Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistence of heroin use despite methadone treatment: poor coping self-efficacy predicts continued heroin use.

AIM To evaluate the association between coping self-efficacy and persistent use of heroin by patients enrolled in a methadone treatment program. DESIGN AND METHODS Cross-sectional survey. One hundred and ninety-one patients attending outpatient methadone clinics in South-East England, United Kingdom. Validated questionnaires were used to assess drug use (Maudsley Addiction Profile), alcohol use (Alcohol Use Disorders Identification Test), mental health (Hospital Anxiety and Depression Scale) and coping self-efficacy (brief 8-item Drug Taking Confidence Questionnaire). RESULTS Half of the participants (95/191) reported heroin use in the preceding 14-day period. Heroin use during methadone treatment was associated with financial problems (P = 0.008), spending time with other drug users (P < 0.001), cocaine use (P = 0.002), low mood (P = 0.002) and dissatisfaction with the daily methadone dose (P = 0.014). Compared with 'Heroin-abstinent' patients, the 'Heroin' group reported significantly lower mean coping self-efficacy scores (t = 9.8, d.f. = 182, P < 0.001, effect size 1.17). After correcting for the effects of co-variants in a logistic regression model, the main determinants of persistent heroin use were 'coping self-efficacy' [B -0.05; standard error (SE) 0.008; Wald 36.6; odds ratio (OR) 0.95, 95% confidence interval (CI) 0.94, 0.97; P < 0.001] and 'dissatisfaction with methadone dose' (B 0.93; SE 0.46; Wald 4.1; OR 2.5, 95% CI 1.03, 6.25; P = 0.042). Satisfaction with methadone dose showed no association with self-efficacy. DISCUSSION AND CONCLUSIONS; While heroin use during methadone treatment can partly be explained by inadequate dosing, our data suggest a more complex picture with significant contribution from poor coping self-efficacy. Efforts aimed at enhancing and maintaining the patients' self-efficacy and social skills are likely to improve heroin and other drug use outcomes with added benefits for treatment completion rates and the throughput of methadone programs.
Prognostic modeling in pediatric acute liver failure

Liver transplantation (LT) is the only proven treatment for pediatric acute liver failure (PALF). However, over a period of time, spontaneous native liver survival is increasingly reported, making us wonder if we are overtransplanting children with acute liver failure (ALF). An effective prognostic model for PALF would help direct appropriate organ allocation. Only patients who would die would undergo LT, and those who would spontaneously recover would avoid unnecessary LT. Deriving and validating such a model for PALF, however, encompasses numerous challenges. In particular, the heterogeneity of age and etiology in PALF, as well as a lack of understanding of the natural history of the disease, contributed by the availability of LT has led to difficulties in prognostic model development. Several prognostic laboratory variables have been identified, and the incorporation of these variables into scoring systems has been attempted. A reliable targeted prognostic model for ALF in Wilson's disease has been established and externally validated. The roles of physiological, immunological, and metabolomic parameters in prognosis are being investigated. This review discusses the challenges with prognostic modeling in PALF and describes predictive methods that are currently available and in development for the future. Liver Transplantation 22 1418–1430 2016 AASLD.
Power Saving Class I Sleep Mode in IEEE802.16e System

This paper investigates energy saving of MS (mobile subscriber) at power saving class I sleep mode in IEEE 802.16e system. In order to minimize the MS power consumption and decrease the occupation of interface resources in serving BS (base station), the sleep mode mechanism is introduced. This paper models the energy consumption of power saving class I sleep mode under the consideration of sleep interval of variable power rather than a constant power, and two-type-returning from sleep mode. Simulation results show that the effect of power saving class I sleep mode varies depending on different parameter configurations.
Combination Immunotherapy for Melanoma.

Advances in precisionmedicine and immunology have led tomajor paradigmshifts in thegeneral approach to treatingpatientswith metastatic cancer. This is perhaps best exemplified by malignant melanoma, an aggressive tumor characterized by alterations in definedcell signalingpathwaysandsusceptibility to recognitionby the immunesystem.Over thepast4years, therehavebeen7newdrugs approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma.1 There has been considerable excitement focusedon the immunotherapyofmelanomabasedon several randomizedclinical trials (RCTs)demonstratingan improvement in overall survival with immunotherapy agents and also on emergingdata supporting theuseof immunotherapy in a variety of other typesof cancer. In contrast to cytotoxic chemotherapyor targeted therapy, immunotherapy is often characterized by a relatively slowonset of action, lack of drug resistance, and induction of durable therapeutic responses,at least inasubsetofpatients. In fact, results in patients with metastatic melanoma treated with highdose interleukin-2 (IL-2), which has been available since 1998, suggest that most patients who achieve an objective complete response remain free of melanoma recurrence 15 years later and are likely curedofmetastatic disease.2More recently, amonoclonal antibody that blocks the cytotoxic T lymphocyte antigen 4 (CTLA-4) and prevents T-cell unresponsiveness (ipilimumab) demonstrated anoverall survivalbenefit inanRCT inpatientswithmetastaticmelanomaandwasapprovedby theFDA.OtherT-cell checkpoint inhibitors targeting theprogrammedcell death 1 (PD-1)pathwayhavealso shown considerable promisewith 2 anti–PD-1 antibodies achieving FDA approval formetastaticmelanomaover the past 12months.3,4 Thus, a better understanding of how immunotherapymediates tumor rejection and new strategies for increasing the number of patients who respond to immunotherapy are high priorities in cancer research today. A logical strategy that has been used in cancer pharmacology is toconsider combinationsof2ormoreagents toexpand the therapeutic activity of a particular class of drugs or to use drugs fromdifferent classes thatmayhave independentmechanismsof action. In JAMA
Pathogenesis of transplacental virus infection: pestivirus replication in the placenta and fetus following respiratory infection.

Although transplacental virus infections account for considerable morbidity and mortality in both animals and humans, very little is so far known about the pathways whereby virus reaches the conceptus, the subsequent virus-host interactions in the early phases of the infections, and the establishment of persistent non-lethal infection. Using a natural animal model we recently demonstrated that bovine pestivirus can spread from the site of infection to the ovine fetus within 72 h, despite the expression of interferon in the reproductive tract [1]. In the present study we demonstrate that pestivirus first establishes infection and spread within the allantoic and amniotic membranes and then the fetus, followed several days later by infection of the uterine glands. However, virus replication and spread within the fetus is, at least in part, controlled by fetal developmental factors. In fetuses less than 25 days of gestational age, the virus remains restricted to the bulbis cordis, the first brachial pouch and occasionally the aorta. Over the next few days the virus spreads to multiple tissues, in addition to becoming more widespread and pronounced within the initially infected tissues. A potential role for the binucleated cells of the allantochorion in the spread of the virus from the fetal to the maternal tissues was also found. These cells expressed high levels of viral antigen just prior to and during the time period in which virus antigen became detectable in the epithelial cells of the uterine glands, in endothelial cells of uterine vessels and in scattered macrophage-like cells in the uterine stroma. Most likely this relatively late virus transfer is inconsequential for the mother, since it occurs at a time when a maternal virus-specific antibody response is becoming measurable. This is in contrast to the fetus, where the infection will have established itself widely prior to the development of lymphoid tissues and a functional immune response, thus setting the scenario for development of specific tolerance to the persisting virus.
PTH analogues and osteoporotic fractures

Importance of the field: At present there are two parathyroid hormone (PTH) analogues (PTH 1 – 34 and PTH 1 – 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 – 34 and PTH 1 – 84) and in men (PTH 1 – 34 only) who are at increased risk of having a fracture. Areas covered in this review: The efficacy and safety of PTH 1 – 34 and PTH 1 – 84 in the management of osteoporosis is evaluated by reviewing published literature and presentations from scientific meetings through to 2010. What the reader will gain: This review focuses on data on fracture risk reduction and safety endpoints of PTH analogues. The adverse reactions reported most are nausea, pain in the extremities, headache and dizziness. Take home message: Exogenous PTH analogues, given as daily subcutaneous injections, stimulate bone formation, increase bone mass and bone strength, and improve calcium balance. In postmenopausal women with osteoporosis, PTH analogues reduced the risk of vertebral (PTH 1 – 34 and PTH 1 – 84) and non-vertebral fractures (only PTH 1 – 34). In men and women with glucocorticosteroid-induced osteoporosis, PTH 1 – 34 reduced the risk of vertebral fractures. In general, PTH analogues are well tolerated with an acceptable safety profile: they can be used for the prevention and treatment of fractures in postmenopausal women with severe, established osteoporosis.
Imaging Tumor Vasculature Noninvasively with Positron Emission Tomography and RGD Peptides Labeled with Copper 64 Using the Bifunctonal Chelates DOTA, Oxo-DO3A. and PCTA

Two novel bifunctional chelates, 3,6,9,15-tetraazabicyclo[9.3. 1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA) and 1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (Oxo-DO3A), were found to radiolabel antibodies with copper 64 (64Cu) well for positron emission tomography (PET). In this study, the same chelators were used to radiolabel peptides with 64Cu for PET imaging of angiogenesis. PCTA, Oxo-DO3A, and 1,4,7,10-tetraazacyclododecane-N,N‘,N“,N”’-tetraacetic acid (DOTA) were conjugated to cyclic-(RGDyK), and their binding affinities were confirmed. Conditions for 64Cu radiolabeling were optimized for maximum yield and specific activity. The in vitro stability of the radiolabeled compounds was challenged with serum incubation. PET studies were carried out in a non-αvβ3-expressing tumor model to evaluate the compounds' specificity for proliferating tumor vasculature and their in vivo pharmacokinetics. The PCTA and Oxo-DO3A bioconjugates were labeled with 64Cu at higher effective specific activity and radiochemical yield than the DOTA bioconjugate. In the imaging studies, all the 64Cu bioconjugates could be used to visualize the tumor and the radiotracer uptake was blocked with cyclic-(RGDyK). Target uptake of each bioconjugate was similar, but differences in other tissues were observed. 64Cu-PCTA-RGD showed the best clearance from nontarget tissue and the highest tumor to nontarget ratios. PCTA was the most promising bifunctional chelate for 64Cu peptide imaging and warrants further investigation.
Time-mode techniques for fast-locking phase-locked loops

A fast-locking phase-locked loop (PLL) with variable loop dynamics is proposed. The PLL employs a time amplifier (TA) with a variable gain to amplify the phase difference between the reference clock and the output of the voltage controlled oscillator (VCO). It operates by dynamically increasing the bandwidth of the PLL during locking state to speed up locking process and decreasing the bandwidth of the PLL in locked state to optimize the performance of the PLL. The insertion of the TA also reduces the time constant of the loop filter without sacrificing performance, thereby allowing the reduction of the resistance and capacitance of the loop filter subsequently their silicon and power consumption. The increased width of Up and Down pulses also enable the reduction of the current of the charge pump while achieving the same variation of the control voltage thereby lowering the power consumption. Two identical PLLs, one with the TA and the other without were designed in an IBM 0. 13 μm CMOS 1.2 V technology and analyzed using SpectreRF from Cadence Design Systems with BSIM4 device models. Both critically damped and under-damped cases were investigated. Simulation results demonstrate that in the critically damped case, the lock time of the PLL with the TA is 0.42 μs while that without is 0.52 μs. In the under damped case, the lock time of the PLL with the TA is 0.30 μs while that without is 1.54 μs.
Holy Foolishness in Russia: New Perspectives

