Unlocking ensemble ecosystem modelling for large and complex networks

The potential effects of conservation actions on threatened species can be predicted using ensemble ecosystem models. These model ensembles commonly assume stable coexistence of species in the absence of available data. However, existing ensemble-generation methods become computationally inefficient as the size of the ecosystem network increases, preventing larger networks from being studied. We present a novel sequential Monte Carlo sampling approach for ensemble generation that is orders of magnitude faster than existing approaches. We demonstrate that the methods produce equivalent parameter inferences, model predictions, and tightly constrained parameter combinations using a novel sensitivity analysis method. For one case study, we demonstrate a speed-up from 108 days to 6 hours, while maintaining equivalent ensembles. Now, for the first time, larger and more realistic networks can be practically simulated

Sensory profiles in women with neuropathic pain after breast cancer surgery

Purpose We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine). Methods 104 patients with at least "probable" NP in the surgical area were included. All patients had been treated for breast cancer 4-9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group. Results Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain. Conclusions Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.Peer reviewe

Respuesta del cultivo de maíz a la fertilización nitrogenada en la pampa ondulada, campañas 1980-81 - 1983-84 : I- análisis de los resultados

p.45-64Se presentan los resultados correspondientes a los experimentos de campo realizados a lo largo de las cuatro últimas campañas agrícolas dentro del marco del Programa de Investigación Experimental sobre Fertilización en el cultivo de maíz. La dosis de nutrientes estudiadas fueron de 0,60 y 120 kg N-ha (Campaña 1980-81) y 0,40 y 80 kg N-ha (restantes campañas), mientras que predominaron los materiales genéticos Dekalb, Cargill y Morgan. La red de ensayos, ubicada en la Pampa Ondulada, cubrió 31 situaciones sometidas a diversas combinaciones de factores culturales, edáficos y climáticos los que sufrieron una marcada variación a lo largo de los distintos años. Variaciones concomitantes fueron registradas tanto en el promedio de los rendimientos del tratamiento testigo (70, 61, 59 y 54 qq-ha, en cada uno de los respectivos años), como en la eficiencia de la primera dosis (7,8; 15,1; 10,9 y 15,3;respectivamente). Se determinó, a través del análisis de regresión del rendimiento en función de la dosis de N que el modelo parabólico presentó, en relación a otros modelos, el mejor ajuste a los datos individuales. Sin embargo, al efectuar un análisis de la población total de ensayos no fue posible obtener un buen ajuste a través de los modelos estudiados. Se demuestra finalmente la necesidad de elaborar modelos multivariados para explicar el hecho de que al pasar de la población de ensayos con respuesta significativa a los restantes, tanto los promedios de la eficiencia como del rendimiento del testigo presentan una marcada discontinuidad (de más de 20 a menos de 6 y de 51 a 69 qq-ha, respectivamente)

Analysis of sloppiness in model simulations: unveiling parameter uncertainty when mathematical models are fitted to data

This work introduces a Bayesian approach to assess the sensitivity of model outputs to changes in parameter values, constrained by the combination of prior beliefs and data. This novel approach identifies stiff parameter combinations that strongly affect the quality of the model-data fit while simultaneously revealing which of these key parameter combinations are informed primarily from the data or are also substantively influenced by the priors. We focus on the very common context in complex systems where the amount and quality of data are low compared to the number of model parameters to be collectively estimated, and showcase the benefits of our technique for applications in biochemistry, ecology, and cardiac electrophysiology. We also show how stiff parameter combinations, once identified, uncover controlling mechanisms underlying the system being modeled and inform which of the model parameters need to be prioritized in future experiments for improved parameter inference from collective model-data fitting

Protocol for a systematic review of guidelines for rigour in the design, conduct and analysis of biomedical experiments involving laboratory animals

Objective: Within the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Additionally, several groups of experts across the biomedical spectrum have published experience and opinion-based guidelines and guidance on potential standardized reporting. While all these guidelines cover reporting of experiments, an important step prior to this should be rigours planning and conduction of studies. The aim of this systematic review is to identify and harmonize existing experimental design, conduct and analysis guidelines relating to internal validity and reproducibility of preclinical animal research. The review will also identify literature describing risks of bias pertaining to the design, conduct and analysis of preclinical biomedical research. Search strategy: PubMed, Embase and Web of Science will be searched systematically to identify guidelines published in English language in peer-reviewed journals before January 2018 (box 1). All articles or systematic reviews in English language that describe or review guidelines on the internal validity and reproducibility of animal studies will be included. Google search for guidelines published on the websites of major funders and professional organisations can be found in (Box 2). Screening and annotation: Unique references will be screened in two phases: screening for eligibility based on title and abstract, followed by screening for definitive inclusion based on full text. Screening will be performed in SyRF (http://syrf.org.uk). Each reference will be randomly presented to two independent reviewers. Disagreements between reviewers will be resolved by additional screening of the reference by a third, senior researcher. Data management and reporting: All data, including extracted text and guidelines, will be stored in the SyRF platform. Elements of the included guidelines will be identified using a standardized extraction form. Reporting will follow the PRISMA guidelines as far as applicable

Improve Management of acute heart failure with ProcAlCiTonin in EUrope:results of the randomized clinical trial IMPACT EU Biomarkers in Cardiology (BIC) 18

Aim: To determine whether initiation of antibiotic therapy (ABX) by procalcitonin (PCT) within 8 h of admission in patients presenting to the emergency department with symptoms and signs of acute heart failure (AHF) and elevated natriuretic peptides would improve clinical outcomes. Methods and results: The study was a randomized multicentre clinical trial conducted at 16 sites in Europe. Patients were randomized to either a PCT-guided strategy or standard care. Patients with PCT-guided strategy (n = 370) had ABX initiated if PCT was > 0.2 μg/L. Patients with standard care (n = 372) had AHF care in accordance with published guidelines without PCT. The primary endpoint was 90-day all-cause mortality. Pre-specified secondary endpoints included 30-day all-cause mortality and readmission and rate of pneumonia. The Data Safety and Review Committee recommended stopping the study for futility when 762 of the planned 792 patients had been enrolled. A total of 742 patients could be analysed. Patients were elderly (median age: 77 years), 38% were women, and had typical signs and symptoms of AHF. All-cause mortality at 90 days was 10.3% in the PCT-guided group vs. 8.2% in standard care (P = 0.316). Thirty-day readmission was significantly higher in the PCT-guided group vs. standard care but the difference vanished until day 90. The rate of pneumonia was overall low (7.5%) and not different between groups. Conclusions: In patients with AHF, a strategy of PCT-guided initiation of ABX was not more effective than a standard care strategy in improving clinical outcomes

Sensory bedside testing: a simple stratification approach for sensory phenotyping

Introduction: Stratification of patients according to the individual sensory phenotype has been suggested a promising method to identify responders for pain treatment. However, many state-of-the-art sensory testing procedures are expensive or time-consuming. Objectives: Therefore, this study aimed to present a selection of easy-to-use bedside devices. Methods: In total, 73 patients (39 m/34 f) and 20 controls (11 m/9 f) received a standardized laboratory quantitative sensory testing (QST) and a bedside-QST. In addition, 50 patients were tested by a group of nonexperienced investigators to address the impact of training. The sensitivity, specificity, and receiver-operating characteristics were analyzed for each bedside-QST parameter as compared to laboratory QST. Furthermore, the patients’ individual sensory phenotype (ie, cluster) was determined using laboratory QST, to select bedside-QST parameters most indicative for a correct cluster allocation. Results: The bedside-QST parameters “loss of cold perception to 22˚C metal,” “hypersensitivity towards 45˚C metal,” “loss of tactile perception to Q-tip and 0.7 mm CMS hair,” as well as “the allodynia sum score” indicated good sensitivity and specificity (ie, ≳70%). Results of interrater variability indicated that training is necessary for individual parameters (ie, CMS 0.7). For the cluster assessment, the respective bedside quantitative sensory testing (QST) parameter combination indicated the following agreements as compared to laboratory QST stratification: excellent for “sensory loss” (area under the curve [AUC] 5 0.91), good for “thermal hyperalgesia” (AUC 5 0.83), and fair for “mechanical hyperalgesia” (AUC 5 0.75). Conclusion: This study presents a selection of bedside parameters to identify the individual sensory phenotype as cost and time efficient as possible

Data-driven recommendations for enhancing real-time natural hazard warnings, communication, and response

The effectiveness and adequacy of natural hazard warnings hinges on the availability of data and its transformation into actionable knowledge for the public. Real-time warning communication and emergency response therefore need to be evaluated from a data science perspective. However, there are currently gaps between established data science best practices and their application in supporting natural hazard warnings. This Perspective reviews existing data-driven approaches that underpin real-time warning communication and emergency response, highlighting limitations in hazard and impact forecasts. Four main themes for enhancing warnings are emphasised: (i) applying best-practice principles in visualising hazard forecasts, (ii) data opportunities for more effective impact forecasts, (iii) utilising data for more localised forecasts, and (iv) improving data-driven decision-making using uncertainty. Motivating examples are provided from the extensive flooding experienced in Australia in 2022. This Perspective shows the capacity for improving the efficacy of natural hazard warnings using data science, and the collaborative potential between the data science and natural hazards communities

Pain thresholds and intensities of CRPS type I and neuropathic pain in respect to sex

Abstract Background and aims Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers. Methods QST data of 1252 patients (669 female, 583 male) with PNI (n=342), PNP (n=571) or CRPS (n=339), and average pain intensity reports from previously published studies were included. Absolute and z-values (adjusted for age and body region) of cold, heat, pressure (PPT) and pinprick pain thresholds were compared in generalized linear models with aetiology, duration of underlying pain disease and average pain intensity as fixed effects. Results Average pain intensity during the past four weeks did not differ between women and men, in both mean and range. In women absolute pain thresholds for cold, heat and pinprick were lower than in males across all diagnoses (pPeer reviewe

Evaluation of Postsurgical Hyperalgesia and Sensitization After Open Inguinal Hernia Repair: A Useful Model for Neuropathic Pain?

Cutaneous mechanical hyperalgesia can be induced in healthy volunteers in early phase analgesic studies to model central sensitization, a key mechanism of persistent pain. However, such hyperalgesia is short-lived (a matter of hours), and is used only for assessing only single drug doses. In contrast, postsurgical peri-incisional hyperalgesia may be more persistent and hence be a more useful model for the assessment of the efficacy of new analgesics. We undertook quantitative sensory testing in 18 patients at peri-incisional and nonoperated sites before open inguinal hernia repair and up to the 24th postsurgical week. The spatial extent of punctate hyperalgesia and brush allodynia at the peri-incisional site were greatest at weeks 2 and 4, but had resolved by week 24. Heat allodynia, suggestive of local inflammation or peripheral sensitization, was not observed; instead, there were deficits in cold and heat sensory detection that persisted until week 24. The findings suggest that central sensitization contributes significantly to mechanical hyperalgesia at the peri-incisional site. The prolonged duration of hyperalgesia would be advantageous as a pain model, but there was considerable variability of mechanical hyperalgesia in the cohort; the challenges of recruitment may limit its use to small, early phase analgesic studies. PERSPECTIVE: Peri-incisional mechanical hyperalgesia persists for ≥4 weeks after open inguinal hernia repair and reflects central sensitization; this may have usefulness as a model of chronic pain to assess the potential of antineuropathic analgesics.Unrestricted educational grant from GlaxoSmithKline U