LLukas22/scidocs huggingface dataset:
Environmental fate of pharmaceuticals in water/sediment systems.

In recent years there has been growing interest on the occurrence and the fate of pharmaceuticals in the aquatic environment. Nevertheless, few data are available covering the fate of the pharmaceuticals in the water/sediment compartment. In this study, the environmental fate of 10 selected pharmaceuticals and pharmaceutical metabolites was investigated in water/sediment systems including both the analysis of water and sediment. The experiments covered the application of four 14C-labeled pharmaceuticals (diazepam, ibuprofen, iopromide, and paracetamol) for which radio-TLC analysis was used as well as six nonlabeled compounds (carbamazepine, clofibric acid, 10,11-dihydro-10,11-dihydroxycarbamazepine, 2-hydroxyibuprofen, ivermectin, and oxazepam), which were analyzed via LC-tandem MS. Ibuprofen, 2-hydroxyibuprofen, and paracetamol displayed a low persistence with DT50 values in the water/sediment system < or =20 d. The sediment played a key role in the elimination of paracetamol due to the rapid and extensive formation of bound residues. A moderate persistence was found for ivermectin and oxazepam with DT50 values of 15 and 54 d, respectively. Lopromide, for which no corresponding DT50 values could be calculated, also exhibited a moderate persistence and was transformed into at least four transformation products. For diazepam, carbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine, and clofibric acid, system DT90 values of >365 d were found, which exhibit their high persistence in the water/sediment system. An elevated level of sorption onto the sediment was observed for ivermectin, diazepam, oxazepam, and carbamazepine. Respective Koc values calculated from the experimental data ranged from 1172 L x kg(-1) for ivermectin down to 83 L x kg(-1) for carbamazepine.
Algorithmic Framework for Model-based Reinforcement Learning with Theoretical Guarantees

Model-based reinforcement learning (RL) is considered to be a promising approach to reduce the sample complexity that hinders model-free RL. However, the theoretical understanding of such methods has been rather limited. This paper introduces a novel algorithmic framework for designing and analyzing model-based RL algorithms with theoretical guarantees. We design a meta-algorithm with a theoretical guarantee of monotone improvement to a local maximum of the expected reward. The meta-algorithm iteratively builds a lower bound of the expected reward based on the estimated dynamical model and sample trajectories, and then maximizes the lower bound jointly over the policy and the model. The framework extends the optimism-in-face-of-uncertainty principle to non-linear dynamical models in a way that requires no explicit uncertainty quantification. Instantiating our framework with simplification gives a variant of model-based RL algorithms Stochastic Lower Bounds Optimization (SLBO). Experiments demonstrate that SLBO achieves stateof-the-art performance when only one million or fewer samples are permitted on a range of continuous control benchmark tasks.1
Coupled synthesis and self-assembly of nanoparticles to give structures with controlled organization

Colloidal inorganic nanoparticles have size-dependent optical, optoelectronic and material properties that are expected to lead to superstructures with a range of practical applications. Discrete nanoparticles with controlled chemical composition and size distribution are readily synthesized using reverse micelles and microemulsions as confined reaction media, but their assembly into well-defined superstructures amenable to practical use remains a difficult and demanding task. This usually requires the initial synthesis of spherical nanoparticles, followed by further processing such as solvent evaporation, molecular cross-linking or template-patterning. Here we report that the interfacial activity of reverse micelles and microemulsions can be exploited to couple nanoparticle synthesis and self-assembly over a range of length scales to produce materials with complex organization arising from the interdigitation of surfactant molecules attached to specific nanoparticle crystal faces. We demonstrate this principle by producing three different barium chromate nanostructures—linear chains, rectangular superlattices and long filaments—as a function of reactant molar ratio, which in turn is controlled by fusing reverse micelles and microemulsion droplets containing fixed concentrations of barium and chromate ions, respectively. If suitable soluble precursors and amphiphiles with headgroups complementary to the crystal surface of the nanoparticle target are available, it should be possible to extend our approach to the facile production of one-dimensional ‘wires’ and higher-order colloidal architectures made of metals and semiconductors.
Copeptin Predicts Mortality in Critically Ill Patients

BACKGROUND
Critically ill patients admitted to a medical intensive care unit exhibit a high mortality rate irrespective of the cause of admission. Besides its role in fluid and electrolyte balance, vasopressin has been described as a stress hormone. Copeptin, the C-terminal portion of provasopressin mirrors vasopressin levels and has been described as a reliable biomarker for the individual's stress level and was associated with outcome in various disease entities. The aim of this study was to analyze whether circulating levels of copeptin at ICU admission are associated with 30-day mortality.


METHODS
In this single-center prospective observational study including 225 consecutive patients admitted to a tertiary medical ICU at a university hospital, blood was taken at ICU admission and copeptin levels were measured using a commercially available automated sandwich immunofluorescent assay.


RESULTS
Median acute physiology and chronic health evaluation II score was 20 and 30-day mortality was 25%. Median copeptin admission levels were significantly higher in non-survivors as compared with survivors (77.6 IQR 30.7-179.3 pmol/L versus 45.6 IQR 19.6-109.6 pmol/L; p = 0.025). Patients with serum levels of copeptin in the third tertile at admission had a 2.4-fold (95% CI 1.2-4.6; p = 0.01) increased mortality risk as compared to patients in the first tertile. When analyzing patients according to cause of admission, copeptin was only predictive of 30-day mortality in patients admitted due to medical causes as opposed to those admitted after cardiac surgery, as medical patients with levels of copeptin in the highest tertile had a 3.3-fold (95% CI 1.66.8, p = 0.002) risk of dying independent from APACHE II score, primary diagnosis, vasopressor use and need for mechanical ventilation.


CONCLUSION
Circulating levels of copeptin at ICU admission independently predict 30-day mortality in patients admitted to a medical ICU.
Statin use after colorectal cancer diagnosis and survival: a population-based cohort study.

PURPOSE
To investigate whether statins used after colorectal cancer diagnosis reduce the risk of colorectal cancer-specific mortality in a cohort of patients with colorectal cancer.


PATIENTS AND METHODS
A cohort of 7,657 patients with newly diagnosed stage I to III colorectal cancer were identified from 1998 to 2009 from the National Cancer Data Repository (comprising English cancer registry data). This cohort was linked to the United Kingdom Clinical Practice Research Datalink, which provided prescription records, and to mortality data from the Office of National Statistics (up to 2012) to identify 1,647 colorectal cancer-specific deaths. Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% CIs by postdiagnostic statin use and to adjust these HRs for potential confounders.


RESULTS
Overall, statin use after a diagnosis of colorectal cancer was associated with reduced colorectal cancer-specific mortality (fully adjusted HR, 0.71; 95% CI, 0.61 to 0.84). A dose-response association was apparent; for example, a more marked reduction was apparent in colorectal cancer patients using statins for more than 1 year (adjusted HR, 0.64; 95% CI, 0.53 to 0.79). A reduction in all-cause mortality was also apparent in statin users after colorectal cancer diagnosis (fully adjusted HR, 0.75; 95% CI, 0.66 to 0.84).


CONCLUSION
In this large population-based cohort, statin use after diagnosis of colorectal cancer was associated with longer rates of survival.
Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline.

BACKGROUND
Stenting is the treatment of choice for inoperable malignant strictures of the common bile duct. Criteria for the choice of stents (plastic versus metallic) remain controversial because predicting survival is difficult.


AIMS
To define prognostic factors in order to improve the cost effectiveness of endoscopic palliation.


PATIENTS
One hundred and one patients were included in a prospective trial. Seven prognostic variables for survival were analysed (age, sex, bilirubinaemia, weight loss, presence of liver metastases, and tumour histology and size). All patients were followed until death or at least one year after inclusion. By the end of the study, 81 (80.2%) patients had died.


RESULTS
In univariate analysis, the variables associated with survival were weight loss (p < 0.05) and tumour size (p < 0.01). By multivariate analysis, tumour size was the only independent prognostic factor (p < 0.05). A threshold of 30 mm at diagnosis distinguished two survival profiles: the median survival of patients with a tumour greater than 30 mm was 3.2 months, whereas it was 6.6 months for patients with a tumour less than 30 mm (p < 0.001).


CONCLUSIONS
A practical strategy could be based on tumour size at diagnosis: a metal stent should be systematically chosen for patients with an inoperable tumour smaller than 30 mm, while larger tumours are efficiently palliated by a plastic stent.
Higher Hemoglobin A1c After Discharge Is an Independent Predictor of Adverse Outcomes in Patients With Acute Coronary Syndrome　- Findings From the PACIFIC Registry.

BACKGROUND
Optimal medical therapy (OMT) and the management of coronary risk factors are necessary for secondary prevention of major adverse cardiac and cerebrovascular events (MACCE) in post-acute coronary syndrome (ACS) patients. However, the effect of post-discharge patient adherence has not been investigated in Japanese patients.


METHODSANDRESULTS
The Prevention of AtherothrombotiC Incidents Following Ischemic Coronary Attack (PACIFIC) registry was a multicenter, prospective observational study of 3,597 patients with ACS. Death or MACCE occurred in 229 patients between hospitalization and up to 1 year after discharge. Among 2,587 patients, the association between OMT adherence and risk factor control at 1 year and MACCE occurring between 1 and 2 years after discharge was assessed. OMT was defined as the use of antiplatelet agents, angiotensin-converting enzyme inhibitors, β-blockers, and statins. Risk factor targets were: low-density lipoprotein-cholesterol <100 mg/dl, HbA1c <7.0%, non-smoking status, blood pressure <130/80 mmHg, and 18.5≤body mass index≤24.9 kg/m(2). The incidence of MACCE was 1.8% and associated with female sex (P=0.020), age ≥75 years (P=0.004), HbA1c ≥7.0% (P=0.004), LV ejection fraction <35% (P<0.001), estimated glomerular filtration rate <60 ml/min (P=0.008), and history of cerebral infarction (P=0.003). In multivariate analysis, lower post-discharge HbA1c was strongly associated with a lower risk of MACCE after ACS (P=0.004).


CONCLUSIONS
Hyperglycemia after discharge is a crucial target for the prevention of MACCE in post-ACS patients. (Circ J 2016; 80: 1607-1614).
A Framework for Identifying Software Project Risks

We've all heard tales of multimillion dollar mistakes that somehow ran off course. Are software projects that risky or do managers need to take a fresh approach when preparing for such critical expeditions? Software projects are notoriously difficult to manage and too many of them end in failure. In 1995, annual U.S. spending on software projects reached approximately $250 billion and encompassed an estimated 175,000 projects [6]. Despite the costs involved, press reports suggest that project failures are occurring with alarming frequency. In 1995, U.S companies alone spent an estimated $59 billion in cost overruns on IS projects and another $81 billion on canceled software projects [6]. One explanation for the high failure rate is that managers are not taking prudent measures to assess and manage the risks involved in these projects. is Advocates of software project risk management claim that by countering these threats to success, the incidence of failure can be reduced [4, 5]. Before we can develop meaningful risk management strategies, however, we must identify these risks. Furthermore, the relative importance of these risks needs to be established, along with some understanding as to why certain risks are perceived to be more important than others. This is necessary so that managerial attention can be focused on the areas that constitute the greatest threats. Finally, identified risks must be classified in a way that suggests meaningful risk mitigation strategies. Here, we report the results of a Delphi study in which experienced software project managers identified and ranked the most important risks. The study led not only to the identification of risk factors and their relative importance, but also to novel insights into why project managers might view certain risks as being more important than others. Based on these insights, we introduce a framework for classifying software project risks and discuss appropriate strategies for managing each type of risk. Since the 1970s, both academics and practitioners have written about risks associated with managing software projects [1, 2, 4, 5, 7, 8]. Unfortunately , much of what has been written on risk is based either on anecdotal evidence or on studies limited to a narrow portion of the development process. Moreover, no systematic attempts have been made to identify software project risks by tapping the opinions of those who actually have experience in managing such projects. With a few exceptions [3, 8], there has been little attempt to understand the …
A 70–90-GHz High-Linearity Multi-Band Quadrature Receiver in ${\hbox{0.35-}}\mu{\hbox {m}}$ SiGe Technology

