Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficient Estimation and Robust Inference of Linear Regression Models in the Presence of Heteroscedastic Errors and High Leverage Points

It is common for linear regression models that the error variances are not the same for all observations and there are some high leverage data points. In such situations, the available literature advocates the use of heteroscedasticity consistent covariance matrix estimators (HCCME) for the testing of regression coefficients. Primarily, such estimators are based on the residuals derived from the ordinary least squares (OLS) estimator that itself can be seriously inefficient in the presence of heteroscedasticity. To get efficient estimation, many efficient estimators, namely the adaptive estimators are available but their performance has not been evaluated yet when the problem of heteroscedasticity is accompanied with the presence of high leverage data. In this article, the presence of high leverage data is taken into account to evaluate the performance of the adaptive estimator in terms of efficiency. Furthermore, our numerical work also evaluates the performance of the robust standard errors based on this efficient estimator in terms of interval estimation and null rejection rate (NRR).
Lifting-based Illumination Adaptive Transform (LIAT) using mesh-based illumination modelling

State-of-the-art video coding techniques employ block-based illumination compensation to improve coding efficiency. In this work, we propose a Lifting-based Illumination Adaptive Transform (LIAT) to exploit temporal redundancy among frames that have illumination variations, such as the frames of low frame rate video or multi-view video. LIAT employs a mesh-based spatially affine model to represent illumination variations between two frames. In LIAT, transformed frames are jointly compressed, together with illumination information, into a layered rate-distortion optimal codestream, using the JPEG2000 format. We show that the LIAT framework significantly improves compression efficiency of temporal subband transforms for both predictive and more general transforms with predict and update steps.
Optimal Neural Net Compression via Constrained Optimization

Compressing neural nets is an active research problem, given the large size of state-of-the-art nets for tasks such as object recognition, and the computational limits imposed by mobile devices. Firstly, we give a general formulation of model compression as constrained optimization. This makes the problem of model compression well defined and amenable to the use of modern numerical optimization methods. Our formulation includes many types of compression: quantization, low-rank decomposition, pruning, lossless compression and others. Then, we give a general algorithm to optimize this nonconvex problem based on a penalty function (quadratic penalty or augmented Lagrangian) and alternating optimization. This results in a “learning-compression” algorithm, which alternates a learning step of the uncompressed model, independent of the compression type, with a compression step of the model parameters, independent of the learning task. This algorithm is guaranteed to find the best compressed model for the task under standard assumptions. It is simple to implement in existing deep learning toolboxes and efficient, with a runtime comparable to that of training a reference model in the first place.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 246 Mechanism-based modeling of biological processes involved in oral absorption

Guiastrennec, B. 2018. Mechanism-based modeling of biological processes involved in oral absorption. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 246. 64 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0225-6. For orally administered drugs, the rate and extent of absorption are governed by the physiology of the gastrointestinal tract, the characteristics of the dosage form and the physico-chemical properties of the drug. This thesis primarily aimed to improve the mechanistic understanding and the predictability of processes involved in the absorption of orally administered drugs using a population modeling approach. A secondary aim was to propose an optimized dosing regimen for first line anti-tuberculosis drugs in underweight Indian children. A model characterized the effect of pH, mechanical stress and formulation on in vitro extended release (ER) tablet erosion. The model was further used in combination with anatomical tablet location data to predict the in vivo erosion dynamics. The proposed approach could help address challenges related to the development of future ER formulations. Gastric emptying regulates the rate of entry of nutrients into the small intestine. Bile acids are essential for the intestinal absorption of lipophilic drugs, but the determination of their local intestinal concentrations is difficult. A modeling framework was developed to characterize the relationships between nutritional intake, rate of gastric emptying, gallbladder emptying–refilling patterns and plasma concentrations of bile acids. This modeling framework could be used in combination with systems pharmacology models to predict the drug-drug interactions and food effects associated with gastric emptying, as well as to link the postprandial changes in plasma bile acid concentrations to the variability in drugs’ absorption. Optimal doses of first-line antituberculosis drugs have not been firmly established. In an underweight Indian children population, the pharmacokinetic-pharmacodynamic model identified rifampin as single predictor of unfavorable treatment outcome. Children with low body weight and/or HIV coinfection had a higher probability of unfavorable treatment outcome. Doses increase were proposed and could provide crucial information for future guidelines. In summary, the developed models enabled the prediction of the in vivo erosion profile of ER formulations based on in vitro dissolution data. A modeling framework predicted the postprandial gastric emptying rate and enterohepatic circulation of bile acids. Finally, a modelbased approach was used to identify risk factors and propose optimized dose recommendations in tuberculosis-infected Indian children.
A New Method to Quantify Morphology of Pyrite, and Application to Magmatic-Hydrothermal Gold Deposits in Jiaodong Peninsula, China

