ABSTRACT
Suppose that the 300+ published asset pricing factors are all spurious. How much p‐hacking is required to produce these factors? If 10,000 researchers generate eight factors every day, it ...takes hundreds of years. This is because dozens of published t‐statistics exceed 6.0, while the corresponding p‐value is infinitesimal, implying an astronomical amount of p‐hacking in a general model. More structure implies that p‐hacking cannot address ≈100 published t‐statistics that exceed 4.0, as they require an implausibly nonlinear preference for t‐statistics or even more p‐hacking. These results imply that mispricing, risk, and/or frictions have a key role in stock returns.
Many types of thermometers have been developed to measure body temperature. Infrared thermometers (IRT) are fast, convenient and ease to use. Two types of infrared thermometers are uses to measure ...body temperature: tympanic and forehead. With the spread of COVID-19 coronavirus, forehead temperature measurement is used widely to screen people for the illness. The performance of this type of device and the criteria for screening are worth studying. This study evaluated the performance of two types of tympanic infrared thermometers and an industrial infrared thermometer. The results showed that these infrared thermometers provide good precision. A fixed offset between tympanic and forehead temperature were found. The measurement values for wrist temperature show significant offsets with the tympanic temperature and cannot be used to screen fevers. The standard operating procedure (SOP) for the measurement of body temperature using an infrared thermometer was proposed. The suggestion threshold for the forehead temperature is 36 °C for screening of fever. The body temperature of a person who is possibly ill is then measured using a tympanic infrared thermometer for the purpose of a double check.
Most of the natural variation in wheat vernalization response is determined by allelic differences in the MADS-box transcription factor VERNALIZATION1 (VRN1). Extended exposures to low temperatures ...during the winter (vernalization) induce VRN1 expression and promote the transition of the apical meristem to the reproductive phase. In contrast to its Arabidopsis homolog (APETALA1), which is mainly expressed in the apical meristem, VRN1 is also expressed at high levels in the leaves, but its function in this tissue is not well understood. Using tetraploid wheat lines with truncation mutations in the two homoeologous copies of VRN1 (henceforth vrn1-null mutants), we demonstrate that a central role of VRN1 in the leaves is to maintain low transcript levels of the VRN2 flowering repressor after vernalization. Transcript levels of VRN2 were gradually down-regulated during vernalization in both mutant and wild-type genotypes, but were up-regulated after vernalization only in the vrn1-null mutants. The up-regulation of VRN2 delayed flowering by repressing the transcription of FT, a flowering-integrator gene that encodes a mobile protein that is transported from the leaves to the apical meristem to induce flowering. The role of VRN2 in the delayed flowering of the vrn1-null mutant was confirmed using double vrn1-vrn2-null mutants, which flowered two months earlier than the vrn1-null mutants. Both mutants produced normal flowers and seeds demonstrating that VRN1 is not essential for wheat flowering, which contradicts current flowering models. This result does not diminish the importance of VRN1 in the seasonal regulation of wheat flowering. The up-regulation of VRN1 during winter is required to maintain low transcript levels of VRN2, accelerate the induction of FT in the leaves, and regulate a timely flowering in the spring. Our results also demonstrate the existence of redundant wheat flowering genes that may provide new targets for engineering wheat varieties better adapted to changing environments.
We zero in on the expected returns of long-short portfolios based on 204 stock market anomalies by accounting for i) effective bid–ask spreads, ii) post-publication effects, and iii) the modern era ...of trading technology that began in the early 2000s. Net of these effects, the average anomaly’s expected return is a measly 4 bps per month. The strongest anomalies net, at best, 10 bps after controlling for data mining. Several methods for combining anomalies net around 20 bps. Expected returns are negligible despite cost mitigations that produce impressive net returns in-sample and the omission of additional trading costs, like price impact.
Glioblastoma multiforme (GBM) is an aggressive form of human brain cancer that is under active study in the field of cancer biology. Its rapid progression and the relative time cost of obtaining ...molecular data make other readily available forms of data, such as images, an important resource for actionable measures in patients. Our goal is to use information given by medical images taken from GBM patients in statistical settings. To do this, we design a novel statistic-the smooth Euler characteristic transform (SECT)-that quantifies magnetic resonance images of tumors. Due to its well-defined inner product structure, the SECT can be used in a wider range of functional and nonparametric modeling approaches than other previously proposed topological summary statistics. When applied to a cohort of GBM patients, we find that the SECT is a better predictor of clinical outcomes than both existing tumor shape quantifications and common molecular assays. Specifically, we demonstrate that SECT features alone explain more of the variance in GBM patient survival than gene expression, volumetric features, and morphometric features. The main takeaways from our findings are thus 2-fold. First, they suggest that images contain valuable information that can play an important role in clinical prognosis and other medical decisions. Second, they show that the SECT is a viable tool for the broader study of medical imaging informatics.
Supplementary materials
for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
Methadone is a synthetic opioid used as maintenance treatment for patients addicted to heroin. Skin irritation is one of the adverse events caused by opioid use. 344 methadone maintenance treatment ...(MMT) patients were recruited with records and measurements on methadone dose, plasma methadone concentrations, and treatment emergent symptom scales (TESS). 15 patients reported with skin irritation. Five SNPs located within the NECTIN4 genetic region were genotyped. The NECTIN4 gene within the adherens junction interaction pathway was associated with methadone dose in pathway-based genome wide association analyses (P = 0.0008). Three highly-linked SNPs, rs11265549, rs3820097, and rs4656978, were significantly associated with methadone dose (P = 0.0003), plasma concentrations of R,S-methadone (P = 0.0004) and TNF-α (P = 0.010) in all 344 MMT patients, and with self-report skin irritation symptom scores (P = 0.010) in the 15 MMT patients who reported with skin irritation. To identify the possible roles of plasma level of Nectin-4 in the responses to MMT and opioid use, additional age- and gender-matched 51 controls and 83 methadone-free abstinent former heroin users were recruited. Plasma level of Nectin-4 was the highest in MMT patients among the three groups. The results suggest involvement of genetic variants on NECTIN4 in methadone dose. Plasma Nectin-4 level is likely an indicator for continued use of opioids.
•Created bilateral chronic windows for imaging through the intact mouse skull.•Includes a head-fixing screw for immobilizing the head during awake imaging.•Preparation is stable for awake, widefield ...imaging of neuronal activity with GCaMP6.•Functional connectivity maps were generated from awake spontaneous activity.
Craniotomy-based window implants are commonly used for microscopic imaging, in head-fixed rodents, however their field of view is typically small and incompatible with mesoscopic functional mapping of cortex.
We describe a reproducible and simple procedure for chronic through-bone wide-field imaging in awake head-fixed mice providing stable optical access for chronic imaging over large areas of the cortex for months.
The preparation is produced by applying clear-drying dental cement to the intact mouse skull, followed by a glass coverslip to create a partially transparent imaging surface. Surgery time takes about 30min. A single set-screw provides a stable means of attachment (in relation to the measured lateral and axial resolution) for mesoscale assessment without obscuring the cortical field of view.
We demonstrate the utility of this method by showing seed-pixel functional connectivity maps generated from spontaneous cortical activity of GCAMP6 signals in both awake and anesthetized mice in longitudinal studies of up to 2 months in duration.
We propose that the intact skull preparation described here may be used for most longitudinal studies that do not require micron scale resolution and where cortical neural or vascular signals are recorded with intrinsic sensors or in transgenic mice expressing genetically encoded sensors of activity.
We characterize the structure and origins of missingness for 159 cross-sectional return predictors and study missing value handling for portfolios constructed using machine learning. Simply imputing ...with cross-sectional means performs well compared to rigorous expectation-maximization methods. This stems from three facts about predictor data: (1) missingness occurs in large blocks organized by time, (2) cross-sectional correlations are small, and (3) missingness tends to occur in blocks organized by the underlying data source. As a result, observed data provide little information about missing data. Sophisticated imputations introduce estimation noise that can lead to underperformance if machine learning is not carefully applied.
Immune checkpoint inhibitors have been successful across several tumor types; however, their efficacy has been uncommon and unpredictable in glioblastomas (GBM), where <10% of patients show long-term ...responses. To understand the molecular determinants of immunotherapeutic response in GBM, we longitudinally profiled 66 patients, including 17 long-term responders, during standard therapy and after treatment with PD-1 inhibitors (nivolumab or pembrolizumab). Genomic and transcriptomic analysis revealed a significant enrichment of PTEN mutations associated with immunosuppressive expression signatures in non-responders, and an enrichment of MAPK pathway alterations (PTPN11, BRAF) in responders. Responsive tumors were also associated with branched patterns of evolution from the elimination of neoepitopes as well as with differences in T cell clonal diversity and tumor microenvironment profiles. Our study shows that clinical response to anti-PD-1 immunotherapy in GBM is associated with specific molecular alterations, immune expression signatures, and immune infiltration that reflect the tumor's clonal evolution during treatment.
Eyes-closed (EC) and eyes-open (EO) are essential behaviors in mammalians, including man. At resting EC-EO state, brain activity in the default mode devoid of task-demand has recently been ...established in fMRI. However, the corresponding comprehensive electrophysiological conditions are little known even though EEG has been recorded in humans for nearly 80 years. In this study, we examined the spatial characteristics of spectral distribution in EEG field powers, i.e., sitting quietly with an EC and EO resting state of 3 min each, measured with high-density 128-ch EEG recording and FFT signal analyses in 15 right-handed healthy college females. Region of interest was set at a threshold at 90% of the spectral effective value to delimit the dominant spatial field power of effective energy in brain activity. Low-frequency delta (0.5–3.5 Hz) EEG field power was distributed at the prefrontal area with great expansion of spatial field and enhancement of field power (t=–2.72, p<0.02) from the EC to the EO state. Theta (4–7 Hz) EEG field power was distributed over the fronto-central area and leaned forward from EC to the EO state but with drastic reduction in field power (t=4.04, p<0.01). The middle-frequency alpha-1 (7.5–9.5 Hz) and alpha-2 (10–12 Hz) EEG powers exhibited bilateral distribution over the posterior areas with an anterior field in lower alpha-1. Both showed significantly reduction of field powers (respectively, W=120, p<0.001 for alpha-1; t=4.12, p<0.001 for alpha-2) from EC to the EO state. Beta-1 (13–23 Hz) exhibited a similar spatial region over the posterior area as in alpha-2 and showed reduction of field power (t=4.42, p<0.001) from EC to the EO state. In contrast, high-frequency beta-2 and gamma band exhibited similar, mainly prefrontal distribution in field power, and exhibited no change from EC to the EO state. Corresponding correlation analyses indicated significant group association between EC and EO only in the field powers of delta (r=0.95, p<0.001) and theta (r=0.77, p<0.001) band. In addition, the great inter-individual variability (90 folds in alpha-1, 62 folds in alpha-2) in regional field power was largely observed in the EC state (10 folds) than the EO state in subjects. To summarize, our study depicts a network of spectral EEG activities simultaneously operative at well defined regional fields in the EC state, varying specifically between EC and EO states. In contrast to transient EEG spectral rhythmic dynamics, current study of long-lasting (e.g. 3 min) spectral field powers can characterize state features in EEG. The EEG default mode network (EEG-DMN) of spectral field powers at rest in the respective EC or EO state is valued to serve as the basal electrophysiological condition in human brain. In health, this EEG-DMN is deemed essential for evaluation of brain functions without task demands for gender difference, developmental change in age span, and brain response to task activation. It is expected to define brain dysfunction in disease at resting state and with consequences for sensory, affective and cognitive alteration in the human brain.
PDF
