EFFECT OF CONSERVATION PRACTICES ON FUNCTIONAL DIVERSITY AND ASSEMBLY OF WEED COMMUNITIES: A DATABASE OF FUNCTIONAL TRAITS

The incorporation of conservation agriculture techniques (e.g. reduced tillage and green manures) in organic farming systems brings many benefits to the environment and reduces energy use (Holland, 2004). One of the main drawbacks of the use of reduced tillage is the potential increase in weed infestation and shifts in the weed community composition, sometimes to the benefit of more difficult-to-control species (Bàrberi, 2002; Peigné et al., 2007; Sans et al., 2011). However, weeds have an important role in maintaining farmland functional biodiversity (Bàrberi et al, 2010; Caballero et al., 2010), and this should be balanced with their potential negative impact on crop yield and quality. Within the frame of the European project “Reduced tillage and green manures for sustainable cropping systems” (TILMAN-ORG), in 2012 we started a study with the aim of evaluating the effects of conservation agricultural methods on functional attributes of weed communities, taking into account both the potential detrimental effects of weeds on crop growth and yield and the potential ecological services or dis-services. Knowledge on the outcome of positive and negative effects will be useful in the context of evaluating soil conservation practices in organic farming. In this paper we highlight the approach used to build the weed functional traits database, the first step in this study

REDUCED TILLAGE AND COVER CROPS IN ORGANIC ARABLE SYSTEMS PRESERVES WEED DIVERSITY WITHOUT JEOPARDISING CROP YIELD

One of the objectives of the TILMAN-ORG Project is to improve weed management under conservation agriculture (reduced tillage and/or cover crops) in organic arable systems. The shift from ploughing to conservation agriculture should not only maintain crop yield but possibly improve weed community diversity. This paper summarises the results on (1) weed abundance, (2) weed diversity and (3) crop yield obtained in the first year of the project (2012) in 13 trials scattered across Europe

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: a quality improvement study

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy

Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients

Background Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for the screening of dysphagia in ALS is validated, and the approach is heterogeneous across the Italian centres.Objective To validate the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire, adapting the DYMUS (dysphagia in multiple sclerosis) questionnaire, for the assessment of dysphagia in ALS patients, in order to uniform the evaluations across the Italian ALS network.Methods We included 197 patients diagnosed with ALS following the El Escorial criteria, in sixteen Italian ALS centres between 1st December 2019 and 1st July 2020. For each patient, we collected clinical and demographic data and obtained ALSFRS-r score, ALSAQ-5 score, DYMUS score, and EAT-10 score.Results Across the 197 patients, the ratio M/F was 113/84, and the median age was 64 years (IQR 56-72.5). Bulbar patients were 20%, and spinal patients 80%. The median ALSFRSr total score of patients was 35 (IQR 28-39). DYALS score was statistically higher in bulbar ALS than in spinal ALS (median = 6, IQR 4.5-9 vs median =1, IQR 0-5, z= 6.253, p < 0.0001). DYALS questionnaire showed a high internal consistency (Cronbach's alpha = 0.88). There was a statistically significant correlation between DYALS and EAT-10 (rho = 0.90, p < 0.0001).Conclusions DYALS scale is reliable, manageable, and easily usable for the screening of dysphagia in ALS. It can be shared with all the Italian ALS centres in order to collect uniform data for therapeutic strategies and clinical trials

Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial

BACKGROUND: VEGF and VEGF receptor 2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether the addition of ramucirumab, a VEGFR-2 antagonist monoclonal antibody, to first-line chemotherapy improves outcomes in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma. METHODS: For this double-blind, randomised, placebo-controlled, phase 3 trial done at 126 centres in 20 countries, we recruited patients aged 18 years or older with metastatic, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. Eligible patients were randomly assigned (1:1) with an interactive web response system to receive cisplatin (80 mg/m2, on the first day) plus capecitabine (1000 mg/m2, twice daily for 14 days), every 21 days, and either ramucirumab (8 mg/kg) or placebo on days 1 and 8, every 21 days. 5-Fluorouracil (800 mg/m2 intravenous infusion on days 1-5) was permitted in patients unable to take capecitabine. The primary endpoint was investigator-assessed progression-free survival, analysed by intention to treat in the first 508 patients. We did a sensitivity analysis of the primary endpoint, including a central review of CT scans. Overall survival was a key secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT02314117. FINDINGS: Between Jan 28, 2015, and Sept 16, 2016, 645 patients were randomly assigned to receive ramucirumab plus fluoropyrimidine and cisplatin (n=326) or placebo plus fluoropyrimidine and cisplatin (n=319). Investigator-assessed progression-free survival was significantly longer in the ramucirumab group than the placebo group (hazard ratio [HR] 0·753, 95% CI 0·607-0·935, p=0·0106; median progression-free survival 5·7 months [5·5-6·5] vs 5·4 months [4·5-5·7]). A sensitivity analysis based on central independent review of the radiological images did not corroborate the investigator-assessed difference in progression-free survival (HR 0·961, 95% CI 0·768-1·203, p=0·74). There was no difference in overall survival between groups (0·962, 0·801-1·156, p=0·6757; median overall survival 11·2 months [9·9-11·9] in the ramucirumab group vs 10·7 months [9·5-11·9] in the placebo group). The most common grade 3-4 adverse events were neutropenia (85 [26%] of 323 patients in the ramucirumab group vs 85 [27%] of 315 in the placebo group), anaemia (39 [12%] vs 44 [14%]), and hypertension (32 [10%] vs 5 [2%]). The incidence of any-grade serious adverse events was 160 (50%) of 323 patients in the ramucirumab group and 149 (47%) of 315 patients in the placebo group. The most common serious adverse events were vomiting (14 [4%] in the ramucirumab group vs 21 [7%] in the placebo group) and diarrhoea (11 [3%] vs 19 [6%]). There were seven deaths in each group, either during study treatment or within 30 days of discontinuing study treatment, which were the result of treatment-related adverse events. In the ramucirumab group, these adverse events were acute kidney injury, cardiac arrest, gastric haemorrhage, peritonitis, pneumothorax, septic shock, and sudden death (n=1 of each). In the placebo group, these adverse events were cerebrovascular accident (n=1), multiple organ dysfunction syndrome (n=2), pulmonary embolism (n=2), sepsis (n=1), and small intestine perforation (n=1). INTERPRETATION: Although the primary analysis for progression-free survival was statistically significant, this outcome was not confirmed in a sensitivity analysis of progression-free survival by central independent review, and did not improve overall survival. Therefore, the addition of ramucirumab to cisplatin plus fluoropyrimidine chemotherapy is not recommended as first-line treatment for this patient population. FUNDING: Eli Lilly and Company.status: publishe

Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study

Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types&nbsp;1–3 SMA. Here, an analysis was performed after all patients had received at least 1&nbsp;year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6&nbsp;months and 60&nbsp;years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2&nbsp;years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0&nbsp;years (1–60&nbsp;years) and 39.1&nbsp;kg (9.2–108.9&nbsp;kg), respectively. About 63% of patients aged 2–60&nbsp;years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients