A MODEL OF NONBELIEF IN THE LAW OF LARGE NUMBERS.

People believe that, even in very large samples, proportions of binary signals might depart significantly from the population mean. We model this "non-belief in the Law of Large Numbers" by assuming that a person believes that proportions in any given sample might be determined by a rate different than the true rate. In prediction, a non-believer expects the distribution of signals will have fat tails.

Incidence of Breakthrough Urinary Tract Infection in Hospitalized Infants Receiving Antibiotic Prophylaxis.

Urinary tract infections (UTIs) are a source of substantial morbidity in children in the neonatal intensive care unit. The incidence of UTIs that occur in critically ill infants during a course of antibiotic prophylaxis (i.e.

Murine mammary stem/progenitor cell isolation: Different method matters?

Murine mammary stem/progenitor cell isolation has been routinely used in many laboratories, yet direct comparison among different methods is lacking. In this study, we compared two frequently used digestion methods and three sets of frequently used surface markers for their efficiency in enriching mammary stem and progenitor cells in two commonly used mouse strains, C57BL/6J and FVB. Our findings revealed that the slow overnight digestion method using gentle collagenase/hyaluronidase could be easily adopted and yielded reliable and consistent results in different batches of animals.

Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants.

Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials.

Solithromycin Pharmacokinetics in Plasma and Dried Blood Spots and Safety in Adolescents.

We assessed the pharmacokinetics and safety of solithromycin, a fluoroketolide antibiotic, in a phase 1, open-label, multicenter study of 13 adolescents with suspected or confirmed bacterial infections. On days 3 to 5, the mean (standard deviation) maximum plasma concentration and area under the concentration versus time curve from 0 to 24 h were 0.74 μg/ml (0.

The Research Optimist's Defense.

Several studies suggest that clinical researchers are prone to overestimating the chance that scientific protocols will succeed, say, by confirming a treatment hypothesis or reaching recruitment targets. In this essay, we address the normative question of whether such "unrealistic optimism" is harmful in clinical research. We entertain five plausible defenses of unrealistic optimism: agnosticism (optimism cannot be objectively assessed), skepticism (expressions of unrealistic optimism are difficult to interpret, since researchers are not accustomed to thinking in terms of probability), contrarianism (unrealistic optimism is salutary), denialism (any effects of unrealistic optimism are neutralized by oversight mechanisms), and fatalism (nothing can be done to alter unrealistic optimism or its effects).

Postnatal Cytomegalovirus Infection and the Risk for Bronchopulmonary Dysplasia.

Importance: Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but in very low-birth-weight (VLBW) infants can cause pneumonitis and sepsislike illness. Whether postnatal CMV infection results in long-term pulmonary sequelae in these infants is unknown.

Objective: To investigate the association between postnatal CMV infection and bronchopulmonary dysplasia (BPD) and mortality in a large multicenter cohort of VLBW infants.

The Fourth Law of Behavior Genetics.

Behavior genetics is the study of the relationship between genetic variation and psychological traits. Turkheimer (2000) proposed "Three Laws of Behavior Genetics" based on empirical regularities observed in studies of twins and other kinships. On the basis of molecular studies that have measured DNA variation directly, we propose a Fourth Law of Behavior Genetics: "A typical human behavioral trait is associated with very many genetic variants, each of which accounts for a very small percentage of the behavioral variability.

Burden of Invasive Staphylococcus aureus Infections in Hospitalized Infants.

Importance: Staphylococcus aureus is a frequent cause of infection in hospitalized infants. These infections are associated with increased mortality and morbidity and longer hospital stays, but data on the burden of S aureus disease in hospitalized infants are limited.

Objectives: To compare demographics and mortality of infants with invasive methicillin-resistant S aureus (MRSA) and methicillin-susceptible S aureus (MSSA), to determine the annual proportion of S aureus infections that were MRSA, and to contrast the risk of death after an invasive MRSA infection with the risk after an invasive MSSA infection.

Cefepime and Ceftazidime Safety in Hospitalized Infants.

Background: Cefepime and ceftazidime are cephalosporins used for the treatment of serious Gram-negative infections. These cephalosporins are used off-label in the setting of minimal safety data for young infants.

Methods: We identified all infants discharged from 348 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012 who were exposed to either cefepime or ceftazidime in the first 120 days of life.

Gaps in Drug Dosing for Obese Children: A Systematic Review of Commonly Prescribed Emergency Care Medications.

Purpose: Approximately 1 of 6 children in the United States is obese. This has important implications for drug dosing and safety because pharmacokinetic (PK) changes are known to occur in obesity due to altered body composition and physiologic mechanisms. Inappropriate drug dosing in an emergency setting can limit therapeutic efficacy and increase drug-related toxic effects for obese children.

Applying Regulatory Science to Develop Safe and Effective Medicines for Neonates: Report of the US Food and Drug Administration First Annual Neonatal Scientific Workshop, October 28-29, 2014.

The First Annual Neonatal Scientific Workshop focused on the needs of the neonate by addressing the basic question: what information is required to inform decision making both at the regulatory level and at the bedside? Priority therapeutic areas include neonatal lung, brain, and gastrointestinal injury, retinopathy of prematurity, sepsis, and neonatal abstinence syndrome. Scientific progress in these therapeutic areas, regulatory standards, and the acceptable design and conduct of clinical trials must be aligned. This report will review potential approaches to enhancing neonatal drug development.

Discovery of Inhibitors for the Ether Lipid-Generating Enzyme AGPS as Anti-Cancer Agents.

Dysregulated ether lipid metabolism is an important hallmark of cancer cells. Previous studies have reported that lowering ether lipid levels by genetic ablation of the ether lipid-generating enzyme alkyl-glycerone phosphate synthase (AGPS) lowers key structural and oncogenic ether lipid levels and alters fatty acid, glycerophospholipid, and eicosanoid metabolism to impair cancer pathogenicity, indicating that AGPS may be a potential therapeutic target for cancer. In this study, we have performed a small-molecule screen to identify candidate AGPS inhibitors.

Survival Benefit of Empirical Therapy for Staphylococcus aureus Bloodstream Infections in Infants.

Background: The impact of early adequate empirical antibiotic therapy on outcomes of infants in the neonatal intensive care unit (NICU) who develop Staphylococcus aureus bloodstream infections (BSI) is unknown.

Methods: Infants with S. aureus BSI discharged in 1997-2012 from 348 NICUs managed by the Pediatrix Medical Group were identified.

Neonatal Escherichia coli Bloodstream Infections: Clinical Outcomes and Impact of Initial Antibiotic Therapy.

Background: Escherichia coli is a common cause of bloodstream infections (BSIs) in infants and is associated with high mortality and morbidity among survivors. The clinical significance of antibiotic resistance and timing of appropriate antimicrobial therapy in this population is poorly understood.

Methods: We identified all infants with E.

Polygenic risk scores for schizophrenia and bipolar disorder predict creativity.

We tested whether polygenic risk scores for schizophrenia and bipolar disorder would predict creativity. Higher scores were associated with artistic society membership or creative profession in both Icelandic (P = 5.2 × 10(-6) and 3.

Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots.

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial drug combination commonly prescribed in children and adults. The study objectives were to validate and apply an HPLC-MS/MS method to quantify TMP-SMX in dried plasma spots (DPS) and dried urine spots (DUS), and perform a comparability analysis with liquid matrices.

Results: For TMP the validated range was 100-50,000 ng/ml for DPS and 500-250,000 ng/ml for DUS; for SMX, the validated range was 1000-500,000 ng/ml for both DPS and DUS.

A Theory of Fairness in Labour Markets.

I study a gift-exchange game, in which a profit-maximizing firm offers a wage to a fair-minded worker, who then chooses how much effort to exert. The worker judges a transaction fairer to the extent that his own gain is more nearly equal to the firm's gain. The worker calculates both players' gains relative to what they would have gained from the "reference transaction," which is the transaction that the worker most recently personally experienced.

Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review.

Importance: Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature regarding obesity's effect on drug safety, pharmacokinetics, and dosing in obese children is unknown.

Objective: To perform a systematic literature review describing the current evidence of the effect of obesity on drug disposition in children.

Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenation.

Candida infections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptimal drug exposures. The objective of our study was to determine the PK of fluconazole in children on ECMO.

Diacylglycerol Metabolism and Signaling Is a Driving Force Underlying FASN Inhibitor Sensitivity in Cancer Cells.

Fatty acid synthase (FASN) generates the de novo source of lipids for cell proliferation and is a promising cancer therapy target. Development of FASN inhibitors, however, necessitates a better understanding of sensitive and resistant cancer types to optimize patient treatment. Indeed, testing the cytotoxic effects of FASN inhibition across human cancer cells revealed diverse sensitivities.

Advances in the treatment of invasive neonatal candidiasis.

Introduction: Invasive candidiasis is responsible for ∼ 10% of nosocomial sepsis in very-low-birth-weight infants and is associated with substantial morbidity and mortality. Over the last two decades, the antifungal armamentarium against Candida spp. has increased; however, efficacy and safety studies in this population are lacking.