In modern market it is very important to deliver products to customers fast. That delivery can be on site or to customer's homes. In order to achieve that it is important to have enough goods stored in warehouses and prepared for delivery. It is not a good decision to clutter up warehouses with the goods because space is limited and expensive and it makes it more complicated to collect orders. Those are the reasons why it is important that number of stored goods converge to the exact number of product units that will be ordered in the future. Demand forecasting tries to solve that problem. In this work demand forecasting algorithm based on Long Short-Term Memory recurrent neural network is described and compared with demand forecasting algorithms developed by authors before.

A number of industrial wireless technologies have emerged over the last decade, promising to replace the need for wires in a variety of use cases. Except for customized time division multiple access (TDMA)-based wireless technologies that can achieve ultralow latency over a very limited area, wireless communication generally has reliability and latency issues when it comes to industrial applications. Closed loop communication requires high reliability (over 99%), limited jitter and latency, which poses a challenge especially over a wide area measuring in hundreds of meters. Extended coverage is promised with the advent of sub-GHz technologies, one of them being IEEE 802.11ah which is the only one that offers sufficient data rate for frequent bidirectional communication. Thus, we evaluated IEEE 802.11ah for low-latency time-critical control loops. We propose the network setup for adjusting the network dynamics to that of control loops, enabling limited jitter and high reliability. We explore the scalability of IEEE 802.11ah network hosting both control loops and monitoring sensors that periodically transmit measurements. Assigning the control loop end-nodes to dedicated restricted access window (RAW) slot results in over 99.99% successful deliveries. Furthermore, interpacket delay is concentrated around the cycle-time in the following or preceding beacon interval in case the beacon interval is at least half the value of the shortest cycle-time. Adjusting the beacon interval to the fastest control loop in the network ensures latency requirements at the cost of maximum achievable throughput and energy consumption.

Abstract Background In 2017 a new PN led clinic was established for immunotherapy patients. At the 1-year mark to ensure patients were satisfied with the service provision, a patient experience survey was conducted. The survey explored if patients felt comfortable in discussing side effects with the PN and if they felt part of their treatment related decisions. Importantly patients were asked if they had confidence and trust in the PN. Methods The survey was provided to all patients whom attended the PN led clinic from May 2017 to May 2018. The survey consisted of 10 closed questions using the Likert scale, with spaces provided for personal comments. Data collection period was 1.06.18 to 29.06.18. Estimated number of patients was 10. Results Questionnaires were provided to a total of 10 patients. Three questionnaires could not be provided to 3 patients whom attended the PN led clinic as they had died. Two patients did not respond back. 6/8 patients strongly agreed (SAg) to feeling comfortable in discussing treatment related side effects and 2/8 patients agreed (Ag). This same result was found when patients were asked if they felt involved in the decisions related to their care e.g. stopping immunotherapy treatment at 2 yrs. With respect to having confidence and trust with the advice and care provided by the PN, 7 patients SAg and 1 Ag. All patients felt that they were being listened to and had the opportunity to ask questions during their consultations (7 patients SAg and 1 Ag). Reassuringly all 8 patients said that they would recommend this service to their friends and family (7 patients SAg and 1 Ag). Conclusions This survey was to ensure patients were satisfied with being reviewed by a PN and as the service was new to the melanoma unit in 2017; it was vital that the patients had the opportunity to evaluate the service provision. With this positive feedback the clinic was expanded from September 2018 and to date 36 patients have now been seen within the PN led immunotherapy clinic and another patient experience survey is due. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Abstract Background Intratumour heterogeneity is recognised across different tumour types and has implications for therapeutic resistance. At present, clinical practice often relies upon molecular information derived from a single biopsy of a primary or metastatic tumour. This information guides treatment choice but may not be representative of the diversity of the tumour. It is currently difficult to evaluate how effectively a single region guides treatment decisions because the formalin-fixed residual surgical sample that is not paraffin embedded for diagnostic purposes is typically thrown away. Retention and homogenisation – ‘blending’- of this residual formalin-fixed leftover tumour tissue creates a more representative sample for analysis. DNA may be extracted from this sample for sequencing. Pilot data in kidney cancer has demonstrated the potential of this methodology for robust mutational calling, accurate determination of cancer cell fraction and the ability to discern clonal from subclonal variants. Such information may be clinically relevant; for example, discerning resistant subclones prior to treatment, or identifying clonal neoantigens worth targeting with immunotherapy. Trial design In order to establish the feasibility of homogenization as a potential companion diagnostic tool, our study aims to 1) identify the proportion of primary tumour cases that have left over tissue amenable to homogenization across multiple tumour types and 2) pilot homogenization across multiple tumour types. The molecular profile of the homogenate will be compared to that obtained from the diagnostic specimen using next generation sequencing techniques. This is a prospective non-interventional study (NCT03832062). Patients undergoing surgical intervention at The Royal Marsden Hospital (NHS Foundation Trust) with leftover tumour tissue from primary breast, colorectal, gastric, pancreatic, ovarian, renal cancer and sarcoma surgeries, as well as melanoma lymph node dissections will be included in the feasibility assessment. We plan to homogenise 500 cases across different tumour types. The study opened in September 2018 and is expected to run for 2 years. Clinical trial identification NCT03832062; Release date: February 2019. Legal entity responsible for the study Royal Marsden NHS Foundation Trust. Funding Ventana Medical Systems (a subsidiary of Roche). Disclosure L. Gallegos: Full / Part-time employment: Roche. S. Hill: Full / Part-time employment: Roche. A. Barhoumi: Full / Part-time employment: Roche. S. Stanislaw: Full / Part-time employment: Roche. M. Mendoza: Full / Part-time employment: Roche. J.M.G. Larkin: Research grant / Funding (institution): Roche; Advisory / Consultancy: Roche. N. Alexander: Full / Part-time employment: Roche; Shareholder / Stockholder / Stock options: Roche. S. Turajlic: Research grant / Funding (institution): Ventana Medical Systems (subsidiary of Roche). All other authors have declared no conflicts of interest.

Abstract Background ADATPeR is the first prospective study evaluating the role of anti-PD1 agents in the neoadjuvant setting prior to cytoreductive nephrectomy in treatment-naive patients with metastatic clear cell renal cell carcinoma (mccRCC). We performed multi-omic analyses to resolve spatial heterogeneity and temporal dynamics in putative biomarkers of response to anti-PD1 blockade. Methods In a single center study, patients received nivolumab (3mg/kg every 2 weeks) pre- and post-operatively until progressive disease (PD). Primary endpoint was safety, secondary endpoints were response evaluation and exploratory biomarker analysis. Multiregion tumour biopsies were obtained at baseline, on-treatment (week 9) and at PD. Whole-exome sequencing was performed to infer somatic mutations and predict candidate neoantigens (NAs). Tumour immune microenvironment was evaluated using a RNA-seq-derived immune signature and by stromal and intraepithelial tumour infiltrating lymphocytes (TILs) assessments. Results 15 patients were treated. At median follow-up of 12.5 months(m), nivolumab had an acceptable side-effect profile. Overall response rate was 37%. Preliminary transcriptome analyses of pre-treatment biopsies (33 samples from 14 patients; up to 4 regions per case) revealed enrichment for primary-resistance (defined as PD within 2m; n = 4) with immune ‘cold’ tumours, distinct from ’hot’ tumours. Histologic TILs scoring showed concordant immune phenotypic clusters. Primary-resistant cases demonstrated 0% on-treatment stromal- and IE-TILs (2 evaluable patients). In contrast, we observed heavy on-treatment stromal TILs (70-90%) and intraepithelial TILs (30-90%) across 7 regions at nephrectomy in an exceptional responder receiving ongoing treatment (>24 cycles). Conclusions ADATPeR is the first neoadjuvant immune checkpoint inhibitor study pre-cytoreductive nephrectomy, and incorporated multi-omic analyses of putative biomarkers. Baseline immune gene expression signature is distinct in responders compared with non-responders. On-treatment intraepithelial TILs were prominent in those deriving durable clinical benefit. Integrative analyses are ongoing. Clinical trial identification NCT02446860. Legal entity responsible for the study The authors. Funding Bristol-Myers Squibb; The National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research; Cancer Research UK (CRUK). Disclosure All authors have declared no conflicts of interest.

In this paper, a stochastic simulation procedure for energy assessment of PV systems is developed and tested. The method is especially adequate for urban applications since the impact of surrounding obstacles both for direct and diffuse irradiance is taken into account. The main input is the system location along with its monthly average irradiance and temperature statistics. Based on the input data, the program generates a set of random years represented by hourly sequences of global horizontal irradiance and ambient temperature. The generated sequences are then converted into the module plane-of-array irradiance and module temperature time series and, consequently, the AC energy production is estimated for each simulated year. The final results are presented in a form of probability density function of the system annual energy output.

Current guidelines do not recommend thrombolytic therapy for the treatment of intermediate-risk pulmonary embolism (PE) because of the tight balance between the benefit and safety with classic protocols. The aim of this study was to compare the new thrombolytic protocol with lower-dose slow-infusion (LDSI) of tissue plasminogen activator (tPA) to classic 2-hours tPA infusion protocol or no-reperfusion in patients with intermediate-high risk PE with higher bleeding risk regarding 30-day efficacy and safety. Among 849 patients with PE from the Serbian multicenter registry, 469 patients who fulfilled criteria for intermediate-risk PE were involved in the study. After propensity score matching 425 patients [263 (61.9%), 99 (23.3%) and 63 (14.8%) were treated with no-reperfusion, classic tPA protocol (100 mg for 2 hours) and LDSI of tPA (2–5 mg/hour either vie local catheter or systemic venous infusion with dose range of 25–50 mg)]. The basic characteristics of patients were well balanced between groups except that patients treated with LDSI of tPA had significantly higher usage of drugs which can be associated to bleeding and more previous bleeding events. Thirty day all-cause and PE-caused mortality and 7-day major bleeding were the main efficacy and safety end-points, respectively. All-cause and PE-cause 30-day mortality were 8.7% vs 16.2% vs 1.6% (Log rank p=0.007) and 4.5% vs 11.0% vs 0.0% (Log rank p=0.008) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. Major bleeding at 7 days were 2.7% vs 8.1% vs 14.3% (Log rank p=0.001) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. There was one fatal intracranial bleeding during catheter infusion of tPA. Lower-dose slow-infusion of tPA protocol decreased significantly all-cause and PE-cause mortality at 30-day at the cost of excess of non-fatal major bleeding at 7-day in patients with intermediate-risk PE and higher risk for bleeding. None

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients’ overall survival was analyzed with the Kaplan–Meier method with the log-rank test. Serum IL-1β concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

Cilj rada bio je ispitati odnos opšteg samopoštovanja, procijenjenog preko Rosenbergove skale samopoštovanja, i prilagodbe na studij, operacionalizirane preko skorova na Baker-Siryk-ovoj skali prilagodbe na studij SACQ. Prilagodba na studij modelirana je preko četiri dimenzije prilagodbe: emocionalne, socijalne, akademske, i institucionalne. Studija je provedena na uzorku od 808 studenata (62.9% ženski; M = 21.88; SD = 2.35). Diskriminativnom analizom preko četiri modaliteta prilagodbe procijenjena je alokacija studenata na grupu visoko/nisko samopoštovanje. Izdvojena je značajna diskriminativna funkcija koja bi se mogla svesti na aspekte emocionalno-socijalne prilagodbe. Ukupno je obuhvaćeno oko 17% preklapanja između studentske prilagodbe i samopoštovanja. Studenti sa višim stepenom samopoštovanja imali su u prosjeku statistički značajno viši nivo prilagodbe na studij u odnosu na studente s nižim samopoštovanjem.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is rare, but life-threatening condition. The treatment of choice in patients with ALCAPA is the establishment of a dual coronary artery system with surgical reimplantation of the left coronary artery in the left coronary sinus. Percutaneous coronary intervention is infrequent in the pediatric population but can be a life-saving by promptly restoring flow to an obstructed coronary artery. It is a highly demanding and high-risk procedure in infants due to the technical difficulties and the small coronary artery diameter in infants.