Morphology of pyrite has been an important indicator of conditions in the ore-forming environment. This study establishes a new pyrite morphology quantification method to characterize different types of magmatic-hydrothermal gold deposits, applying this method to the Linglong, Sanshandao and Xiadian magmatic-hydrothermal gold deposits in Jiaodong peninsula, China. We used K curve and coefficient Y to characterize the Linglong type and Jiaojia type gold deposits. It showed that Linglong type and Jiaojia type gold deposits had different K curves and coefficient Y characteristics. The results showed that this method was proper in magmatic-hydrothermal gold deposits. It is concluded that the K curve and the coefficient Y are important parameters to characterize pyrite morphology in magmatic-hydrothermal gold deposits. This quantification method was called “K curve method”.
The Power of Shared Randomness in Uncertain Communication

In a recent work (Ghazi et al., SODA 2016), the authors with Komargodski and Kothari initiated the study of communication with contextual uncertainty, a setup aiming to understand how efficient communication is possible when the communicating parties imperfectly share a huge context. In this setting, Alice is given a function $f$ and an input string $x$, and Bob is given a function $g$ and an input string $y$. The pair $(x,y)$ comes from a known distribution $\mu$ and $f$ and $g$ are guaranteed to be close under this distribution. Alice and Bob wish to compute $g(x,y)$ with high probability. The previous work showed that any problem with one-way communication complexity $k$ in the standard model has public-coin communication $O(k(1+I))$ bits in the uncertain case, where $I$ is the mutual information between $x$ and $y$. A lower bound of $\Omega(\sqrt{I})$ bits on the public-coin uncertain communication was also shown. An important question that was left open is the power that public randomness brings to uncertain communication. Can Alice and Bob achieve efficient communication amid uncertainty without using public randomness? How powerful are public-coin protocols in overcoming uncertainty? Motivated by these two questions: - We prove the first separation between private-coin uncertain communication and public-coin uncertain communication. We exhibit a function class for which the communication in the standard model and the public-coin uncertain communication are $O(1)$ while the private-coin uncertain communication is a growing function of the length $n$ of the inputs. - We improve the lower-bound of the previous work on public-coin uncertain communication. We exhibit a function class and a distribution (with $I \approx n$) for which the one-way certain communication is $k$ bits but the one-way public-coin uncertain communication is at least $\Omega(\sqrt{k} \cdot \sqrt{I})$ bits.
Feasibility of a novel two-piece nasogastric feeding tube for patients with dysphagia.

INTRODUCTION The exposed section of a traditional nasogastric (NG) tube can interfere with patients' social activities and thereby result in distress. This study was conducted to evaluate the feasibility and safety of a novel two-piece NG tube for patients with dysphagia. METHODS Ten patients with dysphagia were recruited between November 2011 and May 2012. Patients who were unconscious or in critical condition, had a traditional NG tube < 50 cm or > 60 cm in fixed length, or were unable to follow instructions or sign consent forms were excluded. The two-piece NG tube, which was placed in the patients for one week, comprised a removable external tube that can be joined to an internal tube via a T-connector, which was placed close to the naris. Events related to safety (e.g. nasal pressure sores, number of unplanned extubation, displacement and spontaneous migration of the NG tube, other unpredictable injuries) and effectiveness (e.g. liquid food spills, tube obstruction, perfusion rate, other adverse circumstances) were assessed daily. RESULTS All patients received feeding without complication using the two-piece NG tube and none experienced premature removal of the tube. No serious NG tube complications or malfunctions were observed. CONCLUSION The results of this study indicate that the two-piece NG feeding tube is a feasible option for patients with dysphagia. Future improvements to the connector may help enhance its performance. A rigorous randomised controlled trial to examine the effects of the two-piece NG tube on patients' quality of life and quality of medical care is being planned.
Targeted Therapy and Immunotherapy Response Assessment with F-18 Fluorothymidine Positron-Emission Tomography/Magnetic Resonance Imaging in Melanoma Brain Metastasis: A Pilot Study

Introduction This pilot study aimed at exploring the utility of the proliferation tracer F-18 fluorothymidine (FLT) and positron-emission tomography (PET)/magnetic resonance imaging (MRI) (FLT–PET/MRI) for early treatment monitoring in patients with melanoma brain metastasis (MBM) who undergo targeted therapy or immunotherapy. Material and Methods Patients with newly diagnosed MBM underwent baseline and follow-up FLT–PET/MRI scans at 3–4 weeks of targeted therapy or immunotherapy. Up to six measurable brain lesions ≥1.0 cm per subject, as identified on T1-weighted post-gadolinium images, were included for quantitative analyses. The maximum SUV of each lesion was divided by the mean SUV of the pons to obtain the SUV ratio (SUVR). Results Five enrolled subjects underwent the baseline FLT–PET/MRI study in which the MBM showed a median size of 1.7 cm (range 1.0–2.9) and increased metabolic activity with SUVR of 9.9 (range 3.2–18.4). However, only two subjects (cases #1 and #2) returned for a follow-up scan. At baseline, a total of 22 lesions were analyzed in all five subjects, which showed a median size of 1.7 cm (range 1.0–2.9) and median SUVR of 9.9 (range 3.2–18.4). At follow-up, case #1 was a 55-year-old man who received targeted BRAF inhibitor and MEK inhibitor therapy with dabrafenib and trametinib. Fused PET/MRI data of six measured lesions demonstrated a significant reduction in MBM proliferative activity (median −68%; range −38 to −77%) and size (median −23%; range −4 to −55%) at three weeks of therapy. Nevertheless, the subject eventually progressed and died 13 months after therapy initiation. Case #2 was a 36-year-old man who received immunotherapy with nivolumab and ipilimumab. The five measured MBM lesions showed a mixed response at both proliferative and morphologic imaging at 1-month follow-up. Some lesions demonstrated interval decrease while others interval increase in proliferative activity with a median −44% (range −77 to +68%). On MRI, the size change was +7% (range −64 to +50%). The therapy was switched to dabrafenib and trametinib, which led to a partial response. The patient is still alive 16 months following therapy initiation. Conclusion The five cases presented show the potential benefit of hybrid FLT–PET/MRI for the diagnosis of MBM and treatment monitoring of targeted therapy and immunotherapy. However, further studies are required to assess their complementary role in distinguishing true progression from pseudoprogression.
Placental Mitochondrial Toxicity, Oxidative Stress, Apoptosis, and Adverse Perinatal Outcomes in HIV Pregnancies Under Antiretroviral Treatment Containing Zidovudine

Objective: To determine whether mitochondrial, oxidative, and apoptotic abnormalities in placenta derived from HIV and combined antiretroviral therapy (cART) containing zidovudine (AZT) could be associated with adverse perinatal outcome. Design: Cross-sectional, controlled, observational study. Methods: We studied obstetric results and mitochondrial, oxidative, and apoptotic state in placenta of 24 treated HIV-infected and 32 -uninfected pregnant women. We measured mitochondrial DNA (mtDNA) content by quantitative reverse transcriptase–polymerase chain reaction (mtND2/n18SrRNA), oxidative stress by the spectrophotometric quantification of lipid peroxidation and apoptosis by Western blot analysis of active caspase-3 respect to &bgr;-actin content and analysis of the terminal deoxynucleotidyl transferase dUTP nick end labeling. Results: Global adverse perinatal outcome (defined as preterm delivery or/and small newborns for gestational age) was significantly increased in HIV pregnancies [or 6.7 (1.3–33.2); P < 0.05]. mtDNA content in HIV-infected women was significantly depleted (39.20% ± 2.78%) with respect to controls (0.59 ± 0.03 vs. 0.97 ± 0.07; P < 0.001). A significant 29.50% ± 9.14% increase in oxidative stress was found in placentas of HIV-infected women (23.23 ± 1.64 vs. 17.94 ± 1.03; P < 0.01). A trend toward 41.18% ± 29.41% increased apoptosis active caspase-3/&bgr;-actin was found in HIV patients (0.48 ± 0.10 vs. 0.34 ± 0.05; P = not significant), confirmed by transferase dUTP nick end labeling assay. Adverse perinatal outcome did not correlate mitochondrial, oxidative, or apoptotic findings. Conclusions: Placentas of HIV-infected pregnant women under AZT cART showed evidence of mtDNA depletion, increased oxidative stress levels, and apoptosis suggestive of secondary mitochondrial failure, potential base of associated adverse perinatal outcome. Despite the fact that further demonstration of causality would need new approaches and bigger sample sizes, AZT-sparing cART should be considered in the context of pregnancy.
Behavioral Phenotyping of Dopamine Transporter Knockout Rats: Compulsive Traits, Motor Stereotypies, and Anhedonia

Alterations in dopamine neurotransmission are generally associated with diseases such as attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Such diseases typically feature poor decision making and lack of control on executive functions and have been studied through the years using many animal models. Dopamine transporter (DAT) knockout (KO) and heterozygous (HET) mice, in particular, have been widely used to study ADHD. Recently, a strain of DAT KO rats has been developed (1). Here, we provide a phenotypic characterization of reward sensitivity and compulsive choice by adult rats born from DAT–HET dams bred with DAT–HET males, in order to further validate DAT KO rats as an animal model for preclinical research. We first tested DAT KO rats’ sensitivity to rewarding stimuli, provided by highly appetitive food or sweet water; then, we tested their choice behavior with an Intolerance-to-Delay Task (IDT). During these tests, DAT KO rats appeared less sensitive to rewarding stimuli than wild-type (WT) and HET rats: they also showed a prominent hyperactive behavior with a rigid choice pattern and a wide number of compulsive stereotypies. Moreover, during the IDT, we tested the effects of amphetamine (AMPH) and RO-5203648, a trace amine-associated receptor 1 (TAAR1) partial agonist. AMPH accentuated impulsive behaviors in WT and HET rats, while it had no effect in DAT KO rats. Finally, we measured the levels of tyrosine hydroxylase, dopamine receptor 2 (D2), serotonin transporter, and TAAR1 mRNA transcripts in samples of ventral striatum, finding no significant differences between WT and KO genotypes. Throughout this study, DAT KO rats showed alterations in decision-making processes and in motivational states, as well as prominent motor and oral stereotypies: more studies are warranted to fully characterize and efficiently use them in preclinical research.
Blood/Gas Partition Coefficients for Isoflurane, Sevoflurane, and Desflurane in a Clinically Relevant Patient Population

