Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial

The present analysis, carried out in the context of a randomized phase III trial, confirms superior outcomes for breast cancer patients for whom chemotherapy induces pathological complete response (pCR) after adjusting for other important prognostic factors. In contrast, when tumours do not achieve pCR, patients have a higher risk of relapse. This effect is observed in all intrinsic subtypes and justifies the current interest in post-neoadjuvant trial

Heart rate and energy expenditure of incubating wandering albatrosses: basal levels, natural variation, and the effects of human disturbance

We studied the changes in heart rate (HR) associated with metabolic rate of incubating and resting adult wandering albatrosses (Diomedea exulans) on the Crozet Islands. Metabolic rates of resting albatrosses fitted with external HR recorders were measured in a metabolic chamber to calibrate the relationship between HR and oxygen consumption (V̇O2) (V̇O2=0.074×HR+0.019, r2=0.567, P\u3c0.001, where V̇O2 is in ml kg–1 min–1 and HR is in beats min–1). Incubating albatrosses were then fitted with HR recorders to estimate energy expenditure of albatrosses within natural field conditions. We also examined the natural variation in HR and the effects of human disturbance on nesting birds by monitoring the changes in HR. Basal HR was positively related to the mass of the individual. The HR of incubating birds corresponded to a metabolic rate that was 1.5-fold (males) and 1.8-fold (females) lower than basal metabolic rate (BMR) measured in this and a previous study. The difference was probably attributable to birds being stressed while they were held in the metabolic chamber or wearing a mask. Thus, previous measurements of metabolic rate under basal conditions or for incubating wandering albatrosses are likely to be overestimates. Combining the relationship between HR and metabolic rate for both sexes, we estimate that wandering albatrosses expend 147 kJ kg–1 day–1 to incubate their eggs. In addition, the cost of incubation was assumed to vary because (i) HR was higher during the day than at night, and (ii) there was an effect of wind chill (\u3c0°C) on basal HR. The presence of humans in the vicinity of the nest or after a band control was shown to increase HR for extended periods (2–3 h), suggesting that energy expenditure was increased as a result of the disturbance. Lastly, males and females reacted differently to handling in terms of HR response: males reacted more strongly than females before handling, whereas females took longer to recover after being handled

Predictors and risk model for positive circumferential resection margin after robot-assisted total mesorectal excision:retrospective cohort study

Background: Positive circumferential resection margin (CRM) after total mesorectal excision (TME) is associated with higher local and systemic recurrence rates, affecting overall survival in patients with rectal cancer. Although risk factors for positive CRM have been identified for open, laparoscopic, and transanal TME, these may differ for robot-assisted total mesorectal excision (R-TME). This study aimed to assess the incidence of positive CRM following R-TME and identify the associated preoperative risk factors. Method: An international multicentre retrospective study included patients receiving R-TME between January 2013 and January 2022 in centres based in the Netherlands, UK, and France. Endpoints were the incidence of and predictive factors for positive CRM. Univariable and multivariable logistic regression analyses were performed, and factors associated with positive CRM were then assessed by formulating a predictive model. Results: A total of 1390 patients underwent R-TME, and the incidence of positive CRM was 6.0% (n = 83). Multivariable analysis revealed significant associations between positive CRM and cT4 tumours (OR 2.27), involved mesorectal fascia on staging magnetic resonance imaging at diagnosis (OR 1.89), and non-sphincter-saving surgery (OR 2.22). The predictive model exhibited satisfactory discrimination (area under the receiver-operating characteristic curve &gt; 0.7) and predicted a 26% risk of positive CRM when all identified risk factors were present. Conclusion: Preoperative tumour- and procedure-related factors, rather than patient-related factors, are associated with CRM involvement after R-TME. The proposed predictive model allows preoperative calculation of the risk of positive CRM, offering valuable insights for optimizing patient selection and tailoring treatment approaches to enhance oncological outcomes.</p

Effects of tillage systems on soil characteristics, glomalin and mycorrhizal propagules in a Chilean Ultisol

Tillage affects the soil physical and chemical environment in which soil microorganisms live, thereby affecting their number, diversity and activity. However, soil disturbance generally has the greatest impact on biological properties, including both free and symbiotic fungal populations. Interest in more ecologically sustainable agricultural systems is rising with increasing recognition that agricultural intensification can adversely affect environmental quality. This paper discusses the effect of tillage system on some soil characteristics, such as pH, C, N and S levels, total and Olsen-P contents including some P forms associated with organic matter, glomalin contents and arbuscular mycorrhizae (AM) parameters, such as root colonization, spore number and total and active hyphal length. Measurements were in the sixth year of an on-going tillage-rotation experiment conducted on an Ultisol under no-till (NT), reduced tillage (RT) and conventional tillage with stubble mixed into the soil (CTS) or stubble burnt (CTB). Soil was sampled at two dates; after wheat (Triticum aestivum) harvest (autumn) and 6 months after subsequent grassland seeding (spring). Higher C, N, S, total P and fulvic acid-P concentrations and pH occurred under NT and RT than under CTS and CTB after wheat harvest. However, results at the second sampling were not consistent. AM spore number and active hyphal length were highest under NT having the greatest incidence on AM root colonization and P concentration in shoots of the pasture. Glomalin concentration was higher under NT and RT than under CTS and CTB but no differences in calculated glomalin to total C (ca. 5%) were found. It is concluded that a less disruptive effect of NT influences positively all soil characteristics and also increases P acquisition by the following crop in the rotation system