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1.
J Med Genet ; 59(11): 1035-1043, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35115415

RESUMO

BACKGROUND: Nephrolithiasis (NL) is a complex multifactorial disease affecting up to 10%-20% of the human population and causing a significant burden on public health systems worldwide. It results from a combination of environmental and genetic factors. Hyperoxaluria is a major risk factor for NL. METHODS: We used a whole exome-based approach in a patient with calcium oxalate NL. The effects of the mutation were characterised using cell culture and in silico analyses. RESULTS: We identified a rare heterozygous missense mutation (c.1519C>T/p.R507W) in the SLC26A6 gene that encodes a secretory oxalate transporter. This mutation cosegregated with hyperoxaluria in the family. In vitro characterisation of mutant SLC26A6 demonstrated that Cl--dependent oxalate transport was dramatically reduced because the mutation affects both SLC26A6 transport activity and membrane surface expression. Cotransfection studies demonstrated strong dominant-negative effects of the mutant on the wild-type protein indicating that the phenotype of patients heterozygous for this mutation may be more severe than predicted by haploinsufficiency alone. CONCLUSION: Our study is in line with previous observations made in the mouse showing that SLC26A6 inactivation can cause inherited enteric hyperoxaluria with calcium oxalate NL. Consistent with an enteric form of hyperoxaluria, we observed a beneficial effect of increasing calcium in the patient's diet to reduce urinary oxalate excretion.


Assuntos
Antiporters , Hiperoxalúria , Nefrolitíase , Transportadores de Sulfato , Humanos , Antiporters/genética , Cálcio/metabolismo , Oxalato de Cálcio/metabolismo , Hiperoxalúria/complicações , Hiperoxalúria/genética , Mutação , Nefrolitíase/genética , Nefrolitíase/complicações , Nefrolitíase/metabolismo , Oxalatos/metabolismo , Transportadores de Sulfato/genética
2.
Opt Express ; 30(15): 27926-27937, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236951

RESUMO

We report a time-correlated single-photon counting (TCSPC) imaging system based on a line-scanning architecture. The system benefits from the high fill-factor, active area, and large dimension of an advanced CMOS single-photon avalanche diode (SPAD) array line-sensor. A two-dimensional image is constructed using a moving mirror to scan the line-sensor field-of-view (FOV) across the target, to enable the efficient acquisition of a two-dimensional 0.26 Mpixel TCSPC image. We demonstrate the capabilities of the system for TCSPC imaging and locating objects obscured in scattering media - specifically to locate a series of discrete point sources of light along an optical fibre submerged in a highly scattering solution. We demonstrate that by selectively imaging using early arriving photons which have undergone less scattering than later arriving photons, our TCSPC imaging system is able to locate the position of discrete point sources of light than a non-time-resolved imaging system.

3.
Am J Physiol Renal Physiol ; 320(6): F1106-F1122, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33938239

RESUMO

Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system of the mammalian kidney. The principal aim of the present study was to determine if Ksp-cadherin played a critical role in the development and maintenance of the adult mammalian kidney by generating and evaluating a mouse line deficient in Ksp-cadherin. Ksp-null mutant animals were viable and fertile, and kidneys from both neonates and adults showed no evidence of structural abnormalities. Immunolocalization and Western blot analyses of Na+-K+-ATPase and E-cadherin indicated that Ksp-cadherin is not essential for either the genesis or maintenance of the polarized tubular epithelial phenotype. Moreover, E-cadherin expression was not altered to compensate for Ksp-cadherin loss. Plasma electrolytes, total CO2, blood urea nitrogen, and creatinine levels were also unaffected by Ksp-cadherin deficiency. However, a subtle but significant developmental delay in the ability to maximally concentrate urine was detected in Ksp-null mice. Expression analysis of the principal proteins involved in the generation of the corticomedullary osmotic gradient and the resultant movement of water identified misexpression of aquaporin-2 in the inner medullary collecting duct as the possible cause for the inability of young adult Ksp-cadherin-deficient animals to maximally concentrate their urine. In conclusion, Ksp-cadherin is not required for normal kidney development, but its absence leads to a developmental delay in maximal urinary concentrating ability.NEW & NOTEWORTHY Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system. Using knockout mice, we found that Ksp-cadherin is in fact not required for kidney development despite its high and specific expression along the nephron. However, its absence leads to a developmental delay in maximal urinary concentrating ability.


Assuntos
Caderinas/metabolismo , Capacidade de Concentração Renal/fisiologia , Rim/crescimento & desenvolvimento , Animais , Aquaporina 2/genética , Aquaporina 2/metabolismo , Caderinas/genética , Regulação da Expressão Gênica no Desenvolvimento , Rim/fisiologia , Capacidade de Concentração Renal/genética , Masculino , Camundongos , Camundongos Knockout , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo
4.
Clin Exp Immunol ; 196(1): 28-38, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30697704

RESUMO

Lung disease due to nontuberculous mycobacteria (NTM) occurs with disproportionate frequency in postmenopausal women with a unique phenotype and without clinically apparent predisposing factors. Dubbed 'Lady Windermere syndrome', the phenotype includes low body mass index (BMI), tall stature and higher than normal prevalence of scoliosis, pectus excavatum and mitral valve prolapse. Although the pathomechanism for susceptibility to NTM lung disease in these patients remains uncertain, it is likely to be multi-factorial. A role for the immunomodulatory consequences of oestrogen deficiency and altered adipokine production has been postulated. Altered levels of adipokines and dehydroepiandrosterone have been demonstrated in patients with NTM lung disease. Case reports of NTM lung disease in patients with hypopituitarism support the possibility that altered endocrine function influences disease susceptibility. This paper catalogues the evidence for immunomodulatory consequences of predicted endocrine changes in Lady Windermere syndrome, with emphasis on the immune response to NTM. Collectively, the data warrant further exploration of an endocrine link to disease susceptibility in Lady Windermere syndrome.


Assuntos
Glândulas Endócrinas/fisiologia , Estrogênios/metabolismo , Pneumopatias/imunologia , Infecções por Mycobacterium não Tuberculosas/imunologia , Micobactérias não Tuberculosas/fisiologia , Adipocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Tórax em Funil , Humanos , Hipopituitarismo , Imunidade , Imunomodulação , Pneumopatias/metabolismo , Infecções por Mycobacterium não Tuberculosas/metabolismo , Pós-Menopausa , Síndrome
5.
J Dairy Sci ; 102(7): 6477-6484, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030923

RESUMO

To determine whether individual cow milking vacuum (within the short milk tube and the liner mouthpiece) could be substituted for milk flow technology to identify delayed (bimodal) milk ejection, and the possible relationship between bimodal milk flow and milk yield, we recorded milking data from 663 Holstein cows on a 3,600-cow Michigan dairy that milked 3 times per day. Overall, delayed milk ejection occurred in 45.6% of the milkings, and 98% of the cows with delayed milk ejection also had bimodal flow. Multivariable analysis revealed that milk yield during each individual cow milking was positively associated with increasing lactation number but negatively associated with increasing days in milk and delayed milk ejection. As the time between unit attachment and the estimated milk letdown (the lag period) increased, milk yield decreased; relative to a lag of <30 s, milk yield decreased by 1.8 and 3.1 kg for lags of 30-59 and ≥60 s, respectively. The final multivariate model had an adjusted coefficient of determination of 0.27. The negative association between delayed milk ejection and decreased milk yield in this study suggested that milking vacuum parameters from individual cows could serve as a useful tool to qualitatively estimate milk flow within a herd and that this information may be used to enhance herd productivity.


