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1.
Small Methods ; : e2400298, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39015052

RESUMO

Cathodic electrochemical intercalation/exfoliation of transition metal dichalcogenides (TMDs) with bulky tetraalkylammonium-based cations is gaining popularity as it avoids the semiconducting (2H) to metallic (1T) phase transformation in TMDs like molybdenum disulfide (MoS2) and, generally, produces sheets with a larger aspect ratio - important for achieving conformal sheet-to-sheet contact in optoelectronic devices. Large single crystals are typically used as the precursor, but these are expensive, often inaccessible, and result in limited quantities of material. In this paper, a 3D-printable electrochemical cell capable of intercalating gram-scale quantities of commercially available TMD powders is presented. By incorporating a reference electrode in the cell and physically restraining the powder with a spring-loaded mechanism, the system can probe the intercalation electrochemistry, for example, determining the onset of intercalation to be near -2.5 V versus the ferrocene redox couple. While the extent of intercalation depends on precursor quantity and reaction time, a high yield of exfoliated product can be obtained exhibiting average aspect ratios as high as 49 ± 44 similar to values obtained by crystal intercalation. The intercalation and exfoliation of a wide variety of pelletized commercial powders including molybdenum diselenide (MoSe2), tungsten diselenide (WSe2), tungsten disulfide (WS2), and graphitic carbon nitride (gCN) are also demonstrated.

2.
Clin Pediatr (Phila) ; : 99228241235440, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439533

RESUMO

This study explores missed pediatric speech and language pathology (SLP) appointments to identify barriers for patients with speech disorders. Data from 839 referrals at Boston Medical Center, including demographics, appointment details, COVID-19 lockdown, and number of items on patient problem lists, were analyzed using chi-square tests and logistic regression. The findings revealed that lockdown status, appointment timing, appointment type (in-person vs telemedicine), referral department (ear, nose, and throat [ENT] vs non-ENT), sex, race, primary language, birthplace, and primary care provider presence had no significant impact on attendance. However, the number of patient-listed problems, prior cancelations, and missed appointments were significant predictors of patients who did not keep appointments. In conclusion, this research emphasizes the patient's problem list and past appointment behavior as critical factors in predicting missed SLP appointments for pediatric speech disorder patients. These insights can guide targeted interventions to improve attendance and enhance SLP engagement.

3.
Clin Transl Immunology ; 13(2): e1490, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375330

RESUMO

Objectives: Systemic inflammatory response syndrome (SIRS) is a frequent complication of cardiopulmonary bypass (CPB). SIRS is associated with significant morbidity and mortality, but its pathogenesis remains incompletely understood, and as a result, biomarkers are lacking and treatment remains expectant and supportive. This study aimed to understand the pathophysiological mechanisms driving SIRS induced by CPB and identify novel therapeutic targets that might reduce systemic inflammation and improve patient outcomes. Methods: Twenty-one patients undergoing cardiac surgery and CPB were recruited, and blood was sampled before, during and after surgery. SIRS was defined using the American College of Chest Physicians/Society of Critical Care Medicine criteria. We performed immune cell profiling and whole blood transcriptomics and measured individual mediators in plasma/serum to characterise SIRS induced by CPB. Results: Nineteen patients fulfilled criteria for SIRS, with a mean duration of 2.7 days. Neutrophil numbers rose rapidly with CPB and remained elevated for at least 48 h afterwards. Transcriptional signatures associated with neutrophil activation and degranulation were enriched during CPB. We identified a network of cytokines governing these transcriptional changes, including granulocyte colony-stimulating factor (G-CSF), a regulator of neutrophil production and function. Conclusions: We identified neutrophils and G-CSF as major regulators of CPB-induced systemic inflammation. Short-term targeting of G-CSF could provide a novel therapeutic strategy to limit neutrophil-mediated inflammation and tissue damage in SIRS induced by CPB.

4.
Immunol Cell Biol ; 102(1): 8-11, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37982351

RESUMO

The advent and clinical success of immune checkpoint inhibitors Ipilimumab, Nivolumab and Pembrolizumab has had a seismic impact on our drug discovery focus and rationale. Novel extrinsic targets that enhance immune responses to cancer are actively being pursued, while tumor intrinsic targets that render cancer cells more sensitive to the immune system have joined traditional intrinsic targets (e.g. directly cytotoxic) in the drug discovery pipeline. The phosphatase PTPN2 (TC-PTP) and its paralog PTPN1 (PTP-1B) are negative regulators of several cytokine signaling pathways and T cell receptor (TCR) signaling. In a recent publication, Baumgartner et al. demonstrate the pre-clinical efficacy of a first-in-class dual PTPN1/N2 active site inhibitor (ABBV-CLS-484/AC484) in cancer models.


Assuntos
Anticorpos Monoclonais , Neoplasias , Humanos , Anticorpos Monoclonais/uso terapêutico , Nivolumabe/uso terapêutico , Ipilimumab/uso terapêutico , Neoplasias/tratamento farmacológico , Imunoterapia , Biologia
5.
Am J Otolaryngol ; 45(2): 104143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38101130

RESUMO

BACKGROUND: Invasive fungal sinusitis (IFS) is a rare infection with high mortality, mainly impacting immunocompromised patients. Given its significant mortality, timely recognition and treatment is crucial. This study aims to highlight the differences in presentation of IFS between pediatric and adult patients to aid in prompt diagnosis and treatment of this condition. METHODS: A comprehensive literature search of PubMed, EMBASE, Web of Science, Global Index Medicus, Global Health (EBSCO) and Cochrane Database of Systematic Reviews was conducted to identify articles relating to IFS. Patient demographics, comorbidities, presentation, disease characteristics, treatments and outcomes were extracted from the studies, and statistical analyses were conducted to compare these variables between pediatric and adult patients. RESULTS: 111 studies identified 22 pediatric and 132 adult patients worldwide. Children were more likely to have hematologic malignancies compared to adults (59.1 % vs. 15.2 %, p < 0.001). Facial symptoms such as pain, edema, and numbness were the most common symptoms for both age groups. In the pediatric population, fever and nasal or oral mucosal lesions were more common presenting symptoms (both p < 0.001). Pediatric patients were more likely to present without disease extension beyond the sinuses (p < 0.001). There was no significant difference in either medication treatment or mortality between the two cohorts. CONCLUSION: IFS often presents with non-specific symptoms and a unique presentation in pediatric and adult populations. Clinical awareness of the varying presentations in both populations is important to treat in a timely manner given the rapid progression and high mortality rates of IFS.


Assuntos
Infecções Fúngicas Invasivas , Seios Paranasais , Sinusite , Adulto , Criança , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/epidemiologia , Nariz , Sinusite/terapia , Sinusite/tratamento farmacológico , Revisões Sistemáticas como Assunto
6.
Int J Pediatr Otorhinolaryngol ; 175: 111778, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37956556

RESUMO

INTRODUCTION: Feeding and swallowing disorders have become increasingly prevalent among children, necessitating effective management to prevent long-term complications. Speech and language pathology (SLP) services play a crucial role in diagnosing and treating these disorders. The objective of this study was to explore the factors that influence patient attendance to SLP appointments for swallow disorders. METHODS: This study was conducted at Boston Medical Center, involving 359 pediatric patients referred to SLP for swallow-related concerns. De-identified patient and appointment information was obtained from the electronic medical record. Various factors such as age, gender, race/ethnicity, primary language, appointment date/time, and COVID-19 lockdown status were analyzed to determine their impact on patient no-shows. Statistical analyses, including Chi-Square tests and binary logistic regression, were conducted using appropriate methodologies. RESULTS: 355 individual patient records were included in the analysis. Lockdown status and appointment time of day did not significantly affect patient no-shows. However, appointments conducted through telemedicine showed a significant difference in attendance. Patient referral department, gender, race, language, and being born at the medical center did not significantly influence patient attendance. Notably, having a primary care provider (PCP) at the medical center significantly affected patient attendance. Furthermore, previous appointment cancellations made a patient more likely to no-show. CONCLUSION: This study provides valuable insights into the factors influencing patient attendance at SLP appointments for pediatric swallowing disorders. Having a PCP at the medical center and utilizing telemedicine appointments were associated with higher attendance rates. Addressing appointment cancellations and investigating underlying reasons behind missed appointments should be prioritized in future research. Understanding these factors will facilitate the development of interventions to optimize patient attendance and improve the delivery of SLP services in pediatric populations.


