A Value Relevance Examination of the Current Leasing Standard

In the wake of the prominent accounting scandals of the past several years, investors and standard setters are demanding increased corporate transparency. Nowhere is the demand for transparency more salient than with off-balance-sheet financing, of which lease accounting plays a major role. At the end of 2004, total rental commitments by U.S. firms from off balance-sheet operating leases exceeded $1 trillion. As standard setters reconsider leases as part of their broad reexamination of off-balance-sheet financing, they do so without the benefit of empirical research documenting whether capital market participants find the current leasing standard value relevant. This paper examines whether as-if capitalized operating lease liabilities and capital lease liabilities are both relevant and sufficiently reliable to be priced and explores whether equity investors value operating and capital leases differently. The results are consistent with the market viewing both operating and capital leases as economic liabilities of the firm. However, the results also indicate that capital market participants price operating and capital lease liabilities differently, consistent with the bright-line tests of the current leasing standard identifying economic differences in operating and capital leases. Thus, continuing to require lease disclosures by different lease classifications would assure that equity investors will not suffer from a loss of value relevant information in the pricing of leases

Effect of smoking status on total energy expenditure

Individuals who smoke generally have a lower body mass index (BMI) than nonsmokers. The relative roles of energy expenditure and energy intake in maintaining the lower BMI, however, remain controversial. We tested the hypothesis that current smokers have higher total energy expenditure than never smokers in 308 adults aged 40-69 years old of which 47 were current smokers. Energy expenditure was measured by doubly labeled water during a two week period in which the subjects lived at home and performed their normal activities. Smoking status was determined by questionnaire. There were no significant differences in mean BMI (mean ± SD) between smokers and never smokers for either males (27.8+5.1 kg/m2 vs. 27.5+4.0 kg/m2) or females (26.5+5.3 kg/m2 vs. 28.1+6.6 kg/m2), although the difference in females was of similar magnitude to previous reports. Similarly, total energy expenditure of male smokers (3069+764 kcal/d) was not significantly different from that of never smokers (2854+468 kcal/d), and that of female smokers (2266+387 kcal/d) was not different from that of never smokers (2330+415 kcal/d). These findings did not change after adjustment for age, fat-free mass and self-reported physical activity. Using doubly labeled water, we found no evidence of increased energy expenditure among smokers, however, it should be noted that BMI differences in this cohort also did not differ by smoking status

Oropharyngeal Microbiome Profiled at Admission is Predictive of the Need for Respiratory Support Among COVID-19 Patients [preprint]

The clinical course of infection due to respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), the causative agent of Coronavirus Disease 2019 (COVID-19) is thought to be influenced by the community of organisms that colonizes the upper respiratory tract, the oropharyngeal microbiome. In this study, we examined the oropharyngeal microbiome of suspected COVID-19 patients presenting to the Emergency Department and an inpatient COVID-19 unit with symptoms of acute COVID-19. Of 115 enrolled patients, 74 were confirmed COVID-19+ and 50 had symptom duration of 14 days or less; 38 acute COVID-19+ patients (76%) went on to require respiratory support. Although no microbiome features were found to be significantly different between COVID-19+ and COVID-19-patients, when we conducted random forest classification modeling (RFC) to predict the need of respiratory support for the COVID-19+ patients our analysis identified a subset of organisms and metabolic pathways whose relative abundance, when combined with clinical factors (such as age and Body Mass Index), was highly predictive of the need for respiratory support (F1 score 0.857). Microbiome Multivariable Association with Linear Models (MaAsLin2) analysis was then applied to the features identified as predicative of the need for respiratory support by the RFC. This analysis revealed reduced abundance of Prevotella salivae and metabolic pathways associated with lipopolysaccharide and mycolic acid biosynthesis to be the strongest predictors of patients requiring respiratory support. These findings suggest that composition of the oropharyngeal microbiome in COVID-19 may play a role in determining who will suffer from severe disease manifestations. Importance: The microbial community that colonizes the upper airway, the oropharyngeal microbiome, has the potential to affect how patients respond to respiratory viruses such as SARS-CoV2, the causative agent of COVID-19. In this study, we investigated the oropharyngeal microbiome of COVID-19 patients using high throughput DNA sequencing performed on oral swabs. We combined patient characteristics available at intake such as medical comorbidities and age, with measured abundance of bacterial species and metabolic pathways and then trained a machine learning model to determine what features are predicative of patients needing respiratory support in the form of supplemental oxygen or mechanical ventilation. We found that decreased abundance of some bacterial species and increased abundance of pathways associated bacterial products biosynthesis was highly predictive of needing respiratory support. This suggests that the oropharyngeal microbiome affects disease course in COVID-19 and could be targeted for diagnostic purposes to determine who may need oxygen, or therapeutic purposes such as probiotics to prevent severe COVID-19 disease manifestations

The structure–activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface

We recently reported the discovery of UNC1215, a potent and selective chemical probe for the L3MBTL3 methyllysine reader domain. In this article, we describe the development of structure-activity relationships (SAR) of a second series of potent L3MBTL3 antagonists which evolved from the structure of the chemical probe UNC1215. These compounds are selective for L3MBTL3 against a panel of methyllysine reader proteins, particularly the related MBT family proteins, L3MBTL1 and MBTD1. A co-crystal structure of L3MBTL3 and one of the most potent compounds suggests that the L3MBTL3 dimer rotates about the dimer interface to accommodate ligand binding

Neonicotinoid seed treatments of soybean provide negligible benefits to US farmers

Neonicotinoids are the most widely used insecticides worldwide and are typically deployed as seed treatments (hereafter NST) in many grain and oilseed crops, including soybeans. However, there is a surprising dearth of information regarding NST effectiveness in increasing soybean seed yield, and most published data suggest weak, or inconsistent yield benefit. The US is the key soybean-producing nation worldwide and this work includes soybean yield data from 194 randomized and replicated field studies conducted specifically to evaluate the effect of NSTs on soybean seed yield at sites within 14 states from 2006 through 2017. Here we show that across the principal soybean-growing region of the country, there are negligible and management-specific yield benefits attributed to NSTs. Across the entire region, the maximum observed yield benefits due to fungicide (FST = fungicide seed treatment) + neonicotinoid use (FST + NST) reached 0.13 Mg/ha. Across the entire region, combinations of management practices affected the effectiveness of FST + N ST to increase yield but benefits were minimal ranging between 0.01 to 0.22 Mg/ha. Despite widespread use, this practice appears to have little benefit for most of soybean producers; across the entire region, a partial economic analysis further showed inconsistent evidence of a break-even cost of FST or FST + N ST. These results demonstrate that the current widespread prophylactic use of NST in the key soybean-producing areas of the US should be re-evaluated by producers and regulators alike

Neonicotinoid seed treatments of soybean provide negligible benefits to US farmers

Neonicotinoids are the most widely used insecticides worldwide and are typically deployed as seed treatments (hereafter NST) in many grain and oilseed crops, including soybeans. However, there is a surprising dearth of information regarding NST effectiveness in increasing soybean seed yield, and most published data suggest weak, or inconsistent yield benefit. The US is the key soybean-producing nation worldwide and this work includes soybean yield data from 194 randomized and replicated field studies conducted specifically to evaluate the effect of NSTs on soybean seed yield at sites within 14 states from 2006 through 2017. Here we show that across the principal soybean-growing region of the country, there are negligible and management-specific yield benefits attributed to NSTs. Across the entire region, the maximum observed yield benefits due to fungicide (FST = fungicide seed treatment) + neonicotinoid use (FST + NST) reached 0.13 Mg/ha. Across the entire region, combinations of management practices affected the effectiveness of FST + N ST to increase yield but benefits were minimal ranging between 0.01 to 0.22 Mg/ha. Despite widespread use, this practice appears to have little benefit for most of soybean producers; across the entire region, a partial economic analysis further showed inconsistent evidence of a break-even cost of FST or FST + N ST. These results demonstrate that the current widespread prophylactic use of NST in the key soybean-producing areas of the US should be re-evaluated by producers and regulators alike

Functional identification of biological neural networks using reservoir adaptation for point processes

The complexity of biological neural networks does not allow to directly relate their biophysical properties to the dynamics of their electrical activity. We present a reservoir computing approach for functionally identifying a biological neural network, i.e. for building an artificial system that is functionally equivalent to the reference biological network. Employing feed-forward and recurrent networks with fading memory, i.e. reservoirs, we propose a point process based learning algorithm to train the internal parameters of the reservoir and the connectivity between the reservoir and the memoryless readout neurons. Specifically, the model is an Echo State Network (ESN) with leaky integrator neurons, whose individual leakage time constants are also adapted. The proposed ESN algorithm learns a predictive model of stimulus-response relations in in vitro and simulated networks, i.e. it models their response dynamics. Receiver Operating Characteristic (ROC) curve analysis indicates that these ESNs can imitate the response signal of a reference biological network. Reservoir adaptation improved the performance of an ESN over readout-only training methods in many cases. This also held for adaptive feed-forward reservoirs, which had no recurrent dynamics. We demonstrate the predictive power of these ESNs on various tasks with cultured and simulated biological neural networks

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter's transformation

: Richter's Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases

The Naked Truth: The Face and Body Sensitive N170 Response Is Enhanced for Nude Bodies

Recent event-related potential studies have shown that the occipitotemporal N170 component - best known for its sensitivity to faces - is also sensitive to perception of human bodies. Considering that in the timescale of evolution clothing is a relatively new invention that hides the bodily features relevant for sexual selection and arousal, we investigated whether the early N170 brain response would be enhanced to nude over clothed bodies. In two experiments, we measured N170 responses to nude bodies, bodies wearing swimsuits, clothed bodies, faces, and control stimuli (cars). We found that the N170 amplitude was larger to opposite and same-sex nude vs. clothed bodies. Moreover, the N170 amplitude increased linearly as the amount of clothing decreased from full clothing via swimsuits to nude bodies. Strikingly, the N170 response to nude bodies was even greater than that to faces, and the N170 amplitude to bodies was independent of whether the face of the bodies was visible or not. All human stimuli evoked greater N170 responses than did the control stimulus. Autonomic measurements and self-evaluations showed that nude bodies were affectively more arousing compared to the other stimulus categories. We conclude that the early visual processing of human bodies is sensitive to the visibility of the sex-related features of human bodies and that the visual processing of other people's nude bodies is enhanced in the brain. This enhancement is likely to reflect affective arousal elicited by nude bodies. Such facilitated visual processing of other people's nude bodies is possibly beneficial in identifying potential mating partners and competitors, and for triggering sexual behavior