Long-term effects of childhood speech and language disorders : A scoping review

assessed for eligibility (n = 153) Full text assessed for eligibility (n = 57) Studies included in scoping review (n = 51) Records excluded on full text • Aim not relevant for review (n = 4) • Length of follow-up < 2 years (n = 1) • High rates of intellectual disability in study population (n = 1) • No primary data (n = 1) Database search to identify eligible studies published since initial search (n = 1) Records excluded (n = 6610) Id en tif ica tio n


Introduction
Speech and language disorders (SLDs) in childhood are a public health concern. Childhood SLDs are associated with effects on the day-to-day lives of individuals and can potentially have negative long-term personal development and opportunity effects (Arkkila et al. 2009;Beitchman, Brownlie & Bao 2014;Clegg 2006). Speech and language disorder communication difficulties can limit an individual's ability to participate in society and may lead to reduced social and emotional well-being. Speech and language disorders often result in economic effects for the individual and society (Community Affairs References Committee & Siewert 2014). The societal economic burden may be substantial if the individual progresses to criminal behaviours, needs increased mental health services, is unemployed and requires ongoing support, or needs support from adult literacy programmes (Gross 2006). Additionally, a disproportionate number of SLDs are experienced by socio-economically disadvantaged populations, which often means that economic barriers inhibit access to appropriate assistance services (Law et al. 2017;Maggi et al. 2010).
Internationally, the reporting of SLD prevalence varies. This variation is likely a result of the differences in identification methods, reporting requirements and diagnostic criteria between countries. In the United States (US), it has been reported that 8% of children aged 3-17 years have voice, speech, language or swallowing disorders (Black, Vahratian & Hoffman 2015). In the United Kingdom (UK), 6% of children are reported to have speech and language delays (Law et al. 2000), which is similar to the estimated 6% -9% of children in South Africa (Nwosu 2015;Pascoe, Mahura & Le Roux 2018). In Australia, the prevalence of communication impairments ranges from < 1% to 21% amongst Australian children, depending on the reference source, with prevalence highest amongst younger children (McCormack et al. 2007).
To facilitate evidence-based intervention selection and conduct economic evaluations for these treatment options, an overview of the long-term outcomes from SLDs is first required. This review examines the long-term outcomes for individuals who have experienced childhood SLDs. The existing evidence focuses on singular outcome effects resulting from childhood SLDs (Baltaxe & Simmons 1975;Jackson et al. 2009;Kent & Vorperian 2013); this review aims to provide a concise overview of all of the potential long-term effects of having a childhood SLD. The results of this research can provide patients, carers and health professionals with an overview of the current evidence, an essential tool in the era of evidence-based practice (EBP). To gain a holistic picture of the impact of SLDs, all relevant information needs to be examined; this requires the inclusion of many studies that examine SLDs without differentiating between SLDs. Separating the two would likely exclude valuable studies conducted before the two terms were independently defined. This scoping review seeks to answer the question: what are the potential long-term effects of childhood SLDs that have been reported in the literature? To do this, it identifies and analyses the existing evidence base and provides an overview of the long-term impact of SLDs, to provide solid evidence to guide future research, influence public policy and guide clinical practice.

Methods
This scoping review followed the methods outlined by Levac, Colquhoun and O'Brien (2010), comprising five main stages: (1) identify the research question; (2) identify relevant studies; (3) select studies; (4) chart the data; and (5) collate, summarise and report the results. A scoping review is a method for mapping areas of research and presenting the results in an accessible format for knowledge users (Grudniewicz et al. 2016).

Search criteria
In 2017, speechBITE, ERIC, Linguistics and Language Behaviour Abstracts, PubMed, MEDLINE, PsycINFO, SocINDEX and the Cochrane Library were searched. The aim was to identify studies investigating the impact of childhood SLDs or SLD therapy on individual and social aspects during adolescence and adulthood. As there is variation in the historical and international reporting of SLDs, we have not separated speech disorders and language disorders for this scoping review, as is now current practice. The search strategy included the following terms: • speech or language or language development or language disorders or communication disorders • impairment or problem or difficult* or pathology or disorder • long-term or follow-up • psychology or psychosocial or behavio*r or mental health or emotional health.
The terms were adapted as necessary for each database. As there were no previous reviews on the topic, the searches were not time constrained. The final searches were conducted in August 2017. Reference lists of the included studies were searched for additional citations.

Selection criteria
We included only studies that reported primary data and were peer-reviewed academic journal items, PhD dissertations, research reports or full conference papers. Articles were excluded if they were not available in English, did not pertain to humans, specifically examined SLDs resulting from either biomedical conditions such as Down syndrome or neurogenic, neuromotor or neurosensory impairments such as aphasia (Efstratiadou et al. 2018).

Study selection
Titles and abstracts were screened by one researcher (J.V.) against the selection criteria and categorised for inclusion or exclusion. In case of uncertainty, a second researcher (D.L.) screened the title and abstract against the selection criteria. Disagreements were resolved by consensus or consultation with a third researcher (L.J.C. or A.C.S.).
After the review of titles and abstracts, full-text review of the articles was conducted according to criteria. Mental health, social well-being and academic outcomes were defined as the three main outcomes. Studies were excluded when they did not report mental health, social or academic outcomes, had less than 2 years of follow-up, described self-reported SLDs or participants with an intelligence quotient (IQ) of < 80 (to rule out general intellectual disability). In the absence of clinical information that could guide the choice of follow-up period, 2 years was chosen to ensure that study follow-ups occurred after initial assessments, whilst also including as many relevant studies as possible. Studies were not excluded if they presented different results from the same data set. No limitations were placed on participant age at enrolment or for followup for the included studies.

Data extraction
The full text of articles that met the inclusion criteria was read, and data were extracted by one researcher (J.V.) using an abstraction form. Based on the recommendations of Levac et al. (2010), the data abstraction form was collectively and iteratively developed as the scope of the review was clarified. The data abstraction form was pilot-tested by two researchers (J.V. and D.L.) for five articles to ensure consistency and to test the form. The data extracted included the publication details, study design and aim, sample, years of follow-up, type of impairment, age at onset, specific outcomes reported and results on relevant outcomes.

Quality assessment
The quality of included studies was assessed to provide an understanding of the strength of evidence of each study and to inform the interpretation of the review conclusions. A modified Newcastle-Ottawa scale was used to determine a quality rating for each study (Wells et al. 2000). This scale assesses the quality of non-randomised studies by allocating a score based on study group selection, group comparability and the method by which the exposure or outcome of interest is ascertained (Wells et al. 2000). The scale was also modified to remove a criterion not relevant to this review and to score one criterion using two rather than three points. The modified scale and its coding are shown in the Appendix 1. The quality was rated independently by two researchers (J.V. and D.L./ L.J.C.) in an iterative manner, with a discussion of any discrepancies to reach consensus with adjudication from a third member of the research team (A.C.S.). Studies were categorised as a higher or lower quality based on their overall quality rating (QR) using a median split (6+ vs. < 6, respectively, on the 0-8 scale). Studies were not excluded based on quality rating.

Data analysis and synthesis
The study results were broadly categorised into mental health, social well-being and academic outcomes. Some outcomes such as loneliness (measured in relation to quality of life) could be categorised under multiple categories such as mental health or social well-being. Classification of subcategories was determined by consensus between researchers (J.V. and D.L.) and is shown in Figure 1. The results are presented to show an overall coherent picture of the included studies, considering their quality rating and results, including null findings. Synthesis of the findings was performed narratively.
The term 'speech and language disorder' (SLD) as opposed to 'impairment' is used in this review. However, for consistency and accuracy throughout this article, the terminology used by the authors has been preserved where possible.

Review findings
A total of 51 articles were included in the review. The results of the search and screening stages are shown in the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart (see Figure 2).

Study characteristics
All included studies used a cohort design and were largely (n = 36) published after the year 2000 (Table 1). Studies were predominantly conducted in the UK (n = 21), US (n = 10) and Canada (n = 9), on 27 unique cohorts. Most studies reported more than one outcome measure. In total 84 unique outcomes were reported across the 51 studies ( Figure 1 and Table 2); 40 studies reported mental health outcomes, 27 reported social well-being outcomes, and 17 reported academic outcomes ( Table 2). The age of participants at follow-up (7-39 years) and the length of follow-up (4-31 years) varied considerably. The quality rating of the reviewed studies ranged from 3 to 8 with a median of 6, out of a possible total of 8. Specific language impairments (SLIs) and developmental language disorders (DLDs) were the most common diagnoses reported within the studies (determined by use of this specific terminology).

Mental health outcomes
Four studies reported positive associations between childhood SLD and poor mental health (not otherwise specified) (Arkkila et al. 2009;Clegg et al. 2005;   Other 3

School sample
Conti-Ramsden Manchester language study 10 Templin investigation in kindergarten 2 Other 4

United Kingdom 21
United States 10 Canada 9 Denmark 4 Other 7

Psychiatric disorders
Amongst the eight studies examining overall psychiatric disorders (including mood disorders or personality disorders), two reported no association (Howlin et al. 2000;Snowling et al. 2006) and six reported an association with childhood SLD (Baker & Cantwell 1987;Beitchman et al. 1996aBeitchman et al. , 1996bBeitchman et al. , 1999Beitchman et al. , 2001aWhitehouse et al. 2009). Other studies examined psychiatric conditions individually (Table 1). When the subset of mood disorders (i.e. depression, bipolar disorder, anxiety disorder) was examined, two studies with comparable quality ratings reported disparate results. One reported an increased risk of mood disorders amongst participants with deteriorated vocabulary performance over follow-up (Armstrong et al. 2017), while the other reported no difference between SLD participants and their controls (Beitchman et al. 2014). In contrast, for the subset of personality disorders (long-term, extreme and inflexible patterns of thinking, behaviour and emotion), all three studies found more personality disorders in SLD participants than controls, and all three studies received high-quality ratings (Beitchman et al. 1999, Mouridsen & Hauschild 2009b. Eight out of 11 studies examining anxiety reported an association with childhood SLD. Three of these studies were led by Beitchman et al.; two reported higher anxiety problems in their cohort at age 19 years (Beitchman et al. 1999(Beitchman et al. , 2001, while the third reported no difference at age 31 years (Beitchman et al. 2014). The difference could not be explained by dropout or change in language abilities over time. Beitchman et al. proposed that this may be a result of the demanding environment experienced by participants at 19 years of age resulting from their developmental stage, potential academic difficulties and SLD challenges (Beitchman et al. 2014).
There was mixed evidence that childhood SLD was associated with depression (

Behavioural problems
Of the 15 studies that examined behavioural difficulties, 11 studies found a strong association between childhood SLD and behavioural difficulties. Baker and Cantwell (1987) and Yew and O'Kearney (2015) reported more hyperactive behaviour and reactive temperaments amongst participants with a history of SLDs. Similarly, Benasich, Curtiss and Tallal (1993) reported overall behavioural disturbances -hyperactivity in both male and female participants and social withdrawal in female participants.

Substance use disorders
Substance use disorders were investigated by five studies, with one study reporting that adults with deteriorated vocabulary performance had an increased risk for illicit and alcohol misuse or abuse (Armstrong et al. 2017). However, four other studies found no difference in rates of substance use disorders between persons with a history of SLDs and their controls (Beitchman et al. 2014(Beitchman et al. , 1999(Beitchman et al. , 2001Mouridsen & Hauschild 2010).

Health-related quality of life
Mixed results were reported about health-related quality of life (HRQoL). Studies such as that by Arkkila et al. reported no differences in overall HRQoL; however, the results indicated a lower vitality score for participants with a history of SLD (Arkkila et al. 2009). Three studies showed that SLDs had a great effect on HRQoL (Arkkila et al. 2008), assumedly because individuals with SLDs felt lonely (Brinton, Fujiki & Baldridge 2010), reported lower satisfaction with life and felt no control over life compared to the control groups (Schoon et al. 2010). In contrast, two studies reported no difference in quality of life (Johnson, Beitchman & Brownlie 2010), personal happiness or life satisfaction (Records, Tomblin & Freese 1992) between those with a history of SLDs and control groups.

Social behaviour
The majority of the studies that examined social behaviour reported lower social behaviour amongst persons with a history of SLDs compared to controls, although three studies found no discernible difference. These findings included PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses. • Not focussed on speech/language disorders (n = 7) • Self-reported speech/language disorder (n = 4) • High rates of intellectual disability in study population (n = 1) http://www.sajce.co.za Open Access lower social cognition  and social performance (Aram, Ekelman & Nation 1984) and significantly higher rates of social problems (Glogowska et al. 2006;Lewis et al. 2016). Dissimilar results were reported by Wadman et al., who found that although persons with a history of specific language impairment (SLI) were more likely to be shy, they had overall similar social behaviours to controls (Wadman et al. 2011b). This result was supported by two studies that reported similar participation in social activities amongst persons with SLD history compared to control groups (Aram et al. 1984, King, Jones & Lasky 1982, although these studies received lower quality ratings.

Employment
No consensus was found as to whether childhood SLDs were associated with lower employment rates in later life. It was clear, however, that when employed, the socioeconomic status of persons with a history of SLDs was lower than that of control groups. Several studies showed that persons with a history of SLDs were more likely to be in less-skilled jobs than controls (Clegg et al. 2005;Elbro, Dalby & Maarbjerg 2011;Felsenfeld, Broen & Mcgue 1994;Howlin et al. 2000;Parsons et al. 2011;Whitehouse et al. 2009) and less likely to be employed in a full-time job (Arkkila et al. 2008;Armstrong et al. 2017;Beitchman et al. 2001;Snowling et al. 2001). Durkin et al. reported lower part-time employment for participants with a history of an SLD; however, the presence of autism spectrum disorder symptomatology was also found to be a significant predictor of employability in this study (Durkin et al. 2012). Participants with a history of SLDs were reported as unemployed for longer periods than controls in three studies (Clegg et al. 2005;Law et al. 2009;Parsons et al. 2011). Moreover, Clegg et al. and Howlin et al. reported that persons with a history of SLDs had more difficulties in the work environment and that behaviour-related problems were often referenced in reasons for dismissal (Clegg et al. 2005;Howlin et al. 2000). In contrast, other studies reported no substantial difference in employment rates (Felsenfeld et al. 1994;Johnson et al. 2010).

Relationships
There was no reported difference in the number of friendships for participants with SLDs and controls across studies; however, the overall quality of friendships was rated lower by SLD participants. All but one study (King et al. 1982) reported lower peer scores or more peer problems amongst persons with a history of SLDs compared to controls Brinton et al. 2010;Wadman et al. 2011b), although Yew et al. suggested that this was only true for girls (Yew & O'Kearney 2015). Persons with a history of SLDs were reported to experience more instances of bullying (Wadman et al. 2011a), have fewer acquaintances and be more awkward and limited in making contact (Clegg et al. 2005). When romantic relationships were examined, fewer participants with a history of SLDs were in romantic relationships compared to controls (Clegg et al. 2005;Schoon et al. 2010;Wadman et al. 2011b), although no difference was found for participants with a DLD history (Howlin et al. 2000). Additionally, Brownlie et al. (2007) found that language-impaired women were more likely than controls to have experienced sexual assault.

Independent living
All seven studies that examined independent living reported low independency or higher rates of living with parents for persons with a history of SLDs compared to control groups (Arkkila et al. 2008;Clegg 2006, Conti-Ramsden & Durkin 2008aDurkin et al. 2012;Howlin et al. 2000;Schoon et al. 2010;Whitehouse et al. 2009).

Academic outcomes
Overall, academic achievement was lower for participants with an SLD when compared to controls (Durkin et al. 2012;King et al. 1982;Snowling et al. 2001). This finding was supported by the results of studies that examined specific academic outcomes such as the need for special education support or the likelihood of completing education programmes. Although one study (King et al. 1982) was rated lower in quality, most studies showed that SLD individuals were more likely to need special education support and less likely to complete their education programmes (Aram et al. 1984;Armstrong et al. 2017;Durkin & Conti-Ramsden 2007;Elbro et al. 2011;Howlin et al. 2000;Parsons et al. 2011;Whitehouse et al. 2009). More specifically, Johnson et al. (2010) reported lower educational attainment amongst young adults with a history of a language impairment when compared to those without impairments or early speech-only impairment. Although some studies reported reduced academic outcomes, students with an SLD tended to be satisfied with their academic results ); some were even more satisfied than their peers (Felsenfeld et al. 1994). One study found that participants with SLDs received 'acceptable' grades; however, this study lacked a control group for comparison and was a small sample (Brinton et al. 2010). Hall and Tomblin (1978) did not find consistent differences in academic outcomes between cases with a language disorder and articulation disorder controls. Similarly, King et al. (1982) reported no difference in academic achievement between groups with and without SLDs. Conti-Ramsden et al. and Durkin et al. also suggest that participants with a history of SLDs appear to have more opportunities now than in the 1990s Durkin et al. 2009).

Implications and recommendations
This scoping review is the first comprehensive attempt to summarise the data available on the potential long-term effects of SLDs reported in the literature. These results have implications for individuals living with SLDs, their families and the clinicians advising them. Although the results varied, across the 51 studies that met the inclusion criteria, the most common results reported were suboptimal mental health, social well-being and academic outcomes for persons with a history of SLDs. Most studies (n = 40) reported mental health outcomes, while fewer studies (n = 17) explored academic outcomes. However, these findings are limited to only those reported by the authors in the studies reviewed. The average quality rating of the included studies did not seem to differ across these three domains. Studies published before 1990 were given lower quality ratings, predominantly because of the lack of reporting control groups and lower population representation in the samples. The differences in associations between SLDs and outcomes identified in the studies are likely a result of study-related factors, and therefore, clinical implications should be drawn based on study quality and applicability. Thirty-nine studies included more than 60 participants with SLDs, 41 included comparison groups, and 17 studies had a follow-up of 10 years or greater. Within the studies, different assessment tools were used to determine SLD, and terminology defining SLDs was non-uniform between studies. Because of the varied quality of the studies reviewed and the lack of terminology defining disorders, it was not possible to compare the severity of the SLDs described between studies; however, future reviews should seek to do so. Despite the international diagnostic variation, the evidence that childhood SLDs can have long-term impacts on mental health, social well-being and academic outcomes was strong.

Long-term outcomes
Having a childhood diagnosis of an SLD appears to be associated with mental health outcomes, with evidence most consistently indicating associations with personality disorders and behavioural problems. This is important for treating professionals to be aware of, as they are well positioned to refer patients to ancillary support services for early intervention. This review found a high association between SLDs and behavioural disorders; however, the authors were unclear whether this relationship was incidental or causative (Lindsay, Dockrell & Strand 2007;Weinberg et al. 1998). It should be noted that other factors may have been responsible for these effects, including social, cognitive and genetic risk factors (Lau et al. 2007). Multilingual countries like South Africa face unique SLD diagnosis and treatment challenges (Jordaan & Yelland 2003). More research aimed at these constructs will provide a better understanding of these problems in individuals with SLDs and how treating professionals can support them (Kathard & Pillay 2013;Whitehouse et al. 2009). Additionally, studies reported the added difficulty of diagnosing SLDs in individuals with existing childhood behavioural or psychiatric disorders (Sundheim & Voeller 2004). This phenomenon may have resulted in under-or overestimation of the occurrence of SLDs and therefore their impact within the studies. No association was found between childhood SLDs and substance use disorder. However, difficulties that are often comorbid with SLDs, such as self-regulation difficulties, hyperactivity and school-based difficulties, are seen to be potential precursors of substance use disorder (Weinberg et al. 1998).
Evidence for the impact of SLDs on relationships and employment varied. Evidence suggests that persons with a history of SLDs are more likely to be employed in unskilled or manual labour than their peers. In today's knowledge economy, which increasingly relies on knowledge over physical capital and labour (Brinkley 2006), workers who are unable to communicate clearly may be disadvantaged. This effect coupled with the decline in jobs in the manual sector and associated lower incomes may enhance the socioeconomic impacts of SLDs for individuals. This enhanced effect could potentially lead to exacerbation of their condition through reduced access to health services because of financial barriers (Ruben 2000). This could create a cycle of disadvantage and accentuate the impact of the social gradient on health from a young age (Law, Reilly & Snow 2013), further disadvantaging vulnerable populations such as those with SLDs.
Similar to employment, evidence suggests that individuals with a history of SLDs are likely to experience overall lower academic achievement compared to their peers (King et al. 1982;Snowling et al. 2001). However, researchers also noted that individuals with SLDs may be as or more satisfied with their results than their peers (Felsenfeld et al. 1994;Records et al. 1992). These finding may reflect the fact that students with SLDs have to work harder than non-SLD peers for desired results and thus feel more satisfied with the academic outcomes they achieve (Records et al. 1992;Western & Tomaszewski 2016). Regardless of the cause of this discrepancy, the finding that SLDs are associated with lower academic achievement has important implications for early diagnosis and intervention services.

Clinical implications
There is a consensus supporting diagnosis and intervention before formal schooling to improve SLD, and thus to avoid the child experiencing academic failure (Buschmann et al. 2009;Nippold 2012). Interventions that are frequent, intense and systematic, that promote engagement and attention of children within a supportive and positive environment, and that are tailored to focus on normal classroom language needs have been shown to facilitate positive outcomes for children with SLDs (Hartshorne 2009b;Nippold 2012 with individuals with SLDs. These costs are related to employment support, increased educational needs, welfare benefits, social service costs (resulting from behavioural and emotional development effects), mental health services, challenges communicating within the justice or health system and juvenile delinquency (Hartshorne 2009a;Speech Pathology Australia 2014). The healthcare and out-of-pocket costs for children with SLDs was higher in the age groups 4-5 years, 6-7 years and 10-11 years than for children without SLDs (Cronin et al. 2017). Therefore, appropriate early intervention by professionals such as speech pathologists could yield substantial economic and social cost savings, although further research needs to be conducted to quantify these savings.

Limitations
Differences in terminology, definitions and methods to assess outcomes across the included studies were a barrier for comparability and led to limitations within this review. In particular, many terms and different criteria were used to describe participants' SLDs, underlining the importance of the consistent terminology proposed by Bishop et al. (2016). As this review was intended to provide an overview of outcome effects, the results were not reported by disorder type. The studies reported results from individuals with different combinations and severity of SLDs, and this diversity presents difficulty in generalising the findings. Given the complex nature of SLDs, the exclusion of studies that reported SLDs resulting from biomedical conditions may have excluded relevant studies, as the interplay of biomedical and non-biomedical factors affecting SLDs is complex. However, this review provides an excellent collective representation of the effects of childhood SLDs in later life, which is relevant for developing health policy and fuelling advocacy. Additionally, studies were not excluded if they reported new results or results from different time points in the same data. While this has the potential to confound some of the results, as there was no meta-analysis of results it was not deemed inappropriate. Because of lack of terminology within the literature, some eligible studies may not have been captured during the initial searches; however, all search terms, inclusion and exclusion criteria and methods have been outlined clearly to improve reproducibility. The studies included spanned a large range of ages because of variations in their enrolment ages and follow-up periods. This variation may affect the generalisability of results to all age groups; however, this is why the scoping review method was used. Additionally, as the literature searches were conducted in 2017 and the analysis and synthesis of results took an extended period, future research could examine more recent literature and use this review as a foundation.
In this scoping review, a quality assessment tool was used to group studies and potentially explain diverging findings, increasing the quality of the investigation. Despite receiving criticism for rating validity and inter-rater reliability (Hartling et al. 2013;Lo, Mertz & Loeb 2014), the Newcastle-Ottawa scale has been used extensively (Abdel-Latif et al. 2007;Aziz et al. 2006;Margulis et al. 2014;Prins & Van der Wurff 2009). It has also been endorsed by the Cochrane Collaboration for use in assessing the study quality of observational studies and has been reported as a convenient and adaptable tool (Margulis et al. 2014). To minimise these potential shortcomings, two researchers independently rated the quality of each eligible study, with the third researcher adjudicating the differences until consensus was reached.

Conclusion
This review of 51 cohort studies provides evidence that individuals who have childhood SLDs may experience a higher incidence of mental health difficulties, reduced social well-being and reduced academic achievement compared to their peers. The results also indicate that childhood SLDs are complex, and their effects can persist into adolescence and adulthood, potentially causing significant negative effects for the individual, society and the healthcare system, supporting the importance of early intervention and improvements in access. Further research examining the long-term effects of childhood SLDs is required to conclusively determine the impact of SLDs on each of these domains.

Funding information
This review was conducted with the support of the Centre of Research Excellence in Telehealth funded by the National Health and Medical Research Council (NHMRC; APP1061183), and the Health-e-Regions project, which supports the delivery of telehealth services throughout the Western Downs region in Queensland, funded by QGC Pty Ltd.

Data availability statement
Data sharing is not applicable to this article, as no new data were created or analysed in this study.

Disclaimer
The contents of the published material are solely the responsibility of the individual authors and do not reflect the views of NHMRC or other funding agencies.