Priscilla Hunt and Svitlana Kobets. Holy Foolishness in Russia: New Perspectives. Bloomington: Slavica Publishers, 2011. viii, 405 pp. Colour Illustrations. Bibliography. $36.70, paper.Holy Foolishness in Russia: New Perspectives, edited by Priscilla Hunt and Svitlana Kobets, is a collection of essays exploring the phenomenon of holy foolishness in Russia from the eleventh century to the present. From hagiography and hymnology to contemporary Russian performance art, the articles demonstrate the intimate relationship between the stories themselves and the historical contexts in which they were told. Of particular interest in this volume is the comparative analysis of how interpretations of holy foolishness and holy fools have changed over time. The enduring significance of certain texts to the interpretation of holy foolishness in various historical settings, such as the Vita of Andrew the Fool of Constantinople,1 is also evident through the combined efforts of these authors.It is impossible to give every chapter its due; however, a brief overview will provide a glimpse into the breadth and insight available in the book, as well as some of its limitations. The first four articles provide the framework within which the research in this volume is to be understood. Hunt opens the discussion by emphasizing the groundbreaking influence of A. M. Panchenko's phenomenological approach to the topic (p. 3) as well as "the importance of holy foolishness as an ongoing pattern of culture" (p. 5). This is followed by a survey of the historical, cultural, and textual developments regarding holy foolishness, written by Kobets.Next, the work of A. M. Panchenko, "Laughter as Spectacle" (first published in D. S. Likhachev, A. M. Panchenko, and Ν. V. Ponyrko, Smekh ν Drevnei Rusi [Nauka, 1984] 72-153) is translated into English for the first time. Panchenko makes the connections between Russian and European traditions and culture and draws out the similarities and differences between holy fools and jesters (pp. 52,110), identifying holy foolishness as "a 'serious' variation on the world of laughter" (p. 147). He then examines the role of spectacle and the fool's relationship with his audience, and the connection between holy foolishness and social protest, with particular attention to the paradigm of "status reversal" (p. 128) as well as the relationship between Old Believers and holy fools. The translators have provided a great service in making this influential work available to a broader audience. Where possible, they have also updated the footnotes to include information on sources available in translation.The other articles in the book demonstrate the extent to which Panchenko's work has been seminal in this field of research. In her examination of The Vita of Andrew of Constantinople and its relationship to Russian urban holy foolishness, Hunt rejects Panchenko's focus on the language of carnival and instead emphasizes the importance of imperial liturgy and spectacle and the Byzantine model of holy foolishness. …
Investigation of a simplified artificial lighting programme to improve the fertility of sows in commercial piggeries

Two artificial lighting regimens were studied in a commercial unit of 800 sows. The aim was to develop a simplified lighting regimen to overdrive the effects of season on reproduction. A long-day group had a constant 16 hours light and eight hours dark photoperiod in all units during a production cycle. A short-day group had eight hours of light and 16 hours darkness in a farrowing unit for four weeks and in a mating unit for four weeks. After one month of pregnancy the short-day group was transferred to 16 hours light and eight hours dark for the rest of the dry-sow period. Production data were collected for eight months, and the farrowing rate, weaning to oestrus interval, culling rate for fertility problems and the number of live-born piglets were analysed. Seasonal infertility, which had previously affected the herd, was not detected in either group during the follow-up period. The farrowing rate was 90 per cent for both groups. The median weaning to oestrus interval was five days in both lighting regimens with ranges from four to 74 days in the short-day group and three to 55 days in the long-day group. The long-day programme had a positive effect on the weaning to oestrus interval. When the sows were classified as either ‘normal’, with a weaning to oestrus interval of up to 10 days, or ‘problem’ animals, with a weaning to oestrus interval of over 10 days, the short-day programme also had a positive effect. The culling rate for fertility problems was 2·4 per cent for the short-day group and 3·2 per cent for the long-day group (P=0·027). The only significant predictor for the number of live-born piglets was parity (P=0·027).
Neurological comorbidity and epilepsy: implications for treatment

Epilepsy is a chronic condition that may be associated with several other diseases. In these cases, we should consider the following points: (1) antiepileptic drug (AED) treatment may positively or negatively affect comorbid disease, (2) drugs used for treatment of co‐morbid disease may influence seizure threshold, (3) AED toxicity can be affected by a comorbid condition and (4) co‐administration of AEDs with drugs used for treatment of comorbid conditions can be associated with clinically relevant drug–drug interactions. In this article, we discuss problems that are usually encountered when an appropriate AED treatment has to be selected in newly diagnosed epileptic patients who also have (an)other neurological disease(s). Comorbidity of epilepsy with cerebrovascular diseases, dementias, mental retardation, attention deficit and hyperactivity disorder, brain tumours, infections of the CNS, migraine, sleep disturbances (obstructive sleep apnoea syndrome), substance abuse and multiple sclerosis is discussed.
The xenobiotic inhibitor profile of cytochrome P4502C8.

