Anthropogenic climate and land-use change drive short- and long-term biodiversity shifts across taxa.

Climate change and habitat loss present serious threats to nature. Yet, due to a lack of historical land-use data, the potential for land-use change and baseline land-use conditions to interact with a changing climate to affect biodiversity remains largely unknown. Here, we use historical land use, climate data and species observation data to investigate the patterns and causes of biodiversity change in Great Britain. We show that anthropogenic climate change and land conversion have broadly led to increased richness, biotic homogenization and warmer-adapted communities of British birds, butterflies and plants over the long term (50+ years) and short term (20 years). Biodiversity change was found to be largely determined by baseline environmental conditions of land use and climate, especially over shorter timescales, suggesting that biodiversity change in recent periods could reflect an inertia derived from past environmental changes. Climate-land-use interactions were mostly related to long-term change in species richness and beta diversity across taxa. Semi-natural grasslands (in a broad sense, including meadows, pastures, lowland and upland heathlands and open wetlands) were associated with lower rates of biodiversity change, while their contribution to national-level biodiversity doubled over the long term. Our findings highlight the need to protect and restore natural and semi-natural habitats, alongside a fuller consideration of individual species' requirements beyond simple measures of species richness in biodiversity management and policy.

Vaccinating international seafarers during the COVID-19 pandemic.

Despite their key role in the distribution of essential goods, seafarers were often overlooked in international COVID-19 responses. Border closures isolated them at sea, often for months beyond contract. Distributing vaccines to seafarers was inconsistent and often depended on the creativity of charities and industry and labour stakeholders. Even seafarers who received vaccinations often had them unrecognised in the ports they visited. These oversights should not be repeated in preparation for future pandemics. As a vulnerable population and as key international workers, seafarers' health should be prioritised by national and international health policy.

Linking climate warming and land conversion to species' range changes across Great Britain.

Although increased temperatures are known to reinforce the effects of habitat destruction at local to landscape scales, evidence of their additive or interactive effects is limited, particularly over larger spatial extents and longer timescales. To address these deficiencies, we created a dataset of land-use changes over 75 years, documenting the loss of over half (>3000 km2) the semi-natural grassland of Great Britain. Pairing this dataset with climate change data, we tested for relationships to distribution changes in birds, butterflies, macromoths, and plants (n = 1192 species total). We show that individual or additive effects of climate warming and land conversion unambiguously increased persistence probability for 40% of species, and decreased it for 12%, and these effects were reflected in both range contractions and expansions. Interactive effects were relatively rare, being detected in less than 1 in 5 species, and their overall effect on extinction risk was often weak. Such individualistic responses emphasise the importance of including species-level information in policies targeting biodiversity and climate adaptation.

Association between Initial Opioid Prescription and Patient Pain with Continued Opioid Use among Opioid-Naïve Patients Undergoing Elective Surgery in a Large American Health System.

There is growing concern about the over-prescription of opioids and the risks of long-term use. This study examined the relationship between initial need (pre-operative, post-operative, and discharge pain) and dosage of opioids in the first prescription after surgery with continued opioid use through opioid refills over 12 months, while considering patient-level characteristics. A total of 9262 opioid-naïve patients underwent elective surgery, 7219 of whom were prescribed opioids following surgery. The results showed that 17% of patients received at least one opioid refill within one year post-surgery. Higher initial opioid doses, measured in morphine milligram equivalent (MME), were associated with a greater likelihood of continued use. Patients receiving a dose greater than 90 MME were 1.57 times more likely to receive a refill compared to those receiving less than 90 MME (95% confidence interval: 1.30-1.90, p < 0.001). Additionally, patients who experienced pain before or after surgery were more likely to receive opioid refills. Those experiencing moderate or severe pain were 1.66 times more likely to receive a refill (95% confidence interval: 1.45-1.91, p < 0.001). The findings highlight the need to consider surgery-related factors when prescribing opioids and the importance of developing strategies to balance the optimization of pain management with the risk of opioid-related harms.

Evaluation of Policies Limiting Opioid Exposure on Opioid Prescribing and Patient Pain in Opioid-Naive Patients Undergoing Elective Surgery in a Large American Health System.

