Reverse Ramp Lesion Repair in Patients With Meniscotibial Ligament Avulsion Injury: The Hidden AMRI.

Lesions of the meniscocapsular junction and the meniscotibial ligament (MTL) of the posterior horn of the medial meniscus are common with knee ligamentous injuries and associated with residual rotational instability if left untreated. MTL avulsion from its tibial attachment has never been described among different types of meniscocapsular disruptions so far. Both diagnosis and treatment of such an injury can be challenging. This article describes a detailed technique and proposes an algorithm to appropriate management of this rare injury.

OPerative versus non-opERAtive management of isolated ULNAr diaphyseal fractures (OPERA-Ulna): protocol for a randomized controlled trial.

Aims: Isolated fractures of the ulnar diaphysis are uncommon, occurring at a rate of 0.02 to 0.04 per 1,000 cases. Despite their infrequency, these fractures commonly give rise to complications, such as nonunion, limited forearm pronation and supination, restricted elbow range of motion, radioulnar synostosis, and prolonged pain. Treatment options for this injury remain a topic of debate, with limited research available and no consensus on the optimal approach. Therefore, this trial aims to compare clinical, radiological, and functional outcomes of two treatment methods: open reduction and internal fixation (ORIF) versus nonoperative treatment in patients with isolated ulnar diaphyseal fractures. Methods: This will be a multicentre, open-label, parallel randomized clinical trial (under National Clinical Trial number NCT01123447), accompanied by a parallel prospective cohort group for patients who meet the inclusion criteria, but decline randomization. Eligible patients will be randomized to one of the two treatment groups: 1) nonoperative treatment with closed reduction and below-elbow casting; or 2) surgical treatment with ORIF utilizing a limited contact dynamic compression plate and screw construct. The primary outcome measured will be the Disabilities of the Arm, Shoulder and Hand questionnaire score at 12 months post-injury. Additionally, functional outcomes will be assessed using the 36-Item Short Form Health Survey and pain visual analogue scale, allowing for a comparison of outcomes between groups. Secondary outcome measures will encompass clinical outcomes such as range of motion and grip strength, radiological parameters including time to union, as well as economic outcomes assessed from enrolment to 12 months post-injury. Ethics and dissemination: This trial has been approved by the lead site Conjoint Health Research Ethics Board (CHREB; REB14-2004) and local ethics boards at each participating site. Findings from the trial will be disseminated through presentations at regional, national, and international scientific conferences and public forums. The primary results and secondary findings will be submitted for peer-reviewed publication.

Discovery and Preclinical Evaluation of a Novel Inhibitor of FABP5, ART26.12, Effective in Oxaliplatin-Induced Peripheral Neuropathy.

Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose-limiting toxicity characterised by mechanical allodynia and thermal hyperalgesia, without any licensed medications. ART26.12 is a fatty acid-binding protein (FABP) 5 inhibitor with antinociceptive properties, characterised here for the prevention and treatment of OIPN. ART26.12 binds selectively to FABP5 compared to FABP3, FABP4, and FABP7, with minimal off-target liabilities, high oral bioavailability, and a NOAEL of 1,000 mg/kg/day in rats and dogs. In an established preclinical OIPN model, acute oral dosing (25-100 mg/kg) showed a cannabinoid receptor type 1 (CB1)-dependent anti-allodynic effect lasting up to 8 hours (persisting longer than plasma exposure to ART26.12). Antagonists of cannabinoid receptor type 2 (CB2), peroxisome proliferator-activated receptor alpha, and transient receptor potential cation channel subfamily V member 1 (TRPV1) may have also been implicated. Twice daily oral dosing (25 mg/kg bis in die (BID) for 7 days) showed anti-allodynic effects in an established OIPN model without the development of tolerance. In a prevention paradigm, coadministration of ART26.12 (10 and 25 mg/kg BID for 15 days) with oxaliplatin prevented thermal hyperalgesia, mitigated mechanical allodynia, and attenuated OXA-induced weight loss. Multi-scale analyses revealed widespread lipid modulation, particularly among N-acyl amino acids in the spinal cord, including potential analgesic mediators. Additionally, ART26.12 administration led to upregulation of ion channels in the periaqueductal grey, and broad translational upregulation within the plasma proteome. These results show promise that ART26.12 is a safe and well-tolerated candidate for the treatment and prevention of OIPN through lipid modulation. PERSPECTIVE: Inhibition of fatty acid-binding protein 5 (FABP5) is a novel target for reducing pain associated with chemotherapy. ART26.12 is a safe and well-tolerated small molecule FABP5 inhibitor effective at preventing and reducing pain induced with oxaliplatin through lipid modulation and activation of cannabinoid receptors.

