Nonparametric inference under a monotone hazard ratio order

The ratio of the hazard functions of two populations or two strata of a single population plays an important role in time-to-event analysis. Cox regression is commonly used to estimate the hazard ratio under the assumption that it is constant in time, which is known as the proportional hazards assumption. However, this assumption is often violated in practice, and when it is violated, the parameter estimated by Cox regression is difficult to interpret. The hazard ratio can be estimated in a nonparametric manner using smoothing, but smoothing-based estimators are sensitive to the selection of tuning parameters, and it is often difficult to perform valid inference with such estimators. In some cases, it is known that the hazard ratio function is monotone. In this article, we demonstrate that monotonicity of the hazard ratio function defines an invariant stochastic order, and we study the properties of this order. Furthermore, we introduce an estimator of the hazard ratio function under a monotonicity constraint. We demonstrate that our estimator converges in distribution to a mean-zero limit, and we use this result to construct asymptotically valid confidence intervals. Finally, we conduct numerical studies to assess the finite-sample behavior of our estimator, and we use our methods to estimate the hazard ratio of progression-free survival in pulmonary adenocarcinoma patients treated with gefitinib or carboplatin-paclitaxel

Pre-trained transformer for adversarial purification

With more and more deep neural networks being deployed as various daily services, their reliability is essential. It's frightening that deep neural networks are vulnerable and sensitive to adversarial attacks, the most common one of which for the services is evasion-based. Recent works usually strengthen the robustness by adversarial training or leveraging the knowledge of an amount of clean data. However, in practical terms, retraining and redeploying the model need a large computational budget, leading to heavy losses to the online service. In addition, when adversarial examples of a certain attack are detected, only limited adversarial examples are available for the service provider, while much clean data may not be accessible. Given the mentioned problems, we propose a new scenario, RaPiD (Rapid Plug-in Defender), which is to rapidly defend against a certain attack for the frozen original service model with limitations of few clean and adversarial examples. Motivated by the generalization and the universal computation ability of pre-trained transformer models, we come up with a new defender method, CeTaD, which stands for Considering Pre-trained Transformers as Defenders. In particular, we evaluate the effectiveness and the transferability of CeTaD in the case of one-shot adversarial examples and explore the impact of different parts of CeTaD as well as training data conditions. CeTaD is flexible, able to be embedded into an arbitrary differentiable model, and suitable for various types of attacks

Activation Of α7 Nicotinic Acetylcholine Receptors Prevents Monosodium Iodoacetate-Induced Osteoarthritis In Rats

Background/Aims: Although some evidence suggests that the prevalence of osteoarthritis (OA) is lower in smokers compared to nonsmokers, the mechanisms of nicotine-induced protection remain unclear. Stimulation of the α7 nicotinic acetylcholine receptor (α7-nAChR) appears to be a critical mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells. The inhibition of secreted inflammatory molecules and the subsequent inflammatory processes have been proposed as a novel strategy for the treatment of OA. The objective of the present study was to determine whether nicotine-induced protection in a monosodium iodoacetate (MIA) rat model of OA occurs via α7-nAChR-mediated inhibition of chondrocytes. Methods: Both in vivo (MIA) and in vitro (MIA; Interleukin-1β, IL-1β) models of OA were used to investigate the roles and the possible mechanisms whereby α7-nAChRs protect against knee joint degradation. Multiple experimental approaches, including macroscopic, histological analysis, chondrocyte cell cultures, confocal microscopy, and western blotting, were employed to elucidate the mechanisms of α7-nAChR-mediated protection. Results: Systemic administration of nicotine alleviated MIA-induced joint degradation. The protective effects of nicotine were abolished by administration of the α7-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured rat chondrocytes, pretreatment with nicotine suppressed both p38, extracellular regulated kinase (Erk) 1/2 and c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinases (MAPK) phosphorylation and phosphorylated nuclear factor-kappa B (NF-κB) p65 activation induced by MIA- or IL-1β, and these effects were also reversed by MLA. Conclusion: Taken together, our results suggest that activation α7-nAChRs is an important mechanism underlying the protective effects of nicotine

Harnessing the Spatial-Temporal Attention of Diffusion Models for High-Fidelity Text-to-Image Synthesis

Diffusion-based models have achieved state-of-the-art performance on text-to-image synthesis tasks. However, one critical limitation of these models is the low fidelity of generated images with respect to the text description, such as missing objects, mismatched attributes, and mislocated objects. One key reason for such inconsistencies is the inaccurate cross-attention to text in both the spatial dimension, which controls at what pixel region an object should appear, and the temporal dimension, which controls how different levels of details are added through the denoising steps. In this paper, we propose a new text-to-image algorithm that adds explicit control over spatial-temporal cross-attention in diffusion models. We first utilize a layout predictor to predict the pixel regions for objects mentioned in the text. We then impose spatial attention control by combining the attention over the entire text description and that over the local description of the particular object in the corresponding pixel region of that object. The temporal attention control is further added by allowing the combination weights to change at each denoising step, and the combination weights are optimized to ensure high fidelity between the image and the text. Experiments show that our method generates images with higher fidelity compared to diffusion-model-based baselines without fine-tuning the diffusion model. Our code is publicly available at https://github.com/UCSB-NLP-Chang/Diffusion-SpaceTime-Attn.Comment: 20 pages, 16 figure

Risk prediction of placenta previa based on the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy

Objectives: To explore the relationship between the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy and placenta previa. Material and methods: A prospective cohort study of women who underwent pregnancy examination in Weifang People's Hospital or Sunshine Union Hospital from January 2020 to June 2021. The distance from the lower edge of the gestational sac to the internal cervical os was measured at 5–6 weeks’ gestation. There were 86 women with distance < 2.5 cm, and 105 women with distance ≥ 2.5 cm were randomly selected. There were 92 cases of scarred uterus and 99 cases of non-scarred uterus among the 191 women. They were divided into six groups according to the distance: (1) < 1.0 cm; (2) 1.0 cm to < 1.5 cm; (3) 1.5 cm to < 2.0cm; (4) 2.0 cm to < 2.5 cm; (5) 2.5 cm to < 3.0 cm; (6) ≥ 3.0 cm. All included women were followed-up during pregnancy and pregnancy outcome, and the likelihood ratio of different distances in early pregnancy was calculated and risk stratification was performed, and ROC curve was constructed. Results: There were 15 women in the included studies who were lost to follow-up, 47 had a scarred uterus with placenta previa and 29 had a non-scarred uterus with placenta previa after delivery at 28 weeks or later. The distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy of the scarred uterus < 1.5 cm, and the likelihood ratio was ∞; and the distance ≥ 3.0 cm, the likelihood ratio was 0. The distance from the lower edge of the non-scarred gestational sac to the internal cervical os < 1.0 cm, and the likelihood ratio was ∞; and the distance ≥ 3.0 cm, the likelihood ratio was 0. The ROC curve showed that when the area AUC under the curve was 87%, the optimal diagnostic cut-off value was 2.4 cm. Conclusions: When the distance from the lower edge of the gestational sac to the internal cervical os was < 1.5 cm and the distance between the non-scarred uterus was < 1.0 cm, it eventually developed into placenta previa; the distance from the lower edge of the gestational sac to the internal cervical os in the first trimester of pregnancy between the scarred uterus and the non-scarred uterus was ≥ 3.0 cm, and it would hardly develop into placenta previa. When the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy was ≤ 2.4 cm, it could be used as a predictor of placenta previa

Discussion on the construction of food sampling team

Compared with the inspection， the sampling work directly faces the food producers and operators， which is more likely to be challenged and even raise objections in terms of standardization， representativeness， impartiality， randomness and timeliness. With the in-depth development of food safety sampling inspection， the requirements for the sampling team increased gradually. This paper discusses the construction of specialized and professional sampling team from the aspects of personnel， management， principle， reward and punishment in order to provide more ideas for relevant work. Through literature collection and comprehensive analysis， this paper combs the current situation and possible problems of China’s food safety sampling team， and proposes the targeted measures. Referring to the construction requirements of food inspection team， clarifying the qualification conditions， establishing the information base of sampling personnel， strengthening assessment and evaluation， and unifying supervision and management can effectively improve the professional skills， responsibility and professional pride of sampling team， and improve the quality and effectiveness of sampling work

Influence of D-Amino Acids in Beer on Formation of Uric Acid

Prekomjerna konzumacija piva može dovesti do povećanja koncentracije mokraćne kiseline u serumu, čime se povećava rizik nastanka uričnog artritisa (gihta), što se prethodno dovodilo u vezu s velikim udjelom purina u pivu. Međutim, novija istraživanja pokazuju da konzumacija povrća bogatog purinima i grahorica ne povećava koncentraciju mokraćne kiseline, što opovrgava tu tvrdnju. Još uvijek nije objašnjeno zašto povećana konzumacija piva može povećati rizik nastanka gihta, pa su ispitani drugi uzročnici nakupljanja mokraćne kiseline u krvi. Pivo sadržava relativno velike koncentracije D-aminokiselina koje nastaju racemizacijom L-aminokiselina tijekom prerade hrane. Katalizom pomoću D-aminokiselinske oksidaze iz D-aminokiselina nastaje H2O2, čijom oksidacijom u prisutnosti Fe2+ nastaju hidroksilni radikali. Pritom dolazi do oštećenja DNA i nastanka purinskih baza u većoj količini, iz kojih djelovanjem različitih enzima nastaje mokraćna kiselina. Neki dodaci hrani, kao što su vitamini i ioni joda, potiču nastanak mokraćne kiseline iz D-aminokiselina. D-aminokiseline u pivu imaju ključnu ulogu u povećanju koncentracije mokraćne kiseline. Biološka uloga D-aminokiselina može objasniti pojavu gihta kod osoba koje učestalo konzumiraju pivo.Excessive intake of beer could increase serum uric acid levels, leading to high risk of gout, which was previously attributed to high purine content in beer. Recent reports that purine-rich vegetables and bean products do not cause higher uric acid levels do not support this theory. Why excessive intake of beer could increase a high risk of gout has been unclear. Other factors affecting the accumulation of uric acid in the blood have been explored. Beer contains relatively high levels of D-amino acids due to the racemization of l-amino acids induced by food processing. D-amino acid was catalyzed by D-amino acid oxidase to produce H2O2, which is further oxidized in the presence of Fe2+ to produce hydroxyl radicals, resulting in DNA damage and formation of a large amount of purine bases, which are oxidized to uric acid by a series of enzymes. Some food ingredients, such as vitamins and I–, prompt D-amino acids to form uric acid. D-amino acids in beer are one of the key factors responsible for the increase in uric acid levels. The biological response of D-amino acids could explain gout occurrence in beer drinkers

Research progress on detection methods of N-dimethylnitrosamine in foods

N-dimethylnitrosamine is one of the most toxic nitrosamine compounds and can be produced in the process of food processing or storage. The detection methods are various with tedious operation and low accuracy. QuEChERS pretreatment combined with GC/LC-MS has been widely used in the determination of N-dimethylnitrosamine in food due to its advantages of simple operation， good extraction and purification， high sensitivity， stable recovery and effective improvement of detection rate and throughput. The pretreatment methods， detection equipment and detection parameters of N-dimethylnitrosamine in food were compared to analyze the advantages and disadvantages of different methods

Nickel Isotopic Evidence for Late-Stage Accretion of Mercury-Like Differentiated Planetary Embryos

© 2021, The Author(s). Earth’s habitability is closely tied to its late-stage accretion, during which impactors delivered the majority of life-essential volatiles. However, the nature of these final building blocks remains poorly constrained. Nickel (Ni) can be a useful tracer in characterizing this accretion as most Ni in the bulk silicate Earth (BSE) comes from the late-stage impactors. Here, we apply Ni stable isotope analysis to a large number of meteorites and terrestrial rocks, and find that the BSE has a lighter Ni isotopic composition compared to chondrites. Using first-principles calculations based on density functional theory, we show that core-mantle differentiation cannot produce the observed light Ni isotopic composition of the BSE. Rather, the sub-chondritic Ni isotopic signature was established during Earth’s late-stage accretion, probably through the Moon-forming giant impact. We propose that a highly reduced sulfide-rich, Mercury-like body, whose mantle is characterized by light Ni isotopic composition, collided with and merged into the proto-Earth during the Moon-forming giant impact, producing the sub-chondritic Ni isotopic signature of the BSE, while delivering sulfur and probably other volatiles to the Earth