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This Position Statement provides guidelines for health professionals who work with individuals and families seeking predictive genetic testing and laboratory staff conducting the tests. It presents the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity, and adults living with reduced or fluctuating cognitive capacity.Predictive Testing Recommendations: (1) Predictive testing in adults, young people and children should only be offered with pretest genetic counseling, and the option of post-test genetic counseling. (2) An individual considering whether to have a predictive test should be supported to make an autonomous and informed decision. Regarding Children and Young People: (1) Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies, or other medical interventions in the immediate future. (2) Where symptoms are likely to develop in childhood, in the absence of direct medical benefit from this knowledge, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. (3) Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make an autonomous and informed decision. This is applicable regardless of whether there is some action that can be taken in adulthood.
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Aconselhamento Genético , Testes Genéticos , Humanos , Testes Genéticos/ética , Adulto , Criança , Australásia , Genética Humana/ética , Feminino , MasculinoRESUMO
AIMS: Pharmaco-invasive percutaneous coronary intervention (PI-PCI) is recommended for patients with ST-elevation myocardial infarction (STEMI)who are unable to undergo timely primary PCI (pPCI). The present study examined late outcomes after PI-PCI (successful reperfusion followed by scheduled PCI or failed reperfusion and rescue PCI)compared with timely and late pPCI (>120 min from first medical contact). METHODS AND RESULTS: All patients with STEMI presenting within 12 h of symptom onset, who underwent PCI during their initial hospitalization at Liverpool Hospital (Sydney), from October 2003 to March 2014, were included. Amongst 2091 STEMI patients (80% male), 1077 (52%)underwent pPCI (68% timely, 32% late), and 1014 (48%)received PI-PCI (33% rescue, 67% scheduled). Mortality at 3 years was 11.1% after pPCI (6.7% timely, 20.2% late) and 6.2% after PI-PCI (9.4% rescue, 4.8% scheduled); P < 0.01. After propensity matching, the adjusted mortality hazard ratio (HR) for timely pPCI compared with scheduled PCI was 0.9 (95% CIs 0.4-2.0) and compared with rescue PCI was 0.5 (95% CIs 0.2-0.9). The adjusted mortality HR for late pPCI, compared with scheduled PCI was 2.2 (95% CIs 1.2-3.1)and compared with rescue PCI, it was 1.5 (95% CIs 0.7-2.0). CONCLUSION: Patients who underwent late pPCI had higher mortality rates than those undergoing a pharmaco-invasive strategy. Despite rescue PCI being required in a third of patients, a pharmaco-invasive approach should be considered when delays to PCI are anticipated, as it achieves better outcomes than late pPCI.
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Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Intervenção Coronária Percutânea/métodos , Terapia Trombolítica/métodos , Hospitais , Resultado do TratamentoRESUMO
BACKGROUND: Advances in genomics provide improved opportunities for diagnosis of complex neurogenetic disorders, yet the optimal approach to translate these benefits to the outpatient clinic is unclear. AIMS: We retrospectively reviewed referral indications and outcomes of an integrated multidisciplinary team (MDT) clinic pathway for adults with suspected neurogenetic disorders. The associated cost implications were estimated. METHODS: Consecutive patients who attended the neurogenomics clinic from January 2017 to April 2020 were included. The clinic comprised neurologists, clinical geneticists and genetic counsellors, who assessed each patient concurrently. RESULTS: Ninety-nine new patients were referred spanning 45 different clinical diagnoses. Following MDT clinical assessment, 23% (23/99) of referral diagnoses were revised prior to molecular testing. Eighty-one patients (82%) underwent genetic testing, including 43 exome-based panels, 15 whole-genome sequencing, 14 single gene tests, 27 repeat-primed polymerase chain reaction testing and two chromosomal microarrays. Overall, 33/99 patients (33%) received a diagnosis, either a molecular diagnosis (n = 24, of which 22 were diagnostic and two were predictive) or a clinical diagnosis (n = 9). Of the clinical diagnosis cohort, five patients received a diagnosis without molecular testing and four patients whose negative testing (one diagnostic and three predictive) allowed exclusion of genetic differentials and, hence, confirmation of clinical diagnoses. The diagnostic rate following MDT and diagnostic testing was 30% (28/94), excluding the five predictive testing cases. MDT assessment aligned with eventual molecular diagnoses in 96% of cases. The estimated average costs were AU$1386 per patient undergoing MDT assessment and AU$4159 per diagnosis achieved. CONCLUSIONS: We present an integrated multidisciplinary neurogenomics clinic pathway providing a diagnostic yield of 33% (30% excluding predictive testing cases), with costing implications. The relatively high diagnostic yield may be attributed to multidisciplinary input integrating accurate phenotyping of complex disorders and interpretation of genomic findings.
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Instituições de Assistência Ambulatorial , Testes Genéticos , Adulto , Humanos , Estudos Retrospectivos , Exoma , Encaminhamento e ConsultaRESUMO
IMPORTANCE: Concussions are common among children and youth. To date, the pediatric concussion literature has focused on quantitative reports of the effects of concussion and return-to-activity guidelines. However, the subjective experiences of children and youth returning to occupations postconcussion have largely been ignored. An understanding of these experiences is critical to inform effective concussion management. OBJECTIVE: To investigate the experiences of children and youth returning to occupations after sustaining a concussion and the impacts on their future engagement in occupation. DESIGN: Qualitative interpretive description was used for data analysis and interpretation. SETTING: Community. PARTICIPANTS: Children and youth ages 11 to 18 yr from a cohort study were recruited to be interviewed about their experiences of engaging in occupations postconcussion. OUTCOMES AND MEASURES: Interviews were conducted 3 to 24 mo postconcussion, transcribed verbatim, and analyzed using interpretive description to identify themes. RESULTS: Eight children and youth (5 male, 3 female) were included. Analyses revealed three themes of the experiences of children and youth returning to occupations after concussion: diverse experiences of concussion, knowledge is key to concussion management, and concussions affect occupational engagement. CONCLUSIONS AND RELEVANCE: This study highlights the importance of considering a person's needs to enable effective concussion treatment plans. The results suggest the need for an occupation-based framework to guide interventions in pediatric concussion management. What This Article Adds: Our findings indicate that children and youth report variable recovery patterns, a lack of knowledge about concussion recovery, and a negative effect of concussion on occupational engagement.
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Traumatismos em Atletas , Concussão Encefálica , Adolescente , Traumatismos em Atletas/terapia , Concussão Encefálica/terapia , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pesquisa QualitativaRESUMO
OBJECTIVES: To evaluate the temporal stability and responsiveness of the Montreal Cognitive Assessment (MoCA) in acquired brain injury (ABI). RESEARCH DESIGN AND METHODS: English-speaking adults with stroke or moderate-to-severe traumatic brain injury were administered alternate forms of the MoCA (version 1, then 2), 6 weeks apart. Chronic group participants (n = 40) were community-dwelling, at least 1 year post-ABI (mean = 12.1 years, SD = 9.0), and presumed clinically stable. Sub-acute group participants (n = 36) were 30.8 days post-ABI (SD = 12.4) and were undergoing intensive rehabilitation. Individuals with an unstable medical or psychiatric condition or severe receptive aphasia were not eligible. RESULTS: The chronic group scored 21.6 (SD = 4.5) initially and 22.7 (SD = 3.8) on the second administration, demonstrating a small but significant practise effect (p = 0.009). The Pearson test-re-test correlation coefficient was 0.83. Using reliable change methodology in the chronic group, the 80% confidence interval (CI) for change across the two administrations was -2 to +4, adjusting for practise. Applied to the sub-acute group, 39% improved and 0% declined. CONCLUSIONS: The MoCA is a brief standardized tool that appears useful for monitoring cognitive change after ABI. The findings enable clinicians to detect statistically reliable change across serial MoCA administrations in individuals with an ABI.
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Lesões Encefálicas Traumáticas/psicologia , Transtornos Cognitivos/diagnóstico , Testes Neuropsicológicos , Adulto , Cognição/fisiologia , Transtornos Cognitivos/classificação , Transtornos Cognitivos/psicologia , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/psicologia , Resultado do TratamentoRESUMO
Private stem cell clinics throughout Australia are providing autologous stem cell therapies for a range of chronic and debilitating illnesses despite the lack of published literature to support the clinical application of these therapies. The Therapeutic Goods Administration has excluded autologous stem cell therapies from its regulatory domain leaving such therapies to be regulated by the same mechanisms that regulate research, such as the National Health and Medical Research Council Research Ethics Guidelines, and clinical practice, such as the Australian Health Practitioner Regulation Agency. However, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advance--therapeutic innovation or research. The current regulatory framework is failing to achieve its aims of protecting vulnerable patients and ensuring the proper conduct of medical practitioners in the private stem cell industry.
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Regulamentação Governamental , Setor Privado , Transplante de Células-Tronco/legislação & jurisprudência , Publicidade/legislação & jurisprudência , Instituições de Assistência Ambulatorial , Austrália , Terapia Baseada em Transplante de Células e Tecidos , Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Humanos , Imperícia/legislação & jurisprudência , Transplante de Células-Tronco/tendências , Transplante AutólogoRESUMO
Background and Purpose: Consistent measurement of respectful maternity care (RMC) is lacking. This Delphi study assessed consensus about indicators of RMC. Methods: A multidisciplinary panel assessed items (n = 201) drawn from global literature. Over two rounds, the panel rated importance, relevance, and clarity, and ranked priority within 17 domains including communication, autonomy, support, stigma, discrimination, and mistreatment. Qualitative feedback supported the analysis. Results: In Round One, 191 indicators exceeded a content validation index of 0.80. In Round Two, Kendall's W ranged from 0.081 (p = .209) to 0.425 (p < .001) across domains. Fourteen indicators received strong support. Changes in indicator assessment between rounds prevented agreement stability assessment. Conclusion: The indicators comprise a registry of items for use in perinatal care research.
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Serviços de Saúde Materna , Gravidez , Humanos , Feminino , Técnica Delphi , Reprodutibilidade dos Testes , Respeito , ComunicaçãoRESUMO
Objective: To investigate the extent to which multivessel disease, incomplete revascularisation and prescribing differences contribute to sex-based outcome disparities in patients with ST-elevation MI (STEMI) and establish whether differences in cardiac death and MI (CDMI) rates persist at long-term follow-up. Methods and results: This observational study evaluates sex-based outcome differences (median follow-up 3.6 years; IQR [2.4-5.4]) in a consecutive cohort of patients (n=2,083) presenting with STEMI undergoing percutaneous coronary intervention). Of the studied patients 20.3% (423/2,083) were women and 38.3% (810/2,083) had multivessel disease (MVD). Incomplete revascularisation was common. The median residual SYNTAX score (rSS) was 5.0 (IQR [0-9]) in women and 5.0 (IQR [1-11]) in men (p=0.369), and in patients with MVD it was 9 (IQR [6-17]) in women and 10 (IQR [6-15]) in men (p=0.838). The primary endpoint CDMI occurred in 20.3% of women (86/423) and in 13.2% of men (219/1,660) (p=0.028). Differences persisted following multivariable risk adjustment: female sex was independently associated with CDMI (aHR 1.33; IQR [1.02-1.74]). Women with MVD had CDMI more often than all other groups (p<0.001 for all). Significant sex-based prescribing differences were evident: women were less likely to receive guideline-recommended potent P2Y12 inhibitors than men (31% versus 43%; p=0.012), and differences were particularly evident in patients with MVD (25% in women versus 45% in men, p=0.011). Conclusion: Sex-based differences in STEMI patient outcome persist at long-term follow-up. Poor outcomes were disproportionately found in women with MVD and those with rSS>8. Observed differences in P2Y12 prescribing practices may contribute to poor outcomes for women with MVD and incomplete revascularisation.
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OBJECTIVES: The present UK criterion standard for assessing children with suspected inflammatory bowel disease (IBD) is upper endoscopy, ileocolonoscopy, and barium follow-through (BaFT). Significant doses of radiation, unpalatable contrast, and volume intolerance are involved with BaFT. Practice in investigating Crohn disease (CD) is changing with the increasing use of magnetic resonance imaging (MRI). The aim of the present study was to compare BaFT and a new abdominal MRI protocol in a paediatric IBD population. METHODS: All consecutive patients with a new diagnosis of IBD or requiring reassessment from September 2008 to December 2010 were investigated with both abdominal MRI and BaFT in accordance with a specific local paediatric IBD protocol. The studies were reported by nonblinded radiologists with an interest in gastrointestinal imaging. The reports were compared in conjunction with case note review. RESULTS: Eighty-seven patients underwent both BaFT and MRI abdomen. Thirty-one percent of patients had additional pathology on MRI, not seen on the BaFT. Sixty-seven percent of patients (n=59) had an MRI finding equivalent to BaFT. Using histology as a criterion standard for detecting terminal ileal disease, BaFT had a sensitivity and specificity of 76% and 67%, and MRI had a sensitivity and specificity of 83% and 95%, respectively. CONCLUSIONS: This is the largest series of small bowel MRI in a paediatric population. MRI reports were at least equivalent to BaFT. MRI had higher sensitivity and, particularly, specificity in detecting terminal ileal pathology. These findings suggest that MRI should become the criterion standard investigation in children with IBD in centres with appropriate expertise, with zero radiation exposure being highly advantageous.
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Bário , Doença de Crohn/patologia , Diagnóstico por Imagem/métodos , Endoscopia Gastrointestinal/métodos , Intestino Delgado/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Criança , Pré-Escolar , Protocolos Clínicos , Meios de Contraste , Doença de Crohn/diagnóstico por imagem , Humanos , Intestino Delgado/diagnóstico por imagem , Radiografia , Reino UnidoRESUMO
BACKGROUND: Heterozygous KMT2B variants are a common cause of dystonia. A novel synonymous KMT2B variant, c.5073C>T (p.Gly1691=) was identified in an individual with childhood-onset progressive dystonia. METHODS: The splicing impact of c.5073C>T was assessed using an in vitro exon-trapping assay. The genomic region of KMT2B exons 23-26 was cloned into the pSpliceExpress plasmid between exon 2 and 3 of the rat Ins2 gene. The c.5073C>T variant was then introduced through site-directed mutagenesis. The KMT2B wild-type and c.5073C>T plasmids were transfected separately into HeLa cells and RNA was extracted 48 hours after transfection. The RNA was reverse transcribed to produce cDNA, which was PCR amplified using primers annealing to the flanking rat Ins2 sequences. RESULTS: Sanger sequencing of the PCR products revealed that c.5073C>T caused a novel splice donor site and therefore a 5-bp deletion of KMT2B exon 23 in mature mRNA, leading to a coding frameshift and premature stop codon (p.Lys1692AsnfsTer7). CONCLUSION: To our knowledge, this is the first report of a KMT2B synonymous variant associated with dystonia. Reassessment of synonymous variants may increase diagnostic yield for inherited disorders including monogenic dystonia. This is of clinical importance, given the generally favourable response to deep brain stimulation for KMT2B-related dystonia.
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Distonia , Distúrbios Distônicos , Histona-Lisina N-Metiltransferase , Animais , Criança , Distonia/genética , Distúrbios Distônicos/genética , Células HeLa , Histona-Lisina N-Metiltransferase/genética , Humanos , Mutação , Fenótipo , Sítios de Splice de RNA , RatosRESUMO
BACKGROUND: In patients with diabetes mellitus presenting with ST elevation myocardial infarction (STEMI) the degree to which cardiac death rates may be attributed to an increased burden of coronary artery disease is not clear. METHODS: This prospective observational study examines rates of cardiac death between those with and without diabetes at long term follow up, stratified by presence of multivessel disease (MVD), in consecutive STEMI patients from 5 Australian hospitals. RESULTS: Amongst 2083 patients, 393 patients had diabetes (18.8%), and 810 (38.8%) had MVD. Patients with diabetes were more likely to have MVD 48.6% (191/393) than patients without diabetes 36.6% (619/1690; p < .001). At final follow up (median 3.6 years [IQR 2.4-5.4]) cardiac death occurred in 37/393 diabetic patients and 92/1690 nondiabetic patients (adjusted HR1.67, 95% CI 1.10-2.52). In those with MVD cardiac death occurred in 27/191 diabetic patients, and 54/619 non-diabetic patients (adjusted HR 1.94; 95% CI 1.17-3.23). In single vessel disease (SVD) cardiac death occurred in 10/202 diabetic patients, and 38/1071 non-diabetic patients (adjusted HR 1.37; 95% CI 0.65-2.89). Both diabetes and MVD were independently associated with cardiac death. CONCLUSIONS: STEMI patients with diabetes are more likely to have MVD, with an absolute difference in MVD rates of 12%, and higher rates of cardiac death. Randomized trials studying these high risk patients are needed to reduce cardiac mortality in patients with diabetes, MVD and STEMI.
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Doença da Artéria Coronariana , Diabetes Mellitus , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Austrália/epidemiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Humanos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Resultado do TratamentoRESUMO
Positive sense single-stranded RNA viruses undergo three mutually exclusive processes to replicate within a cell. These are translation to produce proteins, replication to produce RNA viral genomes, and packaging to form virions. The allocation of newly synthesised viral genomes to these processes, which can be regarded as life-history traits, may be subject to natural selection for efficient reproduction. Here, we develop a mathematical model of the process of intracellular viral replication to study alternative strategies for the allocation and reallocation of viral genomes to these processes. We explore four cases of the model: (1) Free Movement, in which viral genomes can freely be allocated and reallocated among translation, replication and packaging; (2) Unidirectional Reallocation, in which allocation occurs freely but reallocation can only proceed from translation to replication to packaging; (3) Conveyor Belt, in which viral genomes are first allocated to translation, then passed on to replication and finally to packaging; and (4) Permanent Allocation in which new genomes are allocated to the three processes but not reallocated between them. We apply this model to hepatitis C virus and study changes in the production of virus as the rates of allocation and reallocation are varied. We find that high viral production occurs when allocation and reallocation of the genome are weighted towards the translation and replication processes. The replication process in particular is favoured. The most productive strategy is a form of the Free Movement model in which genomes are allocated entirely to the replication-translation cycle while allowing some genomes to be packaged through reallocation.
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Hepacivirus/crescimento & desenvolvimento , Espaço Intracelular/virologia , Modelos Biológicos , Animais , Humanos , RNA Viral/metabolismoRESUMO
An increasing number of private clinics in Australia are marketing and providing autologous stem cell therapies to patients. Although advocates point to the importance of medical innovation and the primacy of patient choice, these arguments are unconvincing. First, it is a stark truth that these clinics are flourishing while the efficacy and safety of autologous stem cell therapies, outside of established indications for hematopioetic stem cell transplantation, are yet to be shown. Second, few of these therapies are offered within clinical trials. Third, patients with chronic and debilitating illnesses, who are often the ones who take up these therapies, incur significant financial burdens in the expectation of benefiting from these treatments. Finally, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advancement. We argue that greater regulatory oversight and professional action are necessary to protect vulnerable patients and that at this time the provision of unproven stem cell therapies outside of clinical trials is unethical.
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Transplante de Células-Tronco , Células-Tronco/citologia , Animais , Austrália , Autoenxertos , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Transplante de Células-Tronco/economia , Transplante de Células-Tronco/ética , Transplante de Células-Tronco/legislação & jurisprudência , Resultado do TratamentoRESUMO
BACKGROUND: Comprehensive and accurate evaluation is a critical step in the return-to-work process for individuals with head injury. Research findings have been reported on the barriers for a successful return to work. Assessment frameworks have been published, but they do not include a protocol that contains each component for the assessment. METHOD: This paper describes an occupational therapy assessment protocol developed and used in the evaluation of the work skills of individuals with head injury. This protocol focuses on assessment of physical, cognitive and behavioural abilities in relation to the demands of the workplace and measures these within the framework of productivity, interpersonal skills and safety. PRACTICE IMPLICATIONS: The functional approach inherent in this protocol provides information to complement the findings of other interdisciplinary team members. This paper also explores the strengths and limitations of this protocol.
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Lesões Encefálicas/reabilitação , Avaliação da Deficiência , Emprego , Terapia Ocupacional/organização & administração , Reabilitação Vocacional/métodos , Canadá , HumanosRESUMO
PURPOSE: To examine the association between social participation and subjective quality of life (SQOL) for non-employed, community-dwelling adults with moderate to severe traumatic brain injury (TBI) at 1 year or greater post-injury. METHOD: A correlational study was conducted involving 46 participants. Social participation was measured using the Community Integration Questionnaire, Social Provisions Scale and the Adult Subjective Assessment of Participation. SQOL was measured using the Quality of Life and Health Questionnaire, Abdel-Khalek Happiness Scale and UCLA Loneliness Scale. RESULTS: Higher levels of happiness and global quality of life were each associated with higher levels of enjoyment, satisfaction with performance and higher proportion of activities performed with others. Lower levels of loneliness were associated with higher levels of general social integration and higher levels of perceived social supports. There were no associations found between SQOL and the objective social participation measures of diversity, frequency (intensity) or proportion of activities performed outside of home. CONCLUSIONS: Findings contribute to the TBI literature in showing that it is: (a) the more subjective and not objectively measured nature of participation that is associated with SQOL and (b) positive and negative aspects of quality of life show different relationships with social participation variables. Implications for Rehabilitation A high proportion of individuals with traumatic brain injury (TBI) experiences reduced involvement in social participation (involvement in social and leisure activities and within a social network) and low subjective quality of life (SQOL). This study suggests that, by simply increasing the variety and frequency of social and leisure activities, there may be no positive influences on SQOL. Instead, this study suggests that, to increase SQOL, it is important to increase opportunities for individuals to participate with others and also to enhance their subjective experience of social and leisure activities. The large variance obtained of scores for social participation and SQOL provide a reminder to clinicians to maintain an individualized approach when working with individuals with TBI.
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Lesões Encefálicas/reabilitação , Qualidade de Vida , Participação Social , Acidentes de Trânsito/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Humanos , Solidão , Masculino , Pessoa de Meia-Idade , Apoio Social , Adulto JovemRESUMO
Studies of connectivity of natural populations are often conducted at different timescales. Studies that focus on contemporary timescales ask questions about dispersal abilities and dispersal behavior of their study species. In contrast, studies conducted at historical timescales are usually more focused on evolutionary or biogeographic questions. In this paper we present a synthesis of connectivity studies that have addressed both these timescales in Australian Trichoptera and Ephemeroptera. We conclude that: (1) For both groups, the major mechanism of dispersal is by adult flight, with larval drift playing a very minor role and with unusual patterns of genetic structure at fine scales explained by the "patchy recruitment hypothesis"; (2) There is some evidence presented to suggest that at slightly larger spatial scales (~100 km) caddisflies may be slightly more connected than mayflies; (3) Examinations of three species at historical timescales showed that, in southeast Queensland Australia, despite there being no significant glaciation during the Pleistocene, there are clear impacts of Pleistocene climate changes on their genetic structure; and (4) The use of mitochondrial DNA sequence data has uncovered a number of cryptic species complexes in both trichopterans and ephemeropterans. We conclude with a number of suggestions for further work.