Effects of elevated CO2 on the reproductive performance and early life fitness of long-lived woody plant species

Atmospheric concentrations of CO2 have risen considerably since the industrial revolution due to human activity. Without extreme intervention, climate forecasts indicate that atmospheric CO2 concentrations will continue to rise. Plant growth and productivity in response to elevated CO2 has been studied extensively, however, few studies explore how reproduction will be affected under future CO2 concentration; particularly for long-lived woody plant species. This study is undertaken within the EucFACE facility in Western Sydney (Australia), with naturally growing populations, on nutrient limited soils, which form part of the remnant Cumberland Plains Woodland. The effects of elevated CO2 on vegetative growth in this ecosystem have previously been demonstrated to be absent due to phosphorous limitation despite maintaining higher photosynthetic rates. Little is known how reproductive performance of long-lived woody plants species will respond to increased CO2 concentrations in this environment. The main objective of this thesis is to explore direct effects of elevated CO2 on the reproductive performance of a dominant tree, Eucalyptus tereticornis, and a perennial shrub, Hakea sericea, in addition to the subsequent maternal effects on early-life fitness of H. sericea. It is the first study to assess the reproductive performance of mature dominant evergreen angiosperm (E. tereticornis) in response to rising CO2 concentration. Several experiments were undertaken to determine how reproductive performance and subsequent early-life fitness is affected by elevated CO2; (i) The impacts on reproductive effort and output through quantifying the proportion of biomass invested into floral buds, fruit and seeds for E. tereticornis and H. sericea. (ii) Seed quality was assessed through conducting germination experiments for E. tereticornis and H. sericea. (iii) Seed sourced from maternal H. sericea plants grown in ambient and elevated CO2 conditions were propagated into growth chambers simulating pre-industrial, ambient, and future CO2 concentrations to assess early-life fitness through measurements of biomass, photosynthesis, and functional traits. Key findings from these experiments were; (i) Reproductive effort for E. tereticornis is increased for plants growing in elevated CO2, however, there is great interannual variability which will require further exploration, (ii) Germination success is differentially affected by elevated CO2, with H. sericea (large seeded species) seeing greater benefits than E. tereticornis (small seeded species), (iii) Despite having lower biomass, seedlings with maternal plants grown in ambient CO2 conditions had greater photosynthetic capacity than seedlings with maternal plants grown in elevated CO2, and (iv) Photosynthesis was down-regulated in response to long-term exposure of elevated CO2 only for seedlings 7 with maternal plants grown in elevated CO2 indicating acclimation may occur across generations but not necessarily within a generation. Differential responses between species may have profound impacts on vegetation community composition, thereby altering ecosystem structure and function

8-Azatetracyclines: Synthesis and Evaluation of a Novel Class of Tetracycline Antibacterial Agents

bS Supporting Information ABSTRACT: A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection. The tetracycline class of antibacterial agents has seen wide-spread clinical use for over 50 years due to its broad spectrum anti-bacterial activity.1 Tetracyclines inhibit bacterial growth by prevent-ing protein biosynthesis through binding to the 30S ribosome

Co-Flowering Species Richness Increases Pollinator Visitation to Apple Flowers

Co-flowering plants can experience an array of interactions, ranging from facilitation to competition, the direction and strength of which are often dependent on the relative abundance and diversity of the plant species involved and the foraging behavior of their pollinators. Understanding interactions between plant−pollinator networks and how they change over time is particularly important within agricultural systems, such as apples, that flower en masse and that also contain non-crop co-flowering species both within the farm and the surrounding landscape. We determined the degree of overlap between pollinator networks on two varieties of apple (Granny Smith and Pink Lady) and co-flowering plant species within orchards and the wider vegetation matrix in two apple-growing regions (Orange and Bilpin) in Australia. We surveyed plant−pollinator interactions at key stages of the cropping cycle: before mass flowering; during king, peak and late blooms; and, finally, once apple flowering had finished. Overall, we found considerable overlap in the flower visitor assemblage on apples and co-flowering species within the orchard. The introduced honeybee (Apis mellifera) was the most frequent flower visitor to all three vegetation types at all times in Orange. However, in Bilpin, both a native stingless bee (Tetragonula carbonaria) and A. mellifera were highly frequent visitors, both on- and off-crop. Numerous native bees, flies and Lepidoptera also commonly visited apple and co-flowering species within orchards in both locations. We found that native-bee and honeybee visitation to apple flowers was positively correlated with co-flowering species richness (within the orchard and the wider matrix); however, visitation by native bees decreased as the area of co-flowering species in the surrounding landscape increased. Our study highlights the importance of maintaining diverse co-flowering plant communities within the local landscape to increase and support a wide variety of pollinators in horticultural production systems

