Compact X-Band Electron Linac for Radiotherapy and Security Applications.

RadiaBeam has developed a 6 MeV accelerator that is compact and light enough to be placed on a robotic arm or light truck. The main drivers of size and weight in conventional accelerators are the power source and the shielding. Small dimensions are enabled by operation at 9.3 GHz frequency (X-band), which allows reducing the size and weight of all accelerator components. Thanks to the robust design of the accelerating structure, the accelerator can be used as a source for novel cargo inspection and radiotherapy techniques. In this paper, we present the linac design and its components, as well the results of the experimental demonstration of beam acceleration.

The confidence of undergraduate dental students when carrying out prosthodontic treatment and their perception of the quality of prosthodontic education.

INTRODUCTION: Despite the falling number of edentulous patients within the UK, there is still a large demand for the provision of removable prostheses. On qualification, dentists should have the knowledge and skills to provide these prostheses, but previous studies have shown that final-year dental undergraduate confidence in treating denture patients is lacking. AIM: To explore undergraduate dental student confidence whilst carrying out prosthodontic treatment, and to explore their perceptions of the quality of their prosthodontic education. METHOD: An anonymous questionnaire was distributed to all (n=203) dental undergraduates in Years 3 to 5 at the University of Bristol. The questionnaire utilised a range of data collection methods including confidence interval ranked responses and qualitative measures. The data were analysed using SPSS. RESULTS: The response rate was 51%. Undergraduate perception of confidence increased throughout the years of study (P<.001). There was also an increase in the number of partial and complete denture cases treated as students progressed through the course (P<.001). Overall, students were satisfied with their prosthodontic teaching, although students thought that too much time was allocated to laboratory teaching, and that increasing their clinical experience would be most beneficial in increasing their confidence levels. CONCLUSION: Student confidence in carrying out prosthetic treatment increased as students progressed through the course, and confidence levels would be increased further with increased clinical experience.

Using THz time-scale infrared spectroscopy to examine the role of collective, thermal fluctuations in the formation of myoglobin allosteric communication pathways and ligand specificity.

In this investigation we use THz time-scale spectroscopy to conduct an initial set of studies on myoglobin with the aim of providing further insight into the global, collective thermal fluctuations in the protein that have been hypothesized to play a prominent role in the dynamic formation of transient ligand channels as well as in shaping the molecular level basis for ligand discrimination. Using the two ligands O2 and CO, we have determined that the perturbation from the heme-ligand complex has a strong influence on the characteristics of the myoglobin collective dynamics that are excited upon binding. Further, the differences detected in the collective protein motions in Mb-O2 compared with those in Mb-CO appear to be intimately tied with the pathways of long-range allosteric communication in the protein, which ultimately determine the trajectories selected by the respective ligands on the path to and from the heme-binding cavity.

THz time scale structural rearrangements and binding modes in lysozyme-ligand interactions.

Predicting the conformational changes in proteins that are relevant for substrate binding is an ongoing challenge in the aim of elucidating the functional states of proteins. The motions that are induced by protein-ligand interactions are governed by the protein global modes. Our measurements indicate that the detected changes in the global backbone motion of the enzyme upon binding reflect a shift from the large-scale collective dominant mode in the unbound state towards a functional twisting deformation that assists in closing the binding cleft. Correlated motion in lysozyme has been implicated in enzyme function in previous studies, but detailed characterization of the internal fluctuations that enable the protein to explore the ensemble of conformations that ultimately foster large-scale conformational change is yet unknown. For this reason, we use THz spectroscopy to investigate the picosecond time scale binding modes and collective structural rearrangements that take place in hen egg white lysozyme (HEWL) when bound by the inhibitor (NAG)3. These protein thermal motions correspond to fluctuations that have a role in both selecting and sampling from the available protein intrinsic conformations that communicate function. Hence, investigation of these fast, collective modes may provide knowledge about the mechanism leading to the preferred binding process in HEWL-(NAG)3. Specifically, in this work we find that the picosecond time scale hydrogen-bonding rearrangements taking place in the protein hydration shell with binding modify the packing density within the hydrophobic core on a local level. These localized, intramolecular contact variations within the protein core appear to facilitate the large cooperative movements within the interfacial region separating the α- and ß- domain that mediate binding. The THz time-scale fluctuations identified in the protein-ligand system may also reveal a molecular mechanism for substrate recognition.

Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis.

Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.

Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

Size at birth is an important determinant of perinatal survival and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life. Common genetic variation that regulates fetal growth could therefore influence perinatal survival and predispose to the development of adult disease. We have tested the insulin gene (INS) variable number of tandem repeats (VNTR) locus, which in Caucasians has two main allele sizes (class I and class III; ref. 3), as a functional candidate polymorphism for association with size at birth, as it has been shown to influence transcription of INS (refs 3-5). In a cohort of 758 term singletons (Avon Longitudinal Study of Pregnancy and Childhood; ALSPAC) followed longitudinally from birth to 2 years, we detected significant genetic associations with size at birth: class III homozygotes had larger mean head circumference (P=0.004) than class I homozygotes. These associations were amplified in babies who did not show postnatal realignment of growth (45%), and were also evident for length (P=0.015) and weight (P=0.009) at birth. The INS VNTR III/II genotype might have bestowed a perinatal survival during human history by conferring larger size at birth. Common genetic variation of this kind may contribute to reported associations between birth size and adult disease.

Review of the national usage of antibiotics in arthroplasty surgery: a need for evidence-based prescribing.

INTRODUCTION: Surgical site infections (SSI) remain one of the most serious complications of arthroplasty surgery. The role of antibiotic prophylaxis in preventing SSI post-arthroplasty is well established. However, there is considerable heterogeneity in prophylactic prescribing across the United Kingdom (UK), which is contradicted by the contemporaneous evidence. This descriptive study aimed to compare the current first-line antibiotic recommendations across hospitals in the UK and The Republic of Ireland for elective arthroplasty procedures. METHODS: The MicroGuide mobile phone application was used to access hospital antibiotic guidelines. First-line antibiotic recommendation and dosing regimen for primary elective arthroplasties were recorded. FINDINGS: A total of nine distinct antibiotic regimens were identified through our search. The most frequently used first-line antibiotic was cefuroxime. This was recommended by 30 of the 83 (36.1%) hospitals in the study. This was followed by a combination of flucloxacillin and gentamicin, which was used by 38 of 124 (31%) hospitals. There was also significant heterogeneity in dosing regimens. A single prophylactic dose was most commonly recommended (52%); 4% of hospitals recommended two prophylactic doses, 19% three doses and 23% four doses. CONCLUSIONS: Single-dose prophylaxis is recognised as at least noninferior to multiple-dose prophylaxis in primary arthroplasty. There is considerable variation in the local antibiotic recommendations for surgical site prophylaxis post-primary arthroplasty surgery, with respect to both recommended first-line antibiotic and dosing regimens. With increasing emphasis on the importance of antibiotic stewardship and the emergence of antibiotic resistance, this study highlights the need for an evidence-based approach to prophylactic dosing across the UK.

The pattern of paediatric trauma on operations.

OBJECTIVES: Recent military campaigns in Iraq and Afghanistan have resulted in the treatment of children in British Medical facilities. In order to determine how care for children may develop in the future, it is necessary to understand the current situation. The aim of this article is to examine the pattern of paediatric trauma on recent operations in Iraq and Afghanistan. METHODS: Data was requested from the Joint Theatre Trauma Registry, held at the Royal Centre for Defence Medicine in Birmingham, on all trauma calls for patients aged under 16 between the dates 21/3/03 and 31/8/09. Data included age, gender, theatre of operation, injury mechanism and type, trauma scores and destination of the child. RESULTS: 176 children were identified with 16.5% from Iraq and 83.5% from Afghanistan. The overall survival rate was 88.6% with survival rates in Iraq of 89.7% and in Afghanistan of 88.4%. Males accounted for 66.5% of admissions and the commonest age group was age 6-8 years. In 59.1% of total admissions the mechanism of injury was related to explosives. This differed between theatres with explosive injury causing 27.6% of admissions in Iraq and 63.5% in Afghanistan. Injury Severity Scores (ISS) showed equal numbers of minor and severe injuries with fewer moderately injured patients. The median ISS of all data was nine. The median ISS from Iraq was 16 and the median ISS from Afghanistan was nine. CONCLUSIONS: The treatment of children in British medical facilities whilst deployed on operations is likely to continue. An assessment of the injury patterns of paediatric patients on current deployments allows development of training and an understanding of logistic requirements. Data collection will also need to be adapted to meet the needs of paediatric patients. These remain issues that are being addressed by the Defence Medical Services.

