The effects of spring versus summer heat events on two arid zone plant species under field conditions.

Heatwaves are increasingly occurring out-of-season, which may affect plants not primed for the event. Further, heat stress often coincides with water and/or nutrient stress, impairing short-term physiological function and potentially causing downstream effects on reproductive fitness. We investigated the response of water-stressed arid-zone Solanum oligacanthum and Solanum orbiculatum to spring vs summer heat stress under differing nutrient conditions. Heat stress events were imposed in open-topped chambers under in situ desert conditions. To assess short-term impacts, we measured leaf photosystem responses (F v /F m ) and membrane stability; long-term effects were compared via biomass allocation, visible damage, flowering and fruiting. Plants generally fared more poorly following summer than spring heat stress, with the exception of F v /F m . Summer heat stress caused greater membrane damage, reduced growth and survival compared with spring. Nutrient availability had a strong influence on downstream effects of heat stress, including species-specific outcomes for reproductive fitness. Overall, high temperatures during spring posed a lower threat to fitness than in severe arid summer conditions of high temperature and low water availability, which were more detrimental to plants in both the short and longer term. Our study highlights the importance of considering ecologically relevant, multiple-stressor events to understand different species responses to extreme heat.

The culturable seed mycobiome of two Banksia species is dominated by latent saprotrophic and multi-trophic fungi.

Seed fungal endophytes play an important beneficial role in the formation of the seedling mycobiome and contribute to plant establishment, but can also occur as latent pathogens and saprotrophs. Current knowledge on the function and diversity of seed fungal endophytes has been gained through studies in agricultural systems whilst knowledge from natural systems is relatively less. We used two co-occurring species from the genus Banksia from four sites in Australia's Sydney Basin Bioregion to investigate the abundance and diversity of seed fungal endophyte communities present in natural ecosystem hosts. Based on results from culturing and DNA sequence analysis of multiple loci, we found that Banksia seeds house a diverse range of fungal endophyte species, that when assigned to functional guilds belonged to multiple trophic modes. Thirty-one of the fungal taxa identified had not been previously reported as endophytes. Amongst the 58 Operational Taxonomic Units identified, Leotiomycetes and Sordariomycetes were the dominant classes and Banksiamyces (Leotiomycetes) and Penicillium (Sordariomycetes) the dominant genera, with many of the species isolated recorded in the literature as having a limited distribution. The two Banksias shared few fungal endophyte species, which were not always present across all study sites. We revealed a 'hidden diversity' within seeds of Banksia from natural ecosystems and provided insights into the influence host species can have on the seed mycobiome.

Outcomes and complications associated with malar onlays: literature review and case series of 119 implants.

Alloplastic malar onlays have been used by surgeons to correct or enhance the midfacial skeleton for over 40 years. Case series have shown respectable results using different alloplastic materials in various maxillofacial subsites. However, these articles include small numbers of patients with limited follow up. We present a literature review specifically concentrating on porous polyethylene (Medpor, Stryker) and polyethyl ether ketone (PEEK) malar onlays. We illustrate the technique used by a single oral and maxillofacial surgeon for placement of 119 implants in 61 patients over a 14-year period, and show the results of this work with long-term follow up. A complication rate of 2.5% in this cohort was reported, with follow up of three years, demonstrating that this technique for midfacial correction is successful in both the short and the long term.

Reviewing research priorities in weed ecology, evolution and management: a horizon scan.

