Sounding rockets are particularly important for studies in the scientific community and one of the main attractions is their relatively moderated cost compared to more complex manned missions. ...Besides, missions with sounding rockets can have varying high ranges according to their needs. Safety aspects are essential for this type of mission to be successfully accomplished. This work aims to analyze systemic factors that influence safety in Brazilian suborbital launch campaigns. A safety analysis methodology for suborbital launch operations is proposed and carried out for the Alcântara Space Center (CEA) and its iterations with other involved organizations. The study of systems safety techniques applied to Launch Operations at CEA is a truly relevant task because it deals with the preservation of human life, properties, knowledge, and the environment. The Systems-Theoretic Process Analysis (STPA) analysis was used as accident causes analysis, based on systems theory, not on reliability theory. The performed analysis was based on historical data from past launches and eventually accidents that occurred. The resulting analysis by the application of STPA to the evaluation phases of the concept, requirements, architecture, and design of a hypothetical two-stage sounding rocket provided valuable information related to the safety aspects of the mission. The results of this analysis show the effectiveness of analyzing the systemic factors that influence safety in suborbital vehicle launch operations, seeking for existing hazards, and creating safety recommendations or restrictions to minimize the probability of the occurrence of hazard events.
To determine the diagnostic discriminant validity between large vessel giant cell arteritis (LV-GCA) and atherosclerosis using ultrasound (US) intima-media thickness (IMT) measurements.
We included ...44 patients with LV-GCA and 42 with high-risk atherosclerosis. US examinations of the axillary, subclavian, and common carotid arteries (CCA) were systematically performed using a MylabX8 system (Genoa, Italy) with a 4-15-MHz probe. IMT ≥ 1 mm was accepted as pathological.
The LV-GCA cohort included 24 females and 20 males with a mean age of 72.8 ± 7.6 years. The atherosclerosis group included 25 males and 17 females with a mean age of 70.8 ± 6.5 years. The mean IMT values of all arteries included were significantly higher in LV-GCA than in atherosclerosis. Among LV-GCA patients, IMT ≥ 1 mm was seen in 31 axillary, 30 subclavian, and 28 CCA. In the atherosclerotic cohort, 17 (38.6%) had IMT ≥ 1 mm with axillary involvement in 2 patients, subclavian in 3 patients, carotid distal in 14 patients (5 bilateral), and isolated carotid proximal affectation in 1 case. A cutoff point greater than 1 pathological vessel in the summative count of axillary and subclavian arteries or at least 3 vessels in the count of six vessels, including CCA, showed a precision upper 95% for GCA diagnosis.
The IMT is higher in LV-GCA than in atherosclerosis. The proposed US halo count achieves an accuracy of > 95% for the differential diagnosis between LV-GCA and atherosclerosis. The axillary and subclavian arteries have higher discriminatory power, while carotid involvement is less specific in the differential diagnosis.
Celiac disease (CD) occurs in about 1% of people worldwide. Diagnosis rates are increasing due to a true rise in incidence, rather than increased awareness and detection. CD affects genetically ...susceptible individuals who are triggered by the ingestion of gluten. The disease has many clinical manifestations, ranging from severe to minimally symptomatic or non-symptomatic presentations. Diagnosis requires the presence of duodenal chronic inflammation, and most patients have circulating antibodies against tissue transglutaminase. Our understanding of the basic and clinical aspects of CD increases, which is as a major health problem of almost global occurrence. Case finding, distinguishing CD from other gluten-sensitive conditions, better care, and balanced use of resources are the current challenges.
The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; six ...adults) in a prospective pilot study. All of them followed a GFD for one year. The Yale Global Tics Severity Scale (YGTSS), the Yale-Brown Obsessive-Compulsive Scale-Self Report (Y-BOCS) or the Children's Yale-Brown Obsessive-Compulsive Scale-Self Report (CY-BOCS), and the Cavanna's Quality of Life Questionnaire applied to GTS (GTS-QOL) were compared before and after the GFD; 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated obsessive-compulsive disorder (OCD) (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3, (standard deviation (SD) = 12.3) (children) and 26.8 (9.2) (adults) (
= 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (
= 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (
= 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (
= 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (
= 0.001), along with improved generic quality of life (
= 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.
Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present ...study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486-0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower than that observed in the general population. Gene mutations and LDL cholesterol concentrations were not risk factors associated with the prevalence of T2DM in patients with HeFH. The prevalence of T2DM in patients with HeFH was 40% lower than in the general population matched for age and sex.
The proposed analysis consists of identifying systemic aspects that can influence safety and mission fulfillment in the Evaluation and Acceptance Processes of Space Systems and Operations for Launch ...through the application of System-Theoretic Process Analysis, a technique capable of identifying potential hazardous design and operational flaws, including system design errors and unsafe interactions among multiple procedures and system components. This research identifies losses, hazards, system-level safety constraints, the control structure of the general system, unsafe control actions, loss scenarios that could occur and related causal factors, detecting improvement possibilities for future verifications, evaluations, approvals, and acceptances of space systems and launch operations. These findings can promote safety in space system designs and operations, supporting the activities conducted by launch vehicle and payload developers, certification authorities, and launch centers management, enabling means to proactively act in order to mitigate risks, avoiding unsafe actions and undesired system behaviors, or even to mitigating their consequences. The practical applications of this work can result in safety and mission fulfillment improvements for safety management systems, launch approval regulations and standards; launch operation procedures; space systems design; vehicle, payload, and ground support equipment productions; systems testing; and launch authorization processes.
Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high ...variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS criteria. Univariate and multivariate analysis was used to assess the association of CVD with the IAS criteria. About 1,732 HeFH cases were analyzed. Severe HeFH had higher prevalence of familial history of CVD, personal history of tendon xanthomas, LDL cholesterol, and CVD than nonsevere HeFH. A total of 656 (77.1%) and 441 (50.1%) of men and women, respectively, fulfilled the IAS criteria of severe HeFH. In the univariate analysis, subjects defined as severe HeFH showed odds ratio 3.016 (95% CI 3.136 to 4.257, p <0.001) for CVD. However, when traditional risk factors were included in the multivariate analysis, only the presence of cholesterol >400 mg/dl had a statistically significant association with CVD odds ratio 8.76 (95% CI 3.90 to 19.69, p <0.001). In conclusion, the IAS definition of severe HeFH is not significantly associated with CVD when adjusted for classic risk factors. Risk stratification in HeFH is an important issue, but the proposed criteria do not seem to solve this problem.
Few studies have analyzed the relationship between glucose variability (GV) and adverse health outcomes in patients with differences in glycemic status. The present study tests the hypothesis that GV ...predicts all-cause mortality regardless of glycemic status after simple adjustment (age and sex) and full adjustment (age, sex, cardiovascular disease, hypertension, use of aspirin, statins, GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors, baseline FPG and average HbA1c). A total of 1,223 patients (657 men, 566 women) died after a median of 9.8 years of follow-up, with an all-cause mortality rate of 23.35/1,000 person-years. In prediabetes or T2DM patients, the fourth quartile of CV-FPG exerted a significant effect on all-cause mortality after simple and full adjustment. A sensitivity analysis excluding participants who died during the first year of follow-up revealed the following results for the highest quartile in the fully adjusted model: overall, HR (95%CI) = 1.54 (1.26-1.89); dysglycemia (prediabetes and T2DM), HR = 1.41 (1.15-1.73); T2DM, HR = 1.36 (1.10-1.67). We found CV-FPG to be useful for measurement of GV. It could also be used for the prognostic stratification of patients with dysglycemia.
Asthma is a complex and heterogeneous respiratory disorder characterized by chronic airway inflammation. It has generally been associated with allergic mechanisms related to type 2 airway ...inflammation. Nevertheless, between 10 and 33% of asthmatic individuals have nonallergic asthma (NA). Several targeted treatments are in clinical development for patients with Th2 immune response, but few biomarkers are been defined for low or non-Th2-mediated inflammation asthma. We have recently defined by gene expression a set of genes as potential biomarkers of NA, mainly associated with disease severity: IL10, MSR1, PHLDA1, SERPINB2, CHI3L1, IL8, and PI3. Here, we analyzed their protein expression and specificity using sera and isolated peripheral blood mononuclear cells (PBMCs). First, protein quantification was carried out using ELISA (in sera) or Western blot (proteins extracted from PBMCs by Trizol procedure), depending on the biomarker in 30 healthy controls (C) subjects and 30 NA patients. A receiver operating characteristic curve analysis was performed by using the R program to study the specificity and sensitivity of the candidate biomarkers at a gene- and protein expression level. Four kinds of comparisons were performed: total NA group vs C group, severe NA patients vs C, moderate-mild NA patients vs C, and severe NA patients vs moderate-mild NA patients. We found that all the single genes showed good sensitivity vs specificity for some phenotypic discrimination, with CHI3L1 and PI3 exhibiting the best results for C vs NA: CHI3L1 area under the curve (AUC) (CI 95%): 0.95 (0.84-1.00) and PI3 AUC: 0.99 (0.98-1.00); C vs severe NA: PI3 AUC: 1 (0.99-1.00); and C vs moderate-mild NA: CHI3L1 AUC: 1 (0.99-1.00) and PI3 AUC: 0.99 (0.96-1.00). However, the results for discriminating asthma disease and severity with protein expression were better when two or three biomarkers were combined. In conclusion, individual genes and combinations of proteins have been evaluated as reliable biomarkers for classifying NA subjects and their severity. These new panels could be good diagnostic tests.
Celiac disease (CD) is a common systemic disease related to a permanent intolerance to gluten and is often associated with different autoimmune and neurological diseases. Its mean prevalence in the ...general population is 1-2% worldwide. Our aim was to study the prevalence of celiac disease in a prospective series of Multiple Sclerosis (MS) patients and their first-degree relatives.
We analyzed the prevalence of serological, histological and genetic CD markers in a series of 72 MS patients and in their 126 first-degree relatives, compared to 123 healthy controls.
Tissue IgA-anti-transglutaminase-2 antibodies were positive in 7 MS patients (10%), compared to 3 healthy controls (2.4%) (p < 0.05). OR: 5.33 (CI-95%: 1.074-26.425). No differences were found in HLA-DQ2 markers between MS patients (29%) and controls (26%) (NS).We detected mild or moderate villous atrophy (Marsh III type) in duodenal biopsies, in 8 MS patients (11.1%). We also found a high proportion of CD among first-degree relatives: 23/126 (32%). Several associated diseases were detected, mainly dermatitis 41 (57%) and iron deficiency anemia in 28 (39%) MS patients. We also found in them, an increased frequency of circulating auto-antibodies such as anti-TPO in 19 (26%), ANA in 11 (15%) and AMA in 2 (3%).
We have found an increased prevalence of CD in 8 of the 72 MS patients (11.1%) and also in their first-degree relatives (23/126 32%). Therefore, increased efforts aimed at the early detection and dietary treatment of CD, among antibody-positive MS patients, are advisable.
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