OBJECTIVES: Overprescribing to opioid-naive surgical patients substantially contributes to opioid use disorders, which have become increasingly prevalent. Opioid stewardship programs (OSPs) within healthcare settings provide an avenue for introducing interventions to regulate prescribing. This study examined the association of OSP policies limiting exposure on changes in surgery-related opioid prescriptions and patient pain. METHODS: We evaluated policies implemented by an OSP in a large American healthcare system between 2016 and 2018: nonopioid medication during surgery, decrease of available opioid dosage vials in operating rooms, standardization of opioid in-patient practices through electronic health record alerts, and limit to postsurgery opioid supply. Generalized linear mixed effects models examined the association of interventions with outcome changes in 9262 opioid-naive patients undergoing elective surgery. Outcomes were discharge pain, morphine milligram equivalent in the first prescription postsurgery, and opioid prescription refills. RESULTS: Decreases in all prescription outcomes and discharge pain were observed following onset of OSP interventions ( P 's < 0.001). Among individual policies, standardization of in-patient prescribing practices was associated with the strongest decrease in prescribed morphine milligram equivalent. Importantly, there was no evidence of an increase in discharge pain related to any intervention. CONCLUSIONS: This study promotes the potential of OSP formation and policies to reduce opioid prescribing without compromising patient pain. The most effective policy, standardization of in-patient prescribing practices through alerts, suggests that reminding prescribers to re-evaluate the patient's need is effective in changing behavior. The findings offer considerations for OSP formation and policy implementation across health systems to improve quality and safety in opioid prescribing.

Emergency Department Alternatives to Opioids: Adapting and Implementing Proven Therapies in Practice.

The use of opioids to treat pain can increase the risk of long-term opioid dependency and is associated with negative patient outcomes. The objective of this study was to present the initial results following the implementation of Emergency-Department Alternatives to Opioids (ED-ALTO), a program that encourages the use of non-narcotic medications and procedures to treat pain in the Emergency Department (ED). We used a pre- and post-implementation study design to compare in-ED opioid utilization, as well as ED-ALTO medication and procedure use in the year before and after the program's implementation. After ED-ALTO's implementation, there was a decrease in opioid utilization in the ED and an increase in ED-ALTO medication use. Additionally, there was an increase in ED-ALTO procedure utilization and the complexity of conditions treated with ED-ALTO procedures, including the use of regional nerve blocks for shoulder dislocations and hip and rib fractures. In 8 of the 12 months following ED-ALTO's implementation, a lower proportion of patients receiving ED-ALTO procedures received an opioid, and the opioid dosage was lower compared to patients with the same diagnoses who received standard care. The continued expansion of ED-ALTO programs across the US may serve as a mechanism to reduce opioid utilization and safely and successfully treat pain in ED settings.

Redirecting tropane alkaloid metabolism reveals pyrrolidine alkaloid diversity in Atropa belladonna.

Plant-specialized metabolism is complex, with frequent examples of highly branched biosynthetic pathways, and shared chemical intermediates. As such, many plant-specialized metabolic networks are poorly characterized. The N-methyl Δ1 -pyrrolinium cation is a simple pyrrolidine alkaloid and precursor of pharmacologically important tropane alkaloids. Silencing of pyrrolidine ketide synthase (AbPyKS) in the roots of Atropa belladonna (Deadly Nightshade) reduces tropane alkaloid abundance and causes high N-methyl Δ1 -pyrrolinium cation accumulation. The consequences of this metabolic shift on alkaloid metabolism are unknown. In this study, we utilized discovery metabolomics coupled with AbPyKS silencing to reveal major changes in the root alkaloid metabolome of A. belladonna. We discovered and annotated almost 40 pyrrolidine alkaloids that increase when AbPyKS activity is reduced. Suppression of phenyllactate biosynthesis, combined with metabolic engineering in planta, and chemical synthesis indicates several of these pyrrolidines share a core structure formed through the nonenzymatic Mannich-like decarboxylative condensation of the N-methyl Δ1 -pyrrolinium cation with 2-O-malonylphenyllactate. Decoration of this core scaffold through hydroxylation and glycosylation leads to mono- and dipyrrolidine alkaloid diversity. This study reveals the previously unknown complexity of the A. belladonna root metabolome and creates a foundation for future investigation into the biosynthesis, function, and potential utility of these novel alkaloids.

A silver lining for pandemic-weary libraries: How blended and flipped instructional programs have improved upon pre-pandemic norms.

The COVID-19 pandemic presented instructors and learners with novel challenges related to the delivery and consumption of instructional content. Within academic libraries, these changes have resulted in an expanded reliance on asynchronous learning content delivered through a variety of instructional approaches. The study described herein was designed to evaluate the effectiveness of a blended and flipped program of information literacy (IL) instruction. Deploying a pre/post-test methodology within a quasi-experimental study of student learning outcomes, this research compares achievement across two cohorts of students receiving IL instruction as part of a first-year writing program (FYWP) requirement. While one cohort participated in a multi-shot, in-person, synchronous instructional program during the pre-pandemic period, another cohort participated in a blended and flipped instructional program delivered under pandemic-related restrictions. Comparative analysis revealed net positive achievement outcomes for both the pre-pandemic and pandemic cohorts, as well as interesting points of contrast between the two groups. In particular, students in the pandemic cohort arrived to their first year with less research experience than their pre-pandemic peers-signaling a gap in knowledge that pandemic-era library instruction must overcome. Fortunately, the blended and flipped instructional program experienced by the pandemic cohort proved successful in helping those students overcome their research experience gap, while delivering additional benefits that help confirm previous research in this area of practice.

Biocatalysis of precursors to new-generation SB-T-taxanes effective against paclitaxel-resistant cancer cells.

A 10-O-deacetylbaccatin III 10-O-acetyltransferase biocatalyst from Taxus plants was expressed in bacteria whole-cells that were fed 10-O-deacetylbaccatin III and cyclopropane carboxylic acid. Product analysis by qualitative LC/ESI-MS suggested that the C10-acylated products baccatin III, 10-O-n-propionyl-10-O-deacetylbaccatin III, and 10-O-cyclopropanecarbonyl-10-O-deacetylbaccatin III were made in vivo. The results implied that the cells provided non-natural cyclopropanecarbonyl CoA, from a broad-specificity CoA ligase, and natural products, acetyl CoA and n-propionyl CoA, from reserves in the bacteria for use by acyltransferase to acylate 10-O-deacetylbaccatin III in vivo. The 10-acyl-10-O-deacetylbaccatin III are precursors used to synthesize new-generation paclitaxel analogs SB-T-1214 and SB-T-121303, which are effective against cancer cells resistant to paclitaxel and its drug derivatives. The kcat and KM of the acyltransferase for cyclopropanecarbonyl CoA (0.83 s-1, 0.15 M) and n-propionyl CoA (1.2 s-1, 0.15 M) guided scale-up efforts. The 10-acyl-10-O-deacetylbaccatin III analogs (∼45 mg each) were made in vitro by the acyltransferase when incubated with the commercial taxane 10-O-deacetylbaccatin III and synthesized cyclopropanecarbonyl or n-propionyl CoA. The structures of the 10-acyl products were verified by NMR analyses that confirmed C10 acylation of the taxane substrate. LC/ESI-MS/MS analysis also supported the identities of the biocatalyzed products. This effort provides a biocatalysis framework to produce new-generation taxane precursors.

Single shot interscalene regional anesthesia provides noninferior analgesia and decreased complications compared with an indwelling catheter for arthroscopic and reconstructive shoulder surgery.

BACKGROUND: There is an abundance of literature comparing the efficacy, safety, and complication rates of regional anesthesia in shoulder surgery. The purpose of this study was to compare analgesia efficacy, and complication rates between single shot and continuous catheters in patients undergoing arthroscopic or reconstructive shoulder surgery in a large cohort. METHODS: Consecutive patients (n = 1888) who underwent shoulder arthroplasty or arthroscopic shoulder surgery and had regional anesthesia were included. Patients had either a single-shot interscalene block (SSIB) or an SSIB with a continuous interscalene nerve block with a catheter (CIB). The decision for SSIB or CIB was selected based on patient risk factors and surgeon preference. Patients received phone calls on postoperative days 1, 2, 7, and 14 to assess for pain levels (numeric rating scale [NRS]) and complications. RESULTS: One hundred sixty patients received SSIB, and 1728 patients received CIB. The postoperative NRS scores at day 1 were also similar. There were 3 complications (2%) in the SSIB group and 172 complications (10%) in the CIB group. Ten patients in the CIB group required emergency department (ED) visits secondary to block complications compared with no ED visits in the SSIB group. CONCLUSION: In 1888 consecutive patients, SSIB and CIB provided similar pain relief following shoulder surgery. However, patients who received CIB had significantly more complications and ED visits than patients who received SSIB. The potential benefits of longer pain relief may not outweigh the risks of CIB vs. SSIB in common shoulder procedures.

