dataesr/scientific-paragraphs-categorization huggingface dataset:
falciparum infection at any time during pregnancy (yes/no); placental histology (parasites/no parasites); placental histology (parasites and monocytes containing malaria pigment/parasites without monocytes containing malaria pigment/no parasites). Placental histology data were only recorded in the PNG study. Where associations were observed between infection and maternofetal antibody transfer efficiency, path analysis was then conducted to investigate potential mediation of the relationship between infection and cord antibody levels through gestational age at delivery and maternal serum IgG. The proportion of the total effect due to an indirect association via gestation age at delivery or maternal serum IgG was then estimated.
Although some studies have included the potential mediating effects of elevated serum IgG and shorter gestation as confounders  [22, 23, 31, 33] , this is the first study to investigate whether placental infection is mediated via these effects with path analysis. Malaria exposure during pregnancy was captured differently at each study site and therefore separate analyses had to be performed. The prevalence of HIV is very low (<1. 5%) in these populations  [54, 55] ) so HIV is unlikely to have a substantial effect on maternofetal transfer at the population level. The lack of placental histology data from the TMBA prevented an assessment of placental infection in that study site. Maternofetal transfer efficiency of some antibodies was reduced in PNG compared to TMBA. Besides the direct effects of malaria, there are several factors that could account for this difference, including maternal genetic differences, gestational age at delivery and altered levels of total maternal IgG  [22, 23, 32].
falciparum placental infection play a substantial role, emphasising the need for highly efficacious prevention in pregnancy. Our study was subject to limitations. Our knowledge of infection status over the entire course of pregnancy was incomplete as the infection status of a woman was necessarily restricted to instances when they presented to antenatal care. Infection was detected via microscopy, so sub-microscopic infections were not captured. The infection status of cord blood was not determined in both study settings. Notably in the TMBA study we lacked placental histology data, limiting our analysis of placental histology exposures to pregnant women from PNG. We did not have data available on the outcomes of the children in their first year of life, precluding an assessment of the relationship between maternofetal antibody transfer and infant outcomes.
Acknowledgments We thank the  Centro de Produção e Pesquisa de Imunobiológicos of Paraná State  for the technical support and for providing the Montenegro antigen for this study. Financial support We thank financial support from  Conselho Nacional de Desenvolvimento Científico e Tecnológico [(CNPq) ; Grant No. 307387/2011-9  and  480292/2012-4 ],  Fundação Araucária  [Grant No. 122/2010 (Protocol 17401 )], and  Programa Nacional de Pós-Doutorado-Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [(PNPD-CAPES) ;  Protocol 2847/2011 ].
15 In preclinical studies, it appeared that systemic treatment with MVA vectors augments CD8 C T cell proportions in mouse tumors and organs. 4 onsidering these observations, combination of TG4010 and PD1-PD-L1-targeted ICIs has been considered as a promising strategy to augment tumor-specific CD8 C T cell proportions and, activate their cytotoxic action. 16 A clinical study is underway to evaluate TG4010 in combination with Nivolumab, an anti-PD-1 monoclonal antibody (NCT02823990) in patients with advanced NSCLC. The goal of the current preclinical study was to validate such combination regimens in mice presenting tumors in the lung. We could observe that systemic injection of MVA vectors led to the appearance of a defined CD3 dim CD8 dim T cell populations in the lung, comprising short-lived and early effector cells as defined in Plumlee et al.
2, BD Pharmingen) or its isotype control, and anti-Granzy-meB-Pacific Blue (clone GB11, BioLegend). To measure antigen-specific cytotoxic T cells, IFN-g-secreting living CD3 C CD8 C or CD3 dim CD8 dim cells were identified by subtracting non-specific signals observed after staining with its isotype control. The frequency fold-change of IFN-g C CD107A C GranzymeB C CD3 dim CD8 dim or CD3 C CD8 C cells in the presence of the stimulatory peptide is shown in comparison to medium-stimulated control. The mean C/-SEM is calculated for three independent experiments. Fluorescence intensities were measured on a MacsQuant cytometer (Miltenyi Biotec) and data were analysed using Kaluza software (Beckman Coulter). CD45 ¡ cells which could be linked to a reduction of tumor load observed in preliminary histological studies on lung/tumor samples (data not shown).
After permeabilization (Cytofix/ Cytoperm, BD Biosciences), activation was assessed by intracellular staining with anti-IFN-g-FITC (clone XMG1. 2, BD Pharmingen) or its isotype control, and anti-Granzy-meB-Pacific Blue (clone GB11, BioLegend). To measure antigen-specific cytotoxic T cells, IFN-g-secreting living CD3 C CD8 C or CD3 dim CD8 dim cells were identified by subtracting non-specific signals observed after staining with its isotype control. The frequency fold-change of IFN-g C CD107A C GranzymeB C CD3 dim CD8 dim or CD3 C CD8 C cells in the presence of the stimulatory peptide is shown in comparison to medium-stimulated control. The mean C/-SEM is calculated for three independent experiments. Fluorescence intensities were measured on a MacsQuant cytometer (Miltenyi Biotec) and data were analysed using Kaluza software (Beckman Coulter).
1. 1 (DNAStar, Madison, WI, USA). The full genome (STLV-1M10431) is 8,361 bp long and contains the pX gene in addition to the canonical gag, pol, and env genes common to all retroviruses. Interestingly, STLV-1M10431 encoded a functional HBZ protein in the reverse strand of the viral DNA, which was shown to play a role in the proliferation and maintenance of leukemic cells  (13). Phylogenetic analyses showed that this isolate belongs to the PTLV-1 subtype b lineage throughout the whole genome. STLV-1M10431 is thus the first full-length genome of the subtype b STLV-1 sequence in NHP and only the second fully sequenced PTLV-1 subtype b. Accession number(s). STLV-1M10431 was deposited in GenBank under the accession number MF622054.
ACKNOWLEDGMENTS This work was supported, in part, by grants from the  National Institutes of Health  ( RO1 AI 50529 ) and the  Agence Nationale de Recherches sur le Sida  ( ANRS 12125/ 12182/12325 ). We thank the  Flemish Government  for structural support to the  Centre for Research and Conservation. A. A. designed the study, performed experiments, and drafted the manuscript. M. P. designed the study and reviewed the manuscript. A. M. and F. V. took care of the gorilla, Kumba, performed the necropsy and histopathology, and reviewed the manuscript.
gov registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and treated before the age of 2 years with 12-15 months of suppressive twice-daily LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily combination zidovudine (ZDV) or ABC + 3TC + LPV/r (referred to as LPV). The primary endpoint was the difference in the proportion of children with virological suppression by 12 months post-randomisation between arms (14% non-inferiority bound, Chi-squared test).
Study design The MONOD ANRS 12206 study is a non-inferiority, open-label phase 3 randomised clinical trial conducted in Ouagadougou, Burkina Faso, and Abidjan, Côte d'Ivoire (ClinicalTrial. gov registry number: NCT01127204, first registered on 19 May 2010). Study sites were the Abobo-Avocatier urban health clinic, the CePReF-enfant and the Yopougon and Cocody University Hospitals in Abidjan, and the Yalgado Ouédraogo and the Charles de Gaulle University Hospitals in Ouagadougou. The protocol was approved by the Comité d'Ethique pour la Recherche en Santé du Burkina Faso and the Comité National d'Ethique et de la Recherche en Côte d'Ivoire.
The ANRS consensus technique (www. hiv frenchresistance. org) was used to genotype protease and reverse transcriptase genes. Sequences were edited with Bio-Edit sequence Alignment Editor (version 7. 0) and trees constructed with Mega 4. Relevant drug-resistance mutations were interpreted according to the Stanford University HIV Drug Resistance Database (HIVdb Program, http://hivdb. stanford. edu) and the ANRS-v24 interpretation rule (http://www. hivfrenchresistance. org/2011/Algo-2011. pdf). HIV-1 subtypes were assigned using REGA (http://www. bioafrica. net/rega-genotype/html/index. html) and COMET (http://comet. retrovirology. lu) HIV-1 subtyping tools against reference HIV-1 group M sequences from GenBank (http://www. ncbi. nlm. nih. gov/Genbank/ index. html). Blood samples were collected from children and transferred for processing within 4 hours.
Based on our anticipated enrolment of 146 children with 73 children per arm, we expected an 80% power to detect this difference. In the CHER trial, the 12-month survival probability in infants on a LPV/r-based triple therapy was 96%  [4]. Because virological data were not yet available at the time of our protocol, we expected a 95% response on LPV according to the Yeni 2008 report  [11]. Thus, assuming a 12-month virological suppression among survivors on LPV of 90%, we anticipated recruited 162 children in the initial LPV-based cohort. To compare the characteristics of the study population, we used Chi-squared or Fisher's exact tests for categorical variable and t tests or Mann-Whitney tests for continuous variables. We analysed the correlates of viral suppression at 12 months post-randomisation, using a multivariate logistic regression.
Acknowledgements We thank the children, their families and the staff from all participating centres for their dedication. We warmly thank  Andrea Ciaranello  for her helpful comments on an early draft,  Valérie Journot  for her helpful statistical advice, and  Sophie Desmonde  for editing. We thank the MONOD ANRS 12206 trial independent data monitoring committee meeting:  Dominique Costagliola  (Chair; Paris, France),  Mark Cotton  ( Cape Town, South Africa ),  Carlo Giaquito  ( Bologna, Italie ),  Diana Gibb  ( London, UK ) and  Elisabeth Menu  (Paris, France). Désiré Dahourou PhD was funded by the  ANRS  ( ANRS12206-B89 ). Malik Coulibaly PhD was funded by  EDCTP-ANRS-LIH. The  ANRS 12206 MONOD Collaboration Study Group  (as of 7 July 2015): Participating sites. Burkina Faso ,  Ouagadougou: Centre de Recherche International pour la Santé :  Malik Coulibaly ,  Désiré Lucien Dahourou ,  Nicolas Meda  (co-investigator),  Colette Ouédraogo ,  Mamadou Sawadogo ,  Wilfried Somé ,  Désiré Sondo ,  Elisabeth Thio.
However, there is a lack of published data in Myanmar on first-line ART failure and the rate of switching to a second-line regimen, both of which are important indicators for the Myanmar HIV/AIDS Program to assess. The Integrated HIV Care (IHC) program, supported by The Union in Myanmar, has been providing treatment and care to PLHIV from all regions of the country since 2005. By 2015, nearly 30,000 patients were on ART and all patients' data had been routinely collected in an electronic database. In this study, we retrospectively analysed the rates of treatment failure and switching to second-line ART in adolescent and adult patients receiving first-line ART in the IHC program. We also determined risk factors associated with these two outcomes.
These clinical or immunological suspected failures are not routinely documented in the IHC database. The program follows a targeted viral load testing strategy as routine viral load monitoring is not available, but only some of the patients who have clinical and immunological failure on first-line ART are referred for HIV viral load testing by clinicians. Viral load testing using an automated c1000 RealTime PCR system (Bio-Rad Sciences, Hercules, California, USA and HIV Generic Charge Virale, Biocentric, Bandol, France) has been available in the Public Health Laboratory in Mandalay. This laboratory is under the management of the Ministry of Health, Myanmar, which has been supported by the Union since late 2012. Prior to this and since 2009, the samples were sent to an outside laboratory for viral load testing using Rotor-Gene Real-Time Analysis (PG.
Study variables Outcome variables. The two outcome variables were virological failure while on first-line ART and switching to second-line ART. We defined virological failure as a viral load result greater than 5000 copies/mL before March 2015 and greater than 1000 copies/mL after March 2015. Switching to second-line ART was defined as a patient being switched to a protease inhibitor based ART regimen from a nucleoside reverse-transcriptase inhibitor and nonnucleoside reverse-transcriptase inhibitor based ART regimens. For those who switched to second-line ART, we also recorded the reason for switching as documented in the database. Exposure variables. Exposure variables included: gender; age at ART initiation (groups included adolescents (10 to 19 years)  [18]  and adults (>19 years)); marital, employment and literacy status; HIV transmission risk factors; availability of a care taker (someone who comes along with the patient for clinic visit and helps patient for taking drugs at home, usually the patient' family or close friend) when ART was initiated; baseline CD4 cell count and WHO clinical stage; first-line ART regimens at enrolment; history of ART before coming to IHC; baseline hepatitis B and C status; type of current IHC site (ART centre or decentralized site), number of times the patient had been documented as "lost to follow-up" from care; number of times the first-line ART regimen had been modified.
Previous studies have shown that a delay in treatment switching when required is associated with high mortality and lost to follow-up  [5, 9, 10]. Hence, it is important for the program to follow-up those patients who have not switched but are still under care. One of the strengths of this study is the relatively large sample size with individual patient follow-up time data. The study was also conducted within the routine program setting which reflects ground reality. Because of the existing mechanisms of data validity, the data are relatively good and reliable. We also reported this study according to STROBE guidelines  [30]. However, there were several limitations to this study. First, we excluded: 1) women who entered the program for PMTCT interventions as the database does not fully capture their starting ART regimens; 2) 40 patient records with missing ART start date and/or the type of regimen; 3) 6778 patients with follow-up less than 6 months.
Second, although clinical and immunological failure was used as a proxy for virological failure by clinicians for deciding to switch to secondline ART or to refer for a HIV viral load test, there was no data about how many patients had clinical and immunological failure in this program. Moreover, not all viral load measurements were captured because some patients died or were lost to follow-up after testing and before the results were dispatched to be recorded in the patient's file. This may affect the rate of failure observed in this study. Third, as this study was an analysis of a large cohort followed up for 10 years, the viral load cut off points to declare virological failure differed over these years. Fourth, there was no viral load testing or available second-line ART from 2005 to 2008 and patients who experienced virological failure during these four years were not be able to be diagnosed in the program or captured in this database.
Acknowledgments We are grateful to The  Department for International Development (DFID), UK  for funding the  Global Operational Research Fellowship Programme  at the  International Union Against Tuberculosis and Lung Disease (The Union ), Paris, France in which  Nang Thu Thu Kyaw ,  Myo Min Oo ,  Khine Wut Yee Kyaw  [authors] works as operational research fellows and for funding this open access publication. We are also grateful to the patients receiving care at the  Integrated HIV Care Program  and health care providers and administrative staff at the  Union office and Ministry of Health and Sports in Myanmar  for providing treatments and care to patients and collecting this data.
The latter demonstrated that the conclusions of the study were robust to input parameters changes since ICERs remained below or close to CHF 40,000 per QALY gained. Second, resource use and corresponding cost data were taken from a Swiss burden of illness study based on Swiss expert opinions conducted in 2007 In the absence of better data, these were inflated to represent 2014 costs. 26 Sensitivity analysis indicated an only mild impact of these parameters on the ICER result. Third, hospitalization costs were assessed using hospitalization records extracted from only one hospital in Switzerland (CHUV). Thus, hospitalization costs may not be representative for the entire Swiss population. Moreover, the same ICD codes were used to assess HZrelated and PHN-related hospitalizations, and may have led to a flawed estimation of PHN hospitalization costs (no differentiation was possible).
The model uses a Markov cycle length of one month. Within each cycle, members of the cohort can remain in their current health state or make a transition into one of the allowable states. Transitions are governed by a matrix of probability values. The transition probabilities determine the proportion of the cohort moving through the HZ and PHN states, and eventually to death, in each monthly cycle. The model runs until the entire cohort has died. For most epidemiological and cost parameters, age-specific Swiss data were retrieved. HZ-related transition probabilities were derived from published literature. Costs were assessed from a third party payer perspective. Discount rates applied in the base case were 3. 5% for costs and for 1. 5% for outcomes,  49, 50  to maintain comparability with the previous analysis.
Epidemiology of herpes zoster Herpes zoster. Data from the Swiss Sentinel Surveillance Network were used as a source of data for HZ incidence rates (Table  3 ). 53 For HZ duration, information from a clinical trial was used. 4 Most patients experienced a duration of 30 days, as also reported elsewhere in the literature. 4, 54, 55 vidence from the UK indicates no mortality directly linked to HZ. 25  As no information on HZ mortality was available for Switzerland, the UK data was applied in the model and HZ mortality was set at 0% for all age groups. Post-herpetic neuralgia. The proportion of PHN has been reported as a proportion of HZ patients who develop PHN, and has been applied only to those HZ cases presenting with pain (Table  3 ). 25 The literature provides evidence that patients have a higher risk of developing PHN if they experience severe pain during HZ.
Vaccine efficacy Reduction of HZ incidence and PHN proportion. Vaccine efficacy was derived from clinical trials. 4, 20 The reduction in the number of PHN cases is due to the indirect reduction in the HZ cases. The vaccine efficacy data on HZ and PHN cases are expressed as relative risks and differ by age group (Table  3 ). 4, 20 n scenario analyses, alternative inputs for both HZ and PHN incidence were tested. 24, 25 N duration. In addition, vaccination has a positive effect on the duration of PHN. In the model this indirectly impacted the pain severity experienced by the patient since it implied a shorter period of time spent in each painful PHN health state. Within the vaccination group, the PHN duration was assumed to be 8. 07 months and 9. 58 months for the 60-69 y and the 70C years old individuals, respectively.
Unvaccinated individuals experienced a longer PHN duration of 10. 34 months and 12. 90 months for the 60-69 y and the 70C years old individuals, respectively (Table  3 )  4, 56. Vaccine efficacy duration and waning rate for HZ. The HZ vaccine efficacy was assumed to decrease over time. Available HZ: herpes zoster; PHN: indicates post-herpetic neuralgia, defined as pain persisting or occurring after herpes zoster rash onset published data on efficacy decline following vaccination vary between 0% and 8. 3% per year. 21 Given that the waning rate is not constant over time and unequal among different age groups, data from a durability model were incorporated. The durability model was developed to assess the efficacy of HZ vaccine based on long-term efficacy data, the age at time of vaccination and time since vaccination.
Utilities The model contains different pain states and specific utilities associated with these states. The pain states related to HZ cover no pain; mild pain; moderate pain; and severe pain. The pain states related to PHN exclude the no-pain state, as pain is a prerequisite for a PHN diagnosis. The utilities of the various pain states were used to obtain decrements which were subsequently applied to age-specific utilities. 7 Decrements were defined as the part of the baseline utility (i. e. , HZ with no pain) that needed to be subtracted to obtain the utility value for a given health state (Table  4 ). These were combined with age-specific utilities for the general population. UK data from the Health Survey for England were used for this purpose, since no age-specific utility values by gender are available for the Swiss population (65-74 years: 0.
92 male, 0. 85 female; 75-79 years: 0. 85 male, 0. 80 female). 57 Since non-genderseparated 5-year age groups in the Swiss population were evaluated at one time, overall utility values were calculated from this data by weighting the male and female utility values by the gender distribution in the relevant age groups in Switzerland. The final utility values were calculated as the age-specific utilities minus the applicable decrement of the specific health state. Additionally, alternative utility inputs were extracted from other publications and assessed in sensitivity analyses  [21] [22] [23]  (Table  2 ).
Study design Samples and signalment data were collected from dogs in animal shelters, breeding kennels and academic or private veterinary clinics across Europe by collaborating Investigator Centres between October 2011 and August 2013. Dogs were actively recruited onto the study and sampled upon presentation to the veterinarian if they fell into one of three different clinical groups: (A) clinically unaffected but exposed to acute CIRD-affected dogs, (B) acute CIRD-affected dogs (0-3 days post onset of CIRD), or (C) convalescent CIRD-affected dogs (10-12 days post onset of CIRD). Details of the clinical grouping, source (i. e. clientowned, shelter/rehoming kennel, hospital, breeding kennel), recorded or estimated age, vaccination history for Bb, CPIV, CAV-2 and CDV, and clinical respiratory score (1-5) at the time of sample collection were recorded.
Statistical analysis Data were recorded in Excel spreadsheets (Microsoft) and imported into Stata/SE 13 software (Statacorp) for analysis. Continuous variables were summarised using mean (standard deviation) if normally distributed and median (minimum, maximum) if non-normally distributed. Categorical variables were summarised using numbers and percent in each category and 95% confidence intervals (CI) around prevalence estimates calculated using the Clopper-Pearson method. For the purposes of these analyses the clinical score variable was collapsed from the original categorisation of 1-5 (as detailed above) to a threepoint 'severity score' of 'no disease' (clinical score 1), 'mild to moderate disease' (clinical score 2 and 3) and 'severe disease' (clinical score 4 and 5). The presence or absence of disease was also assessed, where the original clinical score of 2-5 indicated the presence of disease and 1 indicated no disease.