Assuntos
Transtornos de Deglutição , Patologia da Fala e Linguagem , Humanos , Criança , Fala , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/terapia , Agendamento de Consultas , Pacientes
7.
Cureus ; 15(9): e45313, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37846256

RESUMO

Objective  This study aimed to investigate the potential relationship between laryngomalacia and obesity as well as explore the interplay between laryngomalacia and obstructive sleep apnea using the Kids' Inpatient Database (KID) for the year 2016. Methods The Healthcare Cost and Utilization Project (HCUP) KID for 2016 provided a dataset for analysis. Patient demographics, diagnoses, and hospital characteristics were considered. Patients less than three years old were included due to the high prevalence of laryngomalacia in this age group. Results Among 4,512,196 neonatal admissions, 1,341 obesity cases and 11,642 laryngomalacia cases were analyzed. The frequency of laryngomalacia in patients with obesity was 578.1% higher than in the general population. Patients with obstructive sleep apnea (OSA) exhibited a 5,243.2% increase in laryngomalacia frequency compared to the overall population. Combining obesity and laryngomalacia resulted in a 6,738.5% increase in OSA frequency. Conclusions This study identified a significant correlation between obesity and increased laryngomalacia risk. The findings have important clinical implications for pediatric care, emphasizing the need to prevent childhood obesity to reduce laryngomalacia risk. Additionally, understanding these risk factors enables better risk stratification for laryngomalacia and potential OSA development.

8.
iScience ; 26(7): 107173, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37456846

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease with significant morbidity and mortality. Type I interferon (IFN) drives SLE pathology and plasmacytoid dendritic cells (pDCs) are potent producers of IFN; however, the specific effects of pDC depletion have not been demonstrated. We show CD123 was highly expressed on pDCs and the anti-CD123 antibody CSL362 potently depleted pDCs in vitro. CSL362 pre-treatment abrogated the induction of IFNα and IFN-induced gene transcription following stimulation with SLE patient-derived serum or immune complexes. RNA transcripts induced in pDCs by ex vivo stimulation with TLR ligands were reflected in gene expression profiles of SLE blood, and correlated with disease severity. TLR ligand-induced protein production by SLE patient peripheral mononuclear cells was abrogated by CSL362 pre-treatment including proteins over expressed in SLE patient serum. These findings implicate pDCs as key drivers in the cellular activation and production of soluble factors seen in SLE.

9.
J Colloid Interface Sci ; 648: 129-140, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37295365

RESUMO

HYPOTHESIS: Coating approaches which trap nanoparticles at an interface have become popular for depositing single-layer films from nanoparticle dispersions. Past efforts concluded that concentration and aspect ratio dominate the impact on aggregation state of nanospheres and nanorods at an interface. Although few works have explored the clustering behaviour of atomically thin, two-dimensional materials, we hypothesize that nanosheet concentration is the dominant factor leading to a particular cluster structure and that this local structure impacts the quality of densified Langmuir films. EXPERIMENTS: We systematically studied cluster structures and Langmuir film morphologies of three different nanosheets, namely chemically exfoliated molybdenum disulfide, graphene oxide and reduced graphene oxide. FINDINGS: We observe cluster structure transitions from island-like domains to more linear networks in all materials as dispersion concentration is reduced. Despite differences in material properties and morphologies, we obtained the same overall correlation between sheet number density (A/V) in the spreading dispersion and cluster fractal structure (df) is observed, with reduced graphene oxide sheets showing a slight delay upon transitioning into a lower-density cluster. Regardless of assembly method, we found that cluster structure impacts the attainable density of transferred Langmuir films. A two-stage clustering mechanism is supported by by considering the spreading profile of solvents and an analysis of interparticle forces at the air-water interface.

