The Sitting Ducks of Securities Class Action Litigation: Bio-Pharmas and the Need for Improved Evaluation of Scientific Data

Rule 10b-5, a powerful weapon against any publicly-listed company whose share price drops on adverse news, is particularly skewed against pharmaceutical and other bio-technology companies (bio-pharmas). It is not a coincidence that there is a disproportionate number of class actions filed against bio-pharmas. The volume and complexity of data underlying most bio-pharma cases create enormous outcome uncertainties, settlement pressures, and potentially huge contingent liabilities over substantial periods of time. The vulnerability and risks that bio-pharmas face in Rule 10b-5 class actions are unique among all publicly-traded industries, yet many cases proceed along traditional grounds without courts employing either their statutory or inherent powers to obtain objective expert assessment of the data underlying plaintiffs\u27 claims. Most judges have neither the training nor the capacity to differentiate between the positions of opposing experts or to reach their own independent assessment of the research data. The unstated premise of the Supreme Court\u27s Daubert v. Merrell Dow Pharmaceuticals opinion is that courts have an obligation to fully understand the evidence prior to any decision-making, and that the use of court-appointed experts will allow judges to decide motions to dismiss with greater confidence and accuracy. The early appointment of such experts may also have the salutary effect of causing plaintiffs to pause and consider whether the claims are sufficient to warrant the up-front imposition of court-appointed expert costs. If courts begin to recognize in greater numbers the importance of obtaining objective expert testimony, we believe that a more level playing field will evolve to reduce the disproportionate vulnerability of bio-pharmas to securities law class actions

Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex

Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences

Leptin constrains acetylcholine-induced insulin secretion from pancreatic islets of ob/ob mice

Abstract Hypersecretion of insulin from the pancreas is among the earliest detectable metabolic alterations in some genetically obese animals including the ob/ob mouse and in some obesity-prone humans. Since the primary cause of obesity in the ob/ob mouse is a lack of leptin due to a mutation in the ob gene, we tested the hypothesis that leptin targets a regulatory pathway in pancreatic islets to prevent hypersecretion of insulin. Insulin secretion is regulated by changes in blood glucose, as well as by peptides from the gastrointestinal tract and neurotransmitters that activate the pancreatic islet adenylyl cyclase (e.g., glucagon-like peptide-1) and phospholipase C (PLC) (e.g., acetylcholine) signaling pathways to further potentiate glucose-induced insulin secretion. Effects of leptin on each of these regulatory pathways were thus examined. Leptin did not influence glucose or glucagon-like peptide-1-induced insulin secretion from islets of either ob/ob or lean mice, consistent with earlier findings that these regulatory pathways do not contribute to the early-onset hypersecretion of insulin from islets of ob/ob mice. However, leptin did constrain the enhanced PLCmediated insulin secretion characteristic of islets from ob/ob mice, without influencing release from islets of lean mice. A specific enhancement in PLC-mediated insulin secretion is the earliest reported developmental alteration in insulin secretion from islets of ob/ob mice, and thus a logical target for leptin action. This action of leptin on PLC-mediated insulin secretion was dose-dependent, rapid-onset (i.e., within 3 min), and reversible. Leptin was equally effective in constraining the enhanced insulin release from islets of ob/ob mice caused by protein kinase C (PKC) activation, a downstream mediator of the PLC signal pathway. One function of leptin in control of body composition is thus to target a PKC-regulated component of the PLC-PKC signaling system within islets to prevent hypersecretion of insulin. ( J

Volatile basic nitrogen measurement in digesta using a Berthelot reaction in automated Skalar instrumentation

The undigested nitrogenous fraction entering the hindgut of chickens is further metabolized by microbiota present producing volatile basic metabolites including amines and ammonia (NH3). Ammonia increases pH and may result in overgrowth of Clostridium perfringens further producing toxic metabolites that cause dysbacteriosis or necrotic enteritis (NE). There are few reports in chickens examining the production and concentration of nitrogenous metabolites in the hindgut. A Berthelot reaction using an automated flow, reaction and spectrophotometric instrumentation to detect volatile basic nitrogen in the form of NH3 from cecal contents was carried out. In the Berthelot reaction, NH3 in the sample is chlorinated to monochloramine using dichloroisocyanuric acid that then reacts with salicylate to form 5-aminosalicylate which is stable under alkaline conditions (pH 12 to 13). After oxidation and oxidative coupling, a coloured complex is formed that can be measured at 660 nm. Cecal contents were collected and pooled from 2 birds per pen with 48 pens total in each of 3 experiments and stored in sealed containers at −20 °C prior to analysis. Experiment 1 compared samples collected from birds fed either no meat and bone meal (MBM) or 6% MBM from d 0 to 14, and samples collected from birds fed either no MBM or 5% MBM from d 14 to 42. All birds were challenged with Eimeria on d 9 and C. perfringens on d 14 and 15. Experiment 2 compared cecal contents from birds fed either 0.5% or 0.9% calcium (Ca), and Exp. 3 compared unchallenged with NE challenge on d 16 and 29. Results demonstrated an increase (

Copper hydroxychloride is more efficacious than copper sulfate in improving broiler chicken's growth performance, both at nutritional and growth-promoting levels

This study was designed to compare the effects of nutritional and growth-promoting levels of copper hydroxychloride (CH) with copper sulfate (CuSO4) on growth, carcass characteristics, tibia traits and mineral concentration in broilers fed a conventional wheat-soybean meal-based diet. Day-old Ross 308 male chicks (n = 864) were randomly assigned into 8 dietary treatments with 6 replicates of 18 chicks per treatment. The dietary treatments included a basal diet containing no supplemental copper (Cu) serving as the negative control (NC); basal diet supplemented with 15 or 200 mg/kg Cu as CuSO4; basal diet supplemented with either 15, 50, 100, 150, or 200 mg/kg Cu from CH. Diets were fed over the starter (day 1–14) and grower (day 14–35) phases. Birds in the NC group gained the same body weight and had similar feed conversion ratio (FCR) to birds receiving 15 mg/kg Cu as CuSO4, but birds receiving 15 mg/kg Cu as CH had a lower FCR than the NC birds (day 0-35; P 4 (P P P > 0.05). The highest and lowest tibia ash content were observed in birds fed diet with 150 mg/kg Cu as CH and 200 mg/kg Cu as CuSO 0.05). The highest and lowest tibia ash content were observed in birds fed diet with 150 mg/kg Cu as CH and 200 mg/kg Cu as CuSO4, respectively (P 4 (P 4 in promoting growth performance, both at nutritional and pharmacological levels

Supplementing glycine, serine, and threonine in low protein diets for meat type chickens

Reducing dietary protein has been of interest to the global poultry industry to improve bird health, welfare, and industry sustainability. Low protein (LP) diets are typically glycine (Gly) deficient and produce poor performance. Supplementing the diet with Gly or precursors of Gly can overcome this deficiency. A feeding experiment was conducted with 330 Ross 308 off-sex males across 5 treatments in a randomized design using 11 birds per pen replicated 6 times. Grower and finisher treatments were fed from day 7 to 21 and day 21 to 35, respectively. The objective was to test the efficacy of supplementation with Gly and Gly equivalents (Glyequiv), serine (Ser) and threonine (Thr), in plant-based LP diets on bird performance against a standard protein (SP) diet containing meat and bone meal. Glycine, Ser, or Thr were supplemented on Glyequiv basis to an approximately 3% lower CP diet to achieve the same digestible Gly and Ser level as the SP diet. Nitrogen efficiency, serum uric acid, blood plasma amino acids (AA) and AA digestibility were also investigated to monitor potential metabolic effects. Birds fed the LP diet were only 3.3% lower in final body weight than the SP treatment (2,556 vs. 2,641 g) while the supplementation of Gly or Ser had no effect. Supplementation of Thr reduced final body weight by 9.5% (P P P P equiv basis