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1.
Nature ; 585(7824): 234-238, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32908266

RESUMEN

The transport of carbon into Earth's mantle is a critical pathway in Earth's carbon cycle, affecting both the climate and the redox conditions of the surface and mantle. The largest unconstrained variables in this cycle are the depths to which carbon in sediments and altered oceanic crust can be subducted and the relative contributions of these reservoirs to the sequestration of carbon in the deep mantle1. Mineral inclusions in sublithospheric, or 'superdeep', diamonds (derived from depths greater than 250 kilometres) can be used to constrain these variables. Here we present oxygen isotope measurements of mineral inclusions within diamonds from Kankan, Guinea that are derived from depths extending from the lithosphere to the lower mantle (greater than 660 kilometres). These data, combined with the carbon and nitrogen isotope contents of the diamonds, indicate that carbonated igneous oceanic crust, not sediment, is the primary carbon-bearing reservoir in slabs subducted to deep-lithospheric and transition-zone depths (less than 660 kilometres). Within this depth regime, sublithospheric inclusions are distinctly enriched in 18O relative to eclogitic lithospheric inclusions derived from crustal protoliths. The increased 18O content of these sublithospheric inclusions results from their crystallization from melts of carbonate-rich subducted oceanic crust. In contrast, lower-mantle mineral inclusions and their host diamonds (deeper than 660 kilometres) have a narrow range of isotopic values that are typical of mantle that has experienced little or no crustal interaction. Because carbon is hosted in metals, rather than in diamond, in the reduced, volatile-poor lower mantle2, carbon must be mobilized and concentrated to form lower-mantle diamonds. Our data support a model in which the hydration of the uppermost lower mantle by subducted oceanic lithosphere destabilizes carbon-bearing metals to form diamond, without disturbing the ambient-mantle stable-isotope signatures. This transition from carbonate slab melting in the transition zone to slab dehydration in the lower mantle supports a lower-mantle barrier for carbon subduction.

2.
Nature ; 568(7750): 65-69, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30944494

RESUMEN

Mechanical resonators are important components of devices that range from gravitational wave detectors to cellular telephones. They serve as high-performance transducers, sensors and filters by offering low dissipation, tunable coupling to diverse physical systems, and compatibility with a wide range of frequencies, materials and fabrication processes. Systems of mechanical resonators typically obey reciprocity, which ensures that the phonon transmission coefficient between any two resonators is independent of the direction of transmission1,2. Reciprocity must be broken to realize devices (such as isolators and circulators) that provide one-way propagation of acoustic energy between resonators. Such devices are crucial for protecting active elements, mitigating noise and operating full-duplex transceivers. Until now, nonreciprocal phononic devices3-11 have not simultaneously combined the features necessary for robust operation: strong nonreciprocity, in situ tunability, compact integration and continuous operation. Furthermore, they have been applied only to coherent signals (rather than fluctuations or noise), and have been realized exclusively in travelling-wave systems (rather than resonators). Here we describe a scheme that uses the standard cavity-optomechanical interaction to produce robust nonreciprocal coupling between phononic resonators. This scheme provides about 30 decibels of isolation in continuous operation and can be tuned in situ simply via the phases of the drive tones applied to the cavity. In addition, by directly monitoring the dynamics of the resonators we show that this nonreciprocity can control thermal fluctuations, and that this control represents a way to cool phononic resonators.

3.
Br J Cancer ; 130(8): 1261-1268, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38383704

RESUMEN

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.


Asunto(s)
Cesárea , Neoplasias , Embarazo , Humanos , Femenino , Estudios Retrospectivos , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapia , Reino Unido/epidemiología , Nacimiento Vivo
4.
Pediatr Crit Care Med ; 25(1): e1-e11, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37732845

RESUMEN

OBJECTIVES: Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs). DESIGN: This is an analysis of of a seven-center prospective cohort study. SETTING: Seven PICUs within academic children's hospitals in the United States. PATIENTS: Critically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours. INTERVENTIONS: We evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen's Kappa were used to assess agreement. MEASUREMENTS AND MAIN RESULTS: Of 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83-0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44-0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 [18.3%] vs 24 [8.1%], p ≤ 0.001). CONCLUSIONS: Viral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology.


Asunto(s)
Enfermedad Crítica , Infecciones del Sistema Respiratorio , Niño , Humanos , Lactante , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estudios Prospectivos , Infecciones del Sistema Respiratorio/diagnóstico , Nasofaringe , Análisis de Secuencia de ARN
5.
J Intellect Disabil Res ; 68(2): 173-180, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37921399

RESUMEN

BACKGROUND: Understanding the specific neurobehavioural profile of rare genetic diseases enables clinicians to provide the best possible care for patients and families, including prognostic and treatment advisement. Previous studies suggested that a subset of individuals with Kabuki syndrome (KS), a genetic disorder causing intellectual disability and other neurodevelopmental phenotypes, have attentional deficits. However, these studies looked at relatively small numbers of molecularly confirmed cases and often used retrospective clinical data instead of standardised assessments. METHODS: Fifty-five individuals or caregivers of individuals with molecularly confirmed KS completed assessments to investigate behaviour and adaptive function. Additionally, information was collected on 23 unaffected biological siblings as controls. RESULTS: Attention Problems in children was the only behavioural category that, when averaged, was clinically significant, with the individual scores of nearly 50% of the children with KS falling in the problematic range. Children with KS scored significantly higher than their unaffected sibling on nearly all behavioural categories. A significant correlation was found between Attention Problems scores and adaptive function scores (P = 0.032), which was not explained by lower general cognitive ability. CONCLUSIONS: We found that the rates of children with attentional deficits are much more elevated than would be expected in the general population, and that attention challenges are negatively correlated with adaptive function. When averaged across KS participants, none of the behavioural categories were in the clinically significant range except Attention Problems for children, which underscores the importance of clinicians screening for attention deficit hyperactivity disorder (ADHD) in children with KS.


Asunto(s)
Anomalías Múltiples , Cara/anomalías , Enfermedades Hematológicas , Discapacidad Intelectual , Enfermedades Vestibulares , Niño , Humanos , Estudios Retrospectivos , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/genética
6.
Rhinology ; 62(3): 330-341, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38189480

RESUMEN

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.


Asunto(s)
Pérdida de Líquido Cefalorraquídeo , Endoscopía , Procedimientos de Cirugía Plástica , Base del Cráneo , Humanos , Femenino , Masculino , Base del Cráneo/cirugía , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/prevención & control , Pérdida de Líquido Cefalorraquídeo/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Endoscopía/métodos , Procedimientos de Cirugía Plástica/métodos , Adulto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anciano , Neoplasias Hipofisarias/cirugía , Neoplasias de la Base del Cráneo/cirugía , Rinorrea de Líquido Cefalorraquídeo/prevención & control , Rinorrea de Líquido Cefalorraquídeo/cirugía , Rinorrea de Líquido Cefalorraquídeo/etiología
7.
J Healthc Manag ; 69(1): 12-28, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38175533

RESUMEN

GOAL: Clinician stress and resilience have been the subjects of significant research and interest in the past several decades. We aimed to understand the factors that contribute to clinician stress and resilience in order to appropriately guide potential interventions. METHODS: We conducted a scoping review (n = 42) of published reviews of research on clinician distress and resilience using the methodology of Peters and colleagues (2020). Our team examined these reviews using the National Academy of Medicine's framework for clinician well-being and resilience. PRINCIPAL FINDINGS: We found that organizational factors, learning/practice environment, and healthcare responsibilities were three of the top four factors identified in the reviews as contributing to clinician distress. Learning/practice environment and organizational factors were two of the top four factors identified in the reviews as contributing to their resilience. PRACTICAL APPLICATIONS: Clinicians continue to face numerous external challenges that complicate their work. Further research, practice, and policy changes are indicated to improve practice environments for healthcare clinicians. Healthcare leaders need to promote resources for organizational and system-level changes to improve clinician well-being.


Asunto(s)
Personal de Salud , Estrés Laboral , Resiliencia Psicológica , Humanos , Personal de Salud/psicología
8.
BMC Microbiol ; 23(1): 312, 2023 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-37891457

RESUMEN

BACKGROUND: Tobramycin inhalation solution (TIS) and chronic azithromycin (AZ) have known clinical benefits for children with CF, likely due to antimicrobial and anti-inflammatory activity. The effects of chronic AZ in combination with TIS on the airway microbiome have not been extensively investigated. Oropharyngeal swab samples were collected in the OPTIMIZE multicenter, randomized, placebo-controlled trial examining the addition of AZ to TIS in 198 children with CF and early P. aeruginosa infection. Bacterial small subunit rRNA gene community profiles were determined. The effects of TIS and AZ were assessed on oropharyngeal microbial diversity and composition to uncover whether effects on the bacterial community may be a mechanism of action related to the observed changes in clinical outcomes. RESULTS: Substantial changes in bacterial communities (total bacterial load, diversity and relative abundance of specific taxa) were observed by week 3 of TIS treatment for both the AZ and placebo groups. On average, these shifts were due to changes in non-traditional CF taxa that were not sustained at the later study visits (weeks 13 and 26). Bacterial community measures did not differ between the AZ and placebo groups. CONCLUSIONS: This study provides further evidence that the mechanism for AZ's effect on clinical outcomes is not due solely to action on airway microbial composition.


Asunto(s)
Fibrosis Quística , Microbiota , Infecciones por Pseudomonas , Humanos , Niño , Azitromicina/farmacología , Azitromicina/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/microbiología , Administración por Inhalación , Pseudomonas aeruginosa/genética , Tobramicina/farmacología , Bacterias/genética , Microbiota/genética
9.
Phys Rev Lett ; 130(21): 216001, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37295082

RESUMEN

We demonstrate the trapping of millimeter-scale superfluid helium drops in high vacuum. The drops are sufficiently isolated that they remain trapped indefinitely, cool by evaporation to 330 mK, and exhibit mechanical damping that is limited by internal processes. The drops are also shown to host optical whispering gallery modes. The approach described here combines the advantages of multiple techniques, and should offer access to new experimental regimes of cold chemistry, superfluid physics, and optomechanics.


Asunto(s)
Frío , Helio , Vacio , Transición de Fase , Física
10.
Pediatr Res ; 94(2): 660-667, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36750739

RESUMEN

BACKGROUND: Tobacco smoke exposure increases the risk and severity of lower respiratory tract infections in children, yet the mechanisms remain unclear. We hypothesized that tobacco smoke exposure would modify the lower airway microbiome. METHODS: Secondary analysis of a multicenter cohort of 362 children between ages 31 days and 18 years mechanically ventilated for >72 h. Tracheal aspirates from 298 patients, collected within 24 h of intubation, were evaluated via 16 S ribosomal RNA sequencing. Smoke exposure was determined by creatinine corrected urine cotinine levels ≥30 µg/g. RESULTS: Patients had a median age of 16 (IQR 568) months. The most common admission diagnosis was lower respiratory tract infection (53%). Seventy-four (20%) patients were smoke exposed and exhibited decreased richness and Shannon diversity. Smoke exposed children had higher relative abundances of Serratia spp., Moraxella spp., Haemophilus spp., and Staphylococcus aureus. Differences were most notable in patients with bacterial and viral respiratory infections. There were no differences in development of acute respiratory distress syndrome, days of mechanical ventilation, ventilator free days at 28 days, length of stay, or mortality. CONCLUSION: Among critically ill children requiring prolonged mechanical ventilation, tobacco smoke exposure is associated with decreased richness and Shannon diversity and change in microbial communities. IMPACT: Tobacco smoke exposure is associated with changes in the lower airways microbiome but is not associated with clinical outcomes among critically ill pediatric patients requiring prolonged mechanical ventilation. This study is among the first to evaluate the impact of tobacco smoke exposure on the lower airway microbiome in children. This research helps elucidate the relationship between tobacco smoke exposure and the lower airway microbiome and may provide a possible mechanism by which tobacco smoke exposure increases the risk for poor outcomes in children.


Asunto(s)
Microbiota , Infecciones del Sistema Respiratorio , Contaminación por Humo de Tabaco , Humanos , Niño , Contaminación por Humo de Tabaco/efectos adversos , Enfermedad Crítica , Respiración Artificial/efectos adversos , Humo/efectos adversos , Nicotiana , Cotinina
11.
J Pediatr Gastroenterol Nutr ; 76(3): 347-354, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36525669

RESUMEN

OBJECTIVE: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls. METHODS: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons. RESULTS: One hundred thirty-nine mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG, and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased ( Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE ( Streptococcus , Gemella ) and EoG ( Leptotrichia ), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls. CONCLUSIONS: Dominant community members ( Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.


Asunto(s)
Esofagitis Eosinofílica , Microbiota , Adulto , Humanos , Niño , Esofagitis Eosinofílica/patología , Estudios Prospectivos
12.
Langenbecks Arch Surg ; 408(1): 21, 2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36635455

RESUMEN

OBJECTIVE: The effectiveness of adjuvant radioiodine (RAI) after reoperation in patients with persistent or recurrent differentiated thyroid cancer (DTC) is controversial. Although various organizations recognize that strong evidence for the use of RAI is lacking, they continue to recommend the use of adjuvant RAI therapy for select groups of patients. This is concerning as RAI therapy has potential side effects such as gastrointestinal symptoms, bone marrow suppression, and gonadal damage. METHODS: Four electronic databases were systematically searched for randomized trials or observational studies that examined the outcomes of adjuvant RAI after reoperation for recurrent DTC, among patients of any age. The baseline characteristics, treatment response, disease progression, and overall survival of these studies were synthesized and reported. A meta-analysis of the use of RAI on progression-free survival was also performed. RESULTS: Six observational studies, comprising a combined cohort of 437 patients who underwent reoperation, were included from 1212 records. Adjuvant RAI after reoperation in recurrent DTC was not associated with longer progression-free or overall survival. There was also no association of RAI with excellent structural or biochemical treatment response, lower thyroglobulin levels, nor a lower rate of second recurrence or distant metastases. CONCLUSIONS: Adjuvant RAI after reoperation in recurrent DTC was not associated with improved cancer or treatment-related outcomes. However, as the included studies were of inadequate quality, there is an urgent need for randomized trials and well-analyzed cohort studies. Physicians should exercise clinical judgment to prescribe adjuvant RAI for only selected, high-risk patients.


Asunto(s)
Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/diagnóstico , Radioisótopos de Yodo/uso terapéutico , Reoperación , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Adenocarcinoma/cirugía , Estudios Retrospectivos , Tiroidectomía
13.
Australas J Dermatol ; 64(4): e348-e351, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37688423

RESUMEN

BACKGROUND/OBJECTIVES: Exposure to chemical phenols, which can act as tyrosine analogues and result in anti-melanocyte autoimmunity, has been associated with vitiligo. Acetaminophen (N-acetyl-p-aminophenol) is an over-the-counter analgesic of phenolic origin. The risk of vitiligo with systemic exposure to acetaminophen has not yet been evaluated. METHODS: We examined the risk of vitiligo with regular use acetaminophen in women, the Nurses' Health Study (NHS) and in men, the Health Professionals Follow-up Study (HPFS). Regular acetaminophen use was asked biennially from 1990 in NHS and from 1986 in HPFS, and the year of clinician-diagnosed vitiligo was asked retrospectively in 2012 in the cohorts. RESULTS: In NHS, a total of 161 vitiligo cases were identified during a follow-up of 571,724 person-years; in HPFS, a total of 183 vitiligo cases were identified during a follow-up of 680,313 person-years. Regular use of acetaminophen was associated with an increased vitiligo risk in NHS but not HPFS. The multivariable relative risk (RR) was 1.52 (95% confidence interval [CI] 1.03-2.25) in NHS and 1.09 (95% CI 0.76-1.55) in HPFS. The higher risk of vitiligo was similar by duration of acetaminophen use in women; the multivariable RRs were 1.47 (95% CI 0.98-2.21) for acetaminophen use under 5 years, and 1.78 (95% CI 1.11-2.84) for acetaminophen use over 5 years. CONCLUSIONS: Acetaminophen may be associated with a higher risk of vitiligo in women.


Asunto(s)
Acetaminofén , Vitíligo , Masculino , Humanos , Femenino , Acetaminofén/efectos adversos , Estudios de Seguimiento , Estudios Prospectivos , Vitíligo/inducido químicamente , Vitíligo/epidemiología , Estudios Retrospectivos , Factores de Riesgo
14.
J Intellect Disabil Res ; 67(2): 101-111, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36437529

RESUMEN

BACKGROUND: Wiedemann-Steiner syndrome (WSS) is a rare genetic disorder caused by heterozygous variants in KMT2A. To date, the cognitive profile associated with WSS remains largely unknown, although emergent case series implicate increased risk of non-verbal reasoning and visual processing deficits. This study examines the academic and learning concerns associated with WSS based on a parent-report screening measure. PARTICIPANTS AND METHODS: A total of 25 parents of children/adults with a molecularly-confirmed diagnosis of WSS (mean age = 12.85 years, SD = 7.82) completed the Colorado Learning Difficulties Questionnaire (CLDQ), a parent-screening measure of learning and academic difficulties. Parent ratings were compared to those from a normative community sample to determine focal areas in Math, Reading and Spatial skills that may be weaker within this clinical population. RESULTS: On average, parent ratings on the Math (mean Z = -3.08, SD = 0.87) and Spatial scales (mean Z = -2.52, SD = 0.85) were significantly more elevated than that of Reading (mean Z = -1.31, SD = 1.46) (Wilcoxon sign rank test Z < -3.83, P < 0.001), reflecting relatively more challenges observed in these areas. Distribution of parent ratings in Math items largely reflect a positively skewed distribution with most endorsing over three standard deviations below a community sample. In contrast, distributions of parent ratings in Reading and Spatial domains were more symmetric but flat. Ratings for Reading items yielded much larger variance than the other two domains, reflecting a wider range of performance variability. CONCLUSIONS: Parent ratings on the CLDQ suggest more difficulties with Math and Spatial skills among those with WSS within group and relative to a community sample. Study results are consistent with recent case reports on the neuropsychological profile associated with WSS and with Kabuki syndrome, which is caused by variants in the related gene KMT2D. Findings lend support for overlapping cognitive patterns across syndromes, implicating potential common disease pathogenesis.


Asunto(s)
Anomalías Múltiples , Discapacidad Intelectual , Niño , Humanos , Anomalías Múltiples/genética , Cognición , Trastornos del Crecimiento , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/genética , Preescolar , Adolescente
15.
J Cell Sci ; 133(17)2020 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-32801124

RESUMEN

Tubulin enters the cilium by diffusion and motor-based intraflagellar transport (IFT). However, the respective contribution of each route in providing tubulin for axonemal assembly remains unknown. Using Chlamydomonas, we attenuated IFT-based tubulin transport of GFP-ß-tubulin by altering the IFT74N-IFT81N tubulin-binding module and the C-terminal E-hook of tubulin. E-hook-deficient GFP-ß-tubulin was incorporated into the axonemal microtubules, but its transport frequency by IFT was reduced by ∼90% in control cells and essentially abolished when the tubulin-binding site of IFT81 was incapacitated. Despite the strong reduction in IFT, the proportion of E-hook-deficient GFP-ß-tubulin in the axoneme was only moderately reduced. In vivo imaging showed more GFP-ß-tubulin particles entering cilia by diffusion than by IFT. Extrapolated to endogenous tubulin, the data indicate that diffusion provides most of the tubulin required for axonemal assembly. We propose that IFT of tubulin is nevertheless needed for ciliogenesis, because it augments the tubulin pool supplied to the ciliary tip by diffusion, thus ensuring that free tubulin there is maintained at the critical concentration for plus-end microtubule assembly during rapid ciliary growth.


Asunto(s)
Chlamydomonas , Tubulina (Proteína) , Axonema/metabolismo , Transporte Biológico , Chlamydomonas/metabolismo , Cilios/metabolismo , Flagelos/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
16.
Phys Rev Lett ; 128(18): 183601, 2022 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-35594119

RESUMEN

We use single photon detectors to probe the motional state of a superfluid ^{4}He resonator of mass ∼1 ng. The arrival times of Stokes and anti-Stokes photons (scattered by the resonator's acoustic mode) are used to measure the resonator's phonon coherences up to the fourth order. By postselecting on photon detection events, we also measure coherences in the resonator when ≤3 phonons have been added or subtracted. These measurements are found to be consistent with predictions that assume the acoustic mode to be in thermal equilibrium with a bath through a Markovian coupling.

17.
Nature ; 537(7618): 80-83, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27454555

RESUMEN

Topological operations can achieve certain goals without requiring accurate control over local operational details; for example, they have been used to control geometric phases and have been proposed as a way of controlling the state of certain systems within their degenerate subspaces. More recently, it was predicted that topological operations can be used to transfer energy between normal modes, provided that the system possesses a specific type of degeneracy known as an exceptional point. Here we demonstrate the transfer of energy between two vibrational modes of a cryogenic optomechanical device using topological operations. We show that this transfer arises from the presence of an exceptional point in the spectrum of the device. We also show that this transfer is non-reciprocal. These results open up new directions in system control; they also open up the possibility of exploring other dynamical effects related to exceptional points, including the behaviour of thermal and quantum fluctuations in their vicinity.

18.
Soc Psychiatry Psychiatr Epidemiol ; 57(7): 1457-1468, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35217891

RESUMEN

PURPOSE: Healthcare workers are at increased risk for mental health problems during disasters such as the COVID-19 pandemic. Identifying resilience mechanisms can inform development of interventions for this population. The current study examined pathways that may support healthcare worker resilience, specifically testing enabling (social support enabled self-efficacy) and cultivation (self-efficacy cultivating support) models. METHODS: Healthcare workers (N = 828) in the Rocky Mountain West completed self-report measures at four time points (once per month from April to July of 2020). We estimated structural equation models to explore the potential mediating effects that received social support and coping self-efficacy had (at time 2 and time 3) between traumatic stress symptom severity (at time 1 and time 4). Models included covariates gender, age, minority status, and time lagged co-variations between the proposed mediators (social support and coping self-efficacy). RESULTS: The full model fit the data well, CFI = .993, SRMR = .027, RMSEA = .036 [90% CIs (0.013, 0.057)]. Tests of sequential mediation supported enabling model dynamics. Specifically, the effects of time 1 traumatic stress severity were mediated through received social support at time 2 and time 3 coping self-efficacy, in sequential order to reduce time 4 traumatic stress severity. CONCLUSIONS: Findings show the importance of received social support and coping self-efficacy in mitigating psychopathology risk. Interventions can support mental health by focusing on social resource engagement that facilitates coping empowerment, which may decrease risk for mental health job-related problems among frontline healthcare workers exposed to highly stressful events.


