Pilgrimages and Local Islam on Java

For muslims with sufficient means at their disposal, the hajj the pilgrimage to Mecca, is one of the ritual obligations of their faith. It is, however, not the only pilgrimage that is made by Muslims. In almost all Islamic countries one finds sacred places that are visited by pilgrims. Indonesia, for example, has thousands of Islamic pilgrim sites scattered over the many islands. Most of them are only of local or regional importance, but some are national or even internationally renoened religious centres. The largest pilgrim sites attract hundreds of thousands of visitors each year. For a great number of sanctuaries, it is not posibble to establish when the site become a pilgromage site. Some date from pre-Islamic times and at a later date were incorporated into the Islamic tradition.DOI: 10.15408/sdi.v5i2.75

Roger Tol, Kees van Dijk & Greg Acciaioli, eds, Authority and Enterprise among the Peoples of South Sulawesi

This reader about the Makassarese and Buginese in South Sulawesi and beyond contains ten interesting articles written by historians, philologists, and anthropologists. At first sight the subject matters do not seem to have much in common, but careful reading proves that there are important and unexpected connections. Above all they have to do with unequality, hierarchy, power, commerce, external influences, tradition, and progress. The opening article by Christian Pelras deals with the import..

Roger Tol, Kees van Dijk & Greg Acciaioli, eds, Authority and Enterprise among the Peoples of South Sulawesi

This reader about the Makassarese and Buginese in South Sulawesi and beyond contains ten interesting articles written by historians, philologists, and anthropologists. At first sight the subject matters do not seem to have much in common, but careful reading proves that there are important and unexpected connections. Above all they have to do with unequality, hierarchy, power, commerce, external influences, tradition, and progress. The opening article by Christian Pelras deals with the import..

Rescue of Murine F508del CFTR Activity in Native Intestine by Low Temperature and Proteasome Inhibitors

Most patients with Cystic Fibrosis (CF) carry at least one allele with the F508del mutation, resulting in a CFTR chloride channel protein with a processing, gating and stability defect, but with substantial residual activity when correctly sorted to the apical membranes of epithelial cells. New therapies are therefore aimed at improving the folding and trafficking of F508del CFTR, (CFTR correctors) or at enhancing the open probability of the CFTR chloride channel (CFTR potentiators). Preventing premature breakdown of F508del CFTR is an alternative or additional strategy, which is investigated in this study. We established an ex vivo assay for murine F508del CFTR rescue in native intestinal epithelium that can be used as a pre-clinical test for candidate therapeutics. Overnight incubation of muscle stripped ileum in modified William's E medium at low temperature (26°C), and 4 h or 6 h incubation at 37°C with different proteasome inhibitors (PI: ALLN, MG-132, epoxomicin, PS341/bortezomib) resulted in fifty to hundred percent respectively of the wild type CFTR mediated chloride secretion (forskolin induced short-circuit current). The functional rescue was accompanied by enhanced expression of the murine F508del CFTR protein at the apical surface of intestinal crypts and a gain in the amount of complex-glycosylated CFTR (band C) up to 20% of WT levels. Sustained rescue in the presence of brefeldin A shows the involvement of a post-Golgi compartment in murine F508del CFTR degradation, as was shown earlier for its human counterpart. Our data show that proteasome inhibitors are promising candidate compounds for improving rescue of human F508del CFTR function, in combination with available correctors and potentiators

Spontaneous rescue from cystic fibrosis in a mouse model

BACKGROUND: From the original Cftr(TgH(neoim)Hgu )mutant mouse model with a divergent genetic background (129P2, C57BL/6, MF1) we have generated two inbred Cftr(TgH(neoim)Hgu )mutant strains named CF/1-Cftr(TgH(neoim)Hgu )and CF/3-Cftr(TgH(neoim)Hgu), which are fertile and show normal growth and lifespan. Initial genome wide scan analysis with microsatellite markers indicated that the two inbred strains differed on the genetic level. In order to further investigate whether these genetic differences have an impact on the disease phenotype of cystic fibrosis we characterised the phenotype of the two inbred strains. RESULTS: Reduced amounts, compared to wild type control animals, of correctly spliced Cftr mRNA were detected in the nasal epithelia, lungs and the intestine of both inbred Cftr(TgH(neoim)Hgu )strains, with higher residual amount observed for CF/1-Cftr(TgH(neoim)Hgu )than CF/3-Cftr(TgH(neoim)Hgu )for every investigated tissue. Accordingly the amounts of wild type Cftr protein in the intestine were 9% for CF/1-Cftr(TgH(neoim)Hgu )and 4% for CF/3-Cftr(TgH(neoim)Hgu). Unlike the apparent strain and/or tissue specific regulation of Cftr mRNA splicing, short circuit current measurements in the respiratory and intestinal epithelium revealed that both strains have ameliorated the basic defect of cystic fibrosis with a presentation of a normal electrophysiology in both tissues. CONCLUSION: Unlike the outbred Cftr(TgH(neoim)Hgu )insertional mouse model, which displayed the electrophysiological defect in the gastrointestinal and respiratory tracts characteristic of cystic fibrosis, both inbred Cftr(TgH(neoim)Hgu )strains have ameliorated the electrophysiological defect. On the basis of these findings both CF/1-Cftr(TgH(neoim)Hgu )and CF/3-Cftr(TgH(neoim)Hgu )offer an excellent model whereby determination of the minimal levels of protein required for the restoration of the basic defect of cystic fibrosis can be studied, along with the modulating factors which may affect this outcome

Mouse models of cystic fibrosis: Phenotypic analysis and research applications

AbstractGenetically modified mice have been studied for more than fifteen years as models of cystic fibrosis (CF). The large amount of experimental data generated illuminates the complex multi-organ pathology of CF and raises new questions relevant to human disease. CF mice have also been used to test experimental therapies prior to clinical trials. This review recapitulates the major phenotypic traits of CF mice and highlights important new findings including aberrant alveolar macrophages, bone and cartilage abnormalities and abnormal bioactive lipid metabolism. Novel data are presented on the intestinal and nasal physiology of F508del-CFTR CF mice backcrossed onto different genetic backgrounds. Caveats, and sources of variability including age, gender and animal husbandry, are discussed. Interspecies differences limit comparison of lung pathology in CF mice to the human disease. The recent development of genetically modified pigs and ferrets heralds the application of more advanced animal models to CF research and drug development

Subanalytic sets and feedback control

AbstractThe theory of subanalytic sets is used to prove: If a real analytic control system is completely controllable, then for every point p in the state space there exists a piecewise analytic feedback control that steers every state into p

Modelling the impact of bias in fecal immunochemical testing on long-term outcomes of colorectal cancer screening

Background: As the impact of unmanaged bias (i.e. systematic source of inaccuracy) in fecal immunochemical test (FIT) analytical performance on long-term colorectal cancer (CRC) outcomes is unknown, we assessed the impact bias in FIT performance in an ongoing FIT-based CRC screening program.Methods: This study consisted of two parts: cross-sectional observational data analysis to estimate change in short-term outcomes and microsimulation modelling to estimate change in long-term outcomes assuming different levels of bias by assuming 15 % lower up to 15 % higher Hemoglobin detected in the stool compared to observed. Two scenarios were considered: bias occurring 1) one-time only, due to the occasional bias associated with the FIT kits used in 2020 and 2) consistently due to a constant bias associated with the FIT kits used from 2020 onwards. Results: With a hypothetical bias of −15 % to +15 %, we observed a positivity rate ranging from 6.7 % to 7.8 %, and a detection rate for CRC between 0.65 % and 0.68 %. Single biases in FIT performance resulted in less than 0.1 % change in long-term CRC screening outcomes, while consistent biases resulted in a much larger change (up to 1.4 % in CRC cases and CRC-related deaths and up to 2.07 % in total costs). Detecting lower Hemoglobin concentrations resulted in a relatively larger change on long-term CRC outcomes in comparison to positive bias. Conclusions: Because of the substantial impact of consistent FIT bias, it is important to set evidence-based acceptance criteria of bias on long-term CRC screening outcomes and in particular, the introduction of an asymmetrical or upward shifted tolerance interval for FIT bias.</p

Low skeletal muscle mass as a risk factor for postoperative delirium in elderly patients undergoing colorectal cancer surgery

Background: Both low skeletal muscle mass (LSMM) and delirium are frequently seen in elderly patients. This study aimed to investigate the association between preoperative LSMM and postoperative delirium (POD) in elderly patients undergoing colorectal cancer (CRC) surgery and to design a model to predict POD. Patients and methods: This is a retrospective observational cohort study. Patients aged 70 years or older undergoing CRC surgery from January 2013 to October 2015 were included in this study. The cross-sectional skeletal muscle area at the level of the third lumbar vertebra using computed tomography was adjusted for patients' height, resulting in the skeletal muscle index. The lowest quartile per sex was defined as LSMM. Short Nutritional Assessment Questionnaire for Residential Care and KATZ-Activities of Daily Living were used to define malnourishment and physical dependency, respectively. POD was diagnosed using the Delirium Observational Screening Scale and geriatricians' notes. Results: Median age of the 251 included patients was 76 years (IQR, 73-80 years), of whom 56% of patients were males, 24% malnourished, and 15% physically impaired. LSMM and POD were diagnosed in 65 and 33 (13%) patients, respectively. POD occurred significantly more in patients with LSMM (25%) compared with patients without LSMM (10%), P=0.006. In the multivariate analysis, age, history of delirium, and LSMM were significantly associated with POD. In addition, this effect increased in patients with LSMM and malnourishment (P=0.019) or physical dependency (P=0.017). Conclusion: Age, history of delirium, LSMM, and malnourishment or physical dependency were independen

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients