Outer apoplastic barriers in roots: prospects for abiotic stress tolerance.

Floods and droughts are becoming more frequent as a result of climate change and it is imperative to find ways to enhance the resilience of staple crops to abiotic stresses. This is crucial to sustain food production during unfavourable conditions. Here, we analyse the current knowledge about suberised and lignified outer apoplastic barriers, focusing on the functional roles of the barrier to radial O2 loss formed as a response to soil flooding and we discuss whether this trait also provides resilience to multiple abiotic stresses. The barrier is composed of suberin and lignin depositions in the exodermal and/or sclerenchyma cell walls. In addition to the important role during soil flooding, the barrier can also restrict radial water loss, prevent phytotoxin intrusion, salt intrusion and the main components of the barrier can impede invasion of pathogens in the root. However, more research is needed to fully unravel the induction pathway of the outer apoplastic barriers and to address potential trade-offs such as reduced nutrient or water uptake. Nevertheless, we suggest that the outer apoplastic barriers might act as a jack of all trades providing tolerance to multiple abiotic and/or biotic stressors.

L-arginine and aged garlic extract for the prevention of migraine: a study protocol for a randomised, double-blind, placebo-controlled, phase-II trial (LARGE trial).

BACKGROUND: Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines. METHODS: The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention. DISCUSSION: The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated. TRIAL REGISTRATION: The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.

Leading trait dimensions in flood-tolerant plants.

BACKGROUND AND AIMS: While trait-based approaches have provided critical insights into general plant functioning, we lack a comprehensive quantitative view on plant strategies in flooded conditions. Plants adapted to flooded conditions have specific traits (e.g. root porosity, low root/shoot ratio and shoot elongation) to cope with the environmental stressors including anoxic sediments, and the subsequent presence of phytotoxic compounds. In flooded habitats, plants also respond to potential nutrient and light limitations, e.g. through the expression of leaf economics traits and size-related traits, respectively. However, we do not know whether and how these trait dimensions are connected. METHODS: Based on a trait dataset compiled on 131 plant species from 141 studies in flooded habitats, we quantitatively analysed how flooding-induced traits are positioned in relation to the other two dominant trait dimensions: leaf economics traits and size-related traits. We evaluated how these key trait components are expressed along wetness gradients, across habitat types and among plant life forms. KEY RESULTS: We found that flooding-induced traits constitute a trait dimension independent from leaf economics traits and size-related traits, indicating that there is no generic trade-off associated with flooding adaptations. Moreover, individual flooding-induced traits themselves are to a large extent decoupled from each other. These results suggest that adaptation to stressful environments, such as flooding, can be stressor specific without generic adverse effects on plant functioning (e.g. causing trade-offs on leaf economics traits). CONCLUSIONS: The trait expression across multiple dimensions promotes plant adaptations and coexistence across multifaceted flooded environments. The decoupled trait dimensions, as related to different environmental drivers, also explain why ecosystem functioning (including, for example, methane emissions) are species and habitat specific. Thus, our results provide a backbone for applying trait-based approaches in wetland ecology by considering flooding-induced traits as an independent trait dimension.

The Pain Medicine Curriculum Framework-structured integration of pain medicine education into the medical curriculum.

Medical practitioners play an essential role in preventing pain, conducting comprehensive pain assessments, as well as promoting evidence-based practices. There is a need for the development of innovative, interprofessional and integrated pain medicine curricula for medical students. The Pain Medicine Curriculum Framework (PMCF) was developed to conceptualise a purposeful approach to the complex process of curriculum change and to prioritise the actions needed to address the gaps in pain medicine education. The PMCF comprises four dimensions: (1) future healthcare practice needs; (2) competencies and capabilities required of graduates; (3) teaching, learning and assessment methods; and (4) institutional parameters. Curricula need to meet the requirements of registration and accreditation bodies, but also equip graduates to serve in their particular local health system while maintaining the fundamental standards and values of these institutions. The curriculum needs to connect knowledge with experience and practice to be responsive to the changing needs of the increasingly complex health system yet adaptable to patients with pain in the local context. Appropriate learning, teaching and assessment strategies are necessary to ensure that medical practitioners of the future develop the required knowledge, skills and attitudes to treat the diverse needs of patients' experiencing pain. The historical, political, social and organisational values of the educational institution will have a significant impact on curriculum design. A more formalised approach to the development and delivery of a comprehensive pain medicine curriculum is necessary to ensure that medical students are adequately prepared for their future workplace responsibilities.

msGBS: A new high-throughput approach to quantify the relative species abundance in root samples of multispecies plant communities.

Plant interactions are as important belowground as aboveground. Belowground plant interactions are however inherently difficult to quantify, as roots of different species are difficult to disentangle. Although for a couple of decades molecular techniques have been successfully applied to quantify root abundance, root identification and quantification in multispecies plant communities remains particularly challenging. Here we present a novel methodology, multispecies genotyping by sequencing (msGBS), as a next step to tackle this challenge. First, a multispecies meta-reference database containing thousands of gDNA clusters per species is created from GBS derived High Throughput Sequencing (HTS) reads. Second, GBS derived HTS reads from multispecies root samples are mapped to this meta-reference which, after a filter procedure to increase the taxonomic resolution, allows the parallel quantification of multiple species. The msGBS signal of 111 mock-mixture root samples, with up to 8 plant species per sample, was used to calculate the within-species abundance. Optional subsequent calibration yielded the across-species abundance. The within- and across-species abundances highly correlated (R2 range 0.72-0.94 and 0.85-0.98, respectively) to the biomass-based species abundance. Compared to a qPCR based method which was previously used to analyse the same set of samples, msGBS provided similar results. Additional data on 11 congener species groups within 105 natural field root samples showed high taxonomic resolution of the method. msGBS is highly scalable in terms of sensitivity and species numbers within samples, which is a major advantage compared to the qPCR method and advances our tools to reveal hidden belowground interactions.

Battlefield acupuncture added no benefit as an adjunct analgesic in emergency department for abdominal, low back or limb trauma pain.

OBJECTIVES: To ascertain whether ear acupuncture (modified Battlefield technique) as an adjunct (Adj-BFA) to standard analgesia care (SAC) significantly reduces pain scores compared with sham acupuncture (Adj-Sham) or SAC alone, when delivered by medical and nursing practitioners in an ED. METHODS: A randomised controlled trial using a convenience sample of 90 patients attending an ED with acute abdominal, limb trauma or low back pain were allocated to three treatment arms: Adj-BFA, Adj-Sham and SAC. The primary outcome of change in pain scores out-of-10 (NPRS-10) from triage were assessed immediately after intervention and at 1 and 2 h post-intervention. Secondary outcomes were the percentage of patients reporting 'adequate analgesia' or ≥30% reduction in pain score, analgesic medication use (in morphine equivalent dose [milligrammes]), analgesics and needle costs (Australian dollars), adverse effects and patient satisfaction (Likert scale). RESULTS: There was no significant difference in pain scores (P = 0.582) or secondary outcomes measures between Adj-BFA, Adj-Sham and SAC. CONCLUSION: The present study on 90 patients did not show a significant difference in analgesia outcomes in the first 2 h using Adj-BFA for acute pain in the ED, and there were no significant differences for secondary outcomes between treatment arms. Given the mixed results of recent BFA trials, further research using the original BFA technique on different painful conditions, as either stand-alone or as-adjunct to non-opioid analgesia are needed before BFA can be recommended as a technique for acute pain management in the ED.

Global patterns of the leaf economics spectrum in wetlands.

