Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Heat Waves on Mortality

Background: Heat waves have been linked with an increase in mortality, but the associated risk has been only partly characterized. Methods: We examined this association by decomposing the risk for temperature into a “main effect” due to independent effects of daily high temperatures, and an “added” effect due to sustained duration of heat during waves, using data from 108 communities in the United States during 1987–2000. We adopted different definitions of heat-wave days on the basis of combinations of temperature thresholds and days of duration. The main effect was estimated through distributed lag nonlinear functions of temperature, which account for nonlinear delayed effects and short-time harvesting. We defined the main effect as the relative risk between the median city-specific temperature during heat-wave days and the 75th percentile of the year-round distribution. The added effect was defined first using a simple indicator, and then a function of consecutive heat-wave days. City-specific main and added effects were pooled through univariate and multivariate meta-analytic techniques. Results: The added wave effect was small (0.2%–2.8% excess relative risk, depending on wave definition) compared with the main effect (4.9%–8.0%), and was apparent only after 4 consecutive heat-wave days. Conclusions: Most of the excess risk with heat waves in the United States can be simply summarized as the independent effects of individual days' temperatures. A smaller added effect arises in heat waves lasting more than 4 days.
Epigenetic Inheritance and Evolution: The Lamarckian Dimension

Since first publication of this controversial book, much of the initial opposition to the ideas it contained has been replaced by a general, although often grudging, acceptance of them. Advances in knowledge, especially at the molecular level, have enhanced general awareness and interest in epigenetics and the evolution of systems that store and transmit information and put any of the authors' speculations on a more solid basis. This paperback edition contains a new Preface that sets out the major changes in the scientific world and in the authors' own thinking that have occurred since the book was published. A new Appendix provides a selected bibliography of the many books and articles about epigenetic inheritance and its role in evolution that have appeared since first publication.
Selective Constraints on Amino Acids Estimated by a Mechanistic Codon Substitution Model with Multiple Nucleotide Changes

Background Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code, and the strength of selective constraints against amino acid replacements can be tailored to a given gene. First, selective constraints averaged over proteins are estimated by maximizing the likelihood of each 1-PAM matrix of empirical amino acid (JTT, WAG, and LG) and codon (KHG) substitution matrices. Then, selective constraints specific to given proteins are approximated as a linear function of those estimated from the empirical substitution matrices. Results Akaike information criterion (AIC) values indicate that a model allowing multiple nucleotide changes fits the empirical substitution matrices significantly better. Also, the ML estimates of transition-transversion bias obtained from these empirical matrices are not so large as previously estimated. The selective constraints are characteristic of proteins rather than species. However, their relative strengths among amino acid pairs can be approximated not to depend very much on protein families but amino acid pairs, because the present model, in which selective constraints are approximated to be a linear function of those estimated from the JTT/WAG/LG/KHG matrices, can provide a good fit to other empirical substitution matrices including cpREV for chloroplast proteins and mtREV for vertebrate mitochondrial proteins. Conclusions/Significance The present codon-based model with the ML estimates of selective constraints and with adjustable mutation rates of nucleotide would be useful as a simple substitution model in ML and Bayesian inferences of molecular phylogenetic trees, and enables us to obtain biologically meaningful information at both nucleotide and amino acid levels from codon and protein sequences.
Lifestyle factors, hormonal contraception, and premenstrual symptoms: the United Kingdom Southampton Women's Survey.

OBJECTIVE To estimate the prevalence of premenstrual symptoms in women from the general population in Southampton, U.K., and examine their association with lifestyle factors and contraceptive use. METHODS This was a cross-sectional survey in the city of Southampton, U.K., of 974 women aged 20-34 years (53% of the 1841 women invited to participate). The survey consisted of interviews, questionnaires, and completion of a prospective 6-week menstrual symptom diary recording on a daily basis the presence and severity of 11 common premenstrual symptoms. Premenstrual symptoms were identified from the diaries by two clinicians who reviewed them independently using a predefined algorithm to assess the onset and decline of symptoms in relation to the start of menstruation. RESULTS Of the women surveyed, 24% were considered to have premenstrual symptoms (95% confidence interval [CI] 21-27). Women were less likely to have symptoms if they had higher levels of educational attainment and suffered less from stress. No associations were found between premenstrual symptoms and diet, alcohol, or strenuous exercise nor after adjustment for other factors, with age, smoking, or body mass index (BMI). Use of any form of hormonal contraceptives was associated with a lower prevalence of premenstrual symptoms (prevalence ratio 0.66, 95% CI 0.52-0.84). CONCLUSIONS Premenstrual symptoms were common in this cohort. Use of hormonal contraceptive methods was associated with a lower prevalence of these symptoms.
The Viral Load of Epstein–Barr Virus (EBV) DNA in Peripheral Blood Predicts for Biological and Clinical Characteristics in Hodgkin Lymphoma

