Shrines of Saints and Dynastic Mausolea: Towards a Typology of Funerary Architecture in the Timurid Period

The history of Islamic funerary architecture in Central Asia is in many ways peculiar and fascinating. The sheer existence of monumental early mausolea is a proof of the discussion opened here against so-called orthodox trends to restrict memorials for the dead. That the oldest Islamic mausoleum preserved, the turba of the Samanids in Bokhara from the first half of the 10th century, is a dynastic mausoleum may be taken as a symbol for a special form of dynastic conscience introduced into or c..

Shrines of Saints and Dynastic Mausolea: Towards a Typology of Funerary Architecture in the Timurid Period

The history of Islamic funerary architecture in Central Asia is in many ways peculiar and fascinating. The sheer existence of monumental early mausolea is a proof of the discussion opened here against so-called orthodox trends to restrict memorials for the dead. That the oldest Islamic mausoleum preserved, the turba of the Samanids in Bokhara from the first half of the 10th century, is a dynastic mausoleum may be taken as a symbol for a special form of dynastic conscience introduced into or c..

Lipidomic and metabolomic characterization of a genetically modified mouse model of the early stages of human type 1 diabetes pathogenesis

The early mechanisms regulating progression towards beta cell failure in type 1 diabetes (T1D) are poorly understood, but it is generally acknowledged that genetic and environmental components are involved. The metabolomic phenotype is sensitive to minor variations in both, and accordingly reflects changes that may lead to the development of T1D. We used two different extraction methods in combination with both liquid- and gas chromatographic techniques coupled to mass spectrometry to profile the metabolites in a transgenic non-diabetes prone C57BL/6 mouse expressing CD154 under the control of the rat insulin promoter (RIP) crossed into the immuno-deficient recombination-activating gene (RAG) knockout (−/−) C57BL/6 mouse, resembling the early stages of human T1D. We hypothesized that alterations in the metabolomic phenotype would characterize the early pathogenesis of T1D, thus metabolomic profiling could provide new insight to the development of T1D. Comparison of the metabolome of the RIP CD154 × RAG(−/−) mice to RAG(−/−) mice and C57BL/6 mice revealed alterations of >100 different lipids and metabolites in serum. Low lysophosphatidylcholine levels, accumulation of ceramides as well as methionine deficits were detected in the pre-type 1 diabetic mice. Additionally higher lysophosphatidylinositol levels and low phosphatidylglycerol levels where novel findings in the pre-type 1 diabetic mice. These observations suggest that metabolomic disturbances precede the onset of T1D. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-015-0889-1) contains supplementary material, which is available to authorized users

Corrigendum on: White paper on European patient needs and suggestions on chronic type 2 inflammation of airways and skin by EUFOREA

Background: Type 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and differences in experiences and perspectives of the current management of patients with comorbid Type 2 inflammatory diseases. Aims: To improve insight into the common and organ-specific needs of patients with Type 2 inflammation and comorbidities, allowing the formulation of recommendations to better address these needs in the future. Methodology: This qualitative study was conducted between July 2021 and December 2021 using semi-structured face-to-face or telephone interviews with patients suffering from year-long severe chronic Type 2 inflammation and at least one co-morbid inflammatory condition. Seven participating academic centers in Europe interviewed asthma (Copenhagen and Leuven), CRSwNP (London, Amsterdam and Crete) and/or AD (Oldenburg and Zurich) patients on patient characteristics, disease severity, shortcomings of current care pathways and suggestions for improvement of care. Transcripts were analyzed using an inductive thematic analysis approach. Results: Eighty-one patients with severe Type 2 inflammation and comorbidities were interviewed. Similar needs were recognized by patients with Type 2 inflammation, with both a lack of coordination in care and a lack of a real cure reported as being most frustrating. However, several needs are specific to asthma, CRSwNP and AD. Suggestions for improvement of care were generic across diseases, such as the implementation of a multidisciplinary approach, the improved facilitation of access to better treatments, the increase of general awareness on disease burden, and better educational programs for healthcare providers and patients. Of note, patients with CRSwNP also stated the need for alternatives to sinus surgery, whereas patients with asthma requested better medical care to prevent exacerbations and patients with AD would warmly welcome the reimbursement of emollients. Conclusion: Patients with asthma, CRSwNP and AD have shared unmet needs that need to be addressed by physicians, the academic community and health policy makers. This survey provides unique recommendations made by patients for the implementation of better care

White Paper on European Patient Needs and Suggestions on Chronic Type 2 Inflammation of Airways and Skin by EUFOREA

Background: Type 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and differences in experiences and perspectives of the current management of patients with comorbid Type 2 inflammatory diseases. Aims: To improve insight into the common and organ-specific needs of patients with Type 2 inflammation and comorbidities, allowing the formulation of recommendations to better address these needs in the future. Methodology: This qualitative study was conducted between July 2021 and December 2021 using semi-structured face-to-face or telephone interviews with patients suffering from year-long severe chronic Type 2 inflammation and at least one co-morbid inflammatory condition. Seven participating academic centers in Europe interviewed asthma (Copenhagen and Leuven), CRSwNP (London, Amsterdam and Crete) and/or AD (Oldenburg and Zurich) patients on patient characteristics, disease severity, shortcomings of current care pathways and suggestions for improvement of care. Transcripts were analyzed using an inductive thematic analysis approach. Results: Eighty-one patients with severe Type 2 inflammation and comorbidities were interviewed. Similar needs were recognized by patients with Type 2 inflammation, with both a lack of coordination in care and a lack of a real cure reported as being most frustrating. However, several needs are specific to asthma, CRSwNP and AD. Suggestions for improvement of care were generic across diseases, such as the implementation of a multidisciplinary approach, the improved facilitation of access to better treatments, the increase of general awareness on disease burden, and better educational programs for healthcare providers and patients. Of note, patients with CRSwNP also stated the need for alternatives to sinus surgery, whereas patients with asthma requested better medical care to prevent exacerbations and patients with AD would warmly welcome the reimbursement of emollients. Conclusion: Patients with asthma, CRSwNP and AD have shared unmet needs that need to be addressed by physicians, the academic community and health policy makers. This survey provides unique recommendations made by patients for the implementation of better care

Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA)

The objective of the Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA) was to identify where and how stake- holder information could be incorporated in the ICES fisheries advice process. It adopted an operational definition of the concept of perception, where perceptions result from observations, interpreted in light of experience, that can be supported by data, information and knowledge to generate evidence about them. Stakeholder information can be either structured (e.g. routinely collected information in a standardized format) or unstructured (e.g. experiential information) and either of those can inform decisions made during the production of ICES advice. Most notably, the group identified there was a need to engage with stakeholders earlier in the process, i.e. before benchmarks meetings take place and before preliminary assessment results are used as the basis to predict total allowable catches for upcoming advice (Figure 4.2). It was therefore recommended to include in the ICES process the organisation of pre-bench- mark/roadmap workshops where science and data needs of upcoming benchmarks can be iden- tified, followed by making arrangements how scientists and stakeholders can collaborate to ac- cess, prepare for use (where relevant) and document the structured and unstructured infor- mation well ahead of the benchmark meetings. It was also recommended to organise ‘sense-checking’ sessions with stakeholders when prelim- inary assessments are available but not yet used as the basis for advisory production. This would allow stakeholders and assessment scientists to verify available knowledge and data against stock perceptions and provide additional considerations relevant for the production of TAC ad- vice. Next to these two additional activities, it is recommended that communication on differ- ences in stakeholder perception or data derived perceptions are communicated within the ICES assessment reports as well as in the ICES advice in a transparent manner. Not only should dif- ferences or similarities be documented and communicated, in those cases where there are differ- ences in perception between ICES stock assessments and stakeholders, a working group, external to the assessment working groups, should evaluate these differences and describe whether these differences can be logically explained or require further investigation. This outcome of this pro- cess may potentially lead to new data collection or additional analyses suitable for input to benchmarks. Essential in this entire process is making sure the same language is spoken between scientists and stakeholders, that there are clear and transparent processes in place on how to deal with stakeholder information and communicate clearly how this information is used in the prepara- tion of ICES advice.info:eu-repo/semantics/publishedVersio

Impact of the first COVID lockdown on accident- and injury-related pediatric intensive care admissions in Germany - a multicenter study

Children’s and adolescents’ lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017–2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85–1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93–1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57–1.02 and 0.26 (0.05–0.75)), whereas household and leisure accidents increased (1.33 (1.06–1.66) and 1.34 (1.06–1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38–1.16) and 2.09 (1.19–3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42–1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51–3.02)), but decreased in adolescent girls (0.56 (0.32–0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation

Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA)

The objective of the Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA) was to identify where and how stakeholder information could be incorporated in the ICES fisheries advice process. It adopted an operational definition of the concept of perception, where perceptions result from observations, interpreted in light of experience, that can be supported by data, information and knowledge to generate evidence about them. Stakeholder information can be either structured (e.g. routinely collected information in a standardized format) or unstructured (e.g. experiential information) and either of those can inform decisions made during the production of ICES advice. Most notably, the group identified there was a need to engage with stakeholders earlier in the process, i.e. before benchmarks meetings take place and before preliminary assessment results are used as the basis to predict total allowable catches for upcoming advice (Figure 4.2). It was therefore recommended to include in the ICES process the organisation of pre-benchmark/roadmap workshops where science and data needs of upcoming benchmarks can be identified, followed by making arrangements how scientists and stakeholders can collaborate to access, prepare for use (where relevant) and document the structured and unstructured information well ahead of the benchmark meetings. It was also recommended to organise ‘sense-checking’ sessions with stakeholders when preliminary assessments are available but not yet used as the basis for advisory production. This would allow stakeholders and assessment scientists to verify available knowledge and data against stock perceptions and provide additional considerations relevant for the production of TAC advice. Next to these two additional activities, it is recommended that communication on differences in stakeholder perception or data derived perceptions are communicated within the ICES assessment reports as well as in the ICES advice in a transparent manner. Not only should differences or similarities be documented and communicated, in those cases where there are differences in perception between ICES stock assessments and stakeholders, a working group, external to the assessment working groups, should evaluate these differences and describe whether these differences can be logically explained or require further investigation. This outcome of this process may potentially lead to new data collection or additional analyses suitable for input to benchmarks. Essential in this entire process is making sure the same language is spoken between scientists and stakeholders, that there are clear and transparent processes in place on how to deal with stakeholder information and communicate clearly how this information is used in the preparation of ICES advice.Peer reviewe

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known