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1.
EMBO Rep ; 24(8): e56430, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37272231

RESUMO

Human Tim8a and Tim8b are paralogous intermembrane space proteins of the small TIM chaperone family. Yeast small TIMs function in the trafficking of proteins to the outer and inner mitochondrial membranes. This putative import function for hTim8a and hTim8b has been challenged in human models, but their precise molecular function(s) remains undefined. Likewise, the necessity for human cells to encode two Tim8 proteins and whether any potential redundancy exists is unclear. We demonstrate that hTim8a and hTim8b function in the assembly of cytochrome c oxidase (Complex IV). Using affinity enrichment mass spectrometry, we define the interaction network of hTim8a, hTim8b and hTim13, identifying subunits and assembly factors of the Complex IV COX2 module. hTim8-deficient cells have a COX2 and COX3 module defect and exhibit an accumulation of the Complex IV S2 subcomplex. These data suggest that hTim8a and hTim8b function in assembly of Complex IV via interactions with intermediate-assembly subcomplexes. We propose that hTim8-hTim13 complexes are auxiliary assembly factors involved in the formation of the Complex IV S3 subcomplex during assembly of mature Complex IV.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial , Proteínas de Saccharomyces cerevisiae , Humanos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/metabolismo , Membranas Mitocondriais/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Mitocondriais/metabolismo
2.
Acta Paediatr ; 113(4): 786-794, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38299226

RESUMO

AIM: To assess parental awareness of respiratory syncytial virus (RSV) and the level of acceptance of future RSV prevention strategies. METHODS: A cross-sectional online survey was implemented targeting "future" and "current" parents of children aged ≤5 years in Australia. RESULTS: From 1992 eligible participants, two non-mutually exclusive subgroups were formed: "current" parents (N = 1931) and "pregnant/planning" parents (N = 464: 403 also "current" parents and 61 "future" parents). Participants were predominantly (86.6%) aged 25-39 years and 68.5% with university education. The majority (89.6% current; 78.7% future) had heard of RSV. Of those, 64.2% (current) and 50.0% (future) were aware that pneumonia is associated with RSV; 71.8% (current) and 52.1% (future) were aware that bronchiolitis is associated with RSV. In multivariable logistic regression analyses, Australian-born parents (aOR = 2.47 [95% CI: 1.48-4.12]), living in the eastern states (e.g., New South Wales: aOR = 6.15 [95% CI:2.10-18.04]), with a university-level education (aOR = 2.61 [95% CI:1.38-4.94]) and being a current parent (aOR = 12.26 [95% CI:2.82-53.28]) were associated with higher RSV awareness. There was a high level of acceptance for maternal vaccines (future: 79.3%) and infant immunisation (all: 81.7%). CONCLUSION: While RSV awareness and immunisation acceptance were high, there was limited knowledge of severity of RSV, especially in future parents. Education campaigns need to be developed to increase RSV knowledge.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Criança , Gravidez , Feminino , Humanos , Pré-Escolar , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Estudos Transversais , Austrália , Pais , Hospitalização
3.
J Hepatol ; 79(6): 1408-1417, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37517455

RESUMO

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). RESULTS: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). CONCLUSION: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. IMPACT AND IMPLICATIONS: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.


Assuntos
Injúria Renal Aguda , Síndrome Hepatorrenal , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Síndrome Hepatorrenal/epidemiologia , Síndrome Hepatorrenal/etiologia , Incidência , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Necrose/complicações , Estudos Retrospectivos
4.
Am J Kidney Dis ; 76(4): 546-557, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32479922

RESUMO

The management of pain in patients with chronic kidney disease (CKD) is challenging for many reasons. These patients have increased susceptibility to adverse drug effects due to altered drug metabolism and excretion, and there are limited safety data for use in this population despite a high pain burden. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been regarded as dangerous for use in patients with CKD because of their risk for nephrotoxicity and thus alternative classes of analgesics, including opioids, have become more commonly used for pain control in this population. Given the well-established risks that opioids and other analgesics pose, further characterization of the risk posed by NSAIDs in patients with CKD is warranted. NSAID use has been associated with acute kidney injury, progressive loss of glomerular filtration rate in CKD, electrolyte derangements, and hypervolemia with worsening of heart failure and hypertension. The risk for these nephrotoxicity syndromes is modified by many comorbid conditions, risk factors, and characteristics of use, and in patients with CKD, the risk differs between levels of glomerular filtration rate. In this review, we offer recommendations for the cautious use of NSAIDs in the CKD population after careful consideration of these risk factors on an individualized basis.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Dor/tratamento farmacológico , Dor/etiologia , Insuficiência Renal Crônica/complicações , Humanos , Nefropatias/induzido quimicamente
5.
Sedimentology ; 66(7): 2749-2768, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31866696

RESUMO

The shape and size of sedimentary bedforms play a key role in the reconstruction of sedimentary processes in modern and ancient environments. Recent laboratory experiments have shown that bedforms in mixed sand-clay develop at a slower rate and often have smaller heights and wavelengths than equivalent bedforms in pure sand. This effect is generally attributed to cohesive forces that can be of physical origin, caused by electrostatic forces of attraction between clay minerals, and of biological origin, caused by 'sticky' extracellular polymeric substances (EPS) produced by micro-organisms, such as microalgae (microphytobenthos) and bacteria. The present study demonstrates, for the first time, that these laboratory experiments are a suitable analogue for current ripples formed by tidal currents on a natural mixed sand-mud-EPS intertidal flat in a macrotidal estuary. Integrated hydrodynamic and bed morphological measurements, collected during a spring tide under weak wave conditions near Hilbre Island (Dee Estuary, north-west England, UK), reveal a statistically significant decrease in current ripple wavelength for progressively higher bed mud and EPS contents, and a concurrent change from three-dimensional linguoid to two-dimensional straight-crested ripple planform morphology. These results agree well with observations in laboratory flumes, but the rate of decrease of ripple wavelength as mud content increased was found to be substantially greater for the field than the laboratory. Since the formation of ripples under natural conditions is inherently more complex than in the laboratory, four additional factors that might affect current ripple development in estuaries, but which were not accounted for in laboratory experiments, were explored. These were current forcing, clay type, pore water salinity and bed EPS content. These data illustrate that clay type alone cannot explain the difference in the rate of decrease in ripple wavelength, because the bed clay contents were too low for clay type to have had a measurable effect on bedform development. Accounting for the difference in current forcing between the field and experiments, and therefore the relative stage of development with respect to equilibrium ripples, increases the difference between the ripple wavelengths. The presence of strongly cohesive EPS in the current ripples on the natural intertidal flat might explain the majority of the difference in the rate of decrease in ripple wavelength between the field and the laboratory. The effect of pore water salinity on the rate of bedform development cannot be quantified at present, but salinity is postulated herein to have had a smaller influence on the ripple wavelength than bed EPS content. The common presence of clay and EPS in many aqueous sedimentary environments implies that a re-assessment of the role of current ripples and their primary current lamination in predicting and reconstructing flow regimes is necessary, and that models that are valid for pure sand are an inappropriate descriptor for more complex mixed sediment. This study proposes that this re-assessment is necessary at all bed clay contents above 3%.

6.
Anesthesiology ; 125(3): 465-73, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27404222

RESUMO

BACKGROUND: Cardiac surgery utilizing cardiopulmonary bypass (CPB) is one of the most common forms of major surgery. Cardiac surgery-associated multiorgan dysfunction (CSA-MOD) is well recognized and includes acute kidney injury (AKI), hepatic impairment, myocardial damage, and postoperative neurologic deficit. Pathophysiology of CSA-MOD involves numerous injurious pathways linked to the use of CPB including oxidative stress and formation of reactive iron species. During cardiac surgery with CPB, arterial return blood is oxygenated to supranormal levels. This study aimed to determine whether the avoidance of arterial hyperoxemia decreased oxidative stress and reduced the severity of the multiorgan dysfunction in patients undergoing cardiac surgery utilizing CPB. METHODS: The study was a multicenter, open-label, parallel-group, randomized controlled study of the avoidance of arterial hyperoxemia versus usual care in patients undergoing cardiac surgery involving CPB. Primary outcome was the incidence and severity of AKI. Secondary outcomes included serum biomarkers for CSA-MOD, duration of mechanical ventilation, and length of intensive care and hospital stay. RESULTS: A total of 298 patients were randomized and analyzed at two hospitals in New Zealand and Australia. Mean PaO2 was significantly different between groups during CPB. There was no difference in the development of AKI (intervention arm 72.0% vs. usual care 66.2%; difference, -5.8% [95% CI, -16.1 to 4.7%]; P = 0.28), other markers of organ damage, or intensive care unit and hospital length of stay. CONCLUSIONS: Avoiding modest hyperoxemia during CPB failed to demonstrate any difference in AKI, markers of organ damage, or length of stay.