Assuntos
Bovinos/metabolismo , Leite/metabolismo , Animais , Indústria de Laticínios/instrumentação , Indústria de Laticínios/métodos , Feminino , Lactação , Ejeção Láctea , Vácuo
6.
J Dairy Sci ; 102(3): 2544-2550, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30639006

RESUMO

The objective of this study was to determine the herd-level variables that were associated with total stimulation time during the premilking routine in 64 Michigan dairy herds. The mean herd size was 452 cows (range = 59 to 2,771 cows). For each herd, surveys were administered to producers to gather mastitis management practices and attitudes. Additionally, milking protocols were observed and milk flow dynamics were measured by use of digital vacuum recorders. Backward multivariate regression analysis was used to determine which of 47 herd-level milking and management variables were associated with mean total stimulation time. Mean total stimulation time was 14.2 s (range = 2.4-40.8 s) and was positively associated with increasing latency period (time interval between first stimulation and cluster attachment). Total stimulation time was negatively associated with greater herd size and number of visits to each cow in the premilking routine. In summary, increased stimulation time is more likely in herds that foster a lower sense of urgency of cow throughput during milking, as evidenced by a positive association with longer latency periods and fewer preparation visits per cow. Tactile stimulation is critical for efficient milk ejection; if inadequate, cows are at greater risk of delayed milk ejection and bimodal milk flow, which in turn has been associated with teat congestion and reduced milk flow. This study offers insight as to some of the herd factors that may be limiting adequate tactile stimulation.


Assuntos
Criação de Animais Domésticos , Bovinos/fisiologia , Glândulas Mamárias Animais/fisiologia , Ejeção Láctea/fisiologia , Animais , Feminino , Michigan , Análise Multivariada
7.
J Dairy Sci ; 102(1): 696-705, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30343911

RESUMO

The objective of this study was to determine which herd-level variables were associated with delayed milk ejection (bimodal milk let-down) in 64 Michigan dairy herds. Median herd size was 294 cows (range 59 to 2,771 cows). For each herd, milking protocols were observed and milk flow dynamics were estimated by use of digital vacuum recorders. Surveys were also administered to the producers to measure mastitis management practices and attitudes. Milk flow dynamics were recorded for a total of 3,824 cow milkings, with a mean of 60 milkings per herd (range of 11 to 154). Backward multivariable analysis was used to determine which of the 47 herd-level milking and management variables were associated with delayed milk ejection (cows with milk let-down periods between milking cluster attachment and the incline phase of milk flow of >30 s). Delayed milk ejection occurred in an average of 25% of the cows in each herd (range 0 to 75%). A multivariable model found that the proportion of cows in a herd with delayed milk ejection was negatively associated with mean total time of tactile stimulation during premilking routines and positively associated with herd size.


Assuntos
Bovinos/fisiologia , Indústria de Laticínios/métodos , Lactação/fisiologia , Ejeção Láctea/fisiologia , Animais , Feminino , Michigan , Leite
8.
J Dairy Sci ; 102(9): 8400-8404, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279548

RESUMO

The objective of this study was to determine the herd-level variables that are associated with overmilking in 64 Michigan dairy herds with a mean herd size of 451 cows (range: 59-2,771 cows). Participating producers completed surveys to indicate their mastitis management practices and attitudes. Additionally, milking protocols were observed and milk flow dynamics for 3,824 cows were estimated using digital vacuum recorders. The median duration of overmilking was 47 s (95% confidence interval, CI: 38.6 to 55.9 s), with a mean of 55% (95% CI: 49.5 to 61.1%) of cows within each herd overmilked by at least 30 s. Median milking time for all herds was 324 s (95% CI: 302 to 346 s) and was found to be positively correlated with median duration of overmilking (r = 0.670). Backward multivariate analysis was used to determine which of 45 herd-level milking and management variables were associated with median duration of overmilking. Median duration of overmilking was negatively associated with the duration of time needed to complete 1 milking for the entire herd (adjusted R2 = 0.13). Herds that operate milking facilities below maximum daily capacity may be prone to overmilking. Given the low coefficient of determination, variables unaccounted for in this study, such as equipment function or manual detachment by milking operators, are likely the most important risk factors for overmilking.


Assuntos
Indústria de Laticínios , Mastite Bovina , Leite , Animais , Bovinos , Indústria de Laticínios/métodos , Feminino , Humanos , Michigan , Análise Multivariada , Fatores de Risco , Inquéritos e Questionários
9.
Public Health ; 168: 67-75, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30690221

RESUMO

OBJECTIVES: Horse riding is a popular activity but has also been found to lead to many injuries and even fatalities. No reduction in the numbers of those being admitted to hospital for equestrian-related injuries have been seen in Sweden in recent years. The aim of this work was to examine injuries, fatalities, and predictors of fatalities in equestrian-related activities and to investigate the cost of these injuries to the public health system. STUDY DESIGN: The study is a retrospective analysis of hospital data. METHODS: National Swedish hospital and mortality registers were retrospectively examined, inclusive of the years 1997-2014. Logistic regression was used to examine the predictors of fatal injuries, and cost of hospital treatment was considered. RESULTS: Over the study period, there were an observed 29,850 injured cases and 51 fatalities. Women comprized almost 90% of those injured and 70% of fatalities. The average age was 26.8 years (range 0-91, standard deviation [SD] = 16.1) for injured and 43 years (range 7-78 years, SD = 20.5) for fatal cases. Men dominated both injured and fatal samples in the older age ranges (Fatal: >50 years; Injured: >70 years), although overall numbers were small. Injuries to the head contributed more than any other body region for both injured and fatal cases, and fractures were the most frequently seen injury type. A chi-squared analysis confirmed that injury type and injured body region were not independent of age. Logistic regression examining the association between fatality and age, gender, home region, and year of injury, indicating trends over time, found that there was an increase of 5.1% in the odds of fatality for every year increase in age of the patient and men had 2.2 times higher odds to be in the fatal sample than women. The conservative estimated cost of injury was 1800 Euro per injury event, equating to over 3 million Euro per year. CONCLUSION: Equestrian-related injury events present a major public health concern. Observed decreases in fatalities suggest improved health care, yet head injury and fatality rates are still high, indicating a need for further intervention. The type of injury changes with the age group, and a better understanding of injury patterns with age is needed to identify protective measures for the different user groups.


Assuntos
Traumatismos em Atletas/economia , Traumatismos em Atletas/epidemiologia , Cavalos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Traumatismos em Atletas/mortalidade , Traumatismos em Atletas/terapia , Criança , Pré-Escolar , Custos e Análise de Custo , Feminino , Hospitalização/economia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Medicina Estatal/economia , Suécia/epidemiologia , Adulto Jovem
10.
Int J Life Cycle Assess ; 24(1): 51-63, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30872902

RESUMO

PURPOSE: To date, very few studies have attempted to quantify the environmental impacts of a wave energy converter, and almost all of these focus solely on the potential climate change impacts and embodied energy. This paper presents a full life cycle assessment (LCA) of the first-generation Pelamis wave energy converter, aiming to contribute to the body of published studies and examine any potential trade-offs or co-benefits across a broad range of environmental impacts. METHODS: The process-based attributional LCA was carried out on the full cradle-to-grave life cycle of the Pelamis P1 wave energy converter, including the device, its moorings and sub-sea connecting cable up to the point of connection with the grid. The case study was for a typical wave farm located off the north-west coast of Scotland. Foreground data was mostly sourced from the manufacturer. Background inventory data was mostly sourced from the ecoinvent database (v3.3), and the ReCiPe and CED impact assessment methods were applied. RESULTS AND DISCUSSION: The Pelamis was found to have significantly lower environmental impacts than conventional fossil generation in 6 impact categories, but performed worse than most other types of generation in 8 of the remaining 13 categories studied. The greatest impacts were from steel manufacture and sea vessel operations. The device performs quite well in the two most frequently assessed impacts for renewable energy converters: climate change and cumulative energy demand. The carbon payback period is estimated to be around 24 months (depending on the emissions intensity of the displaced generation mix), and the energy return on investment is 7.5. The contrast between this and the poor performance in other impact categories demonstrates the limitations of focussing only on carbon and energy. CONCLUSIONS: The Pelamis was found to generally have relatively high environmental impacts across many impact categories when compared to other types of power generation; however, these are mostly attributable to the current reliance on fossil fuels in the global economy and the early development stage of the technology. Opportunities to reduce this also lie in reducing requirements for steel in the device structure, and decreasing the requirements for sea vessel operations during installation, maintenance and decommissioning.