Effects of forest degradation classification on the uncertainty of aboveground carbon estimates in the Amazon.

BACKGROUND: Tropical forests are critical for the global carbon budget, yet they have been threatened by deforestation and forest degradation by fire, selective logging, and fragmentation. Existing uncertainties on land cover classification and in biomass estimates hinder accurate attribution of carbon emissions to specific forest classes. In this study, we used textural metrics derived from PlanetScope images to implement a probabilistic classification framework to identify intact, logged and burned forests in three Amazonian sites. We also estimated biomass for these forest classes using airborne lidar and compared biomass uncertainties using the lidar-derived estimates only to biomass uncertainties considering the forest degradation classification as well. RESULTS: Our classification approach reached overall accuracy of 0.86, with accuracy at individual sites varying from 0.69 to 0.93. Logged forests showed variable biomass changes, while burned forests showed an average carbon loss of 35%. We found that including uncertainty in forest degradation classification significantly increased uncertainty and decreased estimates of mean carbon density in two of the three test sites. CONCLUSIONS: Our findings indicate that the attribution of biomass changes to forest degradation classes needs to account for the uncertainty in forest degradation classification. By combining very high-resolution images with lidar data, we could attribute carbon stock changes to specific pathways of forest degradation. This approach also allows quantifying uncertainties of carbon emissions associated with forest degradation through logging and fire. Both the attribution and uncertainty quantification provide critical information for national greenhouse gas inventories.

Biomechanical Evaluation of Different Plate Configurations for Midshaft Clavicle Fracture Fixation: Single Plating Compared with Dual Mini-Fragment Plating.

Background: Dual-plate constructs have become an increasingly common fixation technique for midshaft clavicle fractures and typically involve the use of mini-fragment plates. The goal of this technique is to reduce plate prominence and implant irritation. However, limited biomechanical data exist for these lower-profile constructs. The study aim was to compare dual mini-fragment orthogonal plating with small-fragment clavicle plates for biomechanical noninferiority and to determine if an optimal plate configuration could be identified using a cadaveric model. Methods: Twenty-four cadaveric clavicles were randomized to 1 of 6 groups, stratified by computed tomography-based bone mineral content (BMC): precontoured superior or anterior fixation using a single 3.5-mm Locking Compression Plate (LCP), and 4 different dual-plating constructs utilizing 2.4-mm and 2.7-mm Adaptation plates or LCPs. An inferior butterfly fracture was created. Axial, torsional, and bending (anterior and superior surface loading) stiffnesses were determined through nondestructive cyclic testing, followed by a load-to-failure test in 3-point superior surface bending. Results: For axial stiffness, the 2 dual-plate constructs with a superior 2.4-mm and anterior 2.7-mm plate (either Adaptation or LCP) were significantly stiffer than the other 4 constructs (p = 0.021 and p = 0.034). For both superior and anterior bending, the superior 2.4-mm and anterior 2.7-mm plate constructs were significantly stiffer when compared with the 3.5-mm superior plate (p = 0.043). No significant differences were found in torsional stiffness or load to failure between the different constructs. Conclusions: Dual plating using mini-fragment plates is biomechanically superior for the fixation of midshaft clavicle fractures when compared with a single, superior, 3.5-mm plate and has biomechanical properties similar to those of a 3.5-mm plate placed anteriorly. With the exception of axial stiffness, no significant differences were found when different dual-plating constructs were compared with each other. Clinical Relevance: This study validates the use of dual plating for midshaft clavicle fractures.

Downhill skiing following total knee arthroplasty: a survey of Alberta orthopedic surgeons.

Background: In older adults facing knee arthroplasty, the ability to resume downhill skiing postoperatively is unclear. This study aimed to determine the perspectives of Alberta orthopedic surgeons and senior residents regarding downhill skiing after total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA). Methods: In May 2019, a Web-based survey was sent through the Alberta Orthopaedic Society to poll orthopedic surgeons performing arthroplasty and senior orthopedic residents (postgraduate year 4 or 5) in Alberta regarding the permissibility of downhill skiing after TKA or UKA. The survey also elicited information regarding under which conditions or restrictions, if any, surgeons would allow patients to return to downhill skiing, whether these recommendations were evidence based, and whether surgeons had seen complications from downhill skiing in their patients who had undergone knee arthroplasty. Results: Of the 41 respondents, 21 (51%) were full-time fellowship-trained orthopedic surgeons, 15 (37%) were specialists with some arthroplasty in their practice, and 5 (12%) were orthopedic residents. Ten of 40 respondents (25%) would allow unrestricted downhill skiing after TKA, and 1 (2%) would not allow any skiing at all. The remaining 29 (72%) indicated that they might allow downhill skiing under specific conditions, with the top 3 being limitations on speed and intensity (29 [71%]), return of full range of motion and strength in the operative knee (26 [63%]), and years of downhill ski experience (23 [56%]). Fourteen respondents (34%) would allow unrestricted downhill skiing after UKA, and 27 (66%) would allow skiing with the same top 3 conditions as for TKA. Thirty-two respondents (78%) reported that their decisions were not evidence based, and 35 (85%) had never seen complications from downhill skiing after TKA or UKA. Conclusion: Alberta orthopedic surgeons and senior residents are cautious regarding skiing after knee arthroplasty. The majority reported that their restrictions were not evidence based, which indicates the need for further investigation to develop an approach for surgeons to consistently and safely address return to downhill skiing after TKA or UKA.

Contexte: Chez les adultes âgés qui doivent subir une arthroplastie du genou, la capacité de reprendre la pratique du ski alpin n'a pas été clairement évaluée. Cette étude visait à clarifier le point de vue des chirurgiens et résidents séniors en orthopédie de l'Alberta au sujet de la pratique du ski alpin après une intervention pour prothèse totale du genou (PTG) ou prothèse partielle du genou (PPG). Méthodes: En mai 2019, un sondage en ligne a été envoyé par l'entremise de l'Alberta Orthopaedic Society afin d'interroger les chirurgiens et résidents séniors (résidents 4 ou 5) en orthopédie pratiquant des arthroplasties en Alberta au sujet de l'autorisation à recommencer le ski alpin après une PTG ou une PPG. Le sondage portait aussi sur les conditions ou les restrictions, le cas échéant, imposées aux patients par leurs chirurgiens pour leur permettre de recommencer à skier, si ces recommandations étaient fondées sur des données probantes, et si les chirurgiens avaient observé des complications chez leurs patients ayant repris le ski après une PTG ou une PPG. Résultats: Sur les 41 répondants, 21 (51 %) étaient des médecins spécialistes en chirurgie orthopédique à temps complet, 15 (37 %) étaient des spécialistes ayant déjà effectué des arthroplasties dans le cadre de leur pratique et 5 (12 %) étaient des résidents en orthopédie. Dix répondants sur 40 (25 %) disaient qu'ils permettraient la pratique du ski alpin sans restrictions après la PTG et 1 (2 %) ne la permettrait pas du tout. Les 29 autres (72 %) ont indiqué qu'ils autoriseraient la pratique du ski alpin à certaines conditions, les 3 principales étant le contrôle de la vitesse et de l'intensité (29 [71 %]), le retour de la pleine amplitude de mouvement et de la force au genou opéré (26 [63 %]) et le nombre d'années d'expérience en ski alpin (23 [56 %]). Quatorze répondants (34 %) permettraient la reprise du ski alpin sans restrictions après la PPG et 27 (66 %) l'autoriseraient en appliquant les 3 mêmes conditions que pour la PTG. Trente-deux répondants (78 %) ont indiqué que leur décision ne reposait pas sur des données probantes et 35 (85 %) n'avaient observé aucune complication après la reprise de la pratique du skin suite à une PTG ou une PPG. Conclusion: Les chirurgiens et les résidents séniors en orthopédie de l'Alberta émettent des réserves relativement à la reprise de la pratique du skin après une arthroplastie du genou. Chez la majorité, les restrictions préconisées ne reposent pas sur des données probantes, ce qui indique que la recherche à ce sujet mérite d'être approfondie afin qu'on puisse élaborer une approche cohérente et sécuritaire en orthopédie pour la reprise de la pratique du ski alpin après une PTG ou une PPG.

Identification of hypercoagulability with thrombelastography in patients with hip fracture receiving thromboprophylaxis.