11.
Am Sociol ; : 1-13, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36855521

RESUMO

In this review essay, we probe three main elements of Laura Ford's Intellectual Property of Nations: her discussion of the structure of moral obligation and its materialization via writing and the institutions of the law; reflections on how the book intersects with questions of textual epistemology (especially the question of inferring intent from texts); and, finally, a self-consciously "presentist" discussion of how the book's findings intersect with our modern world of global legal regimes.

12.
Sci Rep ; 13(1): 2507, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782004

RESUMO

Pilots of aircraft face varying degrees of cognitive workload even during normal flight operations. Periods of low cognitive workload may be followed by periods of high cognitive workload and vice versa. During such changing demands, there exists potential for increased error on behalf of the pilots due to periods of boredom or excessive cognitive task demand. To further understand cognitive workload in aviation, the present study involved collection of electroencephalogram (EEG) data from ten (10) collegiate aviation students in a live-flight environment in a single-engine aircraft. Each pilot possessed a Federal Aviation Administration (FAA) commercial pilot certificate and either FAA class I or class II medical certificate. Each pilot flew a standardized flight profile representing an average instrument flight training sequence. For data analysis, we used four main sub-bands of the recorded EEG signals: delta, theta, alpha, and beta. Power spectral density (PSD) and log energy entropy of each sub-band across 20 electrodes were computed and subjected to two feature selection algorithms (recursive feature elimination (RFE) and lasso cross-validation (LassoCV), and a stacking ensemble machine learning algorithm composed of support vector machine, random forest, and logistic regression. Also, hyperparameter optimization and tenfold cross-validation were used to improve the model performance, reliability, and generalization. The feature selection step resulted in 15 features that can be considered an indicator of pilots' cognitive workload states. Then these features were applied to the stacking ensemble algorithm, and the highest results were achieved using the selected features by the RFE algorithm with an accuracy of 91.67% (± 0.11), a precision of 93.89% (± 0.09), recall of 91.67% (± 0.11), F-score of 91.22% (± 0.12), and the mean ROC-AUC of 0.93 (± 0.06). The achieved results indicated that the combination of PSD and log energy entropy, along with well-designed machine learning algorithms, suggest the potential for the use of EEG to discriminate periods of the low, medium, and high workload to augment aircraft system design, including flight automation features to improve aviation safety.


Assuntos
Pilotos , Humanos , Pilotos/psicologia , Análise e Desempenho de Tarefas , Reprodutibilidade dos Testes , Aeronaves , Eletroencefalografia , Cognição , Aprendizado de Máquina
13.
Ann Emerg Med ; 81(6): 691-698, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36841661