Quinones as dienophiles in the Diels-Alder reaction: history and applications in total synthesis

In the canon of reactions available to the organic chemist engaged in total synthesis, the Diels–Alder reaction is among the most powerful and well understood. Its ability to rapidly generate molecular complexity through the simultaneous formation of two carboncarbon bonds is almost unrivalled, and this is reflected in the great number of reported applications of this reaction. Historically, the use of quinones as dienophiles is highly significant, being the very first example investigated by Diels and Alder. Herein, we review the application of the Diels–Alder reaction of quinones in the total synthesis of natural products. The highlighted examples span some 60 years from the landmark syntheses of morphine (1952) and reserpine (1956) by Gates and Woodward, respectively, through to the present day examples, such as the tetracyclines

RANK, RANKL and osteoprotegerin in bone biology and disease

Upon the discovery of RANK, RANKL and OPG in the late 1990s, their importance in the maintenance of the skeletal structure and their dramatic role in bone disease were largely unexpected. In recent years the understanding of these proteins, in particular their regulation, has greatly increased. This review aims to bring the interested reader up to date with the latest news and views on the mechanisms controlling bone resorption in normal and pathological conditions

Occupational advice for Patients undergoing Arthroplasty of the Lower limb: An intervention development and feasibility study (The OPAL Study)

Background Hip and knee replacements are regularly performed for patients who work. There is little evidence about these patients’ needs and the factors influencing their return to work. There is a paucity of guidance to help patients return to work after surgery and a need for structured occupational advice to enable them to return to work safely and effectively. Objective(s) To develop an occupational advice intervention to support early recovery to usual activities including work which is tailored to the requirements of patients undergoing hip and knee replacements. To test the acceptability, practicality and feasibility of this intervention within current care frameworks Design An intervention mapping (IM) approach was used to develop the intervention. The research methods employed were: rapid evidence synthesis; qualitative interviews with patients and stakeholders; prospective cohort study; survey of clinical practice; modified Delphi consensus process. The developed intervention was implemented and assessed during the final feasibility stage of the IM process. Setting Orthopaedic departments within NHS secondary care. Participants Patients in work, and intending to return to work following primary elective hip and knee replacement surgery; healthcare professionals and employers. Interventions Occupational advice intervention. Main outcome measures Development of an occupational advice intervention. Fidelity of the developed intervention when delivered in a clinical setting. Patient and clinician perspectives of the intervention. Preliminary assessments of intervention effectiveness and cost. Results A cohort study (154 patients), 110 stakeholder interviews, survey of practice (152 respondents) and evidence synthesis provided the necessary information to develop the intervention. The intervention included information resources, personalized return to work plan and co-ordination from the healthcare team to support the delivery of 13 patient and 20 staff performance objectives (POs). To support delivery, a range of tools (e.g. occupational checklists, patient workbooks, employer information), roles (e.g. return-to-work coordinator) and training resources were created. Feasibility was assessed in 21 of the 26 patients recruited from 3 NHS trusts. Adherence with the defined performance objectives was 75% for patient POs and 74% for staff POs. The intervention was generally well received although the short timeframe available for implementation and concurrent research evaluation led to some confusion amongst patients and those delivering the intervention regarding its purpose and the roles and responsibilities of key staff. Limitations Implementation and uptake of the intervention was not standardized and was limited by the study timeframe. Evaluation of the intervention involved a small number of patients which limited the ability to assess it. Conclusions The developed occupational advice intervention supports best practice. Evaluation demonstrated good rates of adherence against defined performance objectives. However, a number of operational and implementation issues require further attention Future work The intervention warrants a randomised controlled trial to assess its clinical and cost effectiveness to improve rates and timing of sustained return to work after surgery. This research should include the development of a robust implementation strategy to ensure adoption is sustained. Funding This project was funded by the NIHR Health Technology Assessment programme (project number 15/28/02) Trial Registrations International Standard Randomised Controlled Trials Number Trial ID: ISRCTN27426982 International prospective register of systematic reviews (PROSPERO) Registration: CRD4201604523

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients