AI4Green: An Open-Source ELN for Green and Sustainable Chemistry.

An Electronic Laboratory Notebook (ELN) combining features, including data archival, collaboration tools, and green and sustainability metrics for organic chemistry, is presented. AI4Green is a web-based application, available as open-source code and free to use. It offers the core functionality of an ELN, namely, the ability to store reactions securely and share them among different members of a research team. As users plan their reactions and record them in the ELN, green and sustainable chemistry is encouraged by automatically calculating green metrics and color-coding hazards, solvents, and reaction conditions. The interface links a database constructed from data extracted from PubChem, enabling the automatic collation of information for reactions. The application's design facilitates the development of auxiliary sustainability applications, such as our Solvent Guide. As more reaction data are captured, subsequent work will include providing "intelligent" sustainability suggestions to the user.

Dynamic tilting in perovskites.

A new computational analysis of tilt behaviour in perovskites is presented. This includes the development of a computational program - PALAMEDES - to extract tilt angles and the tilt phase from molecular dynamics simulations. The results are used to generate simulated selected-area electron and neutron diffraction patterns which are compared with experimental patterns for CaTiO3. The simulations not only reproduced all symmetrically allowed superlattice reflections associated with tilt but also showed local correlations that give rise to symmetrically forbidden reflections and the kinematic origin of diffuse scattering.

A high throughput computational investigation of the solid solution mechanisms of actinides and lanthanides in zirconolite.

In this work, we perform a theoretical investigation of the actinide and lanthanide solid solution mechanisms of zirconolite-2M, prototypically CaZrTi2O7, as a candidate immobilisation matrix for plutonium. Solid solution energies were calculated using static atomistic simulations by means of the General Utility Lattice Program, for formulations of relevance to ceramic wasteform deployment, with substitution on the Ca2+ and Zr4+ sites by Ce4+, Pu4+, Th4+, and U4+, and appropriate charge balance by substitution of Al3+ or Fe3+ on Ti4+ sites. In simple solid solutions involving substitution on the Zr4+ site, we found that whereas substitution of Ce4+, U4+ and Pu4+ were energetically favoured, substitution of Th4+ was not energetically favoured. For more complex solid solutions involving Ce4+, Pu4+, Th4+, and U4+ substitution on the Ca2+ site, we found the most energetically favoured scheme involved co-substitution of Al3+ or Fe3+ on the five-fold co-ordinate Ti4+ site in the zirconolite-2M structure. Comparison of these computational data with experimental evidence, where available, demonstrated broad agreement. Consequently, this study provides useful insight into formulation design and the efficacy of Ce4+, U4+ and Th4+ as Pu4+ surrogates in zirconolite-2M ceramic wasteforms for plutonium disposition.

Validation of an Airborne Doppler Wind Lidar in Tropical Cyclones.

This study presents wind observations from an airborne Doppler Wind Lidar (ADWL) in 2016 tropical cyclones (TC). A description of ADWL measurement collection and quality control methods is introduced for the use in a TC environment. Validation against different instrumentation on-board the National Oceanographic and Atmospheric Administration's WP-3D aircraft shows good agreement of the retrieved ADWL measured wind speed and direction. Measurements taken from instruments such as the global positioning system dropsonde, flight-level wind probe, tail Doppler radar, and Stepped Frequency Microwave Radiometer are compared to ADWL observations by creating paired datasets. These paired observations represent independent measurements of the same observation space through a variety of mapping techniques that account for differences in measurement procedure. Despite high correlation values, outliers are identified and discussed in detail. The errors between paired observations appear to be caused by differences in the ability to capture various length scales, which directly relate to certain regions in a TC regime. In validating these datasets and providing evidence that shows the mitigation of gaps in 3-dimensional wind representation, the unique wind observations collected via ADWL have significant potential to impact numerical weather prediction of TCs.

Extracellular matrix proteins interact with cell-signaling pathways in modifying risk of achilles tendinopathy.

The aim of this study was to investigate interactions between variants within genes encoding components of the collagen fibril and components of cell-signaling pathways within the extracellular matrix, and determine the relative contribution of these variants to Achilles tendinopathy risk in a polygenic model. A total of 339 asymptomatic control participants and 179 participants clinically diagnosed with Achilles tendinopathy were genotyped for variants within six genes encoding components of the collagen fibril and three genes encoding components of cell-signaling pathways. Logistic regression, stepwise selection, and receiver operating characteristic curve (ROC) analysis was used to select and evaluate genetic interactions and determine the relative contribution of these variants to overall genetic risk. The strongest, best fit polygenic risk model included the variables sex, three COL27A1 variants (rs4143245; rs1249744; rs946053), COL5A1 rs12722, CASP8 rs1045485, and CASP8 rs2824129 with an area under the ROC curve of 0.737 and the maximum sum of sensitivity and specificity indicators equal to 134%. Significant interactions between genes encoding components of the collagen fibril and genes encoding components of the cell-signaling pathways modify risk of Achilles tendinopathy.

Functional and return to work outcomes following major trauma involving severe pelvic ring fracture.

BACKGROUND: There is limited evidence describing the long-term outcomes of severe pelvic ring fractures. The aim of this study was to describe the longer term independent living and return to work outcomes following severe pelvic ring fracture. METHODS: Adult survivors to discharge from two major trauma centres with AO/Tile type B and C fractures were followed up at 6, 12 and 24-months post-injury to capture functional (Glasgow Outcome Scale-Extended [GOS-E]) and return to work data. Multivariable, mixed effects models were used to identify predictors of outcome. RESULTS: A total of 111 of 114 (97%) cases were followed up. The mean (SD) age of participants was 41.9 (18.9) years, 77% were male, 81% were transport-related and 90% were multi-trauma patients. Further, 11% were managed conservatively, 10% with external fixation and 79% with open reduction and internal fixation. At 24 months, 77% were living independently (GOS-E > 4) and 59% had returned to work. Higher Injury Severity Scores (ISS) were associated with lower risk-adjusted odds of return to work (P = 0.04) and independent living (P = 0.06). Post-operative infection was associated with living independently (P = 0.02). CONCLUSION: Despite the severity of the injuries sustained, 77% of severe pelvic ring fracture patients were living independently and 59% had returned to work, 2-years post-injury. Fracture type and management were not key predictors of outcome. Large-scale multi-centre studies are needed to fully understand the burden of severe pelvic ring fractures and to guide clinical management.

Variants within the COMP and THBS2 genes are not associated with Achilles tendinopathy in a case-control study of South African and Australian populations.

Cartilage oligomeric matrix protein is a structural protein of the extracellular matrix, while thrombospondin-2 is a matricellular protein involved in cell-matrix interactions. Recent studies have shown that genetic variation is a significant risk factor for Achilles tendinopathy, and the genes encoding cartilage oligomeric matrix protein (COMP) and thrombospondin-2 (THBS2) were identified as good candidate genes for association with Achilles tendinopathy. This study aimed to test the association of sequence variants within these candidate genes with the risk of Achilles tendinopathy in participants from South Africa (SA) and Australia (AUS). Three-hundred and forty (133 SA; 207 AUS) control participants with no history of Achilles tendinopathy and 178 (94 SA; 84 AUS) participants clinically diagnosed with Achilles tendinopathy were genotyped for five single nucleotide polymorphisms within the COMP and THBS2 genes in this case-control study. There was no difference in genotype distributions between control and tendinopathy groups for either the THBS2 variants rs9505888, rs6422747 and rs9283850, or the COMP variants rs730079 and rs28494505 in the SA and AUS populations. As the selection of COMP and THBS2 as candidate genes was hypothesis driven, based on biological function, the possibility that other variants within these genes are associated with Achilles tendinopathy cannot be excluded.

Identification of dynamic prehospital changes with continuous vital signs acquisition.

OBJECTIVE: In most trauma registries, prehospital trauma data are often missing or unreliable because of the difficult dual task consigned to prehospital providers of recording vital signs and simultaneously resuscitating patients. The purpose of this study was to test the hypothesis that the analysis of continuous vital signs acquired automatically, without prehospital provider input, improves vital signs data quality, captures more extreme values that might be missed with conventional human data recording, and changes Trauma Injury Severity Scores compared with retrospectively compiled prehospital trauma registry data. METHODS: A statewide vital signs collection network in 6 medevac helicopters was deployed for prehospital vital signs acquisition using a locally built vital signs data recorder (VSDR) to capture continuous vital signs from the patient monitor onto a memory card. VSDR vital signs data were assessed by 3 raters, and intraclass correlation coefficients were calculated to test interrater reliability. Agreement between VSDR and trauma registry data was compared with the methods of Altman and Bland including corresponding calculations for precision and bias. RESULTS: Automated prehospital continuous VSDR data were collected in 177 patients. There was good agreement between the first recorded vital signs from the VSDR and the trauma registry value. Significant differences were observed between the highest and lowest heart rate, systolic blood pressure, and pulse oximeter from the VSDR and the trauma registry data (P< .001). Trauma Injury Severity Scores changed in 12 patients (7%) when using data from the VSDR. CONCLUSION: Real-time continuous vital signs monitoring and data acquisition can identify dynamic prehospital changes, which may be missed compared with vital signs recorded manually during distinct prehospital intervals. In the future, the use of automated vital signs trending may improve the quality of data reported for inclusion in trauma registries. These data may be used to develop improved triage algorithms aimed at optimizing resource use and enhancing patient outcomes.

Unified approach to multipolar polarisation and charge transfer for ions: microhydrated Na+.

Electrostatic effects play a large part in determining the properties of chemical systems. In addition, a treatment of the polarisation of the electron distribution is important for many systems, including solutions of monatomic ions. Typically employed methods for describing polarisable electrostatics use a number of approximations, including atom-centred point charges and polarisation methods that require iterative calculation on the fly. We present a method that treats charge transfer and polarisation on an equal footing. Atom-centred multipole moments describe the charge distribution of a chemical system. The variation of these multipole moments with the geometry of the surrounding atoms is captured by the machine learning method kriging. The interatomic electrostatic interaction can be computed using the resulting predicted multipole moments. This allows the treatment of both intra- and interatomic polarisation with the same method. The proposed method does not return explicit polarisabilities but instead, predicts the result of the polarisation process. An application of this new method to the sodium cation in a water environment is described. The performance of the method is assessed by comparison of its predictions of atomic multipole moments and atom-atom electrostatic interaction energies to exact results. The kriging models are able to predict the electrostatic interaction energy between the ion and all water atoms within 4 kJ mol(-1) for any of the external test set Na(+)(H2O)6 configurations.

Association of type XI collagen genes with chronic Achilles tendinopathy in independent populations from South Africa and Australia.

BACKGROUND: Type XI collagen, which is expressed in developing tendons and is encoded by the COL11A1, COL11A2 and COL2A1 genes, shares structural and functional homology with type V collagen, which plays an important role in collagen fibril assembly. We investigated the association of these three polymorphisms with Achilles tendinopathy (AT) and whether these polymorphisms interact with COL5A1 to modulate the risk of AT. METHODS: 184 participants diagnosed with chronic AT (TEN) and 338 appropriately matched asymptomatic controls (CON) were genotyped for the three polymorphisms. RESULTS: Although there were no independent associations with AT, the TCT pseudohaplotype constructed from rs3753841 (T/C), rs1676486 (C/T) and rs1799907 (T/A) was significantly over-represented (p=0.006) in the TEN (25.9%) compared with the CON (17.1%) group. The TCT(AGGG) pseudohaplotypes constructed using these type XI collagen polymorphisms and the functional COL5A1 rs71746744 (-/AGGG) polymorphism were also significantly over-represented (p<0.001) in the TEN (25.2%) compared with the CON (9.1%) group. DISCUSSION: The genes encoding structural and functionally related type XI (COL11A1 and COL11A2) and type V (COL5A1) collagens interact with one another to collectively modulate the risk for AT. Although there are no immediate clinical applications, the results of this study provide additional evidence that interindividual variations in collagen fibril assembly might be an important molecular mechanism in the aetiology of chronic AT.

Polymorphic variation within the ADAMTS2, ADAMTS14, ADAMTS5, ADAM12 and TIMP2 genes and the risk of Achilles tendon pathology: a genetic association study.

OBJECTIVES: Achilles tendon pathology (ATP) is a multifactorial condition for which genetic risk factors have been identified. The ADAMTS, ADAM12 and TIMP2 genes encode enzymes that are important regulators of tendon homeostasis. ADAMTS2 and ADAMTS14 proteins are procollagen N-propeptidases for pro-collagen type I, type II, and type III. ADAMTS2, like COL5A1, has been linked to Ehlers-Danlos syndrome. Variants within ADAMTS5 and ADAM12 have been associated with osteoarthritis. TIMP2, a metalloprotease inhibitor, maintains homeostasis in the ECM by inhibiting ADAM, ADAMTS and MMP functions. We sought to determine whether single nucleotide polymorphisms (SNPs) within the ADAMTS2, ADAMTS5, ADAMTS14, ADAM12 and TIMP2 genes were associated with the risk of ATP in two independent populations. DESIGN: 213 (115 ATP cases and 98 asymptomatic controls) South African Caucasian participants and 209 (60 ATP cases and 149 asymptomatic controls) Australian Caucasian participants were recruited for this case-control genetic association study. METHODS: All participants were genotyped using TaqMan technology for the ADAMTS2 rs1054480, ADAMTS5 rs226794, ADAMTS14 rs4747096, ADAM12 rs3740199, and TIMP2 rs4789932 SNPs. RESULTS: We report for the first time a significant (p=0.016) genotypic association between the TIMP2 rs4789932 variant and ATP in a combined Caucasian cohort. We also identify an interaction between the ADAMTS14 rs4747096 variant and age of onset of ATP (p=0.024). CONCLUSIONS: Our data show that DNA sequence variation within the TIMP2 gene is a risk factor for ATP in Caucasians. Furthermore, carriage of the ADAMTS14 rs4747096 GG variant appears to delay onset of the injury in the ATP group.

Investigation of variants within the COL27A1 and TNC genes and Achilles tendinopathy in two populations.

The TNC gene has previously been associated with Achilles tendinopathy (AT) in a South African population. The aims of this study were (i) to investigate the association of single nucleotide polymorphisms within the TNC gene, and the additional candidate gene, COL27A1, with AT in two populations, and (ii) to identify if there is a risk haplotype for AT in both populations. Three hundred and thirty nine healthy control participants (CON) and 179 participants clinically diagnosed with AT (TEN) from South Africa and Australia, were genotyped for variants: rs4143245, rs1249744, rs753085, rs946053 (COL27A1) and rs13321, rs2104772, rs1330363 (TNC). Haplotypes were inferred using the genotype data. The rs2104772 (p = 0.017) and rs1330363 (p = 0.020) variants within TNC showed a significant allele association with AT. The GCA haplotype (rs946053-rs13321-rs2104772) occurred significantly more frequently in TEN participants compared to CON (27% vs. 18%; p = 0.019). This study further implicates the genomic region containing the TNC and COL27A1 genes in influencing risk of AT, and maps the potential risk allele to a genetic interval flanked by rs946053 and rs2104772. This region may have functional effects on the transcription, structure and properties of tenascin-C and the alpha-1 chain of type XXVII collagen.

The apoptosis pathway and the genetic predisposition to Achilles tendinopathy.

Achilles tendinopathy (AT) is a degenerative condition for which several risk factors have been implicated including components of the inflammatory pathway. The aim was to assess functional variants within genes encoding components of the apoptosis signaling cascade and the effectiveness of a polygenic apoptosis profile to capture tendinopathy (TEN) risk. A total of 358 unaffected control (CON) participants [159 South Africa (SA CON) and 199 Australia (AUS CON)] and 166 affected AT (TEN) participants (87 SA TEN and 79 AUS TEN) were genotyped for four variants [CASP8 (rs384129), CASP8 (rs1045485), NOS3 (rs1799983), and NOS2 (rs2779249)]. Logistic regression was used to derive risk models for AT. A receiver operator characteristic (ROC) curve was plotted to determine the effectiveness of a model to capture AT risk. This study indicates the independent association of CASP8_rs1045485 and CASP8_rs3834129 as well as their haplotype with AT risk and the identification of an optimal model which included genetic loci CASP8_rs384129 and CASP8_rs1045485 together with sex to capture AT risk in both SA and AUS. Collectively, these results further implicate the apoptosis signaling cascade as one of the biological pathways involved in the development of AT.

Short- and long-term exposure of articular cartilage to curcumin or quercetin inhibits aggrecan loss.

The aim of this study was to determine if curcumin and quercetin inhibit induced aggrecan loss from bovine articular cartilage explants given that these polyphenols have been shown to suppress the expression of matrix-degrading enzymes. The kinetics of loss of ³5S-aggrecan and the loss of total aggrecan in cartilage explants maintained in catabolic medium containing either 1 µM retinoic acid or 50 ng/ml interleukin (IL)-1α were studied in the presence of either 1-25 µM curcumin or 10-50 µM quercetin. The reversibility of catabolism of ³5S-aggrecan was also studied in catabolically stimulated cultures treated with 25 µM curcumin or 50 µM quercetin for the initial 4-5 days of culture followed by 10-15 days of culture in catabolic medium in the absence of either polyphenol. Curcumin and quercetin suppressed ³5S-aggrecan and total aggrecan loss from the explants in a dose-dependent manner. When the exposure of explants to curcumin or quercetin was limited to the first 4-5 days of culture, the suppression of ³5S-aggrecan loss was maintained in the extended culture period when the tissue was stimulated with either retinoic acid or IL-1α. Quercetin suppressed IL-1α-stimulated expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4. Curcumin suppressed retinoic acid stimulated expression of ADAMTS-5, and both polyphenols suppressed basal expression of ADAMTS-5. The ability of curcumin and quercetin to protect cartilage from stimulated aggrecan loss and to maintain this protection posttreatment may, at least in part, be due to the suppression of gene expression of ADAMTS-4 and -5.

A Multi-Objective Approach to Force Field Optimization: Structures and Spin State Energetics of d(6) Fe(II) Complexes.

The next generation of force fields (FFs), regardless of the accuracy of the potential energy representation, will always have parameters that must be fitted in order to reproduce experimental and/or ab initio data accurately. Single objective methods have been used for many years to automate the obtaining of parameters, but this leads to ambiguity. The solution depends on the chosen weights and is therefore not unique. There have been few advances in solving this problem, which thus remains a major hurdle for the development of empirical FF methods. We propose a solution based on multi-objective evolutionary algorithms (MOEAs). MOEAs allow the FF to be tuned against the desired objectives and offer a powerful, efficient, and automated means to reparameterize FFs, or even discover the parameters for a new potential. Here, we illustrate the application of MOEAs by reparameterizing the ligand field molecular mechanics (LFMM) FF recently reported for modeling spin crossover in iron(II)-amine complexes (Deeth et al. J. Am. Chem. Soc.2010, 132, 6876). We quickly recover the performance of the original parameter set and then significantly improve it to reproduce the geometries and spin state energy differences of an extended series of complexes with RMSD errors in Fe-N and N-N distances reduced from 0.06 Å to 0.03 Å and spin state energy difference RMSDs reduced from 1.5 kcal mol(-1) to 0.2 kcal mol(-1). The new parameter sets highlight, and help resolve, shortcomings both in the non-LFMM FF parameters and in the interpretation of experimental data for several other Fe(II)N6 amine complexes not used in the FF optimization.

Effectiveness of intra-articular hyaluronan (Synvisc, hylan G-F 20) for the treatment of first metatarsophalangeal joint osteoarthritis: a randomised placebo-controlled trial.

OBJECTIVES: To evaluate the effectiveness of a single intra-articular injection of hylan G-F 20 (Synvisc) for symptomatic first metatarsophalangeal joint (MTPJ) osteoarthritis (OA). METHODS: Participants (n = 151) with symptomatic first MTPJ OA were randomly allocated to receive up to 1 ml intra-articular injection of either hylan G-F 20 or placebo (saline). Participants and assessors were blinded. Outcomes were evaluated at 1, 3 and 6 months after injection. The primary outcome measurement was the foot pain domain of the Foot Health Status Questionnaire (FHSQ) at 3 months. Secondary outcome measurements were foot function assessed via the FHSQ, first MTPJ pain and stiffness, magnitude of symptom change, global satisfaction, health-related quality of life (assessed using the Short-Form-36 version two), first MTPJ dorsiflexion range of motion, hallux plantar flexion strength, use of pain-relieving medication or co-interventions and changes in plantar pressures. RESULTS: No statistically significant differences in foot pain were found between the groups at 3 months. There were few statistically significant differences in the secondary outcome measures. Overall, the incidence of adverse effects was not significantly different between groups. CONCLUSIONS: An intra-articular injection of hylan G-F 20 is no more effective than a placebo in reducing symptoms in people with symptomatic first MTPJ OA.Australian New Zealand Clinical Trials Registry: number ACTRN12607000654459.

A pathway-based approach investigating the genes encoding interleukin-1ß, interleukin-6 and the interleukin-1 receptor antagonist provides new insight into the genetic susceptibility of Achilles tendinopathy.

OBJECTIVES: Achilles tendinopathy (AT) is a multifactorial condition for which genetic risk factors have been identified. A pathway-based approach was used to investigate genes within the inflammatory pathway. METHODS: Functional polymorphisms within IL-1ß (-31T→C and -511C→T), IL-1RN (variable number tandem repeat) and IL-6 (-172G→C) were investigated for associations with AT in a South African (SA) and Australian (AUS) case-control studies. A total of 369 (161 SA and 208 AUS) asymptomatic control participants (CON) and 175 (90 SA and 85 AUS) participants with AT (TEN) were genotyped. Allele combinations were constructed using the above polymorphisms in combination with the COL5A1 BstUI RFLP. RESULTS: Independently, no associations were observed between any of the polymorphisms tested and risk of TEN. The allele combinations of five polymorphisms were, however, found to have a highly significant relationship with AT (p=0.005), after adjusting for gender and country (SA or AUS). CONCLUSIONS: Variations within the interleukin genes and the COL5A1 BstUI CC genotype are collectively significantly associated with risk of AT. This research emphasises that a pathway-based genetic association study may be a more effective approach to capture and understand the genetic risk factors underlying the multifactorial conditions, such as AT.

Change in proteoglycan metabolism is a characteristic of human patellar tendinopathy.

OBJECTIVE: To determine differences in the metabolism of proteoglycans and the gene expression of proteinases and their inhibitors between patellar tendons exhibiting chronic overuse tendinopathy and normal patellar tendons in humans. METHODS: Rates of loss and synthesis of proteoglycans were determined. Radiolabeled and total proteoglycans retained in and lost from the tissue were analyzed by fluorography and Western blotting. Levels of messenger RNA for matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-9, MMP-13, ADAMTS-1, ADAMTS-4, ADAMTS-5, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, TIMP-3, and TIMP-4 were determined in fresh tissue. RESULTS: The rate of loss of (35)S-labeled proteoglycans was greater in abnormal tendons, as was the rate of synthesis of proteoglycans. Fluorography and Western blotting revealed the presence of greater amounts of large proteoglycans (aggrecan and versican) in abnormal tendons, and these proteoglycans were rapidly lost from the matrix of abnormal tendons. There was no significant difference in the expression of ADAMTS-1, ADAMTS-4, ADAMTS-5, MMP-1, MMP-2, MMP-3, MMP-13, TIMP-2, TIMP-3, or TIMP-4. There was a significant increase in the expression of MMP-9 and TIMP-1 in abnormal tendons. CONCLUSION: Our findings suggest that a change in the proteoglycan content of the extracellular matrix in abnormal tendons results from the altered metabolism of the cells, reflected in the enhanced synthesis of the large proteoglycans aggrecan and versican, and does not appear to result from changes at the level of gene expression.

Risk factors for organ dysfunction and failure in patients with acute traumatic cervical spinal cord injury.

BACKGROUND: Traumatic injuries to the cervical spine cause significant disability. Much of the morbidity and mortality that occurs in patients afflicted with cervical spinal cord injury (SCI) occurs early after injury due to primary neurologic dysfunction, systemic inflammation, concomitant injuries, treatments to prevent and ameliorate secondary insults, and prolonged immobilization. This study was undertaken to determine the incidence of organ dysfunction and failure using validated measures: the Multiple Organ Dysfunction Score (MODS) and the Sequential Organ Failure Assessment (SOFA). We also sought to determine if certain patient or injury characteristics were associated with the development of organ dysfunction and failure. METHODS: All patients who sustained isolated blunt cervical SCIs admitted to the R Adams Cowley Shock Trauma Center over a 15-month period were identified. American Spinal Injury Association (ASIA) motor scores, ASIA impairment scale (AIS) scores, and level of injury were recorded. Admission, first daily, worst daily, and aggregate MOD and SOFA scores were assigned for each of six organ systems. A P < 0.05 was considered significant for all statistical tests. RESULTS: Of 1,028 patients admitted with blunt spine injuries between January, 2007 and March, 2008, 40 patients were identified with an isolated cervical SCI that required an ICU length of stay (LOS) >24 h. Organ failure of at least one organ system occurred in 75% of patients as calculated by MOD score and 85% of patients calculated using SOFA criteria. Multiple organ failure was found in 55% by MOD and 62.5% by SOFA scores. The most frequent system to fail was the cardiovascular system by aggregate MODS (84%), while the respiratory system was the most frequently failed system by aggregate SOFA criteria (70%). There was a strong inverse correlation between ASIA motor score and aggregate MODS and SOFA scores (r = -0.56, P = 0.0002 and r = -0.51, P = 0.0009). AIS was also found to be inversely correlated with the development of organ failure (r = -0.47, P = 0.002 and r = -0.45, P = 0.004) while anatomic level of injury was found to correlate poorly with the incidence of organ failure (r = -0.11, P = 0.5 and r = -0.10, P = 0.5). Only ASIA motor score was significantly associated with sum aggregate organ dysfunction scores when controlling for age and injury severity score (parameter estimate = -0.082, P = 0.0005 for MODS and parameter estimate = -0.057, P = 0.006 for SOFA). CONCLUSIONS: This study is the first to describe the incidence of organ dysfunction and failure in patients with isolated acute traumatic cervical SCI using validated organ system dysfunction scores. Respiratory, cardiovascular, neurologic, renal, hepatic, and hematologic dysfunction occurred commonly both on admission and over the ICU stay. Respiratory, cardiovascular, and neurologic failure were frequently found, while renal, hepatic, and hematologic failures were uncommon. Multiple organ failure occurred in the majority of patients. ASIA motor score and AIS were found to strongly correlate with the development of organ dysfunction and failure. Level of injury should be used with caution when describing the risk of complications and the need for medical interventions.

Components of the transforming growth factor-beta family and the pathogenesis of human Achilles tendon pathology--a genetic association study.

OBJECTIVES: Achilles tendon pathology is a multifactorial condition for which various risk factors, including genetic factors, have been identified. Gene transfection of two members of the TGF-ß family, TGF-ß1 and growth/differentiation factor-5 (GDF-5), have been shown to enhance tendon repair and mechanical strength within animal Achilles tendon injury models. The objective of this study was to investigate whether two functional 5' untranslated region (UTR) single nucleotide polymorphisms (SNPs), the TGFB1 rs1800469 variant and the GDF5 rs143383 variant, were associated with ATP within an Australian ('AUS') and a South African ('SA') case-control cohort. METHODS: One hundred and seventy-one subjects (58 AUS and 112 SA) with Achilles tendon pathology (ATP group) and 235 (142 AUS and 96 SA) asymptomatic control (CON group) subjects were genotyped for the selected SNPs using custom-designed Taqman assays. A χ(2)-analysis or Fisher's exact test was used to analyse any differences in the genotype and allele frequencies. Significance was accepted when P < 0.05. RESULTS: There were no significant TGFB1 rs1800469 genotype (P = 0.491) or allele (P = 0.400) frequency differences between the ATP and CON groups. The TT genotype of the GDF5 rs143383 variant was significantly over-represented in the ATP group of the AUS cohort [P = 0.011; odds ratio (OR) = 2.24; 95% CI 1.21, 4.16], and when the AUS and SA cohorts were combined (P = 0.004; OR = 1.82; 95% CI 1.23, 2.74). CONCLUSIONS: In conclusion, this study suggests that individuals with a TT genotype of the functional GDF5 rs143383 variant have twice the risk of developing ATP. This finding highlights a role of GDF-5 in the pathogenesis of Achilles tendon pathology.