Weedy plants pose a major threat to food security, biodiversity, ecosystem services and consequently to human health and wellbeing. However, many currently used weed management approaches are increasingly unsustainable. To address this knowledge and practice gap, in June 2014, 35 weed and invasion ecologists, weed scientists, evolutionary biologists and social scientists convened a workshop to explore current and future perspectives and approaches in weed ecology and management. A horizon scanning exercise ranked a list of 124 pre-submitted questions to identify a priority list of 30 questions. These questions are discussed under seven themed headings that represent areas for renewed and emerging focus for the disciplines of weed research and practice. The themed areas considered the need for transdisciplinarity, increased adoption of integrated weed management and agroecological approaches, better understanding of weed evolution, climate change, weed invasiveness and finally, disciplinary challenges for weed science. Almost all the challenges identified rested on the need for continued efforts to diversify and integrate agroecological, socio-economic and technological approaches in weed management. These challenges are not newly conceived, though their continued prominence as research priorities highlights an ongoing intransigence that must be addressed through a more system-oriented and transdisciplinary research agenda that seeks an embedded integration of public and private research approaches. This horizon scanning exercise thus set out the building blocks needed for future weed management research and practice; however, the challenge ahead is to identify effective ways in which sufficient research and implementation efforts can be directed towards these needs.

In vivo validation of spatio-temporal liver motion prediction from motion tracked on MR thermometry images.

PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) of the liver during free-breathing requires spatio-temporal prediction of the liver motion from partial motion observations. The study purpose is to evaluate the prediction accuracy for a realistic MRgFUS therapy scenario, namely for human in vivo data, tracking based on MR images routinely acquired during MRgFUS and in vivo deformations caused by the FUS probe. METHODS: In vivo validation of the motion model was based on a 3D breath-hold image and an interleaved acquisition of two MR slices. Prediction accuracy was determined with respect to manually annotated landmarks. A statistical population liver motion model was used for predicting the liver motion for not tracked regions. This model was individualized by mapping it to end-exhale 3D breath-hold images. Spatial correspondence between tracking and model positions was established by affine 3D-to-2D image registration. For spatio-temporal prediction, MR tracking results were temporally extrapolated. RESULTS: Performance was evaluated for 10 volunteers, of which 5 had a dummy FUS probe put on their abdomen. MR tracking had a mean (95 %) accuracy of 1.1 (2.4) mm. The motion of the liver on the evaluation MR slice was spatio-temporally predicted with an accuracy of 1.9 (4.4) mm for a latency of 216 ms. A simple translation model performed similarly (2.1 (4.8) mm) as the two MR slices were relatively close (mean 38 mm). Temporal prediction was important (10 % error reduction), while registration effects could only partially be assessed and showed no benefits. On average, motion magnitude, motion amplitude and breathing frequency increased by 24, 16 and 8 %, respectively, for the cases with FUS probe placement. This motion increase could be reduced by the spatio-temporal prediction. CONCLUSION: The study shows that tracking liver vessels on MR images, which are also used for MR thermometry, is a viable approach.

Assessing the distribution of sedimentary C40 carotenoids through time.

A comprehensive marine biomarker record of green and purple sulfur bacteria (GSB and PSB, respectively) is required to test whether anoxygenic photosynthesis represented a greater fraction of marine primary productivity during the Precambrian than the Phanerozoic, as current models of ocean redox evolution suggest. For this purpose, we analyzed marine rock extracts and oils from the Proterozoic to the Paleogene for C40 diagenetic products of carotenoid pigments using new analytical methods. Gas chromatography coupled with tandem mass spectrometry provides a new perspective on the temporal distributions of carotenoid biomarkers for phototrophic sulfur bacteria, specifically okenane, chlorobactane, and paleorenieratane. According to conventional paleoredox interpretations, this revised stratigraphic distribution of the GSB and PSB biomarkers implies that the shallow sunlit surface ocean (<24 m) became sulfidic more frequently in the geologic past than was previously thought. We reexamine whether there is evidence supporting a planktonic source of GSB and PSB pigments in marine systems or whether additional factors are required to explain the marine phototrophic sulfur bacteria record. To date, planktonic GSB and PSB and their pigments have been identified in restricted basins and lakes, but they have yet to be detected in the unrestricted, transiently sulfidic, marine systems. Based on modern observations, additional environmental factors, including basin restriction, microbial mats, or sediment transport, may be required to fully explain GSB and PSB carotenoids in the geologic record.

Arrival order among native plant functional groups does not affect invasibility of constructed dune communities.

