The free fibula flap has been one of the most important microvascular grafts for orofacial reconstruction for more than 30 years. The complication rates at the donor-site reported in literature are ...considered to be low, but the published data vary greatly in some cases. In particular, restrictions in the stability and balance of the involved leg and their effects on the quality of life have been described very inconsistently to date. Therefore, this study mainly focuses on the stability and balance of the affected leg in a split-leg design. Between December 2014 and January 2018, out of 119 subjects who underwent mainly jaw ablative tumor surgery and reconstruction using a fibula flap, 68 subjects were examined for donor site morbidity. Besides reporting general types of complications, two specific test procedures were used. The Star Excursion Balance Test (SEBT) as a practical test for ankle function and the Foot and Ankle Disability Index (FADI) as a questionnaire in order to assess quality of life, depending on the lower leg function. SEBT revealed an average of 55.3 cm with the operated leg as the supporting leg, which corresponds to 95.5% of 57.9 cm achieved with the healthy leg as the supporting leg. An average FADI score of 89.4% was recorded. SEBT and FADI seem to be suitable methods of examination for subjects post fibular transplantation and pointed out minimal limitations of the involved legs in comparison to the unaffected legs. These limitations were clinically not relevant and they had minor influence on the subjects’ quality of life and their daily activities.
A diverse antibody repertoire is essential for an effective adaptive immune response to novel molecular surfaces. Although past studies have observed common patterns of V-segment use, as well as ...variation in V-segment use between individuals, the relative contributions to variance from genetics, disease, age, and environment have remained unclear. Using high-throughput sequence analysis of monozygotic twins, we show that variation in naive VH and DH segment use is strongly determined by an individual's germ-line genetic background. The inherited segment-use profiles are resilient to differential environmental exposure, disease processes, and chronic lymphocyte depletion therapy. Signatures of the inherited profiles were observed in class switched germ-line use of each individual. However, despite heritable segment use, the rearranged complementarity-determining region-H3 repertoires remained highly specific to the individual. As it has been previously demonstrated that certain V-segments exhibit biased representation in autoimmunity, lymphoma, and viral infection, we anticipate our findings may provide a unique mechanism for stratifying individual risk profiles in specific diseases.
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from ...27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10
), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
The IntOGen-mutations platform (http://www.intogen.org/mutations/) summarizes somatic mutations, genes and pathways involved in tumorigenesis. It identifies and visualizes cancer drivers, analyzing ...4,623 exomes from 13 cancer sites. It provides support to cancer researchers, aids the identification of drivers across tumor cohorts and helps rank mutations for better clinical decision-making.
Transportation noise leads to sleep disturbance and to psychological and physiological sustained stress reactions, which could impact respiratory health. However, epidemiologic evidence on ...associations of objective transportation noise exposure and also perceived noise annoyance with respiratory morbidity is limited. We investigated independent associations of transportation noise exposure and noise annoyance with prevalent respiratory symptoms and incident asthma in adults.
Using 17,138 observations (from 7049 participants) from three SAPALDIA (Swiss Cohort Study on Lung and Heart Diseases in Adults) surveys, we assessed associations of transportation noise exposure and noise annoyance with prevalent respiratory symptoms, and with incident asthma (in 10,657 nested observations from 6377 participants). Annual day-evening-night transportation noise comprising road, railway and aircraft Lden (Transportation Lden) was calculated for the most exposed façade of participants' residence using Swiss noise models. Transportation noise annoyance was assessed using an 11-point scale, and participants reported respiratory symptoms and doctor-diagnosed asthma at each survey. We estimated associations with transportation Lden (as well as source-specific Lden) and noise annoyance, independent of air pollution and other potential confounders, using mutually-adjusted mixed logistic and Poisson models and applying random intercepts at the level of the participants.
Prevalent respiratory symptoms ranged from 5% (nocturnal dyspnoea) to 23% (regular cough/phlegm). Transportation noise annoyance, but not Lden, was independently associated with respiratory symptoms and current asthma in all participants, with odds ratios (OR) and 95% confidence intervals (CI) ranging between 1.03 (95%CI: 1.01, 1.06) and 1.07 (95% CI: 1.04, 1.11) per 1-point difference in noise annoyance. Both noise annoyance and Lden showed independent associations with asthma symptoms among asthmatics, especially in those reporting adult-onset asthma ORLden: 1.90 (95% CI: 1.25, 2.89) per 10 dB; p-value of interaction (adult-onset vs. childhood-onset): 0.03; ORnoise annoyance: 1.06 (95%CI: 0.97, 1.16) per 1-point difference; p-value of interaction: 0.06. No associations were found with incident asthma.
Transportation noise level and annoyance contributed to symptom exacerbation in adult asthma. This suggests both psychological and physiological noise reactions on the respiratory system, and could be relevant for asthma care. More studies are needed to better understand the effects of objective and perceived noise in asthma aetiology and overall respiratory health.
•We studied association of noise level and annoyance with adult respiratory morbidity.•Noise annoyance was associated with respiratory symptoms and current asthma.•Noise level was only associated with respiratory symptoms in asthmatic participants.•Noise level and annoyance were not associated with the development of asthma.•The results highlight the potential importance of perceived noise and noise annoyance on respiratory health.
The aim of this monocentric, retrospective clinical study was to evaluate the status of osseous union in uni- and poly-segmental mandible reconstructions regarding conventional angle-stable manually ...bent osteosynthesis plates (Unilock 2.0 mm) versus titan laser-melted PSI patient-specific implant's (PSI). The clinical impact of PSI's high stiffness fixation methods on bone healing and regeneration is still not well addressed. The special interest was in evaluating the ossification of junctions between mandible and fibula and between osteotomized fibula free flap (FFF) segments. Panoramic radiograph (OPT), computed tomography (CT) scans, or cone-beam CTs (CBCT) of patients who underwent successful FFF for mandible reconstruction from January 2005 to December 2020 were analyzed. A total number of 89 cases (28 females (31.5%), 61 males (68.5%), mean age 58.2 ± 11.3 years, range: 22.8-82.7 years) fulfilled the chosen inclusion criteria for analysis (conventional:
= 44 vs. PSI:
= 45). The present study found an overall incomplete ossification (IOU) rate of 24.7% (conventional: 13.6% vs. PSI: 35.6%;
= 0.017) for mandible to fibula and intersegmental junctions. Between osteotomized FFF segments, an IOU rate of 16% was found in the PSI-group, while no IOU was recorded in the conventional group (
= 0.015). Significant differences were registered for IOU rates in poly-segmental (
= 0.041), and lateral (
= 0.016) mandibular reconstructions when PSI was used. Multivariate logistic regression analysis identified plate exposure and type of plate used as independent risk factors for IOU. Previous or adjuvant radiotherapy did not impact incomplete osseous union in the evaluated study sample. PSI is more rigid than bent mini-plates and shields functional mechanical stimuli, and is the main reason for increasing the rate of incomplete ossification. To enhance the functional stimulus for ossification it has to be discussed if patient-specific implants can be designed to be thinner, and should be divided into segmental plates. This directs chewing forces through the bone and improves physiological bone remodeling.
The article argues that there is no single globalisation of education systems, but rather multiple globalisations of each system taken in its individual context. We propose three explanatory factors ...to account for these vernacular globalisation processes, that is, for individual policy trajectories in each national context: path dependence on earlier policy choices and institutions, education policy-making through bricolage, and finally the translation by national actors of international-level ideas or tools as a function of the debate, institutions or national power dynamics in question. The research design is based on the study of a most-likely case: accountability policy in two school systems - France and Quebec - which show strong variations. Document analyses and semi-structured interviews were conducted in both cases. In the two countries, distinct vernacular globalisations are at work leading to different neo-statist accountability policies. In Quebec, the reinforcement of state power through a growing vertical accountability and the systematic development of regulation tools between policy actors and levels lead to a 'centralisation by institutional linkage'. In France, we rather witness a 'globalisation by discursive internalisation' in which transnational imperatives are integrated in official discourses on the regulation of the education system, but without radically questioning the mainstays of this regulation.
Constraining the timing of eukaryogenesis and the divergence of eukaryotic clades is a major challenge in evolutionary biology. Here, we present trace metal concentration and zinc isotope data for c. ...2.1 billion-year-old Francevillian Group pyritized structures, previously described as putative remnants of the first colonial multicellular organisms, and their host black shales. Relative to the host rocks, pyritized structures are strongly enriched in zinc, cobalt and nickel, by at least one order of magnitude, with markedly lighter zinc isotope compositions. A metabolic demand for high concentrations of aqueous zinc, cobalt, and nickel combined with preferential uptake of lighter zinc isotopes may indicate metalloenzyme utilization by eukaryotes in marine habitats c. 2.1 billion years ago. Once confirmed, this would provide a critical calibration point for eukaryogenesis, suggesting that this major evolutionary innovation may have happened contemporaneously with elevated atmospheric oxygen levels during the latter part of the Great Oxidation Event, some 400 million years earlier than is currently widely accepted.
•Biogenic origin of the c. 2.1-billion-year-old Francevillian Group biota.•Enrichment of light zinc isotopes in the Francevillian biota is consistent with eukaryotic metabolism.•Utilization of metalloenzymes by possible eukaryotes in the Paleoproterozoic oceans.•Possible eukaryotic biota preserved in the Paleoproterozoic Francevillian Group.•Inferred eukaryogenesis during the Great Oxidation Event.
This is a monocentric, retrospective study of patients who underwent successful immediate or delayed maxilla or mandible reconstructions with FFF from January 2005 to December 2021. Panoramic ...radiograph, computed tomography scans, and cone-beam CTs were analyzed concerning the osseous union of the intersegmental junctions between maxillary or mandibular native jaw and fibular bone. The primary parameter was to estimate the status of osseous union according to osteosynthesis type. A total number of 133 patients (PSI: n = 64, non-PSI: n = 69) were included in the present study. The mean age was 56.7 ± 14.0 (Range: 14.7−82.7); the primary diagnosis was in 105 patients a malignant (78.9%) and in 20 patients a benign (15.0%) tumor. Mandible reconstruction was performed on 103 patients (77.4%), and on 30 patients (22.6%), maxilla reconstruction was performed. The radiographic images provided a rate of incomplete osseous union (IOU) of about 90% in both groups in the first 6 months. Imaging between 6 and 12 months reveals an IOU rate in the non-PSI group of 46.3% vs. 52.5% in the PSI group, between 12 and 24 months, an IOU rate of 19.6% vs. 26.1%, between 24 and 36 months 8.9% vs. 21.7%, and after 36 months the IOU rate decreases to 4.2% vs. 18.2%. Multivariate logistic regression shows that only osteosynthesis type (OR = 3.518 95%-CI = 1.223−10.124, p = 0.02) and adjuvant radiotherapy (OR = 4.804 95%-CI = 1.602−14.409, p = 0.005) are independent risk factors for incomplete osseous union. Cox regression revealed that the variables plate-system (Hazard ratio, HR = 5.014; 95 %-CI: 1.826−3.769; p = 0.002) and adjuvant radiotherapy (HR = 5.710; 95 %-CI: 2.066−15.787; p < 0.001) are predictors for incomplete osseous union. In our study, the rate of incomplete bony fusion was significantly higher in the PSI group. Jaw-to-fibula apposition zones were significantly more affected than intersegmental zones. In multivariate analysis, a combination of osteosynthesis with PSI and adjuvant radiotherapy could be identified as a risk constellation for incomplete ossification.
The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated.
In ...this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel.
At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval CI, 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group.
Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).
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