Miracle-dz/UniFAR-FTUs huggingface dataset:
Comments on the Draft Guidance on “Adaptive Design Clinical Trials for Drugs and Biologics” of the U.S. Food and Drug Administration

The U.S. FDA has published a draft guidance on “Adaptive Design Clinical Trials for Drugs and Biologics”, which gives regulatory guidance on methodological issues in exploratory and confirmatory clinical trials planned with an adaptive design. This comment summarizes the discussion within the joint working group “Adaptive Designs and Multiple Testing Procedures” of the Austro-Swiss and German regions of the International Biometric Society held at the 90-day public comment period in spring 2010.
Invasive Ability of Escherichia coli O18 Isolated from Swine Neonatal Diarrhea

Neonatal diarrhea occurred at two swine breeding farms in Hokkaido. Ten piglets aged 2 to 4 days were examined. Grossly, significant changes were confined to the small intestine. The mucous membrane was muddy and thickened. The intraluminal contents from the jejunum to the colon were liquid and yellow. In the small intestine, numerous Gram-negative bacilli preferentially adhered to the apex of villi. The mucosa was erosive with villous atrophy. There were bacilli also in the lamina propria and in the cytoplasm of degenerated enterocytes. Nonhemolytic Escherichia coli strains, belonging to serogroup E. coli O18 and possessing K88 fimbriae, were isolated from the small intestine. They could not be classified into any of the diarrheagenic E. coli groups because of the absence of genes of LT, STh, STp, VT1, VT2, eae, invE, and ipaH. After inoculation of the isolates on HEp-2 cells, some bacilli were engulfed by cytoplasmic projections resembling membrane ruffles and subsequently were localized in cytoplasmic vacuoles or free in the cytoplasm. These findings support the view that the present E. coli O18 is a new invasive strain enteropathogenic to piglets.
Effects of therapy on haemostasis in dogs infected with Leishmania infantum, Ehrlichia canis, or both combined

CANINE leishmaniosis and canine ehrlichiosis are well-recognised infectious diseases in the Mediterranean. In the same area, coinfection with Leishmania and Ehrlichia is very frequently seen too. Haemostatic disorders (epistaxis, haematuria and haemorrhagic diarrhoea) are common findings in both
Transplantation of mouse induced pluripotent stem cells into the cochlea

This study examined the potential of induced pluripotent stem (iPS) cells for use as a source of transplants for the restoration of auditory spiral ganglion neurons. We monitored neurite outgrowth from iPS cell-derived neural progenitors toward cochlear hair cells ex vivo, and followed their survival and fates after transplantation into mouse cochleae in vivo. Neurons derived from iPS cells projected neurites toward cochlear hair cells. The settlement of iPS cell-derived neurons was observed 1 week after transplantation into the cochlea. Some transplants expressed vesicular glutamate transporter 1, which is a marker for glutamatergic neurons. These findings indicate that iPS cells can be used as a source of transplants for the regeneration of spiral ganglion neurons.
Recurrent acute necrotizing encephalopathy following influenza A in a genetically predisposed family

Acute necrotizing encephalopathy (ANE) typically affects young, healthy children who develop rapid‐onset severe encephalopathy triggered by viral infections. This disease is more commonly reported in Japan but occurs worldwide, although it remains under‐recognized in Western countries. An autosomal dominant form, ANE1, was recently identified. We report the details of a 9‐year‐old Caucasian female who experienced recurrent ANE episodes at the ages of 9 months and 9 years. Brain magnetic resonance imaging findings were characteristic of ANE during both episodes, although more extensive in the recent episode, which resulted in severe neurological sequelae; influenza A was identified on bronchoalveolar lavage during this episode. Interestingly, there was evidence of peripheral polyneuropathy during the recent episode, which has not previously been described in sporadic ANE. Both the patient and her mother, who had also had postviral polyneuritis in the past, harbour a mutation in Ran‐binding protein 2 (RANBP2); this occurred de novo in the mother and confers genetic susceptibility to ANE. Our case suggests that recurrent disease and/or an expanded clinical phenotype raises the possibility of ANE1; positive family history, although supportive, is not necessary as the mutation can occur de novo. Increased awareness may lead to earlier recognition and better treatment options.
Housing Temperature–Induced Stress Is Suppressing Murine Graft-versus-Host Disease through β2-Adrenergic Receptor Signaling

Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic cell transplantation, a potentially curative therapy for hematologic diseases. It has long been thought that murine bone marrow–derived T cells do not mediate severe GVHD because of their quantity and/or phenotype. During the course of experiments testing the impact of housing temperatures on GVHD, we discovered that this apparent resistance is a function of the relatively cool ambient housing temperature. Murine bone marrow–derived T cells have the ability to mediate severe GVHD in mice housed at a thermoneutral temperature. Specifically, mice housed at Institutional Animal Care and Use Committee–mandated, cool standard temperatures (∼22°C) are more resistant to developing GVHD than are mice housed at thermoneutral temperatures (∼30°C). We learned that the mechanism underlying this housing-dependent immunosuppression is associated with increased norepinephrine production and excessive signaling through β-adrenergic receptor signaling, which is increased when mice are cold stressed. Treatment of mice housed at 22°C with a β2-adrenergic antagonist reverses the norepinephrine-driven suppression of GVHD and yields similar disease to mice housed at 30°C. Conversely, administering a β2-adrenergic agonist decreases GVHD in mice housed at 30°C. In further mechanistic studies using β2-adrenergic receptor–deficient (β2-AR−/−) mice, we found that it is host cell β2-AR signaling that is essential for decreasing GVHD. These data reveal how baseline levels of β-adrenergic receptor signaling can influence murine GVHD and point to the feasibility of manipulation of β2-AR signaling to ameliorate GVHD in the clinical setting.
Anaesthetic risks in children with obstructive sleep apnea syndrome undergoing adenotonsillectomy.

OBJECTIVE To determine the frequency of anaesthetic risks in children having Obstructive Sleep Apnea Syndrome (OSAS), undergoing adenotonsillectomy. STUDY DESIGN A case-control study. PLACE AND DURATION OF STUDY Department of Anaesthesiology, Armed Forces Hospital, Najran, Saudi Arabia from November 2006 to January 2008. METHODOLOGY The study was carried out in 60 children scheduled to undergo adenotonsillectomy and divided into two equal groups of 30 each. Group-1 had obstructive sleep apnoea syndrome and group-2 had children without it. Both groups were given a standard general anaesthesia and frequency and rate of complications and medical interventions taken in such children were studied. P-value and odds ratio were determined. RESULTS The age ranged from 3 to 10 years. The frequency of difficult intubation was higher in the group-1 than in the control group (16.6 vs. 3.3%, odds ratio 5.8). At the time of induction of anaesthesia desaturation was higher in group-1 (33.3 vs. 6.6%, p=0.021, odds ratio 7). At the time of extubation, desaturation was significantly higher in group-1 (43.3 vs. 6.6%, p=0.002, odds ratio 10.70). The complications at extubation, for example cough, laryngospasm and postoperative nausea and vomiting were higher in group-1 but not statistically significant. In the postanaesthesia care unit, the frequency of complications and medical interventions were also higher in group-1. More patients of group-1 required oxygen (63.3 vs. 10%, p < 0.001, odds ratio 15.54) and insertion of an oropharyngeal airway (20% vs. nil, p=0.023) respectively. CONCLUSION Children with OSAS, operated for adenotonsillectomy, are at significant risk of certain life-threatening perioperative anaesthetic complications. These results may be used as a guideline for safe and successful anaesthetic management of these children.
Continuity and change in party positions towards Europe in Italian parties: an examination of parties' manifestos

This paper analyses Italian parties' manifestos for national and European elections from 1979 to 1999 with the 'Wordscore' programme in order to gauge whether party positions with regard to the European Union have changed and whether the salience of the European Union has increased. Results indicate that, although there is no sign of increased salience, the leading Italian political parties have repositioned themselves in their attitudes towards the European Union, indicating that the European political space matters for national parties.
System Justification’s Opposite Effects on Psychological Wellbeing: Testing a Moderated Mediation Model in a Gay Men and Lesbian Sample in Chile

ABSTRACT Those who adhere to system-justifying beliefs benefit from a palliative function that buffers negative effects on psychological wellbeing. This has been consistently observed for high-status groups, whereas for members of low-status groups, it remains rather unclear whether system justification exerts a positive or a negative effect. This study tested the palliative effect of system justification on symptoms of anxiety-depression in a gay men and lesbian sample (N = 467) in Chile. Results from moderated mediation analyses revealed that system justification beliefs buffer symptoms of anxiety and depression. However, system justification enhances anxious and depressive symptoms through internalized homonegativity; this mediation effect was significant for gay men. We pose that justifying the social order comprises two contradictory functions: system justification as a coping source and, otherwise, as a source of distress under conditions of in-group derogation, posing a threat to wellbeing among members of low-status groups (as observed in gay and lesbian individuals). Implications of the opposing effects and gender differences are further discussed in this study.
Double Blind Study on the Effect of Œstrogen on Sleep, Anxiety and Depression in Perimenopausal Women: Preliminary Results

16 women aged 45-55 with at least 3 months amenorrhea and symptoms of hot flushes anxiety depression and insomnia were studied for 14 weeks. Patients were paired 1 serving as a control for the effects of time placebo and attention from researchers. Both patients got a placebo for the first 6 weeks and 1 received piperazine estrone sulphate (Harmogen) in a dose of 3 mg/day for the remaining 8 weeks while the other remained on the placebo. The results failed to show that estrogen is better than a placebo in relieving depression anxiety and hot flushes in premenopausal women possibly because of the small group or the placebo effect on menopausal symptoms. Estrogen did produce a significant increase in sleep duration and a decrease in intervening wakefulness in the first 6 hours of sleep that borders on statistical significance. It is possible that insomnia in menopausal women is due to falling estrogen levels producing a fall in free plasma tryptophan which then influences cerebral serotonin metabolism. The increase in sleep duration with therapy may be due to exogenous estrogen causing an increase in free plasma tryptophan.
Epistatic and pleiotropic effects of polymorphisms in the fibrinogen and coagulation factor XIII genes on plasma fibrinogen concentration, fibrin gel structure and risk of myocardial infarction

Summary An intricate interplay between the genes encoding fibrinogen gamma (FGG), alpha (FGA) and beta (FGB), coagulation factor XIII (F13A1) and interleukin6 (IL6) and environmental factors is likely to influence plasma fibrinogen concentration, fibrin clot structure and risk of myocardial infarction (MI). In the present study, the potential contribution of SNPs harboured in the fibrinogen, IL6 and F13A1 genes to these biochemical and clinical phenotypes was examined. A database and biobank based on 387 survivors ofa first MI and population-based controls were used. Sixty controls were selected according to FGG 9340T>C [rs1049636] genotype for studies on fibrin clot structure using the liquid permeation method. The multifactor dimensionality reduction method was used for interaction analyses. We here report that the FGA 2224G>A [rs2070011] SNP (9.2%), plasma fibrinogen concentration (13.1%) and age (8.1%) appeared as independent determinants of fibrin gel porosity. The FGA 2224G>A SNP modulated the relation between plasma fibrinogen concentration and fibrin clot porosity. The FGG-FGA*4 haplotype, composed of the minor FGG 9340C and FGA 2224A alleles, had similar effects, supporting its reported protective role in relation to MI. Significant epistasis on plasma fibrinogen concentration was detected between the FGA 2224G>A and F13A1 Val34Leu [rs5985] SNPs (p<0.001). The FGG 9340T>C and FGB 1038G>A [rs1800791] SNPs appeared to interact on MI risk, explaining the association of FGG-FGB haplotypes with MI in the absence of effects of individual SNPs. Thus, epistatic and pleiotropic effects of polymorphisms contribute to the variation in plasma fibrinogen concentration, fibrin clot structure and risk of MI.
The Road to Quality in the Theory and Practice of Early Learning: Identity of the Preschool Teacher Profession / Put prema kvaliteti u teoriji i praksi ranog odgoja: identitet profesije odgojitelja

Abstract The profession of preschool teachers is extremely complex, requiring high professional awareness, continuous research of educational practice, responsibility, ethics, creativity, continuous reflective judgement, and it is almost impossible to achieve professional advancement without lifelong learning and professional development. The study, the results of which are presented in this paper, was conducted in order to determine the attitudes of preschool teachers towards the need and importance of their further professional development in relation to some socio-demographic factors (the current initial training of preschool teachers, age, years of work experience, the number and size of the preschool institutions located in a town or a village). This study included 573 preschool teachers from Zagreb, Karlovac, Međimurje, Bjelovar-Bilogora, and Virovitica-Podravina counties. The results of this study show that with respect to age, the existing level of initial education and years of work experience of preschool teachers, a statistically significant difference was obtained only regarding the first of the five items in total (Knowledge acquired during my study has significantly improved my theoretical expertise). The values of descriptive statistics indicate that the existing initial education has more or less met their theoretical and practical expectations in terms of the acquisition of overall knowledge. Key words: attitudes of preschool teachers; early childhood education; lifelong learning; quality of theory and practice. --- Sažetak Odgojiteljska profesija iznimno je složena, zahtijeva visoku profesionalnu svijest, kontinuirano istraživanje odgojno-obrazovne prakse, odgovornost, eticnost, kreativnost, sposobnost stalne refleksivne prosudbe i gotovo je nemoguce zamisliti napredovanje unutar profesije bez cjeloživotnoga ucenja i profesionalnoga usavrsavanja. Istraživanje ciji rezultati slijede u ovom radu provedeno je s ciljem utvrđivanja stajalista odgojitelja o potrebi i važnosti njihova cjeloživotnog ucenja i daljnjeg profesionalnog razvoja u odnosu na postojece inicijalno obrazovanje odgojitelja, njihovu životnu dob i godine radnog iskustva. U ovom istraživanju sudjelovala su 573 odgojitelja Zagrebacke, Karlovacke, Međimurske, Bjelovarsko-bilogorske i Viroviticko-podravske županije. Rezultati istraživanja pokazuju da je s obzirom na životnu dob, postojecu razinu inicijalnog obrazovanja i godine radnog iskustva odgojitelja od ukupno pet cestica dobivena statisticki znacajna razlika samo na prvoj cestici (Znanja stecena tijekom mojega studiranja znacajno su unaprijedila moju teorijsku strucnost). Iz vrijednosti deskriptivne statistike vidljivo je da postojece inicijalno obrazovanje relativno zadovoljava njihova teorijska i prakticna ocekivanja u smislu stjecanja ukupnog znanja. Kljucne rijeci: cjeloživotno ucenje; kvaliteta teorije i prakse; rani odgoj i obrazovanje; stajalista odgojitelja
Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects.

To The Editor: We congratulate the authors of the excellent study “Recombinant Human BMP-2 and Allograft Compared with Autogenous Bone Graft for Reconstruction of Diaphyseal Tibial Fractures with Cortical Defects. A Randomized, Controlled Trial” (2006;88:1431-41), by Jones et al., which demonstrated that autograft is as safe and effective as allograft/BMP in the reconstruction of tibial cortical defects. Although safety has been shown in the short term …
Key constructs in "classical" and "new wave" cognitive behavioral psychotherapies: relationships among each other and with emotional distress.

