Search for Baryon Number Violation in Top Quark Production and Decay Using Proton-Proton Collisions at sqrt[s]=13 TeV.

A search is presented for baryon number violating interactions in top quark production and decay. The analysis uses data from proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the CMS detector at the LHC with an integrated luminosity of 138 fb^{-1}. Candidate events are selected by requiring two oppositely charged leptons (electrons or muons) and exactly one jet identified as originating from a bottom quark. Multivariate discriminants are used to separate the signal from the background. No significant deviation from the standard model prediction is observed. Upper limits are placed on the strength of baryon number violating couplings. For the first time the production of single top quarks via baryon number violating interactions is studied. This allows the search to set the most stringent constraints to date on the branching fraction of the top quark decay to a lepton, an up-type quark (u or c), and a down-type quark (d, s, or b). The results improve the previous bounds by 3 to 6 orders of magnitude based on the fermion flavor combination of the baryon number violating interactions.

Search for exotic decays of the Higgs boson to a pair of pseudoscalars in the µµbb and ττbb final states.

A search for exotic decays of the Higgs boson (H) with a mass of 125GeV to a pair of light pseudoscalars a1 is performed in final states where one pseudoscalar decays to two b quarks and the other to a pair of muons or τ leptons. A data sample of proton-proton collisions at s=13TeV corresponding to an integrated luminosity of 138fb-1 recorded with the CMS detector is analyzed. No statistically significant excess is observed over the standard model backgrounds. Upper limits are set at 95% confidence level (CL) on the Higgs boson branching fraction to µµbb and to ττbb, via a pair of a1s. The limits depend on the pseudoscalar mass ma1 and are observed to be in the range (0.17-3.3) ×10-4 and (1.7-7.7) ×10-2 in the µµbb and ττbb final states, respectively. In the framework of models with two Higgs doublets and a complex scalar singlet (2HDM+S), the results of the two final states are combined to determine upper limits on the branching fraction B(H→a1a1→ℓℓbb) at 95% CL, with ℓ being a muon or a τ lepton. For different types of 2HDM+S, upper bounds on the branching fraction B(H→a1a1) are extracted from the combination of the two channels. In most of the Type II 2HDM+S parameter space, B(H→a1a1) values above 0.23 are excluded at 95% CL for ma1 values between 15 and 60GeV.

Observation of WWγ Production and Search for Hγ Production in Proton-Proton Collisions at sqrt[s]=13 TeV.

The observation of WWγ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138 fb^{-1} is presented. The observed (expected) significance is 5.6 (5.1) standard deviations. Events are selected by requiring exactly two leptons (one electron and one muon) of opposite charge, moderate missing transverse momentum, and a photon. The measured fiducial cross section for WWγ is 5.9±0.8(stat)±0.8(syst)±0.7(modeling) fb, in agreement with the next-to-leading order quantum chromodynamics prediction. The analysis is extended with a search for the associated production of the Higgs boson and a photon, which is generated by a coupling of the Higgs boson to light quarks. The result is used to constrain the Higgs boson couplings to light quarks.

New Structures in the J/ψJ/ψ Mass Spectrum in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search is reported for near-threshold structures in the J/ψJ/ψ invariant mass spectrum produced in proton-proton collisions at sqrt[s]=13 TeV from data collected by the CMS experiment, corresponding to an integrated luminosity of 135 fb^{-1}. Three structures are found, and a model with quantum interference among these structures provides a good description of the data. A new structure is observed with a local significance above 5 standard deviations at a mass of 6638_{-38}^{+43}(stat)_{-31}^{+16}(syst) MeV. Another structure with even higher significance is found at a mass of 6847_{-28}^{+44}(stat)_{-20}^{+48}(syst) MeV, which is consistent with the X(6900) resonance reported by the LHCb experiment and confirmed by the ATLAS experiment. Evidence for another new structure, with a local significance of 4.7 standard deviations, is found at a mass of 7134_{-25}^{+48}(stat)_{-15}^{+41}(syst) MeV. Results are also reported for a model without interference, which does not fit the data as well and shows mass shifts up to 150 MeV relative to the model with interference.

Search for Inelastic Dark Matter in Events with Two Displaced Muons and Missing Transverse Momentum in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search for dark matter in events with a displaced nonresonant muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138 fb^{-1} of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed. Upper limits are set on the product of the inelastic dark matter production cross section σ(pp→A^{'}→χ_{1}χ_{2}) and the decay branching fraction B(χ_{2}→χ_{1}µ^{+}µ^{-}), where A^{'} is a dark photon and χ_{1} and χ_{2} are states in the dark sector with near mass degeneracy. This is the first dedicated collider search for inelastic dark matter.

Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pp Collisions at sqrt[s]=13 TeV.

The first search for scalar leptoquarks produced in τ-lepton-quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138 fb^{-1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength.

Observation of the Rare Decay of the η Meson to Four Muons.

A search for the rare η→µ^{+}µ^{-}µ^{+}µ^{-} double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101 fb^{-1}. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→µ^{+}µ^{-} decay as normalization, the branching fraction B(η→µ^{+}µ^{-}µ^{+}µ^{-})=[5.0±0.8(stat)±0.7(syst)±0.7(B_{2µ})]×10^{-9} is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions.

Integrating hepatitis C treatment into multidrug-resistant TB care.

BACKGROUND: Direct-acting antivirals (DAAs) are not widely used for patients with chronic hepatitis C virus (HCV) infection and multidrug- or rifampicin-resistant TB (MDR/RR-TB). We describe the implementation aspects of a new integrated model of care in Armenia and the perceptions of the healthcare staff and patients. METHODS: We used qualitative methods, including a desktop review and semi-structured individual interviews with healthcare staff and with patients receiving HCV and MDR/RR-TB treatment. RESULTS: The new integrated model resulted in simplified management of HCV and MDR/RR-TB at public TB facilities. Training on HCV was provided for TB clinic staff. All MDR/RR-TB patients were systematically offered HCV testing and those diagnosed with HCV, offered treatment with DAAs. Treatment monitoring was performed by TB staff in coordination with a hepatologist. The staff interviewed had a positive opinion of the new model. They suggested that additional training should be provided. Most patients were fully satisfied with the care received. Some were concerned about the increased pill burden. CONCLUSION: Integrating HCV treatment into MDR/ RR-TB care was feasible and appreciated by patients and staff. This new model facilitated HCV diagnosis and treatment among people with MDR/RR-TB. Our results encourage piloting this model in other settings.

CONTEXTE: Les antiviraux à action directe (DAA) sont peu prescrits aux patients atteints d'hépatite C (HCV) chronique et de TB multirésistante ou résistante à la rifampicine (MDR/RR-TB). Nous décrivons la mise en place d'un nouveau modèle de soins intégrés en Arménie, ainsi que l'opinion du personnel soignant et des patients. MÉTHODES: Nous avons utilisé des méthodes qualitatives, comprenant un examen électronique de la documentation et des entretiens individuels semi-structurés avec le personnel soignant et les patients sous traitement pour HCV et MDR/RR-TB. RÉSULTATS: Le nouveau modèle intégré a permis de simplifier la prise en charge du HCV et de la MDR/RR-TB dans les centres de soins publics de la TB. Une formation sur le HCV a été dispensée au personnel des centres antituberculeux. Tous les patients atteints de MDR/RR-TB se sont vu systématiquement proposer un test de dépistage du HCV, et un traitement par DAA a été proposé à ceux dont le résultat était positif. Le suivi du traitement a été réalisé par le personnel des centres antituberculeux, conjointement à un hépatologue. Les membres du personnel interrogés avaient une opinion positive du nouveau modèle et suggéraient de dispenser d'autres formations. La plupart des patients étaient pleinement satisfaits des soins reçus, mais certains étaient inquiets au vu du nombre accru de comprimés à prendre. CONCLUSION: L'intégration du traitement du HCV aux soins de la MDR/RR-TB s'est avérée possible et a été appréciée par les patients et le personnel soignant. Ce nouveau modèle a facilité le diagnostic et le traitement du HCV chez les patients atteints de MDR/RR-TB. Ce modèle devrait être testé dans d'autres contextes.

What is the best culture conversion prognostic marker for patients treated for multidrug-resistant tuberculosis?

INTRODUCTION: Identification of good prognostic marker for tuberculosis (TB) treatment response is a necessary step on the path towards a surrogate marker to reduce TB trial duration.METHODS: We performed a retrospective analysis on routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture conversion, defined as two consecutive negative cultures, was assessed, and performance of culture conversion at Month 2 and Month 6 to predict treatment success were explored. To explore factors associated with positive predicted value (PPV) and the specificity of culture conversion, a multinomial logistic regression was fitted.RESULTS: This study included 634 patients: 68.5% were males; the median age was 35 years, 75.2% were previously treated for TB, 59.4% were resistant only to isoniazid and rifampicin and 18.1% resistant to fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while specificity was much higher for culture conversion at Month 2: 91.3% (95%CI 86.1-95.1). PPV of culture conversion at Month 2 did not vary strongly according to patients' characteristics, while specificity was slightly higher among patients with fluoroquinolone-resistant strains.CONCLUSION: Culture conversion at Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the advantage of using an earlier marker, further evaluation as a surrogate marker is warranted to shorten TB trials.

[CORRELATION OF INDIVIDUAL AND JOINT INTEREST WITHIN MEDICAL LEGAL RELATIONS (REVIEW)].

The objective of the article is to determine the content and correlation of individual and joint interest within medical legal relations in Ukraine. To achieve this objective the authors have applied general scientific and special methods of cognition. The materials of research were statistical data on infectious diseases about the state of vaccinations in Ukraine, judicial practice, and national legislation. It has been concluded that individual and joint interest within medical legal relations are aimed at various objects: individual and public health. These objects are interconnected as general and special, since public health is a combination of individual health. It has been established that public and individual health does not have an economic content, cannot participate in the economic turnover, but have a social value. The prevalence of joint interest over the individual has been grounded. Individual interest within medical legal relations has been defined as the orientation of an individual to protect own health. It has been proved that joint (public) interest within medical legal relations is a set of individual (private) interests of individuals in the health care area. This interest is manifested in the formation of collective immunity, control over the spread of infectious diseases, the creation of conditions for affordable medical care, etc.

Is 6 months of bedaquiline enough? Results from the compassionate use of bedaquiline in Armenia and Georgia.

BACKGROUND AND SETTING: Bedaquiline (BDQ) was initially only available through compassionate use programmes. OBJECTIVE: To assess the effectiveness and safety of multidrug-resistant tuberculosis (MDR-TB) treatment containing BDQ. METHOD: Retrospective analysis of data from patients receiving BDQ through compassionate use in Armenia and Georgia from April 2013 to April 2015. Logistic regression was used to assess the risk factors associated with unsuccessful treatment outcomes. RESULTS: Of 82 patients included, 84.2% (69/82) had fluoroquinolone-resistant MDR-TB and 43.4% (23/53) were seropositive for the hepatitis C virus (HCV). The culture conversion rate was 84.4% (54/64), and 18.5% (10/54) reverted back to positive. In total, 79.3% (65/82) of the patients reported at least one adverse event. Serious adverse events were reported in 14 patients, with 10/14 patients experiencing fatal outcomes-6/10 related to advanced TB and 2/10 assessed as possibly related to BDQ. Treatment outcomes were as follows: 58.5% treatment success, 12.2% deaths, 7.3% failures and 21.9% lost to follow-up. HCV coinfection was associated with unsuccessful outcomes (adjusted OR 4.45, 95%CI 1.23-16.13). CONCLUSION: BDQ through compassionate use showed relatively good success rates and safety profiles in a cohort with difficult-to-treat MDR-TB. High rates of reversion may indicate that >24 weeks of BDQ is necessary in some cases. HCV coinfection should be diagnosed and treatment considered in MDR-TB patients.

Identification of patients who could benefit from bedaquiline or delamanid: a multisite MDR-TB cohort study.

BACKGROUND: The World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome. OBJECTIVE: To identify patients at risk of unfavourable outcomes who may benefit from the new drugs. METHODS: Retrospective cohort study of treatment outcomes involving four to five effective drugs for 15-24 months in programmes in Uzbekistan, Georgia, Armenia, Swaziland and Kenya between 2001 and 2011. RESULTS: Of 1433 patients, 48.5% had body mass index (BMI) <18.5 kg/m(2), 72.9% had a high bacillary load, 16.7% were resistant to two injectables, 2.9% were resistant to ofloxacin (OFX) and 3.0% had extensively drug-resistant TB (XDR-TB). Treatment success ranged from 59.7% (no second-line resistance) to 27.0% (XDR-TB). XDR-TB (aOR 8.16, 95%CI 3.22-20.64), resistance to two injectables (aOR 1.90, 95%CI 1.00-3.62) or OFX (aOR 5.56, 95%CI 2.15-14.37), past incarceration (aOR 1.88, 95%CI 1.11-3.2), history of second-line treatment (aOR 3.24, 95%CI 1.53-6.85), low BMI (aOR 2.22, 95%CI 1.56-3.12) and high bacillary load (aOR 2.32, 95%CI 1.15-4.67) were associated with unfavourable outcomes. Patients started on capreomycin rather than kanamycin were more likely to have an unfavourable outcome (aOR 1.54, 95%CI 1.04-2.28). CONCLUSION: In our cohort, patients who may benefit from bedaquiline and delamanid represented up to two thirds of all MDR-TB patients.

Ethambutol-resistance testing by mutation detection using MTBDRsl.

AIMS AND OBJECTIVES: Despite the successes in managing drug-susceptible TB, drug-resistant (DR) tuberculosis is a major challenge to the effectiveness of National Tuberculosis Program in Armenia, placing the country in the list of 18 high-burden countries for MDR-TB in the WHO European Region. Estimated burden of MDR-TB in 2012 was 9.4 (7-12) and 43 (38-49) among retreatment TB cases. A total of 92 laboratory confirmed cases had been reported to the WHO (57 new and 35 previously treated) out of 511 cases tested for MDR-TB. GenoType MTBDRsl is a new molecular kit designed for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. The aim of this study was to identify the mutation that confers resistance to ethambutol (EMB) in Mycobacterium tuberculosis in comparison with the phenotypic drug susceptibility test (DST). Ethambutol is used in M/XDR-TB regimens only if it is susceptible by DST results. METHODS: A set of 173 drug resistances TB isolates during 2011 and 2012 period, being either acid fast bacterium positive or negative but culture positive resistant to isoniazid, rifampin, or both according to the GenoType MTBDR plus assay were consecutively tested, using the GenoType MTBDRsl (MTBDR plus version 1.0 and MTBDRsl version 2.0 Hain Lifescience, Nehren). embB gene analysis and the results were compared to phenotypic EMB testing (DST). The DNA preparation method used as described recommended by the manufacturer. RESULTS: Genotypic analysis identified mutations at codon 306 of the embB gene in 20.8% (36/173) and miss band of wild type in 12.71% (22/173) of the resistant isolates in comparison to only 14.45% (25/173) of those that were phenotypically resistant to EMB by DST MGIT liquid media. Mutation locus were identified in embB MUT1B and embB MUT1A 8.67% (15/173) and 12.13% (21/173), simultaneously. Phenotypic retesting in MGIT demonstrated that 45 (306 of the embB gene and miss band of wild type together) genotypically resistant isolates were phenotypically resistant to EMB. This implies that 58.62% (33/58) of EMB resistance had been phenotypically missed by routine laboratory procedures. EMB resistance was closely linked to multidrug resistance (MDR); 70.69% (41/58) of the EMB-resistant isolates were resistant to both isoniazid and rifampicin. CONCLUSION: Implementation of more accurate diagnosis of EMB resistance may enhance patient management in Armenia, as standardized treatment of MDR-TB with second-line drugs is currently dependent on the outcome of the EMB resistance test.

Reasons for defaulting from drug-resistant tuberculosis treatment in Armenia: a quantitative and qualitative study.

SETTING: Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB). OBJECTIVE: To identify factors related to default from DR-TB treatment in Yerevan. DESIGN: Using a retrospective cohort design, we compared defaulters with patients who were cured, completed or failed treatment. Patients who initiated DR-TB treatment from 2005 to 2011 were included in the study. A qualitative survey was conducted including semi-structured interviews with defaulters and focus group discussions with care providers. RESULTS: Of 381 patients, 193 had achieved treatment success, 24 had died, 51 had failed treatment and 97 had defaulted. The number of drugs to which the patient was resistant at admission (aRR 1.16, 95%CI 1.05-1.27), the rate of treatment interruption based on patient's decision (aRR 1.03, 95%CI 1.02-1.05), the rate of side effects (aRR 1.18, 95%CI 1.09-1.27), and absence of culture conversion during the intensive phase (aRR 0.47, 95%CI 0.31-0.71) were independently associated with default from treatment. In the qualitative study, poor treatment tolerance, a perception that treatment was inefficient, lack of information, incorrect perception of being cured, working factors and behavioural problems were factors related to treatment default. CONCLUSION: In addition to economic reasons, poor tolerance of and poor response to treatment were the main factors associated with treatment default.

Performance of decentralised facilities in tuberculosis case notification and treatment success in Armenia.

We assessed the performance of decentralised tuberculosis (TB) out-patient centres in tuberculosis (TB) case notification and treatment success in Armenia. An average threshold case notification of ⩾37/100 000 was seen in centres that had higher numbers of presumptive TB patients, where more TB was diagnosed by in-patient facilities and where TB contacts were examined. The number of doctors and/or TB specialists at centres did not influence case notification. Onsite smear microscopy was significantly associated with a treatment success rate of ⩾85% for new TB patients. Addressing specific characteristics of TB centres associated with lower case notification and treatment success and optimising their location may improve performance.