The leaf economics spectrum (LES) describes consistent correlations among a variety of leaf traits that reflect a gradient from conservative to acquisitive plant strategies. So far, whether the LES holds in wetland plants at a global scale has been unclear. Using data on 365 wetland species from 151 studies, we find that wetland plants in general show a shift within trait space along the same common slope as observed in non-wetland plants, with lower leaf mass per area, higher leaf nitrogen and phosphorus, faster photosynthetic rates, and shorter leaf life span compared to non-wetland plants. We conclude that wetland plants tend to cluster at the acquisitive end of the LES. The presented global quantifications of the LES in wetland plants enhance our understanding of wetland plant strategies in terms of resources acquisition and allocation, and provide a stepping-stone to developing trait-based approaches for wetland ecology.

A Paradoxical Vasodilatory Nutraceutical Intervention for Prevention and Attenuation of Migraine-A Hypothetical Review.

Studies suggest that migraine pain has a vascular component. The prevailing dogma is that peripheral vasoconstriction activates baroreceptors in central, large arteries. Dilatation of central vessels stimulates nociceptors and induces cortical spreading depression. Studies investigating nitric oxide (NO) donors support the indicated hypothesis that pain is amplified when acutely administered. In this review, we provide an alternate hypothesis which, if substantiated, may provide therapeutic opportunities for attenuating migraine frequency and severity. We suggest that in migraines, heightened sympathetic tone results in progressive central microvascular constriction. Suboptimal parenchymal blood flow, we suggest, activates nociceptors and triggers headache pain onset. Administration of NO donors could paradoxically promote constriction of the microvasculature as a consequence of larger upstream central artery vasodilatation. Inhibitors of NO production are reported to alleviate migraine pain. We describe how constriction of larger upstream arteries, induced by NO synthesis inhibitors, may result in a compensatory dilatory response of the microvasculature. The restoration of central capillary blood flow may be the primary mechanism for pain relief. Attenuating the propensity for central capillary constriction and promoting a more dilatory phenotype may reduce frequency and severity of migraines. Here, we propose consideration of two dietary nutraceuticals for reducing migraine risk: L-arginine and aged garlic extracts.

Reduction in Migraine and Headache Frequency and Intensity With Combined Antioxidant Prophylaxis (N-acetylcysteine, Vitamin E, and Vitamin C): A Randomized Sham-Controlled Pilot Study.

OBJECTIVE: To investigate the preventive effects of a combined antioxidant drug (N-acetylcysteine, vitamin E, and vitamin C [NEC]) on migraine outcomes. Migraine is characterized by increased oxidative stress and neurogenic inflammation in the brain; therefore, antioxidants may have a migraine preventive effect. DESIGN: Randomized, double-blind, sham-controlled pilot study. SETTING: Australian community. SUBJECTS: Adults reporting 2 to 8 migraines per month for at least a year. METHODS: After a 1-month baseline period, 35 subjects completed 3 months of treatment with NEC (n = 19) or sham (n = 16) capsules. The primary outcome was the difference in mean number of headaches per month between baseline and final month of the trial for NEC and sham groups; secondary outcomes are listed below. RESULTS: For NEC there was a significant decrease in mean number of headaches by 3.0 per month (P = 0.004) compared with 1.4 for sham (P = 0.073); there was no significant difference in these changes between the 2 groups (P = 0.052). Average monthly headache (P = 0.041) and migraine frequency (P = 0.018) were significantly less for NEC vs. sham. In NEC subjects, there was a significant decrease in average monthly migraine days (-3.1), moderate/severe headache days (-3.2), migraine duration, headache pain scores, and acute headache medication use. CONCLUSIONS: This is the first randomized controlled trial to find that combined antioxidant therapy with NEC reduces headaches and migraines in adult migraineurs. Given the limitations of this pilot study, an adequately powered randomized controlled trial is planned to further investigate antioxidant prophylaxis in migraine.

PET-Based Human Dosimetry of 68Ga-NODAGA-Exendin-4, a Tracer for ß-Cell Imaging.

68Ga-NODAGA-exendin-4 is a promising tracer for ß-cell imaging using PET/CT. Possible applications include preoperative visualization of insulinomas and discrimination between focal and diffuse forms of congenital hyperinsulinism. There is also a significant role for this tracer in extending our knowledge on the role of ß-cell mass in the pathophysiology of type 1 and type 2 diabetes by enabling noninvasive quantification of tracer uptake as a measure for ß-cell mass. Calculating radiation doses from this tracer is important to assess its safety for use in patients (including young children) with benign diseases and healthy individuals. Methods: Six patients with hyperinsulinemic hypoglycemia were included. After intravenous injection of 100 MBq of the tracer, 4 successive PET/CT scans were obtained at 30, 60, 120, and 240 min after injection. Tracer activity in the pancreas, kidneys, duodenum, and remainder of the body were determined, and time-integrated activity coefficients for the measured organs were calculated. OLINDA/EXM software, version 1.1, was applied to calculate radiation doses using the reference adult male and female models and to estimate radiation doses to children. Results: The mean total effective dose for adults was very low (0.71 ± 0.07 mSv for a standard injected dose of 100 MBq). The organ with the highest absorbed dose was the kidney (47.3 ± 10.2 mGy/100 MBq). The estimated effective dose was 2.32 ± 0.32 mSv for an injected dose of 20 MBq in newborns. This dose decreased to 0.77 ± 0.11 mSv/20 MBq for 1-y-old children and 0.59 ± 0.05 mSv for an injected dose of 30 MBq in 5-y-old children. Conclusion: Our human PET/CT-based dosimetric calculations show that the effective radiation doses from the novel tracer 68Ga-NODAGA-exendin-4 are very low for adults and children. The doses are lower than reported for other polypeptide tracers such as somatostatin analogs (2.1-2.6 mSv/100 MBq) and are beneficial for application as a research tool, especially when repeated examinations are needed.

Expression of Cutaneous Beta-2 Adrenoceptors Is Similar in Patients with Complex Regional Pain Syndrome and Pain-Free Controls.

OBJECTIVE: Studies in rodents suggest that cutaneous beta-2 adrenoceptors (ß2-ARs) mediate inflammation and pain after tissue injury and that inflammation and peripheral nerve injury trigger increases in neuronal ß2-AR expression. Hence, the aim of this study was to investigate the expression of ß2-ARs on keratinocytes and dermal nerves in patients with complex regional pain syndrome (CRPS). DESIGN, SETTING, AND SUBJECTS: Fifty-eight patients with CRPS were recruited for this study. In addition, skin biopsies were obtained from 13 pain-free women and three pain-free men of similar age and sex distribution as the patients. METHODS: Quantitative sensory tests for assessing sensitivity to pressure, pinprick, light touch, heat, and cold were administered, and skin biopsies were obtained from the affected and contralateral limbs. Skin biopsies were also obtained from a similar site on the dorsal hand or foot of pain-free controls. Immunohistochemistry and confocal microscopy were used to identify ß2-ARs on keratinocytes, dermal nerves, and blood vessels in the skin samples. RESULTS: The distribution of ß2-ARs in keratinocytes and nerves was similar in the affected and contralateral limbs of patients and was similar for target cells in patients and controls. However, elevated ß2-AR expression in reticular nerve bundles was associated with heightened sensitivity to heat pain. CONCLUSIONS: These findings do not support a major role of cutaneous ß2-ARs in CRPS. However, activation of neuronal ß2-ARs may contribute to thermal hyperalgesia in a subgroup of patients. Whether activation of ß2-ARs on keratinocytes mediates inflammation early in the course of CRPS requires further investigation.

Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study.

Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC). METHODS: Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5-26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions). RESULTS: RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml). CONCLUSION: Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT.

Ethylene-mediated nitric oxide depletion pre-adapts plants to hypoxia stress.

Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops.

Effects of extreme rainfall events are independent of plant species richness in an experimental grassland community.

Global climate models predict more frequent periods of drought stress alternated by heavier, but fewer rainfall events in the future. Biodiversity studies have shown that such changed drought stress may be mitigated by plant species richness. Here, we investigate if grassland communities, differing in species richness, respond differently to climatic extremes within the growing season. In a 3-year outdoor mesocosm experiment, four grassland species in both monoculture and mixture were subjected to a rainfall distribution regime with two levels: periods of severe drought in the summer intermitted by extreme rainfall events versus regular rainfall over time. Both treatments received the same amount of water over the season. Extreme rainfall combined with drought periods resulted in a 15% decrease in aboveground biomass in the second and third year, compared to the regular rainfall regime. Root biomass was also reduced in the extreme rainfall treatment, particularly in the top soil layer (- 40%). All species developed higher water use efficiencies (less negative leaf δ13C) in extreme rainfall than in regular rainfall. These responses to the rainfall/drought treatment were independent of species richness, although the mixtures were on an average more productive in terms of biomass than the monocultures. Our experimental results suggest that mixtures are similarly able to buffer these within-season rainfall extremes than monocultures, which contrasts with findings in the studies on natural droughts. Our work demonstrates the importance of investigating the interactions between rainfall distribution and drought periods for understanding effects of climate change on plant community performance.

Parallels between lumbosacral radiculopathy and complex regional pain syndrome: α1-adrenoceptor upregulation, reduced dermal nerve fibre density, and hemisensory disturbances in postsurgical sciatica.

Residual lower-limb pain after low back surgery (postsurgical sciatica) and complex regional pain syndrome (CRPS) involving a lower limb are separate conditions but may share some mechanisms (eg, tissue inflammation, neuroimmune disturbances, and central neuroplasticity). As adrenergically evoked pain contributes, in part, to CRPS, whether an adrenergic mechanism also contributes to postsurgical sciatica was investigated in this study. Immunohistochemistry was used to identify α1-adrenoceptors (α1-AR) on nerve fibres and other targets in the affected and contralateral skin of 25 patients with postsurgical sciatica, and α1-AR expression was investigated in relation to pain and pinprick hyperalgesia after intradermal injection of the α1-AR agonist phenylephrine. In addition, quantitative sensory testing was performed on all 4 limbs and on each side of the forehead. α1-AR expression was greater in keratinocytes (but not blood vessels or nerve fibres) in the symptomatic than contralateral leg, and dermal nerve fibre density was reduced in both legs. However, distal adrenergic involvement in pain in postsurgical sciatica seems unlikely, as neither heightened α1-AR expression in keratinocytes nor reduced dermal nerve fibre density were associated with pain or hyperalgesia to intradermal phenylephrine injection. Sensitivity to pressure-pain, pinprick, and cold-pain was greater in the ipsilateral than contralateral forehead of the entire cohort, but sensory disturbances were most pronounced in patients with additional CRPS-like features. Together, these findings suggest that bilateral distal neuropathy and central neuroplastic changes are involved not only in the pathophysiology of CRPS but also in postsurgical sciatica. This may have treatment implications for patients with postsurgical sciatica.

Symmetry and spatial distribution of muscle glucose uptake in the lower limbs during walking measured using FDG-PET.

PURPOSE: This study aimed to elucidate whether muscle activity (in terms of glucose uptake) between the legs can be considered symmetrical during walking. Furthermore, we aimed to determine whether the [18F]-fluorodeoxyglucose was distributed heterogeneously throughout each muscle, and if so, whether areas of high uptake would be clustered. METHODS: Ten healthy participants walked on a treadmill at self-selected comfortable walking speed for a total of 90 minutes, 60 minutes before and 30 minutes after intravenous injection of 50 MBq [18F]-fluorodeoxyglucose. Thereafter, a positron emission tomography/computed tomography scan of the lower limb was acquired. Three-dimensional muscle contours of 78 (= 39x2) muscles of the left and right lower limb were semi-automatically determined from magnetic resonance imaging scans. After non-rigid registration, those muscle contours were used to extract [18F]-fluorodeoxyglucose uptake from the positron emission tomography scans. RESULTS: Large asymmetries were observed in the lower leg muscles (e.g. median absolute asymmetry index of 42% in the gastrocnemius medialis) and in the gluteus minimus (30% asymmetry) and gluteus medius (15% asymmetry), whereas the uptake in the thighs was relatively symmetrical between the limbs (<6% asymmetry). These were not related to limb-dominance nor to inter-limb differences in muscle volume. The [18F]-fluorodeoxyglucose distribution was not distributed normally; most voxels had a relatively low standardized uptake value, and a minority of voxels had a relatively high standardized uptake value. The voxels with higher [18F]-fluorodeoxyglucose uptake were distributed heterogeneously; they were clustered in virtually all muscles. CONCLUSION: The findings in this study challenge the common assumption of symmetry in muscle activity between the limbs in healthy subjects. The clustering of voxels with high uptake suggests that even in this prolonged repetitive task, different spatial regions of muscles contribute differently to walking than others.

Exploring assessment of medical students' competencies in pain medicine-A review.

INTRODUCTION: Considering the continuing high prevalence and public health burden of pain, it is critical that medical students are equipped with competencies in the field of pain medicine. Robust assessment of student expertise is integral for effective implementation of competency-based medical education. OBJECTIVE: The aim of this review was to describe the literature regarding methods for assessing pain medicine competencies in medical students. METHOD: PubMed, Medline, EMBASE, ERIC, and Google Scholar, and BEME data bases were searched for empirical studies primarily focusing on assessment of any domain of pain medicine competencies in medical students published between January 1997 and December 2016. RESULTS: A total of 41 studies met the inclusion criteria. Most assessments were performed for low-stakes summative purposes and did not reflect contemporary theories of assessment. Assessments were predominantly undertaken using written tests or clinical simulation methods. The most common pain medicine education topics assessed were pain pharmacology and the management of cancer and low-back pain. Most studies focussed on assessment of cognitive levels of learning as opposed to more challenging domains of demonstrating skills and attitudes or developing and implementing pain management plans. CONCLUSION: This review highlights the need for more robust assessment tools that effectively measure the abilities of medical students to integrate pain-related competencies into clinical practice. A Pain Medicine Assessment Framework has been developed to encourage systematic planning of pain medicine assessment at medical schools internationally and to promote continuous multidimensional assessments in a variety of clinical contexts based on well-defined pain medicine competencies.

Alternative transient states and slow plant community responses after changed flooding regimes.

Climate change will have large consequences for flooding frequencies in freshwater systems. In interaction with anthropogenic activities (flow regulation, channel restoration and catchment land-use) this will both increase flooding and drought across the world. Like in many other ecosystems facing changed environmental conditions, it remains difficult to predict the rate and trajectory of vegetation responses to changed conditions. Given that critical ecosystem services (e.g. bank stabilization, carbon subsidies to aquatic communities or water purification) depend on riparian vegetation composition, it is important to understand how and how fast riparian vegetation responds to changing flooding regimes. We studied vegetation changes over 19 growing seasons in turfs that were transplanted in a full-factorial design between three riparian elevations with different flooding frequencies. We found that (a) some transplanted communities may have developed into an alternative stable state and were still different from the target community, and (b) pathways of vegetation change were highly directional but alternative trajectories did occur, (c) changes were rather linear but faster when flooding frequencies increased than when they decreased, and (d) we observed fastest changes in turfs when proxies for mortality and colonization were highest. These results provide rare examples of alternative transient trajectories and stable states under field conditions, which is an important step towards understanding their drivers and their frequency in a changing world.