Exploring the feasibility of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis.

OBJECTIVES: It is suggested that exercise can improve the vascular function and quality of life (QoL) in people with systemic sclerosis (SSc), potentially offering clinical benefits to this population. Yet the feasibility of such an intervention remains untested. Therefore, the purpose of this study is to examine the feasibility of a combined exercise protocol (aerobic and resistance training) in people with limited cutaneous SSc (lcSSc). METHODS: Thirty-two lcSSc patients (66.5 ± 12 years old) were randomly allocated in two groups (exercise and control group). The exercise group underwent a 12-week exercise programme, twice per week. All patients performed the baseline, three- and six-month follow-up measurements where functional ability, body composition and QoL were assessed. Participants' experiences were explored through interviews. RESULTS: Compliance was 92.6% with no dropouts. The individuals' confidence to participate in the study's exercise protocol for twice per week was 95%. The average value for the physical activity enjoyment scale was 103 ± 10 out of 119 (highest score). The mean values for the intention to engage in exercise twice per week were 6.4 ± 1 (likely) out of 7 (very likely). QoL for the exercise group showed to have a better life satisfaction, less anxiety and Raynaud's phenomenon-accompanied pain. CONCLUSIONS: Our results suggest that a combined exercise protocol was feasible for people with lcSSc, with no adverse events, resulting in high adherence and low attrition rates, high enjoyment levels and intentions for future engagement to this exercise. Thus, the specific protocol is a safe adjunct therapy for people with lcSSc. TRIAL REGISTRATION: ClinicalTrials.gov (NCT number): NCT03058887, February 23, 2017, https://clinicaltrials.gov/ct2/show/NCT03058887?term=NCT03058887&rank=1Key Points• High-intensity interval training in combination with resistance training constitutes a feasible exercise protocol for people with lcSSc.• Overall, the exercise programme demonstrated high adherence and enjoyment levels and low attrition rates.• The exercise protocol was proved to be safe with no adverse events for people with lcSSc

Exploring the microcirculatory effects of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis.

Purpose of the study High intensity interval training (HIIT) is able to improve the endothelial-dependent microvascular function is people with limited cutaneous systemic sclerosis (lcSSc). Resistance training (RT) alone has shown significant improvements in the function of the vasculature; moreover, a combination of aerobic and RT have shown both in the past and recently to significantly improve the vascular function and the microcirculation. Therefore, the purpose of this study is to explore the effectiveness of a combined exercise protocol (aerobic and resistance training) on microvascular function in people with lcSSc. Methods Thirty-two lcSSc patients (66.5 ± 12 years old) were randomly allocated in two groups (exercise and control group). The exercise group underwent a 12-week exercise programme twice per week. All patients performed the baseline, three- and six-month follow up measurements where microvascular function, transcutaneous oxygen tension (ΔTcpO2) and body composition were assessed. Results The time to peak endothelial-dependent reactivity was significantly improved (91 ± 42 s, d = 1.06, p = 0.007) when compared to control group after the exercise intervention. Endothelial-independent function was also significantly improved (3.16 ± 2, d = 1.17, p = 0.005) when compared to the control group. Baseline (5.71 ± 4.4, p < 0.05)) and peak (15.4 ± 7.5, p < 0.05) transcutaneous oxygen pressure were also significantly improved compared to the control group. Conclusions Our results suggest that a combined exercise protocol (aerobic and RT) was effective in improving endothelial-dependent reactivity in people with lcSSc. The next step would be to explore its clinical- and cost- effectiveness. Therefore, we recommend a large, community-based intervention against standard pharmacotherapy only, which would assess these important factors and support a change in therapeutic protocols and guidelines for this clinical population

An evaluation of the implications of imposing speed limits on major roads

PhD ThesisThe effectiveness of speed limits has been the subject of considerable debate over the years. In most cases in the past, speed limits have been changed because of a single factor (e. g. improving the safety of road traffic or saving energy). In this thesis an attempt has been made to evaluate the consequences of changing a speed limit using cost-benefit analysis which formed the principle objective of this study. The scope was confined to motorways and similar high-quality roads operating under free-flow traffic conditions where speed limits were believed to be most effective. To achieve the main goal, the effect of the speed limit on the mean speed of traffic was investigated which was the second objective of the study. The third objective was to find the effect of the speed of traffic, and especially the mean speed of traffic, on the frequency and severity of personal injury accidents. There was a need to investigate these two relationships as the literature was not consistent on these relationships. A hypothesis was proposed to achieve the second objective. This was tested by defining criteria that had to be met for each of the data collection sites and measuring the speed of vehicles. There were II sites in Tyne & Wear, England and 14 sites in the State of Bahrain. A statistical analysis was applied to the data collected. It was found, from both sets of data, that speed limits had a positive effect on the mean speed and the eighty-fifth percentile speed of traffic. Linear and non-linear (multiplicative) models were developed for each set of data. In addition to the speed limit, the trip length and the length of the section were shown to affect significantly the mean speed of traffic. The amount of change in the mean speed of traffic varied between the models tested but, generally, for every 4 to 5 km/h change in the speed limit the mean speed of traffic changed by, about, I km/h. In a similar way, a hypothesis was proposed to pursue the third objective. Criteria were established for the selection of suitable data collection sites and for the types of accidents. 9 sites were selected in Tyne & Wear and 10 sites in the State of Bahrain. Data was drawn from a5 year set of accident records in Tyne and Wear and a four year set in the State of Bahrain. A statistical analysis was applied to the data. The set of data from Tyne & Wear revealed no significant relationship between the mean speed of traffic and the frequency of accidents but the speed differentials affected the frequency of the personal injury accidents. The data from Bahrain showed that both the mean speed of traffic and the speed differentials of vehicles affected the frequency of the personal injury accidents. No significant relationships were found between the speed of vehicles and the severity of the personal injury accidents. The principle objective of the study was achieved by applying cost-benefit analysis to the consequences of changing the speed limit for a hypothetical typical section of road. The components of cost were the cost of travel-time, the vehicle operating cost, and the cost of accidents. No monetary values were assigned to the environmental effects so it was not possible to include them in the cost-benefit analysis but they were acknowledged. Any changes in air pollution and noise annoyance due to a change in the mean speed of traffic following a change in a speed limit were likely to be small and were not considered in the study. The significance of the uncertainty in the frequency and severity of personal injury accidents in relation to the mean speed of traffic was studied using 'break-even analysis'. Generally, it was believed that lowering the speed limit on motorways and similar high-quality roads would produce negative benefits, even if the frequency and severity of personal injury accidents decreasedw ithin expectedr anges. Increasing the speed limits would produce positive economic benefits but the conclusion was less firm than the previous case. Sensitivity analysis was applied to the variables used in the cost-benefit analysis. It was found that the net benefits were most sensitive to the estimation of the effect of the speed limits on the mean speed of traffic, the initial mean speed of traffic in the base year of the assessment, the travel-time cost, the changes in the frequency of the personal injury accidents, and changes in the number of fatal injury casualties per average personal injury accident as the speed limit varied (i. e. in descending order for most speed limits). The ranking of these variables differed as the speed limit was changed.University of Bahrai

Survey of ethno-veterinary medicinal plants at selected districts of Harari Regional State, Eastern Ethiopia

The survey of ethno-veterinary medicinal plants was conducted from November,2014 to April, 2015 at selected districts of Harari Regional State, eastern Ethiopia.The aim of the study was to identify and document medicinal plants and the associated ethno-medicinal knowledge of the local community. Semi-structured interview, guided field observation, group discussion and market survey were used to collect the required data. Informant consensus method and group discussion wereconducted for crosschecking and verification of the information. Both descriptivestatistics and quantitative methods were used for data analysis. About 46 plantspecies belonging to 33 families were identified and documented based on the localclaims of the plants. Majority plant taxa were collected from the wild (54.4%) followed by domestic once (24%). Among these plant families, Fabaceae, Solanaeceae and Euphorbiaceae were commonly used to treat Equine colic, retained placenta and Black leg respectively. The most frequently used plant parts were reported to be the leaves (37%) and then the roots (30.4%). The condition of preparation was in the fresh form (82.5%) and fresh/dry form (17.5%). Oral  administration (65.3%) was the most common route of administration. In  conclusion, the participants have a wealth of indigenous knowledge about plant medicines for treating their livestock but, agricultural expansion was the major threats to medicinal plants in the study area. Thus, awareness creation should be done in order to conserve and document the plants. Keywords: Ethno-veterinary, Medicinal plants, Indigenous knowledge, HarariRegional Stat

The BILAG2004-Pregnancy Index is a valid disease activity outcome measure for pregnant SLE patients

OBJECTIVES: This study was to determine whether the BILAG2004-Pregnancy Index (BILAG2004-P) has construct/criterion validity and is sensitive to change. METHODS: This was an observational multicentre study that recruited pregnant SLE patients. Data were collected on disease activity [using the BILAG2004-P and Physician Global Assessment (PGA)], investigations and therapy at each assessment. The overall BILAG2004-P score as determined by the highest score achieved by any system was used in the analysis. Cross-sectional analysis was used for construct and criterion validity. The comparison was with C3, C4 and anti-dsDNA for construct validity, while it was with change in therapy and PGA in criterion validity. Sensitivity to change was assessed by determining the relationship between the change in BILAG2004-P and the change in therapy between two consecutive visits. RESULTS: A total of 97 patients with 112 pregnancies were recruited. There were 610 assessments available for construct/criterion validity analysis (98.2% of pregnancies had more than one assessment) and 497 observations for sensitivity to change analysis. Increasing BILAG2004-P scores were associated with low C3. The active BILAG2004-P score (grade A or B) was associated with an increase in therapy and the PGA of active disease. There was an increasing likelihood of higher overall scores with an increase in therapy and the PGA of active disease. In the sensitivity to change analysis, an increase in the BILAG2004-P score was associated with an increase in therapy and inversely associated with a decrease in therapy. A decrease in the BILAG2004-P score was associated with a decrease in therapy and inversely associated with an increase in therapy. CONCLUSION: The BILAG2004-P has criterion validity and is sensitive to change

Conventional Electrode Materials for Microbial Fuel Cells

The use of microbial fuel cells (MFCs) has gained a lot of attention as a means to combat both energy shortages and water pollution. Despite their best efforts, MFCs are unable to produce substantial amounts of energy or effectively remove pollutants due to a number of difficulties, one of which being the electrode. One of the most significant components of an MFC is the electrode. Different types of electrode materials have recently been developed to boost pollutant removal rates and energy production efficiency. Carbon-based materials have been used as the most often used electrode material in MFCs. A wide range of potentials is now accessible for use in the manufacturing of electrode materials, which can significantly reduce current issues such as the demand for high-quality materials and their cost. In the present chapter, the conventional electrode material is briefly discussed with their influence and role in MFC operation and performance. A brief discussion of the current issues and future views of electrode materials is also included

Design and synthesis of new thiazolidinone/uracil derivatives as antiproliferative agents targeting EGFR and/or BRAFV600E^{V600E}

Thiourea derivatives of uracil were efficiently synthesized via the reaction of 5-aminouracil with isothiocyanates. Then, we prepared uracil-containing thiazoles via condensation of thioureas with diethyl/dimethyl acetylenedicarboxylates. The structures of the products were confirmed by a combination of spectral techniques including infra-red (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS) and elemental analyses. A rationale for the formation of the products is presented. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against four cancer cell lines. The compounds tested showed promising antiproliferative activity, with GI$_{50}$ values ranging from 1.10 µM to 10.00 µM. Compounds 3c, 5b, 5c, 5h, 5i, and 5j were the most potent derivatives, with GI$_{50}$ values ranging from 1.10 µM to 1.80 µM. Compound 5b showed potent inhibitory activity against EGFR and BRAF$^{V600E}$ with IC$_{50}$ of 91 ± 07 and 93 ± 08 nM, respectively, indicating that this compound could serve as a dual inhibitor of EGFR and BRAF$^{V600E}$ with promising antiproliferative properties. Docking computations revealed the great potency of compounds 5b and 5j towards EGFR and BRAF$^{V600E}$ with docking scores of −8.3 and −9.7 kcal/mol and −8.2 and −9.3 kcal/mol, respectively

Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents

In this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition to elemental analyses. The cell viability of the new compounds was assessed against normal human mammary gland epithelial (MCF-10A) cell line. Data revealed that none of the compounds examined exhibited cytotoxic effects, and the cell viability for the compounds examined at 50 µM was greater than 87%. The antiproliferative activity of 3a-l and 5a-e was evaluated against four human cancer cell lines where the compounds showed promising activity. The most potent derivatives were compounds 3a, 3c, 3f, 3i, and 5b with GI$_{50}$ values ranging from 0.90 µM to 1.70 µM against the four cancer cell lines in comparison to doxorubicin (GI$_{50}$ = 1.10 µM). Compounds 3a, 3c and 3i showed potent antiproliferative activity with dual inhibitory action against EGFR and BRAF$^{V600E}$. Compounds 3a, 3c, and 3i demonstrated promising AutoDock scores towards EGFR and BRAF$^{V600E}$ with values of − 9.1 and − 8.6, −9.0 and − 8.5, and − 8.4 and − 8.0 kcal/mol, respectively. The physicochemical and pharmacokinetic characteristics of 3a, 3c, and 3i were anticipated, demonstrating their oral bioavailability

Sensitivity to Change (Responsiveness) and Minimal Important Differences of the LupusQoL in patients with Systemic Lupus Erythematosus

Objective: The LupusQoL is a reliable and valid health-related quality of life (HRQoL) measure for adults with systemic lupus erythematosus (SLE). This study evaluates the responsiveness and minimal important differences (MID) for the eight LupusQoL domains. Methods: Patients experiencing a flare were recruited from nine UK centres. At each of the ten monthly visits, HRQoL (LupusQoL, SF-36), global rating of change (GRC) and disease activity (DA) using the BILAG-2004 index were assessed. The responsiveness of the LupusQoL and the SF-36 was evaluated primarily when patients reported an improvement or deterioration on the GRC scale and, secondly, with changes in physician-reported DA. MIDs were estimated as mean changes when minimal change was reported on the GRC scale. Results: 101 patients were recruited. For all LupusQoL domains, mean HRQoL worsened when patients reported deterioration and improved when patients reported an improvement in GRC; SF-36 domains showed comparable responsiveness. Improvement in some domains of the LupusQoL/SF-36 was observed with a decrease in DA but when DA worsened, there was no significant change. LupusQoL MID estimates for deterioration ranged from -2.4 to -8.7 and for improvement, 3.5 to 7.3; for the SF-36, -2.0 to -11.1, and 2.8 to 10.9 respectively. Conclusion: All LupusQoL domains are sensitive to change with patient-reported deterioration or improvement in health status. For DA, some LupusQoL domains showed responsiveness when there was improvement but none for deterioration. LupusQoL items were derived from SLE patients and provide the advantage of disease-specific domains, important to them, not captured by the SF-36

The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients

Objective. To assess the inter-rater reliability of the BILAG2004-Pregnancy index for assessment of SLE disease activity in pregnancy. Methods. Pregnant SLE patients were recruited from four centres and assessed separately by two raters/physicians in routine clinical practice. Disease activity was determined using the BILAG2004-Pregnancy index. Reliability was assessed using level of agreement, κ-statistics and analysis of disagreement. Major disagreement was defined as a score difference of A and C/D/E or B and D/E between the two raters, and minor disagreement was a score difference of A and B or B and C between raters. Results. A total of 30 patients (63.3% Caucasian, 13.3% Afro-Caribbean, 16.7% South Asian) were recruited. The majority of patients had low-level disease activity according to the local rater’s assessment, and there was no grade A activity, with grade B activity present in the following systems: mucocutaneous (nine patients), musculoskeletal (two patients), cardiorespiratory (one patient) and renal (one patient). The distribution of disease activity was similar to the external rater’s assessment. Good levels of agreement (>70%) were achieved in all systems. κ-statistics were not appropriate for use in the gastrointestinal, ophthalmic, constitutional and neuropsychiatric systems, as there was minimal variation between patients but good levels of agreement otherwise. There were three major disagreements (0.1 per patient, all differences between B and D/E) and five minor disagreements (0.17 per patient). Conclusion. The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients