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Paternal factors in neurodevelopmental toxicology: THC exposure of male rats causes long-lasting neurobehavioral effects in their offspring.
No full textThe potential health risks of cannabis are of growing concern, including effects on reproduction and development. Extensive research has investigated risks associated with maternal exposure to THC during gestation and its impacts on the development of offspring, but little research has been done regarding paternal THC exposure effects prior to conception. We have previously found that paternal THC exposure in rats causes changes in sperm methylation. In an initial study we also showed that a 12-day paternal THC exposure prior to conception alters locomotor activity and impairs cognitive function of their offspring. This study investigated the cross-generational effects of chronic paternal THC exposure in rats (0, 2, or 4 mg/kg/day SC for 28 days) prior to mating with drug naïve females. The offspring of THC-exposed male rats had significant alterations in locomotor activity and cognitive function. Specifically, during adolescence there was significant locomotor hyperactivity in the offspring of males exposed to 2 mg/kg/day of THC. During the novel object recognition task, the controls maintained their relative preference for the novel object across the duration of the ten-min session while the rats whose fathers received THC (2 mg/kg/day) showed a significantly greater drop-off in interest in the novel object during the second half of the session. Learning in the radial-arm maze was significantly delayed in the offspring of males exposed to 4 mg/kg/day of THC. This study shows that premating chronic paternal THC exposure at multiple dose regimens can cause long-lasting detrimental behavioral effects in their offspring, including abnormal locomotor activity and impaired cognitive function. Future studies should investigate the underlying mechanisms driving these aberrant developmental outcomes and seek to identify possible treatments of alleviation in the presence of paternal THC exposure
Predictive model for long-term patient satisfaction after surgery for grade I degenerative lumbar spondylolisthesis: insights from the Quality Outcomes Database.
No full textOBJECTIVESince the enactment of the Affordable Care Act in 2010, providers and hospitals have increasingly prioritized patient-centered outcomes such as patient satisfaction in an effort to adapt the "value"-based healthcare model. In the current study, the authors queried a prospectively maintained multiinstitutional spine registry to construct a predictive model for long-term patient satisfaction among patients undergoing surgery for Meyerding grade I lumbar spondylolisthesis.METHODSThe authors queried the Quality Outcomes Database for patients undergoing surgery for grade I lumbar spondylolisthesis between July 1, 2014, and June 30, 2016. The primary outcome of interest for the current study was patient satisfaction as measured by the North American Spine Surgery patient satisfaction index, which is measured on a scale of 1-4, with 1 indicating most satisfied and 4 indicating least satisfied. In order to identify predictors of higher satisfaction, the authors fitted a multivariable proportional odds logistic regression model for ≥ 2 years of patient satisfaction after adjusting for an array of clinical and patient-specific factors. The absolute importance of each covariate in the model was computed using an importance metric defined as Wald chi-square penalized by the predictor degrees of freedom.RESULTSA total of 502 patients, out of a cohort of 608 patients (82.5%) with grade I lumbar spondylolisthesis, undergoing either 1- or 2-level decompression (22.5%, n = 113) or 1-level decompression and fusion (77.5%, n = 389), met the inclusion criteria; of these, 82.1% (n = 412) were satisfied after 2 years. On univariate analysis, satisfied patients were more likely to be employed and working (41.7%, n = 172, vs 24.4%, n = 22; overall p = 0.001), more likely to present with predominant leg pain (23.1%, n = 95, vs 11.1%, n = 10; overall p = 0.02) but more likely to present with lower Numeric Rating Scale score for leg pain (median and IQR score: 7 [5-9] vs 8 [6-9]; p = 0.05). Multivariable proportional odds logistic regression revealed that older age (OR 1.57, 95% CI 1.09-2.76; p = 0.009), preoperative active employment (OR 2.06, 95% CI 1.27-3.67; p = 0.015), and fusion surgery (OR 2.3, 95% CI 1.30-4.06; p = 0.002) were the most important predictors of achieving satisfaction with surgical outcome.CONCLUSIONSCurrent findings from a large multiinstitutional study indicate that most patients undergoing surgery for grade I lumbar spondylolisthesis achieved long-term satisfaction. Moreover, the authors found that older age, preoperative active employment, and fusion surgery are associated with higher odds of achieving satisfaction
Essays in Currency Markets
No full textThis dissertation is comprised of three chapters, all with the aim to better understand currency behavior. The first chapter brings well-known, profitable currency trading signals to bear on the Meese-Rogoff puzzle (Meese and Rogoff (1983)), a robust finding regarding the difficulty of outperforming the random walk in forecasting nominal exchange rates in an out-of-sample fashion, particularly at short horizons, using macro aggregates. Using carry, momentum, and value trading signals, which resemble macro variables that have traditionally been considered in forecasting exchange rates, we find much more evidence of out-of-sample forecastability at short horizons when the signals are used in a cross-sectional, multilateral manner than in a time-series, bilateral manner. This suggests macro fundamentals may be more informative of exchange rates than previously thought, if considered jointly rather than pairwise as has conventionally been done. A caveat is that the forecast noise stemming from limited data availability renders both time-series and cross-sectional signals' outperformance against the random walk unreliable at short horizons in practice. The second chapter revisits the question of whether cross-sectional differences in currency excess returns can be accounted for by downside market risk. Estimating the downside risk model proposed by Burnside and Graveline (2014), a piecewise linear factor model that subsumes previous downside risk models of currencies, we find that downside market risk does a poor job in explaining the cross-section of currency portfolio returns, regardless of whether we use an equity-based or currency-based market factor. Even if the model were to price the cross-sectional returns well, we would still face counterintuitive factor model estimates that go against the basic assumption of risk aversion. That is, we find a downside market risk puzzle for currencies. The third chapter examines the relationship between fiscal sustainability and nominal exchange rate. Using the annual change in debt to GDP ratio as our measure of fiscal sustainability, we find that fiscal sustainability contains predictive information on exchange rate in both the time-series and cross-sectional dimensions, controlling for potentially confounding macroeconomic factors, and for up to three years. Impulse response estimates show that a shock to fiscal sustainability, i.e., an unanticipated increase in the debt ratio, induces a contemporaneous depreciation in exchange rate lasting for three to five years. All in all, we find strong evidence of a linkage between fiscal sustainability and nominal exchange rate.</p
Vertical sleeve gastrectomy associates with airway hyperresponsiveness in a murine model of allergic airway disease and obesity.
No full textIntroductionAsthma is a chronic airway inflammatory disease marked by airway inflammation, remodeling and hyperresponsiveness to allergens. Allergic asthma is normally well controlled through the use of beta-2-adrenergic agonists and inhaled corticosteroids; however, a subset of patients with comorbid obesity experience resistance to currently available therapeutics. Patients with asthma and comorbid obesity are also at a greater risk for severe disease, contributing to increased risk of hospitalization. Bariatric surgery improves asthma control and airway hyperresponsiveness in patients with asthma and comorbid obesity, however, the underlying mechanisms for these improvements remain to be elucidated. We hypothesized that vertical sleeve gastrectomy (VSG), a model of metabolic surgery in mice, would improve glucose tolerance and airway inflammation, resistance, and fibrosis induced by chronic allergen challenge and obesity.MethodsMale C57BL/6J mice were fed a high fat diet (HFD) for 13 weeks with intermittent house dust mite (HDM) allergen administration to induce allergic asthma, or saline as control. At week 11, a subset of mice underwent VSG or Sham surgery with one week recovery. A separate group of mice did not undergo surgery. Mice were then challenged with HDM or saline along with concurrent HFD feeding for 1-1.5 weeks before measurement of lung mechanics and harvesting of tissues, both of which occurred 24 hours after the final HDM challenge. Systemic and pulmonary cytokine profiles, lung histology and gene expression were analyzed.ResultsHigh fat diet contributed to increased body weight, serum leptin levels and development of glucose intolerance for both HDM and saline treatment groups. When compared to saline-treated mice, HDM-challenged mice exhibited greater weight gain. VSG improved glucose tolerance in both saline and HDM-challenged mice. HDM-challenged VSG mice exhibited an increase in airway hyperresponsiveness to methacholine when compared to the non-surgery group.DiscussionThe data presented here indicate increased airway hyperresponsiveness in allergic mice undergoing bariatric surgery
Transmission of Olfactory Information between Three Populations of Neurons in the Antennal Lobe of the Fly
No full textDo institutional investors facilitate corporate environmental innovation?
