Why Social Enterprises Are Asking to Be Multi-stakeholder and Deliberative: An Explanation around the Costs of Exclusion.

The study of multi-stakeholdership (and multi-stakeholder social enterprises in particular) is only at the start. Entrepreneurial choices which have emerged spontaneously, as well as the first legal frameworks approved in this direction, lack an adequate theoretical support. The debate itself is underdeveloped, as the existing understanding of organisations and their aims resist an inclusive, public interest view of enterprise. Our contribution aims at enriching the thin theoretical reflections on multi-stakeholdership, in a context where they are already established, i.e. that of social and personal services. The aim is to provide an economic justification on why the governance structure and decision-making praxis of the firm needs to account for multiple stakeholders. In particular with our analysis we want: a) to consider production and the role of firms in the context of the “public interest” which may or may not coincide with the non-profit objective; b) to ground the explanation of firm governance and processes upon the nature of production and the interconnections between demand and supply side; c) to explain that the costs associated with multi-stakeholder governance and deliberation in decision-making can increase internal efficiency and be “productive” since they lower internal costs and utilise resources that otherwise would go astray. The key insight of this work is that, differently from major interpretations, property costs should be compared with a more comprehensive range of costs, such as the social costs that emerge when the supply of social and personal services is insufficient or when the identification of aims and means is not shared amongst stakeholders. Our model highlights that when social costs derived from exclusion are high, even an enterprise with costly decisional processes, such as the multistakeholder, can be the most efficient solution amongst other possible alternatives

Humanizar el mercado: propuestas para la sociedad post-industrial

Este ensayo se propone dar una contestación a un doble interrogante. Por un lado, qué significa hoy en día humanizar la economía, es decir, ¿es posible concebir una sociedad de mercado en la que los individuos de la sociedad civil, portadores de cultura, puedan perseguir objetivos libremente elegidos? Y por otro, ¿qué vía seguir para que este objetivo se pueda conseguir

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

The meta-crisis of secular capitalism

The current global economic crisis concerns the way in which contemporary capitalism has turned to financialisation as a double cure for both a falling rate of profit and a deficiency of demand. Although this turning is by no means unprecedented, policies of financialisation have depressed demand (in part as a result of the long-term stagnation of average wages) while at the same time not proving adequate to restore profits and growth. This paper argues that the current crisis is less the ‘normal’ one that has to do with a constitutive need to balance growth of abstract wealth with demand for concrete commodities. Rather, it marks a meta-crisis of capitalism that is to do with the difficulties of sustaining abstract growth as such. This meta-crisis is the tendency at once to abstract from the real economy of productive activities and to reduce everything to its bare materiality. By contrast with a market economy that binds material value to symbolic meaning, a capitalist economy tends to separate matter from symbol and reduce materiality to calculable numbers representing ‘wealth’. Such a conception of wealth rests on the aggregation of abstract numbers that cuts out all the relational goods and the ‘commons’ on which shared prosperity depends

Calcium and phosphate homeostasis in dogs with newly diagnosed naturally occurring hypercortisolism

Background: Hypercortisolism affects calcium and phosphate metabolism in dogs; however, the exact mechanisms are not completely understood. Objectives: To evaluate circulating concentrations of whole parathormone (wPTH), 25-hydroxyvitamin D (25-(OH)D), calcitriol, and fibroblast growth factor-23 (FGF-23) in dogs with naturally occurring hypercortisolism (NOHC) and healthy dogs, and their association with calcium and phosphate homeostasis. Animals: Twenty-three client-owned dogs with NOHC, and 12 client or staff-owned healthy dogs. Methods: Prospective cross-sectional study. The circulating concentrations of total calcium, ionized calcium (iCa), phosphate, wPTH, 25-(OH)D, calcitriol and FGF-23, and the urinary fractional excretion of phosphate (FEP) and calcium (FECa) were compared between dogs with NOHC before treatment and healthy dogs. Results: Dogs with NOHC had higher mean serum phosphate concentrations (4.81 mg/dL, SD ± 0.71 vs 3.86 mg/dL, SD ± 0.60; P <.001), median FECa (0.43%, range, 0.03-2.44 vs 0.15%, range, 0.06-0.35; P =.005), and median serum wPTH concentrations (54.6 pg/mL, range, 23.7-490 vs 24.6 pg/mL, range, 5.5-56.4; P =.003) as compared to the controls. Circulating concentrations of total calcium, iCa, and calcitriol and the FEP did not differ between groups, whereas the serum 25-(OH)D concentrations were lower in dogs with NOHC as compared to the controls (70.2 pg/mL, SD ± 42.3 vs 106.3 pg/mL, SD ± 35.3; P =.02). The dogs with NOHC had lower plasma FGF-23 concentrations than controls (316.6 pg/mL, range, 120.8-575.6 vs 448.7 pg/mL, range, 244.8-753; P =.03). Conclusions and Clinical Importance: Urine loss of calcium and hyperphosphatemia could contribute to the adrenal secondary hyperparathyroidism

Challenge clusters facing LCA in environmental decision-making—what we can learn from biofuels

Purpose Bioenergy is increasingly used to help meet greenhouse gas (GHG) and renewable energy targets. However, bioenergy’s sustainability has been questioned, resulting in increasing use of life cycle assessment (LCA). Bioenergy systems are global and complex, and market forces can result in significant changes, relevant to LCA and policy. The goal of this paper is to illustrate the complexities associated with LCA, with particular focus on bioenergy and associated policy development, so that its use can more effectively inform policymakers. Methods The review is based on the results from a series of workshops focused on bioenergy life cycle assessment. Expert submissions were compiled and categorized within the first two workshops. Over 100 issues emerged. Accounting for redundancies and close similarities in the list, this reduced to around 60 challenges, many of which are deeply interrelated. Some of these issues were then explored further at a policyfacing workshop in London, UK. The authors applied a rigorous approach to categorize the challenges identified to be at the intersection of biofuels/bioenergy LCA and policy. Results and discussion The credibility of LCA is core to its use in policy. Even LCAs that comply with ISO standards and policy and regulatory instruments leave a great deal of scope for interpretation and flexibility. Within the bioenergy sector, this has led to frustration and at times a lack of obvious direction. This paper identifies the main challenge clusters: overarching issues, application and practice and value and ethical judgments. Many of these are reflective of the transition from application of LCA to assess individual products or systems to the wider approach that is becoming more common. Uncertainty in impact assessment strongly influences planning and compliance due to challenges in assigning accountability, and communicating the inherent complexity and uncertainty within bioenergy is becoming of greater importance. Conclusions The emergence of LCA in bioenergy governance is particularly significant because other sectors are likely to transition to similar governance models. LCA is being stretched to accommodate complex and broad policy-relevant questions, seeking to incorporate externalities that have major implications for long-term sustainability. As policy increasingly relies on LCA, the strains placed on the methodology are becoming both clearer and impedimentary. The implications for energy policy, and in particular bioenergy, are large

Difficult-to-treat patients with relapsed/refractory multiple myeloma:A review of clinical trial results

Overall outcomes for multiple myeloma have improved due to the availability of new therapies, but patients with relapsed/refractory multiple myeloma harbouring certain factors continue to pose a therapeutic challenge. These challenging features include high-risk cytogenetics, renal impairment, patient characteristics such as age and frailty, and extramedullary disease. Prior refractory status and number of prior lines add further complexity to the treatment of these patients. While newer regimens are available and have suggested efficacy in these patient populations through subgroup analyses, differences in trial definitions and cut-offs make meaningful comparisons difficult. This review aims to examine the available clinical trial data for patients with high-risk cytogenetics, renal impairment, age and frailty and extramedullary disease.</p

Intrapartum ultrasound for cervical dilatation: Inter- and intra-observer agreement

Introduction: Digital vaginal examination (DVE) is considered the standard of care for assessing labor progress and cervical dilatation. However, it may be painful and is a subjective method that can increase the risk of chorioamnionitis. Known inter- and intra-observer variability exists in measurements of cervical dilatation obtained digitally. However, little is known about the inter- and intra-observer variability when using intrapartum transperineal ultrasound (TPUS). Our objectives were to investigate the relationship between cervical dilatation as assessed by TPUS and DVE. To assess inter- and intra-observer variability in both single and repeated ultrasound assessments of cervical dilatation during active labor. Material and Methods: This single-center study was conducted at an inner-city maternity unit in London, UK. Nulliparous participants at term with a live, singleton fetus in cephalic presentation were recruited between May 2021 and November 2022. During active labor, TPUS was performed subsequent to DVE. Repeat ultrasound assessments were performed where feasible. Participants were in a supine position, with flexed hips and knees and with an empty bladder. The ultrasound transducer was placed transversely on the maternal perineum. The anteroposterior (AP) diameter of the cervix was measured, and two-dimensional (2D) cine-loop videos were analyzed to obtain accurate measurements. Data were excluded if the time difference between DVE and TPUS exceeded 60 min. Results: Of the 206 participants who consented to the study, complete data were obtained from 110 participants, yielding 147 paired TPUS and DVE observations. Ninety-six participants were excluded. The absolute difference between TPUS and DVE assessments was 0 cm in 34% of the observations, 1 cm in 46.3%, and between 2 and 4 cm in 19.7%. The mean difference was −0.9 cm (intraclass correlation coefficient = 0.85; p < 0.001). Data from 30 participants, with 50 cervical dilatation measurements, were used to assess inter- and intra-observer variability. The mean difference for the first ultrasound assessment was 0.07 cm (95% limit of agreement = −0.96 to 1.10, p < 0.001), for inter-observer variability, and 0.01 cm (95% limit of agreement = −0.29 to 0.30; p < 0.001) for intra-observer variability. Conclusions: Assessment of the cervix with TPUS during active labor is feasible and shows a strong correlation with DVE measurements. The majority of ultrasound measurements yielded readings within 1 cm of the corresponding DVE values, demonstrating high intraclass correlation and good inter- and intra-observer agreement

Anti-BCMA CAR-T cell-based therapies and bispecific antibodies in the immunotherapy era: are we ready for this?

Introduction: Therapeutic strategies against multiple myeloma (MM) have evolved dramatically in recent decades, with unprecedent results in the treatment landscape, culminating in the recent incorporation of novel agents in the anti-myeloma armamentarium. Areas covered: BCMA represents one of the most promising targets in MM and currently available immune approaches, either approved or under active investigation, are clearly showing their greater potential over standard regimens. In this context, immunotherapies based on chimeric antigen receptor (CAR)-engineered T-cells and bispecific antibodies (BsAbs) have taken center stage, being the ones that are yielding the most promising results in clinical trials. This review focuses on the current landscape of BsAbs and CAR-T, summarizing the latest advances and possible future developments. Expert opinion: CAR-T and BsAbs anti-BCMA strategies represent breakthrough therapies against MM. However, their inclusion in clinical practice is almost feared, due to the associated limitations, some of which have been addressed here. Meanwhile, all the efforts should be focused on individualizing and choosing the most suitable candidates for each treatment and to understand how to combine, or sequence, these therapies to improve efficacy and minimize toxicity, especially for those patients with limited available treatment options

Growth and cycles of the Italian economy since 1861: the new evidence

Based on a newly-available large set of historical national accounts, the paper revisits the main features of economic growth and cycles in Italy for the post-Unification period 1861-2011. Alongside the structural changes in growth dynamics, the main sources of output and productivity growth are identified. As regards the analysis of the underlying cyclical component, a business cycle chronology is first established and then both the specific patterns of individual cycles and the co-movements of output with key macroeconomic variables are investigated. In the 150 years since its political Unification, Italy's economic growth was mainly propelled by consumption and investments, whereas on the supply side the industry and services sectors were by far the main contributors, also because of the positive effect of labour reallocation to nonfarm activities. Over the same period, Italy experienced approximately 20 business cycles of varying duration and amplitude. Output fluctuations were dominated by the short-term variability of agricultural production before World War II and by fluctuations of the industry sector thereafter. The cyclical behaviour exhibited by aggregate demand components conforms quite well to that evidenced in the standard international business cycle literature, although some exceptions arise in the pre-World War II years