Freedom and Responsibility in Context

Freedom and Responsibility in Context argues for a contextualist account of freedom and moral responsibility. It aims to challenge the largely unarticulated orthodoxy of invariantism, by arguing that contextualism is crucial to an understanding of both freedom and moral responsibility. The argument for contextualism regarding freedom and moral responsibility focuses upon their respective control conditions. Abilities are argued to be central to an understanding of the control required for freedom and moral responsibility. A unified ability analysis of control is developed, which supports the thesis that attributions of freedom and moral responsibility are context dependent. The resulting contextualism offers a rapprochement of compatibilism and incompatibilism. By going beyond the false dichotomy of invariant compatibilism and invariant incompatibilism, it is argued that both positions can be given their due, since there is no ‘right’ answer to the question of whether or not determinism undermines freedom and moral responsibility.

Discursive Representations of Digital Artifacts in an EFL Classroom: Analysing Discursive Voices of Pre-Service Teachers of English

The present article presents and discusses a study that seeks to analyse discursive representations of digital artifacts in the teaching and learning of English as a Foreign Language (EFL) by pre-service EFL teachers (henceforth – participants). The study involves a corpus of argumentative essays on a range of topics in EFL didactics written by the participants and their respective control group which is comprised of non-teacher EFL students. The analysis of the corpus of essays reveals that whilst there are discursive representations of digital artifacts that are shared between the groups of participants and controls, there appear to be discursive representations of digital artifacts that are group-specific. These findings and their linguo-didactic implications are further described in the article.

Yield Performance of Newly Developed Cassava Varieties in Response to Inorganic Fertilizers

A study was conducted at Kyambogo University Farm in randomized complete block design with three replications to assess the effect of NPK (17:17:17) fertilizer on the growth and tuber yields of two newly developed cassava (Manihot esculenta Crantz) varieties, NAROCASS 1 and NASE 14. Cassava varieties were assigned to the main plots, while fertilizer rates (zero/control, 200, 400, 600 kg/ha) were sub-plots. Fertilizer was applied in two splits, at planting and four months after planting. Fertilizer application significantly (P<0.05) increased the cassava stem heights to first branching and at harvest, and the number of stems per plant when compared with the control treatments. Mean stem heights to first branching and at harvest of plants that received NPK were higher than those of the respective control treatments by 62.8 and 70.5% for NAROCASS 1, and 57.0 and 76.5% for NASE 14, respectively. Fertilizer rate of 400 kg/ha significantly increased the lengths, numbers of tubers and tuber yields per plant when compared with the control treatments. Mean lengths, numbers of tubers and tuber yields of plants that received NPK were higher than those of respective control treatments by 48.2, 36.9 and 68.3% for NAROCASS 1, and 39.9, 50.5 and 67.6% for NASE 14, respectively. Therefore, to achieve optimum tuber yields of newly developed cassava varieties, farmers should integrate NPK fertilizer application into already existing management practices, particularly the use of high quality planting materials and integrated pest, disease and weed management. However, government ministries concerned should ensure that inorganic fertilizers are readily accessible and affordable to farmers.

A Phase II Dose Escalation Study of Intraarterial (Hepatic) Adult Human Bone Marrow Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells (Stempeucel®) in Patients with Alcoholic Liver Cirrhosis

Background: Alcoholic liver cirrhosis is an end-stage alcoholic liver disease with a poor prognosis. The definitive treatment of alcoholic liver cirrhosis is orthotopic liver transplantation, which is expensive, requires long-term immunosuppression and is limited by the supply of organs. Being an unmet medical need, cell therapy is under investigation for alcoholic liver cirrhosis. Aims: This study was designed primarily for assessing the safety and feasibility of administering stempeucel® through the hepatic artery in alcoholic liver cirrhosis and secondarily to assess possible efficacy and dose-response. Methods: Sixty patients with alcoholic cirrhosis (18-65 years/Child-Pugh class B or C/Model for End-Stage Liver Disease score of minimum 10) were planned to be included in 6 groups: 2.5 million cells/kg Body Weight (2.5M Cell) and respective control (2.5M Control); 5 million cells/kg Body Weight (5M Cell) and respective control (5M Control); 7.5 million cells/kg Body Weight (5M Cell) and respective control (7.5M Control) with 10 patients in each group. Cell groups received stempeucel® administered via hepatic artery by catheterization through the femoral artery (Seldinger technique) and Standard Protocol of Care. The control group received Standard Protocol of Care. Patients were followed up at 1 week, 1 month, 3 months and 6 months. Efficacy evaluations included liver function test, Model for End-Stage Liver Disease score, Child-Pugh score, Short Form-36 questionnaire, liver stiffness using Fibroscan (Transient Elastography), and liver volume using Computerized Tomography scan. Results: Stempeucel® injection was well tolerated. Common treatment-emergent adverse events were gastrointestinal disorders, general disorders and administration site conditions and infections and infestations. Most of the treatment-emergent adverse events were unrelated / remotely related to stempeucel®. Thirty serious adverse events occurred in 10 patients (3 in 2.5M Cell, 5 in 5M Cell and one each in control groups). Three patients died due to SAEs: Two in 2.5M and one in 5M Cell group, none were related to stempeucel®. Statistically significant improvement was seen in 2.5M group compared to the control group in Short Form-36 score: bodily pain, mental component summary, vitality and social functioning. Conclusion: Stempeucel® was safe, well-tolerated and subjective improvement in Short Form-36 (bodily pain, mental component summary, vitality and social functioning and mental health) score was seen in the 2.5M cell group.

Salt stress induced accumulation of biomolecules in groundnut genotypes

Salinity is one of the environmental limiting factors in agricultural production. The aim of this study was to find out one of more salt tolerant groundnut genotypes through monitoring the growth and changes in biomolecules under salt stress condition. Purposively four groundnut genotypes, including a Traditional variety, Zhingabadam, Binachinabadam-1 and Dacca-1 were grown under three salinity levels viz. 0, 3 and 5 dSm-1. The experiment was laid out in two factorial completely randomized design with three replications. This experiment was done in soil based pot culture up to 40 days. Increasing salt concentration drastically reduced all the growth parameters, and increase proline and sugar content of leaf. Among the varieties Traditional variety, Zhingabadam and Dacca-1 had statistically similar shoot and root dry weight. The leaves of the Traditional variety contain the highest amount of proline of 14.52 and 36.24 mg/100g fresh leaves in 3 and 5 dS/m salinity, respectively which was 236 and 737 % higher than that of respective control. At EC of 3 and 5 dS/m, the variety Binachinabadam-1 was appeared to be susceptible, having an increase of 6 and 113% proline content over the respective control. Based on the shoot dry weight, root dry weight, proline content, total sugar, reducing sugar and relative water content, the Traditional variety was strongly recommended to be grown in the coastal salt affected soils. The Zhingabadam and Dacca-1 variety also could be recommended as they had comparable performance of the Traditional variety.

Prefrontal dopamine D1 receptor manipulation influences anxiety behavior and induces neuroinflammation within the hippocampus

Background Prefrontal dopamine D1 receptor (D1R) mediates behavior related to anxiety, reward and memory, and is involved in inflammatory processes, all of which are affected in bipolar disorder. Interleukin-6 (IL-6), a pro-inflammatory cytokine, is increased in patients with bipolar disorder in plasma samples, imaging studies and postmortem tissue and is an indicator for an inflammatory state. We could previously show that lentiviral overexpression of D1R in the medial prefrontal cortex (mPFC) of male adult rats and its termination induces bipolar disorder-like behavior. The purpose of this study was to investigate anxiety and the role of the immune system, specifically IL-6 positive neurons in this animal model. Due to its high density of inflammatory mediator receptors and therewith sensibility to immune activation, the hippocampus was investigated. Methods Expression of the gene for D1R in glutamatergic neurons within the mPFC of male, adult rats was manipulated through an inducible lentiviral vector. Animals over-expressing the gene (mania-like state), after termination of the expression (depressive-like) and their respective control groups were investigated. Anxiety behavior was studied in the elevated plus maze and marble burying test. Furthermore, IL-6-positive cells were counted within several subregions of the hippocampus. Results D1R manipulation in the mPFC had only mild effects on anxiety behavior in the elevated plus maze. However, subjects after termination buried more marbles compared to D1R over-expressing animals and their respective control animals indicating elevated anxiety behavior. In addition, animals in the depressive-like state showed higher numbers of IL-6 positive cells reflecting an elevated pro-inflammatory state in the hippocampus, in the CA3 and dentate gyrus. Consistently, inflammatory state in the whole hippocampus and anxiety behavior correlated positively, indicating a connection between anxiety and inflammatory state of the hippocampus. Conclusions Behavioral and neurobiological findings support the association of manipulation of the D1R in the mPFC on anxiety and inflammation in the hippocampus. In addition, by confirming changes in the inflammatory state, the proposed animal model for bipolar disorder has been further validated.

A comparative study of physiological and hematological profile of preeclampsia in relation to body mass index

Preeclampsia (PE) is a major reason for maternal morbidity and mortality globally. Studies showed that body mass index (BMI) is one of the risk factors of PE. In this study, the BMI and physiological and hematological profile were associated with predicting the severity of preeclampsia, so that proper counseling and antenatal care could be given for good pregnancy outcome. The study was carried out on 100 healthy normotensive pregnant and 100 diagnosed preeclamptic women. Healthy pregnant and PE were categorized into three groups based on BMI, on WHO criteria. BMI group 1 (<25 Kg/m2) considered as normal, group 2 (25 – 30 Kg/m2) as over-weight and group 3 (>30 Kg/m2) obese. Systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin (Hb), white blood corpuscles (WBC), red blood corpuscles (RBC) and platelets were compared in control and PE groups. Then the respective control groups were compared with PE groups. The prevalence of overweight was more in PE groups when compared to normotensive pregnancy (P=0.004). Statistically, a significant difference was not observed in BMI group1, group 2 and group 3 of control and PE in relation to SBP, DBP, Hb, WBC, RBC and platelets. But a statistically significant difference was made when respective control groups were compared with PE (P<0.005). BMI does not have any statistically significant association with SBP, DBP, Hb, WBC, RBC and platelets. BMI could not be considered as a predictor or severity of preeclampsia.

The effect of Arthrospira platensis (spirulina) addition on the content of selected mineral elements, carotenes, and antioxidant potential in alginate gel beads

Alginate, a heteropolysaccharide extracted from brown algae Laminaria digitata, has non-toxic status and good physical and chemical properties, was used in this study for encapsulation of the cyanobacterium Arthrospira platensis. Results indicated that adding A. platensis to alginate beads increased the level of mineral elements: magnesium by 55–60 mg/kg, iron by 38–40 mg/kg, and iodine by 88–107 μg/kg, as compared to respective control samples without microalgae addition. Adding A. platensis within alginate beads resulted in an increased antioxidative potential and consequent higher inhibition of the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) by 15–25% compared to the respective control alginate beads. Finally, the content of beta-carotene in alginate beads fortified with A. platensis biomass amounts on average to 51 μg/g. Due to their health-promoting potential, alginate beads enriched with A. platensis biomass can, therefore, be used as a functional ingredient in the nutraceutical sector.

P200 Characterisation of remission in patients with rheumatoid arthritis treated with upadacitinib or comparators

Background Across all phase 3 studies, treatment with upadacitinib (UPA), a JAK1-selective inhibitor, was associated with significantly higher remission (REM) rates, compared to placebo (PBO) or active comparators, in RA patients who were methotrexate (MTX)-naive, had inadequate response to conventional synthetic (csDMARD-IR) or had inadequate response or intolerance to biologic DMARDs (bDMARD-IR). Methods REM definitions are based on composite scores of various individual assessments of disease activity. To determine the response to UPA on REM and component assessments, we assessed the proportions of patients achieving REM using multiple REM definitions, and the improvement in their respective individual components, compared to PBO or active comparators, in 3 different RA patient populations spanning a range of RA patient populations. Methods: Three phase 3 studies included patients who were MTX naïve (SELECT EARLY, n = 945), MTX-IR (SELECT COMPARE, n = 1629) and bDMARD-IR (SELECT BEYOND, n = 498). The proportion of patients achieving REM at Week 12 by 4 definitions (DAS28-CRP&lt;2.6; CDAI &lt;2.8; SDAI &lt;3.3 and Boolean, defined as &lt; 1 for TJC, SJC, patient’s global assessment of disease activity [PtGA], and CRP &lt;1 mg/L) were determined. For each definition of REM, the mean change in each of the respective component scores was also assessed. Binary endpoints are based on Non-responder imputation (NRI), and continuous endpoints on mixed-effect model repeat measurement (MMRM). Comparisons were made between UPA-treated groups vs respective control arms (MTX, adalimumab [ADA] or PBO). Results Patient demographics and disease characteristics have been previously reported. 1-3 At 12 weeks, in EARLY and COMPARE, a significantly greater proportion of patients receiving UPA 15 mg or 30 mg QD achieved REM by all 4 definitions vs MTX, PBO or ADA (Table). In BEYOND, (a refractory population many of whom had inadequate response to multiple bDMARDs), a significantly greater proportion of patients receiving UPA 30mg achieved all REM definitions vs PBO within the first 12 weeks, with significantly greater proportions on UPA 15mg achieving DAS28-CRP&lt;2.6 and Boolean REM. Rates of REM in BEYOND further increased through Wk 24 for both dose groups. Compared to respective control groups, patients receiving UPA 15 or 30 mg QD had significantly greater improvements in each REM disease component (except for PhGA vs ADA in COMPARE). Significantly more patients receiving UPA also achieved the required cutoffs on the individual components of Boolean REM compared to respective controls. Conclusion Significantly greater proportions of patients receiving UPA 15 or 30mg achieved REM by multiple definitions at 12 weeks compared to PBO, MTX or ADA. All disease activity components of each REM definition were significantly improved in patients receiving UPA compared to MTX or PBO, and all Boolean components were significantly improved in patients receiving UPA 15mg compared to ADA. Disclosures S. Hall: Grants/research support; AbbVie, BMS, Lilly, Janssen, Pfizer, UCB, Novartis. T. Takeuchi: Honoraria; Mitsubishi-Tanabe Pharma Corp, Janssen Pharma KK, Chugai Pharma, Astellas Pharma Inc., AbbVie GK, Eisai Co., Ltd, BMS, Daiichi Sankyo Company Ltd, Eli Lilly Japan KK, Pfizer Japan Inc. Grants/research support; Pfizer Japan Inc., Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corp, Nippon Kayaku Co., Ltd, Taisho Toyama Pharma, Takeda Pharma, AYUMI Pharma, Takahashi Industrial. G. Thomson: Consultancies; Amgen. Grants/research support; AbbVie. P. Emery: Grants/research support; Research grants and consulting fees from Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. B. Combe: Grants/research support; Consultancy fees from Abbvie, BMS, Jansen, Lilly, MSD, Pfizer, Roche Chugai, UCB. A. Everding: None. K. Pavelka: Honoraria; Honoraria for lectures and consultations from companies: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie. Y. Song: Corporate appointments; Employee of AbbVie. T. Shaw: Corporate appointments; Employee of AbbVie. A. Friedman: Corporate appointments; Employee of AbbVie. I. Song: Corporate appointments; Employee of AbbVie. E. Mysler: Grants/research support; Research grants and consulting fees from AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz.

Effects of Laser at 810 Nm on Wound Healing in Albino Mice

Many researches focused on laser therapy of wound healing in different animal models due to the lack of a standard protocol in the application of such phototherapy. Objective: To study the effects of 810nm laser at a constant irradiance of 41.63 mw/cm2 and exposure (illumination) time of 5,15 minutes on wounds created on Albino mice (BALB/c). Skin wound with elliptic shape and full thickness was created on the dorsal side of ‘45 mature male albino mice. Irradiated animals were divided into two main groups based on irradiation time, the first was irradiated for 5 min and the second for 15 min, each was subdivided into three subgroups (n=5) according to number of treatment days (3, 5 and 10 days). Both treated and respective control (n=15) subgroups were sacrificed on days 3, 5 and 10 posttreatment. Laser therapy was applied using a 810 nm diode laser with a continuous wave, an output power of 400 mw, and irradiance of 41.63. The 5 min dose was 12 .5 J/cm2, whereas the 15 min dose was 37.4 J/cm2. The shape of the laser beam was fitted with a convex lens as ‘beam expander’ to irradiate a circular area of 3.4 cm diameter. Laser therapy was started after surgery and repeated for 3, 5 and 10 days, while its effects were examined by histological evaluation. Results: At day 3 of treatment with near infrared 810nm laser at doses of 12.5J/cm² and 37.4J/cm², there was no evidence of wounds healing in irradiated groups which showed no differences with the respective control groups. At day 5 of treatment, the results showed an important increase in the scores of the parameters of wound healing (formation of granulation tissue and collagen deposition) in the irradiated groups. Near infrared 810nm laser had photobiostimulation effects on wound healing at irradiance of 41.63mW/cm² and doses of 12.5J/cm² for 5 minutes and 37.4J/cm² for 15 minutes exposure time. A complete picture of wound healing response appeared in all irradiated groups within 10 days of treatment, as expressed by complete ‘re-epithelialization’, moderate granulation tissue formation, and presence of collagen fibers, while incomplete wound healing response was observed in un-irradiated control groups within the same period. The study showed that 810 nm laser therapies had significant effects on wound healing, especially at a dose of 37.4J/cm².