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This survey aimed to understand how far the Italian infectious diseases (ID) specialists are confident in the "Undetectable = Untransmittable" (U = U) message and translate this concept into clinical practice. An anonymous survey was distributed by e-mail to 286 clinicians to collect their opinions regarding six situations potentially at risk of HIV transmission between virologically suppressed patients and seronegative individuals who possibly require postexposure prophylaxis (PEP). Overall, 51% of ID specialists deemed zero risk of HIV transmission through condomless sex for undetectable patients. This answer was more frequent among HIV specialists (30% vs. 21%, p = .01) and clinicians working in teaching hospitals (35% vs. 16%, p = .03). Remarkably, 61% of participants would advise taking PEP for the HIV-negative partner in case of sexual intercourse with a seropositive person with a recent blip occurrence or absence of an HIV RNA test performed within the last 6 months (63%). Seventy-three percent of respondents deemed it essential to know patients' history of adherence to interpreting an HIV RNA test, regardless of its timing. When applying the U = U concept to daily clinical decisions, we observed an overall cautious attitude among physicians. Concerns mainly regarded the timing of the last HIV RNA test to the exposure event, especially in the absence of details on the patient's adherence. Wider diffusion and application of the U = U message are needed.

This study aims to scope the literature around PrEP/PEP in India. The Objectives of the study are; 1) To review the attitudes towards PrEP/PEP among people at risk of HIV in India 2) To summarize the evidence related to the attitudes towards PrEP/PEP among healthcare professionals in India.

Two randomized controlled trials demonstrated no clinical benefit of hydroxychloroquine (HCQ) for either postexposure prophylaxis or early treatment of SARS-CoV-2 infection. Using data from these studies, we calculated the time-weighted average change from baseline SARS-CoV-2 viral load and demonstrated that HCQ did not affect viral clearance.

Background. Hyperglycemia affects cardiac activity at basal states (Paolisso et al., 2000, 1997), yet its effect on cardiac reactivity in response to environmental changes has not been investigated extensively. In a previous experiment, we found evidence for an amplification of the physiological response to slow paced breathing following sugar ingestion (Meier et al., 2022). In an attempt to replicate and extend these findings, we study the effect of glucose ingestion on the autonomic relaxation response triggered by a soft-shoulder massage. In an exploratory manner, we will test whether the expected glucose-related amplification has a potential cognitive effect on sustained attention. Methods. Participants are randomly assigned to ingest a drink containing glucose, or pure water. After a waiting period, during which participants fill in questionnaires, they either receive a 10-min soft-shoulder massage or are allowed to rest. After the intervention, participants complete the d2 sustained attention test before a recovery period. Throughout the experiment, we repeatedly assess participants’ blood glucose concentration, blood pressure, and mood. Further, we monitor cardiorespiratory activity using electrocardiography (ECG) and impedance cardiography (ICG), and cortical activity using functional near-infrared spectroscopy (fNIRS*). Research question. With this preregistered analysis, we primarily plan to answer the research question: does glucose ingestion amplify autonomic reactivity to a massage? Further, we plan to explore whether this glucose-related amplification of autonomic reactivity has cognitive-behavioral consequences. This preregistration will thus focus on the effect of glucose intake on the parasympathetic and sympathetic responses to relaxation as induced by a massage, and on potential subsequent cognitive effects on sustained attention. * the fNIRS data are considered pilot data, as this is the first experiment in which we use fNIRS. If the data quality allows it, we will further explore cortical activation patterns in repone to our experimental manipulations.

Preregistration for testing the sensitivity of the PEP to relational information.

This component of the project examines perceived discrimination and stress reactivity/recovery in the context of a discrimination-related stress task

The component of the project focuses on self-reported physical health in AI/AN, including reports of overall health, limitations in activities, medical conditions, and bodily pain

In this study we want to figure out if the Propositional Evaluation Paradigm (PEP) can be used as a tool for changing self-esteem. Therefore, we will test if people learn contingencies of self-evaluative statements and truth values in a manipulated PEP. We will test if this PEP influences affect.

Background Human Immunodeficiency Virus (HIV) is a global public health threat, and all frontline Health care workers (HCWs) are at a higher risk of exposure to body fluids from potential HIV patients and to sharp instruments. Though timely Post Exposure Prophylaxis (PEP) decreases the possibility of seroconversion to HIV after occupational exposure, most HCWs rarely adhere to the PEP protocol. This study aims to determine the predictors of adherence to PEP among frontline healthcare workers in the Ho Teaching Hospital, Ghana. Methods A facility-based cross-sectional study was conducted among 199 frontline HCWs. Data were collected using a pretested self-administered questionnaire and analyzed using STATA version 14 software. Binomial logistic regression was performed at the 0.05 level of significance and 95% confidence interval. Findings Overall, 17.9% of HCWs adhered to PEP. Frontline HCWs who perceived they had low and very low risk of occupational exposure to HIV transmission were 96% [AOR = 0.04 (95% C.I: 0.00, 0.39) P = 0.006] and 94% [AOR = 0.06 (95% C.I: 0.00, 0.62) P = 0.019] respectively less likely to adhere to PEP. HCWs who received training on PEP were 4 times more likely to adhere to PEP compared to those who had never received it [AOR = 4.24 (1.31, 13.19) P = 0.013]. Conclusion Adherence to PEP protocol among HCWs was low. Therefore, there is a need for interventions to increase the perception of risk of occupational exposure to HIV transmission and to intensify training on PEP among frontline HCWs in the Ho Teaching Hospital. This will go a long way to increase their adherence to PEP.

The European Men-Who-Have-Sex-With-Men Internet Survey (EMIS-2017) is an international survey for men who have sex with men (MSM) designed to measure the level and distribution of four dimensions: (a) sexual health outcomes, (b) risk and precaution behaviors, (c) health promotion needs, and (d) coverage/uptake of interventions. The aim of the current work is to provide an overview of key demographics and findings for MSM in Greece covering the abovementioned dimensions of EMIS-2017, especially regarding HIV. Overall, 2909 men met the inclusion criteria for the analysis. The participants’ age ranged between 15 and 74 years old (median 35 years). According to the descriptive analysis, 14.4% of the participants reported moderate and 8.9% severe anxiety and depression. The self-reported HIV prevalence was 11%. A high number of participants had non-steady male partners (74%, n = 2153). The number of non-steady intercourse partners in the last 12 months was over two for about 61.5% (n = 1321) of the participants. A very small number of participants had ever tried to get pre-exposure prophylaxis (PrEP) (2.2%, n = 63), and 41.2% of the participants (n = 1199) were unaware of PrEP. About half of the participants (51.6%, n = 1501) did not know that vaccination against both hepatitis A and B viruses is recommended for MSM. The results of EMIS-2017 identify important needs and can help policy making and prevention planning.

Introduction: Rabies is a viral zoonosis still posing a significant threat to public health worldwide, especially in developing countries. The disease can be controlled by animal vaccination and appropriate post-exposure prophylaxis in humans administered in the earliest possible time. Aim: To study and analyze animal-related injuries and post-exposure prophylaxis for rabies. Materials and methods: Between 2014 and 2018, a retrospective epidemiological study was conducted in Varna region, which in-cluded 1462 persons who suffered injuries from animals. The study was based on the official data in the annual analysis of the Regional Health Inspectorate (RHI) in Varna. The information was summarized, analyzed, and graphically illustrated. The results were statisti-cally analysed using SPSS v. 20 employing variational and comparative (χ2) analyses. The statistical significance level was set at p Results: Of 1462 registered post-injury care seekers, 642 (42.7%) had to be given post-exposure prophylaxis on an emergency basis. The latter were mainly city residents (91.8%). Immunization against rabies was given in the first two days after exposure in 477 (76.4%) subjects. The average number of doses per immunized person was 3.63. The injuries were mainly from stray dogs (58.14%), followed by domestic (37.41%) and wild (4.45%) animals. According to the anatomical site of injury, limb injuries predominated in 88.65% (lower limbs 45% and upper limbs 43.64%). Most of the injuries were light (71.54%), followed by moderate (18.91%) and severe injuries (9.61%). Conclusions: Rabies prevention can be much more facilitated by the combined efforts of doctors, veterinarians, animal welfare orga-nizations and, last but not least, responsible population behavior. Post-exposure prophylaxis is an integral part of successfully curbing rabies programs but effective disease control can be achieved only through health education and vaccination of animals.

RESUMEN : Introducción: La presencia de síntomas depresivos en primeros episodios de psicosis supone un factor de gravedad para el desarrollo y curso de un cuadro psicótico. La dificultad de discernir entre los síntomas psicóticos negativos y los síntomas depresivos suponen un obstáculo en la identificación, diagnóstico y tratamiento de estos últimos y por tanto, en el pronóstico de un PEP. Objetivo: Estudiar los factores clínicos y sociodemográficos asociados a la presencia basal de un cuadro depresivo comórbido en una muestra de pacientes con un primer episodio de psicosis no afectiva, y su posible impacto sobre la gravedad clínica del cuadro psicótico. Material y métodos: Estudio longitudinal de 3 años, con la participación de 659 pacientes del Programa PAFIP. Se compararon variables cualitativas y cuantitativas entre grupos, usando chi-cuadrado y ANOVA. Los síntomas clínicos de psicosis se evaluaron mediante las escalas SANS y SAPS y el nivel de depresión de los pacientes se midió mediante CDSS. Además se utilizaron escalas para determinar el nivel de funcionamiento de los pacientes (GAF). Resultados: Los pacientes con depresión basal en PEP presentaron mayor gravedad del cuadro clínico, con mayor gravedad de los síntomas negativos y menor gravedad de los síntomas positivos psicóticos. La presencia de síntomas depresivos se asoció a mayor nivel de discapacidad y peor funcionamiento basal, ambos, factores considerados como predictores de una peor evolución del cuadro psicótico. Conclusiones: Los Pacientes con PEP tienen una alta predisposición a presentar síntomas depresivos al inicio del cuadro psicótico y la presencia de estos síntomas parece determinar una peor evolución del cuadro psicótico a largo plazo. ABSTRACT : Introduction: The presence of depressive symptoms in first episodes of psychosis is a serious factor in the development and course of a psychotic condition. The difficulty of distinguishing between negative psychotic symptoms and depressive symptoms represents an obstacle in the identification, diagnosis and treatment of latter and therefore in the prognosis of a first episode of psychosis. Objective: To study the clinical and socio-demographic factors associated with the baseline presence of comorbid depressive symptoms in a sample of patients with a first episode of non-affective psychosis, and its possible impact on the clinical severity of the psychotic condition. Material and methods: Longitudinal study of 3 years, with the participation of 659 patients of the PAFIP Program. Qualitative and quantitative variables were compared between groups, using the Chi-Square Test and ANOVA. The clinical symptoms of psychosis were evaluated using the SANS and SAPS scales, and the level of depression of the patients was measured using the CDSS. Furthermore, scales were used to determine the level of functioning of the patients (GAF) Results: Patients with baseline depression in FEP presented greater severity of the clinical condition, with greater severity of negative symptoms and less severity of positive psychotic symptoms. The presence of depressive symptoms was associated with a higher level of disability and worse baseline functioning, both of which are factors considered to be predictors of a worse evolution of the psychotic condition. Discussion: Patients with FEP have a high tendency to present depressive symptoms at the beginning of the psychotic condition, and the presence of these symptoms seems to determine a worse long-term evolution of this psychotic condition. Máster en Iniciación a la Investigación en Salud Mental

Tiesību zinātne Tiesību zinātne Law Science Law Science Maģistra darba tēma ir “Klientu izpētes tiesiskais regulējums un aktuālās problēmas kredītiestādēs”. Maģistra darbā ir izpētīts klientu izpētes tiesiskais regulējums Latvijas Republikā, tas vērtēts Eiropas Savienības tiesību kontekstā. Maģistra darba aktualitāte it pamatojama ar to, ka ņemot vērā tādus faktorus kā tehnoloģiju attīstība, atšķirīgs tiesiskais regulējums starp jurisdikcijām, kredītiestādes, kā nozīmīgākais finanšu plūsmas nodrošinātājas, ir pakļautas riskam tikt izmantotām noziedzīgi iegūtu līdzekļu legalizācijā. Lai pārvaldītu risku, kredītiestādes pielieto klientu izpēti, kas paredz virkni darbību, piemēram, klientu identifikācija, patiesā labuma guvēja noskaidrošana, kas saistāma ar tādu problemātiku kā datu patiesuma pārbaude, tiesiskā regulējuma interpretācija. Turklāt tiesiskais pamats pieprasīt datus klientu izpētes kārtībā ir vērtējams samērīgi ar tiesībām veikt brīvu uzņēmējdarbību un personas datu aizsardzību, ka ne vienmēr ir viennozīmīgs. Maģistra darba mērķis ir, izmantojot zinātniski pētnieciskās metodes un pieejamos informācijas avotus, izvērtēt kredītiestādēs īstenotās klientu izpētes tiesiskā regulējuma aktuālās problēmas, kā rezultātā izstrādāt priekšlikumus normatīvo aktu grozījumiem. Kopējais darba apjoms sastāv no 81 lappuses. The title of the Master’s thesis is “Know your customer” legal regulation and current challenges in credit institutions”. During the master thesis the research has been done in context of legal regulations of the Republic of Latvia and European Union. The topicality is justified that several factors, such as technological development, different legal regulations between jurisdictions, create positive environment to legalize illicit funds, thus credit institutions as the main provider of financial flow, are likely to be used in money laundering. To manage the risk, credit institutions apply “know your customer” procedure, that consists of series of activities, such as customer identification, determining the beneficial owners, that often are connected to issues, such as, data verification, interpretations of the legal framework. In addition, the legal basis for requesting “know your customer” data has a risk to conflict with the right to conduct free business and the protection of personal data. The aim of the Master's thesis is to evaluate the current problems of “know your customer” legal regulation in credit institutions, as well as to develop proposals for amendments to regulatory acts, by using scientific research methods and information sources. The total volume of work consists of 81 pages

Very few studies have investigated the neural underpinnings of bifocal-multisensory interventions such as acupoint tapping (tapping) despite their well-documented efficacy. The present study aims to investigate the neural and behavioral responses to tapping during the perception of phobic and generally fear-inducing stimulation in a group of participants with fear of flying. We studied 29 flight-phobic participants who were exposed to phobia-related, fear-inducing and neutral stimulation while undergoing fMRI and a bifocal-multisensory intervention session consisting of tapping plus cognitive restructuring in a within-subject design. During tapping we found an up-regulation of neural activation in the amygdala, and a down-regulation in the hippocampus and temporal pole. These effects were different from automatic emotion regulatory processes which entailed down-regulation in the amygdala, hippocampus, and temporal pole. Mean scores (±SD) on the Fear of Flying scale dropped from 2.51(±0.65) before the intervention to 1.27(±0.68) after the intervention (p .001). The proportion of participants meeting the criteria for fear of flying also dropped from 89.7 percent before the intervention to 24.0 percent after the intervention (p .001). Taken together, our results lend support to the effectiveness of tapping as a means of emotion regulation across multiple contexts and add to previous findings of increased amygdala activation during tapping, as opposed to amygdala down-regulation found in other emotion regulation techniques. They expand on previous knowledge by suggesting that tapping might modulate the processing of complex visual scene representations and their binding with visceral emotional reponses, reflected by the down-regulation of activation in the hippocampus and temporal pole. Bifocal emotion regulation was useful in ameliorating aversive reactions to phobic stimuli in people with fear of flying.

BACKGROUND: Positive expiratory pressure (PEP) devices are widely used in clinical settings, yet the performance characteristics of these devices remain relatively unknown. This study compared the performance characteristics of 6 airway clearance devices by varying resistance and flow. METHODS: Mean PEP, peak PEP, oscillation frequency, and amplitude PEP of the Flutter, Pari PEP S, Acapella Choice, Acapella DM, Acapella DH, and Aerobika devices were obtained across flows of 5, 10, 15, 20, 25 and 30 L/min and at low, medium, and high resistance using an experimental apparatus custom-built for this bench study. RESULTS: Performance characteristics of the devices differed across flows and resistance settings (device × flow/resistance interaction; P < .001). At a fixed resistance, increasing flows increased mean PEP produced by the Acapella Choice, Acapella DH, Aerobika, and Pari PEP S. Increasing flow resulted in minimal change in mean PEP produced by the Flutter and Acapella DM. Increasing flow increased peak PEP and amplitude PEP produced by all devices except the Acapella DH and Acapella Choice. Increasing flow maintained or increased oscillation frequency for all devices except the Flutter. At a fixed flow, increasing resistance increased mean PEP produced by all devices except the Acapella Choice. Increasing resistance increased peak PEP produced by the Acapella DM, Aerobika, and Pari PEP S but resulted in minimal change in peak PEP for the Flutter and Acapella Choice. Increasing resistance either maintained or increased oscillation frequency for all devices. Amplitude PEP was either maintained or increased during oscillations when increasing resistance for all devices except the Flutter. CONCLUSIONS: PEP devices produced small but statistically significant variations in performance characteristics across a range of flows and resistance settings. There appear to be flow-dependent and non–flow-dependent devices. Varying flow or resistance typically maintained or increased the production of mean, peak, and amplitude PEP and oscillation frequency.

There is increasing interest in gluten degrading enzymes for use during food and drink processing. The industrially available enzymes usually work best at low to ambient temperatures. However, food manufacturing is often conducted at higher temperatures. Therefore, thermostable gluten degrading enzymes are of great interest. We have identified a new thermostable gluten degrading proline specific prolyl endoprotease from the archaea Thermococcus kodakarensis. We then cloned and expressed it in Escherichia coli. The prolyl endoprotease was found to have a size of 70.1 kDa. The synthetic dipeptide Z-Gly-Pro-p-nitroanilide was used to characterise the prolyl endoprotease and it had maximum activity at pH 7 and 77°C. The VmaxKm and kcat values of the purified prolyl endoprotease were calculated to be 3.14 mM/s, 1.10 mM and 54 s–1 respectively. When the immunogenic gluten peptides PQPQLPYPQPQLPY (alpha-gliadin) and SQQQFPQPQQPFPQQP (gamma-hordein) were used as substrates, the prolyl endoprotease was able to degrade these. Furthermore, gluten in wort was reduced when the prolyl endoprotease was used during mashing of barley malt. The discoveries open up for new food processing possibilities and further the understanding of proline specific protease diversity.

Introduction: Preventing human immunodeficiency virus (HIV) infection is central to containing the HIV pandemic. For pre- and post-exposure prophylaxis (PrEP and PEP), drugs approved in Germany are available. Basic information on this should be obtained from physicians in further training to become specialists in General Practice (GP) since they may have to deal with this topic of high relevance for the health of patients at risk and also the physicians' health after a possible exposure in the professional context. Methodology: A multiple-choice questionnaire was handed out to doctors in further training in General Practice on seminar days of the Competence Centre for General Practice Saxony-Anhalt for an immediate answer. Results: Of the 109 doctors, 73 completed the questionnaire. A general high relevance of the topic HIV was stated by 95%. In contrast, 71% said it was relevant for family doctor activities. The knowledge questions on the prevalence were answered correctly for all questions with less than 40%; 21% stated that they knew the indication prerequisite for a PEP; 49% answered the question about the period of the highest efficacy of PEP correctly. PrEP as a drug option for prophylaxis is known to a part of the respondents, 79% would prescribe PrEP, 69% were in favour of a health insurance benefit. Discussion: The results show that the necessary basic knowledge about HIV is partly available. Basic knowledge on structured action in the fields of HIV testing, PEP and PrEP should be taught in a manner appropriate to the relevance of the topic in the context of the German general practice setting. Even a basic knowledge about PEP may help to ensure that the general practice teams receive proper measures after a possible exposition.

Background Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M; PCK2) is expressed in all cancer types examined and in neuroprogenitor cells. The gene is upregulated by amino acid limitation and ER-stress in an ATF4-dependent manner, and its activity modulates the PEP/Ca2+ signaling axis, providing clear arguments for a functional relationship with metabolic adaptations for cell survival. Despite its potential relevance to cancer metabolism, the mechanisms responsible for its pro-survival activity have not been completely elucidated. Methods [U-13C]glutamine and [U-13C]glucose labeling of glycolytic and TCA cycle intermediates and their anabolic end-products was evaluated quantitatively using LC/MS and GC/MS in conditions of abundant glucose and glucose limitation in loss-of-function (shRNA) and gain-of-function (lentiviral constitutive overexpression) HeLa cervix carcinoma cell models. Cell viability was assessed in conjunction with various glucose concentrations and in xenografts in vivo. Results PEPCK-M levels linearly correlated with [U-13C]glutamine label abundance in most glycolytic and TCA cycle intermediate pools under nutritional stress. In particular, serine, glycine, and proline metabolism, and the anabolic potential of the cell, were sensitive to PEPCK-M activity. Therefore, cell viability defects could be rescued by supplementing with an excess of those amino acids. PEPCK-M silenced or inhibited cells in the presence of abundant glucose showed limited growth secondary to TCA cycle blockade and increased ROS. In limiting glucose conditions, downregulation of PKC-ζ tumor suppressor has been shown to enhance survival. Consistently, HeLa cells also sustained a survival advantage when PKC-ζ tumor suppressor was downregulated using shRNA, but this advantage was abolished in the absence of PEPCK-M, as its inhibition restores cell growth to control levels. The relationship between these two pathways is also highlighted by the anti-correlation observed between PEPCK-M and PKC-ζ protein levels in all clones tested, suggesting co-regulation in the absence of glucose. Finally, PEPCK-M loss negatively impacted on anchorage-independent colony formation and xenograft growth in vivo. Conclusions All in all, our data suggest that PEPCK-M might participate in the mechanisms to regulate proteostasis in the anabolic and stalling phases of tumor growth. We provide molecular clues into the clinical relevance of PEPCK-M as a mechanism of evasion of cancer cells in conditions of nutrient stress.

The QUIC (Quick UDP Internet Connection) protocol suite is going to approach its final stages of standardization to become part of the official Internet standards (RFCs) and of the new HTTP/3 specification. Some of its disruptive characteristics, such as the 0-RTT establishment of secure communications and a connection-oriented management over a UDP-based connection-less transport, can be reused and tailored in the framework of a Performance Enhancing Proxy (PEP) architecture for the effective management of multiple links. In this paper, we describe the design and implementation of a QUIC-based splitting solution to enhance the communication across multiple backhaul links, each associated with a different network technology (e.g., satellite and terrestrial). After discussing the working principles of the designed QUIC-based proxy, we present a software implementation, as well as preliminary results obtained, through a set of meaningful test-cases deployed over a Linux based testbed.

Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays.Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity.Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14).Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34–65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (−17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity.Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.

Plastid-encoded RNA polymerase (PEP)-dependent transcription is an essential process for chloroplast development and plant growth. It is a complex event that is regulated by numerous nuclear-encoded proteins. In order to elucidate the complex regulation mechanism of PEP activity, identification and characterization of PEP activity regulation factors are needed. Here, we characterize Plastid Deficient 1 (PD1) as a novel regulator for PEP-dependent gene expression and chloroplast development in Arabidopsis. The PD1 gene encodes a protein that is conserved in photoautotrophic organisms. The Arabidopsis pd1 mutant showed albino and seedling-lethal phenotypes. The plastid development in the pd1 mutant was arrested. The PD1 protein localized in the chloroplasts, and it colocalized with nucleoid protein TRXz. RT-quantitative real-time PCR, northern blot, and run-on analyses indicated that the PEP-dependent transcription in the pd1 mutant was dramatically impaired, whereas the nuclear-encoded RNA polymerase-dependent transcription was up-regulated. The yeast two-hybrid assays and coimmunoprecipitation experiments showed that the PD1 protein interacts with PEP core subunit β (PEP-β), which has been verified to be essential for chloroplast development. The immunoblot analysis indicated that the accumulation of PEP-β was barely detected in the pd1 mutant, whereas the accumulation of the other essential components of the PEP complex, such as core subunits α and β′, were not affected in the pd1 mutant. These observations suggested that the PD1 protein is essential for the accumulation of PEP-β and chloroplast development in Arabidopsis, potentially by direct interaction with PEP-β.

Cell culture rabies vaccines were initially licensed in the 1980s and are essential in the prevention of human rabies. The first post-exposure prophylaxis (PEP) vaccination regimen recommended by the World Health Organization (WHO) was administered intramuscularly over a lengthy three-month period. In efforts to reduce the cost of PEP without impinging on safety, additional research on two strategies was encouraged by the WHO including the development of less expensive production methods for CCVs and the administration of reduced volumes of CCVs via the intradermal (ID) route. Numerous clinical trials have provided sufficient data to support a reduction in the number of doses, a shorter timeline required for PEP, and the approval of the intradermal route of administration for PEP and pre-exposure prophylaxis (PreP). However, the plethora of data that have been published since the development of CCVs can be overwhelming for public health officials wishing to review and make a decision as to the most appropriate PEP and PreP regimen for their region. In this review, we examine three critical benchmarks that can serve as guidance for health officials when reviewing data to implement new PEP and PreP regimens for their region including: evidence of immunogenicity after vaccination; proof of efficacy against development of disease; and confirmation that the regimen being considered elicits a rapid anamnestic response after booster vaccination.

Background and Aims: The before-procedure or after-procedure rectal indomethacin administration was shown to be useful in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We designed this prospective randomized study to compare the efficacy of single-dose and double-dose rectal indomethacin administration in preventing post-ERCP pancreatitis (PEP). Methods: We enrolled patients who underwent the ERCP in Taipei Mackay Memorial Hospital from 2016 June to 2017 November. Patients were randomly assigned to 2 groups: single and double-dose groups. The primary endpoint was the frequency of post-ERCP pancreatitis. Results: A total 162 patients participated in this study, and there were 87 patients randomly assigned to the single-dose group, and 75 patients were assigned to the double-dose group. In the high-risk patients, the incidence of PEP was lower in double-dose patients (4.8%) than the single-dose patients (9.5%), but there was no significant difference (P =.24). Difficult cannulation was the only 1 risk factor for PEP after rectal indomethacin treatment. Conclusions: Single-dose rectal indomethacin administration immediately after ERCP in general population is good enough to prevent PEP, but difficult cannulation could induce the PEP frequency up to 15.4% even under rectal indomethacin use.

Tryptophan, an aromatic amino acid, has been widely used in food industry because it participates in the regulation of protein synthesis and metabolic network in vivo. In this study, we obtained a strain named TRP03 by enhancing the tryptophan synthesis pathway, which could accumulate tryptophan at approximately 35 g/L in a 5 L bioreactor. We then modified the central metabolic pathway of TRP03, to increase the supply of the precursor phosphoenolpyruvate (PEP), the genes related to PEP were modified. Furthermore, citric acid transport system and TCA were upregulated to effectively increase cell growth. We observed that strain TRP07 that could accumulate tryptophan at approximately 49 g/L with a yield of 0.186 g tryptophan/g glucose in a 5 L bioreactor. By-products such as glutamate and acetic acid were reduced to 0.8 g/L and 2.2 g/L, respectively.

Background Globally, the number of HIV cases continue to increase, despite the development of multiple prevention strategies. New cases of HIV have been reported disproportionately more in men who have sex with men and other vulnerable populations. Issues such as internalized and structural homophobia prevent these men from accessing prevention strategies such as postexposure prophylaxis (PEP). Mobile health (mHealth) interventions are known to be one of the newest and preferred options to enhance PEP knowledge and access. Objective The aim of this study was to identify and analyze the mobile apps addressing PEP for HIV infections. Methods We conducted a descriptive exploratory study in 3 sequential phases: systematic literature review, patent analysis, and systematic search of app stores. For the systematic review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines adapted for an integrative review in the databases of PubMed, Web of Knowledge, Scopus, Cochrane, Embase, Science Direct, Eric, Treasure, and CINAHL. The patent analysis was performed by exploring the databases of the Brazilian National Institute of Industrial Property, the United States Patent and Trademark Office, and the European Patent Office. For the systematic search, we analyzed mHealth apps related to HIV in 2 major app libraries, that is, Google Play Store and App Store. The apps were evaluated by name, characteristics, functions, and availability in iPhone operating system/Android phones. Results We analyzed 22 studies, of which 2 were selected for the final stage. Both studies present the use of apps as mHealth strategies aimed at improving the sexual health of men who have sex with men, and they were classified as decision support systems. The search in the patent databases showed only 1 result, which was not related to the topic since it was a drug intervention. In the app libraries, 25 apps were found and analyzed, with 15 (60%) apps available for Android systems but only 3 (12%) addressing PEP. In general, the apps inform about HIV and HIV prevention and treatment, with the focus users being health care providers, people with HIV, or the general population, but they have only limited features available, that is, mainly text, images, and videos. The 3 apps exclusively focusing on PEP were created by researchers from Brazilian universities. Conclusions Our review found no connection between the scientific studies, registered patents, and the available apps related to PEP; this finding indicates that these available apps do not have a theoretical or a methodological background in their creation. Thus, since the scientific knowledge on HIV is not translated into technological products, preventing the emergence of new infections, especially in the more vulnerable groups, is difficult. In the future, researchers and the community must work in synergy to create more mHealth tools aimed at PEP.

Biomanufactured parts, for implant or generally in-vivo use, have high requirements for surface properties. Depending on their field of application, not only smooth, but also well-defined surfaces, i.e. roughness parameters, must be set to allow for the respective functionalities such as optimal cell growth or minimal friction and wear. While for many parts mechanical polishing procedures are state-of-the-art, which are time-consuming and limited in their flexibility, established electrolytic polishing processes often incorporate aggressive media such as acids. Plasma electrolytic Polishing (PeP), a high-voltage process combining anode dissolution and plasma-chemical processes, can be considered a suitable alternative. The paper focusses on current investigations of PeP and shows application scenarios, also pointing out necessary development directions to introduce PeP to industrial biomanufacturing process chains.

Background: Several medical therapies have been proposed for the treatment of premature ejaculation (PE). Paroxetine and tramadol were both reported to be effective in treatment of PE. In this study, the therapeutic effects of tramadol, paroxetine and placebo were compared in treatment of primary PE. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 150 patients were divided into 3 groups. One group was treated with tramadol 50 mg ondemand, the other group took paroxetine 20 mg on-demand and the third group was treated with placebo. Before starting treatment and after 12 weeks, patients were asked to measure their average intravaginal ejaculation latency time (IELT) and fill the PEP (Premature Ejaculation Profile) questionnaire. Results: At the end of the 12th week, the mean IELT and average of PEP scores improved in all 3 groups. The increase in tramadol group was significantly higher than the paroxetine and placebo groups (p

To the Editor: Dog bites are a serious public health problem because of the associated risk for rabies virus exposure in countries to which the virus is endemic (1,2). Human rabies can be prevented by administration of postexposure prophylaxis (PEP). However, PEP rabies vaccine may be unavailable or prohibitively expensive (3). Delay in or failure to receive PEP after possible rabies virus exposure contributes to increased incidence of human rabies deaths (3). We performed a retrospective investigation of animal bites and postbite treatment in Laikipia North sub-county, Kenya, during January 2013–February 2014. Laikipia North is 1 of 3 sub-counties in Laikipia County and has a population of 32,726 (4). Our investigation was instigated by 3 suspected human rabies deaths that were informally reported to the Kenya Government Zoonotic Disease Unit (ZDU) during early 2014. We reviewed animal bite records from sub-county health facilities and veterinary offices and administered a structured household questionnaire to determine outcomes, knowledge of rabies, bite management, healthcare-seeking behavior, and economic costs. This public health response was government coordinated and approved; no personal identifiers were retained. During January 1, 2013–February 10, 2014, a total of 106 bites were recorded by 6 government-run health facilities in Laikipia North. Median reported bite incidence per month was 24 bites/100,000 persons (range 6–45 bites/100,000 persons). The median age of bite victims was 13 years (range 1–81 years); 61 (58%) bites occurred in males. Of all bites recorded, 94 (88%) were by dogs, 8 (8%) by scorpions, and 4 (4%) by humans. The deaths of 3 humans reported to the ZDU occurred in November and December 2013. To assess whether these cases were part of an exposure cluster, we followed up on bite cases during November 1–December 31, 2013. During this period, 17 additional animal bite cases were recorded. Of these 20 bite cases, we successfully traced the households of 11 (55%) case-patients, including 2 of the 3 who died from rabies. Bites were predominantly received from owned pets (82%), and most bites (82%) were reported to be unprovoked. All bites were inflicted on extremities, and almost all (91%) were single-bite injuries (Table). Table Responses to questionnaire interview of 11 animal bite victims assessed for rabies, Laikipia County, Kenya, 2014* Of 11 animals that bit case-patients, 7 had unknown histories of rabies vaccination and 4 were not vaccinated (Table). Four of the 11 animals were suspected to be rabid, including 1 cat and 3 dogs. All the suspected rabid animals were reported to exhibit aggressive or abnormal behavior, drooling or salivation, vocalization, and roaming tendencies (5; Technical Appendix Table 1). Three of the animals reportedly died; status was unknown for 1. Of the 11 traced bite case-patients, 9 washed their wound before going to a healthcare facility and 8 were prescribed PEP. The median time from bite to reporting to a health facility was 1 day (range 0–3 days). Four respondents delayed in starting PEP: 3 after 3 days, and 1 after 2 days. Reasons given for delay included the high cost of PEP by 3 (including 1 who died); a health facility being too far away by 1, who died; and vaccine unavailable at nearest health facility by 2, 1 of whom died. Of 8 respondents who received PEP, 7 traveled >10 km to reach the nearest health facility. PEP availability was inconsistent at the sub-county hospital and local dispensaries; 6 of 8 respondents seeking PEP visited multiple facilities to receive PEP, including a county referral facility that was >100 km away. The World Health Organization’s 5-dose PEP regimen is recommended in Kenya (1). However, only 3 case-patients were prescribed and received 5 doses. Five respondents were prescribed 3, 4, or 6 doses (Technical Appendix Table 2). This finding indicates large inconsistencies in the PEP prescribing practices in this region of Kenya, a pattern that is similar in other parts of East Africa (6). Respondents bore all medical costs without subsidy. Direct medical costs were ≈$2–$500 (US) per bite victim, and indirect medical costs were ≈$4–$100. The average cost of obtaining a single dose of PEP ranged from $8 to $120 (Table; Technical Appendix Table 2). All respondents had heard of rabies. Nine (82%) knew it was transmitted to humans through a bite from a rabid dog, and 4 (36%) knew that rabies among dogs could be prevented through vaccination. During 2014, at least 3 suspected human rabies deaths and 4 domestic animal deaths were associated with this cluster. Postbite care, including PEP, is a heavy economic burden on this community, moreso because rabies vaccine is not always locally accessible. Dog vaccination rates are low in this region and rabies in suspected animals is rarely definitively diagnosed, increasing risks for human rabies virus exposures and the economic burden of PEP administration. We recommend implementation of regular and comprehensive mass dog vaccination campaigns, in line with Kenya’s National Rabies Elimination Strategy (7), and further detailed studies on the epidemiology of rabies in this ecosystem, which supports human, wildlife, and domestic dog populations. Technical Appendix. Questionnaire for persons bitten by animals to assess rabies status of the animals and discussion of direct and indirect costs related to rabies post-exposure prophylaxis. Click here to view.(151K, pdf)

Background The purpose of this study was to describe what is known about HIV infection and other sexually transmitted diseases, infection transmission routes, care, and sources of information, from the viewpoint of men having sex with men. Methods National data (n = 2,072) was collected from June to August 2010 in Finland as part of a joint internet-based survey conducted in 38 countries (EMIS, European MSM Internet Sex Survey). Results The respondents’ age, place of residence, highest education and employment status were statistically significantly related to how often the respondent sought information on HIV, testing and treatments, and what they knew about infection transmission routes. The respondents’ information seeking behavior was not seen as active regarding HIV infection and other sexually transmitted diseases. Conclusions We should also consider the possibility of using internet-based interventions, especially in smaller and northern catchment areas, in order to improve the knowledge level of men having sex with men.

The non-invasively measured initial systolic time interval (ISTI) reflects a time difference between the electrical and pumping activity of the heart and depends on cardiac preload, afterload, autonomic nervous control and training level. However, the duration of the ISTI has not yet been compared to other time markers of the heart cycle. The present study gauges the duration of the ISTI by comparing the end point of this interval, the C-point, with heart cycle markers obtained by echocardiography. The heart rate of 16 healthy subjects was varied by means of an exercise stimulus. It was found that the C-point, and therefore the end point of ISTI, occurred around the moment of the maximum diameter of the aortic arch in all subjects and at all heart rates. However, while the time difference between the opening of the aortic valves and the maximum diameter of the aortic arch decreased significantly with decreasing RR-interval, the time difference with respect to the moment of the C-point remained constant within the subjects. This means that the shortening of the ISTI with increasing heart rate in response to an exercise stimulus was caused by a shortening of the pre-ejection period (PEP). It is concluded that the ISTI can be used as a non-invasive parameter indicating the time difference between the electrical and mechanical pumping activity of the heart, both inside and outside the clinic.

In most organisms, the mitochondrial genes are transcribed by RNA polymerases related to the single-subunit RNA polymerases of bacteriophages like T3 and T7. In flowering plants, duplication(s) of the RpoTm gene coding for the mitochondrial RNA polymerase (RPOTm) led to the evolution of additional RNA polymerases transcribing genes in plastids (RPOTp) or in both mitochondria and plastids (RPOTmp). Two putative RPOTmp enzymes were previously described to be encoded by the nuclear genes RpoTmp1 and RpoTmp2 in the moss Physcomitrella patens. Here, we report on a third PhyscomitrellaRpoT gene. We determined the sequence of the cDNA. Comparison of the deduced amino acid sequence with sequences of plant organellar RNA polymerases suggests that this gene encodes a functional phage-type RNA polymerase. The 78 N-terminal amino acids of the putative RNA polymerase were fused to GFP and found to target the fusion protein exclusively to mitochondria in Arabidopsis protoplasts. P. patens is the only known organism to possess three mitochondrial RNA polymerases. Electronic supplementary material The online version of this article (doi:10.1007/s00294-013-0405-y) contains supplementary material, which is available to authorized users.

Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans.

International audience; Plastids display a high morphological and functional diversity. Starting from an undifferentiated small proplastid, these plant cell organelles can develop into four major forms: etioplasts in the dark, chloroplasts in green tissues, chromoplasts in colored flowers and fruits and amyloplasts in roots. The various forms are interconvertible into each other depending on tissue context and respective environmental condition. Research of the last two decades uncovered that each plastid type contains its own specific proteome that can be highly different from that of the other types. Composition of these proteomes largely defines the enzymatic functionality of the respective plastid. The vast majority of plastid proteins is encoded in the nucleus and must be imported from the cytosol. However, a subset of proteins of the photosynthetic and gene expression machineries are encoded on the plastid genome and are transcribed by a complex transcriptional apparatus consisting of phage-type nuclear-encoded RNA polymerases and a bacterial-type plastid-encoded RNA polymerase. Both types recognize specific sets of promoters and transcribe partly over-lapping as well as specific sets of genes. Here we summarize the current knowledge about the sequential activity of these plastid RNA polymerases and their relative activities in different types of plastids. Based on published plastid gene expression profiles we hypothesize that each conversion from one plastid type into another is either accompanied or even preceded by significant changes in plastid transcription suggesting that these changes represent important determinants of plastid morphology and protein composition and, hence, the plastid type.

This paper investigates a TCP proxy, called a PEP, which splits a TCP connection to employ a specially tailored TCP connection over a satellite link. This paper describes how large size data is forwarded inside the PEP when a packet loss occurs on the satellite link. It also identifies a problem that the output traffic from the PEP becomes bursty due to the large size forward data. To mitigate bursts of packets by the PEP this paper proposes a scheme that the PEP performs a shaping function which places a gap between two consecutive segments sent by the PEP. Simulation results using ns-2 show that bursty packets are issued by the conventional PEP and the shaping function suppresses them effectively.

In IP networks, where bandwidth-delay product is large, a PEP (Performance Enhancing Proxy) is effective for improving the performance of TCP. The PEP splits an end-to-end TCP connection into two parts; it forwards received data from one TCP connection to another. If the maximum throughput of one TCP connection is larger than the other, the PEP has to buffer forwarding data and perform a flow control to adjust the throughput. To confirm the mechanism of the flow control and to evaluate the required volume of buffers, we investigate the flow control by experiments using Linux and report their results.

In IP networks, where bandwidth-delay product is large, a PEP (Performance Enhancing Proxy) is effective for improving the performance of TCP. The PEP splits an end-to-end TCP connection into two parts; it forwards received data from one TCP connection to another. If the maximum throughput of one TCP connection is larger than the other, the PEP has to buffer forwarding data and perform a flow control to adjust the throughput. To confirm the mechanism of the flow control and to evaluate the required volume of buffers, we investigate the flow control by experiments using Linux and report their results.

Plant floral transition is a major developmental switch regulated by an integrated network of pathways. Arabidopsis FLOWERING LOCUS K (FLK), a protein with three KH RNA-binding domains, operates in the autonomous flowering-promotive pathway by decreasing the transcript levels of the key flowering repressor FLOWERING LOCUS C (FLC). Here we report that PEPPER (PEP), an FLK paralog previously shown to affect vegetative and pistil development, antagonizes FLK by positively regulating FLC. Lack of PEP function rescues the flk late-flowering phenotype with a concomitant decrease in FLC RNA levels. Loss of HUA2, another FLC activator encoding an RNA-binding protein, further rescues flk, being flk hua2 pep triple mutants virtually wild-type regarding flowering time. Consistently, PEP overexpression determines high levels of FLC transcripts and flowering delay. Genetic and molecular analyses indicate that FLK and PEP act independently of FCA, another important FLC repressor in the autonomous pathway. In addition, we present data suggesting that PEP may affect FLC expression at both transcriptional and post-transcriptional levels. Overall, our results uncover PEP as a new factor for FLC upregulation, underscoring the importance of RNA-binding activities during developmental timing of flowering.

Highlight Dysfunction of the Pep-PEPR system and its interplay with JA signalling results in increased plant susceptibility towards herbivore attack indicating that endogenous signalling also contributes to herbivore defence., A number of plant endogenous elicitors have been identified that induce pattern-triggered immunity upon perception. In Arabidopsis thaliana eight small precursor proteins, called PROPEPs, are thought to be cleaved upon danger to release eight peptides known as the plant elicitor peptides Peps. As the expression of some PROPEPs is induced upon biotic stress and perception of any of the eight Peps triggers a defence response, they are regarded as amplifiers of immunity. Besides the induction of defences directed against microbial colonization Peps have also been connected with herbivore deterrence as they share certain similarities to systemins, known mediators of defence signalling against herbivores in solanaceous plants, and they positively interact with the phytohormone jasmonic acid. A recent study using maize indicated that the application of ZmPep3, a maize AtPep-orthologue, elicits anti-herbivore responses. However, as this study only assessed the responses triggered by the exogenous application of Peps, the biological significance of these findings remained open. By using Arabidopsis GUS-reporter lines, it is now shown that the promoters of both Pep-receptors, PEPR1 and PEPR2, as well as PROPEP3 are strongly activated upon herbivore attack. Moreover, pepr1 pepr2 double mutant plants, which are insensitive to Peps, display a reduced resistance to feeding Spodoptera littoralis larvae and a reduced accumulation of jasmonic acid upon exposure to herbivore oral secretions. Taken together, these lines of evidence extend the role of the AtPep-PEPR system as a danger detection mechanism from microbial pathogens to herbivores and further underline its strong interaction with jasmonic acid signalling.

Pistil final morphology relies on floral meristem homeostasis, proper organ specification and regional differentiation. These are developmental processes in which sophisticated signaling networks are being uncovered. However, further elements for fine-tuning adjustment still remain to be disclosed. At the molecular level, posttranscriptional modulators may fit such a profile. In this work, we describe the characterization of PEPPER (PEP), a novel Arabidopsis gene encoding a polypeptide with K-homology (KH) RNA-binding modules, which acts on vegetative growth and pistil development. PEP was initially identified as one of the gene functions affected in a complex mutant carrying a chromosomal reorganization, which exhibits aberrant phyllotaxy and small fruits with supernumerary carpels. In contrast, plants carrying single-gene pep null mutations exhibit subtle morphological alterations. Individuals bearing a stronger-than-null allele present a phenotype comprising leaf alterations, phyllotactic errors and sporadic presence of fruits with multiple valves. Accordingly, dynamic PEP expression was detected in all major organs examined. Complementation experiments with a PEP genomic clone confirmed a role for PEP as a regulator in vegetative and reproductive development. Moreover, our genetic studies suggest that PEP interacts with element(s) of the CLAVATA signaling pathway.

Post-Exposure Prophylaxis (PEP) is a preventive strategy that aims to avert the transmission of HIV to an exposed individual following occupational and non-occupational exposure, e.g. sexual contact, injecting drug use (IDU), needle stick injuries. Timely access to PEP (Within 72 hours) is an integral component to treatment as prevention alongside early treatment to achieve a significant reduction in a new transmission of HIV. In Queensland, it is estimated that around 5000 people live with HIV. The year 2014 saw an increase of 35% newly diagnosed cases of HIV as compared to the year 2013, thus the need to impede the spread of this pandemic is crucial. This project aims to improve the out of hour access to PEP in Queensland through Emergency Departments(ED). A mapping activity of access to PEP across Queensland was carried out by the project team through: • Consultation with the Queensland Department of Health, Communicable Diseases Branch (CDB) • A Community Survey to scope the experiences of people accessing PEP. • Consultation with Community organisations, Public/Private hospitals, HIV Public Health Team, Sexual Health Clinics to scope issues received regarding access to PEP. • Enquiry to all HHS Emergency Departments, Directors of Emergency Medicine and Nurse Unit Managers prescribing PEP to obtain local PEP protocol implementation. A PEP working group was formed that comprised of state-wide representatives from HIVFQ, sexual health clinics, hospital emergency dept., community groups and the Communicable Disease Branch of Queensland Department of Health. Some of the key points identified by the working group were: • Demand for PEP is steadily increasing each year. • People have positive experiences accessing PEP at sexual health clinics, however, some negative experiences were reported by those accessing PEP out of hours at Hospital Emergency Departments (EDs). • Some hospital EDs were less knowledgeable about PEP and were unable to locate the clinical guidelines in a timely manner. • Wait times in EDs averaged 4 hours, which was an added stressor for people waiting for PEP. • Some people experienced stigma, discrimination and judgements when trying to access PEP at EDs. The working group met to review the current PEP landscape and developed the following interventions to improve access to PEP: • Development of a user-friendly PEP Folder for Emergency and Pharmacy Departments including algorithms and flowcharts. This will be rolled out with nursing and pharmacy champions around Queensland, who are best placed to raise awareness of PEP (and PrEP3). • Coordination of resources available to the community including updating the clinic search tool on the ENDHIV website and PEP Emergency Card. • Production of PEP education/training videos for hospital staff to be incorporated into all Queensland hospital pre-vocational trainings and other clinical inductions • Endorsement of the resources from the Queensland Emergency Department State Advisory Panel. We hope these interventions will not only help reduce new transmission of HIV, but also educate clinicians and community on testing, treatment and stigma associated with HIV, thus working towards an HIV-free generation

Plastid transcription is crucial for plant growth and development. There exist two types of RNA polymerases in plastids: a nuclear-encoded RNA polymerase (NEP) and plastid-encoded RNA polymerase (PEP). PEP is the major RNA polymerase activity in chloroplast. Its core subunits are encoded by the plastid genome, and these are embedded into a larger complex of nuclear-encoded subunits. Biochemical and genetics analysis identified at least twelve proteins are tightly associated with the core subunit, while about thirty-four further proteins are associated more loosely generating larger complexes such as the transcriptionally active chromosome or a part of the nucleoid. Domain analyses and functional investigations suggested that these nuclear-encoded factors may form several functional modules that mediate regulation of plastid gene expression by light, redox, phosphorylation, and heat stress. Genetic analyses also identified that some nuclear-encoded proteins in the chloroplast that are important for plastid gene expression, although a physical association with the transcriptional machinery is not observed. This covers several PPR proteins including CLB19, PDM1/SEL1, OTP70 and YS1 which are involved in the processing of transcripts for PEP core subunit as well as AtECB2, Prin2, SVR4-Like and NARA5 that are also important for plastid gene expression, although their functions are unclear.

This paper focuses on geostationary satellite scenarios and investigates the performance of several Transmission Control Protocol (TCP) variants in a novel Performance Enhancing Proxy (PEP) architecture solution, whose added value is the use of network coding beneath the transport layer. Comparison of TCP New-Reno, Vegas, Scalable, CUBIC, Hybla, and HTCP and the cases where these transport protocols are used along with network coding is carried out by means of simulation campaigns. The obtained results show the potentials of the proposed network coding technique, resulting in the improvement of TCP connections performance in a wide range of channel conditions and the possible exploitation of future increase of the satellite link capacity.

Clinical recommendations for the prevention and treatment of anthrax among pregnant women are updated., In August 2012, the Centers for Disease Control and Prevention, in partnership with the Association of Maternal and Child Health Programs, convened a meeting of national subject matter experts to review key clinical elements of anthrax prevention and treatment for pregnant, postpartum, and lactating (P/PP/L) women. National experts in infectious disease, obstetrics, maternal fetal medicine, neonatology, pediatrics, and pharmacy attended the meeting, as did representatives from professional organizations and national, federal, state, and local agencies. The meeting addressed general principles of prevention and treatment for P/PP/L women, vaccines, antimicrobial prophylaxis and treatment, clinical considerations and critical care issues, antitoxin, delivery concerns, infection control measures, and communication. The purpose of this meeting summary is to provide updated clinical information to health care providers and public health professionals caring for P/PP/L women in the setting of a bioterrorist event involving anthrax.

En aquest treball es modifica una variant del ja conegut sistema de control d'accés anomenat ABAC. Aquesta variant s'implementa dins d'una DTN activa, permetent així afegir un component de seguretat dins la xarxa. Al ser un tipus de xarxa que permet endarreriments de la transmissió, ABAC ha de ser adaptat per aquest cas, variant els mòduls interns del que es composa, evitant d'aquesta manera que hi hagi pèrdua de dades per falta de connectivitat. Al llarg de l'article es pot observar: l'entorn en que s'aplicarà aquest TFG; els petits canvis que es realitzaran, tant d'ABAC, que per aquest projecte els seus mòduls no estaran directament connectats, com dels components de la xarxa; petites variacions en el codi i l'agregació d'algunes comparacions per fer servir el filtre proposat; i finalment, la metodologia utilitzada per arribar a la solució proposada, juntament amb la conclusió extreta després de trobar una de les possibles respostes al problema. In this work, a modification of the already well known access control system ABAC is presented. Implementing this variant inside an active DTN, allowing to add a security component into the network. As DTN allows transmission delays, ABAC had to be adapted in order to work correctly with this case. Changes its internal modules have been preventing leaks in case of connectivity losses. Along the present paper, it may be observed: the environment where the TFG will be applied; the changes implemented, both in ABAC, which modules will not be connected directly, as well as in the network components, some code variations and the integration of some comparisons in order to use the ABAC's filter; and finally, the methodology used to find the proposed solution, together with the conclusion after reaching a possible answer to the problem.

Chloroplasts are semiautonomous organelles which possess their own genome and gene expression system. However, extant chloroplasts contain only limited coding information, and are dependent on a large number of nucleus-encoded proteins. During plant evolution, chloroplasts have lost most of the prokaryotic DNA-binding proteins and transcription regulators that were present in the original endosymbiont. Thus, chloroplasts have a unique hybrid transcription system composed of the remaining prokaryotic components, such as a prokaryotic RNA polymerase as well as nucleus-encoded eukaryotic components. Recent proteomic and transcriptomic analyses have provided insights into chloroplast transcription systems and their evolution. Here, we review chloroplast-specific transcription systems, focusing on the multiple RNA polymerases, eukaryotic transcription regulators in chloroplasts, chloroplast promoters, and the dynamics of chloroplast nucleoids.

Antigen receptor–triggered T-cell activation is mediated by the sequential action of the Src and Syk/Zap-70 families of protein tyrosine kinases (PTKs). Previously, we reported that another PTK termed p50csk was a potent negative regulator of T-cell receptor (TCR) signaling because of its ability to inactivate Src-related kinases. This inhibitory effect required the catalytic activity of Csk, as well as its Src homology (SH)3 and SH2 domains. Subsequent studies uncovered that, via its SH3 domain, p50csk was associated with PEP, a proline-enriched protein tyrosine phosphatase (PTP) of unknown function expressed in hemopoietic cells. Herein, we have attempted to identify the role of the Csk-PEP complex in T lymphocytes. The results of our experiments showed that, like Csk, PEP was a strong repressor of TCR signaling. This property was dependent on the phosphatase activity of PEP, as well as on the sequence mediating its binding to p50csk. Through reconstitution experiments in Cos-1 cells, evidence was obtained that Csk and PEP act synergistically to inhibit protein tyrosine phosphorylation by Src-related kinases, and that this effect requires their association. Finally, experiments with a substrate-trapping mutant of PEP suggested that PEP functions by dephosphorylating and inactivating the PTKs responsible for T-cell activation. In addition to giving novel insights into the mechanisms involved in the negative regulation of T-cell activation, these findings indicate that the association of an inhibitory PTK with a PTP constitutes a more efficient means of inhibiting signal transduction by Src family kinases in vivo.

A policy-based access control architecture com- prises Policy Enforcement Points (PEPs), which are modules that intercept subjects access requests and enforce the access decision reached by a Policy Decision Point (PDP), the module implementing the access decision logic. In applications, PEPs are generally implemented manually, which can introduce errors in policy enforcement and lead to security vulnerabilities. In this paper, we propose an approach to systematically test and validate the correct enforcement of access control policies in a given target application. More specifically, we rely on a two folded approach where a static analysis of the target application is first made to identify the sensitive accesses that could be regulated by the policy. The dynamic analysis of the application is then conducted using mutation to verify for every sensitive access whether the policy is correctly enforced. The dynamic analysis of the application also gives the exact location of the PEP to enable fixing enforcement errors detected by the analysis. The approach has been validated using a case study implementing an access control policy.

RNA polymerase type I (plastid-encoded polymerase, PEP) is one of the key chloroplast enzymes. However, the rpo genes that encode its subunits (rpoA, rpoB, rpoC1 and rpoC2) are relatively rapidly evolving sequences. The aim of this study was to investigate the rate of the molecular evolution of rpo genes and to evaluate them as phylogenetic markers on the example of the genus Lamium L. (Lamiaceae). The analyzed genes were shown to differ in the level of variation, rate of intragenic mutations, phylogenetic informativeness, and in the impact of these mutations on the properties of encoded peptides. Destabilizing effects of the positive pressure were observed in all genes examined coding for PEP enzyme. We have demonstrated the relationship between mutations fixed by positive selection and the separation of phylogenetic lines within the genus Lamium. The study showed also that the rpo genes were reliable phylogenetic markers, useful in the reconstruction of interconnections of species belonging to the same genus. Of the four tested genes, the most promising phylogenetic marker was rpoA gene, while the least useful gene appeared to be rpoC1.

Mitigation of Transmission Control Protocol (TCP) performance degradation over satellite has been extensively studied over the last two decades by the scientific community, which has come up with a large set of protocol and architecture solutions. This paper proposes a novel end-to-end (E2E) transport layer protocol, namely Advanced Transport Satellite Protocol (ATSP), which is built around consolidated control theory concepts already infused in Active Queue Management (AQM) control schemes. ATSP exploits the knowledge of the bandwidth allocated to each terminal, as available from the satellite network operator. Besides, the satellite network property of being completely under control allows the joint collaboration of sender, receiver and routers in order to acquire a complete knowledge of the network status and eventually optimize the overall performance. The performance analysis shows that ATSP achieves a fair bandwidth share for all the satellite users and outperforms TCP Hybla, which is optimized for satellite links, in terms of throughput.

A lot of applications enhance their security via access-control systems. XACML (exten­ sible Access Control Markup Language) is a standardized policy language, which has been widely used in access-control systems. In an XACML-based access-control system, policies, requests, and responses are encoded in XACML. An XACML implementation provides func­ tionalities to evaluate XACML requests against XACML policies. There are many XACML libraries implemented in the Java programming language which are supposed to provide a set of Java classes that understand the XACML language, as well as the rules about how to process requests and how to manage attributes and other related data. This thesis focuses on the performance analysis of such libraries. We first implement a framework for analysis of Java-based XACML engines. This is accomplished by creating the hierarchy of Java classes representing the main functionality of XACML engines. We then conduct experiments by means of our framework investigating performance features of such XACML engines as Sun XACML, XEngine, and Enterprise Java XACML. The proposed approach differs from previous work in the engines chosen as well as the variety of experiments conducted and their parameters.