In recent years, Internet of Things (IoT) industry has developed rapidly thanks to the rise of the smart objects and devices with processing, sensing and actuating capabilities. In order to satisfy a broad range of applications, a variety of application layer protocols has been taken into consideration, since IoT still does not have widely accepted standard protocol. One of prime candidate solutions is HTTP, as a well-known, fundamental client-server protocol and the protocol that is the most compatible with existing network infrastructure. Due to strict IoT specific requirements, however, a detailed characterization of the performance of HTTP for IoT applications is required. This paper presents a detailed analysis of throughput and latency for HTTP/1.1 with pipelining, by evaluating the impact that pipelining factor has on the latency. Based on these performance results, we analyze whether this HTTP/1.1 model should be implemented in IoT systems with significant latency constraints.

OBJECTIVES The aim of this survey was to describe the current status of HIV care in the countries of Central and Eastern Europe and to investigate how close the region is to achieving the UNAIDS 2020 target of 90-90-90. METHODS In 2014, data were collected from 24 Central and Eastern European countries using a 38-item questionnaire. RESULTS All countries reported mandatory screening of blood and organ donors for HIV. Other groups subjected to targeted screening included people who inject drugs (PWID) (15/24, 62.5%), men who have sex with men (MSM) (14/24, 58.3%), and sex workers (12/24, 50.0%). Only 14 of the 24 countries (58.3%) screened pregnant women. The percentages of late presentation and advanced disease were 40.3% (range 14-80%) and 25.4% (range 9-50%), respectively. There was no difference between countries categorized by income or by region in terms of the percentages of persons presenting late or with advanced disease. The availability of newer antiretroviral drugs (rilpivirine, etravirine, darunavir, maraviroc, raltegravir, dolutegravir) tended to be significantly better with a higher country income status. Ten countries reported initiating antiretroviral therapy (ART) regardless of CD4+ T cell count (41.7%), five countries (20.8%) used the threshold of <500 cells/μl, and nine countries (37.5%) used the threshold of <350cells/μl. Initiation of ART regardless of the CD4+ T cell count was significantly more common among high-income countries than among upper-middle-income and lower-middle-income countries (100% vs. 27.3% and 0%, respectively; p=0.001). Drugs were provided free of charge in all countries and mostly provided by governments. There were significant discrepancies between countries regarding the follow-up of people living with HIV. CONCLUSIONS There are major disparities in the provision of HIV care among sub-regions in Europe, which should be addressed. More attention in terms of funding, knowledge and experience sharing, and capacity building is required for the resource-limited settings of Central and Eastern Europe. The exact needs should be defined and services scaled up in order to achieve a standard level of care and provide an adequate and sustainable response to the HIV epidemic in this region.

Oncoviruses are implicated in around 20% of all human cancers including both solid and non-solid malignancies. Epstein–Barr virus (EBV) and human papillomaviruses (HPVs) are the most common oncoviruses worldwide. Currently, it is well established that onco-proteins of EBV (LMP1, LMP2A, and EBNA1) and high-risk HPVs (E5 and E6/E7) play an important role in the initiation and/or progression of several human carcinomas, including cervical, oral, and breast. More significantly, it has been recently pointed out that viral onco-proteins of EBV and high-risk HPVs can be co-present and consequently cooperate to initiate and/or amplify epithelial–mesenchymal transition (EMT), which is the hallmark of cancer progression and metastasis. This could occur by β-catenin, JAK/STAT/SRC, PI3k/Akt/mTOR, and/or RAS/MEK/ERK signaling pathways, which onco-proteins of EBV and HPVs share. This review presents the most recent advances related to EBV and high-risk HPVs onco-proteins interactions and their roles in the progression of human carcinomas especially oral and breast via the initiation of EMT.

BACKGROUND Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Avoiding immune destruction is a major cancer characteristic and therapies aimed at immune checkpoint blockade are in use for several specific cancer types. A comprehensive survey of predictive biomarkers to immune checkpoint blockade in CUP were explored in this study. METHODS About 389 cases of CUP were analysed for mutations in 592 genes and 52 gene fusions using a massively parallel DNA sequencing platform (next-generation sequencing [NGS]). Total mutational load (TML) and microsatellite instability (MSI) were calculated from NGS data. PD-L1 expression was explored using immunohistochemistry (with 5% cutoff value). RESULTS High TML was seen in 11.8% (46/389) of tumours. MSI-high (MSI-H) was detected in 7/384 (1.8%) of tumours. Tumour PD-L1 expression was detected in 80/362 CUP (22%). A small proportion of CUP cases harboured genetic alterations of negative predictive biomarkers to immune checkpoint inhibitors (predictors to hyperprogression) including MDM2 gene amplification (2%) and loss of function JAK2 gene mutations (1%). Amplifications of CD274 (PD-L1) and PDCD1LG2 (PD-L2) genes were also rare (1.4% and 0.8%, respectively). The most frequently mutated genes were TP53 (54%), KRAS (22%), ARID1A (13%), PIK3CA (9%), CDKN2A (8%), SMARCA4 (7%) and PBRM1, STK11, APC, RB1 (5%, respectively). CONCLUSIONS Using a multiplex testing approach, 28% of CUP carried one or more predictive biomarkers (MSI-H, PD-L1 and/or TML-H) to the immune checkpoint blockade, providing a novel option for treatment in patients with CUP.

Parental health literacy plays an important role in children’s health. Experiences from pharmacy practice show that is necessary to check if parents understand instructions about use of medicines for children. This study aimed to assess pharmacotherapy literacy of parents of pre-school children and to examine association of parental pharmacotherapy literacy level with parent’s socio-demographic characteristics. The study was cross-sectional, conducted among parents of pre-school children (1–7 years of age), in kindergartens in several municipalities of Belgrade, Serbia, during regular parents meetings, from May to October 2016. Functional health literacy was measured by the Serbian version of the Short Test of Functional Health Literacy in Adults (S-TOFHLA). Parental pharmacotherapy literacy was assessed with newly constructed PTHL-SR questionnaire with good psychometric characteristics (Parental pharmacotherapy literacy questionnaire—Serbian). Overall, 813 parents participated in the study, mostly females (81.30%), between 30 to 40 years of age (70.85%) with two children (56.70%). Almost all of our study participants (99%) had adequate health literacy as assessed by S-TOFHLA. Mean score on PTHL-SR was 72.83% (standard deviation was 13.37), with better results among females than males (72% of women were in the group of highest PTHL-SR results). Our study showed that many parents (76.5%) knew the appropriate usage of non-prescription medicine for children, 57.2% parents were able to correctly calculate the dose of oral syrup for a child, and only 43.3% were able to interpret non-prescription dosage information written on the package. The majority of parents (61.3%) would make a dosage to child based on age and not on their weight. Every fifth parent with adequate functional health literacy measured by S-TOFHLA test, achieved the lowest results measured by PTHL-SR. Higher performance of the PTHL-SR was significantly correlated with education (p < 0.001), female sex (p < 0.001), married parents and those living in common-law (p < 0.001), older parents (p < 0.05) and parents who have more children (p < 0.05), and are non-smokers (p < 0.05). These results provide evidence that limitations in understanding common information about use of medicines are widespread among parents of pre-school children and encourage efforts for further investigation. PTHL-SR questionnaire may be a useful tool for identification of parents who need more instructions and assistance from healthcare providers, above all in providing better communication, written or spoken at community pharmacy settings.

The aim of this study was to determine the serum level of calcium (Ca), phosphorus (P) and magnesium (Mg) and hence determine the relationship and the effect of daily milk production on the mentioned essential macro elements. The metabolism and neurohumoral regulation of Ca, P and Mg are closely related, and the metabolic disorder of one of these electrolytes inevitably affects the metabolism of the other two. The study was carried out in the winter period of animal keeping and nutrition, and it included 63 Holstein-Friesian breed cows in the northern region of Bosnia and Herzegovina, aged 2-9 years in different lactation stages (1-8). The largest number of cows, eighteen of them, were in the second, third and fourth lactation stage, while nine cows were in the first lactation stage. This study was conducted on three different groups of cows corresponding to the amount of daily milk production. First was the group of lower daily milk production n=21, the second group of examined cows was the group of medium daily milk production n=23 and third was the group of higher daily milk production n=19. Ca, P and Mg were determined in blood plasma using the Beckmann spectrophotometer. By examining the obtained results and the dynamics of the tested mineral substances, we point out the different behaviour of the Ca-P relationship in correlation with the different level of daily milk produced. Although the average values ​​of both minerals are lowered with an increase in daily milk production, the analysis of single linear regression shows that there is a negative correlation between P concentration in blood plasma and the amount of daily milk produced, while for Ca it has not been established . Although the concentration of Mg in the blood plasma increases as the daily milk production increases, the analysis of single linear regression does not show a significant interconnection of these two values. Lower average values of Ca and P concentrations in the blood of cows with higher daily milk production may be associated with increased total excretion of these minerals through milk, unlike the cows which daily produced lower amounts of milk.

We analyze the spectrum of the massless Dirac operator on the 3-torus $\mathbb{T}^3$. It is known that it is possible to calculate this spectrum explicitly, that it is symmetric about zero and that each eigenvalue has even multiplicity. However, for a general oriented closed Riemannian 3-manifold $(M,g)$ there is no reason for the spectrum of the massless Dirac operator to be symmetric. Using perturbation theory, we derive the asymptotic formulae for the eigenvalues $\pm 1$ and prove that by the perturbation of the Euclidean metric on the 3-torus, it is possible to obtain spectral asymmetry of the massless Dirac operator in the axisymmetric case.