RESUMO

STUDY OBJECTIVE: Bystander cardiopulmonary resuscitation increases the likelihood of out-of-hospital cardiac arrest survival by more than two-fold. A common barrier to the prompt initiation of compressions is moving victims to the floor, but compression quality on a "floor" versus a "mattress" has not been tested among lay bystanders. METHODS: We conducted a prospective, randomized, cross-over trial comparing lay bystander compression quality using a manikin on a bed versus the floor. Participants included adults without professional health care training. We randomized participants to the order of manikin placement, either on a mattress or on the floor. For both, participants were instructed to perform 2 minutes of chest compressions on a cardiopulmonary resuscitation Simon manikin Gaumard (Gaumard Scientific, Miami, FL). The primary outcome was mean compression depth (cm) over 2 minutes. We fit a linear regression model adjusted for scenario order, age, sex, and body mass index with robust standard errors to account for repeated measures and reported mean differences with 95% confidence intervals (CIs). RESULTS: Our sample of 80 adults was 66% female with a mean age of 50.5 years (SD 18.2). The mean compression depth on the mattress was 2.9 cm (SD 2.3) and 3.5 cm (SD 2.2) on the floor, a mean difference of 0.58 cm (95% CI 0.18, 0.98). Compression depth fell below the 5 to 6 cm depth recommended by the American Heart Association on both surfaces. In the adjusted model, the mean depth was greater when the manikin was on the floor than the mattress (adjusted mean difference 0.62 cm; 95% CI 0.23 to 1.01), and mean depth was less for females than males (adjusted mean difference -1.42 cm, 95% CI -2.59, -0.25). In addition, the difference in compression depth was larger for female participants (mean difference 0.94 cm; 95% CI 0.54, 1.34) than for male participants (mean difference -0.01 cm; 95% CI -0.80, 0.78), and the interaction was statistically significant (P = .04). CONCLUSION: The mean compression depth was significantly smaller on the mattress and with female bystanders. Further research is needed to understand the benefit of moving out-of-hospital cardiac arrest victims to the floor relative to the detrimental effect of delaying chest compressions.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Cross-Over , Estudos Prospectivos , Reanimação Cardiopulmonar/educação , Mãos , Manequins
14.
Clin Transl Med ; 13(1): e1150, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36653319

RESUMO

BACKGROUND: Low-density neutrophils (LDN) are a distinct subset of neutrophils rarely detected in healthy people but appear in the blood of patients with autoimmune diseases, including systemic lupus erythematosus (SLE), and are mobilised in response to granulocyte colony-stimulating factor (G-CSF). The aim of this study was to identify novel mechanisms responsible for the pathogenic capacity of LDN in SLE. METHODS: Neutrophils were isolated from donors treated with G-CSF, and whole-cell proteomic analysis was performed on LDN and normal-density neutrophils. RESULTS: CD98 is significantly upregulated in LDN from G-CSF donors and defines a subset of LDN within the blood of SLE patients. CD98 is a transmembrane protein that dimerises with L-type amino acid transporters. We show that CD98 is responsible for the increased bioenergetic capacity of LDN. CD98 on LDN mediates the uptake of essential amino acids that are used by mitochondria to produce adenosine triphosphate, especially in the absence of glucose. Inhibition of CD98 reduces the metabolic flexibility of this population, which may limit their pathogenic capacity. CD98+ LDN produce more proinflammatory cytokines and chemokines than their normal density counterparts and are resistant to apoptosis, which may also contribute to tissue inflammation and end organ damage in SLE. CONCLUSIONS: CD98 provides a phenotypic marker for LDN that facilitates identification of this population without density-gradient separation and represents a novel therapeutic target to limit its pathogenic capacity.


Assuntos
Proteína-1 Reguladora de Fusão , Lúpus Eritematoso Sistêmico , Neutrófilos , Humanos , Citocinas/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Neutrófilos/metabolismo , Proteômica , Proteína-1 Reguladora de Fusão/metabolismo
15.
Ann Surg ; 277(2): 238-245, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34102667

RESUMO

OBJECTIVE: To develop a COS, an agreed minimum set of outcomes to measure and report in all studies evaluating the introduction and evaluation of novel surgical techniques. SUMMARY OF BACKGROUND DATA: Agreement on the key outcomes to measure and report for safe and efficient surgical innovation is lacking, hindering transparency and risking patient harm. METHODS: (I) Generation of a list of outcome domains from published innovation-specific literature, policy/regulatory body documents, and surgeon interviews; (II) Prioritization of identified outcome domains using an international, multi-stakeholder Delphi survey; (III) Consensus meeting to agree the final COS. Participants were international stakeholders, including patients/public, surgeons, device manufacturers, regulators, trialists, methodologists, and journal editors. RESULTS: A total of 7972 verbatim outcomes were identified, categorized into 32 domains, and formatted into survey items/questions. Four hundred ten international participants (220 professionals, 190 patients/public) completed at least one round 1 survey item, of which 153 (69.5%) professionals and 116 (61.1%) patients completed at least one round 2 item. Twelve outcomes were scored "consensus in" ("very important" by ≥70% of patients and professionals) and 20 "no consensus." A consensus meeting, involvingcontext: modifications, unexpected disadvantages, device problems, technical procedure completion success, patients' experience relating to the procedure being innovative, surgeons'/operators' experience. Other domains relate to intended benefits, whether the overall desired effect was achieved and expected disadvantages. CONCLUSIONS: The COS is recommended for use in all studies before definitive randomized controlled trial evaluation to promote safe, transparent, and efficient surgical innovation.


Assuntos
Projetos de Pesquisa , Cirurgiões , Humanos , Técnica Delphi , Consenso , Avaliação de Resultados em Cuidados de Saúde/métodos
16.
Am J Bot ; 110(2): e16112, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36478327

RESUMO

PREMISE: Phenological variation among individuals within populations is common and has a variety of ecological and evolutionary consequences, including forming the basis for population-level responses to environmental change. Although the timing of life-cycle events has genetic underpinnings, whether intraspecific variation in the duration of life-cycle events reflects genetic differences among individuals is poorly understood. METHODS: We used a common garden experiment with 10 genotypes of Salix hookeriana (coastal willow) from northern California, United States to investigate the extent to which genetic variation explains intraspecific variation in the timing and duration of multiple, sequential life-cycle events: flowering, leaf budbreak, leaf expansion, fruiting, and fall leaf coloration. We used seven clones of each genotype, for a total of 70 individual trees. RESULTS: Genotype affected each sequential life-cycle event independently and explained on average 62% of the variation in the timing and duration of vegetative and reproductive life-cycle events. All events were significantly heritable. A single genotype tended to be "early" or "late" across life-cycle events, but for event durations, there was no consistent response within genotypes. CONCLUSIONS: This research demonstrates that genetic variation can be a major component underlying intraspecific variation in the timing and duration of life-cycle events. It is often assumed that the environment affects durations, but we show that genetic factors also play a role. Because the timing and duration of events are independent of one another, our results suggest that the effects of environmental change on one event will not necessarily cascade to subsequent events.


Assuntos
Salix , Animais , Estações do Ano , Salix/fisiologia , Estágios do Ciclo de Vida , Folhas de Planta , Genótipo
17.
Sci Rep ; 12(1): 22511, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36581688

RESUMO

Tinnitus, a phantom perception of sound in the absence of any external sound source, is a prevalent health condition often accompanied by psychiatric comorbidities. Recent genome-wide association studies (GWAS) highlighted a polygenic nature of tinnitus susceptibility. A shared genetic component between tinnitus and psychiatric conditions remains elusive. Here we present a GWAS using the UK Biobank to investigate the genetic processes linked to tinnitus and tinnitus-related distress, followed by gene-set enrichment analyses. The UK Biobank sample comprised 132,438 individuals with tinnitus and genotype data. Among the study sample, 38,525 individuals reported tinnitus, and 26,889 participants mentioned they experienced tinnitus-related distress in daily living. The genome-wide association analyses were conducted on tinnitus and tinnitus-related distress. We conducted enrichment analyses using FUMA to further understand the genetic processes linked to tinnitus and tinnitus-related distress. A genome-wide significant locus (lead SNP: rs71595470) for tinnitus was obtained in the vicinity of GPM6A. Nineteen independent loci reached suggestive association with tinnitus. Fifteen independent loci reached suggestive association with tinnitus-related distress. The enrichment analysis revealed a shared genetic component between tinnitus and psychiatric traits, such as bipolar disorder, feeling worried, cognitive ability, fast beta electroencephalogram, and sensation seeking. Metabolic, cardiovascular, hematological, and pharmacological gene sets revealed a significant association with tinnitus. Anxiety and stress-related gene sets revealed a significant association with tinnitus-related distress. The GWAS signals for tinnitus were enriched in the hippocampus and cortex, and for tinnitus-related distress were enriched in the brain and spinal cord. This study provides novel insights into genetic processes associated with tinnitus and tinnitus-related distress and demonstrates a shared genetic component underlying tinnitus and psychiatric conditions. Further collaborative attempts are necessary to identify genetic components underlying the phenotypic heterogeneity in tinnitus and provide biological insight into the etiology.


Assuntos
Transtorno Bipolar , Zumbido , Humanos , Estudo de Associação Genômica Ampla , Zumbido/genética , Encéfalo , Transtorno Bipolar/complicações , Transtorno Bipolar/genética , Genótipo , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único
18.
BMJ Open ; 12(9): e059228, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36581966

RESUMO

OBJECTIVE: To review guidance, included in written local UK National Health Service (NHS) organisation policies, on information provision and consent for the introduction of new invasive procedures- including surgeries, and devices (IPs/Ds). DESIGN: A qualitative documentary analysis of data on patient information provision and consent extracted from policies for the introduction of IP/Ds from NHS organisations in England and Wales. SETTING: NHS trusts in England and health boards in Wales, UK. PARTICIPANTS: Between December 2017 and July 2018, 150 acute trusts in England and 7 health boards in Wales were approached for their policies for the introduction of new IP/Ds. In total, 123 policies were received, 11 did not fit the inclusion criteria and a further policy was included from a trust website resulting in 113 policies included for review. RESULTS: From the 113 policies, 22 did not include any statements on informed consent/information provision or lacked guidance on the information to be provided to patients and were hence excluded. Consequently, 91 written local NHS policies were included in the final dataset. Within the guidance obtained, variation existed on disclosure of the procedure's novelty, potential risks, benefits, uncertainties, alternative treatments and surgeon's experience. Few policies stated that clinicians should discuss the existing evidence associated with a procedure. Additionally, while the majority of policies referred to patients needing written information, this was often not mandated and few policies specified the information to be included. CONCLUSIONS: Nearly a fifth of all the policies lacked guidance on information to be provided to patients. There was variability in the policy documents regarding what patients should be told about innovative procedures. Further research is needed to ascertain the information and level of detail appropriate for patients when considering innovative procedures. A core information set including patients' and clinicians' views is required to address variability around information provision/consent for innovative procedures.


Assuntos
Política de Saúde , Medicina Estatal , Humanos , País de Gales , Inglaterra , Consentimento Livre e Esclarecido
20.
Proc Natl Acad Sci U S A ; 119(38): e2208814119, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36095186

RESUMO

Ureilite meteorites are arguably our only large suite of samples from the mantle of a dwarf planet and typically contain greater abundances of diamond than any known rock. Some also contain lonsdaleite, which may be harder than diamond. Here, we use electron microscopy to map the relative distribution of coexisting lonsdaleite, diamond, and graphite in ureilites. These maps show that lonsdaleite tends to occur as polycrystalline grains, sometimes with distinctive fold morphologies, partially replaced by diamond + graphite in rims and cross-cutting veins. These observations provide strong evidence for how the carbon phases formed in ureilites, which, despite much conjecture and seemingly conflicting observations, has not been resolved. We suggest that lonsdaleite formed by pseudomorphic replacement of primary graphite shapes, facilitated by a supercritical C-H-O-S fluid during rapid decompression and cooling. Diamond + graphite formed after lonsdaleite via ongoing reaction with C-H-O-S gas. This graphite > lonsdaleite > diamond + graphite formation process is akin to industrial chemical vapor deposition but operates at higher pressure (∼1-100 bar) and provides a pathway toward manufacture of shaped lonsdaleite for industrial application. It also provides a unique model for ureilites that can reconcile all conflicting observations relating to diamond formation.

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