AIMS To investigate inhibition of recombinant CYP2C8 by: (i) prototypic CYP isoform selective inhibitors (ii) imidazole/triazole antifungal agents (known inhibitors of CYP), and (iii) certain CYP3A substrates (given the apparent overlapping substrate specificity of CYP2C8 and CYP3A). METHODS CYP2C8 and NADPH-cytochrome P450 oxidoreductase were coexpressed in Spodoptera frugiperda (Sf21) cells using the baculovirus expression system. CYP isoform selective inhibitors, imidazole/triazole antifungal agents and CYP3A substrates were screened for their inhibitory effects on CYP2C8-catalysed torsemide tolylmethylhydroxylation and, where appropriate, the kinetics of inhibition were characterized. The conversion of torsemide to its tolylmethylhydroxy metabolite was measured using an h.p.l.c. procedure. RESULTS At concentrations of the CYP inhibitor 'probes' employed for isoform selectivity, only diethyldithiocarbamate and ketoconazole inhibited CYP2C8 by > 10%. Ketoconazole, at an added concentration of 10 microM, inhibited CYP2C8 by 89%. Another imidazole, clotrimazole, also potently inhibited CYP2C8. Ketoconazole and clotrimazole were both noncompetitive inhibitors of CYP2C8 with apparent Ki values of 2.5 microM. The CYP3A substrates amitriptyline, quinine, terfenadine and triazolam caused near complete inhibition (82-91% of control activity) of CYP2C8 at concentrations five-fold higher than the known CYP3A Km. Kinetic studies with selected CYP3A substrates demonstrated that most inhibited CYP2C8 noncompetitively. Apparent Ki values for midazolam, quinine, terfenadine and triazolam ranged from 5 to 25 microM. CONCLUSIONS Inhibition of CYP2C8 occurred at concentrations of ketoconazole and diethyldithiocarbamate normally employed for selective inhibition of CYP3A and CYP2E1, respectively. Some CYP3A substrates have the capacity to inhibit CYP2C8 activity and this may have implications for inhibitory drug interactions in vivo.
Prognostic Factors in Older Patients with Advanced Non-small Cell Lung Cancer in China

Aims and Background The human life expectancy and the incidence of lung cancer have increased dramatically in recent years. As a result, there is a high demand for the management of older patients with advanced non-small cell lung cancer (NSCLC) in clinical practice. The purpose of this study is to evaluate the prognostic factors in ≥65-year-old patients with advanced NSCLC in China. Method This study involved a retrospective review of 78 ≥65-year-old patients with a diagnosis of NSCLC and at an advanced stage of disease, defined as stage IIIB or IV. All patients were followed up for a 3-year interval to determine the survival rates. Clinical data including gender, smoking history, comorbidities, performance status (PS), histological differentiation, disease stage, treatment and overall survival were recorded. The log-rank test was used to calculate survival rates. Multivariate Cox regression analysis was performed to determine independent prognostic factors. Results The 1-year, 2-year and 3-year survival rates of the 78 patients were 44.9%, 23.1% and 9.0%, respectively. In univariate analysis by the log-rank test, the 3-year survival rate was significantly associated with PS (P <0.01), disease stage (P <0.01) and chemotherapy treatment (P <0.01). The results of multivariate Cox regression analysis confirmed that PS and disease stage were independent prognostic factors. Conclusion The 3-year survival rate in ≥65-year-old patients with advanced NSCLC was significantly associated with PS, disease stage and chemotherapy. PS and disease stage were independent prognostic factors. Older patients with advanced NSCLC in China might benefit from chemotherapy.