BACKGROUND:The blood/gas partition coefficient of a certain volatile anesthetic is of clinical importance because it determines its velocity of uptake into and elimination from the body of a patient and thus its pharmacokinetic behavior. To date, the blood/gas partition coefficients of isoflurane, sevoflurane, and desflurane have been measured in small numbers of subjects or in particular study groups, for example, healthy volunteers, patients experiencing a common kind of disease, or mothers immediately after giving birth. The objective of this study was to determine the blood/gas partition coefficients of these volatile anesthetics at 37°C in a larger clinically relevant and adult patient population. Furthermore, we tested whether age, gender, body mass index, hemoglobin concentration, or hematocrit had an influence on the coefficients. METHODS:Blood samples were taken from 120 fasting operative patients with ASA physical status I to III and aged 19 to 86 years. All subjects were randomly enrolled in study groups for the separate determinations of the blood/gas partition coefficients of isoflurane (n = 41), sevoflurane (n = 41), and desflurane (n = 38) by headspace gas chromatography. To check the quality of the measurements, we determined the distilled water/gas partition coefficients of those anesthetics and compared them with previously published values. RESULTS:We found a blood/gas partition coefficient of 1.45 ± 0.12 (mean ± SD) for isoflurane, 0.74 ± 0.06 for sevoflurane, and 0.57 ± 0.04 for desflurane. Values of this study are 5.07%, 12.12%, and 7.55% higher for isoflurane, sevoflurane, and desflurane, respectively, than the previously published mean values (all P ⩽ 0.001). There were only trends for small correlations between the blood/gas partition coefficient of isoflurane and hemoglobin concentration (Pearson r = 0.32; P = 0.041) and hematocrit (r = 0.37; P = 0.016). We found no other potentially significant correlations of the partition coefficients with patient age, body mass index, hemoglobin concentration, or hematocrit (all remaining P > 0.069). Furthermore, the coefficients did not differ significantly between female and male patients. The evaluation of the distilled water/gas partition coefficients of isoflurane (0.59 ± 0.04), sevoflurane (0.37 ± 0.04), and desflurane (0.27 ± 0.03) proved the validity of the gas chromatography method used in this study. CONCLUSIONS:The blood/gas partition coefficients of the modern volatile anesthetics, in particular, those of sevoflurane and desflurane, may be higher than that has been hitherto reported. Therefore, their uptake and elimination may occur more slowly in some patients than has been supposed. The blood/gas partition coefficients of isoflurane, sevoflurane, and desflurane measured in this study appear to be representative because they were determined in a clinically and numerically relevant patient cohort.
Aortic valve replacement with and without combined coronary bypass grafts in very elderly patients: early and long-term results.

OBJECTIVE The number of older patients being referred for aortic valve replacement with or without combined coronary bypass grafting (CABG) is increasing. The aim of this study was to evaluate operative risk factors, early and long-term results of isolated aortic valve and aortic valve replacement combined with CABG in octogenarians and nonagenarians. METHODS In the last 10 years, 285 very elderly patients who underwent aortic valve replacement either alone or in combination with coronary artery bypass grafts were retrospectively studied. The population was divided into two groups; isolated aortic valve replacement was performed in 188 patients (group A) and 97 patients had aortic valve replacement combined with coronary surgery (group B). RESULTS The overall hospital mortality was 5.3%, without statistical difference between groups. The incidence of low-output syndrome was higher in group B (P = 0.0001). The multivariate analysis for hospital mortality showed that urgency status, ejection fraction (EF) <35%, intra-operative variables such as clamping time, need for intra aortic balloon pump and post-operative variables such as prolonged ventilation, dialysis, post-operative myocardial infarction and re-thoracotomy for bleeding were independent prognostic factors for hospital mortality. The mean follow-up time was 49.03 ± 19 months. Survival at one, three and five years was 97.1 ± 1.8%, 92.2 ± 2.2% and 82.4 ± 3.6% for group A and 97.2 ± 2.0%, 88.4 ± 2.7% and 75.6 ± 3.2% for group B (P = 0.62), respectively. Age, male gender, post-operative myocardial infarction, urgency status, dialysis, low EF, mean aortic gradient were risk factors for the impaired survival. CONCLUSIONS In our experience, a careful pre-operative evaluation has yielded good surgical results even in older patients with different comorbidities. Associated coronary grafts slightly increase the surgical risk. The role of revascularization on long-term morbidity and mortality is still not clear. It is essential to compare the results of percutaneous and trans-apical aortic valve replacement with the literature results of conventional aortic valve replacement with and without CABG before it can be used as an alternative for very older patients.