The effects of intramuscular tenotomy on the lengthening characteristics of tibialis posterior: high versus low intramuscular tenotomy

BACKGROUND: Lengthening of soft-tissue contractures is frequently required in children with a wide variety of congenital and acquired deformities. However, little is known about the biomechanics of surgical procedures which are commonly used in contracture surgery, or if variations in technique may have a bearing on surgical outcomes. We investigated the hypothesis that the site of intramuscular tenotomy (IMT) within the muscle-tendon-unit (MTU) of the tibialis posterior (TP) would affect the lengthening characteristics. METHODS: We performed a randomized trial on paired cadaver tibialis posterior muscle-tendon-units (TP-MTUs). By random allocation, one of each pair of formalin-preserved TP-MTUs received a high IMT, and the other a low IMT. These were individually tensile-tested with an Instron(®) machine under controlled conditions. A graph of load (Newtons) versus displacement (millimetres) was generated for each pair of tests. The differences in lengthening and load at failure for each pair of TP-MTUs were noted and compared using paired t tests. RESULTS: We found 48% greater lengthening for low IMT compared to high IMT for a given load (P = 0.004, two tailed t test). Load at failure was also significantly lower for the low IMT. These findings confirm our hypothesis that the site of the tenotomy affects the amount of lengthening achieved. This may contribute to the reported variability in clinical outcome. CONCLUSIONS: Understanding the relationship between tenotomy site and lengthening may allow surgeons to vary the site of the tenotomy in order to achieve pre-determined surgical goals. It may be possible to control the surgical "dose" by altering the position of the intramuscular tenotomy within the muscle-tendon-unit

The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer

© The Author 2015.Background: The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. Patients and methods: The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. Conclusion: The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC

The Biomechanical Profile of an Osseo-Integrated Rectangular Block Implant: A Pilot In Vivo Strain Analysis

Aim: To load-test the osseo-integrated rectangular block implant (RBI), measure the generated cortical peri-implant strains, and relate these findings to known human physiological parameters. Materials and methods: Two RBIs were placed into the posterior mandibular saddle in a mature greyhound dog and allowed to osseo-integrate. The half mandible (implants in situ) was mounted in a servohydraulic system. Four triple-stacked rosette gauges were placed cortically (mesial, distal, buccal, and lingual). A modified ISO-14801 protocol was used (1000 N, 300, 2 Hz, 1 h) and the generated principal strains (ep, eq) and their angular orientations (F), were calculated. Results: (1) Bucco-lingual “horizontal” dimension: dominant “horizontal” compressive stresses were on the lingual aspect and “horizontal” tensile stresses on the buccal aspect. The buccal cortex was elastically tensile-stretched, while the lingual cortex was elastically compressed. (2) Bucco-lingual “vertical” dimension: dominant vertical torsional stresses were oriented buccally and apically, with an overall buccally inclined torsional effect. This was also evidenced on the lingual aspect, where there remained high torsional rotation elements (high F and e2). (3) Mesio-distal “horizontal” dimension: dominant torsional stresses oriented as a distal-lingual “counter-clockwise” rotation. Conclusions: The applied off-axial loads generated a heterogeneous pattern of bucco-lingual and mesio-distal cortical strains, both vertically and horizontally. The short dimensioned osseo-integrated RBI design appeared to biomechanically withstand the applied loads and to maintain the strains generated to levels that were within physiological limits. More studies and statistical analyses are needed to confirm these findings

Press-Fit Placement of a Rectangular Block Implant in the Resorbed Alveolar Ridge: Surgical and Biomechanical Considerations

Rectangular Block Implant (RBIs) were manufactured, using computer-aided-design lathe turning, surface roughened with grit blasting and gamma irradiated. Implants were surgically placed into the resorbed edentulous mandibular ridges of both greyhound dogs (ex vivo and in vivo) and humans; the pooled total was 17 placements. The aim was to achieve mechanical stability and full implant submergence without damage to the mandibular canal and without bone fracture: fulfilment of all of these criteria was deemed to be a successful surgical outcome. Rectangular osteotomy sites were prepared with piezo surgical instrumentation. Sixteen implants were fully submerged and achieved good primary stability without bone fracture and without evidence of impingement of the mandibular canal. One implant placement was deemed a failure due to bone fracture: the event of a random successful outcome was rejected (p < 0.01 confidence, binomial analysis). Technique of placement yielded excellent mechanical retention: key biomechanical factors that emerged in this process included under preparation of the osteotomy site with the use of specifically designed trial-fit gauges, the viscoelastic property of the peri-implant bone, the flat faces and cornered edges of the block surfaces which enhance stress distribution and mechanical retention, respectively. It was concluded that the surgical protocol for the RBI placement in the resorbed alveolus is a predictable clinical procedure tailored to its specific, unique biomechanical profile

Casein Phosphopeptide-Amorphous Calcium Phosphate Reduces <i>Streptococcus mutans</i> Biofilm Development on Glass Ionomer Cement and Disrupts Established Biofilms - Fig 3

<p>Representative images of <i>S</i>. <i>mutans</i> biofilm formation on Fuji VII GIC (A) and Fuji VII EP GIC (B) after 16 h growth in a flow cell system.</p

Biometric parameters of 16 h flow cell <i>S</i>. <i>mutans</i> biofilms cultured using Fuji VII or Fuji VII EP as the substratum.

<p>Values are the mean and standard deviation of three biological replicates.</p

Effect of a single CPP-ACP treatment on an established 16 h <i>S</i>. <i>mutans</i> biofilm cultured in a 3-channel flow cell system as determined using COMSTAT analysis of CLSM images.

<p>Values are the mean and standard deviation of three biological replicates. The percentage change relative to the control is shown in brackets.</p

Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk

Biological interpretation of genome-wide association study data frequently involves assessing whether SNPs linked to a biological process, for example, binding of a transcription factor, show unsigned enrichment for disease signal. However, signed annotations quantifying whether each SNP allele promotes or hinders the biological process can enable stronger statements about disease mechanism. We introduce a method, signed linkage disequilibrium profile regression, for detecting genome-wide directional effects of signed functional annotations on disease risk. We validate the method via simulations and application to molecular quantitative trait loci in blood, recovering known transcriptional regulators. We apply the method to expression quantitative trait loci in 48 Genotype-Tissue Expression tissues, identifying 651 transcription factor-tissue associations including 30 with robust evidence of tissue specificity. We apply the method to 46 diseases and complex traits (average n = 290 K), identifying 77 annotation-trait associations representing 12 independent transcription factor-trait associations, and characterize the underlying transcriptional programs using gene-set enrichment analyses. Our results implicate new causal disease genes and new disease mechanisms