Asunto(s)
COVID-19 , Pandemias , Adaptación Psicológica , COVID-19/epidemiología , Cognición , Personal de Salud/psicología , Humanos
19.
J Eur Acad Dermatol Venereol ; 36(10): 1831-1844, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35611638

RESUMEN

BACKGROUND: Vitiligo, an autoimmune disorder characterised by skin depigmentation, is associated with reduced quality of life (QoL). Vitiligo may be under-reported, in part because of misconceptions that it is a cosmetic disease. OBJECTIVES: This survey sought to characterise vitiligo prevalence and explore the relationship between sociodemographic and clinical characteristics with QoL in a population-based, multinational study. METHODS: Participants aged ≥18 years were recruited via an online panel in Europe, Japan and the USA to answer questions regarding skin disorders they may have experienced. Those reporting vitiligo (diagnosed or undiagnosed) or vitiligo signs (experiencing loss of skin colour but unaware of vitiligo and not diagnosed) were included in the analyses of vitiligo prevalence. Participants who self-reported physician-diagnosed vitiligo were given a broader survey to characterise disease progression, management and QoL (as measured with the Vitiligo-specific QoL [VitiQoL] instrument). RESULTS: The total estimated vitiligo prevalence among 35 694 survey participants (Europe, n = 18 785; USA, n = 8517; Japan, n = 8392) was 1.3% (diagnosed, 0.6%; undiagnosed, 0.4%; vitiligo signs, 0.3%). Among 219 patients formally diagnosed with vitiligo (Europe, n = 150; USA, n = 48; Japan, n = 21), total VitiQoL scores were associated with age (P = 0.00017), disease extent (P < 0.0001), disease progression (P < 0.0001), disease management (P < 0.0001) and time since diagnosis (P = 0.0015). Behaviour scores varied based on skin phototype (P = 0.024) and ethnicity (P = 0.048). Higher total VitiQoL scores were reported in patients with head lesions (P = 0.027) and those with head and hand and/or wrist lesions (P = 0.018). Substantial high concern (rated 8-10 on an 11-point Likert scale) for lesions was found across all body areas and varied with geographical region. CONCLUSIONS: The vitiligo prevalence rate may be higher than previously reported, with a substantial proportion attributed to people who have not received a formal diagnosis. Among formally diagnosed patients with vitiligo, QoL was most severely impacted by more progressive and higher extent of disease.


Asunto(s)
Calidad de Vida , Vitíligo , Adolescente , Adulto , Progresión de la Enfermedad , Humanos , Japón/epidemiología , Prevalencia , Encuestas y Cuestionarios , Vitíligo/epidemiología , Vitíligo/terapia
20.
Dis Aquat Organ ; 150: 37-51, 2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35796510

RESUMEN

Water temperatures that exceed thermal optimal ranges (~19 to 22°C for greenlip abalone Haliotis laevigata, depending on stock genetics) can be associated with abalone mortalities. We assessed histopathological changes in H. laevigata gills held in control (22°C) or elevated (25°C) water temperature conditions for 47 d by developing a new scoring protocol that incorporates histopathological descriptions and relative score summary. Lesions were allocated to 1 of 3 reaction patterns, (1) epithelial, (2) circulatory or (3) inflammatory, and scored based on their prevalence in gill leaflets. Indices for each reaction pattern were calculated and combined to provide an overall gill index. H. laevigata held in 25°C water temperature had significantly more epithelial lifting and hemolymph channel enlargement and significantly higher gill and circulatory reaction pattern indices than H. laevigata held in 22°C water temperature. One H. laevigata had a proliferation of unidentified cells in the v-shaped skeletal rod of a gill leaflet. The unidentified cells contained enlarged nuclei, a greater nucleus:cytoplasm ratio and, in some cases, mitotic figures. This cell population could represent a region of hematopoiesis in response to hemocyte loss or migration to a lesion. Without thorough diagnostic testing, the origin of these larger cells cannot be confirmed. The new scoring protocol developed will allow the standard quantification of gill lesions for H. laevigata, specifically for heat-related conditions, and could further be adapted for other Haliotis spp.


Asunto(s)
Gastrópodos , Branquias , Animales , Calor , Temperatura , Agua
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