The European Union's (EU) Common Commercial Policy (CCP) is more fragile than the label 'exclusive competence' suggests. Ratification conflicts have increased since the 1980s and have further ...intensified in recent years. Simultaneously, the EU's trade competence witnessed a progressive expansion in consecutive treaty reforms. In recourse to the 'failing forward' (Jones et al., 2016) argument, this paper argues that recurring failure and progressive integration have been equally constitutive elements in the CCP's historical development. The substantive expansion of the international 'deep trade' agenda repeatedly laid bare the gaps in and fuelled intergovernmental conflict over the scope of the EU's competences. Over time, these instabilities acted as a catalyst of integration, supporting supranational entrepreneurs' quest for - and member state governments' acceptance of - further yet ever-incomplete delegation. The paper thus demonstrates that, under certain conditions, the failing forward argument is applicable even to the EU's historical core of regulatory market-making.
Full text
Available for:
BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
No consensus has been reached regarding the best treatment option for early-stage lesions in medication-related osteonecrosis of the jaw (MRONJ). The purpose of the present study was to evaluate the ...long-time outcomes of conservative non-surgical management in stage I patients with underlying malignant disease.
We designed and implemented a retrospective cohort study and enrolled, between 2008 and 2018, a sample of patients with the indication for non-surgical conservative treatment stage I lesions. The primary outcome variable was treatment success defined as mucosal integrity without signs of infection. Secondary outcomes were: (i) worsening stage, (ii) necessity for surgical intervention over time, and (iii) discontinuation of antiresorptive therapy.
The sample included 75 patients with 92 lesions. Eight lesions showed full mucosal coverage, whereas 84 continued with exposed jaw bone (91.3%). Of the treatment-resistent 84 lesions, 67 presented a worsening stage shift over time. Indication for surgical intervention was set in 57 lesions. Of all lesions, 28 developed highly advanced necrotic bone destruction. Antiresorptive medication was paused in all evaluated patients after the first diagnosis of MRONJ.
Conservative non-surgical therapy in MRONJ stage I leads to a healing in rare cases. Conservative management might be a good option to preserve symptoms in patients either unwilling to undergo surgery or in those whose reduced general condition does not allow surgery. Early and consequent surgical advances should be performed throughout all stages of the disease to prevent the possibility of silent disease progression with the risk of large-scale bone loss.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective The value of surgery in advanced stages of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still controversial. Hence, we evaluated the effect of surgical therapy in BRONJ stages ...II and III in combination with a standardized perioperative adjuvant treatment. Study Design We included 39 patients who presented with BRONJ in a total of 47 locations and stages II (n = 23) and III (n = 24). All patients had exclusively received a monthly intravenous application of zoledronic acid. Surgical therapy consisted of complete removal of the necrotic jaw, accompanied by a standardized perioperative adjuvant treatment including intravenous antibiotic prophylaxis, gastric feeding, and an antimicrobiologic mouth rinsing. Results Overall, 35 (74.5%) of the 47 BRONJ sites were treated successfully, with success defined as complete mucosal healing of the exposed jaw (n = 24) or as relative healing when surgical therapy downscaled BRONJ II or III to asymptomatic BRONJ stage I (n = 11). Interestingly, perioperative adjuvant treatment or bisphosphonate therapy parameters showed no statistical effect on the treatment outcome. Conclusions The results of the present study prove the effectiveness of surgical therapy for BRONJ stage II or III.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a ...chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
To evaluate whether magnetic resonance imaging (MRI) can serve as an alternative diagnostic tool to the “gold standard” cone-beam computed tomography (CBCT) in 3D cephalometric analysis.
...Methods
In this prospective feasibility study, 12 patients (8 males, 4 females; mean age ± SD, 26.1 years ± 6.6) underwent 3D MRI and CBCT before orthognathic surgery. 3D cephalometric analysis was performed twice by two independent observers on both modalities. For each dataset, 27 cephalometric landmarks were defined from which 35 measurements (17 angles, 18 distances) were calculated. Statistical analyses included the calculation of Euclidean distances, intraclass correlation coefficients (ICCs), Bland-Altman analysis, and equivalence testing (linear mixed effects model) with a predefined equivalence margin of ± 1°/1 mm.
Results
Analysis of reliability for CBCT vs. MRI (intra-rater I/intra-rater II/inter-rater) revealed Euclidean distances of 0.86/0.86/0.98 mm vs. 0.93/0.99/1.10 mm for landmarks, ICCs of 0.990/0.980/0.986 vs. 0.982/0.978/0.980 for angles, and ICCs of 0.992/0.988/0.989 vs. 0.991/0.985/0.988 for distances. Bland-Altman analysis showed high levels of agreement between CBCT and MRI with bias values (95% levels of agreement) of 0.03° (− 1.49; 1.54) for angles and 0.02 mm (− 1.44; 1.47) for distances. In the linear mixed effects model, the mean values of CBCT and MRI measurements were equivalent.
Conclusion
This feasibility study indicates that MRI enables reliable 3D cephalometric analysis with excellent agreement to corresponding measurements on CBCT. Thus, MRI could serve as a non-ionizing alternative to CBCT for treatment planning and monitoring in orthodontics as well as oral and maxillofacial surgery.
Key Points
• Clinically established 3D cephalometric measurements performed on MRI are highly reliable and show an excellent agreement with CBCT (gold standard).
• The MRI technique applied in this study could be used as a non-ionizing diagnostic tool in orthodontics as well as oral and maxillofacial surgery.
• Since most patients benefiting from 3D cephalometry are young in age, the use of MRI could substantially contribute to radiation protection and open up new possibilities for treatment monitoring.
Whereas some federations reacted to the expanding international trade agenda by 'federalizing' trade policy-making and allowing sub-federal governments a substantial involvement, others did not. ...Comparing Canada and the United States, this paper investigates the conditions and potentials of federalization on the case of public procurement liberalization. The first section argues that the institutionalization of intergovernmental relations depends on the incontestability of sub-federal claims to authority and the absence of cheaper alternatives. In the US, the availability of federal pre-emption and the possibility to exclude sub-federal competencies from international agreements acted as a brake on state involvement. In Canada, 'watertight' provincial competencies and a non-representative second chamber enabled a gradual federalization. The second section argues that federalization holds the potential to increase constituent units' openness to procurement liberalization. While their deficient involvement has constrained US states' openness, federalization was instrumental in Canadian provinces' recently growing openness for international suppliers.
Full text
Available for:
BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Comparative federalism contributes to a better understanding of the relationship between 'Brussels' and member states in international trade policy. Analysing the understudied field of international ...procurement liberalization and comparing the European Union (EU), the United States (US) and Canada, the article observes that sub-federal resistance has differed across federations. It finds that the more 'voice' sub-federal executives enjoy, the less they 'exit' from international commitments. Voice hinges on their representation in federation-wide decision-making (council or senate) and the sectoral nature of vertical relations (collaborative or competitive). In the US senate federation, effective means of joint policy-making have not evolved in this non-coercive field, inciting states to exit. In Canada, increasing collaboration has compensated provinces for senate federalism's low voice, reducing their resistance. EU 'second chamber federalism' proves peculiar for constituent units' decisive role and its dense and trusting regime of collaboration. Member states' high voice has encouraged their low resistance.
Full text
Available for:
BFBNIB, NUK, ODKLJ, PILJ, SAZU, UL, UM, UPUK
The aim of this study was to validate geometric accuracy and in vivo reproducibility of landmark-based cephalometric measurements using high-resolution 3D Magnetic Resonance Imaging (MRI) at 3 Tesla. ...For accuracy validation, 96 angular and 96 linear measurements were taken on a phantom in 3 different positions. In vivo MRI scans were performed on 3 volunteers in five head positions. For each in vivo scan, 27 landmarks were determined from which 19 angles and 26 distances were calculated. Statistical analysis was performed using Bland-Altman analysis, the two one-sided tests procedure and repeated measures one-way analysis of variance. In comparison to ground truth, all MRI-based phantom measurements showed statistical equivalence (p < 0.001) and an excellent agreement in Bland-Altman analysis (bias ranges: -0.090-0.044°, -0.220-0.241 mm). In vivo cephalometric analysis was highly reproducible among the five different head positions in all study participants, without statistical differences for all angles and distances (p > 0.05). Ranges between maximum and minimum in vivo values were consistently smaller than 2° and 2 mm, respectively (average ranges: 0.88°/0.87 mm). In conclusion, this study demonstrates that accurate and reproducible 3D cephalometric analysis can be performed without exposure to ionizing radiation using MRI.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The human leukocyte antigene E (HLA-E) is associated with tumorigenesis in various cancers. Immunoncology along with sex-specific aspects in cancer therapy are now in scientific focus. Therefore, ...immunohistochemical HLA-E expression was retrospectively analysed in a cohort of oral squamous cell carcinomas (OSCC) after surgical therapy. Then, serum concentration of HLA-E (sHLA-E) was quantified in a prospective cohort by enzyme-linked immunosorbent assay. High HLA-E expression was associated with advanced UICC stage (Spearman's correlation:
= 0.002) and worse survival (Cox-regression: progression-free survival: hazard ratio (HR) 3.129, confidence range (CI) 1.443-6.787,
= 0.004; overall survival: HR 2.328, CI 1.071-5.060,
= 0.033). The sHLA-E concentration was significantly higher in the control group than in tumor group (Mann-Whitney U-test (MW-U):
= 0.021). Within the tumor group, women showed significantly higher sHLA-E levels than men (MW-U:
= 0.049). A closer look at the tumor group and the control group showed that gender-specific differences exist: while no differences in sHLA-E concentration were detectable between female subjects of tumor group and control group (MW-U:
= 0.916), male subjects of tumor group had a significantly lower sHLA-E concentration compared to those of control group (MW-U:
= 0.001). In summary, our results provide evidence for sex-specific differences in immune responses in OSCC. This fact should be considered regarding future immunotherapy regimens.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF