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1.
Nature ; 612(7939): 240-245, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36477133

RESUMO

Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.

2.
Nature ; 594(7864): 508-512, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34163052

RESUMO

A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform1-4. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10-4 rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation5,6 and paves the way to study new quantum materials with superconducting qubits.

3.
Cytokine ; 157: 155965, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35843124

RESUMO

The purpose of this study was to determine whether six weeks of high intensity interval training (HIIT) would lead to greater changes in resting concentrations of salivary IL-8 and IL-1ra than moderate intensity continuous training (MICT) in young, healthy adults, and to determine whether changes in IL-8 and IL-1ra after six weeks of either HIIT or MICT were associated with changes in maximal exercise capacity (VO2max). Participants were randomly assigned to 6 weeks of HIIT (n = 12) or MICT (n = 11), matched for workload. Saliva samples were collected at the beginning (T1) and end (T2) of the intervention, and analyzed for IL-8 and IL-1ra. Participants in both groups had significant improvements in VO2max; there were no group differences in improvements. A greater reduction in IL-8 was observed in the MICT group when compared to the HIIT group (HIIT median: -9.5; MICT median: -82.3 pg/µg of protein; U = 11.5, p < 0.001). When combining the HIIT and MICT group, there were significant reductions in IL-8 from T1 to T2. There was no correlation between changes in IL-8 (r < 0.00) or IL-1ra (r = -0.013) with changes in VO2max. In conclusion, 6 weeks of exercise training leads to a reduction in IL-8; MICT may lead to greater reductions when compared to HIIT. Future research examining longer intervention periods is needed to further elucidate the effects of HIIT and MICT on different pro and anti-inflammatory cytokines.


Assuntos
Treinamento Intervalado de Alta Intensidade , Adulto , Exercício Físico , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-8 , Consumo de Oxigênio
4.
Nature ; 534(7606): 222-6, 2016 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-27279216

RESUMO

Quantum mechanics can help to solve complex problems in physics and chemistry, provided they can be programmed in a physical device. In adiabatic quantum computing, a system is slowly evolved from the ground state of a simple initial Hamiltonian to a final Hamiltonian that encodes a computational problem. The appeal of this approach lies in the combination of simplicity and generality; in principle, any problem can be encoded. In practice, applications are restricted by limited connectivity, available interactions and noise. A complementary approach is digital quantum computing, which enables the construction of arbitrary interactions and is compatible with error correction, but uses quantum circuit algorithms that are problem-specific. Here we combine the advantages of both approaches by implementing digitized adiabatic quantum computing in a superconducting system. We tomographically probe the system during the digitized evolution and explore the scaling of errors with system size. We then let the full system find the solution to random instances of the one-dimensional Ising problem as well as problem Hamiltonians that involve more complex interactions. This digital quantum simulation of the adiabatic algorithm consists of up to nine qubits and up to 1,000 quantum logic gates. The demonstration of digitized adiabatic quantum computing in the solid state opens a path to synthesizing long-range correlations and solving complex computational problems. When combined with fault-tolerance, our approach becomes a general-purpose algorithm that is scalable.

5.
Phys Rev Lett ; 126(13): 132701, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33861111

RESUMO

We compute continuum and infinite volume limit extrapolations of the structure factors of neutron matter at finite temperature and density. Using a lattice formulation of leading-order pionless effective field theory, we compute the momentum dependence of the structure factors at finite temperature and at densities beyond the reach of the virial expansion. The Tan contact parameter is computed and the result agrees with the high momentum tail of the vector structure factor. All errors, statistical and systematic, are controlled for. This calculation is a first step towards a model-independent understanding of the linear response of neutron matter at finite temperature.

6.
Br J Dermatol ; 184(3): 482-494, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32348549

RESUMO

BACKGROUND: The epidermal barrier is important for water conservation, failure of which is evident in dry-skin conditions. Barrier function is fulfilled by the stratum corneum, tight junctions (TJs, which control extracellular water) and keratinocyte mechanisms, such as organic osmolyte transport, which regulate intracellular water homeostasis. Organic osmolyte transport by keratinocytes is largely unexplored and nothing is known regarding how cellular and extracellular mechanisms of water conservation may interact. OBJECTIVES: We aimed to characterize osmolyte transporters in skin and keratinocytes, and, using transporter inhibitors, to investigate whether osmolytes can modify TJs. Such modification would suggest a possible link between intracellular and extracellular mechanisms of water regulation in skin. METHODS: Immunostaining and quantitative polymerase chain reaction of organic osmolyte-treated organ-cultured skin were used to identify changes to organic osmolyte transporters, and TJ protein and gene expression. TJ functional assays were performed on organic osmolyte-treated primary human keratinocytes in culture. RESULTS: Immunostaining demonstrated the expression of transporters for betaine, taurine and myo-inositol in transporter-specific patterns. Treatment of human skin with either betaine or taurine increased the expression of claudin-1, claudin-4 and occludin. Osmolyte transporter inhibition abolished this response. Betaine and taurine increased TJ function in primary human keratinocytes in vitro. CONCLUSIONS: Treatment of skin with organic osmolytes modulates TJ structure and function, which could contribute to the epidermal barrier. This emphasizes a role for organic osmolytes beyond the maintenance of intracellular osmolarity. This could be harnessed to enhance topical therapies for diseases characterized by skin barrier dysfunction.


Assuntos
Queratinócitos , Proteínas de Junções Íntimas , Epiderme , Humanos , Proteínas de Membrana Transportadoras , Pele , Junções Íntimas
7.
Nature ; 519(7541): 66-9, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25739628

RESUMO

Quantum computing becomes viable when a quantum state can be protected from environment-induced error. If quantum bits (qubits) are sufficiently reliable, errors are sparse and quantum error correction (QEC) is capable of identifying and correcting them. Adding more qubits improves the preservation of states by guaranteeing that increasingly larger clusters of errors will not cause logical failure-a key requirement for large-scale systems. Using QEC to extend the qubit lifetime remains one of the outstanding experimental challenges in quantum computing. Here we report the protection of classical states from environmental bit-flip errors and demonstrate the suppression of these errors with increasing system size. We use a linear array of nine qubits, which is a natural step towards the two-dimensional surface code QEC scheme, and track errors as they occur by repeatedly performing projective quantum non-demolition parity measurements. Relative to a single physical qubit, we reduce the failure rate in retrieving an input state by a factor of 2.7 when using five of our nine qubits and by a factor of 8.5 when using all nine qubits after eight cycles. Additionally, we tomographically verify preservation of the non-classical Greenberger-Horne-Zeilinger state. The successful suppression of environment-induced errors will motivate further research into the many challenges associated with building a large-scale superconducting quantum computer.

8.
Phys Rev Lett ; 125(12): 120504, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33016760

RESUMO

Quantum algorithms offer a dramatic speedup for computational problems in material science and chemistry. However, any near-term realizations of these algorithms will need to be optimized to fit within the finite resources offered by existing noisy hardware. Here, taking advantage of the adjustable coupling of gmon qubits, we demonstrate a continuous two-qubit gate set that can provide a threefold reduction in circuit depth as compared to a standard decomposition. We implement two gate families: an imaginary swap-like (iSWAP-like) gate to attain an arbitrary swap angle, θ, and a controlled-phase gate that generates an arbitrary conditional phase, ϕ. Using one of each of these gates, we can perform an arbitrary two-qubit gate within the excitation-preserving subspace allowing for a complete implementation of the so-called Fermionic simulation (fSim) gate set. We benchmark the fidelity of the iSWAP-like and controlled-phase gate families as well as 525 other fSim gates spread evenly across the entire fSim(θ,ϕ) parameter space, achieving a purity-limited average two-qubit Pauli error of 3.8×10^{-3} per fSim gate.

9.
Nature ; 508(7497): 500-3, 2014 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-24759412

RESUMO

A quantum computer can solve hard problems, such as prime factoring, database searching and quantum simulation, at the cost of needing to protect fragile quantum states from error. Quantum error correction provides this protection by distributing a logical state among many physical quantum bits (qubits) by means of quantum entanglement. Superconductivity is a useful phenomenon in this regard, because it allows the construction of large quantum circuits and is compatible with microfabrication. For superconducting qubits, the surface code approach to quantum computing is a natural choice for error correction, because it uses only nearest-neighbour coupling and rapidly cycled entangling gates. The gate fidelity requirements are modest: the per-step fidelity threshold is only about 99 per cent. Here we demonstrate a universal set of logic gates in a superconducting multi-qubit processor, achieving an average single-qubit gate fidelity of 99.92 per cent and a two-qubit gate fidelity of up to 99.4 per cent. This places Josephson quantum computing at the fault-tolerance threshold for surface code error correction. Our quantum processor is a first step towards the surface code, using five qubits arranged in a linear array with nearest-neighbour coupling. As a further demonstration, we construct a five-qubit Greenberger-Horne-Zeilinger state using the complete circuit and full set of gates. The results demonstrate that Josephson quantum computing is a high-fidelity technology, with a clear path to scaling up to large-scale, fault-tolerant quantum circuits.

10.
Nature ; 515(7526): 241-4, 2014 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-25391961

RESUMO

Topology, with its abstract mathematical constructs, often manifests itself in physics and has a pivotal role in our understanding of natural phenomena. Notably, the discovery of topological phases in condensed-matter systems has changed the modern conception of phases of matter. The global nature of topological ordering, however, makes direct experimental probing an outstanding challenge. Present experimental tools are mainly indirect and, as a result, are inadequate for studying the topology of physical systems at a fundamental level. Here we employ the exquisite control afforded by state-of-the-art superconducting quantum circuits to investigate topological properties of various quantum systems. The essence of our approach is to infer geometric curvature by measuring the deflection of quantum trajectories in the curved space of the Hamiltonian. Topological properties are then revealed by integrating the curvature over closed surfaces, a quantum analogue of the Gauss-Bonnet theorem. We benchmark our technique by investigating basic topological concepts of the historically important Haldane model after mapping the momentum space of this condensed-matter model to the parameter space of a single-qubit Hamiltonian. In addition to constructing the topological phase diagram, we are able to visualize the microscopic spin texture of the associated states and their evolution across a topological phase transition. Going beyond non-interacting systems, we demonstrate the power of our method by studying topology in an interacting quantum system. This required a new qubit architecture that allows for simultaneous control over every term in a two-qubit Hamiltonian. By exploring the parameter space of this Hamiltonian, we discover the emergence of an interaction-induced topological phase. Our work establishes a powerful, generalizable experimental platform to study topological phenomena in quantum systems.

11.
Phys Rev Lett ; 123(21): 210501, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31809160

RESUMO

We demonstrate diabatic two-qubit gates with Pauli error rates down to 4.3(2)×10^{-3} in as fast as 18 ns using frequency-tunable superconducting qubits. This is achieved by synchronizing the entangling parameters with minima in the leakage channel. The synchronization shows a landscape in gate parameter space that agrees with model predictions and facilitates robust tune-up. We test both iswap-like and cphase gates with cross-entropy benchmarking. The presented approach can be extended to multibody operations as well.

12.
J Intellect Disabil Res ; 63(4): 338-345, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30569576

RESUMO

BACKGROUND: The prevalence of asthma among athletes with intellectual disabilities, and the asthma knowledge levels of their coaches, is unknown. METHODS: Special Olympics Canada athletes completed a demographic questionnaire (n = 208). Athletes who identified as having ever or current asthma completed the Asthma Control Questionnaire and the Mini Asthma Quality of Life Questionnaire and were measured for height, weight and lung function (n = 73). National level coaches (n = 27) completed a questionnaire pertaining to asthma knowledge. RESULTS: The prevalence of ever and current asthma were 35.5% (n = 73) and 21.1% (n = 44), respectively. Athletes with asthma reported that they had inadequately controlled asthma, but good quality of life. Coaches correctly answered 43% true/false questions on the survey, indicating suboptimal asthma knowledge. CONCLUSIONS: Athletes with intellectual disabilities appear to have a greater prevalence of asthma than the general population; however, coaches of these athletes appear to have limited knowledge pertaining to asthma and exercise-induced asthma.


Assuntos
Asma/epidemiologia , Atletas/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Deficiência Intelectual/epidemiologia , Tutoria , Adulto , Canadá/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Adulto Jovem
13.
Hum Reprod ; 33(5): 935-941, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29546326

RESUMO

STUDY QUESTION: Is there a benefit to assessing ploidy in delayed embryos reaching the morula stage on Day 6 of development? SUMMARY ANSWER: Day-6 morulae should be considered for biopsy in women <40 years old undergoing preimplantation genetic testing for aneuploidy (PGT-A) because they are associated with acceptable, albeit reduced, euploidy and implantation rates (IRs). WHAT IS KNOWN ALREADY: Embryo development and morphology have been shown to correlate with aneuploidy and pregnancy rates. During PGT-A cycles, embryos are biopsied if they reach the blastocyst stage by Day 5 or 6, whereas slow-developing embryos are typically deselected and discarded. Determining the viability of slow-developing embryos is particularly relevant for women undergoing PGT-A who have diminished ovarian reserve and a relatively low blastocyst yield. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study that was performed at an academic medical center. Patients who underwent IVF with PGT-A were reviewed for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1615 cycles were reviewed. All cycles which involved a biopsy of a cavitating or compacted morula on Day 6 were included (n = 763). PGT-A was performed using array comparative genomic hybridization. The aneuploidy and implantation of morulae were compared to those of blastocysts originating from the same couples. MAIN RESULTS AND THE ROLE OF CHANCE: The study included 763 cycles in which 1260 morulae and 3014 blastocysts were biopsied. Women were divided into four age groups (<35, 35-37, 38-39 and ≥40 years): the prevalence of aneuploidy was consistently lower among blastocysts (40.3, 50.8, 56 and 78.3%, respectively) than among compacted morulae (68.7, 75.5, 88.9 and 98.1%, respectively) and cavitating morulae (57, 66.4, 81 and 91.6%, respectively) throughout the different age groups (P < 0.001). Of note, the majority of compacted morulae (98.1%) and cavitating morulae (91.6%) were aneuploid in women aged ≥40 years. Compacted and cavitating morulae had significantly higher rates of complex aneuploidy, which involves ≥3 chromosomes, compared with blastocysts (P < 0.001). Furthermore, euploid morulae were associated with a significantly lower IR (28.2 versus 54.6%; P = 0.002) and live birth rate (23.1 versus 55.0%; P = 0.001) compared to euploid blastocysts. LIMITATIONS REASONS FOR CAUTION: This study confirms that Day-6 morulae should not be discarded in young women undergoing PGT-A. However, a potential drawback of biopsying embryos at the morula stage is the inability to distinguish between inner cell mass and trophectoderm cell origin. The sample size of euploid morula transfer cycles in this study was limited. Thus, a larger cohort would be beneficial to validate the reassuring live birth and spontaneous abortion rates reported here. Furthermore, the reproducibility of our findings should be determined at different centers. WIDER IMPLICATIONS OF THE FINDINGS: Although Day-6 morulae are associated with higher aneuploidy rates and lower IRs compared to blastocysts, they still yielded successful pregnancies. Therefore, testing Day-6 morulae should be considered, especially for women <40 years old who are undergoing PGT-A with a small cohort of available blastocysts for biopsy. STUDY FUNDING/COMPETING INTEREST(S): The authors have nothing to disclose. They received no specific funding for this work. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Aneuploidia , Testes Genéticos , Mórula , Diagnóstico Pré-Implantação/métodos , Adulto , Hibridização Genômica Comparativa , Técnicas de Cultura Embrionária , Feminino , Fertilização in vitro/métodos , Humanos , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Estudos Retrospectivos
14.
Reproduction ; 156(1): F51-F58, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29636404

RESUMO

The first conception outside of the human body that led to the birth of Louise Brown was a tremendous accomplishment, which opened the door to the utilization of assisted reproductive techniques globally. This brought the understanding that accomplishing life in a dish required several steps, the most obvious being the timing and characteristics of fertilization. It soon became obvious in the 1980s that the most disappointing phenomenon was unexpected and complete fertilization failure. Among the approaches that were attempted to treat male factor infertility, ICSI surfaced as the technique that brought the ratio of the gametes to 1:1 and was also able to grant consistent fertilization and a higher pregnancy rate. ICSI has now been implemented for a quarter of a century, proving itself as the ultimate technique utilizing ejaculated spermatozoa independent of the semen parameters and is the sole insemination method to be used with surgically retrieved spermatozoa. There are currently various indications for ICSI that are widely adopted, rendering it the most popular insemination method worldwide. The reliability of ICSI ensures its employment in upcoming techniques involving in vitro spermatogenesis and neogametogenesis.


Assuntos
Injeções de Esperma Intracitoplásmicas/métodos , Espermatozoides , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Análise do Sêmen
15.
Phys Rev Lett ; 121(19): 191602, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30468605

RESUMO

We present Monte Carlo calculations of the thermodynamics of the (2+1)-dimensional Thirring model at finite density. We bypass the sign problem by deforming the domain of integration of the path integral into complex space in such a way as to maximize the average sign within a parameterized family of manifolds. We present results for lattice sizes up to 10^{3} and we find that at high densities and/or temperatures the chiral condensate is abruptly reduced.

16.
Phys Rev Lett ; 121(9): 090502, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30230854

RESUMO

Superconducting qubits are an attractive platform for quantum computing since they have demonstrated high-fidelity quantum gates and extensibility to modest system sizes. Nonetheless, an outstanding challenge is stabilizing their energy-relaxation times, which can fluctuate unpredictably in frequency and time. Here, we use qubits as spectral and temporal probes of individual two-level-system defects to provide direct evidence that they are responsible for the largest fluctuations. This research lays the foundation for stabilizing qubit performance through calibration, design, and fabrication.

17.
Exp Cell Res ; 358(2): 227-233, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28663058

RESUMO

The early preimplantation embryo is susceptible to a range of exogenous stresses which result in their reduced long-term developmental potential. The P53 tumour suppressor protein is normally held at low levels in the preimplantation embryo and we show that culture stress induces the expression of a range of canonical P53-response genes (Mdm2, Bax and Cdkn1a). Culture stress caused a P53-dependent loss of cells from resulting blastocysts, and this was most evident within the inner cell mass population. Culture stress increased the proportion of cells expressing active caspase-3 and undergoing apoptosis, while inhibition of caspase-3 increased the number of cells within the inner cell mass. The P53-dependent loss of cells from the inner cell mass was accompanied by a loss of NANOG-positive epiblast progenitors. Pharmacological activation of P53 by the MDM2 inhibitor, Nutlin-3, also caused increased P53-dependent transcription and the loss of cells from the inner cell mass. This loss of cells could be ameliorated by simultaneous treatment with the P53 inhibitor, Pifithrin-α. Culture stress causes reduced signalling via the phosphatidylinositol-3-kinase signalling pathway, and blocking this pathway caused P53-dependent loss of cells from the inner cell mass. These results point to P53 acting to limit the accumulation and survival of cells within the pluripotent lineage of the blastocyst and provide a molecular framework for the further investigation of the factors determining the effects of stressors on the embryo's developmental potential.


Assuntos
Blastocisto/citologia , Linhagem da Célula , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Benzotiazóis/metabolismo , Desenvolvimento Embrionário , Genes Homeobox , Imidazóis/metabolismo , Camundongos Transgênicos , Piperazinas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tolueno/análogos & derivados , Tolueno/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-27001026

RESUMO

There is a paucity of knowledge about fathers' experiences of cancer. This study explored the experiences of fathers diagnosed and living with cancer while also having parental responsibility for children. A hermeneutic phenomenological approach guided the study. Data were generated through 22 in-depth interviews with 10 fathers throughout Northern Ireland. The findings evidenced that fathers' identities are challenged and frequently re-shaped by the cancer experience, in many cases leading to an improved lifestyle behaviour. Heightened engagement with their children can provide a protective effect from the illness. On the other hand a lack of involvement led to frustration and low mood. The findings also demonstrated that father/child relationships were adversely affected by the social complexities that exist in the variances and diversity of fathers parenting roles and status. This knowledge contributes to our understanding of the complex relationships of fathers in non-traditional roles. It extends our understanding of how, when stereotyped gendered roles are ascribed to fathers it can impact on a fathers' ability to fulfil the traditional breadwinner's role. This is knowledge that will inform health care professionals and enable them to provide gendered-sensitive care that takes account of the masculine psychological responses that can shape the cancer experience.


Assuntos
Pai/psicologia , Neoplasias/psicologia , Adaptação Psicológica , Adulto , Atitude Frente a Saúde , Tomada de Decisões , Relações Pai-Filho , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Poder Familiar/psicologia , Inquéritos e Questionários , Revelação da Verdade
19.
J Eur Acad Dermatol Venereol ; 32(12): 2191-2199, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29729105

RESUMO

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE: This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS: A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI <50). Responders at week 16 continued initial treatment, whereas partial responders and non-responders were switched to standard of care, which included methotrexate, cyclosporine, phototherapy and topical corticosteroids. Sustained response was defined as 16-week response maintained at week 52. A German healthcare system perspective was adopted. Clinical efficacy data were obtained from a mixed-treatment comparison; 2016 resource unit costs from national sources; and adverse events and discontinuation rates from the literature. We calculated cost per PASI 90 responder over week 16 and week 52, as well as cost per sustained responder between weeks 16 and 52. RESULTS: Secukinumab had the lowest cost per PASI 90 responder over 16 weeks (€18 026) compared with ustekinumab (€18 080), adalimumab (€23 499), infliximab (€29 599) and etanercept (€34 037). Over 52 weeks, costs per PASI 90 responder ranged from €42 409 (secukinumab) to €70 363 (etanercept). Likewise, secukinumab had the lowest cost per sustained 52-week PASI 90 responder (€22 690) compared with other biologic treatments. Sensitivity analyses, excluding patient copayments, showed similar results. CONCLUSIONS: First biologic treatment with secukinumab for moderate to severe psoriasis is cost-effective, with lowest cost per responder compared with other biologic treatments in Germany.


Assuntos
Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/economia , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adalimumab/economia , Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados , Produtos Biológicos/economia , Produtos Biológicos/uso terapêutico , Análise Custo-Benefício , Etanercepte/economia , Etanercepte/uso terapêutico , Alemanha , Humanos , Infliximab/economia , Infliximab/uso terapêutico , Psoríase/economia , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/economia , Ustekinumab/uso terapêutico
20.
J Assist Reprod Genet ; 35(10): 1911-1917, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30056595

RESUMO

OBJECTIVE: To design a reproductive treatment algorithm based on the sperm DNA fragmentation (SDF) for couples with unexplained infertility following a poor intrauterine insemination (IUI) outcome. DESIGN: Couples that failed IUI with no apparent reproductive issue in both partners were allocated to diverse reproductive treatments on the basis of SDF. SETTING: Reproductive medical center in an academic setting. PATIENT(S): Over 4 years, couples with an unexpected poor IUI outcome and no apparent female or male partner reproductive issues were recruited. INTERVENTION(S): IUI, IVF, and ICSI were performed in the standard fashion following sperm SDF assays. MAIN OUTCOMES MEASURE(S): Fertilization rate, implantation rate, pregnancy characteristics, and delivery rates. RESULT(S): A total of 354 couples with unexplained infertility and normal semen parameters underwent 1133 IUI cycles. Clinical pregnancy rate (CPR) with IUI at our center in an age-matched cohort is 23.9% while the study cohort had 1.8%. Following SDF assessment, couples with failed IUI attempts but normal SDF (SCSA 9.8 ± 4.6%; TUNEL 11.8 ± 6.2%) underwent IVF with a CPR of 12.7%; those with abnormal SDF underwent ICSI with ejaculated spermatozoa, resulting in a CPR of 18.7%. This group included couples with normal SDF that had failed IVF. Couples with abnormal SDF that failed ICSI with ejaculated spermatozoa achieved a CPR of 31.0% with surgically retrieved spermatozoa. CONCLUSION(S): Couples with unexplained infertility that present with unexpectedly poor IUI outcomes can be funneled into a treatment algorithm guided by the integrity of the sperm genome for higher chances of pregnancy using an alternate method of insemination.


Assuntos
Cromatina/genética , Infertilidade Masculina/terapia , Sêmen , Espermatozoides/patologia , Adulto , Cromatina/patologia , Fragmentação do DNA , Feminino , Fertilização in vitro , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Masculino , Gravidez , Taxa de Gravidez , Análise do Sêmen , Contagem de Espermatozoides , Injeções de Esperma Intracitoplásmicas , Recuperação Espermática , Resultado do Tratamento
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