No full textThis paper addresses whether institutional investors drive firms’ innovation direction toward environmentally friendly technologies. The data pertain to comprehensive environmental patents filed by Chinese publicly-listed firms in the manufacturing and public utility sectors during the 2003–2015 period. We find that institutional investors are associated with higher ratios of environmental patents in total patents for firms in the pollution-intensive sectors than those in the non-pollution-intensive sectors. Institutional investors exert the roles of financial support and corporate governance in pursuit of monitoring firms’ long-term sustainable innovation. They further facilitate the information disclosure on corporate social responsibility
Morbidity and mortality in the surgical treatment of six hundred five pediatric patients with isthmic or dysplastic spondylolisthesis.
No full textStudy designRetrospective analysis of prospectively collected database.ObjectiveTo analyze the rate of complications, including neurologic deficits, associated with operative treatment of pediatric isthmic and dysplastic spondylolisthesis.Summary of background dataPediatric isthmic and dysplastic spondylolisthesis are relatively uncommon dis-orders. Several prior studies have suggested a high rate of complication associated with operative intervention. How-ever, most of these studies were performed with sufficiently small sample sizes such that the presence of one complication could significantly affect the overall rate. The Scoliosis Research Society (SRS) prospectively collects morbidity and mortality (M&M) data from its members. This multicentered, multisurgeon database permits analysis of the surgical treatment of this relatively rare condition on an aggregate scale and provides surgeons with useful information for preoperative counseling.MethodsPatients who underwent surgical treatment for isthmic or dysplastic spondylolisthesis from 2004 to 2007 were identified from the SRS M&M database. Inclusion criteria for analysis included age ≤ 21 and a primary diagnosis of isthmic or dysplastic spondylolisthesis.ResultsOf 25,432 pediatric cases reported, there were a total of 605 (2.4%) cases of pediatric dysplastic (n ∇ 62, 10%) and isthmic (n ∇ 543, 90%) spondylolisthesis, with a mean age of 15 years (range, 4-21). Approximately 50% presented with neural element compression, and less than 1% of cases were revisions. Surgical procedures included fusions in 92%, osteotomies in 39%, and reductions in 38%. The overall complication rate was 10.4%. The most common complications included postoperative neurologic deficit (n ∇ 31, 5%), dural tear (n ∇ 8, 1.3%), and wound infection (n ∇ 12, 2%). Perioperative deep venous thrombosis and pulmonary embolus were reported in 2 (0.3%) and 1 (0.2%) patients, respectively. There were no deaths in this series.ConclusionPediatric isthmic and dysplastic spondylolisthesis are relatively uncommon disorders, representing only 2.4% of pediatric spine procedures in the present study. Even among experienced spine surgeons, surgical treatment of these spinal conditions is associated with a relatively high morbidity
When can we expect global sagittal alignment to reach a stable value following cervical deformity surgery?
No full textObjectiveCervical deformity (CD) is a complex condition with a clear impact on patient quality of life, which can be improved with surgical treatment. Previous study following thoracolumbar surgery demonstrated a spontaneous and maintained improvement in cervical alignment following lumbar pedicle subtraction osteotomy (PSO). In this study the authors aimed to investigate the complementary questions of whether cervical alignment induces a change in global alignment and whether this change stabilizes over time.MethodsTo analyze spontaneous changes, this study included only patients with at least 5 levels remaining unfused following surgery. After data were obtained for the entire cohort, repeated-measures analyses were conducted between preoperative baseline and 3-month and 1-year follow-ups with a post hoc analysis and Bonferroni correction. A subanalysis of patients with 2-year follow-up was performed.ResultsOne-year follow-up data were available for 121 of 168 patients (72%), and 89 patients had at least 5 levels remaining unfused following surgery. Preoperatively there was a moderate anterior cervical alignment (C2-7, -7.7° [kyphosis]; T1 slope minus cervical lordosis, 37.1°; cervical sagittal vertebral axis [cSVA], 37 mm) combined with a posterior global alignment (SVA, -8 mm) with lumbar hyperextension (pelvic incidence [PI] minus lumbar lordosis [LL] mismatch [PI-LL], -0.6°). Patients underwent a significant correction of the cervical alignment (median ΔC2-7, 13.6°). Simultaneously, PI-LL, T1 pelvic angle (TPA), and SVA increased significantly (all p ConclusionsCorrection of cervical malalignment can have a significant impact on thoracolumbar regional and global alignment. Peak relaxation of compensatory mechanisms is achieved by the 3-month follow-up and tends to remain stable. Subanalysis with 2-year data further supports this finding. These findings can help to identify when the results of cervical surgery on global alignment can be best evaluated
Translating Neurobehavioral Toxicity Across Species From Zebrafish to Rats to Humans: Implications for Risk Assessment.
No full textThere is a spectrum of approaches to neurotoxicological science from high-throughput in vitro cell-based assays, through a variety of experimental animal models to human epidemiological and clinical studies. Each level of analysis has its own advantages and limitations. Experimental animal models give essential information for neurobehavioral toxicology, providing cause-and-effect information regarding risks of neurobehavioral dysfunction caused by toxicant exposure. Human epidemiological and clinical studies give the closest information to characterizing human risk, but without randomized treatment of subjects to different toxicant doses can only give information about association between toxicant exposure and neurobehavioral impairment. In vitro methods give much needed high throughput for many chemicals and mixtures but cannot provide information about toxicant impacts on behavioral function. Crucial to the utility of experimental animal model studies is cross-species translation. This is vital for both risk assessment and mechanistic determination. Interspecies extrapolation is important to characterize from experimental animal models to humans and between different experimental animal models. This article reviews the literature concerning extrapolation of neurobehavioral toxicology from established rat models to humans and from zebrafish a newer experimental model to rats. The functions covered include locomotor activity, emotion, and cognition and the neurotoxicants covered include pesticides, metals, drugs of abuse, flame retardants and polycyclic aromatic hydrocarbons. With more complete understanding of the strengths and limitations of interspecies translation, we can better use animal models to protect humans from neurobehavioral toxicity
Could a Sustainable Bio-Based Plastics Supply Chain Become a Commercial Reality?
No full textThe objective of this research is to examine the feasibility of scaling the bio-based plastics industry in a sustainable manner and to evaluate the commercial viability of its supply chain. Bio-based plastics present a viable alternative to the use of fossil fuels in conventional plastics by creating innovative plastics from renewable resources that have the potential to be compostable and emit less carbon dioxide than petroleum-based plastics. Nevertheless, the use of bio-based plastics presents certain obstacles, such as competition with food production, limited consumer awareness, and obstacles to achieving cost competitiveness with conventional plastics.
The report analyzes the current state of the bio-based plastics sector, identifies key challenges and opportunities, and presents recommendations for sustainably scaling the industry. As of 2021, the bio-based plastic market is valued at 46.1B USD by 2030 (Precedence Research). To identify opportunities for meeting this level of growth sustainably, the Master’s Project team conducted semi-structured interviews with stakeholders in the bio-based plastics industry and conducted desk research. The original scope of research was to determine how waste-based feedstocks for bio-based plastics are defined, however, based on feedback from interviewees, the Master’s Project team pivoted due to limited demand for waste-based solutions. The team adopted a more holistic approach to understand the market by analyzing different feedstock sources and end-of-life (EOL) options for bio-based plastics, as well as the role of the government and certification services to develop a sustainable, competitive alternative to the plastics industry.
Based on the report’s findings, a commercially viable and sustainable supply chain for bio-based plastic can be feasible. The report drew on desk-based research and interviews with ten stakeholders in the bio-based plastics sector including producers, buyers, certification services, and non-governmental organizations. As a result, five key areas were identified that stakeholders in the bio-based plastic value chain should consider to enhance the industry’s sustainability. These areas include: 1) Design with EOL in mind, 2) Create partnerships with stakeholders across the bio-based materials value chain, 3) Urge for a global standardized labeling process, 4) Consider bio-based plastic terminology and use of EOL terms carefully for better consumer education, and 5) Confirm how feedstock is sourced with suppliers