Liability Waivers and Participation Rates in Youth Sports: An Empirical Investigation

In this Article, we offer an empirical analysis of the relationship between liability waivers signed by parents and participation rates in youth sports. Specifically, we explore whether waiver enforcement is statistically associated with increased participation in youth sports. Our study finds no significant evidence of such a relationship. The impetus for this investigation comes from an experience shared by parents all over the United States. A parent enrolls his minor child in a sports activity like a school team, club sport, skating party, or tennis camp. Organizers condition the child’s participation on the parent signing a liability waiver in the organizers’ favor. Legally, doctrinal reasons exist to doubt the enforceability of these releases. Despite these concerns, many courts enforce youth sports releases. Although these decisions could be justified on grounds of parental autonomy and freedom of contract, the primary argument favoring enforcement asserts that youth sports releases serve minors’ interests, even at the cost of greater uncompensated injury. Without enforceable waivers, youth sports providers may reduce their offerings or go out of business to avoid tort liability risks. Conversely, allowing youth sports providers to avoid liability increases youth sports opportunities, and youth sports participation by extension, which confers benefits on youths outweighing any increased risk of uncompensated injury. This policy argument might be right. However, it is plausible only if youth sports participation increases when courts enforce exculpatory agreements signed by parents. However, no prior study has tested whether enforcing youth sports releases has the hypothesized effect. The study described here therefore provides valuable information about the persuasiveness of arguments on either side of a split in contract and tort law. We conducted our study by applying a linear mixed effects regression analysis6 to a dataset containing information about high school sports participation rates and the fifty states’ law including the District of Columbia from 1988-2014. This allowed us to test for an association between enforcing youth sports releases and high school sports participation rates. Our analysis uncovered no statistically significant association. This implies that the major argument given by courts for enforcing youth sports releases lacks empirical support

Prenatal Lead Levels, Plasma Amyloid β Levels, and Gene Expression in Young Adulthood

Background: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer’s disease (AD)

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities

Low-level environmental lead exposure in childhood and adult intellectual function: a follow-up study

<p>Abstract</p> <p>Background</p> <p>Early life lead exposure might be a risk factor for neurocognitive impairment in adulthood.</p> <p>Objectives</p> <p>We sought to assess the relationship between early life environmental lead exposure and intellectual function in adulthood. We also attempted to identify which time period blood-lead concentrations are most predictive of adult outcome.</p> <p>Methods</p> <p>We recruited adults in the Boston area who had participated as newborns and young children in a prospective cohort study that examined the relationship between lead exposure and childhood intellectual function. IQ was measured using the Wechsler Abbreviated Scale of Intelligence (WASI). The association between lead concentrations and IQ scores was examined using linear regression.</p> <p>Results</p> <p>Forty-three adults participated in neuropsychological testing. Childhood blood-lead concentration (mean of the blood-lead concentrations at ages 4 and 10 years) had the strongest relationship with Full-Scale IQ (β = -1.89 ± 0.70, p = 0.01). Full-scale IQ was also significantly related to blood-lead concentration at age 6 months (β = -1.66 ± 0.75, p = 0.03), 4 years (β = -0.90 ± 0.41, p = 0.03) and 10 years (β = -1.95 ± 0.80, p = 0.02). Adjusting for maternal IQ altered the significance of the regression coefficient.</p> <p>Conclusions</p> <p>Our study suggests that lead exposure in childhood predicts intellectual functioning in young adulthood. Our results also suggest that school-age lead exposure may represent a period of increased susceptibility. Given the small sample size, however, the potentially confounding effects of maternal IQ cannot be excluded and should be evaluated in a larger study.</p

Low-level environmental lead exposure in childhood and adult intellectual function: a follow-up study

<p>Abstract</p> <p>Background</p> <p>Early life lead exposure might be a risk factor for neurocognitive impairment in adulthood.</p> <p>Objectives</p> <p>We sought to assess the relationship between early life environmental lead exposure and intellectual function in adulthood. We also attempted to identify which time period blood-lead concentrations are most predictive of adult outcome.</p> <p>Methods</p> <p>We recruited adults in the Boston area who had participated as newborns and young children in a prospective cohort study that examined the relationship between lead exposure and childhood intellectual function. IQ was measured using the Wechsler Abbreviated Scale of Intelligence (WASI). The association between lead concentrations and IQ scores was examined using linear regression.</p> <p>Results</p> <p>Forty-three adults participated in neuropsychological testing. Childhood blood-lead concentration (mean of the blood-lead concentrations at ages 4 and 10 years) had the strongest relationship with Full-Scale IQ (β = -1.89 ± 0.70, p = 0.01). Full-scale IQ was also significantly related to blood-lead concentration at age 6 months (β = -1.66 ± 0.75, p = 0.03), 4 years (β = -0.90 ± 0.41, p = 0.03) and 10 years (β = -1.95 ± 0.80, p = 0.02). Adjusting for maternal IQ altered the significance of the regression coefficient.</p> <p>Conclusions</p> <p>Our study suggests that lead exposure in childhood predicts intellectual functioning in young adulthood. Our results also suggest that school-age lead exposure may represent a period of increased susceptibility. Given the small sample size, however, the potentially confounding effects of maternal IQ cannot be excluded and should be evaluated in a larger study.</p

Universal surface-enhanced Raman tags : individual nanorods for measurements from the visible to the infrared (514 – 1064 nm)

Surface-enhanced Raman scattering (SERS) is a promising imaging modality for use in a variety of multiplexed tracking and sensing applications in biological environments. However, the uniform production of SERS nanoparticle tags with high yield and brightness still remains a significant challenge. Here, we describe an approach based on the controlled co-adsorption of multiple dye species onto gold nanorods to create tags that can be detected across a much wider range of excitation wavelengths (514 – 1064 nm) compared to conventional approaches that typically focus on a single wavelength. This was achieved without the added complexity of nanoparticle aggregation or growing surrounding metallic shells to further enhance the surface-enhanced resonance Raman scattering (SERRS) signal. Correlated Raman and scanning electron microscopy mapping measurements of individual tags were used to clearly demonstrate that strong and reproducible SERRS signals at high particle yields (>92 %) were readily achievable. The polyelectrolyte-wrapped nanorod-dye conjugates were also found to be highly stable as well as non-cytotoxic. To demonstrate the use of these universal tags for the multimodal optical imaging of biological specimens, confocal Raman and fluorescence maps of stained immune cells following nanoparticle uptake were acquired at several excitation wavelengths and compared with dark-field images. The ability to colocalize and track individual optically encoded nanoparticles across a wide range of wavelengths simultaneously will enable the use of SERS alongside other imaging techniques for the real-time monitoring of cell-nanoparticle interactions

Raman spectroscopy: techniques and applications in the life sciences

Raman spectroscopy is an increasingly popular technique in many areas including biology and medicine. It is based on Raman scattering, a phenomenon in which incident photons lose or gain energy via interactions with vibrating molecules in a sample. These energy shifts can be used to obtain information regarding molecular composition of the sample with very high accuracy. Applications of Raman spectroscopy in the life sciences have included quantification of biomolecules, hyperspectral molecular imaging of cells and tissue, medical diagnosis, and others. This review briefly presents the physical origin of Raman scattering explaining the key classical and quantum mechanical concepts. Variations of the Raman effect will also be considered, including resonance, coherent, and enhanced Raman scattering. We discuss the molecular origins of prominent bands often found in the Raman spectra of biological samples. Finally, we examine several variations of Raman spectroscopy techniques in practice, looking at their applications, strengths, and challenges. This review is intended to be a starting resource for scientists new to Raman spectroscopy, providing theoretical background and practical examples as the foundation for further study and exploration

Development of Plasmonics-active Nanoconstructs for Targeting, Tracking, and Delivery in Single Cells

<p>Although various proof-of-concept studies have demonstrated the eventual potential of a multifunctional SERS-active metallic nanostructures for biological applications such as single cell analysis/measurement and drug delivery, the actual development and testing of such a system in vitro has remained challenging. One key point at which many potentially useful biomethods encounter difficulty lies in the translation of early proof-of-concept experiments in a clean, aqueous solution to complex, crowded, biologically-active environments such as the interior of living cells. The research hypotheses for this work state that multifunctional nanoconstructs can be fabricated and used effectively in conjunction with surface-enhanced Raman scattering (SERS) spectroscopy and other photonics-based methods to make intracellular measurements in and deliver treatment to single cells. The results of experimental work address the specific research aims, to 1) establish temporal and spatial parameters of nanoprobe uptake and modulation, 2) demonstrate targeting of functionalized nanoparticles to the cytoplasm and nucleus of single cells, 3) deliver to and activate drug treatment in cells using a multifunctional nanosystem, and 4) make intracellular measurements in normal and disease cells using external nanoprobes,</p><p>Raman spectroscopy and two-dimensional Raman imaging were used to identify and locate labeled silver nanoparticles in single cells using SERS detection. To study the efficiency of cellular uptake, silver nanoparticles were functionalized with three differently charged SERS/Raman labels and co-incubated with J774 mouse macrophage cell cultures for internalization via normal cellular processes. The surface charge on the nanoparticles was observed to modulate uptake efficiency, demonstrating a dual function of the surface modifications as tracking labels and as modulators of cell uptake. </p><p>To demonstrate delivery of functionalized nanoparticles to specific locations within the cell, silver nanoparticles were co-functionalized with the HIV-1 TAT (49-57) peptide for cell-penetrating and nuclear-targeting ability and p-mercaptobenzoic acid (pMBA) molecules as a surface-enhanced Raman scattering (SERS) label for tracking and imaging. Two-dimensional SERS mapping was used to track the spatial and temporal progress of nanoparticle uptake in PC-3 human prostate cells and to characterize localization at various time points, demonstrating the potential for an intracellularly-targeted multiplexed nanosystem. Silver nanoparticles co-functionalized with the TAT peptide showed greatly enhanced cellular uptake and nuclear localization as compared with the control nanoparticles lacking the targeting moiety. </p><p>The efficacy of targeted nanoparticles as a drug delivery vehicle was demonstrated with development and testing of an anti-cancer treatment in which novel scintillating nanoparticles functionalized with HIV-1 TAT (49-57) for cell-penetrating and nuclear-targeting ability were loaded with tethered psoralen molecules as cargo. The experiments were designed to investigate a nanodrug system consisting of psoralen tethered to a nuclear targeting peptide anchored to UVA-emitting, X-ray luminescent yttrium oxide nanoparticles. Absorption of the emitted UVA photons by nanoparticle-tethered psoralen has the potential to cross-link adenine and thymine residues in DNA located in the nucleus. Such cross-linking by free psoralen following activation with UVA light has previously been shown to cause apoptosis in vitro and an immunogenic response in vivo. Experimental results using the PC-3 human prostate cancer cell line demonstrate that X-ray excitation of these psoralen-functionalized Y2O3 nanoscintillators yields concentration-dependent reductions in cell number density when compared to control cultures containing psoralen-free Y2O3 nanoscintillators. </p><p>The development and demonstration of a small molecule-sensitive SERS-active fiber-optic nanoprobe suitable for intracellular bioanalysis was demonstrated using pH measurements in single living human cells. The proof-of-concept for the SERS-based fiber-optic nanoprobes was illustrated by measurements of intracellular pH in MCF-7 human breast cancer, HMEC-15/hTERT immortalized normal human mammary epithelial, and PC-3 human prostate cancer cells. Clinical relevance was demonstrated by pH measurements in patient biopsy cell samples. The results indicated that that fiber-optic nanoprobe insertion and interrogation provide a sensitive and selective means to monitor biologically relevant small molecules at the single cell level.</p>Dissertatio

Trajectories of Change in Body Weight During Inpatient Treatment for Anorexia Nervosa

BACKGROUND: Identifying distinct trajectories of change in body weight during inpatient treatment for anorexia nervosa (AN) may provide knowledge about the process of weight restoration and may help detect optimal body weight response patterns among individuals who are at risk for not achieving weight restoration or leaving treatment prematurely. OBJECTIVE: This study explored the extent to which distinct trajectories of change in body weight existed among individuals during inpatient treatment for AN. DESIGN: Group-based trajectory modeling was used to identify distinct trajectories of change in body weight among 500 individuals receiving inpatient treatment for AN. RESULTS: Four distinct trajectories were identified: weight gain (n = 197), treatment resistant (n = 177), weight plateau (n = 82), and weight fluctuate (n = 44). CONCLUSION: Clinically, it is important to consider the heterogeneity of changes in body weight during inpatient treatment to help guide interventions and outcomes

Risperidone use in autism spectrum disorders: a retrospective review of a clinic-referred patient population.

Risperidone is widely used in children with autism spectrum disorders for behavioral modification. In this study, the authors aimed to (1) describe a clinic-referred sample of patients with an autism spectrum disorder on risperidone, (2) identify differences between the success and nonsuccess groups, and (3) describe our experience with young children (&lt; age 5 years) on risperidone. Eighty patients were initiated on risperidone. Indications included aggression (66%), impulsivity (14%), and stereotypies (4%). Sixty-six percent met criteria for success at 6 months and 53% at 1 year. Sixty-seven percent of the nonsuccess group reported side effects, compared to 47% of the success group. Weight gain was the most common side effect in both groups, followed by somnolence. Somnolence was the most robust predictor of nonsuccess. In our clinic-referred sample, the short-term success rate of risperidone was more than 50%, and side effects limited its use. Although weight gain was common, somnolence more significantly influenced treatment discontinuation