215 resultados para POPULATION VIABILITY ANALYSIS


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Breast cancer is a common disease in both developing and developed countries with early identification and treatment improving prognosis and survival. Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix (ECM) that mediate cell adhesion, motility, proliferation, invasion and cell signalling. Members of the syndecan family of HSPGs have been identified to be involved in breast cancer progression through their varied interactions with a number of growth factors, ligands and receptors. Specifically, high expression levels of syndecan-1 (SDC1) have been demonstrated in more invasive breast tumours while elevated syndecan-4 (SDC4) levels have been identified to correspond with improved prognosis. With genetic changes in the syndecans and their association with breast cancers plausible, we examined two single nucleotide polymorphisms in SDC1 (rs1131351) and SDC4 (rs67068737) within an Australian Caucasian breast cancer case/control population. No association was found with SDC4 and breast cancer in our population. However, a significant association between SDC1 and breast cancer was identified in both our case/control population and in a replication cohort. When both populations were combined for analysis, this association became more significant (genotype, p = 0.0003; allele, p = 0.0001). This data suggests an increased risk of developing breast cancer associated with the presence of the C allele of the SDC1 rs1131351 single nucleotide polymorphism (SNP) and may provide a marker toward early breast cancer detection.

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One of the problems to be solved in attaining the full potentials of hematopoietic stem cell (HSC) applications is the limited availability of the cells. Growing HSCs in a bioreactor offers an alternative solution to this problem. Besides, it also offers the advantages of eliminating labour intensive process as well as the possible contamination involved in the periodic nutrient replenishments in the traditional T-flask stem cell cultivation. In spite of this, the optimization of HSC cultivation in a bioreactor has been barely explored. This manuscript discusses the development of a mathematical model to describe the dynamics in nutrient distribution and cell concentration of an ex vivo HSC cultivation in a microchannel perfusion bioreactor. The model was further used to optimize the cultivation by proposing three alternative feeding strategies in order to prevent the occurrence of nutrient limitation in the bioreactor. The evaluation of these strategies, the periodic step change increase in the inlet oxygen concentration, the periodic step change increase in the media inflow, and the feedback control of media inflow, shows that these strategies can successfully improve the cell yield of the bioreactor. In general, the developed model is useful for the design and optimization of bioreactor operation.

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Traditional sensitivity and elasticity analyses of matrix population models have been used to inform management decisions, but they ignore the economic costs of manipulating vital rates. For example, the growth rate of a population is often most sensitive to changes in adult survival rate, but this does not mean that increasing that rate is the best option for managing the population because it may be much more expensive than other options. To explore how managers should optimize their manipulation of vital rates, we incorporated the cost of changing those rates into matrix population models. We derived analytic expressions for locations in parameter space where managers should shift between management of fecundity and survival, for the balance between fecundity and survival management at those boundaries, and for the allocation of management resources to sustain that optimal balance. For simple matrices, the optimal budget allocation can often be expressed as simple functions of vital rates and the relative costs of changing them. We applied our method to management of the Helmeted Honeyeater (Lichenostomus melanops cassidix; an endangered Australian bird) and the koala (Phascolarctos cinereus) as examples. Our method showed that cost-efficient management of the Helmeted Honeyeater should focus on increasing fecundity via nest protection, whereas optimal koala management should focus on manipulating both fecundity and survival simultaneously. These findings are contrary to the cost-negligent recommendations of elasticity analysis, which would suggest focusing on managing survival in both cases. A further investigation of Helmeted Honeyeater management options, based on an individual-based model incorporating density dependence, spatial structure, and environmental stochasticity, confirmed that fecundity management was the most cost-effective strategy. Our results demonstrate that decisions that ignore economic factors will reduce management efficiency. ©2006 Society for Conservation Biology.

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Long-term systematic population monitoring data sets are rare but are essential in identifying changes in species abundance. In contrast, community groups and natural history organizations have collected many species lists. These represent a large, untapped source of information on changes in abundance but are generally considered of little value. The major problem with using species lists to detect population changes is that the amount of effort used to obtain the list is often uncontrolled and usually unknown. It has been suggested that using the number of species on the list, the "list length," can be a measure of effort. This paper significantly extends the utility of Franklin's approach using Bayesian logistic regression. We demonstrate the value of List Length Analysis to model changes in species prevalence (i.e., the proportion of lists on which the species occurs) using bird lists collected by a local bird club over 40 years around Brisbane, southeast Queensland, Australia. We estimate the magnitude and certainty of change for 269 bird species and calculate the probabilities that there have been declines and increases of given magnitudes. List Length Analysis confirmed suspected species declines and increases. This method is an important complement to systematically designed intensive monitoring schemes and provides a means of utilizing data that may otherwise be deemed useless. The results of List Length Analysis can be used for targeting species of conservation concern for listing purposes or for more intensive monitoring. While Bayesian methods are not essential for List Length Analysis, they can offer more flexibility in interrogating the data and are able to provide a range of parameters that are easy to interpret and can facilitate conservation listing and prioritization. © 2010 by the Ecological Society of America.

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Quantifying the competing rates of intake and elimination of persistent organic pollutants (POPs) in the human body is necessary to understand the levels and trends of POPs at a population level. In this paper we reconstruct the historical intake and elimination of ten polychlorinated biphenyls (PCBs) and five organochlorine pesticides (OCPs) from Australian biomonitoring data by fitting a population-level pharmacokinetic (PK) model. Our analysis exploits two sets of cross-sectional biomonitoring data for PCBs and OCPs in pooled blood serum samples from the Australian population that were collected in 2003 and 2009. The modeled adult reference intakes in 1975 for PCB congeners ranged from 0.89 to 24.5 ng/kg bw/day, lower than the daily intakes of OCPs ranging from 73 to 970 ng/kg bw/day. Modeled intake rates are declining with half-times from 1.1 to 1.3 years for PCB congeners and 0.83 to 0.97 years for OCPs. The shortest modeled intrinsic human elimination half-life among the compounds studied here is 6.4 years for hexachlorobenzene, and the longest is 30 years for PCB-74. Our results indicate that it is feasible to reconstruct intakes and to estimate intrinsic human elimination half-lives using the population-level PK model and biomonitoring data only. Our modeled intrinsic human elimination half-lives are in good agreement with values from a similar study carried out for the population of the United Kingdom, and are generally longer than reported values from other industrialized countries in the Northern Hemisphere.

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Background There is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its receptor, the growth hormone secretagogue receptor (GHSR), play a role in cancer progression. Ghrelin gene and ghrelin receptor gene polymorphisms have been reported to have a range of effects in cancer, from increased risk, to protection from cancer, or having no association. In this study we aimed to clarify the role of ghrelin and ghrelin receptor polymorphisms in cancer by performing a meta-analysis of published case–control studies. We conducted searches of the literature published up to January 2013 in MEDLINE using the PubMed search engine. Individual data on 8,430 cases and 14,008 controls from six case–control studies of an all Caucasian population were evaluated for three ghrelin gene (GHRL; rs696217, rs4684677, rs2075356) and one ghrelin receptor (GHSR; rs572169) polymorphism in breast cancer, esophageal cancer, colorectal cancer and non-Hodgkins lymphoma. Results In the overall analysis, homozygous and recessive associations indicated that the minor alleles of rs696217 and rs2075356 GHRL polymorphisms conferred reduced cancer risk (odds ratio [OR] 0.61-0.78). The risk was unchanged for breast cancer patients when analysed separately (OR 0.73-0.83). In contrast, the rs4684677 GHRL and the rs572169 GHSR polymorphisms conferred increased breast cancer risk (OR 1.97-1.98, p = 0.08 and OR 1.42-1.43, p = 0.08, respectively). All dominant and co-dominant effects showed null effects (OR 0.96-1.05), except for the rs572169 co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05). Conclusions This study suggests that the rs696217 and rs2075356 ghrelin gene (GHRL) polymorphisms may protect carriers against breast cancer, and the rs4684677 GHRL and rs572169 GHSR polymorphisms may increase the risk among carriers. In addition, larger studies are required to confirm these findings.

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Polybrominated diphenyl ethers (PBDEs) are considered to be a cost effective and efficient way to reduce flammability therefore reducing harm caused by fires. PBDEs are incorporated into a variety of manufactured products and are found worldwide in biological and environmental samples (e.g. Hites et al. 2004). Unlike other persistent organic pollutants there is limited data on PBDE concentrations by age and/or other population specific factors. Some studies have shown no variation in adult serum PBDE concentrations with age (e.g. Mazdai et al., 2003, Meironyte Guvenius et al., 2003) while Petreas et al. (2003) and Schecter et al. (2005) found results to be suggestive of an age trend in adult data but no statistically significant correlation was found. In addition to the data on adult concentrations there is limited data which investigates the levels of PBDEs in infants and young children. Fangström et al. (2005) showed that in seven year olds there was no difference in PBDE concentration when compared to adult concentrations. While Thomsen et al. (2002, 2005) found the concentration of PBDEs in pooled samples of blood serum from a 0-4 years age group to be higher than other age groups (4 to > 60 years). In addition, a family of four was studied in the U.S. and the concentrations were found to be greatest in the 18-month-old infant followed by the 5 year old child, then the mother and father (Fischer et al., 2006). The objectives of this study were to assess age, gender and regional trends of PBDE concentrations in a representative sample of the Australian population.

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Polybrominated diphenyl ethers (PBDEs), a common class of brominated flame retardants, are a ubiquitous part of our built environment, and for many years have contributed to improved public safety by reducing the flammability of everyday goods. Recently, PBDEs have come under increased international attention because of their potential to impact upon the environment and human health. Some PBDE compounds have been nominated for possible inclusion on the Stockholm Convention on Persistent Organic Pollutants, to which Australia is a Party. Work under the Stockholm Convention has demonstrated the capacity of some PBDEs to persist and accumulate in the environment and to be carried long distances. Much is unknown about the impact of PBDEs on living organisms, however recent studies show that some PBDEs can inhibit growth in colonies of plankton and algae and depress the reproduction of zooplankton. Laboratory mice and rats have also shown liver disturbances and damage to developing nervous systems as a result of exposure to PBDEs. In 2004, the Australian Government Department of the Environment and Water Resources began three studies to examine levels of PBDEs in aquatic sediments, indoor environments and human blood, as knowledge about PBDEs in Australia was very limited. The aim of these studies was to improve this knowledge base so that governments were in a better position to consider appropriate management actions. Due to the high costs for laboratory analysis of PBDEs, the number of samples collected for each study was limited and so caution is required when interpreting the findings. Nevertheless, these studies will provide governments with an indication of how prevalent PBDEs are in the Australian population and the environment and will also contribute to international knowledge about these chemicals. The Department of the Environment and Water Resources will be working closely with othergovernment agencies, industry and the community to investigate any further action that may be required to address PBDEs in Australia.

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Background: Preventing risk factor exposure is vital to reduce the high burden from lung cancer. The leading risk factor for developing lung cancer is tobacco smoking. In Australia, despite apparent success in reducing smoking prevalence, there is limited information on small area patterns and small area temporal trends. We sought to estimate spatio-temporal patterns for lung cancer risk factors using routinely collected population-based cancer data. Methods: The analysis used a Bayesian shared component spatio-temporal model, with male and female lung cancer included separately. The shared component reflected exposure to lung cancer risk factors, and was modelled over 477 statistical local areas (SLAs) and 15 years in Queensland, Australia. Analyses were also run adjusting for area-level socioeconomic disadvantage, Indigenous population composition, or remoteness. Results: Strong spatial patterns were observed in the underlying risk factor exposure for both males (median Relative Risk (RR) across SLAs compared to the Queensland average ranged from 0.48-2.00) and females (median RR range across SLAs 0.53-1.80), with high exposure observed in many remote areas. Strong temporal trends were also observed. Males showed a decrease in the underlying risk across time, while females showed an increase followed by a decrease in the final two years. These patterns were largely consistent across each SLA. The high underlying risk estimates observed among disadvantaged, remote and indigenous areas decreased after adjustment, particularly among females. Conclusion: The modelled underlying exposure appeared to reflect previous smoking prevalence, with a lag period of around 30 years, consistent with the time taken to develop lung cancer. The consistent temporal trends in lung cancer risk factors across small areas support the hypothesis that past interventions have been equally effective across the state. However, this also means that spatial inequalities have remained unaddressed, highlighting the potential for future interventions, particularly among remote areas.

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Background The impact of socio-environmental factors on suicide has been examined in many studies. Few of them, however, have explored these associations from a spatial perspective, especially in assessing the association between meteorological factors and suicide. This study examined the association of meteorological and socio-demographic factors with suicide across small areas over different time periods. Methods Suicide, population and socio-demographic data (e.g., population of Aboriginal and Torres Strait Islanders (ATSI), and unemployment rate (UNE) at the Local Government Area (LGA) level were obtained from the Australian Bureau of Statistics for the period of 1986 to 2005. Information on meteorological factors (rainfall, temperature and humidity) was supplied by Australian Bureau of Meteorology. A Bayesian Conditional Autoregressive (CAR) Model was applied to explore the association of socio-demographic and meteorological factors with suicide across LGAs. Results In Model I (socio-demographic factors), proportion of ATSI and UNE were positively associated with suicide from 1996 to 2000 (Relative Risk (RR)ATSI = 1.0107, 95% Credible Interval (CI): 1.0062-1.0151; RRUNE = 1.0187, 95% CI: 1.0060-1.0315), and from 2001 to 2005 (RRATSI = 1.0126, 95% CI: 1.0076-1.0176; RRUNE = 1.0198, 95% CI: 1.0041-1.0354). Socio-Economic Index for Area (SEIFA) and IND, however, had negative associations with suicide between 1986 and 1990 (RRSEIFA = 0.9983, 95% CI: 0.9971-0.9995; RRATSI = 0.9914, 95% CI: 0.9848-0.9980). Model II (meteorological factors): a 1°C higher yearly mean temperature across LGAs increased the suicide rate by an average by 2.27% (95% CI: 0.73%, 3.82%) in 1996–2000, and 3.24% (95% CI: 1.26%, 5.21%) in 2001–2005. The associations between socio-demographic factors and suicide in Model III (socio-demographic and meteorological factors) were similar to those in Model I; but, there is no substantive association between climate and suicide in Model III. Conclusions Proportion of Aboriginal and Torres Strait Islanders, unemployment and temperature appeared to be statistically associated with of suicide incidence across LGAs among all selected variables, especially in recent years. The results indicated that socio-demographic factors played more important roles than meteorological factors in the spatial pattern of suicide incidence.

