An integrated analysis of Maglemose bone points reframes the Early Mesolithic of Southern Scandinavia

The extensive peat bogs of Southern Scandinavia have yielded rich Mesolithic archaeological assemblages, with one of the most iconic artefacts being the bone point. Although great in number they remain understudied. Here we present a combined investigation of the typology, protein-based species composition, and absolute chronology of Maglemosian bone points. The majority of the bone points are made from cervids and bovines. However, changes both in species composition and barb morphology can be directly linked to a paucity of finds lasting nearly 600 years in Southern Scandinavia around 10,300 cal BP. We hypothesize that this hiatus was climate-driven and forced hunter-gatherers to abandon the lakes. Furthermore, the marked change in bone points coincides with a change in lithic technology. We, therefore, propose that the Maglemose culture in Southern Scandinavia is fundamentally divided into an Early Complex and a Late Complex

A Dominant-Negative Mutation of Mouse Lmx1b Causes Glaucoma and Is Semi-lethal via LBD1-Mediated Dimerisation

Mutations in the LIM-homeodomain transcription factor LMX1B cause nail-patella syndrome, an autosomal dominant pleiotrophic human disorder in which nail, patella and elbow dysplasia is associated with other skeletal abnormalities and variably nephropathy and glaucoma. It is thought to be a haploinsufficient disorder. Studies in the mouse have shown that during development Lmx1b controls limb dorsal-ventral patterning and is also required for kidney and eye development, midbrain-hindbrain boundary establishment and the specification of specific neuronal subtypes. Mice completely deficient for Lmx1b die at birth. In contrast to the situation in humans, heterozygous null mice do not have a mutant phenotype. Here we report a novel mouse mutant Icst, an N-ethyl-N-nitrosourea-induced missense substitution, V265D, in the homeodomain of LMX1B that abolishes DNA binding and thereby the ability to transactivate other genes. Although the homozygous phenotypic consequences of Icst and the null allele of Lmx1b are the same, heterozygous Icst elicits a phenotype whilst the null allele does not. Heterozygous Icst causes glaucomatous eye defects and is semi-lethal, probably due to kidney failure. We show that the null phenotype is rescued more effectively by an Lmx1b transgene than is Icst. Co-immunoprecipitation experiments show that both wild-type and Icst LMX1B are found in complexes with LIM domain binding protein 1 (LDB1), resulting in lower levels of functional LMX1B in Icst heterozygotes than null heterozygotes. We conclude that Icst is a dominant-negative allele of Lmx1b. These findings indicate a reassessment of whether nail-patella syndrome is always haploinsufficient. Furthermore, Icst is a rare example of a model of human glaucoma caused by mutation of the same gene in humans and mice

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol

Introduction: Fracture healing can fail in up to 10% of cases despite appropriate treatment. While lithium has been the standard treatment for bipolar disorder, it may also have a significant impact to increase bone healing in patients with long bone fractures. To translate this knowledge into clinical practice, a randomised clinical trial (RCT) is proposed. Methods and analysis: A multicentre double blind, placebo-controlled RCT is proposed to evaluate the efficacy of lithium to increase the rate and predictability of long bone fracture healing in healthy adults compared to lactose placebo treatment. 160 healthy individuals from 18 to 55 years of age presenting with shaft fractures of the femur, tibia/fibula, humerus or clavicle will be eligible. Fractures will be randomised to placebo (lactose) or treatment (300 mg lithium carbonate) group within 2 weeks of the injury. The primary outcome measure will be radiographic union defined as visible callus bridging on three of the four cortices at the fracture site using a validated radiographic union score. Secondary outcome measures will include functional assessment and pain scoring. Ethics and dissemination: Participant confidentiality will be maintained with publication of results. Research Ethics Board Approval: Sunnybrook Research Institute (REB # 356–2016). Health Canada Approval (HC6-24-C201560). Results of the main trial and secondary endpoints will be submitted for publication in a peer-reviewed journal and presented at conferences. Trial registration number: NCT02999022.This work was supported by CIHR (2016- HC6-24-C201560)

Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol

IntroductionFracture healing can fail in up to 10% of cases despite appropriate treatment. While lithium has been the standard treatment for bipolar disorder, it may also have a significant impact to increase bone healing in patients with long bone fractures. To translate this knowledge into clinical practice, a randomised clinical trial (RCT) is proposed.Methods and analysisA multicentre double blind, placebo-controlled RCT is proposed to evaluate the efficacy of lithium to increase the rate and predictability of long bone fracture healing in healthy adults compared to lactose placebo treatment. 160 healthy individuals from 18 to 55 years of age presenting with shaft fractures of the femur, tibia/fibula, humerus or clavicle will be eligible. Fractures will be randomised to placebo (lactose) or treatment (300 mg lithium carbonate) group within 2 weeks of the injury. The primary outcome measure will be radiographic union defined as visible callus bridging on three of the four cortices at the fracture site using a validated radiographic union score. Secondary outcome measures will include functional assessment and pain scoring.Ethics and disseminationParticipant confidentiality will be maintained with publication of results. Research Ethics Board Approval: Sunnybrook Research Institute (REB # 356–2016). Health Canada Approval (HC6-24-C201560). Results of the main trial and secondary endpoints will be submitted for publication in a peer-reviewed journal and presented at conferences.Trial registration numberNCT02999022.</jats:sec

An integrated analysis of Maglemose bone points reframes the Early Mesolithic of Southern Scandinavia

AbstractThe extensive peat bogs of Southern Scandinavia have yielded rich Mesolithic archaeological assemblages, with one of the most iconic artefacts being the bone point. Although great in number they remain understudied. Here we present a combined investigation of the typology, protein-based species composition, and absolute chronology of Maglemosian bone points. The majority of the bone points are made from cervids and bovines. However, changes both in species composition and barb morphology can be directly linked to a paucity of finds lasting nearly 600 years in Southern Scandinavia around 10,300 cal BP. We hypothesize that this hiatus was climate-driven and forced hunter-gatherers to abandon the lakes. Furthermore, the marked change in bone points coincides with a change in lithic technology. We, therefore, propose that the Maglemose culture in Southern Scandinavia is fundamentally divided into an Early Complex and a Late Complex.</jats:p

A pilot multicenter randomized controlled trial comparing Bankart repair and remplissage with the Latarjet procedure in patients with subcritical bone loss (STABLE): study protocol

Introduction: Anterior dislocations, the most common type of shoulder dislocation, are often complicated by subsequent instability. With recurrent dislocations there often is attrition of the labrum and progressive loss of the anterior bony contour of the glenoid. Treatment options for this pathology involve either soft tissue repair or bony augmentation procedure. The optimal management remains unknown and current clinical practice is highly varied. Methods and analysis:The Shoulder instability Trial comparing Arthroscopic stabilization Benefits compared with Latarjet procedure Evaluation (STABLE) is an ongoing multi-centre, pilot randomized controlled trial of 82 patients who have been diagnosed with recurrent anterior shoulder instability and subcritical glenoid bone loss. Patients are randomized to either soft tissue repair (Bankart + Remplissage) or bony augmentation (Latarjet procedure). The primary outcome for this pilot is to assess trial feasibility and secondary outcomes include recurrent instability as well as functional outcomes up to two years post-operatively. Conclusions: This trial will help to identify the optimal treatment for patients with recurrent shoulder instability with a focus on determining which treatment option results in reduced risk of recurrent dislocation and improved patient outcomes. Findings from this trial will guide clinical practice and improve care for patients with shoulder instability. Ethics and dissemination: This study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB) (approval #4942). Successful completion will significantly impact the global management of patients with recurrent instability. This trial will develop a network of collaboration for future high-quality trials in shoulder instability

A pilot multicenter randomized controlled trial comparing Bankart repair and remplissage with the Latarjet procedure in patients with subcritical bone loss (STABLE): study protocol

Abstract Introduction Anterior dislocations, the most common type of shoulder dislocation, are often complicated by subsequent instability. With recurrent dislocations there often is attrition of the labrum and progressive loss of the anterior bony contour of the glenoid. Treatment options for this pathology involve either soft tissue repair or bony augmentation procedure. The optimal management remains unknown and current clinical practice is highly varied. Methods and analysis The Shoulder instability Trial comparing Arthroscopic stabilization Benefits compared with Latarjet procedure Evaluation (STABLE) is an ongoing multi-centre, pilot randomized controlled trial of 82 patients who have been diagnosed with recurrent anterior shoulder instability and subcritical glenoid bone loss. Patients are randomized to either soft tissue repair (Bankart + Remplissage) or bony augmentation (Latarjet procedure). The primary outcome for this pilot is to assess trial feasibility and secondary outcomes include recurrent instability as well as functional outcomes up to two years post-operatively. Conclusions This trial will help to identify the optimal treatment for patients with recurrent shoulder instability with a focus on determining which treatment option results in reduced risk of recurrent dislocation and improved patient outcomes. Findings from this trial will guide clinical practice and improve care for patients with shoulder instability. Trial registration This study has been registered on http://www.ClinicalTrials.gov with the following identifier: ClinicalTrials.gov Identifier: NCT03585491, registered 13 July 2018, https://www.clinicaltrials.gov/ct2/show/NCT03585491?term=NCT03585491&amp;draw=2&amp;rank=1. Ethics and dissemination This study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB) (approval #4942). Successful completion will significantly impact the global management of patients with recurrent instability. This trial will develop a network of collaboration for future high-quality trials in shoulder instability. </jats:sec