Assuntos
Injúria Renal Aguda/epidemiologia , Ponte Cardiopulmonar/efeitos adversos , Hiperóxia/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Injúria Renal Aguda/sangue , Injúria Renal Aguda/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Biomarcadores/sangue , Feminino , Humanos , Hiperóxia/sangue , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/prevenção & controle , Nova Zelândia/epidemiologia , Estresse Oxidativo , Complicações Pós-Operatórias/sangue , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
7.
Blood ; 122(19): 3365-75, 2013 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-24041574

RESUMO

Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Approximately 35% to 50% of HCT recipients develop aGVHD; however, there are no validated diagnostic and predictive blood biomarkers for aGVHD in clinical use. Here, we show that plasma samples from aGVHD patients have a distinct microRNA (miRNA) expression profile. We found that 6 miRNAs (miR-423, miR-199a-3p, miR-93*, miR-377, miR-155, and miR-30a) were significantly upregulated in the plasma of aGVHD patients (n = 116) when compared with non-GVHD patients (n = 52) in training and validation phases. We have developed a model including 4 miRNAs (miR-423, miR-199a-3p, miR-93*, and miR-377) that can predict the probability of aGVHD with an area under the curve of 0.80. Moreover, these elevated miRNAs were detected before the onset of aGVHD (median = 16 days before diagnosis). In addition, the levels of these miRNAs were positively associated with aGVHD severity, and high expression of the miRNA panel was associated with poor overall survival. Furthermore, the miRNA signature for aGVHD was not detected in the plasma of lung transplant or nontransplant sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as an independent biomarker for the prediction, diagnosis, and prognosis of aGVHD.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/genética , Transplante de Células-Tronco Hematopoéticas , MicroRNAs/genética , Doença Aguda , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Transplante de Pulmão , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Transplante Homólogo
8.
Infant Ment Health J ; 36(2): 179-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25704237

RESUMO

This study evaluated the new online Emotional Attachment and Emotional Availability (EA2) Intervention for use with adoptive families in enhancing parent-child EA, parental perceptions of EA, child attachment behaviors, parent-child emotional attachment, and reducing parent-reported child behavioral problems and parenting-related stress. Participants in this study were adoptive parents and their adopted children ages 1.5 to 5 years old (N = 15 dyads). Participants were placed in an immediate intervention group (IG) or a delayed intervention group (DG) that would receive the 6-week EA2 Tele-Intervention after the IG. Results revealed significant differences in the IG in child behavioral problems, parent-child EA, parental perceptions of EA, and parent-child emotional attachment, improvements not seen in the DG. Analysis of effects of the DG after receiving the EA2 Tele-Intervention revealed significant differences over time also in most of these qualities.


Assuntos
Adoção/psicologia , Comportamento Infantil/psicologia , Relações Pais-Filho , Poder Familiar/psicologia , Pais/psicologia , Adulto , Pré-Escolar , Emoções , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Estresse Psicológico , Inquéritos e Questionários , Telemedicina , Resultado do Tratamento
9.
Ann Rev Mar Sci ; 16: 105-133, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-37487592

RESUMO

Submarine turbidity currents form the largest sediment accumulations on Earth, raising the question of their role in global carbon cycles. It was previously inferred that terrestrial organic carbon was primarily incinerated on shelves and that most turbidity current systems are presently inactive. Turbidity currents were thus not considered in global carbon cycles, and the burial efficiency of global terrestrial organic carbon was considered low to moderate (∼10-44%). However, recent work has shown that burial of terrestrial organic carbon by turbidity currents is highly efficient (>60-100%) in a range of settings and that flows occur more frequently than once thought, although they were far more active at sea-level lowstands. This leads to revised global estimates for mass flux (∼62-90 Mt C/year) and burial efficiency (∼31-45%) of terrestrial organic carbon in marine sediments. Greatly increased burial fluxes during sea-level lowstands are also likely underestimated; thus, organic carbon cycling by turbidity currents could play a role in long-term changes in atmospheric CO2 and climate.


Assuntos
Ciclo do Carbono , Clima , Carbono
10.
Shoulder Elbow ; 16(2): 200-205, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38655413

RESUMO

Introduction: Terrible triad injuries (TTIs) of the elbow have traditionally been reported to have poor outcomes, hence requiring surgical stabilisation. We identified and reviewed patients with TTIs treated non-operatively within our department. Methods: We retrospectively reviewed patients with TTI treated non-operatively with standardised elbow-instability rehabilitation from 2010 to 2020. We used Mason and Morrey classifications for radial head and coronoid fractures, respectively. Non-operative indications included a congruent joint on CT, significant co-morbidities pre-disposing to high-risk surgery and/or patient preference. Outcomes included Oxford Elbow Score (OES), ROM and complications. Results: Nineteen patients were included (mean age 49; 37% female). At an average of 6 years (range 2-11 years) post-treatment, mean OES was 46 ± 7. At last clinic review, mean 6 months (2-15), average ROM was 131 ± 11° flexion, 8 ± 10° extension, 85 ± 12° supination and 85 ± 13° pronation. One patient required arthrolysis and another had an incongruent ulnohumeral joint which developed clicking with a functional ROM. Conclusion: Our report suggests non-operatively managed and appropriately rehabilitated TTI injuries can achieve good function and ROM. We recommend conservative management as a viable option in cases with joint congruency and no mechanical block in patients with significant co-morbidities or those refusing surgery but patients must be assessed on a case-by-case basis.

11.
J Cell Biol ; 223(3)2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38270563

RESUMO

CLPB is a mitochondrial intermembrane space AAA+ domain-containing disaggregase. CLPB mutations are associated with 3-methylglutaconic aciduria and neutropenia; however, the molecular mechanism underscoring disease and the contribution of CLPB substrates to disease pathology remains unknown. Interactions between CLPB and mitochondrial quality control (QC) factors, including PARL and OPA1, have been reported, hinting at dysregulation of organelle QC in disease. Utilizing proteomic and biochemical approaches, we show a stress-specific aggregation phenotype in a CLPB-null environment and define the CLPB substrate profile. We illustrate an interplay between intermembrane space proteins including CLPB, HAX1, HTRA2, and the inner membrane quality control proteins (STOML2, PARL, YME1L1; SPY complex), with CLPB deficiency impeding SPY complex function by virtue of protein aggregation in the intermembrane space. We conclude that there is an interdependency of mitochondrial QC components at the intermembrane space/inner membrane interface, and perturbations to this network may underscore CLPB disease pathology.


Assuntos
Endopeptidase Clp , Membranas Intracelulares , Proteínas de Membrana , Proteínas de Membrana/genética , Mitocôndrias/genética , Proteólise , Proteômica , Humanos , Endopeptidase Clp/genética
12.
Lancet Digit Health ; 6(5): e334-e344, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38670742

