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Molecular nanomagnets (MNMs), molecules containing interacting spins, have been a playground for quantum mechanics. They are characterized by many accessible low-energy levels that can be exploited to store and process quantum information. This naturally opens the possibility of using them as qudits, thus enlarging the tools of quantum logic with respect to qubit-based architectures. These additional degrees of freedom recently prompted the proposal for encoding qubits with embedded quantum error correction (QEC) in single molecules. QEC is the holy grail of quantum computing and this qudit approach could circumvent the large overhead of physical qubits typical of standard multi-qubit codes. Another important strength of the molecular approach is the extremely high degree of control achieved in preparing complex supramolecular structures where individual qudits are linked preserving their individual properties and coherence. This is particularly relevant for building quantum simulators, controllable systems able to mimic the dynamics of other quantum objects. The use of MNMs for quantum information processing is a rapidly evolving field which still requires to be fully experimentally explored. The key issues to be settled are related to scaling up the number of qudits/qubits and their individual addressing. Several promising possibilities are being intensively explored, ranging from the use of single-molecule transistors or superconducting devices to optical readout techniques. Moreover, new tools from chemistry could be also at hand, like the chiral-induced spin selectivity. In this paper, we will review the present status of this interdisciplinary research field, discuss the open challenges and envisioned solution paths which could finally unleash the very large potential of molecular spins for quantum technologies.
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BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase. If untreated, the complications of PKU lead to significant neucognitive and neuropsychiatric impairments, placing a burden on both the individual's quality of life and on the healthcare system. We conducted a systematic literature review to characterize the impact of PKU on affected individuals and on healthcare resources in Latin American (LATAM) countries. METHODS: Searches of the global medical literature as well as regional and local medical literature up to September 2021. Observational studies on patients with PKU from any LATAM country. Pairs of reviewers independently screened eligible articles, extracted data from included studies, and assessed their risk of bias. RESULTS: 79 unique studies (47 cross-sectional studies, 18 case series, 12 case reports, and two cohort studies) with a total of 4090 patients were eligible. Of these studies, 20 had data available evaluating early-diagnosed PKU patients for meta-analysis of burden outcomes. Intellectual disability in the pooled studies was 18% [95% Confidence Interval (CI) 0.04-0.38; I2 = 83.7%, p = 0.0133; two studies; n = 114]. Motor delay was 15% [95% CI 0.04-0.30; I2 = 74.5%, p = 0.0083; four studies; n = 132]. Speech deficit was 35% [95% CI 0.08-0.68; I2 = 93.9%, p < 0.0001; five studies; n = 162]. CONCLUSIONS: There is currently evidence of high clinical burden in PKU patients in LATAM countries. Recognition that there are many unmet neuropsychological needs and socioeconomic challenges faced in the LATAM countries is the first step in planning cost-effective interventions.
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Fenilalanina Hidroxilase , Fenilcetonúrias , Estudos Transversais , Humanos , América Latina/epidemiologia , Fenilcetonúrias/complicações , Qualidade de VidaRESUMO
We pinpoint the key ingredients ruling decoherence in multispin clusters, and we engineer the system Hamiltonian to design optimal molecules embedding quantum error correction. These are antiferromagnetically coupled systems with competing exchange interactions, characterized by many low-energy states in which decoherence is dramatically suppressed and does not increase with the system size. This feature allows us to derive optimized code words, enhancing the power of the quantum error correction code by orders of magnitude. We demonstrate this by a complete simulation of the system dynamics, including the effect of decoherence driven by a nuclear spin bath and the full sequence of pulses to implement error correction and logical gates between protected states.
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Understanding chiral-induced spin selectivity (CISS), resulting from charge transport through helical systems, has recently inspired many experimental and theoretical efforts but is still the object of intense debate. In order to assess the nature of CISS, we propose to focus on electron-transfer processes occurring at the single-molecule level. We design simple magnetic resonance experiments, exploiting a qubit as a highly sensitive and coherent magnetic sensor, to provide clear signatures of the acceptor polarization. Moreover, we show that information could even be obtained from time-resolved electron paramagnetic resonance experiments on a randomly oriented solution of molecules. The proposed experiments will unveil the role of chiral linkers in electron transfer and could also be exploited for quantum computing applications.
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This corrects the article DOI: 10.1103/PhysRevLett.110.157204.
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We show that molecular nanomagnets have a potential advantage in the crucial rush toward quantum computers. Indeed, the sizable number of accessible low-energy states of these systems can be exploited to define qubits with embedded quantum error correction. We derive the scheme to achieve this crucial objective and the corresponding sequence of microwave/radiofrequency pulses needed for the error correction procedure. The effectiveness of our approach is shown already with a minimal S = 3/2 unit corresponding to an existing molecule, and the scaling to larger spin systems is quantitatively analyzed.
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The management of positive resection margins in micro-endoscopic glottic laser surgery remains a controversial and critical point. This study aims to assess the impact of margin status after transoral laser surgery on local control, survival and organ preservation rates; the decision-making process and treatment options in cases with positive margins are also discussed. We retrospectively reviewed the clinical and histological records of 308 consecutive patients with primary early glottic carcinoma (T1a, T1b, selected T2) and treated with endoscopic laser cordectomy. Recurrence rates and survival related to margin status were analysed using the Kaplan-Meier method. Local relapses and disease-free-survival rates were significantly related to excision margin status (p < 0.001). In the T1a category (n = 228) no significant differences were observed in disease-free-survival (p = 0.889) and overall survival (p = 0.426) between patients submitted to further treatment (revision endoscopic surgery or radiotherapy) for positive excision margins and patients who were left untreated. In 20 of 24 (83%) patients with positive margins that were surgically re-excised, no residual carcinoma was detected. Margin status (mainly multifocal and deep positive margins) at first surgery was significantly related to the final organ preservation rate (p < 0.001). Margin status during laser cordectomy in early glottic cancer has a prognostic impact on local control of disease without compromising survival. Patients with multifocal and deep positive borders should be surgically retreated and strictly monitored to increase the organ preservation rates. Careful preparation and mapping of the surgical specimen enhances the accuracy of pathological examination by reducing the risk of overestimate positive margins.
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Glote , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Terapia a Laser , Lasers de Gás/uso terapêutico , Margens de Excisão , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The discovery of magnetic bistability in Mn_{12} more than 20 years ago marked the birth of molecular magnetism, an extremely fertile interdisciplinary field and a powerful route to create tailored magnetic nanostructures. However, the difficulty to determine interactions in complex polycentric molecules often prevents their understanding. Mn_{12} is an outstanding example of this difficulty: although it is the forefather and most studied of all molecular nanomagnets, an unambiguous determination of even the leading magnetic exchange interactions is still lacking. Here we exploit four-dimensional inelastic neutron scattering to portray how individual spins fluctuate around the magnetic ground state, thus fixing the exchange couplings of Mn_{12} for the first time. Our results demonstrate the power of four-dimensional inelastic neutron scattering as an unrivaled tool to characterize magnetic clusters.
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We introduce a scheme to perform quantum information processing that is based on a hybrid spin-photon qubit encoding. The proposed qubits consist of spin ensembles coherently coupled to microwave photons in coplanar waveguide resonators. The quantum gates are performed solely by shifting the resonance frequencies of the resonators on a nanosecond time scale. An additional cavity containing a Cooper-pair box is exploited as an auxiliary degree of freedom to implement two-qubit gates. The generality of the scheme allows its potential implementation with a wide class of spin systems.
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The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.
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Transplante de Rim , Rim/patologia , Rim/fisiologia , Doadores Vivos , Síndrome Metabólica/fisiopatologia , Adulto , Feminino , Humanos , Rim/anatomia & histologia , Estilo de Vida , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/terapia , Pessoa de Meia-Idade , Nefrectomia , Prevalência , Redução de PesoRESUMO
We present a flexible and effective ab initio scheme to build many-body models for molecular nanomagnets, and to calculate magnetic exchange couplings and zero-field splittings. It is based on using localized Foster-Boys orbitals as a one-electron basis. We apply this scheme to three paradigmatic systems, the antiferromagnetic rings Cr8 and Cr7Ni, and the single-molecule magnet Fe4. In all cases we identify the essential magnetic interactions and find excellent agreement with experiments.
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OBJECTIVE: This study investigated whether selected D-amino acid oxidase activator (DAOA) gene single nucleotide polymorphisms (SNPs; rs3916966, rs3916967, rs2391191, rs3916968, rs7139958, rs9558571, rs778293) are associated with major depressive disorder (MDD) and bipolar disorder (BD), and whether they can predict clinical outcomes in Korean in-patients treated with antidepressants and mood stabilizers, respectively. METHODS: In total, 145 patients with MDD, 132 patients with BD and 170 psychiatrically healthy controls were genotyped for the DAOA SNPs. Baseline and final clinical assessments included the Montgomery-Asberg Depression Rating Scale and Young Mania Rating Scale for patients with MDD and BD, respectively. RESULTS: There was no association between DAOA SNP genotypes or alleles with diagnosis, clinical improvement, response rates or remission rates for MDD and BD. Haplotype analyses found no association with MDD or BD diagnosis or clinical outcomes. CONCLUSIONS: The findings suggest that the DAOA SNPs investigated may not affect MDD or BD phenotype, clinical symptoms or other clinical factors, and are unlikely to be involved in MDD or BD development and treatment outcomes. Given the study's limitations, further investigation should be carried out.
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Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Proteínas de Transporte/genética , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Adulto , Antidepressivos/uso terapêutico , Povo Asiático , Transtorno Bipolar/tratamento farmacológico , Estudos de Casos e Controles , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Frequência do Gene/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , República da Coreia , Resultado do TratamentoRESUMO
INTRODUCTION: The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. MATERIAL AND METHODS: We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. RESULTS: All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. CONCLUSIONS: Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies.
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Doenças do Sistema Endócrino/congênito , Doenças do Sistema Endócrino/complicações , Hipoglicemia/etiologia , Icterícia/etiologia , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2months-20year). To compare with an adequate control population, we established reference levels for serum anti-Müllerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.
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Hormônio Antimülleriano/sangue , Síndrome de Down/fisiopatologia , Hipogonadismo/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Síndrome de Down/complicações , Hormônio Foliculoestimulante/sangue , Humanos , Hipogonadismo/sangue , Hipogonadismo/etiologia , Lactente , Recém-Nascido , Células Intersticiais do Testículo/fisiologia , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Células de Sertoli/fisiologia , Testículo/anatomia & histologia , Testosterona/sangueRESUMO
Control of human cytomegalovirus (HCMV) infection during the posttransplant period was investigated in 134 solid-organ transplant recipients by monitoring in parallel virologic and immunologic parameters for at least 1 year of follow-up. Virologic monitoring was achieved by determining HCMV DNAemia with real-time PCR, using the threshold of 300 000 DNA copies/mL blood as a cutoff for starting preemptive therapy. Immunologic monitoring included measurement of HCMV-specific CD4+ and CD8+ T cells by cytokine flow cytometry, using HCMV-infected dendritic cells as a stimulus. HCMV infection was diagnosed in 110 (82%) and required treatment in 49 (36%) patients. At 12 months after transplantation 'protective' immunity (≥0.4 CD4+ and CD8+ HCMV-specific T cells/µL blood) was achieved in 115/129 (89%) patients. During the entire study period, 122 patients reconstituting HCMV-specific CD4+ and CD8+ T-cell immunity at 60 days posttransplant onward were able to control HCMV infection, except for one patient who developed HCMV disease because of a rejection episode. Patients reconstituting HCMV-specific CD8+ only did not control HCMV infection. In conclusion, the presence of both HCMV-specific CD4+ and CD8+ T cells ≥ 0.4/µL blood appears to be protective against HCMV disease. This result does not apply to patients undergoing antirejection treatment, or reconstituting HCMV-specific CD8+ T cells only.
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Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/diagnóstico , DNA Viral/sangue , Transplante de Coração/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Pulmão/efeitos adversos , Adulto , Idoso , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Citomegalovirus/genética , Citomegalovirus/imunologia , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Células Dendríticas/virologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Carga ViralRESUMO
This study presents a new automatic spike sorting method based on feature extraction by Laplacian eigenmaps combined with k-means clustering. The performance of the proposed method was compared against previously reported algorithms such as principal component analysis (PCA) and amplitude-based feature extraction. Two types of classifier (namely k-means and classification expectation-maximization) were incorporated within the spike sorting algorithms, in order to find a suitable classifier for the feature sets. Simulated data sets and in-vivo tetrode multichannel recordings were employed to assess the performance of the spike sorting algorithms. The results show that the proposed algorithm yields significantly improved performance with mean sorting accuracy of 73% and sorting error of 10% compared to PCA which combined with k-means had a sorting accuracy of 58% and sorting error of 10%.A correction was made to this article on 22 February 2011. The spacing of the title was amended on the abstract page. No changes were made to the article PDF and the print version was unaffected.
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Potenciais de Ação/fisiologia , Algoritmos , Modelos Neurológicos , Neurônios/fisiologia , Análise por Conglomerados , Bases de Dados Factuais , Análise de Componente PrincipalRESUMO
Since the introduction of psychiatric medications with relatively good safety profiles, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors, increasing attention has been given to side effects such as sexual dysfunction (SD), which, although unrelated to risks of mortality, could undermine compliance with treatment regimens and impair quality of life. Indeed,there is consistent evidence to suggest that a large number of psychiatric medications adversely affect one or more of the three phases of normal sexual response: desire, arousal, and orgasm.