11.
J Public Health (Oxf) ; 40(2): 419-425, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28453666

RESUMO

Background: Deprivation indices have been widely used in healthcare research and planning in the United Kingdom. Existing indices, however, are dominated by characteristics of urban populations that may be less relevant in capturing the nature of rural deprivation. We explore if deprivation indices can be modified to make them more sensitive to displaying rural disadvantage in England. Methods: The analysis focussed on the 2011 Carstairs Index (Carstairs2011) and the 2010 English Index of Multiple Deprivation (IMD2010). We removed all urban areas as identified by the Office for National Statistics Rural-Urban Area Classifications and mapped the Carstairs2011 and IMD2010 across the remaining rural areas using rural-specific quintiles. Results: Our method was effective in displaying much greater heterogeneity in rural areas than was apparent in the original indices. We received positive feedback from Directors of Public Health who confirmed that the observed patterns mirror their experiences and first-hand knowledge on the ground. Conclusions: Our maps of Carstairs2011 and IMD2010 for rural areas might strengthen the evidence base for rural planning and service provision. The modified deprivation indices, however, were not specifically formulated for rural populations and further work is needed to explore alternative input variables to produce a more rural-specific measure of deprivation.


Assuntos
Pobreza/estatística & dados numéricos , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Feminino , Humanos , Masculino , Modelos Estatísticos , Reino Unido
12.
Clin Otolaryngol ; 43(1): 117-123, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28544805

RESUMO

DESIGN: Time trade-off choice experiment. SETTING: Two large head and neck cancer centres. PARTICIPANTS: Patients who have received treatment for head and neck cancer and members of the head and neck cancer multidisciplinary team. MAIN OUTCOME MEASURES: Participants were asked to rank the outcome scenarios, assign utility values using time trade-off and rate the importance of survival on treatment choice. RESULTS: A total of 49 patients with head and neck cancer and 73 staff members were recruited. Chemoradiotherapy (CRT) optimal outcome was the most preferred health state (34 of 49, 69% patients, and 50 of 73, 68% staff), and CRT with complications was least preferred (27 of 49, 55% patients, and 51 of 73, 70% staff). Using time trade-off, mean utility values were calculated for CRT optimal outcome (0.73 for patients, 0.77 for staff), total laryngectomy (TL) optimal outcome (0.67 for patients, 0.69 for staff), TL outcome with complications (0.46 for patients, 0.51 for staff) and CRT with complications (0.36 for patients, 0.49 for staff). The average survival advantage required for a participant to change their preferred choice was 2.6 years. CONCLUSIONS: We have demonstrated that a significant proportion of patients with head and neck cancer and staff members would not choose CRT to manage locally advanced laryngeal cancer. Staff members rated the health states associated with laryngeal cancer treatment higher than patients who have experienced them, and this is particularly evident when considering the poorer outcomes. The head and neck cancer community should develop methods of practice and decision-making which incorporate elicitation and reporting of patient values as a central principle.


Assuntos
Atitude , Carcinoma de Células Escamosas/terapia , Tomada de Decisões , Indicadores Básicos de Saúde , Neoplasias Laríngeas/terapia , Laringectomia/métodos , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Opt Express ; 25(17): 19966-19967, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-29041682

RESUMO

The first Optics Express Focus Issue on Astrophotonics was published in 2009. Since that time the field has experienced substantial growth and pathfinder astrophotonic systems are routinely being tested on large telescopes around the globe. This second Focus Issue on Astrophotonics is intended to capture some of these significant developments and convey a sense of future directions for the field.

14.
Opt Express ; 25(25): 30976-30986, 2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29245776

RESUMO

Full exploitation of fibre Raman probes has been limited by the obstruction of weak Raman signals by background fluorescence of the sample and the intrinsic Raman signal of the delivery fibre. Here we utilised functionalised gold nanoshells (NS) to take advantage of the surface-enhanced Raman spectroscopy (SERS) effect to enhance the pH responsive spectrum of 4-mercaptobenzoic acid (MBA). However, the fibre background is still dominant. Using the photon arrival time-resolving capability of a CMOS single-photon avalanche diode (SPAD) based line sensor, we recover the SERS spectrum without a fibre background in a 10 s measurement. In this manner, pH sensing through a multimode fibre at a low excitation power that is safe for future in vivo applications, with short acquisition times (10 or 60 s), is demonstrated. A measurement precision of ± 0.07 pH units is thus achieved.

15.
Am J Physiol Cell Physiol ; 311(6): C866-C873, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27681177

RESUMO

The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. Previous in vitro studies have suggested that SLC26A6 is heavily N-glycosylated. N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N-glycosidic linkage, and that there are tissue-specific differences in glycosylation. In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function.


Assuntos
Antiporters/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Oxalatos/metabolismo , Animais , Células CACO-2 , Linhagem Celular , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Membrana Celular/fisiologia , Cloretos/metabolismo , Glicosilação , Homeostase/fisiologia , Humanos , Transporte de Íons/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nefrolitíase/metabolismo , Gambás , Transporte Proteico/fisiologia , Transportadores de Sulfato
16.
Mol Psychiatry ; 20(2): 183-92, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25644384

RESUMO

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.


Assuntos
Transtornos Cognitivos/genética , Cognição/fisiologia , Predisposição Genética para Doença/genética , Proteína HMGN1/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/complicações , Transtornos Cognitivos/etiologia , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fenótipo , Escócia
17.
Emerg Med J ; 32(5): 357-63, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24838424

RESUMO

OBJECTIVE: Communicating treatment risks and benefits to patients and their carers is central to clinical practice in modern healthcare. We investigated the challenges of risk communication by clinicians offering thrombolytic therapy for hyperacute stroke where treatment must be administered rapidly to maximise benefit. METHOD: Semistructured interviews with 13 clinicians from three acute stroke units involved in decision making and/or information provision about thrombolysis. We report on clinicians' accounts of communicating risks and benefits to patients and carers. Framework analysis was employed. RESULTS: We identified the major challenges facing clinicians in communicating risk in this context that is, disease complexity, patients' capacity and time constraints, and communicating quality of life after stroke. We found significant variation in the data on risks and benefits that clinicians provide, and ways these were communicated to patients. Clinicians' communication strategies varied and included practices such as: a phased approach to communicating information, being responsive to the patient and family and documenting information they gave to patients. CONCLUSIONS: Risk communication about thrombolysis involves complex uncertainties. We elucidate the challenges of effective risk communication in a hyperacute setting and identify the issues regarding variation in risk communication and the use of less effective formats for the communication of numerical risks and benefits. The paper identifies good practice, such as the phased transfer of information over the care pathway, and ways in which clinicians might be supported to overcome challenges. This includes standardised risk and benefit information alongside appropriate personalisation of risk communication. Effective risk communication in emergency settings requires presentation of high-quality data which is amenable to tailoring to individual patients' circumstances. It necessitates clinical skills development supported by personalised risk communication tools.


Assuntos
Comunicação , Tomada de Decisões , Educação de Pacientes como Assunto , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Atitude do Pessoal de Saúde , Unidades Hospitalares , Humanos , Consentimento Livre e Esclarecido , Entrevistas como Assunto , Participação do Paciente , Relações Médico-Paciente , Padrões de Prática Médica , Relações Profissional-Família , Medição de Risco , Reino Unido
18.
Epidemiol Infect ; 142(10): 2057-64, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24398184

RESUMO

M. fortuitum is a rapidly growing mycobacterium associated with community-acquired and nosocomial wound, soft tissue, and pulmonary infections. It has been postulated that water has been the source of infection especially in the hospital setting. The aim of this study was to determine if municipal water may be the source of community-acquired or nosocomial infections in the Brisbane area. Between 2007 and 2009, 20 strains of M. fortuitum were recovered from municipal water and 53 patients' isolates were submitted to the reference laboratory. A wide variation in strain types was identified using repetitive element sequence-based PCR, with 13 clusters of ⩾2 indistinguishable isolates, and 28 patterns consisting of individual isolates. The clusters could be grouped into seven similar groups (>95% similarity). Municipal water and clinical isolates collected during the same time period and from the same geographical area consisted of different strain types, making municipal water an unlikely source of sporadic human infection.


Assuntos
Infecções Comunitárias Adquiridas/microbiologia , DNA Ribossômico/genética , Água Potável/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium fortuitum/genética , RNA Ribossômico 16S/genética , Infecções dos Tecidos Moles/microbiologia , Tuberculose Pulmonar/microbiologia , Austrália , Infecções Comunitárias Adquiridas/transmissão , Feminino , Humanos , Sequências Repetitivas Dispersas/genética , Masculino , Infecções por Mycobacterium não Tuberculosas/transmissão , Mycobacterium fortuitum/isolamento & purificação , Reação em Cadeia da Polimerase , Infecções dos Tecidos Moles/transmissão , Tuberculose Pulmonar/transmissão , Abastecimento de Água
19.
Women Birth ; 36(2): 193-204, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36050269

RESUMO

BACKGROUND: Multiple-mini interviews (MMI) are increasingly used as part of the admission process into healthcare degrees. Evaluations have found MMIs to be a fair assessment tool in terms of reliability and validity and viewed positively by those involved in the MMI process. The use of MMIs in midwifery is novel and evaluation is lacking. AIM: To evaluate the use of MMIs as part of the admission process for the Bachelor of Midwifery in one Australian university. METHODS: A basic convergent mixed methods study design was utilised. Data included linked data sets, Likert scale responses to survey questions, focus groups and open-ended survey questions. Integration took place at the interpretation and reporting stage. FINDINGS: Participants viewed the MMI experience positively. The study confirmed the reliability of the MMIs as an assessment tool. Most variance in MMI scores was attributed to the candidate at 31.4 % with the interviewer and the interview station having less influence on the MMI score at 11 % and 6.4 % variance. Older applicants on average achieved higher MMI scores, and those who spoke a language other than English at home or were first in family to attend university had lower on average MMI scores. Being born overseas did not impact an applicant's MMI score. The overall experience was seen as fair, offering further opportunity to gain entry into the Bachelor of Midwifery. CONCLUSION: MMIs were viewed positively and findings support the use of MMIs as part of an admissions process for the Bachelor of Midwifery.


Assuntos
Tocologia , Humanos , Gravidez , Feminino , Reprodutibilidade dos Testes , Critérios de Admissão Escolar , Austrália , Idioma
20.
J Hosp Infect ; 132: 133-139, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36309203

RESUMO

BACKGROUND: Mycobacterium abscessus (MABS) group are environmental organisms that can cause infection in people with cystic fibrosis (CF) and other suppurative lung diseases. There is potential for person-to-person airborne transmission of MABS among people with CF attending the same care centre. Ultraviolet light (band C, UV-C) is used for Mycobacterium tuberculosis control indoors; however, no studies have assessed UV-C for airborne MABS. AIM: To determine whether a range of UV-C doses increased the inactivation of airborne MABS, compared with no-UVC conditions. METHODS: MABS was generated by a vibrating mesh nebulizer located within a 400 L rotating drum sampler, and then exposed to an array of 265 nm UV-C light-emitting diodes (LED). A six-stage Andersen Cascade Impactor was used to collect aerosols. Standard microbiological protocols were used for enumerating MABS, and these quantified the effectiveness of UV-C doses (in triplicate). UV-C effectiveness was estimated using the difference between inactivation with and without UV-C. FINDINGS: Sixteen tests were performed, with UV-C doses ranging from 276 to 1104 µW s/cm2. Mean (±SD) UV-C effectiveness ranged from 47.1% (±13.4) to 83.6% (±3.3). UV-C led to significantly greater inactivation of MABS (all P-values ≤0.045) than natural decay at all doses assessed. Using an indoor model of the hospital environment, it was estimated that UV-C doses in the range studied here could be safely delivered in clinical settings where patients and staff are present. CONCLUSION: This study provides empirical in-vitro evidence that nebulized MABS are susceptible to UV-C inactivation.


Assuntos
Mycobacterium abscessus , Mycobacterium tuberculosis , Humanos , Raios Ultravioleta , Aerossóis e Gotículas Respiratórios , Desinfecção/métodos
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