RESUMO

BACKGROUND: The CSC study found that the universal delivery of a school-based, online programme for the prevention of mental health and substance use disorders among adolescents resulted in improvements in mental health and substance use outcomes at 30-month follow-up. We aimed to compare the long-term effects of four interventions-Climate Schools Combined (CSC) mental health and substance use, Climate Schools Substance Use (CSSU) alone, Climate Schools Mental Health (CSMH) alone, and standard health education-on mental health and substance use outcomes among adolescents at 72-month follow-up into early adulthood. METHODS: This long-term study followed up adolescents from a multicentre, cluster-randomised trial conducted across three states in Australia (New South Wales, Queensland, and Western Australia) enrolled between Sept 1, 2013, and Feb 28, 2014, for up to 72 months after baseline assessment. Adolescents (aged 18-20 years) from the original CSC study who accepted contact at 30-month follow-up and provided informed consent at 60-month follow-up were eligible. The interventions were delivered in school classrooms through an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. Participants took part in two web-based assessments at 60-month and 72-month follow-up. Primary outcomes were alcohol use, cannabis use, anxiety, and depression, measured by self-reported surveys and analysed by intention to treat (ie, in all students who were eligible at baseline). This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785), including the extended follow-up study. FINDINGS: Of 6386 students enrolled from 71 schools, 1556 (24·4%) were randomly assigned to education as usual, 1739 (27·2%) to CSSU, 1594 (25·0%) to CSMH, and 1497 (23·4%) to CSC. 311 (22·2%) of 1401 participants in the control group, 394 (26·4%) of 1495 in the CSSU group, 477 (37·%) of 1289 in the CSMH group, and 400 (32·5%) of 1232 in the CSC group completed follow-up at 72 months. Adolescents in the CSC group reported slower year-by-year increases in weekly alcohol use (odds ratio 0·78 [95% CI 0·66-0·92]; p=0·0028) and heavy episodic drinking (0·69 [0·58-0·81]; p<0·0001) than did the control group. However, significant baseline differences between groups for drinking outcomes, and no difference in the predicted probability of weekly or heavy episodic drinking between groups were observed at 72 months. Sensitivity analyses increased uncertainty around estimates. No significant long-term differences were observed in relation to alcohol use disorder, cannabis use, cannabis use disorder, anxiety, or depression. No adverse events were reported during the trial. INTERPRETATION: We found some evidence that a universal online programme for the prevention of anxiety, depression, and substance use delivered in early adolescence is effective in reducing the use and harmful use of alcohol into early adulthood. However, confidence in these findings is reduced due to baseline differences, and we did not see a difference in the predicted probability of drinking between groups at 72-month follow-up. These findings suggest that a universal prevention programme in adolescence is not sufficient to have lasting effects on mental health and substance use disorders in the long term. In addition to baseline differences, substantial attrition warrants caution in interpretation and the latter factor highlights the need for future long-term follow-up studies to invest in strategies to increase engagement. FUNDING: Australian National Health and Medical Research Council.


Assuntos
Ansiedade , Depressão , Serviços de Saúde Escolar , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Feminino , Masculino , Austrália , Ansiedade/prevenção & controle , Depressão/prevenção & controle , Adulto Jovem , Instituições Acadêmicas , Internet
13.
Infant Ment Health J ; 34(5): 435-445, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-27127309

RESUMO

This study assessed relations among number of out-of-home placement changes, time in caregivers' care, caregiver type (i.e., foster parent, adoptive parent, kinship relation, and biological parent), child gender, and caregiver-child Emotional Availability (EA) as predictive of child attachment security when children were 3 years old in a sample of 104 caregivers and children. Children entered court-ordered care by six months of age. On average, children at the age of three spent 30 months with their caregivers, and nearly half of them were adopted by that time. Child attachment was assessed using the Attachment Q-set (Waters & Deane, 1985), and caregiver-child EA was assessed using the EA Scales, 4th edition (Biringen, 2008). Sixty-six percent of children at age 3 showed secure attachments with caregivers, and EA subscale scores were also relatively high on average. The study predictor variables of EA Caregiver Sensitivity, Child Responsiveness, and Child Involvement predicted attachment security, with girls more likely to be securely attached to their substitute caregivers at age three than boys. Study limitations and directions for future research are discussed.

14.
Kidney360 ; 4(6): e841-e850, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37019177

RESUMO

The high-capacity vessels of the lymphatic system drain extravasated fluid and macromolecules from nearly every part of the body. However, far from merely a passive conduit for fluid removal, the lymphatic system also plays a critical and active role in immune surveillance and immune response modulation through the presentation of fluid, macromolecules, and trafficking immune cells to surveillance cells in regional draining lymph nodes before their return to the systemic circulation. The potential effect of this system in numerous disease states both within and outside of the kidney is increasingly being explored for their therapeutic potential. In the kidneys, the lymphatics play a critical role in both fluid and macromolecule removal to maintain oncotic and hydrostatic pressure gradients for normal kidney function, as well as in shaping kidney immunity, and potentially in balancing physiological pathways that promote healthy organ maintenance and responses to injury. In many states of kidney disease, including AKI, the demand on the preexisting lymphatic network increases for clearance of injury-related tissue edema and inflammatory infiltrates. Lymphangiogenesis, stimulated by macrophages, injured resident cells, and other drivers in kidney tissue, is highly prevalent in settings of AKI, CKD, and transplantation. Accumulating evidence points toward lymphangiogenesis being possibly harmful in AKI and kidney allograft rejection, which would potentially position lymphatics as another target for novel therapies to improve outcomes. However, the extent to which lymphangiogenesis is protective rather than maladaptive in the kidney in various settings remains poorly understood and thus an area of active research.


Assuntos
Injúria Renal Aguda , Vasos Linfáticos , Humanos , Sistema Linfático/fisiologia , Vasos Linfáticos/metabolismo , Linfangiogênese , Linfonodos
15.
Eur Respir Rev ; 32(167)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-36889787

RESUMO

BACKGROUND: Patient-reported outcome measures (PROMs) are recommended for capturing meaningful outcomes in clinical trials. The use of PROMs for children with acute lower respiratory infections (ALRIs) has not been systematically reported. We aimed to identify and characterise patient-reported outcomes and PROMs used in paediatric ALRI studies and summarise their measurement properties. METHODS: Medline, Embase and Cochrane were searched (until April 2022). Studies that reported on patient-reported outcome (or measure) use or development and included subjects aged <18 years with ALRIs were included. Study, population and patient-reported outcome (or measure) characteristics were extracted. RESULTS: Of 2793 articles identified, 18 met inclusion criteria, including 12 PROMs. Two disease-specific PROMs were used in settings in which they had been validated. The Canadian Acute Respiratory Illness and Flu Scale was the most frequently used disease-specific PROM (five studies). The EuroQol-Five Dimensions-Youth system was the most frequently used generic PROM (two studies). There was considerable heterogeneity in validation methods. The outcome measures identified in this review lack validation for young children and none involve sufficient content validity for use with First Nations children. CONCLUSIONS: There is an urgent need for PROM development that considers the populations in which the burden of ALRI predominates.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Infecções Respiratórias , Adolescente , Humanos , Criança , Pré-Escolar , Canadá , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/terapia , Qualidade de Vida
16.
Front Psychol ; 14: 1277741, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38274692

RESUMO

We re-examined whether different time scales such as week, day of week, and hour of day are independently used during memory retrieval as has been previously argued (i.e., independence of scales). To overcome the limitations of previous studies, we used experience sampling technology to obtain test stimuli that have higher ecological validity. We also used pointwise mutual information to directly calculate the degree of dependency between time scales in a formal way. Participants were provided with a smartphone and were asked to wear it around their neck for two weeks, which was equipped with an app that automatically collected time, images, GPS, audio and accelerometry. After a one-week retention interval, participants were presented with an image that was captured during their data collection phase, and were tested on their memory of when the event happened (i.e., week, day of week, and hour). We find that, in contrast to previous arguments, memories of different time scales were not retrieved independently. Moreover, through rendering recurrence plots of the images that the participants collected, we provide evidence the dependency may have originated from the repetitive events that the participants encountered in their daily life.

17.
J Am Acad Psychiatry Law ; 51(2): 255-262, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37257906

RESUMO

There are approximately 500,000 children in the foster care system in the United States of America. With exposure to chronic and cumulative trauma, they constitute a population with an increased risk of developing mental health concerns and adverse outcomes in later life, including contact with the forensic system. Legislative frameworks that have been developed to facilitate improved outcomes are outlined, although these vary between states, and the focus is often on the parental relationship. Several studies have emphasized the importance of sibling relationships and that placing siblings in the same foster home is associated with higher rates of placement stability, reunification, adoption and guardianship, and fostering positive sibling relations. The multifaceted role of the clinician in promoting recovery from trauma, enhancing resiliency, and thoughtfully prescribing and advocating for familial relationships is discussed.


Assuntos
Maus-Tratos Infantis , Relações entre Irmãos , Criança , Humanos , Estados Unidos , Irmãos , Cuidados no Lar de Adoção , Proteção da Criança
18.
BMJ Open ; 13(4): e071968, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-37068906

RESUMO

INTRODUCTION: Although studies have examined the utility of clinical decision support tools in improving acute kidney injury (AKI) outcomes, no study has evaluated the effect of real-time, personalised AKI recommendations. This study aims to assess the impact of individualised AKI-specific recommendations delivered by trained clinicians and pharmacists immediately after AKI detection in hospitalised patients. METHODS AND ANALYSIS: KAT-AKI is a multicentre randomised investigator-blinded trial being conducted across eight hospitals at two major US hospital systems planning to enrol 4000 patients over 3 years (between 1 November 2021 and 1 November 2024). A real-time electronic AKI alert system informs a dedicated team composed of a physician and pharmacist who independently review the chart in real time, screen for eligibility and provide combined recommendations across the following domains: diagnostics, volume, potassium, acid-base and medications. Recommendations are delivered to the primary team in the alert arm or logged for future analysis in the usual care arm. The planned primary outcome is a composite of AKI progression, dialysis and mortality within 14 days from randomisation. A key secondary outcome is the percentage of recommendations implemented by the primary team within 24 hours from randomisation. The study has enrolled 500 individuals over 8.5 months. Two-thirds were on a medical floor at the time of the alert and 17.8% were in an intensive care unit. Virtually all participants were recommended for at least one diagnostic intervention. More than half (51.6%) had recommendations to discontinue or dose-adjust a medication. The median time from AKI alert to randomisation was 28 (IQR 15.8-51.5) min. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of each study site (Yale University and Johns Hopkins institutional review board (IRB) and a central IRB (BRANY, Biomedical Research Alliance of New York). We are committed to open dissemination of the data through clinicaltrials.gov and sharing of data on an open repository as well as publication in a peer-reviewed journal on completion. TRIAL REGISTRATION NUMBER: NCT04040296.


Assuntos
Injúria Renal Aguda , COVID-19 , Humanos , SARS-CoV-2 , Diálise Renal , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Rim , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
19.
Neural Netw ; 160: 274-296, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36709531

RESUMO

Despite the advancement of machine learning techniques in recent years, state-of-the-art systems lack robustness to "real world" events, where the input distributions and tasks encountered by the deployed systems will not be limited to the original training context, and systems will instead need to adapt to novel distributions and tasks while deployed. This critical gap may be addressed through the development of "Lifelong Learning" systems that are capable of (1) Continuous Learning, (2) Transfer and Adaptation, and (3) Scalability. Unfortunately, efforts to improve these capabilities are typically treated as distinct areas of research that are assessed independently, without regard to the impact of each separate capability on other aspects of the system. We instead propose a holistic approach, using a suite of metrics and an evaluation framework to assess Lifelong Learning in a principled way that is agnostic to specific domains or system techniques. Through five case studies, we show that this suite of metrics can inform the development of varied and complex Lifelong Learning systems. We highlight how the proposed suite of metrics quantifies performance trade-offs present during Lifelong Learning system development - both the widely discussed Stability-Plasticity dilemma and the newly proposed relationship between Sample Efficient and Robust Learning. Further, we make recommendations for the formulation and use of metrics to guide the continuing development of Lifelong Learning systems and assess their progress in the future.


Assuntos
Educação Continuada , Aprendizado de Máquina
20.
Dev Psychopathol ; 24(1): 23-34, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22292991

RESUMO

According to data from the 1997 NICHD Study of Child Care, center-based child care can have deleterious effects on children's social-emotional development. We hypothesized that training child care professionals to develop positive relationships with children in their care would improve the quality of center-based child care. Thirty-three professional caregiver-child pairs participated in the intervention group and 24 professional caregiver-child pairs were assigned to a care as usual comparison group. The intervention consisted of an informational and a practice component with an emotional availability (EA) coach. The infants and toddlers (ages 11 to 23 months) in the classrooms were enrolled in the project only if they spent at least 20 hr per week in center-based care. The measures included were (a) the EA Scales, (b) the Attachment Q-Sort, and (c) the Classroom Interaction Scale. The intervention group professional caregiver-child relationships showed improvements on the EA Scales, Attachment Q-Sort, and the Classroom Interaction Scale from pre- to posttest, compared to the comparison group, who showed some decrements over a comparable period of time.


Assuntos
Cuidadores/psicologia , Creches , Desenvolvimento Infantil , Emoções , Apego ao Objeto , Pré-Escolar , Feminino , Humanos , Lactente , Relações Interpessoais , Masculino
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