Different arrival order scenarios of native functional groups to a site may influence both resource use during development and final community structure. Arrival order may then indirectly influence community resistance to invasion. We present a mesocosm experiment of constructed coastal dune communities that monitored biotic and abiotic responses to different arrival orders of native functional groups. Constructed communities were compared with unplanted mesocosms. We then simulated a single invasion event by bitou (Chrysanthemoides monilifera ssp. rotundata), a dominant exotic shrub of coastal communities. We evaluated the hypothesis that plantings with simultaneous representation of grass, herb and shrub functional groups at the beginning of the experiment would more completely sequester resources and limit invasion than staggered plantings. Staggered plantings in turn would offer greater resource use and invasion resistance than unplanted mesocosms. Contrary to our expectations, there were few effects of arrival order on abiotic variables for the duration of the experiment and arrival order was unimportant in final community invasibility. All planted mesocosms supported significantly more invader germinants and significantly less invader abundance than unplanted mesocosms. Native functional group plantings may have a nurse effect during the invader germination and establishment phase and a competitive function during the invader juvenile and adult phase. Arrival order per se did not affect resource use and community invasibility in our mesocosm experiment. While grass, herb and shrub functional group plantings will not prevent invasion success in restored communities, they may limit final invader biomass.

Treatment of intracerebral hemorrhage with tranexamic acid after thrombolysis with tissue plasminogen activator.

BACKGROUND: Thrombolytic treatment with intravenous tissue plasminogen activator (i.v. tPA) is the only FDA-approved therapy for acute ischemic stroke. There are risks associated with thrombolytics, including intracranial and extracranial hemorrhage and hypersensitivity reactions. Established treatment for post-tPA hemorrhage includes administration of blood products including cryoprecipitate, fresh frozen plasma, and platelets which have poorly established efficacy. Tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) have been studied as hemostatic therapies in post-operative hemorrhage, menorrhagia, intracranial hemorrhage (ICH), subarachnoid hemorrhage, and trauma patients. There is no reported literature on the use of TXA to reverse thrombolytic therapy with tPA. METHODS: This is a case report of a Jehovah's Witness patient who was unwilling to receive blood products after developing symptomatic ICH following i.v. tPA. He consequently received TXA for reversal of thrombolytic therapy. RESULTS: The patient received a total of 1.675 g of i.v. TXA within 3 h of finishing the iv tPA. Repeat brain imaging with computed tomography and magnetic resonance imaging revealed no further expansion of hemorrhages. CONCLUSION: TXA is an inexpensive medication which competitively inhibits the activation of plasminogen and can be given to reverse thrombolysis in the setting of hemorrhage after i.v. thrombolytic therapy.

Shared care of patients with ocular hypertension in the Community and Hospital Allied Network Glaucoma Evaluation Scheme (CHANGES).

AIMS: The Community and Hospital Allied Network Glaucoma Evaluation Scheme (CHANGES) used accredited community-based optometrists with a special interest (OSIs) in glaucoma to monitor ocular hypertensive (OHT) patients under virtual supervision of the Hospital Glaucoma Service (HGS). The purpose of this paper was to report the outcomes of the first completed community-based visit. METHODS: Eligible patients underwent a glaucoma consultant-led clinical examination before transfer to CHANGES. Individualised intraocular pressure (IOP) and follow-up time interval targets were set for each patient. OSIs used applanation tonometry, slit-lamp biomicroscopy, automated visual field testing and digital optic disc photography. The hospital-based glaucoma team evaluated the data virtually. Patients were referred back to the HGS according to specific criteria. RESULTS: One hundred and sixty eight OHT patients were invited to attend their first OSI appointment. Of these, 144 attended their appointment (attendance rate 85.7%). Outcomes of 130 patients with complete data sets are reported. Sixteen patients (12.3%) were referred back to the HGS due to IOP above target, new visual field defects and/or optic nerve changes. The glaucoma consultant retained eight patients (6.1%) within the HGS on the basis of definite or probable glaucomatous conversion. CONCLUSIONS: CHANGES freed up capacity within a busy HGS. However, improvements need to be made regarding non-attendance rates in the community. The relatively high one-year definite or probable conversion rate emphasises the importance of the comprehensive review of OHT patients and of hospital-led virtual supervision to maintain patient safety.