Paediatric trauma management on deployment.

There remains a significant paediatric workload through the military hospital in Camp Bastion. In this paper the authors review and discuss particular problems with resuscitation, investigation, anaesthetic and surgical issues in dealing with children suffering from ballistic injuries. Personal experience and recent papers are used for a qualitative analysis of difficult decisions in the management of paediatric ballistic trauma. Key questions are answered in separate paragraphs for each specialty. The information described in this paper should assist any deployed physician deal with paediatric casualties particularly if they are unaccustomed to paediatric patients in their normal practice.

Two Fatalities Involving Mebroqualone.

Mebroqualone is an analogue of methaqualone, and there is a very little published information regarding the toxicity of this designer drug. We describe two cases with non-lethal levels of mebroqualone in blood collected at autopsy. Case 1 was an accidental death that involved a house fire, and the decedent was found to have a blood mebroqualone concentration of 10,228 ng/mL. Case 2 was a completed suicide by train, and the decedent was found to have a blood concentration of 115 ng/mL. To our knowledge, this is the first report in the scientific literature to compare two postmortem blood concentrations of mebroqualone. Mebroqualone was extracted from postmortem blood using a simple liquid-liquid extraction procedure and analyzed via gas chromatography-mass spectrometry.

Current epidural practice--results of a survey of military anaesthetists.

OBJECTIVES: As epidurals are now used for pain relief on deployment a survey was conducted to look at the current epidural practice of U.K. military anaesthetists. The aim was to identify any potential issues with regard to equipment and training to allow future development ofpre-deployment training. METHODS: An Internet based survey was carriedout. All military anaesthetistswere sent an e-mail containing a link to the survey and the results of those who responded were analysed. RESULTS: A total of 49 surveys were completed. 78% of respondents carried out epidurals more than once a month, in a wide range of specialities. There was considerable variation in methods of securing epidurals and in drug choice amongst respondents. CONCLUSIONS: The results of this survey show that whilst epidurals are commonly carried out amongst military anaesthetists during their U.K. practice, there is significant variation within the practice. Areas have been identified for development of educational courses, for example methods of securing epidurals, and these have already been acted upon.

Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD).

OBJECTIVE: Homozygous mutations in the gene encoding the pituitary transcription factor PROP1 are associated with combined pituitary hormone deficiency (CPHD) in both mice and humans with a highly variable phenotype with respect to the severity and time of initiation of pituitary hormone deficiency. We have ascertained three pedigrees with PROP1 mutations from a large cohort of patients with variable degrees of CPHD who were screened for mutations in PROP1. RESULTS: Affected individuals from all three pedigrees were found to harbour novel PROP1 mutations. We have identified two siblings in one family who were homozygous for an intronic mutation (c.343-11C > G) that disrupts correct splicing resulting in the loss of exon 3 from the PROP1 transcript. Two siblings from a second, unrelated family are compound heterozygotes for two point mutations in the coding region, a missense mutation (p.R125W) that leads to impaired transcriptional activation, and a deletion of a single nucleotide (c.310delC) resulting in a frameshift and nonfunctional mutant protein. Additionally, we identified a homozygous deletion of the PROP1 locus in two patients born to consanguineous parents. CONCLUSION: Mutations in PROP1 are a frequent cause of familial CPHD. We have described four novel mutations in PROP1 in 3 pedigrees, all resulting in PROP1 deficiency by different mechanisms. The phenotypic variation observed in association with PROP1 mutations both within and between families, together with the evolving nature of hormone deficiencies and sometimes changing pituitary morphology indicates a need for continual monitoring of these patients.

Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition.

Rapamycin, a natural product inhibitor of the Raptor-mammalian target of rapamycin complex (mTORC1), is known to induce Protein kinase B (Akt/PKB) Ser-473 phosphorylation in a subset of human cancer cell lines through inactivation of S6K1, stabilization of insulin receptor substrate (IRS)-1, and increased signaling through the insulin/insulin-like growth factor-I/phosphatidylinositol 3-kinase (PI3K) axis. We report that A-443654, a potent small-molecule inhibitor of Akt serine/threonine kinases, induces Akt Ser-473 phosphorylation in all human cancer cell lines tested, including PTEN- and TSC2-deficient lines. This phenomenon is dose-dependent, manifests coincident with Akt inhibition and likely represents an alternative, rapid-feedback pathway that can be functionally dissociated from mTORC1 inhibition. Experiments performed in TSC2-/- cells indicate that TSC2 and IRS-1 cooperate with, but are dispensable for, A-443654-mediated Akt phosphorylation. This feedback event does require PI3K activity, however, as it can be inhibited by LY294002 or wortmannin. Small interfering RNA-mediated knockdown of mTOR or Rictor, components of the rapamycin-insensitive mTORC2 complex, but not the mTORC1 component Raptor, also inhibited Akt Ser-473 phosphorylation induced by A-443654. Our data thus indicate that Akt phosphorylation and activity are coupled in a manner not previously appreciated and provide a novel mode of Akt regulation that is distinct from the previously described rapamycin-induced IRS-1 stabilization mechanism.

One-Day Behavioral Intervention for Distressed Veterans with Migraine: Results of a Multimethod Pilot Study.

Introduction: Migraine, a chronic neurological disorder characterized by episodic severe headache pain and functional impairment, affects approximately 12% of the general US population. Veterans returning from Iraq or Afghanistan have two to four times the incidence of migraine of the general population. Veterans with migraines are more than twice as likely to have comorbid psychiatric conditions as veterans without migraines, with depression and post-traumatic stress disorder being most prevalent. This psychiatric-migraine comorbidity is of major public health significance, as it leads to decreased quality of life, poorer response to migraine and mental health treatment, and overall worse prognosis. Unfortunately, acceptable and effective treatments for these comorbid problems have rarely been investigated. The aims of this study are to examine the acceptability, feasibility, and preliminary efficacy of a 1-d acceptance and commitment therapy (ACT) plus Migraine Education workshop. Method: Twenty-five veterans with migraines and co-occurring depression and/or anxiety completed the 1-d ACT plus Migraine Education workshop. Veterans completed assessments of depressive and anxiety symptoms, general functioning, headache-related disability, and ACT-specific skills at baseline and 3 mo after the workshop. Changes from baseline to 3-mo follow-up on the self-report and clinician-rated measures were assessed using the paired t-test and Wilcoxon signed-rank test. Veterans also completed semistructured qualitative interviews documenting their experiences with the workshop 2 wk and 3 mo following the intervention. Qualitative data were analyzed via directed content analysis. Individual codes were aggregated into larger themes agreed upon by consensus. Results: At 3-mo follow-up, veterans significantly improved in depressive and anxiety symptoms, general functioning, and headache-related disability compared with baseline. Additionally, veterans significantly improved in pain acceptance and engagement in valued life areas. In interviews, veterans indicated that the migraine education helped them feel more knowledgeable about their condition, and this empowered them to better manage their headaches, including talking to their physician about medication adjustments. The ACT component led to greater awareness of the role stress plays in exacerbating pain and ways to manage this stress, including greater acceptance and greater engagement in valued life activities. For some, however, the role of stress in exacerbating migraines needed to be highlighted more. Veterans appreciated being in a group with other veterans with similar health difficulties and wanted this to be incorporated into ongoing care at the Veterans Affairs medical center. The patient education manuals were useful to the veterans, with some referring to them during the months following the workshop. Conclusion: Findings of this small trial have important implications pending replication in a more rigorously designed large-scale study. A 1-d ACT plus Migraine Education workshop is an acceptable and feasible treatment approach for veterans with migraines and significant distress. Significantly reduced distress and disability, as well as improved coping skills, suggest that veterans were activated to engage more fully in their lives and clinical care. The availability of an effective transdiagnostic intervention that can be completed in 1 d is particularly valuable for veterans who have multiple comorbid conditions and who encounter practical barriers to engaging in the usual prescribed weekly therapy treatments.

A comparison of two molecular methods for diagnosing leptospirosis from three different sample types in patients presenting with fever in Laos.

OBJECTIVES: To compare two molecular assays (rrs quantitative PCR (qPCR) versus a combined 16SrRNA and LipL32 qPCR) on different sample types for diagnosing leptospirosis in febrile patients presenting to Mahosot Hospital, Vientiane, Laos. METHODS: Serum, buffy coat and urine samples were collected on admission, and follow-up serum ∼10 days later. Leptospira spp. culture and microscopic agglutination tests (MAT) were performed as reference standards. Bayesian latent class modelling was performed to estimate sensitivity and specificity of each diagnostic test. RESULTS: In all, 787 patients were included in the analysis: 4/787 (0.5%) were Leptospira culture positive, 30/787 (3.8%) were MAT positive, 76/787 (9.7%) were rrs qPCR positive and 20/787 (2.5%) were 16SrRNA/LipL32 qPCR positive for pathogenic Leptospira spp. in at least one sample. Estimated sensitivity and specificity (with 95% CI) of 16SrRNA/LipL32 qPCR on serum (53.9% (33.3%-81.8%); 99.6% (99.2%-100%)), buffy coat (58.8% (34.4%-90.9%); 99.9% (99.6%-100%)) and urine samples (45.0% (27.0%-66.7%); 99.6% (99.3%-100%)) were comparable with those of rrs qPCR, except specificity of 16SrRNA/LipL32 qPCR on urine samples was significantly higher (99.6% (99.3%-100%) vs. 92.5% (92.3%-92.8%), p <0.001). Sensitivities of MAT (16% (95% CI 6.3%-29.4%)) and culture (25% (95% CI 13.3%-44.4%)) were low. Mean positive Cq values showed that buffy coat samples were more frequently inhibitory to qPCR than either serum or urine (p <0.001). CONCLUSIONS: Serum and urine are better samples for qPCR than buffy coat, and 16SrRNA/LipL32 qPCR performs better than rrs qPCR on urine. Quantitative PCR on admission is a reliable rapid diagnostic tool, performing better than MAT or culture, with significant implications for clinical and epidemiological investigations of this global neglected disease.

RNAi-based screening of the human kinome identifies Akt-cooperating kinases: a new approach to designing efficacious multitargeted kinase inhibitors.

Tumors comprise genetically heterogeneous cell populations, whose growth and survival depend on multiple signaling pathways. This has spurred the development of multitargeted therapies, including small molecules that can inhibit multiple kinases. A major challenge in designing such molecules is to determine which kinases to inhibit in each cancer to maximize efficacy and therapeutic index. We describe an approach to this problem implementing RNA interference technology. In order to identify Akt-cooperating kinases, we screened a library of kinase-directed small interfering RNAs (siRNAs) for enhanced cancer cell killing in the presence of Akt inhibitor A-443654. siRNAs targeting casein kinase I gamma 3 (CSNK1G3) or the inositol polyphosphate multikinase (IPMK) significantly enhanced A-443654-mediated cell killing, and caused decreases in Akt Ser-473 and ribosomal protein S6 phosphorylation. Small molecules targeting CSNK1G3 and/or IPMK in addition to Akt may thus exhibit increased efficacy and have the potential for improved therapeutic index.

A meta-analysis of the placebo response in complementary and alternative medicine trials of irritable bowel syndrome.

Among patients with irritable bowel syndrome (IBS) enrolled in clinical trials of conventional medical therapy, the placebo response rate is high. IBS patients also frequently use complementary and alternative medicine (CAM), which may act through an 'enhanced placebo effect'. The purpose of this study was to estimate the magnitude of the placebo response rate in CAM trials for IBS and to identify factors that influence this response. We performed a systematic review and meta-analysis of randomized, placebo-controlled clinical trials of CAM therapies for IBS identified from MEDLINE/EMBASE/PsychLIT databases from 1970 to 2006. Placebo and active treatment response rates for global symptom improvement were assessed. Nineteen studies met the inclusion criteria. The pooled estimate of the placebo response rate was 42.6% (95% confidence interval, 38.0-46.5%). Significant heterogeneity existed across trials (range 15.0-72.2%, P < 0.00001). Higher placebo response rates correlated with a longer duration of treatment (r = 0.455, P = 0.05) and a greater number of office visits (r = 0.633, P = 0.03). Among IBS patients in CAM trials, the placebo response rate is high. That this rate is similar in magnitude to that seen in conventional medicine trials suggests that the placebo response is independent of the type of therapy used and that it is not particularly 'enhanced' in CAM trials.

Skin chemistry of nudibranchs from the west coast of North America.

The Pacific coastline of North America extends from Alaska in the north to Panama in the south. Chemical studies of skin extracts from nudibranchs collected along this coast have resulted in the isolation of over 100 chemically diverse secondary metabolites. The majority of the compounds are terpenoids, but polyketides, steroids, and alkaloids have also been found. Observations of geographic variation in metabolite content and stable isotope-feeding experiments have provided information about the de novo biosynthetic or dietary sequestration origins of the skin extract metabolites.

Degree of facial and body terminal hair growth in unselected black and white women: toward a populational definition of hirsutism.

CONTEXT: Hirsutism (i.e. facial and body terminal hair growth in a male-like pattern in women) is the principal clinical sign of hyperandrogenism, although its definition remains unclear. OBJECTIVE: The purposes of the present study were to define 1) the degree of facial and body terminal hair, as assessed by the modified Ferriman-Gallwey (mFG) score, in unselected women from the general population; 2) the effect of race (Black and White) on the same; and 3) the normative cutoff values. DESIGN AND SETTING: We conducted a prospective observational study at a tertiary academic medical center. PATIENTS/PARTICIPANTS: Participants included 633 unselected White (n = 283) and Black (n = 350) women presenting for a preemployment physical exam. INTERVENTIONS: Interventions included history and physical examination. MAIN OUTCOME MEASURES: Terminal body hair growth was assessed using the mFG scoring system; nine body areas were scored from 0-4 for terminal hair growth distribution. RESULTS: The mFG scores were not normally distributed; although cluster analysis failed to identify a natural cutoff value or clustering of the population, principal component and univariate analyses denoted two nearly distinct clusters that occurred above and below an mFG value of 2, with the bulk of the scores below. Overall, an mFG score of at least 3 was observed in 22.1% of all subjects (i.e. the upper quartile); of these subjects, 69.3% complained of being hirsute, compared with 15.8% of women with an mFG score below this value, and similar to the proportion of women with an mFG score of at least 8 who considered themselves to be hirsute (70.0%). Overall, there were no significant differences between Black and White women. CONCLUSIONS: Our data indicate that the prevalence and degree of facial and body terminal hair growth, as assessed by the mFG score, is similar in Black and White women and that an mFG of at least 3 signals the population of women whose hair growth falls out of the norm.

Does anterior cruciate ligament reconstruction restore normal knee kinematics?: A prospective MRI analysis over two years.

This prospective study used magnetic resonance imaging to record sagittal plane tibiofemoral kinematics before and after anterior cruciate ligament reconstruction using autologous hamstring graft. Twenty patients with anterior cruciate ligament injuries, performed a closed-chain leg-press while relaxed and against a 150 N load. The tibiofemoral contact patterns between 0 degrees to 90 degrees of knee flexion were recorded by magnetic resonance scans. All measurements were performed pre-operatively and repeated at 12 weeks and two years. Following reconstruction there was a mean passive anterior laxity of 2.1 mm (sd 2.3), as measured using a KT 1000 arthrometer, and the mean Cincinnati score was 90 (sd 11) of 100. Pre-operatively, the medial and lateral contact patterns of the injured knees were located posteriorly on the tibial plateau compared with the healthy contralateral knees (p=0.014), but were no longer different at 12 weeks (p=0.117) or two years postoperatively (p=0.909). However, both reconstructed and healthy contralateral knees showed altered kinematics over time. At two years, the contact pattern showed less posterior translation of the lateral femoral condyle during flexion (p<0.01).