A taxonomic, genetic and ecological data resource for the vascular plants of Britain and Ireland.

The vascular flora of Britain and Ireland is among the most extensively studied in the world, but the current knowledge base is fragmentary, with taxonomic, ecological and genetic information scattered across different resources. Here we present the first comprehensive data repository of native and alien species optimized for fast and easy online access for ecological, evolutionary and conservation analyses. The inventory is based on the most recent reference flora of Britain and Ireland, with taxon names linked to unique Kew taxon identifiers and DNA barcode data. Our data resource for 3,227 species and 26 traits includes existing and unpublished genome sizes, chromosome numbers and life strategy and life-form assessments, along with existing data on functional traits, species distribution metrics, hybrid propensity, associated biomes, realized niche description, native status and geographic origin of alien species. This resource will facilitate both fundamental and applied research and enhance our understanding of the flora's composition and temporal changes to inform conservation efforts in the face of ongoing climate change and biodiversity loss.

Semibiocatalytic Approach toward Regioisomerically Enriched Ethyl Dimethylpyrazines Important in Flavor Industries.

Alkylpyrazines are important heterocyclic compounds used as flavorants in food and beverage industries. In this study, a regioselective semibiocatalytic process was developed to synthesize 2-ethyl-3,5-dimethylpyrazine (235-EDMP) over its 3-ethyl-2,5-dimethyl pyrazine (325-EDMP) isomer and vice versa. We initially explored how sterics could direct the coupling orientations between diamines and diketones to access 235- or 325-EDMP selectively. Also, the physical parameters of the reaction conditions were changed, such as reduced temperature, the order-of-addition of the reactants, and supplementation with chiral zeolites to template the orientation of the coupling partners to direct the reaction regiochemistry. Each reaction trial resulted in 50:50 mixtures of the EDMP isomers. An alternative approach was explored to control the regioselectivity of the reactions; α-hydroxy ketones replaced the diketones as the electrophilic coupling reactant used in previous trial experiments. The hydroxy ketone reactants were made biocatalytically with pyruvate decarboxylase. The coupling reaction between 2-hydroxypentan-3-one and propane-1,2-diamine resulted in the desired 235-EDMP at >70% (∼77 mg) relative to 325-EDMP in the mixture. The 3-hydroxypentan-2-one congener was biocatalyzed and reacted with propane-1,2-diamine as a proof of principle to synthesize 325-EDMP (∼60% relative abundance, ∼73 mg) over 235-EDMP. These results suggested a mechanism that was directed by the hydroxy ketone electrophilicity and the sterics at the diamine nucleophilic centers.

Characterizing the environmental drivers of the abundance and distribution of Alopecurus myosuroides on a national scale.

BACKGROUND: Arable weeds threaten farming and food production, impacting on productivity. Large-scale data on weed populations are typically lacking, and changes are frequently undocumented until they reach problem levels. Managing the future spread of weeds requires that we understand the factors that influence current densities and distributions. In doing so, one of the challenges is to measure populations at a large enough scale to be able to accurately measure changes in densities and distributions. Here we analyse the density and distribution of a major weed (Alopecurus myosuroides) on a large scale. Our objectives were to (i) develop a methodology for rapid measurement of occurrence and abundance, (ii) test hypotheses about the roles of soils and climate variation in determining densities, and (iii) use this information to identify areas in which occurrence could increase in the future. RESULTS: Populations were mapped through England over 4 years in 4631 locations. We also analysed UK atlas data published over the past 50 years. Densities of populations show significant interannual variability, but historical data show that the species has spread. We find significant impacts of soil and rainfall on densities, which increase with the proportion of heavy soils, but decrease with increasing rainfall. Compared with independent atlas data we found that our statistical models provide good predictions of large-scale occupancy and we provide maps of current and potential densities. CONCLUSION: Models of spread highlight the localised nature of colonisation, and this emphasises the need for management to limit dispersal. Comparisons of current, historical and potential distributions suggest sizeable habitable areas in which increases in abundance are still possible. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Intraoperative Neurological Monitoring in Lower Limb Surgery for Patients With Mucopolysaccharidoses.

BACKGROUND: There are reports of spinal cord injury (SCI) occurring after lower extremity (LE) surgery in children with mucopolysaccharidoses (MPS). Intraoperative neurological monitoring (IONM) has been adopted in some centers to assess real-time spinal cord function during these procedures. The aim of this investigation was to review 3 specialty centers' experiences with MPS patients undergoing LE surgery. We report how IONM affected care and the details of spinal cord injuries in these patients. METHODS: All pediatric MPS patients who underwent LE surgery between 2001 and 2018 were reviewed at 3 children's orthopaedic specialty centers. Demographic and surgical details were reviewed. Estimated blood loss (EBL), surgical time, positioning, use of IONM, and changes in management as a result of IONM were recorded. Details of any spinal cord injuries were examined in detail. RESULTS: During the study period, 92 patients with MPS underwent 252 LE surgeries. IONM was used in 83 of 252 (32.9%) surgeries, and intraoperative care was altered in 17 of 83 (20.5%) cases, including serial repositioning (n=7), aggressive blood pressure management (n=6), and abortion of procedures (n=8). IONM was utilized in cases with larger EBL (279 vs. 130 mL) and longer operative time (274 vs. 175 min) compared with procedures without IONM. Three patients without IONM sustained complete thoracic SCI postoperatively, all from cord infarction in the upper thoracic region. These 3 cases were characterized by long surgical time (328±41 min) and substantial EBL (533±416 mL or 30.5% of total blood volume; range, 11% to 50%). No LE surgeries accompanied by IONM experienced SCI. CONCLUSIONS: Patients with MPS undergoing LE orthopaedic surgery may be at risk for SCI, particularly if the procedures are long or are expected to have large EBL. One hypothesis for the etiology of SCI in this setting is hypoperfusion of the upper thoracic spinal cord due to prolonged intraoperative or postoperative hypotension. IONM during these procedures may mitigate the risk of SCI by identifying real-time changes in spinal cord function during surgery, inciting a change in the surgical plan. LEVEL OF EVIDENCE: Level III-retrospective comparative series.

Self and sibling care attitudes, personal loss, and stress-related growth among siblings of adults with mental illness.

Although sibling ties are typically among the longest lasting family relationships, relatively little is known about how adult siblings navigate family caregiving when a brother or sister has a serious mental illness. The present study examined the role of primary caregiver status, perceived sibling illness severity, sibling relationship quality, and self and sibling caregiving attitudes in understanding reports of personal loss and stress-related personal growth among siblings of adults with serious mental illness. Online surveys were completed by 226 adult siblings (141 women; 85 men; mean age = 34 years; SD = 9.05). Results suggest that well siblings' reports of self and sibling caregiving attitudes significantly differed as a function of primary caregiver status (i.e., sibling, parents, or others as primary caregiver or no caregiver). Sibling caregiving attitudes differentially predicted well siblings' experience of personal loss and stress-related growth, regardless of demographics and primary caregiver status, perceived sibling illness severity, and sibling relationship quality. Greater ambivalence about providing care to their sibling with mental illness was associated with adults' reports of greater personal loss while higher levels of sibling balanced care priorities were significantly related to higher levels of personal growth. Greater self-care attitudes were significantly related to lower levels of both personal loss and personal growth for well siblings. Understanding sibling caregiving attitudes has important implications for research and interventions with families coping with mental illness. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

CoA recycling by a benzoate coenzyme A ligase in cascade reactions with aroyltransferases to biocatalyze paclitaxel analogs.