Purpose: The Epstein–Barr virus (EBV) is present in the malignant Hodgkin/Reed–Sternberg (HRS) cells of 20% to 40% cases of Hodgkin lymphoma (HL) in Western countries. We were interested in the detection and quantification of cell-free plasma EBV-DNA as an indicator of biological and clinical characteristics in EBV-associated HL. Experimental Design: EBV was detected in peripheral blood compartments (whole blood, plasma, and mononuclear cells) at diagnosis by real-time PCR for the EBNA (EB nuclear antigen) region (n = 93) and in HRS cells by in situ hybridization for EBV-encoded small RNAs (EBER; n = 63). These data were correlated to histological and clinical characteristics, EBV serology, circulating cell-free DNA, and interleukin (IL)-6 levels. Results: Detection of EBV-DNA in plasma had a high specificity (90%), but a relatively low sensitivity (65%) to predict for EBV association. The viral load was higher in patients with advanced stage disease, older age in the presence of B-symptoms, and international prognostic score more than 2. The presence of EBV in HRS cells and higher plasma EBV-DNA copy numbers correlated to an increased frequency of tumor-infiltrating CD68+ macrophages in lymph node biopsies. Plasma EBV-DNA load correlated to circulating cell-free DNA and IL-6 levels, and inversely correlated to lymphocyte counts and EBNA1 antibody titers. Conclusion: Although the presence of EBV-DNA in peripheral blood cannot be regarded as a surrogate marker for EBER, the plasma EBV-DNA load at HL diagnosis is an indicator of disease activity and biological characteristics associated with negative prognosis. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immunosurveillance, favoring the expansion of EBV-HRS cells in HL. Clin Cancer Res; 17(9); 2885–92. ©2011 AACR.
A spectral-timing model for ULXs in the supercritical regime

Ultraluminous X-ray sources (ULXs) with luminosities lying between ∼3 × 10^(39) and 2 × 10^(40) erg s^(−1) represent a contentious sample of objects as their brightness, together with a lack of unambiguous mass estimates for the vast majority of the central objects, leads to a degenerate scenario where the accretor could be a stellar remnant (black hole or neutron star) or intermediate-mass black hole (IMBH). Recent, high-quality observations imply that the presence of IMBHs in the majority of these objects is unlikely unless the accretion flow somehow deviates strongly from expectation based on objects with known masses. On the other hand, physically motivated models for supercritical inflows can re-create the observed X-ray spectra and their evolution, although have been lacking a robust explanation for their variability properties. In this paper, we include the effect of a partially inhomogeneous wind that imprints variability on to the X-ray emission via two distinct methods. The model is heavily dependent on both inclination to the line of sight and mass accretion rate, resulting in a series of qualitative and semiquantitative predictions. We study the time-averaged spectra and variability of a sample of well-observed ULXs, finding that the source behaviours can be explained by our model in both individual cases as well as across the entire sample, specifically in the trend of hardness-variability power. We present the covariance spectra for these sources for the first time, which shed light on the correlated variability and issues associated with modelling broad ULX spectra.
A mathematical model and metaheuristics for Time Dependent Orienteering Problem

This paper presents a generalization of the Orienteering Problem, the Time-Dependent Orienteering Problem (TDOP) which is based on the real-life application of providing automatic tour guidance to a large leisure facility such as a theme park. In this problem, the travel time between two nodes depends on the time when the trip starts. We formulate the problem as an integer linear programming (ILP) model. We then develop various heuristics in a step by step fashion: greedy construction, local search and variable neighborhood descent, and two versions of iterated local search. The proposed metaheuristics were tested on modied benchmark instances, randomly generated problem instances, and two real world problem instances extracted from two popular theme parks in Asia. Experimental results conrm the eectiv eness of the developed metaheuristic ap- proaches, especially an iterated local search with adaptive perturbation size and probabilistic intensied restart mechanism. It n ds within an acceptably short computation time, the optimal or near optimal solutions for TDOP instances of realistic size as in our target application.
Culturing adult rat hippocampal neurons with long-interval changing media.

BACKGROUND Primary cultures of embryonic neurons have been used to introduce a model of neurons in physiological and pathological conditions. However, age-related cellular events limit this method as an optimal model in adult neurodegenerative diseases studies. Besides, short-interval changing media in previous cultures decreases the effectiveness of this model. As an example of this matter, we can refer to the study on some special neuronal secreted factors or the influence of some experimental materials on neurons. Meanwhile, short-interval changing media could remove the effects of some released factors from the environment. In this study, the method for isolation and culturing adult rat hippocampal neurons with long-intervals medium changing has been described. METHODS The hippocampal neurons of adult male rats were cultured. We used Neurobasal A/B27 culture medium, papain (2 mg/ml), trypsin 0.25% and collagenase (1 mg/ml) for neuronal isolation, OptiPrep density gradient for separation of neurons from other cell types and also debris and FGF2 (10 ng/ml) for increasing neuronal survival and regeneration. RESULTS The neuronal sprouting and viability were increased by using papain and mild triturating (P<0.05). Adult neuronal culturing and their regeneration were impossible without FGF2. It was shown that adding new fresh medium every 4 days and exchanging half of it every 8 days had no detrimental effect on neuronal viability. CONCLUSION This investigation shows the possibility of culturing adult neuronal cells and their maintaining in long-interval media. It could be happened because of adult neurons rely significantly on the neighboring cells secreted factors for living and making synaptic connections. This model is very useful in physiological and pathological studies which need stable conditions of neuronal culture in a long period of time.
Secondary Primary Prostate Cancer after Colorectal Cancer: A Nationwide Population-based Cohort Study in Korea

Background Colorectal cancer (CRC) and prostate cancer frequently occur in developed countries. There are several reports on the association between CRC and prostate cancer; however, the conclusions are inconsistent to investigate the association of the development of secondary primary prostate cancer among patients with prior primary CRC using a nationwide population-based dataset. Methods Patients registered in the Republic of Korea National Health Insurance System database who were diagnosed with CRC between 2007 and 2012 were followed-up until the end of 2015, and we investigated the new diagnosis secondary primary prostate cancer. We compared the incidence of prostate cancer in age-matched controls using the Cox proportional hazards models. Results We analyzed a total of 85,455 first primary CRC survivors. During the follow-up period of 494,222 person-years, 2,005 patients (2.30%) developed secondary primary prostate cancer (incidence rate 4.06/1,000 person-years). The median duration of follow-up was 5.78 years. Compared with the general population, CRC patients had a significantly increased risk of secondary primary prostate cancer (HR = 2.30, 95% CI = 2.18–2.43; P < 0.001). Multivariate analysis (including age, sex, body mass index, hypertension, diabetes mellitus, dyslipidemia, and income) showed that age < 55 years (HR = 20.74, 95% CI = 11.81–36.41; P < 0.001) is a significant independent predictor of secondary primary prostate cancer development. Conclusions Men diagnosed with colorectal cancer are at an increased risk of secondary primary prostate cancer, particularly those aged < 55 years. The data suggests that colorectal cancer patients aged < 55 years require regular screening for prostate cancer.
Es la memoria del optimista menos influenciable por las emociones negativas

Is an optimistic memory less easily influenced by negative than by positive emotions? This work examines whether a positive personality trait, such as optimism, can reduce bias in differential words recalled after inducing a certain emotion. After showing a list of words with various emotional valences to a group of 59 subjects, a specific emotional state was induced. Subsequently, the subjects were asked to recall the list of words. The results obtained indicated that less optimistic subjects had a tendency to recall and recognize a greater number of negative words when in a negative emotional condition. Statistical significance was reached in the female group's negative word recognition when experiencing negative emotion.
RSMG Progress Report 2 Social-Emotional Relationships With Embodied Interface Agents

Human-computer relationships are social and emotional in nature. We willingly (often unconsciously) interact with computers as though they are social entities and as such, our interaction with computers can have a strong impact upon our emotional states. This socialemotional interaction with computers forms the basis of my research interests and the work which I have investigated to date. Abstract questions, such as which relational strategies can be used to enhance human-computer relationships and what effect does the “expression” of emotion by a computer have on our performance and perceptions of that computer, are questions of particular interest to me. Furthermore, this interest extends to that of interface agents of varying types. Which type of interface agent (e.g. embodied, textual or speechbased), used in which domain (e.g. entertainment, business, education), affects which aspects of our behaviour, responses and perceptions? How can relational strategies be incorporated into interface agents of different types? What influence do these relational strategies, or illusions of human emotion, have over our perceptions of interface agents? These are the types of questions that I am particularly interested in investigating further.
Trust, privacy and security in digital business