The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia.

BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy expenditure. This qualifies MC-4R blockade as an attractive mode of action for the treatment of cachexia. Based on this rationale, a novel series of small-molecule MC-4R antagonists was designed, from which the orally active compound BL-6020/979 (formerly known as SNT207979) emerged as the first promising development candidate showing encouraging pre-clinical efficacy and safety properties which are presented here. METHODS AND RESULTS: BL-6020/979 is an orally available, selective and potent MC-4R antagonist with a drug-like profile. It increased food intake and decreased energy expenditure in healthy wild-type but not in MC-4R deficient mice. More importantly, it ameliorated cachexia-like symptoms in the murine C26 adenocarcinoma model; with an effect on body mass and body composition and on the expression of catabolic genes. Moreover, BL-6020/979 showed antidepressant-like properties in the chronic mild stress model in rats and exhibits a favorable safety profile. CONCLUSION: The properties of BL-6020/979 demonstrated in animal models and presented here make it a promising candidate suitable for further development towards a first-in-class treatment option for cachexia that potentially opens up the opportunity to treat two hallmarks of the disease, i.e., decreased food intake and increased energy expenditure, with one drug.

Cerebral air emboli with atrial-esophageal fistula following atrial fibrillation ablation: a case report and review.

BACKGROUND: Atrial-esophageal fistula (AEF) is a rare and early complication of radiofrequency ablation for medically refractory atrial fibrillation, but has devastating consequences when the diagnosis is delayed or difficult to make. METHODS: Single case in a neurosciences critical care center. RESULTS: A 69-year-old man with significant cardiac and neurologic medical history who underwent atrial fibrillation ablation 50 days prior to admission to the neurocritical care unit presented with acute left-sided weakness and gram-positive bacterial sepsis. This is an exceptional case discussing the need for early detection of AEF presenting with sepsis, neurologic deficit along with complicated decision-making in the neurocritical care setting. His hospital course was complicated by acute stroke, left ventricular (LV) aneurysm with thrombus, gastrointestinal (GI) bleed discovered to be from left atrial esophageal fistula, and subsequent cerebral air emboli leading to death. CONCLUSIONS: This is the most delayed presentation of AEF following atrial fibrillation ablation reported in the literature to date. We emphasize the need for awareness of this complication even after such an unexpected time-frame postprocedure as well as the unintended complications of cerebral air emboli following upper endoscopy.

Can a community optometrist-based referral refinement scheme reduce false-positive glaucoma hospital referrals without compromising quality of care? The community and hospital allied network glaucoma evaluation scheme (CHANGES).

BACKGROUND/AIMS: To describe the design, activity, and quality of the referral refinement phase of a novel glaucoma shared-care scheme. METHODS: Eight Optometrists with a Specialist Interest in glaucoma (OSI) were trained to perform a community-based comprehensive glaucoma evaluation of low-risk glaucoma hospital referrals (only one/none of the following factors noted for either eye: abnormal optic disc, abnormal visual field, abnormal intraocular pressure (IOP; 22-28 mmHg or IOP asymmetry)) using equipment standardized to that of the hospital glaucoma service. RESULTS: One hundred and thirty-eight (27%) of a total of 512 glaucoma-related referrals were deemed 'low risk'. Their choice of OSI discharged 40 (35%). The consultant agreed (virtually) with the decision to discharge with 28 (70%) and disagreed with 12 (30%). Comparing findings between OSI and consultant for 99 referred patients, sensitivity, specificity, and negative predictive values for a suspicious optic disc were 78, 61, and 79%, respectively. For an IOP of >21 mmHg, they were 74, 85, and 90%, respectively. For an occludable anterior chamber angle (Van Herick's versus gonioscopy), they were 69, 88, and 94%, respectively. CONCLUSION: This referral refinement process can reduce numbers of false-positive referrals attending the hospital glaucoma service while retaining a relatively high level of examination quality.

