Dental and Anaesthetic Challenges in a Patient with Dystrophic Epidermolysis Bullosa

Epidermolysis bullosa is a group of rare genetic disorders characterised by skin and mucous membrane fragility and systemic manifestations of variable severity. We report a case of dystrophic epidermolysis bullosa in an 18-year-old male patient who presented to the Department of Oral Health at Sultan Qaboos University Hospital, Muscat, Oman, in 2015 with recurrent dental pain and infections. Due to the poor dental status of the patient and anticipated operative difficulties due to microstomia and limited mouth opening, the patient underwent full dental clearance under general anaesthesia. This article discusses the dental and anaesthetic challenges encountered during the management of this patient and provides a brief literature review

The Star Formation History in The Far Outer Disc of M33

The outer regions of disc galaxies are becoming increasingly recognized as key testing sites for models of disc assembly and evolution. Important issues are the epoch at which the bulk of the stars in these regions formed and how discs grow radially over time. To address these issues, we use Hubble Space Telescope Advanced Camera for Surveys imaging to study the star formation history (SFH) of two fields at 9.1 and 11.6 kpc along M33's northern major axis. These fields lie at ~ 4 and 5 V-band disc scale-lengths and straddle the break in M33's surface brightness profile. The colour-magnitude diagrams (CMDs) reach the ancient main sequence turnoff with a signal-to-noise ratio of ~ 5. From detailed modelling of the CMDs, we find that the majority of stars in both fields combined formed at z < 1. The mean age in the inner field, S1, is ~ 3 +/- 1 Gyr and the mean metallicity is [M/H] ~ -0.5 +/- 0.2 dex. The star formation history of S1 unambiguously reveals how the inside-out growth previously measured for M33's inner disc out to ~ 6 kpc extends out to the disc edge at ~ 9 kpc. In comparison, the outer field, S2, is older (mean age ~ 7 +/- 2 Gyr), more metal-poor (mean [M/H] ~ -0.8 +/- 0.3 dex), and contains ~ 30 times less stellar mass. These results provide the most compelling evidence yet that M33's age gradient reverses at large radii near the disc break and that this reversal is accompanied by a break in stellar mass surface density. We discuss several possible interpretations of this behaviour including radial stellar mixing, warping of the gaseous disc, a change in star formation efficiency, and a transition to another structural component. These results offer one of the most detailed views yet of the peripheral regions of any disc galaxy and provide a much-needed observational constraint on the last major epoch of star formation in the outer disc.Comment: 15 pages, 9 figures, accepted to MNRAS, hi-res version available at http://www.roe.ac.uk/~mkb/astroph/m33hires.pd

Revisiting Egyptian Foreign Policy towards Israel under Mubarak: From Cold Peace to Strategic Peace

This article is the first academic study of Egyptian foreign policy towards Israel under Hosni Mubarak (1981–2011). It challenges a deeply entrenched conventional wisdom that Egypt pursued a cold-peace foreign policy towards Israel throughout this period. We demonstrate that Egyptian foreign policy towards Israel was dynamic – comprising cold peace (1981–91), a hybrid foreign policy of cold peace and strategic peace (1991–2003), and a pure strategic peace posture (2003–11). We also use the case of Egyptian foreign policy towards Israel as a heuristic to develop a conception of a new type of peace, strategic peace, as an intermediary analytical category between cold and stable peace

Interaction between Free-Stream Turbulence and Tip-Vortices of Wind Turbine Blades with and without Winglets

Abstract Experimental investigations of the free-stream turbulence impact on the tip-vortices generated in wind turbine blades have been performed. The investigation is done by exposing an efficient laboratory scale wind turbine to different turbulence levels generated by two static grids installed in the cross section of a wind tunnel. Different winglet configurations to figure out the optimum design that can prevent the tip induced flow are studied. The power gained when adding different winglets is measured when exposing the turbine to turbulence. It is found that the strength of the vortices is reduced depending on the turbulence levels. Furthermore, higher power extraction associated with more expansion of wake and wake-border is shown. This is an indication for increasing of the mixing between the free-stream and the wake. Tip-vortex analysis of high turbulence levels has shown additional interaction of large-eddy scales contained in the free-stream turbulence. The turbulence helps to suppress the tip vortices, and thus, reduces the tip losses. Further investigations of the near and far wake-surrounding intersection are performed to understand the energy exchange and the free stream entrainment that help in wake recovery

Interaction between free-stream turbulence and tip-vortices of wind turbine blades with and without winglets

Experimental investigations of the free-stream turbulence impact on the tip-vortices generated in wind turbine blades have been performed. The investigation is done by exposing an efficient laboratory scale wind turbine to different turbulence levels generated by two static grids installed in the cross section of a wind tunnel. Different winglet configurations to figure out the optimum design that can prevent the tip induced flow are studied. The power gained when adding different winglets is measured when exposing the turbine to turbulence. It is found that the strength of the vortices is reduced depending on the turbulence levels. Furthermore, higher power extraction associated with more expansion of wake and wake-border is shown. This is an indication for increasing of the mixing between the free-stream and the wake. Tip-vortex analysis of high turbulence levels has shown additional interaction of large-eddy scales contained in the free-stream turbulence. The turbulence helps to suppress the tip vortices, and thus, reduces the tip losses. Further investigations of the near and far wake-surrounding intersection are performed to understand the energy exchange and the free stream entrainment that help in wake recovery

Modeling of groundwater potential using cloud computing platform: A case study from nineveh plain, Northern Iraq

Knowledge of the groundwater potential, especially in an arid region, can play a major role in planning the sustainable management of groundwater resources. In this study, nine machine learning (ML) algorithms—namely, Artificial Neural Network (ANN), Decision Jungle (DJ), Aver-aged Perceptron (AP), Bayes Point Machine (BPM), Decision Forest (DF), Locally-Deep Support Vector Machine (LD-SVM), Boosted Decision Tree (BDT), Logistic Regression (LG), and Support Vector Machine (SVM)—were run on the Microsoft Azure cloud computing platform to model the groundwater potential. We investigated the relationship between 512 operating boreholes with a specified specific capacity and 14 groundwater-influencing occurrence factors. The unconfined aquifer in the Nineveh plain, Mosul Governorate, northern Iraq, was used as a case study. The groundwater-influencing factors used included elevation, slope, curvature, topographic wetness index, stream power index, soil, land use/land cover (LULC), geology, drainage density, aquifer saturated thickness, aquifer hydraulic conductivity, aquifer specific yield, depth to groundwater, distance to faults, and fault density. Analysis of the contribution of these factors in groundwater potential using information gain ratio indicated that aquifer saturated thickness, rainfall, hydraulic conductivity, depth to groundwater, specific yield, and elevation were the most important factors (average merit > 0.1), followed by geology, fault density, drainage density, soil, LULC, and distance to faults (average merit < 0.1). The average merits for the remaining factors were zero, and thus, these factors were removed from the analysis. When the selected ML classifiers were used to esti-mate groundwater potential in the Azure cloud computing environment, the DJ and BDT models performed the best in terms of all statistical error measures used (accuracy, precision, recall, F-score, and area under the receiver operating characteristics curve), followed by DF and LD-SVM. The probability of groundwater potential from these algorithms was mapped and visualized into five groundwater potential zones: very low, low, moderate, high, and very high, which correspond to the northern (very low to low), southern (moderate), and middle (high to very high) portions of the study area. Using a cloud computing service provides an improved platform for quickly and cheaply running and testing different algorithms for predicting groundwater potential

Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the ISG15 gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/β signalling. Due to this dual role, ISG15 deficiency can present with various clinical phenotypes, ranging from susceptibility to mycobacterial infection to autoinflammation characterised by necrotising skin lesions, intracerebral calcification, and pulmonary involvement. In this report, we describe novel variants found in two different families that result in complete ISG15 deficiency and severe skin ulceration. Whole exome sequencing identified a heterozygous missense p.Q16X ISG15 variant and a heterozygous multigene 1p36.33 deletion in the proband from the first family. In the second family, a homozygous total ISG15 gene deletion was detected in two siblings. We also conducted further analysis, including characterisation of cytokine dysregulation, interferon-stimulated gene expression, and p-STAT1 activation in lymphocytes and lesional tissue. Finally, we demonstrate the complete and rapid resolution of clinical symptoms associated with ISG15 deficiency in one sibling from the second family following treatment with the Janus kinase (JAK) inhibitor baricitinib

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Validation of childhood lupus specific targets: Ensuring accurate assessment of disease control in younger, lighter paediatric patients

\ua9 2025 The Author(s).Objectives: To validate novel childhood-onset systemic lupus erythematosus (cSLE) treat-To-Target targets including childhood lupus low disease activity state (cLLDAS), cSLE clinical remission on steroids (cCR) and cSLE clinical remission off steroids (cCR-0), as compared with adult-onset SLE (aSLE) targets. Methods: Attainment of the aforementioned cSLE-specific and aSLE-specific targets (LLDAS, DORIS 2021 Remission) was assessed at each visit in UK JSLE Cohort Study patients. Univariable and multivariable Prentice-Williams-Peterson (PWP) gap-Time models investigated the impact of target attainment on new damage and severe flare. Results: The cohort included 430 cSLE patients. Attainability was comparable between corresponding cSLE and aSLE targets. Achieving cLLDAS (hazard ratio [HR] 0.18 [95% CI: 0.14, 0.23]), cCR (HR 0.18 [0.13, 0.23]) and cCR-0 (HR 0.17 [0.13, 0.23]) reduced the risk of severe flare (all P &lt; 0.001). Risk of new damage was reduced in those reaching cLLDAS (HR 0.22 [0.11, 0.44]), cCR (HR 0.25 [0.13, 0.49]) and cCR-0 (HR 0.30 [0.15, 0.60]) (all P &lt; 0.001). Inappropriate attainment of LLDAS and DORIS remission occurred at 35 and 52 visits, respectively, in younger (median age 7.3 and 8.8 years, respectively) and lighter (median weight 26.8 and 37.1 kg, respectively) patients whilst on prednisolone doses that precluded cSLE target attainment (median 0.17 [IQR 0.16-0.24] and 0.13 [IQR 0.11-0.16] mg/kg/day, respectively). Conclusions: This study validates novel paediatric-specific targets, demonstrating that achieving cLLDAS, cCR and cCR-0 reduces risks of new damage and severe flare, which is comparable to aSLE targets. Using cSLE-specific targets prevents misclassification of disease activity in paediatric patients, enabling more accurate disease control assessments in younger, lighter patients

Contributors to organ damage in childhood lupus: Corticosteroid use and disease activity

\ua9 2024 The Author(s) 2024 Published by Oxford University Press on behalf of the British Society for Rheumatology.Objectives: Awareness of paediatric-specific predictors of damage in childhood lupus is needed to inform mitigation measures. The objective of this study was to ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage. Methods: This analysis included UK JSLE Cohort Study participants. Univariable and multivariable Prentice-Williams-Peterson models investigated how demographic and clinical factors influenced the hazards of new damage. Analyses were performed across the entire cohort, in patients with minimal disease activity marked by a time-adjusted average SLEDAI-2K score (AMS) of ≤2, in patients with low activity (AMS of ≤4), patients with moderate-to-high activity (AMS of &gt;4) and patients with no CS use. Results: Within the entire cohort (n = 430), factors associated with damage included: any methylprednisolone [hazard ratio, HR 2.20 (CI 1.33-3.62)], time-adjusted mean Physician\u27s Global Assessment (PGA) [HR 2.87 (CI 1.48-5.56)] and AMS score [HR 1.13 (CI 1.03-1.24), all P &lt; 0.05]. Within the low activity subgroup, any methylprednisolone [HR 2.61 (CI 1.04-6.53)] and time-adjusted mean PGA [HR 3.41 (CI 1.52-7.76)] were associated with damage (both P &lt; 0.05). Within the moderate-to-high activity subgroup, any methylprednisolone [HR 2.29 (CI 1.31-4.00)], time-adjusted mean PGA [HR 2.66, (CI 1.20-5.87)] and AMS score [HR 1.15 (CI 1.03-1.29)] were predictive of damage (all P &lt; 0.05). Baseline organ damage was predictive of subsequent damage accrual in the minimal disease activity subgroup [HR 1.33 (CI 1.78-8.08)] and the no CSs subgroup [HR 3.64 (CI 1.83-7.24), both P &lt; 0.005]. Conclusion: Disease activity levels (AMS/PGA) and proxy indicators (methylprednisolone exposure, baseline damage) were found to be key predictors of damage accrual. This highlights the importance of practical strategies, such as treat-to-target, for reducing disease activity and long-term treatment toxicity