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Executive Summary: Completion of the Veloway 1 (V1) will provide a dedicated and safe route for cyclists between the Brisbane CBD and the Gateway Motorway off-ramp at Eight Mile Plains alongside the South East Motorway. The V1 is being delivered in stages and when completed will provide a dedicated 3m wide cycleway 17km in length. Two stages (D and E) remain to be constructed to complete the V1. Major trip attractors along the V1 include the Mater, Princes Alexandra and Greenslopes Hospitals, two campuses of Griffith University, Garden City shopping centre and the Australian Tax Office. This report assesses the available evidence on the impacts on cycling behaviour of the recently completed V1 Stage C. The data sources informing this review include three intercept surveys, motion activated traffic cameras and travel time surveys on the V1 and adjoining South East Freeway Bikeway (SEFB), Strava app data, and cyclist crash data along Logan Road. The key findings from the evidence are that the completed V1 Stage C has: a Attracted cyclists from Holland Park, Holland Park West, Mt Gravatt and southern parts of Tarragindi onto the V1 Stage C. b Reduced the crash exposure of pedestrians to cyclists by attracting higher speed cyclists off the adjoining SEFB onto the cycling dedicated V1 Stage C. c Reduced the potential crash exposure of cyclists to motor vehicles by attracting cyclists off Logan Road on to the V1. d Provided travel time benefits to cyclists and reduced road crossings (eight down to two). e Predominantly attracted adults commuting alone to and from work and university. The evidence shows that the two traffic crossings across Birdwood Road (required as a temporary measure until the V1 is completed) negate much of the travel time gains of the V1 Stage C compared to the adjoining SEFB for southbound cyclists. Many cyclists accessing the V1 Stage C from the south are cycling in high-volume vehicular traffic lanes to reduce their travel time along Birdwood Road, but in the process are increasing their exposure to crashes with motor vehicles. Based on these findings this report recommends that TMR: a. Continue with plans to complete the V1 Veloway b. Undertake an engineering feasibility assessment to determine the viability of constructing a section of the V1 Stage E from the intersection Weller and Birdwood Roads over Marshall Road and along Bapaume Road on the western side of the Motorway to the intersection of Bapaume and Sterculia Roads. c. In the interim, improve signage and Birdwood Road crossing points for cyclists accessing and egressing the southern end of the V1 Stage C. d. Work with Brisbane City Council to identify the safest and most practical bicycle facilities to facilitate cycle travel between Logan Road and the V1 south of Birdwood Road. e. Improve the awareness of the V1 Stage C through signage for cyclists approaching from the north with the aim of providing a better understanding of the route of the V1 to the south. f. Refine the use of motion activated traffic cameras to improve the capture rate of useable images and obtain an ongoing collection over time of V1 usage data. g. Undertake discussions with Strava, Inc. to refine the presentation of Strava data to improve visual understanding of maps showing before and after cycle route volumes along and on roads leading to the V1.

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BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10(-8)), including rs12700667 on 7p15.2 (P = 1.6 × 10(-9)), rs7521902 near WNT4 (P = 1.8 × 10(-15)), rs10859871 near VEZT (P = 4.7 × 10(-15)), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10(-8)), rs7739264 near ID4 (P = 6.2 × 10(-10)) and rs13394619 in GREB1 (P = 4.5 × 10(-8)). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10(-8)) and rs4141819 on 2p14 (P = 9.2 × 10(-8)). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways.

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BACKGROUND Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.

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Background The Spine Functional Index (SFI) is a patient reported outcome measure with sound clinimetric properties and clinical viability for the determination of whole-spine impairment. To date, no validated Turkish version is available. The purpose of this study is to cross-culturally adapted the SFI for Turkish-speaking patients (SFI-Tk) and determine the psychometric properties of reliability, validity and factor structure in a Turkish population with spine musculoskeletal disorders. Methods The SFI English version was culturally adapted and translated into Turkish using a double forward and backward method according to established guidelines. Patients (n = 285, cervical = l29, lumbar = 151, cervical and lumbar region = 5, 73% female, age 45 ± 1) with spine musculoskeletal disorders completed the SFI-Tk at baseline and after a seven day period for test-retest reliability. For criterion validity the Turkish version of the Functional Rating Index (FRI) was used plus the Neck Disability Index (NDI) for cervical patients and the Oswestry Disability Index (ODI) for back patients. Additional psychometric properties were determined for internal consistency (Chronbach’s α), criterion validity and factor structure. Results There was a high degree of internal consistency (α = 0.85, item range 0.80-0.88) and test-retest reliability (r = 0.93, item range = 0.75-0.95). The factor analysis demonstrated a one-factor solution explaining 24.2% of total variance. Criterion validity with the ODI was high (r = 0.71, p < 0.001) while the FRI and NDI were fair (r = 0.52 and r = 0.58, respectively). The SFI-Tk showed no missing responses with the ‘half-mark’ option used in 11.75% of total responses by 77.9% of participants. Measurement error from SEM and MDC90 were respectively 2.96% and 7.12%. Conclusions The SFI-Tk demonstrated a one-factor solution and is a reliable and valid instrument. The SFI-Tk consists of simple and easily understood wording and may be used to assess spine region musculoskeletal disorders in Turkish speaking patients.