The comparison of the three assays for determination of fecal calprotectin in inflammatory bowel disease

Fecal calprotectin is a biomarker for monitoring inflammatory bowel disease (IBD) activity. Our aim, therefore, was to evaluate two new assays, the point of care test Quantum Blue and the Liaison Calprotectin with respect to the Calprest, commonly used assay, and to determine their performance for IBD diagnosis. We included 73 prospective patients with IBD. Fecal calprotectin was measured and analysed with the routine Calprest assay and two recently introduced assays, the Quantum Blue and the Liaison Calprotectin. Furthermore, we compared the results by Bland and Altman analysis, and Passing-Bablok regression. We observed no difference in median calprotectin values obtained by the Calprest (94.6 µg/g, 95%CI 66.5 to 166.1) and Liaison assay (101.0 µg/g, 95%CI 48.1 to 180.1) whereas significantly higher concentrations were obtained with the Quantum Blue assay (240.0 µg/g, 95%CI 119.9 to 353.2). The mean absolute and relative difference between the Calprest and Quantum Blue methods was statistically significant (- 162.3 µg/g and - 143.1%). Mean absolute difference between the Calprest and Liaison calprotectin methods was positive (2.2 µg/g). The agreement between assays revealed that Quantum Blue and Calprest have fair agreement with Kappa coefficient of 0.38 (95%CI 0.26 to 0.51). Liaison Calprotectin and Calprest revealed moderate agreement with a weak Kappa coefficient of 0.47 (95%CI 0.32 to 0.62). Clinicians should be aware of these differences between the assays and avoid comparison of their respective results

Invasive alien species of plants as an object of biology and science classes in primary school

Invasive alien species represent a threat to ecology and economy and may can even cause diseases. To tackle this problem properly we have to warn, inform and educate wider public and raise awareness as well as teach children about this problem from the earliest stages of education. In my thesis I examined invasive alien plant species using reference books. Based on the handbook Invazivne tujerodne rastline pri pouku naravoslovja in biologije (Strgulc Krajšek and Bačič, 2013a), I prepared additional materials for biology teachers and natural sciences teachers, as well as for children in primary school, I also reviewed primary school websites and determined the degree of quality the teachers assign to invasive species for their lessons, if at any all. In addition I examined syllabuses covering all natural science subjects. On the bases of my findings I included the topic of invasive alien species in the syllabuses, and I, moreover, prepared a list of existing textbooks to help teaching

Lone wolf terrorists - case study of Eric Robert Rudolph

V 21. stoletju vsakdanje življenje poteka po ustaljenih tirnicah, toda po svetu smo izpostavljeni povečani nevarnosti terorističnih napadov, saj smo lahko pogosto soočeni z odmevnimi morilskimi pohodi, ki v družbi izzovejo občutke strahu, negotovosti in apatijo. Izvedeni so teroristični napadi, ko posamezniki svoja dejanja izvajajo povsem samostojno, kjer je preizkušena nova oblika – napad terorista samotarja (angl. lone wolf terrorist). Gre za medijsko odmevne primere, ki sprožijo val ugibanj o motivih in vzrokih za delovanje, saj se na svoj napad pripravljajo izolirano, neodvisno in na lastno pobudo ter po navadi iz zavetja lastnega doma, zato je njihovo ravnanje nemogoče predvideti. Za pripravo in izvedbo svojih dejanj torej ne potrebujejo visoke tehnologije, večjih količin eksploziva ali finančnih sredstev, prav tako ne veliko časa. V večini primerov so teroristi samotarji visoko izobraženi posamezniki z izoblikovanim političnim, ideološkim ali kulturnim prepričanjem, ki se s spretno uporabo virtualne skupnosti ali podporo teroristične skupne v osami radikalizirajo in izvedejo napad. Takšen napad je 27. julija 1996 izvedel desničarski skrajnež Eric Robert Rudolph, ki je v Atlanti na olimpijskih igrah aktiviral doma izdelano cevno bombo. Njegov razlog za napad je bil političen: povzročitev čim večje finančne izgube in izgube nadzora nad dogajanjem ter s tem namenom doseči ukinitev izvajanja splavov v ZDA. Na napad se je temeljito pripravljal, saj je po aretaciji priznal, da je ubijal zavestno in da ne obžaluje svojih dejanj. V izogib smrtni kazni je priznal krivdo in bil obsojen na kazen doživljenjskega zapora brez možnosti pogojne izpustitve. Obveščevalno-varnostne službe, policija in anonimni hekerji se skupaj trudijo prepoznati in prestreči potencialne teroriste samotarje, vendar si le-ti izbirajo vse drznejše napade, saj se na ta način izmuznejo nadzornemu sistemu in udarijo tam, kjer preiskovalci ne pričakujejo. Teroristi samotarji razvijajo tehniko, kot je npr. šifriranje sporočil, s katero poskušajo zaobiti obrambo visoke tehnologije. Sprašujemo se, kako bi končali dobo terorja, saj teroristi iščejo nove in bolj sofisticirane načine, kako znova napasti.In the 21st Century everyday life follows a predictable path, but throughout the world we are exposed to intensified danger of terrorist attackswe’re often faced with attention-grabbing death marches, which in society provoke feelings of fear, insecurity and apathy. Terrorist attacks are carried out, when the individuals execute their actions completely autonomously, where a new form is tested – an attack of a lone wolf terrorist. Cases like that are much noticed in the media and they start a wave of guessing about the motives and causes for the action, since the aggressors prepare for their attack in isolation, independently and on their own initiative, usually from the shelter of their own home, therefore their behaviour is impossible to predict. For the preparation of the execution of their actions they, thus, don’t need high technology, larger amounts of explosives or financial means or even a lot of time. In the majority of cases the lone wolf terrorists are highly educated individuals with formed political, ideological and cultural opinion, who with a skilful usage of virtual society or support from a terrorist group in isolation radicalize themselves and carry out an attack. Such an attack was carried out on 27th July 1996 by a rightist extremist Eric Robert Rudolph, who at the Olympic games in Atlanta activated a homemade pipe bomb. His reason for the attack was political: to cause as much financial damage and loss of control over the happening and thus achieve an abolition of abortions in USA. His preparations for the attack were extensive, since after the arrest he admitted that he killed wilfully and that he has no remorse. To avoid death sentence, he admitted his guilt and was condemned to life in prison without a possibility of parole. Intelligence and security services, police and anonymous hackers are collectively trying to recognize and intercept the potential lone wolf terrorists, but the attacks of the latter are becoming more and more bold, since in such a way they avoid the control system and hit where the investigators don’t expect. The lone wolf terrorists are developing a technique, such as coded messages, with which they try to bypass the defence of the high technology. Our questions are concerned with how to end the era of terror, since the terrorist keep seeking new and more sophisticated means for yet another attack

Spolne zlorabe otrok na internetu in pravne možnosti za uporabo prikritih preiskovalnih ukrepov : diplomsko delo univerzitetnega študija

V diplomskem delu obravnavamo tematiko spolnih zlorab otrok na internetu in pravne možnosti za uporabo prikritih preiskovalnih ukrepov. Spolna zloraba otrok na internetu je eno od področij kriminalitete z največjim temnim poljem, saj predstavlja glavni problem obravnavanja kaznivega dejanja, kako se dokopati do materialne resnice. Naša in tudi evropska zakonodaja ščitita otroke oziroma mladoletnike in v predpisih točno opredeljujeta, katera so kazniva dejanja zoper spolno nedotakljivost, kakšni so zakonski znaki, ki definirajo takšna dejanja, in kazni, ki so za to predpisane. Navsezadnje pa tudi zakonodaja ne pomaga, če takšna dejanja ostanejo skrita, zato utegnejo biti prikriti preiskovalni ukrepi (v nadaljevanju PPU) ključna sestavina za odkrivanje in preprečevanje kriminalitete zoper spolno nedotakljivost otrok v povezavi s kibernetskim prostorom oziroma s pomočjo interneta. V osrednjem delu naloge smo prikazali tipičen način storitve kaznivega dejanja s tega področja in enega od načinov in postopkov odkrivanja, s katerimi se srečujejo vladne organizacije v predkazenskem postopku. Ker gre za občutljivo področje, ki v veliki meri posega v človekove pravice in svoboščine, vsaka posamezna uporaba PPU pa vzbuja velik odziv javnosti, smo se v diplomskem delu osredotočili na pravno ureditev v Republiki Sloveniji in njeno problematiko odkrivanja, zbiranja in dokazovanja zlorab in nasilja nad otroci (zlasti v primeru spoprijateljevanja storilcev z otroki preko interneta). Pri tem poskušamo predstaviti, katere varovalke je zakonodajalec uzakonil, da bi preprečil nedovoljeno uporabo PPU, in katera pravna sredstva imamo na voljo zoper takšno dejanje, saj se organi odkrivanja in pregona vse pogosteje srečujejo s specifičnimi težavami pri odkrivanju internetnih storilcev spolnih zlorab otrok.In the thesis, we discuss the issue of online child sexual abuse and legal possibilities for the use of covert investigative measures. Online child sexual abuse is one of the fields of criminality with the largest dark field, since the main problem of the discussed crime investigation is how to determine the substantive truth. Our legislation as well as the European one protects children or minors and through regulations exactly defines crimes against sexual inviolability, statutory signs, which define such crimes, and penalties for them. At the end, even the legislation does not help, if such acts remain hidden, therefore covert investigative measures (in continuation CIM) could be of key-importance in identifying and preventing of crime against sexual inviolability of children in connection with the cyberspace or the internet. In the main part of the thesis we presented a typical committing of crime from this field and one of the ways and procedures of its detection, faced by governmental organization in pre-trials. Because it is a sensitive area that heavily interferes with human rights and freedoms and every single use of CIM provokes a great public response, we focused on legal regulations in the Republic of Slovenia and the issue of identification, collection and proving of child abuse and violence against them (in particular online grooming case). By doing so we tried to present, which safety measures were legislated by the legislator in order to prevent unauthorized use of CIM and which legal means do we have against such acts, since law enforcement authorities increasingly face specific problems in identifying online child sexual offenders

Hip stress distribution - Predictor of dislocation in hip arthroplasties. A retrospective study of 149 arthroplasties.

Dislocation after hip arthroplasty is still a major concern. Recent study of the volumetric wear of the cup has suggested that stresses studied in a one-legged stance model could predispose arthroplasty dislocation. The aim of this work was to study whether biomechanical parameters of contact stress distribution in total hip arthroplasty during a neutral hip position can predict a higher possibility of the arthroplasty dislocating. Biomechanical parameters were determined using 3-dimensional mathematical models of the one-legged stance within the HIPSTRESS method. Geometrical parameters were measured from standard anteroposterior X-ray images of the pelvis and proximal femora. Fifty-five patients subjected to total hip arthroplasty that later suffered dislocation of the head and, for comparison, ninety-four total hip arthroplasties that were functional at least 10 years after the implantation, were included in the study. Arthroplasties that suffered dislocation had on average a 6% higher resultant hip force than the control group (p = 0.004), 11% higher peak stress on the load-bearing area (p = 0.001) and a 50% more laterally positioned stress pole (p = 0.026), all parameters being less favorable in the group of unstable arthroplasties. There was no statistically significant difference in the gradient index or in the functional angle of the weight bearing. Our study showed that arthroplasties that show a tendency to push the head out of the cup in the representative body position-the one-legged stance-are prone to dislocation. An unfavorable resultant hip force, peak stress on the load bearing and laterally positioned stress pole are predictors of arthroplasty dislocation

Remission Is Maintained after Switch from Dose-Optimised Intravenous Treatment to Subcutaneous Treatment with Vedolizumab in Inflammatory Bowel Disease

Background and Objectives: The subcutaneous (SC) formulation of vedolizumab has proven to be effective for the maintenance of remission after intravenous induction. Little is known about the efficacy of switching from intravenous maintenance treatment to SC. We aimed to assess the real-world efficacy of switching to SC treatment and to assess the impact of a baseline treatment regimen. Materials and Methods: In this observational cohort study, adult patients with inflammatory bowel disease who were switched to SC vedolizumab maintenance treatment were enrolled. Patients after intravenous induction and patients who switched from intravenous maintenance treatment (every 8 weeks or every 4 weeks) were included. The SC vedolizumab dosing was 108 mg every 2 weeks, regardless of the previous regimen. The clinical, biochemical, and endoscopic disease activity parameters and vedolizumab serum concentrations at the time of the switch and at the follow-up were assessed. Results: In total, 135 patients (38% Crohn’s disease, 62% ulcerative colitis) were switched to SC vedolizumab treatment. The median time to the first follow-up (FU) was 14.5 weeks (IQR 12–26), and the median time to the second FU was 40 weeks (IQR 36–52). Nine patients (7%) discontinued SC vedolizumab treatment, with two-thirds of them discontinuing due to active disease. In all dosing regimens, there were no significant changes in the clinical scores and CRP at the baseline and first and second FUs. Clinical and biochemical remission appeared to be maintained irrespective of the previous dosing regimen. Conclusions: The results of this real-world study suggest that the maintenance of clinical and biomarker remission can be achieved in patients who switched from intravenous to SC vedolizumab. The baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes

Endoscopic remission can be predicted by golimumab concentrations in patients with ulcerative colitis treated with the changed label.

BACKGROUND: In 2018, the European Medicines Agency (EMA) replaced a fixed 50 mg every 4-week maintenance regimen of golimumab for ulcerative colitis (UC) patients weighing 10.7 µg/ml were a strong predictor for achievement and maintenance of endoscopic remission during the first year of treatment, while concentrations <5.1 µg/ml identified the opposite. CONCLUSION: One-third of the patients reached and maintained endoscopic remission during the first year of golimumab treatment, but the need for dose optimization to 100 mg every 4 weeks of maintenance was high in patients weighing <80 kg. Golimumab concentrations <5.1 µg/ml at week 6 identified patients who are unlikely to reach and maintain endoscopic remission with the new, flexible EMA label.status: publishe

Peak Concentrations of Ustekinumab After Intravenous Induction Therapy Identify Patients With Crohn's Disease Likely to Achieve Endoscopic and Biochemical Remission.

BACKGROUND & AIMS: Little is known about the relationship between ustekinumab exposure during the first 2 weeks of treatment and outcomes of patients with Crohn's disease (CD). We investigated the relationship between serum concentrations of ustekinumab during the first 2 weeks of treatment and endoscopic and biochemical remission in patients with CD. METHODS: In a prospective observational study, we measured concentrations of ustekinumab in serum samples from 41 consecutive patients who started treatment with ustekinumab (approximately 6 mg/kg, intravenously, then 90 mg every 8 weeks), due to endoscopic markers of active CD, at a single center from October 2017 through January 2019. We measured ustekinumab exposure parameters during the first 2 weeks (peak concentration measured immediately after intravenous infusion, week 2 concentration, and area under the curve through week 2). We investigated the correlation between these parameters and endoscopic remission (simple endoscopic score for CD scores of 3 or less without ulceration, assessed centrally) and biochemical remission (level of fecal calprotectin below 100 mg/kg) using the Mann-Whitney U test. RESULTS: Endoscopic remission was achieved in 10 patients (24.4%) at week 24; biochemical remission was achieved in 17 patients (41.5%) at week 8, 17 patients (41.5%) at week 16, and 21 patients (51.2%) at week 24. Peak concentrations associated with endoscopic remission (area under the receiver operating characteristic curve, 0.717; 95% CI, 0.517-0.916); 6 of 13 patients (46%) with peak concentrations above 105 μg/mL (upper tercile) achieved endoscopic remission, compared with only 1 of 14 patients (7%) with peak concentrations below 88 μg/mL (lower tercile). All exposure parameters during the first 2 weeks were associated with biochemical remission. There was no significant difference between the associations of peak concentrations, week-2 concentrations, area under the curve through week 2, or later exposure measures (at weeks 4 and 8) with biochemical or endoscopic remission. CONCLUSIONS: In a prospective study, we found that serum concentrations of ustekinumab as early as 1 hour after intravenous infusion might be used to identify patients with CD most likely to achieve endoscopic remission. This early measurement might be used to optimize treatment of CD.status: Published onlin

Ustekinumab Dosing Individualization in Crohn's Disease Guided by a Population Pharmacokinetic-Pharmacodynamic Model

Ustekinumab is a monoclonal antibody used in Crohn's disease (CD). Dose optimization in case of non-response and the role of pharmacokinetic-pharmacodynamic (PK-PD) monitoring remain unresolved dilemmas in clinical practice. We aimed to develop a population PK-PD model for ustekinumab in CD and simulate efficacy of alternative dosing regimens. We included 57 patients and recorded their characteristics during 32 weeks after starting with ustekinumab therapy. Serum ustekinumab concentration was prospectively measured and fecal calprotectin (FC) concentration was used to monitor the disease activity. Ustekinumab PK-PD was described by a two-compartment target-mediated drug disposition model linked to an indirect response model. Lower fat-free mass, higher serum albumin, previous non-exposure to biologics, FCGR3A-158 V/V variant and lower C-reactive protein were associated with higher ustekinumab exposure. Model-based simulation suggested that 41.9% of patients receiving standard dosing achieve biochemical remission at week 32. In patients not achieving remission with standard dosing at week 16, transition to 4-weekly subcutaneous maintenance dosing with or without intravenous reinduction resulted in comparably higher remission rates at week 32 (51.1% vs. 49.2%, respectively). Our findings could be used to guide stratified ustekinumab treatment in CD, particularly in patients with unfavorable characteristics, who might benefit from early transition to 4-weekly maintenance dosing