Background: Venous thromboembolism (VTE) is the second most common complication after hip fracture surgery. We used thrombelastography (TEG), a whole-blood, point-of-care test that can provide an overview of the clotting process, to determine the duration of hypercoagulability after hip fracture surgery. Methods: In this prospective study, consecutive patients aged 51 years or more with hip fractures (trochanteric region or neck) amenable to surgical treatment who presented to the emergency department were eligible for enrolment. Thrombelastography, including calculation of the coagulation index (CI) (combination of 4 TEG parameters for an overall assessment of coagulation) was performed daily from admission until 5 days postoperatively, and at 2 and 6 weeks postoperatively. All patients received 28 days of thromboprophylaxis. We used single-sample t tests to compare mean maximal amplitude (MA) values (a measure of clot strength) to the hypercoagulable threshold of greater than 65 mm, a predictor of in-hospital VTE. Results: Of the 35 patients enrolled, 11 (31%) were hypercoagulable on admission based on an MA value greater than 65 mm, and 29 (83%) were hypercoagulable based on a CI value greater than 3.0; the corresponding values at 6 weeks were 23 (66%) and 34 (97%). All patients had an MA value greater than 65 mm at 2 weeks. Patients demonstrated normal coagulation on admission (mean MA value 62.2 mm [standard deviation (SD) 6.3 mm], p = 0.01) but became significantly hypercoagulable at 2 weeks (mean 71.6 mm [SD 2.6 mm], p < 0.001). There was a trend toward persistent hypercoagulability at 6 weeks (mean MA value 66.2 mm [SD 3.8 mm], p = 0.06). Conclusion: More than 50% of patients remained hypercoagulable 6 weeks after fracture despite thromboprophylaxis. Thrombelastography MA thresholds or a change in MA over time may help predict VTE risk; however, further study is needed.

Contexte: La thromboembolie veineuse (TEV) est la deuxième complication la plus courante après une chirurgie pour fracture de la hanche. Nous avons eu recours à la thromboélastographie, un test de sang total effectué au point d'intervention et donnant une idée du processus de coagulation, pour évaluer la durée de l'hypercoagulabilité à la suite d'une chirurgie pour fracture de la hanche. Méthodes: Cette étude prospective a été menée auprès de patients consécutifs admissibles de 51 ans et plus qui se sont présentés à l'urgence pour une fracture de la hanche (région trochantérienne ou col du fémur) pouvant faire l'objet d'un traitement chirurgical. Une thromboélastographie (TEG), qui comprenait le calcul de l'indice de coagulation (IC) [combinaison de 4 paramètres du TEG permettant une évaluation globale de la coagulation], a été réalisée chaque jour, de l'admission au cinquième jour postopératoire, de même qu'à 2 et à 6 semaines postopératoires. Tous les patients ont suivi une thromboprophylaxie de 28 jours. Nous avons réalisé des tests t pour échantillon unique afin de comparer l'amplitude maximale (AM) moyenne (une mesure de la résistance d'un caillot) au seuil d'hypercoagulabilité de plus de 65 mm, un prédicteur de TEV à l'hôpital. Résultats: Des 35 patients recrutés, 11 (31 %) présentaient une hypercoagulabilité à l'admission selon une AM supérieure à 65 mm, et 29 (83 %) présentaient une hypercoagulabilité selon un IC supérieur à 3,0; les valeurs correspondantes à 6 semaines étaient de 23 (66 %) et de 34 (97 %), respectivement. Tous les patients avaient une AM de plus de 65 mm à 2 semaines. Dans l'ensemble, les patients avaient une coagulation normale à l'admission (AM moyenne 62,2 mm [écart type (E.T.) 6,3 mm], p = 0,01), mais présentaient une hypercoagulabilité importante à 2 semaines (moyenne 71,6 mm [E.T. 2,6 mm], p < 0,001). L'hypercoagulabilité avait tendance à persister à 6 semaines (AM moyenne 66,2 mm [E.T. 3,8 mm], p = 0,06). Conclusion: Malgré la thromboprophylaxie, plus de 50 % des patients présentaient toujours une hypercoagulabilité 6 semaines après leur fracture. Les seuils d'AM à la thromboélastographie et les changements de l'AM au fil du temps pourraient aider à prédire le risque de TEV, mais d'autres études sur le sujet sont nécessaires.

Porous Carbon Microparticles as Vehicles for the Intracellular Delivery of Molecules.

