Agri-food importing firms amid a global health crisis

This paper exploits daily customs transaction data on the universe of Swiss agri-food importing firms to assess the response of firms to a global shock. Estimating a linear model that regresses product-level import margins on daily COVID19 shocks and a host of fixed effects, we find that the pandemic had a substantial trade-reducing effect on imports. The trade effects were driven mainly by a reduction in the number of importing firms (i.e., 63% of the total effect), and much less by the number of products imported and the average import value per product per firm. We explore several sources of heterogeneity and show, among others, that larger and incumbent firms were affected more by the trade adjustments. Our results also reveal that the relative contribution of each import margin to the decline in aggregate imports depends on the level of data aggregation (i.e., daily, weekly or monthly). Finally, we validate and confirm our main findings by testing two mechanisms: (i) third-country supply-side effects using insights from structural gravity models and (ii) changes to consumer demand using consumer mobility, and retailer and consumer scanner data

Patient-level meta-analysis of the EDITION 1, 2 and 3 studies : glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes

AimsTo conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively. MethodsThe EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249). ResultsNo significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with 1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low ( ConclusionGla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia.Peer reviewe

Livestock Selective Behaviour in Natural Grasslands Challenges the Concept of Plant Preference in the Elaboration of a Successful Diet

Conciliating livestock production and conservation of grassland biodiversity is now an imperative. We propose that a way to reach that goal is to take advantage of the natural tendency of herbivores to exploit environmental heterogeneity. However, it would go against the well-rooted concept that mammalian herbivores have invariable preference for some plants. Preference was defined as being “what the animal selects when given the minimum of physical constraints” (Parsons et al. 1994). But after decades of studies, the concept of preference remains particularly inefficient in predicting observed patterns of selection by herbivores (e.g. Newman et al. 1992; Parsons et al. 1994; Provenza 2006). We performed detailed descriptions of cattle diet composition and foraging strategy in highly diversified natural pasture of South Brazil. We present here preliminary results that seriously question the concept of plant preference

Glycaemic control and hypoglycaemia risk with insulin glargine 300 U/mL versus glargine 100 U/mL: A patient-level meta-analysis examining older and younger adults with type 2 diabetes

Abstract Aim Older people with type 2 diabetes (T2DM) are at an increased risk of hypoglycaemia and its consequences. However, efficacy and safety data for basal insulin therapy are limited in these individuals. This patient-level meta-analysis assessed the treatment effects of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with T2DM ≥ 65 years old. Methods Data were pooled for patients randomised to receive Gla-300 or Gla-100 in the Phase 3a, treat-to-target EDITION 1, 2 and 3 trials. Glycaemic efficacy, hypoglycaemia, changes in body weight and insulin dosage and adverse events were examined over 6 months' treatment with Gla-300 versus Gla-100 for participants aged ≥ 65 and  Results Of 2496 participants randomised, 662 were ≥ 65 years (Gla-300, n = 329; Gla-100, n = 333). Glycaemic control was comparable for Gla-300 and Gla-100 in participants ≥ 65 years (LS mean [95% CI] difference in HbA1c change from baseline to month 6: 0.00 [−0.14 to 0.15] %; 0.00 [−1.53 to 1.64] mmol/mol) and  Conclusion Gla-300 was associated with a reduced risk of nocturnal hypoglycaemia versus Gla-100, accompanied by comparable glycaemic improvement, for people aged ≥ 65 an

Cyclin-Dependent Kinase 5 Promotes Pancreatic β-Cell Survival via Fak-Akt Signaling Pathways

ObjectiveCyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 has recently been linked to type 2 diabetes by genome-wide association studies. While CDK5 and its regulatory protein p35 are both expressed and display enzymatic activity in pancreatic β-cells, their precise role in the β-cell remains unknown. Because type 2 diabetes is characterized by a deficit in β-cell mass and increased β-cell apoptosis, we investigated the role of CDK5 in β-cell survival.Research design and methodsWe used INS 832/13 cells, rat islets isolated from wild-type or human islet amyloid polypeptide (h-IAPP) transgenic rats, and pancreatic tissue from rats and humans with and without type 2 diabetes and investigated the effect of CDK5/p35 inhibition (by small interfering RNA or by chemical inhibition) as well as CDK5/p35 overexpression on β-cell vulnerability to apoptosis.ResultsCDK5 inhibition led to increased β-cell apoptosis. To identify the mechanisms involved, we examined the phosphorylation state of focal adhesion kinase (Fak)(Ser732), a known target of CDK5. Following CDK5 inhibition, the phosphorylation of Fak(Ser732) decreased with resulting attenuation of phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway. Conversely, CDK5 overexpression increased Fak(Ser732) phosphorylation and protected β-cells against apoptosis induced by the inhibition of the β-1 integrin signaling pathway. Also, Fak(Ser732) phosphorylation was less abundant in β-cells in both h-IAPP transgenic rats and humans with type 2 diabetes.ConclusionsThis study shows that by regulating Fak phosphorylation and subsequently PI3K/Akt survival pathway, CDK5 plays a previously unrecognized role in promoting β-cell survival

Selection of Evolutionary Multicriteria Strategies: Application in Designing a Regional Water Restoration Management Plan

Sustainability of water resources has become a challenging problem worldwide, as the pollution levels of natural water resources (particularly of rivers) have increased drastically in the last decades. Nowadays, there are many Waste Water Treatment Plant (WWTP) technologies that provide different levels of efficiency in the removal of water pollutants, leading to a great number of combinations of different measures (PoM) or strategies. The management problem, then, involves finding which of these combinations are efficient, regarding the desired objectives (cost and quality). Therefore, decisions affecting water resources require the application of multi-objective optimization techniques which will lead to a set of tradeoff solutions, none of which is better or worse than the others, but, rather, the final decision must be one particular PoM including representative features of the whole set of solutions. Besides, there is not a universally accepted standard way to assess the water quality of a river. In order to consider simultaneously all these issues, we present in this work a hydroinformatics management tool, designed to help decision makers with the selection of a PoM that satisfies the WFD objectives. Our approach combines: 1) a Water Quality Model (WQM), devised to simulate the effects of each PoM used to reduce pollution pressures on the hydrologic network; 2) a Multi-Objective Evolutionary Algorithm (MOEA), used to identify efficient tradeoffs between PoMs’ costs and water quality; and 3) visualization of the Pareto optimal set, in order to extract knowledge from optimal decisions in a usable form. We have applied our methodology in a real scenario, the inner Catalan watersheds with promising results

Δ40 Isoform of p53 Controls β-Cell Proliferation and Glucose Homeostasis in Mice

Objective: Investigating the dynamics of pancreatic $\beta$-cell mass is critical for developing strategies to treat both type 1 and type 2 diabetes. p53, a key regulator of the cell cycle and apoptosis, has mostly been a focus of investigation as a tumor suppressor. Although p53 alternative transcripts can modulate p53 activity, their functions are not fully understood. We hypothesized that $\beta$-cell proliferation and glucose homeostasis were controlled by $\Delta$40p53, a p53 isoform lacking the transactivation domain of the full-length protein that modulates total p53 activity and regulates organ size and life span in mice. Research Design and Methods: We phenotyped metabolic parameters in $\Delta$40p53 transgenic (p44tg) mice and used quantitative RT-PCR, Western blotting, and immunohistochemistry to examine $\beta$-cell proliferation. Results: Transgenic mice with an ectopic p53 gene encoding $\Delta$40p53 developed hypoinsulinemia and glucose intolerance by 3 months of age, which worsened in older mice and led to overt diabetes and premature death from $\sim$14 months of age. Consistent with a dramatic decrease in $\beta$-cell mass and reduced $\beta$-cell proliferation, lower expression of cyclin D2 and pancreatic duodenal homeobox-1, two key regulators of proliferation, was observed, whereas expression of the cell cycle inhibitor p21, a p53 target gene, was increased. Conclusions: These data indicate a significant and novel role for $\Delta$40p53 in $\beta$-cell proliferation with implications for the development of age-dependent diabetes

Successful Versus Failed Adaptation to High-Fat Diet–Induced Insulin Resistance: The Role of IAPP-Induced β-Cell Endoplasmic Reticulum Stress

ObjectiveObesity is a known risk factor for type 2 diabetes. However, most obese individuals do not develop diabetes because they adapt to insulin resistance by increasing beta-cell mass and insulin secretion. Islet pathology in type 2 diabetes is characterized by beta-cell loss, islet amyloid derived from islet amyloid polypeptide (IAPP), and increased beta-cell apoptosis characterized by endoplasmic reticulum (ER) stress. We hypothesized that IAPP-induced ER stress distinguishes successful versus unsuccessful islet adaptation to insulin resistance.Research design and methodsTo address this, we fed wild-type (WT) and human IAPP transgenic (HIP) rats either 10 weeks of regular chow or a high-fat diet and prospectively examined the relations among beta-cell mass and turnover, beta-cell ER stress, insulin secretion, and insulin sensitivity.ResultsA high-fat diet led to comparable insulin resistance in WT and HIP rats. WT rats compensated with increased insulin secretion and beta-cell mass. In HIP rats, in contrast, neither beta-cell function nor mass compensated for the increased insulin demand, leading to diabetes. The failure to increase beta-cell mass in HIP rats was the result of ER stress-induced beta-cell apoptosis that increased in proportion to diet-induced insulin resistance.ConclusionsIAPP-induced ER stress distinguishes the successful versus unsuccessful islet adaptation to a high-fat diet in rats. These studies are consistent with the hypothesis that IAPP oligomers contribute to increased beta-cell apoptosis and beta-cell failure in humans with type 2 diabetes