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AIMS/HYPOTHESIS: Roux-en-Y gastric bypass surgery (RYGB) frequently results in remission of type 2 diabetes as well as exaggerated secretion of glucagon-like peptide-1 (GLP-1). Here, we assessed RYGB-induced transcriptomic alterations in the small intestine and investigated how they were related to the regulation of GLP-1 production and secretion in vitro and in vivo. METHODS: Human jejunal samples taken perisurgically and 1 year post RYGB (n=13) were analysed by RNA-seq. Guided by bioinformatics analysis we targeted four genes involved in cholesterol biosynthesis, which we confirmed to be expressed in human L cells, for potential involvement in GLP-1 regulation using siRNAs in GLUTag and STC-1 cells. Gene expression analyses, GLP-1 secretion measurements, intracellular calcium imaging and RNA-seq were performed in vitro. OGTTs were performed in C57BL/6j and iScd1-/- mice and immunohistochemistry and gene expression analyses were performed ex vivo. RESULTS: Gene Ontology (GO) analysis identified cholesterol biosynthesis as being most affected by RYGB. Silencing or chemical inhibition of stearoyl-CoA desaturase 1 (SCD1), a key enzyme in the synthesis of monounsaturated fatty acids, was found to reduce Gcg expression and secretion of GLP-1 by GLUTag and STC-1 cells. Scd1 knockdown also reduced intracellular Ca2+ signalling and membrane depolarisation. Furthermore, Scd1 mRNA expression was found to be regulated by NEFAs but not glucose. RNA-seq of SCD1 inhibitor-treated GLUTag cells identified altered expression of genes implicated in ATP generation and glycolysis. Finally, gene expression and immunohistochemical analysis of the jejunum of the intestine-specific Scd1 knockout mouse model, iScd1-/-, revealed a twofold higher L cell density and a twofold increase in Gcg mRNA expression. CONCLUSIONS/INTERPRETATION: RYGB caused robust alterations in the jejunal transcriptome, with genes involved in cholesterol biosynthesis being most affected. Our data highlight SCD as an RYGB-regulated L cell constituent that regulates the production and secretion of GLP-1.
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Diabetes Mellitus Tipo 2 , Derivación Gástrica , Humanos , Animales , Ratones , Péptido 1 Similar al Glucagón/metabolismo , Derivación Gástrica/métodos , Células L , Diabetes Mellitus Tipo 2/metabolismo , ARN , Ratones Endogámicos C57BL , Análisis de Secuencia de ARN , Colesterol , ARN Mensajero , Glucemia/metabolismoRESUMEN
BACKGROUND: Children with established kidney failure may have additional medical conditions influencing kidney care and outcomes. This cross-sectional study aimed to examine the prevalence of co-existing diseases captured in the electronic hospital record compared to UK Renal Registry (UKRR) data and differences in coding. METHODS: The study population comprised children aged < 18 years receiving kidney replacement therapy (KRT) in England and Wales on 31/12/2016. Comorbidity data at KRT start was examined in the hospital record and compared to UKRR data. Agreement was assessed by the kappa statistic. Associations between patient and clinical factors and likelihood of coding were examined using multivariable logistic regression. RESULTS: A total of 869 children (62.5% male) had data linkage for inclusion. UKRR records generally reported a higher prevalence of co-existing disease than electronic health records; congenital, non-kidney disease was most commonly reported across both datasets. The highest sensitivity in the hospital record was seen for congenital heart disease (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.51, 0.78) and malignancy (OR 0.63, 95% CI 0.41, 0.85). At best, moderate agreement (kappa ≥ 0.41) was seen between the datasets. Factors associated with higher odds of coding in hospital records included age, while kidney disease and a higher number of comorbidities were associated with lower odds of coding. CONCLUSIONS: Health records generally under-reported co-existing disease compared to registry data with fair-moderate agreement between datasets. Electronic health records offer a non-selective overview of co-existing disease facilitating audit and research, but registry processes are still required to capture paediatric-specific variables pertinent to kidney disease.
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Imposing an external periodic electrostatic potential to the electrons confined in a quantum well makes it possible to engineer synthetic two-dimensional band structures, with electronic properties different from those in the host semiconductor. Here we report the fabrication and study of a tunable triangular artificial lattice on a GaAs/AlGaAs heterostructure where it is possible to transform from the original GaAs band structure and a circular Fermi surface to a new band structure with multiple artificial Fermi surfaces simply by altering a gate bias. For weak electrostatic modulation magnetotransport measurements reveal multiple quantum oscillations and commensurability oscillations due to the electron scattering from the artificial lattice. Increasing the strength of the modulation reveals new commensurability oscillations of the electrons from the artificial Fermi surface scattering from the triangular artificial lattice. These results show that low disorder gate-tunable lateral superlattices can be used to form artificial two-dimensional crystals with designer electronic properties.
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The development of devices that exhibit both superconducting and semiconducting properties is an important endeavor for emerging quantum technologies. We investigate superconducting nanowires fabricated on a silicon-on-insulator (SOI) platform. Aluminum from deposited contact electrodes is found to interdiffuse with Si along the entire length of the nanowire, over micrometer length scales and at temperatures well below the Al-Si eutectic. The phase-transformed material is conformal with the predefined device patterns. The superconducting properties of a transformed mesoscopic ring formed on a SOI platform are investigated. Low-temperature magnetoresistance oscillations, quantized in units of the fluxoid, h/2e, are observed.
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Holes in silicon quantum dots are receiving attention due to their potential as fast, tunable, and scalable qubits in semiconductor quantum circuits. Despite this, challenges remain in this material system including difficulties using charge sensing to determine the number of holes in a quantum dot, and in controlling the coupling between adjacent quantum dots. We address these problems by fabricating an ambipolar complementary metal-oxide-semiconductor (CMOS) device using multilayer palladium gates. The device consists of an electron charge sensor adjacent to a hole double quantum dot. We demonstrate control of the spin state via electric dipole spin resonance. We achieve smooth control of the interdot coupling rate over 1 order of magnitude and use the charge sensor to perform spin-to-charge conversion to measure the hole singlet-triplet relaxation time of 11 µs for a known hole occupation. These results provide a path toward improving the quality and controllability of hole spin-qubits.
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The highly tunable band structure of the zero-energy Landau level (zLL) of bilayer graphene makes it an ideal platform for engineering novel quantum states. However, the zero-energy Landau level at high electric fields has remained largely unexplored. Here we present magnetotransport measurements of bilayer graphene in high transverse electric fields. We observe previously undetected Landau level crossings at filling factors ν = -2, 1, and 3 at high electric fields. These crossings provide constraints for theoretical models of the zero-energy Landau level and show that the orbital, valley, and spin character of the quantum Hall states at high electric fields is very different from low electric fields. At high E, new transitions between states at ν = -2 with different orbital and spin polarization can be controlled by the gate bias, while the transitions between ν = 0 â 1 and ν = 2 â 3 show anomalous behavior.
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We previously reported that loss of mitochondrial transcription factor B1 (TFB1M) leads to mitochondrial dysfunction and is involved in the pathogenesis of type 2 diabetes (T2D). Whether defects in ribosomal processing impact mitochondrial function and could play a pathogenetic role in ß-cells and T2D is not known. To this end, we explored expression and the functional role of dimethyladenosine transferase 1 homolog (DIMT1), a homolog of TFB1M and a ribosomal RNA (rRNA) methyltransferase implicated in the control of rRNA. Expression of DIMT1 was increased in human islets from T2D donors and correlated positively with expression of insulin mRNA, but negatively with insulin secretion. We show that silencing of DIMT1 in insulin-secreting cells impacted mitochondrial function, leading to lower expression of mitochondrial OXPHOS proteins, reduced oxygen consumption rate, dissipated mitochondrial membrane potential, and a slower rate of ATP production. In addition, the rate of protein synthesis was retarded upon DIMT1 deficiency. Consequently, we found that DIMT1 deficiency led to perturbed insulin secretion in rodent cell lines and islets, as well as in a human ß-cell line. We observed defects in rRNA processing and reduced interactions between NIN1 (RPN12) binding protein 1 homolog (NOB-1) and pescadillo ribosomal biogenesis factor 1 (PES-1), critical ribosomal subunit RNA proteins, the dysfunction of which may play a part in disturbing protein synthesis in ß-cells. In conclusion, DIMT1 deficiency perturbs protein synthesis, resulting in mitochondrial dysfunction and disrupted insulin secretion, both potential pathogenetic processes in T2D.
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Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Metiltransferasas , Mitocondrias , Ribosomas , Animales , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/metabolismo , Secreción de Insulina , Células Secretoras de Insulina/metabolismo , Metiltransferasas/deficiencia , Metiltransferasas/metabolismo , Mitocondrias/metabolismo , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Ribosomas/metabolismo , Transferasas/metabolismoRESUMEN
A supersolid, a counterintuitive quantum state in which a rigid lattice of particles flows without resistance, has to date not been unambiguously realized. Here we reveal a supersolid ground state of excitons in a double-layer semiconductor heterostructure over a wide range of layer separations outside the focus of recent experiments. This supersolid conforms to the original Chester supersolid with one exciton per supersolid site, as distinct from the alternative version reported in cold-atom systems of a periodic density modulation or clustering of the superfluid. We provide the phase diagram augmented by the supersolid. This new phase appears at layer separations much smaller than the predicted exciton normal solid, and it persists up to a solid-solid transition where the quantum phase coherence collapses. The ranges of layer separations and exciton densities in our phase diagram are well within reach of the current experimental capabilities.
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BACKGROUND: Informal caregivers (i.e. family and friends) provide essential support to people with chronic kidney disease (CKD). Many informal caregivers experience mental health problems such as anxiety and depression due to the caregiving role, and commonly have unmet psychological support needs. One potential solution is cognitive behavioural therapy (CBT) self-help interventions that are less reliant on extensive involvement of healthcare professionals, which may increase access. Within the intervention development phase of the MRC framework, the study's primary objective was to examine informal caregivers' self-help intervention preferences (e.g. delivery format, content). Secondary objectives were to describe the informal caregiver's situation (e.g. type of care activities) and mental health (symptoms of depression, anxiety, and stress). METHODS: An online cross-sectional survey conducted in the United Kingdom. Informal caregivers of adults living with CKD were recruited via social media, websites, newsletters, magazine articles, a podcast episode, and paid Facebook advertisements. The survey examined: informal caregiver characteristics; care recipient characteristics; self-help intervention preferences; and informal caregiver's mental health using the DASS-21. Data were analysed using descriptive statistics. RESULTS: Sixty-five informal caregivers participated. The majority (85%) were female, caring for a male (77%) spouse/partner (74%). Responses indicated 58% of informal caregivers were experiencing at least mild depression. In total, 48% indicated they were likely to use a CBT self-help intervention, preferring an intervention provided via internet (e.g. website) (64%), workbook (56%), or individually in-person (54%). Regarding content, interventions should cover a wide range of topics including living with CKD, support services, informal caregiver's physical health, and diet. Overall, 48% reported a preference for a supported intervention, with support delivered in-person or via email by a trained professional at a community organisation. CONCLUSIONS: Results suggest CBT self-help interventions may be an acceptable way to provide psychological support to informal caregivers, however the study is limited by the small sample size. A wide range of intervention preferences were identified indicating a need to tailor intervention content and delivery to enhance acceptability and engagement. Results will inform development of a CBT self-help intervention for informal caregivers of people with CKD.
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Terapia Cognitivo-Conductual , Insuficiencia Renal Crónica , Humanos , Masculino , Adulto , Femenino , Cuidadores/psicología , Estudios Transversales , Salud Mental , Insuficiencia Renal Crónica/terapiaRESUMEN
OBJECTIVE: To assess whether women who experience stressful life events during the periconceptional period are at higher risk of giving birth to a baby with an orofacial cleft (OFC). DESIGN: Systematic review and meta-analysis of studies reporting the proportion of babies born with OFC to mothers exposed and unexposed to population-level or personal-level stressful life events during the periconceptional period. Six electronic databases were searched from inception to August 2020. Risk of bias was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) for the odds of OFC in babies of exposed mothers relative to unexposed controls were extracted and/or calculated. Random effects meta-analysis was undertaken, stratified by cleft subtype. RESULTS: Of 12 eligible studies, 8 examined experience of personal events and 4 examined population-level events. Studies demonstrated low-moderate risk of bias and there was indication of publication bias. There was some evidence that personal stressful life events were associated with greater odds of cleft lip and/or palate (six studies, OR 1.63, 95% confidence interval (CI) 1.16, 2.30, P = 0.001) and cleft palate only (six studies, OR 1.45, 95% CI 1.02, 2.06, P = 0.04). Population-level events were associated with higher odds of OFC in studies that did not specify subtype (three studies, OR 1.64, 95% CI 1.19, 2.25, P = 0.002), but subtype stratified analyses were underpowered. Heterogeneity was high. CONCLUSIONS: Limited evidence indicated a weak positive association between maternal stressful life events during the periconceptional period and risk of OFC in the offspring, but further studies with greater consistency in research design are needed.
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Labio Leporino , Fisura del Paladar , Estudios de Casos y Controles , Femenino , Humanos , Oportunidad Relativa , Embarazo , Factores de RiesgoRESUMEN
BACKGROUND: The burden of chronic kidney disease (CKD) and its treatment may severely limit the ability of children with CKD to do daily tasks and participate in family, school, sporting and recreational activities. Life participation is critically important to affected children and their families; however, the appropriateness and validity of available measures used to assess this outcome are uncertain. The aim of this study was to identify the characteristics, content and psychometric properties of existing measures for life participation used in children with CKD. METHODS: We searched MEDLINE, Embase, PsychINFO, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Kidney and Transplant register to August 2019 for all studies that used a measure to report life participation in children with CKD. For each measure, we extracted and analyzed the characteristics, dimensions of life participation and psychometric properties. RESULTS: From 128 studies, we identified 63 different measures used to assess life participation in children with CKD. Twenty-five (40%) of the measures were patient reported, 7 (11%) were parent proxy reported and 31 (49%) had both self and parent proxy reports available. Twenty-two were used in one study only. The Pediatric Quality of Life Inventory version 4.0 generic module was used most frequently in 62 (48%) studies. Seven (11%) were designed to assess ability to participate in life, with 56 (89%) designed to assess other constructs (e.g. quality of life) with a subscale or selected questions on life participation. Across all measures, the three most frequent activities specified were social activities with friends and/or family, leisure activities and self-care activities. Validation data in the pediatric CKD population were available for only 19 (30%) measures. CONCLUSIONS: Life participation is inconsistently measured in children with CKD and the measures used vary in their characteristics, content and validity. Validation data supporting these measures in this population are often incomplete and are sparse. A meaningful and validated measure for life participation in children with CKD is needed.
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Conductas Relacionadas con la Salud , Padres/psicología , Participación del Paciente/psicología , Medición de Resultados Informados por el Paciente , Calidad de Vida , Insuficiencia Renal Crónica/rehabilitación , Niño , Humanos , Participación del Paciente/estadística & datos numéricosRESUMEN
BACKGROUND: Although young adulthood is associated with transplant loss, many studies do not examine eGFR decline. We aimed to establish clinical risk factors to identify where early intervention might prevent subsequent adverse transplant outcomes. METHODS: Retrospective cohort study using UK Renal Registry and UK Transplant Registry data, including patients aged < 30 years transplanted 1998-2014. Associations with death-censored graft failure were investigated with multivariable Cox proportional hazards. Multivariable linear regression was used to establish associations with eGFR slope gradients calculated over the last 5 years of observation per individual. RESULTS: The cohort (n = 5121, of whom n = 371 received another transplant) was 61% male, 80% White and 36% had structural disease. Live donation occurred in 48%. There were 1371 graft failures and 145 deaths with a functioning graft over a 39,541-year risk period. Median follow-up was 7 years. Fifteen-year graft survival was 60.2% (95% CI 58.1, 62.3). Risk associations observed in both graft loss and eGFR decline analyses included female sex, glomerular diseases, Black ethnicity and young adulthood (15-19-year and 20-24-year age groups, compared to 25-29 years). A higher initial eGFR was associated with less risk of graft loss but faster eGFR decline. For each additional 10 mL/min/1.73m2 initial eGFR, the hazard ratio for graft loss was 0.82 (95% CI 0.79, 0.86), p < 0.0001. However, compared to < 60 mL/min/1.73m2, higher initial eGFR was associated with faster eGFR decline (> 90 mL/min/1.73m2; - 3.55 mL/min/1.73m2/year (95% CI -4.37, - 2.72), p < 0.0001). CONCLUSIONS: In conclusion, young adulthood is a key risk factor for transplant loss and eGFR decline for UK children and young adults. This study has an extended follow-up period and confirms common risk associations for graft loss and eGFR decline, including female sex, Black ethnicity and glomerular diseases. A higher initial eGFR was associated with less risk of graft loss but faster rate of eGFR decline. Identification of children at risk of faster rate of eGFR decline may enable early intervention to prolong graft survival.
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Tasa de Filtración Glomerular , Supervivencia de Injerto/fisiología , Trasplante de Riñón , Adolescente , Adulto , Factores de Edad , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Reino Unido , Adulto JovenRESUMEN
RATIONALE & OBJECTIVE: Patients in late adolescence and early adulthood receiving renal replacement therapy (RRT) face disruption to normal activities, which affects well-being. We aimed to define psychosocial and lifestyle outcomes for young adults on RRT compared to the general population. STUDY DESIGN: We undertook a cross-sectional survey (the SPEAK [Surveying Patients Experiencing Young Adult Kidney Failure] Study) using validated measures and general population comparator data from the Health Survey for England and Avon Longitudinal Study of Parents and Children. Additional clinical information was obtained from the UK Renal Registry. SETTING & PARTICIPANTS: 16- to 30-year-olds receiving RRT. OUTCOMES: Psychosocial health and lifestyle behaviors. ANALYTICAL APPROACH: We compared outcomes between populations using age- and sex-adjusted regression models, weighted to account for response bias by sex, ethnicity, and socioeconomic status. Our findings were used to update recent meta-analyses. RESULTS: We recruited 976 young adults and 64% responded to the survey: 417 (71%) with kidney transplants and 173 (29%) on dialysis therapy. Compared to the general population, young adults on RRT were less likely to be in a relationship and have children and more likely to live in the family home, receive no income, and be unable to work due to health. They had poorer quality of life, worse well-being, and twice the likelihood of a psychological disturbance (OR, 2.7; 95% CI, 2.0-3.7; P<0.001). They reported less smoking, alcohol and drug abuse, and crime. In a meta-analysis, our study showed the greatest differences in quality of life compared to the general population. LIMITATIONS: Cross-sectional study design, meaning that we could not track the impact of treatment changes on the outcomes. CONCLUSIONS: This study involving a large cohort of young adult transplant recipients and dialysis patients provides evidence of worse psychosocial outcomes but more positive lifestyle behaviors in young adults on RRT compared to the age-matched general population.
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Conductas Relacionadas con la Salud , Estado de Salud , Fallo Renal Crónico/terapia , Trasplante de Riñón/métodos , Estilo de Vida , Diálisis Renal/métodos , Adolescente , Factores de Edad , Actitud Frente a la Salud , Estudios Transversales , Inglaterra , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Trasplante de Riñón/psicología , Estudios Longitudinales , Masculino , Psicología , Sistema de Registros , Diálisis Renal/mortalidad , Diálisis Renal/psicología , Índice de Severidad de la Enfermedad , Factores Sexuales , Análisis de Supervivencia , Adulto JovenRESUMEN
Background: Clinical epidemiology data for young adults on renal replacement therapy (RRT) are lacking. While mostly transplanted, they have an increased risk of graft loss during young adulthood. Methods: We combined the UK Renal Registry paediatric and adult databases to describe patient characteristics, transplantation and survival for young adults. We grouped patients 11-30 years of age starting RRT from 1999 to 2008 by age band and examined their course during 5 years of follow-up. Results: The cohort (n = 3370) was 58% male, 79% white and 29% had glomerulonephritis. Half (52%) started RRT on haemodialysis (HD). Most (78%) were transplanted (18% pre-emptive, 61% as second modality); 11% were not listed for transplant. Transplant timing varied by age group. The deceased:living donor kidney transplant ratio was 2:1 for 11-<16 year olds and 1:1 otherwise. Median deceased donor transplant waiting times ranged from 6 months if <16 years of age to 17 months if ≥21 years. Overall 8% died, with being on dialysis and not transplant listed versus transplanted {hazard ratio [HR] 16.6 [95% confidence interval (CI) 10.8-25.4], P < 0.0001} and diabetes versus glomerulonephritis [HR 4.03 (95% CI 2.71-6.01), P < 0.0001] increasing mortality risk. Conclusions: This study highlights the frequent use of HD and the importance of transplant listing and diabetes for young adults. More than half the young adults in our cohort started renal replacement therapy on HD. One in 10 young adults were not listed for transplant by 5 years and were â¼20 times more likely to die than those who were transplanted. Diabetes as a primary renal disease was common among young adults and associated with increased mortality. Overall, almost 1 in 10 young adults had died by 5 years from the start of RRT.
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Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Sistema de Registros/estadística & datos numéricos , Terapia de Reemplazo Renal/mortalidad , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapia , Masculino , Pronóstico , Tasa de Supervivencia , Reino Unido/epidemiología , Adulto JovenRESUMEN
A disease registry uses observational study methods to collect defined data on patients with a particular condition for a predetermined purpose. By providing comprehensive standardised data on patients with kidney disease, renal registries aim to provide a 'real world' representation of practice patterns, treatment and patient outcomes that may not be captured accurately by other methods, including randomised controlled trials. Additionally, using registries to measure variations in outcomes and audit care against standards is crucial to understanding how to improve quality of care for patients in an efficacious and cost-effective manner. Registries also have the potential to be a powerful scientific tool that can monitor and support the translational process between research and routine clinical practice, although their limitations must be borne in mind. In this review, we describe the role of the UK Renal Registry as a tool to support translational research. We describe its involvement across each stage of the translational pathway: from hypothesis generation, study design and data collection, to reporting of long-term outcomes and quality improvement initiatives. Furthermore we explore how this role may bring about improvements in care for adults and children with kidney disease.
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Enfermedades Renales/terapia , Salud Pública/normas , Sistema de Registros , Nivel de Atención/normas , Investigación Biomédica Traslacional/métodos , Niño , Humanos , Riñón , Proyectos de Investigación , Reino UnidoRESUMEN
Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8)) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, Pâ=â8.1×10(-8)), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, Pâ=â2.9×10(-6)), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, Pâ=â6.5×10(-4)). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22-1.54, Pâ=â1.2×10(-7) and OR: 1.25, 95% CI 1.12-1.39, Pâ=â6.2×10(-5)). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, Pâ=â1.9×10(-3)). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.
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Autoanticuerpos/genética , Enfermedad de Graves/genética , Enfermedad de Hashimoto/genética , Yoduro Peroxidasa/genética , Autoanticuerpos/aislamiento & purificación , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Enfermedad de Graves/patología , Enfermedad de Hashimoto/patología , Humanos , Yoduro Peroxidasa/inmunología , Factores de Riesgo , Tiroiditis Autoinmune , Tirotropina/metabolismoRESUMEN
In this work, we study hole transport in a planar silicon metal-oxide-semiconductor based double quantum dot. We demonstrate Pauli spin blockade in the few hole regime and map the spin relaxation induced leakage current as a function of interdot level spacing and magnetic field. With varied interdot tunnel coupling, we can identify different dominant spin relaxation mechanisms. Application of a strong out-of-plane magnetic field causes an avoided singlet-triplet level crossing, from which the heavy hole g-factor ~0.93 and the strength of spin-orbit interaction ~110 µeV can be obtained. The demonstrated strong spin-orbit interaction of heavy holes promises fast local spin manipulation using only electric fields, which is of great interest for quantum information processing.
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Hydrogenated diamond possesses a unique surface conductivity as a result of transfer doping by surface acceptors. Yet, despite being extensively studied for the past two decades, little is known about the system at low temperature, particularly whether a two-dimensional hole gas forms at the diamond surface. Here we report that (100) diamond, when functionalized with hydrogen, supports a p-type spin-3/2 two-dimensional surface conductivity with a spin-orbit interaction of 9.74 ± 0.1 meV through the observation of weak antilocalization effects in magneto-conductivity measurements at low temperature. Fits to 2D localization theory yield a spin relaxation length of 30 ± 1 nm and a spin-relaxation time of â¼ 0.67 ± 0.02 ps. The existence of a 2D system with spin orbit coupling at the surface of a wide band gap insulating material has great potential for future applications in ferromagnet-semiconductor and superconductor-semiconductor devices.