A Pseudomonas CoA ligase (BadA) biocatalyzed aroyl CoA thioesters used by a downstream N-benzoyltransferase (NDTNBT) in a cascade reaction made aroyl analogs of the anticancer drug paclitaxel. BadA kept the high-cost aroyl CoA substrates at saturation for the downstream NDTNBT by recycling CoA when it was added as the limiting reactant. A deacylated taxane substrate N-debenzoyl-2'-deoxypaclitaxel was converted to its benzoylated product at a higher yield, compared to the converted yield in assays in which the BadA ligase chemistry was omitted, and benzoyl CoA was added as a cosubstrate. The resulting benzoylated product 2'-deoxypaclitaxel was made at 196% over the theoretical yield of product that could be made from the CoA added at 50 µM, and the cosubstrates benzoic acid (100 µM), and N-debenzoyl-2'-deoxypaclitaxel (500 µM) added in excess. In addition, a 2-O-benzoyltransferase (mTBT) was incubated with BadA, aroyl acids, CoA, a 2-O-debenzoylated taxane substrate, and cofactors under the CoA-recycling conditions established for the NDTNBT/BadA cascade. The mTBT/BadA combination also made various 2-O-aroylated products that could potentially function as next-generation baccatin III compounds. These ligase/benzoyltransferase cascade reactions show the feasibility of recycling aroyl CoA thioesters in vitro to make bioactive acyl analogs of paclitaxel precursors.

The Impact of the Long-term Care Homes Act and Public Reporting on Physical Restraint and Potentially Inappropriate Antipsychotic Use in Ontario's Long-term Care Homes.

BACKGROUND: We report on the impact of two system-level policy interventions (the Long-Term Care Homes Act [LTCHA] and Public Reporting) on publicly reported physical restraint use and non-publicly reported potentially inappropriate use of antipsychotics in Ontario, Canada. METHODS: We used interrupted time series analysis to model changes in the risk-adjusted use of restraints and antipsychotics before and after implementation of the interventions. Separate analyses were completed for early ([a] volunteered 2010/2011) and late ([b] volunteered March 2012; [c] mandated September 2012) adopting groups of Public Reporting. Outcomes were measured using Resident Assessment Instrument Minimum Data Set (RAI-MDS) data from January 1, 2008 to December 31, 2014. RESULTS: For early adopters, enactment of the LTCHA in 2010 was not associated with changes in physical restraint use, while Public Reporting was associated with an increase in the rate (slope) of decline in physical restraint use. By contrast, for the late-adopters of Public Reporting, the LTCHA was associated with significant decreases in physical restraint use over time, but there was no significant increase in the rate of decline associated with Public Reporting. As the LTCHA was enacted, potentially inappropriate use of antipsychotics underwent a rapid short-term increase in the early volunteer group, but, over the longer term, their use decreased for all three groups of homes. CONCLUSIONS: Public Reporting had the largest impact on voluntary early adopters while legislation and regulations had a more substantive positive effect upon homes that delayed public reporting.

Triphasic Pulses in Cochlear Implant Patients With Facial Nerve Stimulation.

OBJECTIVE: Evaluation of triphasic pulse stimulation in comparison to the traditional biphasic pulse stimulation in cochlear implant (CI) patients with unintended facial nerve costimulation. STUDY DESIGN: Retrospective case review. SETTING: Cochlear Implant Center of a University Department of Otolaryngology, Head and Neck Surgery. PATIENTS: Fifteen CI patients (MED-EL, Innsbruck, Austria) received a triphasic fitting map instead of a biphasic fitting map due to a previous diagnosis of facial nerve stimulation or stimulus induced pain during the years 2014 to 2017. INTERVENTION(S): Application of a triphasic stimulation strategy. MAIN OUTCOME MEASURE(S): Reduction of facial nerve costimulation and speech understanding. Biphasic and triphasic fitting maps were compared to accurately assess the effects of the switch, and hearing tests (monosyllables and sentences in noise tests) were analyzed. RESULTS: Triphasic pulse stimulation showed a significant reduction of unintended side effects and resulted in an observed improved quality of life in most cases. Although there was no significant change in the understanding of speech with CI in all test situations, in many cases, improvement was observed. CONCLUSIONS: Triphasic pulse stimulation had a beneficial effect for CI patients with severe, unintended costimulation and should be considered a valuable tool during CI fitting.