An important aspect of e-business is the area of e-commerce. According to recent surveys, one of the most severe restraining factors for the proliferation of ecommerce, as measured by the gap between predicted market value and actual development is the (lack of) security measures required to assure both businesses and customers that their business relationship and transactions will be carried out in privacy, correctly, and timely. A large number of individuals are not willing to engage in e-commerce (or are only participating at a reduced level) simply because they do not trust the e-commerce sites and the underlying information and communication technologies to be secure enough. This paper first considers privacy and security requirements for e-commerce applications; it then discusses methods and technologies that can be used to fulfil these requirements.
Loneliness and Health in Older Adults: A Mini-Review and Synthesis

Increasing evidence suggests that perceived social isolation or loneliness is a major risk factor for physical and mental illness in later life. This review assesses the status of research on loneliness and health in older adults. Key concepts and definitions of loneliness are identified, and the prevalence, correlates, and health effects of loneliness in older individuals are reviewed. Theoretical mechanisms that underlie the association between loneliness and health are also described, and illustrative studies examining these mechanisms are summarized. Intervention approaches to reduce loneliness in old age are highlighted, and priority recommendations for future research are presented.
Epidemiology of Methicillin-Resistant Staphylococcus aureus Bacteremia in Gaborone, Botswana

This cross-sectional study at a tertiary-care hospital in Botswana from 2000 to 2007 was performed to determine the epidemiologic characteristics of Staphylococcus aureus bacteremia. We identified a high prevalence (11.2% of bacteremia cases) of methicillin-resistant S. aureus (MRSA) bacteremia. MRSA isolates had higher proportions of resistance to commonly used antimicrobials than did methicillin-susceptible isolates, emphasizing the need to revise empiric prescribing practices in Botswana.
Preparation and Bioavailability Assessment of SMEDDS Containing Valsartan

A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance diffusion rate and oral bioavailability of valsartan. The solubility of valsartan was checked in different oils, surfactants, and cosurfactants and ternary phase diagrams were constructed to evaluate the microemulsion domain. The valsartan SMEDDS was prepared using Capmul MCM (oil), Tween 80 (surfactant), and polyethylene glycol 400 (cosurfactant). The particle size distribution, zeta potential, and polydispersity index were determined and were found to be 12.3 nm, −0.746, and 0.138, respectively. Diffusion rate of valsartan was measured by in vitro dialysis bag method using phosphate buffer pH 6.8 as diffusion media. Developed high-performance liquid chromatography method was used to determine drug content in diffusion media. Oral bioavailability of valsartan SMEDDS was checked by using rabbit model. Results of diffusion rate and oral bioavailability of valsartan SMEDDS were compared with those of pure drug solution and of marketed formulation. Diffusion of valsartan SMEDDS showed maximum drug release when compared to pure drug solution and marketed formulation. The area under curve and time showed significant improvement as the values obtained were 607 ng h/mL and 1 h for SMEDDS in comparison to 445.36 and 1.36 h for market formulation suggesting significant increase (p < 0.01) in oral bioavailability of valsartan SMEDDS.
Phase II Trial of Curcumin in Patients with Advanced Pancreatic Cancer

Purpose: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration–approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-κB (NF-κB) and tumor inhibitory properties, against advanced pancreatic cancer. Experimental Design: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-κB and cyclooxygenase-2 were monitored. Results: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-κB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. Conclusions: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.
On the construction of components with explicit protocols

Component-based programming promises to facilitate the construction of large-scale applications, which is supported by the important concept of interfaces. In most current component models, interfaces essentially declare types and sets of services that a component implements. They are not expressive enough to formulate many properties important for component collaboration. In this paper we consider an important class of such properties, sequencing constraints, which components must obey when calling one another services. We consider the integration into interfaces of sequencing properties by means of protocols formalized in terms of finite-state machines. The paper presents three contributions. First, a set of protocol composition operators and a discussion of correctness properties of such operators useful for component assembly. Second, we provide a first step toward the integration of additional state information into protocols. Finally, we show how JavaBeans can benefit from the techniques we present. Technical Report No: 02/4/INFO ∗This work has been partially funded by the EU project “EasyComp” (www.easycomp.org), no. IST-1999-014191