Immune checkpoint inhibitors are a novel class of cancer treatment that have improved outcomes for a subset of cancer patients. They work by antagonising inhibitory immune pathways, thereby augmenting immune-mediated antitumour responses. However, immune activation is not cancer-specific and often results in the activation of immune cells in non-cancer tissues, resulting in off-target immune-mediated injury and organ dysfunction. Diarrhoea and gastrointestinal tract inflammation are common and sometimes serious side-effects of this type of therapy. Prompt recognition of gastrointestinal toxicity and, in many cases, rapid institution of anti-inflammatory or biologic therapy (or both) is required to reverse these complications. Management of organ-specific complications benefits from multidisciplinary input, including engagement with gastroenterologists for optimal management of immune checkpoint inhibitor-induced enterocolitis. In this British Society of Gastroenterology endorsed guidance document, we have developed a consensus framework for the investigation and management of immune checkpoint inhibitor-induced enterocolitis.

Background Immune-related diarrhoea/colitis (ir-D/C) is a common adverse event of immune checkpoint inhibitor (ICI) therapy. Guidelines recommend corticosteroid (CS) treatment; however, the average treatment duration for ir-D/C remains poorly defined. Methods All advanced melanoma patients treated with ICI therapy at the Royal Marsden Hospital between 2011 and 2016 were reviewed to identify ir-D/C cases alongside clinical variables. Results 117 any-grade ir-D/C episodes occurred in 109 (21%) patients out of a total of 519 patients treated (ipilimumab=77 episodes, anti-PD1=17 (nivolumab or pembrolizumab), ipilimumab and nivolumab=23 (ipi+nivo)) (seven patients had ir-D/C more than once on different lines of treatment) and >/=grade 3 ir-D/C occurred most frequently (63/519 patients (12%) vs 29/519 (5%) grade 1, and 25/519 (5%) grade 2). Median onset (days) of all-grade ir-D/C after starting ICI therapy was 41 for ipilimumab (IQR 24 to 59, n=77), 91 for anti-PD1 (IQR 46 to 355, n=17) and 45 for ipi+nivo (IQR 24 to 67, n=23). In 71/117 (61%) patients, ir-D/C episodes were treated with CS (17% grade 2; 79% grade 3/4): 54 being steroid-responsive; 17 being steroid-refractory and received additional anti-tumor necrosis factor (TNF) treatment. Median grade 3 ir-D/C CS duration was similar across treatments, averaging 58 days. Median overall CS duration (days) was longer in the grade 3/4 D/C steroid-refractory group (94 vs 45 days). Infection developed in 11/71 (15%) CS recipients and in 6/17 (35%) anti-TNF recipients. In 65/117 (55%) patients, ir-D/C episodes were investigated with flexible sigmoidoscopy. Of these patients, 38/65 (58%) had macroscopic colitis and 12/65 (18%) had microscopic colitis. The steroid-refractory group had more macroscopic changes, 13/17 (76%), than the steroid-responsive group, 22/41 (54%). Conclusion Rates of grade 3 ir-D/C were higher than reported in clinical trials. The 58-day median duration of CS therapy for grade 3 ir-D/C places a significant number of patients at risk of complications. We demonstrate that microscopic colitis is an important subgroup, advocating biopsies in ir-D/C even with macroscopically normal bowel.

Wireless networked control systems (WNCSs) provide a key enabling technique for Industrial Internet of Things (IIoT). However, in the literature of WNCSs, most of the research focuses on the control perspective and has considered oversimplified models of wireless communications that do not capture the key parameters of a practical wireless communication system, such as latency, data rate, and reliability. In this article, we focus on a WNCS, where a controller transmits quantized and encoded control codewords to a remote actuator through a wireless channel, and adopt a detailed model of the wireless communication system, which jointly considers the interrelated communication parameters. We derive the stability region of the WNCS. If and only if the tuple of the communication parameters lies in the region, the average cost function, i.e., a performance metric of the WNCS, is bounded. We further obtain a necessary and sufficient condition under which the stability region is $n$ -bounded, where $n$ is the control codeword blocklength. We also analyze the average cost function of the WNCS. Such analysis is nontrivial because the finite-bit control-signal quantizer introduces a nonlinear and discontinuous quantization function that makes the performance analysis very difficult. We derive tight upper and lower bounds on the average cost function in terms of latency, data rate, and reliability. Our analytical results provide important insights into the design of the optimal parameters to minimize the average cost within the stability region.

We propose a framework for designing observers possessing global convergence properties and desired asymptotic behaviors for the state estimation of nonlinear systems. The proposed scheme consists in combining two given continuous-time observers: One, denoted as global, ensures (approximate) convergence of the estimation error for any initial condition ranging in some prescribed set, while the other, denoted as local, guarantees a desired local behavior. We make assumptions on the properties of these two observers, and not on their structures, and then explain how to unite them as a single scheme using hybrid techniques. Two case studies are provided to demonstrate the applicability of the framework. Finally, a numerical example is presented.

We study the design of state observers for nonlinear networked control systems (NCSs) affected by disturbances and measurement noise, via an emulation-like approach. That is, given an observer designed with a specific stability property in the absence of communication constraints, we implement it over a network, and we provide sufficient conditions on the latter to preserve the stability property of the observer. In particular, we provide a bound on the maximum allowable transmission interval (MATI) that guarantees an input-to-state stability (ISS) property for the corresponding estimation error system. The stability analysis is trajectory-based, utilizes small-gain arguments, and exploits a persistently exciting property of the scheduling protocols. This property is key in our analysis and allows us to obtain significantly larger MATI bounds in comparison to the ones found in the literature. Our results hold for a general class of NCSs; however, we show that these results are also applicable to NCSs implemented over a specific physical network called WirelessHART (WH). The latter is mainly characterized by its multihop structure, slotted communication cycles, and the possibility to simultaneously transmit over different frequencies. We show that our results can be further improved by taking into account the intrinsic structure of the WH–NCS model. That is, we explicitly exploit the model structure in our analysis to obtain an even tighter MATI bound that guarantees the same ISS property for the estimation error system. Finally, to illustrate our results, we present analysis and numerical simulations for a class of Lipschitz nonlinear systems and high-gain observers.

Darovano humano mlijeko je najbolja zamjena za majčino mlijeko u okolnostima kad ona ne može hraniti svoje dijete. Sigurno ikvalitetno darovano humano mlijeko osiguravaju banke humanog mlijeka. S tim ciljem u Hrvatskoj banci tkiva i stanica Kliničkogbolničkog centra Zagreb osnovana je Banka humanog mlijeka u siječnju 2020. Rad Banke u skladu je sa Zakonom o primjeni ljudskihtkiva i stanica. U ovom radu prikazujemo rezultate njenog rada od otvaranja do lipnja 2020. godine. Iz logističkih razloga uzrokovanih epidemijom COVID-19 i potresom u Zagrebu Banka humanog mlijeka nije prikupljala mlijeko 43 dana.Mlijeko je darovala 31 majka. Medijan dobi bio je 31 godina a 81% ih je bilo visokoobrazovanih. U 52% slučajeva majke su počeledarivati mlijeko tri mjeseca nakon porođaja. Najviše darivateljica darovalo je mlijeko samo jedan put (45%). Medijan razdoblja darivanja bio je 46 dana. Većina (52%) darivateljica rodilo je prvi put, u očekivanom terminu porođaja (94%), djecu porođajne mase>2 500 gr. Samo troje od njihove djece (9%) bilo je na intenzivnom liječenju. Ukupno je prikupljeno 175,5 L mlijeka (prosječno5,7 L/darivateljici), od kojih je 151,5 L zadovoljilo zahtjeve ulazne kontrole kakvoće, a 141 L je bila i pasterizirana. Kritičan broj vijabilnih, aerobnih i fakultativnih bakterija imalo je 32,6% mješavina mlijeka pripremljenih za pasterizaciju, a nakon nje 8,9%. Za kliničkuprimjenu izdano je 78,7 L u tri jedinice intenzivnog liječenja novorođenčadi. Već u prvim mjesecima rada Banka humanog mlijekapokazala je važnost svog djelovanja. Kako bi mogli zadovoljiti potrebe za darovanim humanim mlijekom na nacionalnoj razini,potrebno je trajno podučavati/educirati majke o važnosti humanog mlijeka i promicati njegovo darivanje.

During the flu season that can impair human health, it is difficult to determine whether a patient has a bacterial or viral infection. The C-Reactive Protein marker is one of the markers in laboratory diagnostics that shows inflammatory processes in the body. The purpose of this study was to prove that the CRP marker is an indicator of bacterial infections and that it is presented in higher concentration in patients with bacterial infection than in patients with a viral infection. Therefore it is helpful in the differentiating bacterial infections from viral infections.

Abstract Objective: To determine the incidence of gliomas in Zenica - Doboj Canton. Moreover, to analyse its potential connection to sociodemographic characteristics and its distribution throughout municipalities of Zenica - Doboj Canton in the period of 2009-2019. Method: This retrospective, descriptive - analytical, 10 - year study included 146 patients from Zenica -Doboj Canton. Data were obtained and reviewed from patient’s medical records. Patients’ sociodemographic characteristics and pathohistological diagnosis were included in the study. Age, gender, and the place of birth were analysed and correlated with types and grades of glial tumors according to the World Health Organisation’s latest classification. Results: The study consisted of 146 patients including 84 (58%) males and 62 (42%) females. The most common pathohistological diagnosis was glioblastoma multiforme, a grade IV glioma in both females (26%) and males (35%), in total 91 (62%) patients, and the rarest was oligoastrocytoma, in 2 (1%) cases. The municipality of Kakanj had the highest incidence of glioma with 29 out of total of 146 cases (0.077%) and the highest incidence in females (0.069%) with 13 cases. The municipality of Vareš had the highest incidence of glioma (0.114%) with 5 out of 84 male cases, while in the cities of Breza and Olovo any cases with glioma were not detected The results showed statistically significant differences in incidences of gliomas according to the region of residence. Conclusion The analysis of data indicated that there are significant connections between the occurrence of gliomas and sociodemographic characteristics of patients from Zenica - Doboj Canton.

In today’s modern world, more than ever before, students are faced with entrepreneurship based on the use of information and communication technology (ICT) as a reasonable and justified career choice. Whether their career choice would be successful or not depends a lot on the level of system support through entrepreneurial ecosystem during their education. The main objective of this paper is to present the current assessment, indicate the problems and possible solutions regarding the entrepreneurial infrastructure, culture and potential of higher education institutions in Banja Luka, Bosnia and Herzegovina. To achieve this, we have researched the level of the system support to students for development and launch of their ICT based start-ups during and after their university education respecting different educational profiles and demographic characteristics. The research covers the sample of 436 students from seven higher education institutions in Banja Luka at their bachelor studies and includes focus groups, survey, descriptive and inferential statistical methods. We have found significant discrepancy between university ICT programs and infrastructure and student needs. For instance, a quite large number of students interested in ICT industry attended some kind of informal education from this domain and at the same time they were unaware that those and similar programs were freely available at their universities. In this paper we have identified those and similar gaps and compared our research results with similar results in other countries.

Introduction: Needlestick injuries (NSIs) are one of the most frequent routes of the transmission of bloodborne pathogens in health care settings and the substantial source of occupationally acquired bloodborne infections. They remain a significant problem for developing countries that lack the ability to implement more reliable technologies and available guidance because of the economic situation. The objectives of the study were to determine the frequency of NSIs among healthcare workers (HCWs) and supporting staff in primary health care, to investigate the factors that caused these injuries and to evaluate a set of implemented guides. Methods: A retrospective study of the Department of infection control records of NSIs between January 2003 and January 2016 was conducted. Incidence proportion (rate of injury risk) was calculated for each profession with reported NSIs. Results: A total of 156 NSIs and sharp injuries were reported to the Department of infection control during the 12-year period. Among the group of HCWs, medical nurses/technicians (54.49%) were the most common injured workers, and the lowest numbers were reported by a physical therapist and dental technicians (0.64%). In a total number of cases, support staff accounted for 16.67%. The most incidents occurred during the use of needles, in 146 (90.6%) cases. Calculated incidence proportion for medical doctors is 0.24%, 5.33% for dentists, and 13.8% for medical and dental nurses/technicians and laboratory technicians. For support staff, the calculated rate is 6.04%. Conclusions: At the primary health care level, the NSIs frequency among all employee profiles is lower and it is suggesting the possibility of underreporting cases. Healthcare facility management should consider introducing new and more reliable technologies to reduce the number of NSIs especially among nurses/technicians, laboratory technicians, and cleaning staff. Additional training and preventive measures should be directed towards the proper disposal of medical waste. Management of the Institution presented engagement to prevent the occurrence of NSIs, and it is a positive example for all countries in transition.