOXBASE accesses (t = -1.713, P = 0.089) for NPS between June 2016 and December 2018. Increases in telephone enquiries for cocaine and reductions TOXBASE accesses for MDMA were also observed over that period. CONCLUSIONS: There have been significant recent reductions in NPIS enquiry activity relating to NPS; although these began before enactment of the PSA in May 2016.

Antarctic Futures: An Assessment of Climate-Driven Changes in Ecosystem Structure, Function, and Service Provisioning in the Southern Ocean.

In this article, we analyze the impacts of climate change on Antarctic marine ecosystems. Observations demonstrate large-scale changes in the physical variables and circulation of the Southern Ocean driven by warming, stratospheric ozone depletion, and a positive Southern Annular Mode. Alterations in the physical environment are driving change through all levels of Antarctic marine food webs, which differ regionally. The distributions of key species, such as Antarctic krill, are also changing. Differential responses among predators reflect differences in species ecology. The impacts of climate change on Antarctic biodiversity will likely vary for different communities and depend on species range. Coastal communities and those of sub-Antarctic islands, especially range-restricted endemic communities, will likely suffer the greatest negative consequences of climate change. Simultaneously, ecosystem services in the Southern Ocean will likely increase. Such decoupling of ecosystem services and endemic species will require consideration in the management of human activities such as fishing in Antarctic marine ecosystems.

Mapping co-benefits for carbon storage and biodiversity to inform conservation policy and action.

Integrated high-resolution maps of carbon stocks and biodiversity that identify areas of potential co-benefits for climate change mitigation and biodiversity conservation can help facilitate the implementation of global climate and biodiversity commitments at local levels. However, the multi-dimensional nature of biodiversity presents a major challenge for understanding, mapping and communicating where and how biodiversity benefits coincide with climate benefits. A new integrated approach to biodiversity is therefore needed. Here, we (a) present a new high-resolution map of global above- and below-ground carbon stored in biomass and soil, (b) quantify biodiversity values using two complementary indices (BIp and BIr) representing proactive and reactive approaches to conservation, and (c) examine patterns of carbon-biodiversity overlap by identifying 'hotspots' (20% highest values for both aspects). Our indices integrate local diversity and ecosystem intactness, as well as regional ecosystem intactness across the broader area supporting a similar natural assemblage of species to the location of interest. The western Amazon Basin, Central Africa and Southeast Asia capture the last strongholds of highest local biodiversity and ecosystem intactness worldwide, while the last refuges for unique biological communities whose habitats have been greatly reduced are mostly found in the tropical Andes and central Sundaland. There is 38 and 5% overlap in carbon and biodiversity hotspots, for proactive and reactive conservation, respectively. Alarmingly, only around 12 and 21% of these proactive and reactive hotspot areas, respectively, are formally protected. This highlights that a coupled approach is urgently needed to help achieve both climate and biodiversity global targets. This would involve (1) restoring and conserving unprotected, degraded ecosystems, particularly in the Neotropics and Indomalaya, and (2) retaining the remaining strongholds of intactness. This article is part of the theme issue 'Climate change and ecosystems: threats, opportunities and solutions'.

Author Correction: The importance of Antarctic krill in biogeochemical cycles.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The importance of Antarctic krill in biogeochemical cycles.

Antarctic krill (Euphausia superba) are swarming, oceanic crustaceans, up to two inches long, and best known as prey for whales and penguins - but they have another important role. With their large size, high biomass and daily vertical migrations they transport and transform essential nutrients, stimulate primary productivity and influence the carbon sink. Antarctic krill are also fished by the Southern Ocean's largest fishery. Yet how krill fishing impacts nutrient fertilisation and the carbon sink in the Southern Ocean is poorly understood. Our synthesis shows fishery management should consider the influential biogeochemical role of both adult and larval Antarctic krill.

Krill faecal pellets drive hidden pulses of particulate organic carbon in the marginal ice zone.

The biological carbon pump drives a flux of particulate organic carbon (POC) through the ocean and affects atmospheric levels of carbon dioxide. Short term, episodic flux events are hard to capture with current observational techniques and may thus be underrepresented in POC flux estimates. We model the potential hidden flux of POC originating from Antarctic krill, whose swarming behaviour could result in a major conduit of carbon to depth through their rapid exploitation of phytoplankton blooms and bulk egestion of rapidly sinking faecal pellets (FPs). Our model results suggest a seasonal krill FP export flux of 0.039 GT C across the Southern Ocean marginal ice zone, corresponding to 17-61% (mean 35%) of current satellite-derived export estimates for this zone. The magnitude of our conservatively estimated flux highlights the important role of large, swarming macrozooplankton in POC export and, the need to incorporate such processes more mechanistically to improve model projections.

Serum and plasma metabolites associated with postpartum ovulation and pregnancy risks in suckled beef cows subjected to artificial insemination.

Two experiments were conducted to determine relationships of blood metabolite concentrations, BW, BCS, and rump fat depth with postpartum ovulation and pregnancy risks, as well as their utility in predicting those outcomes in suckled beef cows. In experiment 1, plasma glucose collected 10 and 3 d before AI of suckled beef cows at seven locations did not differ between cows that had resumed estrous cycles (ovulated) before AI compared with anovulatory cows, whereas plasma glucose 3 d before AI was greater (P < 0.01) in cows that became pregnant compared with nonpregnant cows. Serum beta-hydroxybutyrate (BHB) tended (P = 0.09) to be less in ovulatory cows compared with anovulatory cows 10 d before AI, but was unrelated to pregnancy status. Receiver-operator derived true-positive (sensitivity) and false-positive (1-specificity) risks were determined for plasma glucose and serum BHB as predictors for postpartum ovulation and pregnancy status. Serum BHB 3 d before AI produced true-positive and false-positive risks of 82% and 37%, respectively, when predicting ovulatory status before AI. Serum BHB 10 d before AI produced a true-positive and false-positive risks of 92% and 25%, respectively, when predicting pregnancy status. In experiment 2, blood was collected weekly for 12 wk from multiparous suckled beef cows to assess blood metabolite concentrations in addition to concurrent weekly assessments of BW, BCS, and rump fat. When blood metabolites and physical measures were normalized to parturition reflecting changes occurring during the first 6 wk after calving, we observed reduced (P < 0.05) concentrations of serum BHB and NEFA, and greater (P < 0.05) rump fat and BCS in cows that ovulated before first AI, whereas reduced (P < 0.05) plasma glucose was characteristic of cows that became pregnant. When blood metabolites and physical measures were normalized to the onset of the AI program reflecting changes during 6 wk before AI, ovulatory cows had increased (P < 0.05) BCS and lower (P < 0.05) NEFA from 3 to 6 wk before the onset of the AI program compared with anovulatory cows. With all predictor variables in regression models, some multiple correlation coefficients (R2) exceeded 50% when predicting postpartum ovulatory status, but those for predicting pregnancy risk were less than 25%. Although measures of BCS and BHB during 6 wk after calving were related to postpartum ovulation risk, rump fat, glucose, BCS, and NEFA were associated with cows that were ovulatory and pregnant.

OSIRIS-REx Contamination Control Strategy and Implementation.

OSIRIS-REx will return pristine samples of carbonaceous asteroid Bennu. This article describes how pristine was defined based on expectations of Bennu and on a realistic understanding of what is achievable with a constrained schedule and budget, and how that definition flowed to requirements and implementation. To return a pristine sample, the OSIRIS-REx spacecraft sampling hardware was maintained at level 100 A/2 and <180 ng/cm2 of amino acids and hydrazine on the sampler head through precision cleaning, control of materials, and vigilance. Contamination is further characterized via witness material exposed to the spacecraft assembly and testing environment as well as in space. This characterization provided knowledge of the expected background and will be used in conjunction with archived spacecraft components for comparison with the samples when they are delivered to Earth for analysis. Most of all, the cleanliness of the OSIRIS-REx spacecraft was achieved through communication among scientists, engineers, managers, and technicians.

Nitric oxide inhibits viral replication in murine myocarditis.

Nitric oxide (NO) is a radical molecule that not only serves as a vasodilator and neurotransmitter but also acts as a cytotoxic effector molecule of the immune system. The inducible enzyme making NO, inducible NO synthase (iNOS), is transcriptionally activated by IFN-gamma and TNF-alpha, cytokines which are produced during viral infection. We show that iNOS is induced in mice infected with the Coxsackie B3 virus. Macrophages expressing iNOS are identified in the hearts and spleens of infected animals with an antibody raised against iNOS. Infected mice have increased titers of virus and a higher mortality when fed NOS inhibitors. Thus, viral infection induces iNOS in vivo, and NO inhibits viral replication. NO is a novel, nonspecific immune defense against viruses in vivo.

Can vacuum assisted venous drainage be achieved using a roller pump in an emergency? A pilot study using neonatal circuitry.

There has been much advancement in perfusion technology over its 50 years of progression. One of these techniques is vacuum-assisted venous drainage (VAVD). Many perfusionists augment venous drainage using VAVD, typically from a wall vacuum source. This study explores alternates to providing VAVD if the wall vacuum fails. In two porcine laboratories, approximately 36 in. of 3/16-in. tubing was connected to a sucker return port and placed into the roller head next to the arterial pump. The vacuum was monitored with a DLP pressure monitoring system (Medtronic). This system was connected to small-bore tubing and attached to a stopcock on top of the reservoir. The vacuum was regulated using another stopcock connected to a non-filtered luer lock port on top of the reservoir or by a segment of 3 x 0.25-in.-diameter tubing attached to the vent port with a c-clamp. Vacuum drainage was achieved, ranging from -18 mmHg to -71 mmHg by manipulating the stopcock or c-clamp. Changes in venous drainage were seen by volume fluctuations in the venous reservoir. The vacuum was adjusted to account for dramatic changes. Augmented venous drainage using a roller pump can be achieved successfully during cardiopulmonary bypass (CPB). This method of active drainage can be used in lieu of wall suction or during times of emergency if wall suction fails.