Seroepidemiology as basis for design of a human papillomavirus vaccination program.

We have performed a serological survey of HPV type 16-antibody prevalence by age and sex in Sweden and used it as a basis for modelling the optimal vaccination strategies in this population. Samples of 3,317 subjects were tested for HPV16-specific antibodies. The observed age-specific seroprevalences along with sexual behaviour data were used to infer parameter values for a mathematical model representing Sweden and the preventive effect of possible strategies estimated. By the year 2055, vaccination of females starting at age 12 in 2008 was most efficient, estimated to prevent 5.8 million cumulative HPV16 infections. Catch-up programs had a strong additional preventive effect. Vaccination also targeting males increased protective effect by about 4%, but had lower preventive effect per vaccination given. Addition of an HPV serosurvey to existing models and data has enabled us to estimate effect of different vaccination strategies, optimized to the HPV epidemiology in our population.

Food-entrained rhythmic expression of PER2 and BMAL1 in murine megakaryocytes does not correlate with circadian rhythms in megakaryopoiesis.

BACKGROUND: Circadian rhythms control a vast array of biological processes in a broad spectrum of organisms. The contribution of circadian rhythms to the development of megakaryocytes and the regulation of platelet biology has not been defined. OBJECTIVES: This study tested the hypothesis that murine megakaryocytes exhibit hallmarks of circadian control. METHODS: Mice expressing a PER2::LUCIFERASE circadian reporter protein and C57BI/6 mice were used to establish if megakaryocytes expressed circadian genes in vitro and in vivo. Mice were also subjected to 3 weeks on a restricted feeding regime to separate food-entrained from light-entrained circadian rhythms. Quantitative real time polymerase chain reaction (PCR), flow cytometry and imunohistochemistry were employed to analyse gene expression, DNA content and cell-cycle behavior in megakaryocytes collected from mice over a 24-h period. RESULTS: Megakaryocytes exhibited rhythmic expression of the clock genes mPer2 and mBmal1 and circadian rhythms in megakaryopoiesis. mPer2 and mBmal1 expression phase advanced 8 h to coincide with the availability of food; however, food availability had a more complex effect on megakaryopoiesis, leading to a significant overall increase in megakaryocyte ploidy levels and cell-cycle activity. CONCLUSIONS: Normal megakaryopoiesis requires synchrony between food- and light-entrained circadian oscillators.

Galantamine effects on memory, spatial cue utilization, and neurotrophic factors in aged female rats.

Galantamine is an acetylcholine esterase inhibitor that has been approved for use in Alzheimer's disease. However, even though clinical studies indicate efficacy in attenuating some of the symptoms associated with the disease, there are a paucity of studies evaluating the effects of galantamine administration on cognitive performance and brain parameters in aged rats. Further, because all previous animal studies using galantamine have been performed in male rats, there is no information on how females respond to galantamine treatment. Therefore, we studied the effects of 0.3, 0.6, and 1.2 mg/kg/day galantamine in 20-month-old female rats in terms of performance on the working and reference memory water radial arm maze task. Galantamine did not influence maze performance. Furthermore, a probe trial procedure to determine extra-maze cue utilization while solving the water radial arm maze established that aged female rats utilized extramaze cues, and that they did not rely on a nonspatial chaining strategy to locate hidden platforms. Galantamine treatment had no effect on use of extramaze cues or chaining. In addition, there were no significant changes in neurotrophin levels in the frontal cortex, entorhinal cortex, hippocampus, or basal forebrain after galantamine administration. Therefore, the data reported here suggest that aged animals do utilize spatial strategies for solving a working memory task, but galantamine has no appreciable effects on this task, at least not at the doses tested.

Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland.

Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed.