Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychosocial illness. Community, primary health care and individual perspectives

The aim of the thesis is to contribute to knowledge of (1) psychosocial illness in the population, (2) the prevalence and nature of psychosocial illness encountered in primary health care, and (3) encountered among persons with long-term illness. The data collected include the results of a questionnaire given to a population-based sample of 13 000 persons (20-84 years), a questionnaire given to general practitioners (GP) (N=199), and interviews with 30 persons with long-term illness and results of psychological testing of them (Sense of Coherence, SOC, and Karolinska Scales of Personality, KSP). The GPs estimated that approximately one third of their patients in primary health care had problems that could be attributed to psychosocial causes. GPs with a psychosocial orientation, as well as female GPs generally, gave higher estimates of the proportion of patients suffering from psychosocial illness. Pain, fatigue and multiple symptoms were the most frequently reported complaints, and loneliness, family problems and conflict at the work-place the most frequent psychosocial problems. A majority of the GPs felt that their medical training gave them inadequate knowledge of psychological and psychosocial issues. One third of the GPs considered their present level of education and experience to be insufficient to give patients with psychosocial problems adequate help. A majority of the respondents in the population study considered their health and life-situation to be satisfactory. Health and living conditions were unequally distributed between groups, however. High-risk groups, defined as those with poor health and psychosocial problems, included persons with long-term illness, as well as unemployed persons, women, immigrants, single persons, low-educated persons, workers and farmers. The same high-risk groups were overrepresented on nearly all variables included in the study. Patients in primary health care reported a greater number of symptoms and of psychosocial problems than the remaining participants in the population sample did. A certain degree of correspondence was found between the symptoms and the psychosocial problems found in the population study and the GPs’ appraisal of their patients’ concerns. The 30 persons with long-term illness who were interviewed reported that they had been exposed to various adverse conditions. Two thirds of them had experienced a harsh upbringing and had received only a minimal level of education. Half of the group had no vocational education at all and one fifth was unemployed. One third of the total group had been exposed to a variety of hardships concerning their health and their life situation. This subgroup had significantly lower SOC scores than the remaining individuals, as well as higher scores on somatic anxiety, muscular tension, psychasthenia and lower scores on socialization in terms of the KSP. A significant decrease in SOC scores was shown in a follow-up study six years later, indicating a continuous deterioration of the patients’ overall well-being.
Joint Pitch and DOA Estimation Using the ESPRIT Method

In this paper, the problem of joint multi-pitch and direction-of-arrival (DOA) estimation for multichannel harmonic sinusoidal signals is considered. A spatio-temporal matrix signal model for a uniform linear array is defined, and then the ESPRIT method based on subspace techniques that exploits the invariance property in the time domain is first used to estimate the multi pitch frequencies of multiple harmonic signals. Followed by the estimated pitch frequencies, the DOA estimations based on the ESPRIT method are also presented by using the shift invariance structure in the spatial domain. Compared to the existing state-of-the-art algorithms, the proposed method based on ESPRIT without 2-D searching is computationally more efficient but performs similarly. An asymptotic performance analysis of the DOA and pitch estimation of the proposed method are also presented. Finally, the effectiveness of the proposed method is illustrated on a synthetic signal as well as real-life recorded data.
Postnatal development of the innervation and paraganglia in the porcine pulmonary arterial bed

The innervation of the pulmonary trunk and pulmonary arterial bed was studied in 17 pigs from birth to 6 months of age. After birth, the pulmonary trunk and extra‐and intra‐pulmonary arteries contained neurofilament and protein gene‐product‐immunoreactive nerve fibres in both the adventitia and media. The density of nerve fibres increased from birth to 2 months, this being most marked during the first 2 weeks of life. Most of the fibres in the media were presumed to be sympathetic in origin as they contained both neuropeptide tyrosine and tyrosine hydroxylase immunoreactivity. Fibres were associated with the vasa‐vasorum and vascular smooth muscle running around the vessel, between the elastic laminae and smooth muscle cells, in the outer two‐thirds of the media. Vasoactive intestinal polypeptide and calcitonin gene‐related peptide‐immunoreactive nerve fibres were found to be associated with the pulmonary trunk and extra‐pulmonary artery, but generally not with the intra‐pulmonary arteries. Tyrosine hydroxylase immunoreactivity was detected in the glomus cells at birth, but peptide immunoreactivity (enkephalin) was not demonstrated in paraganglia until 14 days of age. Adaptation to extra‐uterine life is associated with rapid development changes in the innervation of the pig pulmonary trunk, extra‐and intra‐pulmonary arteries and in the expression of peptide immunoreactivity in both nerve fibres and glomus cells. These changes may have a role in the postnatal adaptation of the pulmonary circulation.
Marine Actinomycetes: A New Source of Compounds against the Human Malaria Parasite

Background Malaria continues to be a devastating parasitic disease that causes the death of 2 million individuals annually. The increase in multi-drug resistance together with the absence of an efficient vaccine hastens the need for speedy and comprehensive antimalarial drug discovery and development. Throughout history, traditional herbal remedies or natural products have been a reliable source of antimalarial agents, e.g. quinine and artemisinin. Today, one emerging source of small molecule drug leads is the world's oceans. Included among the source of marine natural products are marine microorganisms such as the recently described actinomycete. Members of the genus Salinispora have yielded a wealth of new secondary metabolites including salinosporamide A, a molecule currently advancing through clinical trials as an anticancer agent. Because of the biological activity of metabolites being isolated from marine microorganisms, our group became interested in exploring the potential efficacy of these compounds against the malaria parasite. Methods We screened 80 bacterial crude extracts for their activity against malaria growth. We established that the pure compound, salinosporamide A, produced by the marine actinomycete, Salinispora tropica, shows strong inhibitory activity against the erythrocytic stages of the parasite cycle. Biochemical experiments support the likely inhibition of the parasite 20S proteasome. Crystal structure modeling of salinosporamide A and the parasite catalytic 20S subunit further confirm this hypothesis. Ultimately we showed that salinosporamide A protected mice against deadly malaria infection when administered at an extremely low dosage. Conclusion These findings underline the potential of secondary metabolites, derived from marine microorganisms, to inhibit Plasmodium growth. More specifically, we highlight the effect of proteasome inhibitors such as salinosporamide A on in vitro and in vivo parasite development. Salinosporamide A (NPI-0052) now being advanced to phase I trials for the treatment of refractory multiple myeloma will need to be further explored to evaluate the safety profile for its use against malaria.
Evaluation of blood pressure pulse wave velocity and arterial relaxation constant

The paper discussed the relationship between blood pressure pulse wave velocity and arterial relaxation constant at brachial artery. The Windkessels model of brachial artery was assumed to simulate blood pressure decay waveform. The pulse wave velocity and noninvasive blood pressure wave form were acquired along with invasive aortic pressure. The result showed that the relaxation constant of aortic pressure waveform and brachial blood pressure waveform were −0.5±0.067 and −0.549±0.067 respectively. The relationship of higher pulse wave velocity and relaxation constant was 0.8.
Regulation of Tissue-Specific Carboxylesterase Expression by Pregnane X Receptor and Constitutive Androstane Receptor

The liver- and intestine-enriched carboxylesterase 2 (CES2) enzyme catalyzes the hydrolysis of several clinically important anticancer agents administered as prodrugs. For example, irinotecan, a carbamate prodrug used in the treatment of colorectal cancer, is biotransformed in vivo by CES2 in intestine and liver, thereby producing a potent topoisomerase I inhibitor. Pregnane X receptor (PXR) and constitutive androstane receptor (CAR), two members of the nuclear receptor superfamily of ligand-activated transcription factors, mediate gene activation in response to xenobiotic stress. Together, these receptors comprise a protective response in mammals that coordinately regulate hepatic transport, metabolism, and elimination of numerous xenobiotic compounds. In the present study, microarray analysis was used to identify PXR target genes in duodenum in mice. Here, we show that a gene encoding a member of the CES2 subtype of liver- and intestine-enriched CES enzymes, called Ces6, is induced after treatment with pregnenolone 16α-carbonitrile in a PXR-dependent manner in duodenum and liver in mice. Treatment of mice with the CAR activator 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene also induced expression of Ces6 in duodenum and liver in a CAR-dependent manner, whereas treatment with phenobarbital produced induction of Ces6 exclusively in liver. These data identify a key role for PXR and CAR in regulating the drug-inducible expression and activity of an important CES enzyme in vivo. Future studies should focus on determining whether these signaling pathways governing drug-inducible CES expression in intestine and liver are conserved in humans.
Be Careful When Assuming the Obvious: Commentary on "The placement of the head that minimizes online memory: a complex systems approach"

Ferrer-i-Cancho (2015) presents a mathematical model of both the synchronic and diachronic nature of word order based on the assumption that memory costs are a never decreasing function of distance and a few very general linguistic assumptions. However, even these minimal and seemingly obvious assumptions are not as safe as they appear in light of recent typological and psycholinguistic evidence. The interaction of word order and memory has further depths to be explored.
ULTRA-WIDEFIELD FUNDUS IMAGING: A Review of Clinical Applications and Future Trends

Purpose: To review the basic principles of ultra-widefield fundus imaging and discuss its clinical utility for a variety of retinal and choroidal disorders. Methods: A systematic review of the PubMed database was performed using the search terms Optos, optomap, panoramic, ultra-widefield, wide-angle, and ellipsoid mirror. This yielded 158 publications of which 128 were selected based on content and relevance. Results: A total of 128 articles pertaining to ultra-widefield imaging were cited in this review. Conclusion: Optos ultra-widefield imaging has become an essential tool for the identification of peripheral retinal and vascular pathology. The high resolution and multimodal capabilities of this device are also providing new insights into a variety of disorders, even those that primarily involve the posterior pole. Although the presence of artifact and the need for clinical validation are significant hurdles to more widespread use, ultra-widefield is evolving to become the standard-of-care imaging modality for many diseases and is finding new clinical and research applications such as for screening and telemedicine.
Patient Evaluation of Emotional Comfort Experienced (PEECE): developing and testing a measurement instrument

Objectives The Patient Evaluation of Emotional Comfort Experienced (PEECE) is a 12-item questionnaire which measures the mental well-being state of emotional comfort in patients. The instrument was developed using previous qualitative work and published literature. Design Instrument development. Setting Acute Care Public Hospital, Western Australia. Participants Sample of 374 patients. Interventions A multidisciplinary expert panel assessed the face and content validity of the instrument and following a pilot study, the psychometric properties of the instrument were explored. Main outcome measures Exploratory and confirmatory factor analysis assessed the underlying dimensions of the PEECE instrument; Cronbach's α was used to determine the reliability; κ was used for test–retest reliability of the ordinal items. Results 2 factors were identified in the instrument and named ‘positive emotions’ and ‘perceived meaning’. A greater proportion of male patients were found to report positive emotions compared with female patients. The instrument was found to be feasible, reliable and valid for use with inpatients and outpatients. Conclusions PEECE was found to be a feasible instrument for use with inpatient and outpatients, being easily understood and completed. Further psychometric testing is recommended.
The Generality of Drug Resistance Self-Efficacy across Social Situations and Solitary Contexts.

According to a recent national survey, 9 out of 10 high school students in the United States reported that they had tried alcohol at least once. Previous research has identified drug resistance self-efficacy (DRSE) as an important construct in adolescent drug use, which is the focus of this research study. A total of 361 students in grades 9-12 completed a 121-item questionnaire which focused on their use of beer, wine coolers, liquor, and marijuana. Results indicate that adolescents' perception of their ability to resist generalizes across situations, particularly for wine coolers and liquor. As perceptions of resistance in one situation increased, perceptions of resistance in another situation also increased. However, differences were observed in the magnitude of the relationship for certain drugs, specifically beer, wine coolers, and marijuana. Analysis of results show strong intercorrelations for each drug studied among the DRSE situations. Party DRSE was the strongest predictor of DRSE in a solitary context. Different predictive models, though, were found for the high frequency beer and marijuana users with respect to DRSE in solitary/angry situations. (RJM) ******************************************************************************** * Reproductions supplied by EDRS are the best that can be made * * from the original document. * ********************************************************************************
Functional Domains of the α1 Catalytic Subunit of the AMP-activated Protein Kinase*

The AMP-activated protein kinase is a heterotrimeric enzyme, important in cellular adaptation to the stress of nutrient starvation, hypoxia, increased ATP utilization, or heat shock. This mammalian enzyme is composed of a catalytic α subunit and noncatalytic β and γ subunits and is a member of a larger protein kinase family that includes the SNF1 kinase of Saccharomyces cerevisiae. In the present study, we have identified by truncation and site-directed mutagenesis several functional domains of the α1 catalytic subunit, which modulate its activity, subunit association, and protein turnover. C-terminal truncation of the 548-amino acid (aa) wild-type α1 protein to aa 312 or 392 abolishes the binding of the β/γ subunits and dramatically increases protein expression. The full-length wild-type α1 subunit is only minimally active in the absence of co-expressed β/γ, and α1(1–392) likewise has little activity. Further truncation to aa 312, however, is associated with a large increase in enzyme specific activity, thus revealing an autoinhibitory sequence between aa 313 and 392. α-1(1–312) still requires the phosphorylation of the activation loop Thr-172 for enzyme activity, yet is now independent of the allosteric activator, AMP. The increased levels of protein expression on transient transfection of either truncated α subunit cDNA are because of a decrease in enzyme turnover by pulse-chase analysis. Taken together, these data indicate that the α1 subunit of AMP-activated protein kinase contains several features that determine enzyme activity and stability. A constitutively active form of the kinase that does not require participation by the noncatalytic subunits provides a unique reagent for exploring the functions of AMP-activated protein kinase.
Serotonin and Immune Response: Effect of the Amine on in vitro Proliferation of Rat Lymphocytes

Objective: The effect of serotonin (5-hydroxytryptamine; 5HT) on the in vitro proliferation of mitogen-stimulated lymphocytes was studied in primary cultures of rat spleen cells. Methods: 5HT was added to the cultures 1 h prior to the mitogen, at final concentrations from 10–13 up to 10–2M. T and B cell mitogens (concanavalin A, pokeweed mitogen and lipopolysaccharide) were used at suboptimal and optimal concentrations. The cell proliferation was measured 24–72 h after the addition of mitogen. The effect of each 5HT concentration was studied on a group of 6–12 animals and was expressed as a percentage of the control values obtained with mitogen alone. Results: No significant effect of 5HT at concentrations from 10–13 to 10–5M was found. At concentrations of ≧10–4M, a regular dose-dependent inhibition of the lymphocyte proliferation appeared, the concentration producing the half-maximal effect being 6 × 10–4M. The observed suppression was not due to 5HT cytotoxicity toward spleen cells. Conclusion: With the experimental system used, we failed to confirm an immunostimulatory effect of 5HT in the range of concentrations of its receptor sensitivities or lower, but found a clear-cut immunoinhibitory effect at higher concentrations.
Genetic Variation of Bordetella pertussis in Austria

In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. Waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. In this study we therefore addressed the genetic variability in B. pertussis strains from several Austrian cities. Between the years 2002 and 2008, 110 samples were collected from Vienna (n = 32), Linz (n = 63) and Graz (n = 15) by nasopharyngeal swabs. DNA was extracted from the swabs, and bacterial sequence polymorphisms were examined by MLVA (multiple-locus variable number of tandem repeat analysis) (n = 77), by PCR amplification and conventional Sanger sequencing of the polymorphic regions of the prn (pertactin) gene (n = 110), and by amplification refractory mutation system quantitative PCR (ARMS-qPCR) (n = 110) to directly address polymorphisms in the genes encoding two pertussis toxin subunits (ptxA and ptxB), a fimbrial adhesin (fimD), tracheal colonisation factor (tcfA), and the virulence sensor protein (bvgS). Finally, the ptxP promoter region was screened by ARMS-qPCR for the presence of the ptxP3 allele, which has been associated with elevated production of pertussis toxin. The MLVA analysis revealed the highest level of polymorphisms with an absence of MLVA Type 29, which is found outside Austria. Only Prn subtypes Prn1/7, Prn2 and Prn3 were found with a predominance of the non-vaccine type Prn2. The analysis of the ptxA, ptxB, fimD, tcfA and bvgS polymorphisms showed a genotype mixed between the vaccine strain Tohama I and a clinical isolate from 2006 (L517). The major part of the samples (93%) displayed the ptxP3 allele. The consequences for the vaccination strategy are discussed.
Significant synovial pathology in a meniscectomy model of osteoarthritis: modification by intra-articular hyaluronan therapy

Objective. IA therapy with hyaluronan (HA) is reported to provide symptomatic relief and disease modification in OA. This study assessed the pathological changes in the synovium of an ovine model of OA and evaluated the effects of two HA preparations on this pathology. Methods. Eighteen sheep had bilateral lateral meniscectomy to induce OA. Four months post-surgery animals received IA saline or HA (Hyalgan®) weekly for 5 weeks or three injections of an amide derivative of HA (HYADD®4-G) every 2 weeks (n = 6 per group). Six months after meniscectomy, sheep were killed, knee joint synovium processed, scored for pathological change and compared with synovium from non-operated animals. Sections of synovium from normal and treated joints were also immunostained for TNF-α, HSP-47, TGF-β, CD44, connective tissue growth factor (CTGF) or iNOS. HA synthesis by synovial fibroblasts isolated from each OA joint was quantified. Results. Aggregate scores of pathological change were higher in OA joint synovia compared with controls, with individual measures of subintimal fibrosis and vascularity predominantly affected. Depth of intimal fibrosis was also significantly higher in meniscectomized joints. IA treatment with Hyalgan® decreased aggregate score, vascularity and depth of fibrosis. HYADD®4-G treatment decreased vascularity, intimal hyperplasia and increased high-molecular weight HA synthesis by synovial fibroblasts. CD44, CTGF or iNOS expression was increased in the synovial lining of OA joints compared with normal, but there was no significant modulation of this increase by either HA preparation. Conclusion. Increased fibrosis and vascularity are hallmarks of pathological change in synovium in this meniscectomy model of OA. Both the IA HA and an amide derivative of HA reduced aspects of this pathology thus providing a potential mechanism for improving joint mobility and function in OA.
Image volume denoising using a Fourier-wavelet basis

A novel approach to the removal of noise from threedimensional image data is described. The image sequence is represented using a non-adaptive wavelet basis, carefully chosen for its ability to compactly represent locally planar surfaces. This is important in many 3-D applications, including video sequences, where they represent moving luminance edges, and medical volume data, where they represent the interfaces between tissue and bone, for example. The new basis, called a Fourier-Wavelet Basis, is an extension of the complex wavelet bases which have been increasing in popularity in recent years. Because transformation to the new basis is efficient computationally, the overall denoising algorithm is highly efficient. The success of the approach is demonstrated using a noisy video sequence and a noisy human knee MR image volume.
Algebraic Multigrid Preconditioning of High-Order Spectral Elements for Elliptic Problems on a Simplicial Mesh

Algebraic multigrid is investigated as a solver for linear systems that arise from high-order spectral element discretizations. An algorithm is introduced that utilizes the efficiency of low-order finite elements to precondition the high-order method in a multilevel setting. In particular, the efficacy of this approach is highlighted on simplexes in two and three dimensions with nodal spectral elements up to order $n=11$. Additionally, a hybrid preconditioner is also developed for use with discontinuous spectral element methods. The latter approach is verified for the discontinuous Galerkin method on elliptic problems.