OBJECTIVE We aimed to relate key constructs from three forms of cognitive behavioral therapy that are often placed in competition: rational emotive behavior therapy, cognitive therapy, and acceptance and commitment therapy. The key constructs of the underlying theories (i.e., irrational beliefs/unconditional self-acceptance, dysfunctional cognitions, experiential avoidance/psychological inflexibility) of these therapies have not been explicitly studied in their relationships to each other and with emotional distress. METHOD We used a cross-sectional design. The variables were selected to indicate key constructs of the three major forms of therapy considered. Study 1 used a sample of 152 students, who were assessed during a stressful period of their semester (mean age = 21.71; 118 females), while Study 2 used a clinical sample of 28 patients with generalized anxiety disorder (mean age = 26.67; 26 females). RESULTS Results showed that these constructs, central in the therapies considered, had medium to high associations to each other and to distress. Experiential avoidance was found to mediate the relationship between the other, schema-type cognitive constructs and emotional distress. Moreover, multiple mediation analysis in Study 2 seemed to indicate that the influence of the more general constructs on distress was mediated by experiential avoidance, whose effect seemed to be carried on further by automatic thoughts that were the most proximal to distress. CONCLUSIONS Although each of the cognitive constructs considered comes with its underlying theory, the relationships between them can no longer be ignored and cognitive behavioral therapy theoretical models reliably accounting for these relationships should be proposed and tested.
Production and catabolite repression of Penicillium italicum beta-glucanases

The filamentous fungus Penicillium italicum, grown in a defined liquid medium, produced beta-1,3-glucanase, which remained essentially bound to the cells, and beta-1,6-glucanase, an essentially extracellular enzyme. When glucose was depleted from the medium, when a limited concentration of glucose (0.2%) was maintained, or when the carbon source was galactose (3%) or lactose (3%), a significant increase in the specific activity of beta-1,3-glucanase, in cell extracts, took place. This was paralleled by a very slow rate of growth, and under glucose limitation, the appearance of beta-1,3-glucanase in the medium was also observed. On the other hand, when an excess of glucose, fructose, or sucrose was present, the specific activity remained constant and active growth was promoted. Laminarin, cellobiose, gentiobiose, and isolated Penicillium italicum walls were not capable of significantly inducing beta-1,3-glucanase synthesis to a level beyond that attained by glucose limitation. A similar behavior was observed for beta-1,6-glucanase. beta-1,3-Glucanase and beta-1,6-glucanase are therefore constitutive enzymes subjected to catabolite repression. The results are discussed in the context of the possible functions that have been suggested for glucanases and related enzymes.
The IgD‐binding domain of the Moraxella IgD‐binding protein MID (MID962‐1200) activates human B cells in the presence of T cell cytokines

Moraxella catarrhalis immunoglobulin D (IgD)‐binding protein (MID) is an outer membrane protein with specific affinity for soluble and cell‐bound human IgD. Here, we demonstrate that mutated M. catarrhalis strains devoid of MID show a 75% decreased activation of human B cells as compared with wild‐type bacteria. In contrast to MID‐expressing Moraxella, the MID‐deficient Moraxella mutants did not bind to human CD19+ IgD+ B cells. The smallest MID fragment with preserved IgD‐binding capacity comprises 238 amino acids (MID962‐1200). To prove the specificity of MID962‐1200 for IgD, a Chinese hamster ovary (CHO) cell line expressing membrane‐anchored human IgD was manufactured. MID962‐1200 bound strongly to the recombinant IgD on CHO cells. Moreover, MID962‐1200 stimulated peripheral blood lymphocyte (PBL) proliferation 5‐ and 15‐fold at 0.1 and 1.0 μg/ml, respectively. This activation could be blocked completely by antibodies directed against the CD40 ligand (CD154). MID962‐1200 also activated purified B cells in the presence of interleukin (IL)‐2 or IL‐4. An increased IL‐6 production was seen after stimulation with MID962‐1200, as revealed by a human cytokine protein array. MID962‐1200 fused to green fluorescent protein (GFP) bound to human B cells and activated PBL to the same degree as MID962‐1200. Taken together, MID is the only IgD‐binding protein in Moraxella. Furthermore, the novel T cell‐independent antigen MID962‐1200 may, together with MID962‐1200–GFP, be considered as promising reagents in the study of IgD‐dependent B cell activation.
Circularly polarized textile antenna for personal satellite communication

This paper describes how the performance of wearable textile antenna is affected by antenna bending. Here, we will focus on the resonance frequency fluctuation and input-match bandwidth variation due to the antenna bending as well as the changes in radiation pattern and antenna efficiency. This study is carried out for a circularly polarized textile patch antenna operating at Iridium satellite system. The results show that high efficiency and robustness against bending effects are maintained. A 5 % return loss bandwidth is measured.