An integrated frequency agile quadrature E-band receiver is presented in this paper. The complete receiver is realized in a commercial 0.35-μm SiGe:C technology with an ft/fmax of 170/250 GHz. The receiver covers the two point-to-point communication bands from 71 to 76 GHz and from 81 to 86 GHz and the automotive radar band at 77 GHz. A wide tuning range modified Colpitts oscillator provides a local oscillator (LO) tuning range > 30%. A two-stage constant phase RC polyphase network is implemented to provide wideband in-phase quadrature LO signals. The measured phase imbalance of the network stays below 8° over the receiver's frequency range. In addition the chip includes a wideband low-noise amplifier, Wilkinson power divider, down conversion mixers, and frequency prescaler. Each of the chip's receiver I/Q paths shows a measured conversion gain above 19 dB and an input referred 1-dB compression point of -22 dBm. The receiver's measured noise figure stays below 11 dB over the complete frequency range. Furthermore, the receiver has a measured IF bandwidth of 6 GHz. The complete chip including prescaler draws a current of 230 mA from a 3.3-V supply, and consumes a chip area of 1628 μm×1528 μm.
Fuzzy Perceptive Values for MDPs with Discounting

In this paper, we formulate the fuzzy perceptive model for discounted Markov decision processes in which the perception for transition probabilities is described by fuzzy sets. The optimal expected reward, called a fuzzy perceptive value, is characterized and calculated by a new fuzzy relation. As a numerical example, a machine maintenance problem is considered.
Estimates of beneficial and harmful sun exposure times during the year for major Australian population centres.

OBJECTIVE
To examine the influence of geographical and seasonal factors on duration of solar ultraviolet (UV) radiation exposure of skin to produce recommended vitamin D levels without producing erythema.


DESIGN AND SETTING
An ecological study using daily Ultraviolet Index (UVI) data collected in major population centres across Australia for 1 year (1 January - 31 December 2001) to calculate sun exposure times for recommended vitamin D production and erythema.


MAIN OUTCOME MEASURES
Sun exposure times to produce either serum vitamin D concentrations equivalent to an oral intake of 200-600 IU/day or erythema for people aged 19-50 years with fair skin (Fitzpatrick type II skin) exposing 15% of the body.


RESULTS
In January, across Australia, 2-14 minutes of sun three to four times per week at 12:00 is sufficient to ensure recommended vitamin D production in fair-skinned people with 15% of the body exposed. However, erythema can occur in as little as 8 minutes. By contrast, at 10:00 and 15:00, there is a greater difference between exposure time to produce erythema and that to produce recommended vitamin D levels, thereby reducing the risk of sunburn from overexposure. From October to March, around 10-15 minutes of sun exposure at around 10:00 or 15:00 three to four times per week should be enough for fair-skinned people across Australia to produce recommended vitamin D levels. Longer exposure times are needed from April to September, particularly in southern regions of Australia.


CONCLUSION
Our study reinforces the importance of existing sun protection messages for the summer months throughout Australia. However, fair-skinned people should be able to obtain sufficient vitamin D from short periods of unprotected sun exposure of the face, arms and hands outside of the peak UV period (10:00-15:00) throughout Australia for most of the year. The greater variability in sun exposure times during winter, means that optimal sun exposure advice should be tailored to each location.
Considerations and recent advances in QSAR models for cytochrome P450-mediated drug metabolism prediction

Quantitative structure-activity relationships (QSAR) methods are urgently needed for predicting ADME/T (absorption, distribution, metabolism, excretion and toxicity) properties to select lead compounds for optimization at the early stage of drug discovery, and to screen drug candidates for clinical trials. Use of suitable QSAR models ultimately results in lesser time-cost and lower attrition rate during drug discovery and development. In the case of ADME/T parameters, drug metabolism is a key determinant of metabolic stability, drug-drug interactions, and drug toxicity. QSAR models for predicting drug metabolism have undergone significant advances recently. However, most of the models used lack sufficient interpretability and offer poor predictability for novel drugs. In this review, we describe some considerations to be taken into account by QSAR for modeling drug metabolism, such as the accuracy/consistency of the entire data set, representation and diversity of the training and test sets, and variable selection. We also describe some novel statistical techniques (ensemble methods, multivariate adaptive regression splines and graph machines), which are not yet used frequently to develop QSAR models for drug metabolism. Subsequently, rational recommendations for developing predictable and interpretable QSAR models are made. Finally, the recent advances in QSAR models for cytochrome P450-mediated drug metabolism prediction, including in vivo hepatic clearance, in vitro metabolic stability, inhibitors and substrates of cytochrome P450 families, are briefly summarized.
Autoradiographic mapping of beta-adrenoceptors in human skin

A high density of β2-adrenoceptors has been found in human skin. Using autoradiographic mapping we investigated the distribution of β1- β2-receptors in normal and diseased human skin. Cryostat sections of human skin obtained at biopsy were incubated with [125I]-iodocyanopindolol and nonspecific binding was identified by incubation of adjacent sections with 200 μM (-)-isoproterenol; β2-receptors were visualized using CGP 20712A and β1-receptors using ICI 118,551 as competing agents. The epidermis was densely labelled with an even distribution throughout all layers. Most of the β-receptors were of the β2-subtype with practically no β1-receptors. β-Receptors were also localized to eccrine sweat glands, dermal blood vessels, and perivascular inflammatory cells, but there was no labelling of sebaceous glands. Topical glucocorticoids caused an increase in the density of epidermal β-receptors. We conclude that keratinocytes and eccrine sweat glands express high densities of β2-receptors suggesting that they may have a physiological role in the regulation of these cells.
Daily functioning and self-management in patients with chronic low back pain after an intensive cognitive behavioral programme for pain management

Chronic low back pain (CLBP) is associated with persistent or recurrent disability which results in high costs for society. Cognitive behavioral treatments produce clinically relevant benefits for patients with CLBP. Nevertheless, no clear evidence for the most appropriate intervention is yet available. The purpose of this study is to evaluate the mid-term effects of treatment in a cohort of patients with CLBP participating in an intensive pain management programme. The programme provided by RealHealth-Netherlands is based on cognitive behavioral principles and executed in collaboration with orthopedic surgeons. Main outcome parameters were daily functioning (Roland and Morris Disability Questionnaire and Oswestry Disability Questionnaire), self-efficacy (Pain Self-Efficacy Questionnaire) and quality of life (Short Form 36 Physical Component Score). All parameters were measured at baseline, last day of residential programme and at 1 and 12 months follow-up. Repeated measures analysis was applied to examine changes over time. Clinical relevance was examined using minimal clinical important differences (MCID) estimates for main outcomes. To compare results with literature effect sizes (Cohen’s d) and Standardized Morbidity Ratios (SMR) were determined. 107 patients with CLBP participated in this programme. Mean scores on outcome measures showed a similar pattern: improvement after residential programme and maintenance of results over time. Effect sizes were 0.9 for functioning, 0.8 for self-efficacy and 1.3 for physical functioning related quality of life. Clinical relevancy: 79% reached MCID on functioning, 53% on self-efficacy and 80% on quality of life. Study results on functioning were found to be 36% better and 2% worse when related to previous research on, respectively, rehabilitation programmes and spinal surgery for similar conditions (SMR 136 and 98%, respectively). The participants of this evidence-based programme learned to manage CLBP, improved in daily functioning and quality of life. The study results are meaningful and comparable with results of spinal surgery and even better than results from less intensive rehabilitation programmes.