In this study the application of porous carbon microparticles for the transport of a sparingly soluble material into cells is demonstrated. Carbon offers an intrinsically sustainable platform material that can meet the multiple and complex requirements imposed by applications in biology and medicine. Porous carbon microparticles are attractive as they are easy to handle and manipulate and combine the chemical versatility and biocompatibility of carbon with a high surface area due to their highly porous structure. The uptake of fluorescently labeled microparticles by cancer (HeLa) and normal human embryonic Kidney (HEK 293) cells was monitored by confocal fluorescence microscopy. In this way the influence of particle size, surface functionalization and the presence of transfection agent on cellular uptake were studied. In the presence of transfection agent both large (690 nm) and small microparticles (250 nm) were readily internalized by both cell lines. However, in absence of the transfection agent the uptake was influenced by particle size and surface PEGylation with the smaller nanoparticle size being delivered. The ability of microparticles to deliver a fluorescein dye model cargo was also demonstrated in normal (HEK 293) cell line. Taken together, these results indicate the potential use of these materials as candidates for biological applications.

River networks and funerary metal in the Bronze Age of the Carpathian Basin.

Archaeologists use differences in metals from burial contexts to identify variation in social inequalities during the European Bronze Age. Many have argued that these social inequalities depended on access to, and control of, trade routes. In this paper, I model critical gateways in the Tisza river-a river system in the Carpathian Basin that might have enabled privileged access to metal in some areas but not others. I then evaluate the concentration of metal on different topological nodes of the river network in an attempt to understand what best explains the distribution of metals across this landscape. I do this by describing Bronze Age metal consumption and display in cemeteries from four micro-regions of the Tisza, and compare them with network 'betweenness centrality' values for locations along the river. I find support for the argument that favourably located river nodes had better access to metal in the earlier part of the Bronze Age.

Outcomes of total hip arthroplasty using dual mobility components in patients with a femoral neck fracture.

AIMS: Dislocation is the most common indication for further surgery following total hip arthroplasty (THA) when undertaken in patients with a femoral neck fracture. This study aimed to assess the complication rates of THA with dual mobility components (THA-DMC) following a femoral neck fracture and to compare outcomes between THA-DMC, conventional THA, and hemiarthroplasty (HA). METHODS: We performed a systematic review of all English language articles on THA-DMC published between 2010 and 2019 in the MEDLINE, EMBASE, and Cochrane databases. After the application of rigorous inclusion and exclusion criteria, 23 studies dealing with patients who underwent treatment for a femoral neck fracture using THA-DMC were analyzed for the rate of dislocation. Secondary outcomes included reoperation, periprosthetic fracture, infection, mortality, and functional outcome. The review included 7,189 patients with a mean age of 77.8 years (66.4 to 87.6) and a mean follow-up of 30.9 months (9.0 to 68.0). RESULTS: THA-DMC was associated with a significantly lower dislocation rate compared with both THA (OR 0.26; 95% CI 0.08 to 0.79) and HA (odds ratio (OR) 0.27; 95% confidence interval (CI) 0.15 to 0.50). The rate of large articulations and of intraprosthetic dislocation was 1.5% (n = 105) and 0.04% (n = 3) respectively. CONCLUSION: THA-DMC when used in patients with a femoral neck fracture is associated with a lower dislocation rate compared with conventional arthroplasty options. There was no increase in the rates of other complication when THA-DMC was used. Future cost analysis and prospective, comparative studies are required to assess the potential benefit of using THA-DMC in these patients. Cite this article: Bone Joint J 2020;102-B(7):811-821.

Acute Disseminated Intravascular Coagulation After Prophylactic Nailing of the Femur in a Patient with Metastatic Prostate Cancer: A Case Report.

CASE: We present a case of acute disseminated intravascular coagulation (DIC) after prophylactic femoral intramedullary stabilization in a patient with metastatic prostate cancer. Preoperative international normalized ratio of 1.4 was attributed to malnutrition, and the patient was not medically optimized. DIC developed 1 hour postoperatively and was managed with blood product resuscitation. At the 4-month follow-up, the patient presented with bilateral pulmonary emboli and was transitioned to palliative care. CONCLUSIONS: DIC after intramedullary stabilization in patients with metastatic bone disease is a rare condition with high mortality rate. Early recognition, blood product resuscitation, and involvement of appropriate subspecialty services are imperative in DIC management.

The visual nonverbal memory trace is fragile when actively maintained, but endures passively for tens of seconds.

Despite attempts at active maintenance in the focus of attention, the fragile nature of the visual nonverbal memory trace may be revealed when the retention interval between target memoranda and probed recall on a trial is extended. In contrast, a passively maintained or unattended visual memory trace may be revealed as persisting proactive interference extending across quite extended intervals between trials in a recent probes task. The present study, comprising five experiments, used this task to explore the persistence of such a passive visual memory trace over time. Participants viewed some target visual items (for example, abstract colored patterns) followed by a variable retention interval and a probe item. The task was to report whether the probe matched one of the targets or not. A decaying active memory trace was indicated by poorer performance as the memory retention interval was extended on a trial. However, when the probe was a member of the target set from the preceding trial, task performance was poorer than a comparison novel probe, demonstrating proactive interference. Manipulations of the intertrial interval revealed that the temporal persistence of the passive memory trace of an old target was impressive, and proactive interference was largely resilient to a simple 'cued forgetting' manipulation. These data support the proposed two-process memory conception (active-passive memory) contrasting fragile active memory traces decaying over a few seconds with robust passive traces extending to tens of seconds.

A sub-meniscal arthrotomy improves the medium-term patient outcome of tibial plateau fractures.

PURPOSE: This trial was conducted to determine the medium-term functional outcome of displaced tibial plateau fracture patients treated with closed fluoroscopic assisted reduction and internal fixation (CRIF) versus patients treated with standard open reduction with sub-meniscal arthrotomy and internal fixation (ORIF). METHODS: A prospective trial was conducted in adult patients with displaced AO/OTA 41 B and 41 C tibial plateau fractures. Patients were assigned to treatment based upon the standard treatment of the surgeon involved following the call schedule for the day, either CRIF or ORIF. Postoperative radiographs and CT were performed on all patients and patients were followed for a minimum of 2 years. Primary outcome measures were the KOOS, SMFA and SF-36. RESULTS: Seventy patients were recruited with 2 year follow-up on 35 patients in the CRIF group and 27 patients in the ORIF group. Postoperative CT scans showed that reductions were better with the ORIF group especially in the posterolateral quadrant as compared to the CRIF group. The frequency of mal-reductions was higher in the CRIF group. The KOOS, at two years, showed that the CRIF had significantly less good outcomes in the subcategories of SPORT (p = 0.03) and QOL (p = 0.01) measurements. CONCLUSIONS: ORIF with a sub-meniscal arthrotomy provides better quality reductions and better medium-term results as compared to CRIF for tibial plateau fractures. This may provide more long-term benefit from osteoarthritic symptoms in this patient group. LEVEL OF EVIDENCE: Therapeutic, Level 2.

Single-Screw Fixation Compared With Double Screw Fixation for Treatment of Medial Malleolar Fractures: A Prospective Randomized Trial.

OBJECTIVES: To determine whether single or double screw (DS) fixation of medial malleolar fractures results in better long-term health outcomes. DESIGN: Randomized clinical trial; sealed envelope technique. SETTING: Level 1 Trauma Hospital at University of Calgary, Canada. PATIENTS: One hundred forty patients were randomized to receive either 1 or 2 screws to reduce a medial malleolar fracture. Thirteen patients were excluded because of loss to follow-up (n = 127). INTERVENTION: Surgical fixation of the medial malleolar fracture was performed using 1 or 2 stainless steel screws. MAIN OUTCOME MEASUREMENTS: Primary outcome was comparison of physical functioning summary score on Short Form 36 questionnaires between patients in the 2 groups. Secondary objectives were to compare the Ankle Hindfoot Scale and operating room time. Clinical and radiographic assessment occurred at the time of injury and 2, 6 weeks, 3, 6, 12, and 24 months postoperatively. RESULTS: Fourteen patients crossed over from the DS group to the single screw (SS) group based on intraoperative decisions by the surgeon (fragment too small for 2 screws), leaving the SS (n = 75) and DS groups (n = 52). There was no difference in the operating room time, SF36, or Ankle Hindfoot Scale at all follow-up time points. CONCLUSIONS: SS medial malleolar fixation provides an equally safe and effective method of fracture care as compared to DS fixation. Twenty percent of patients receiving 2 screws can be expected to crossover to receive SS fixation as a safer alternative. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Serialized holography for brand protection and authentication.

The problems presented by counterfeit products and documentation are discussed. Limitations of existing holograms for anti-counterfeit applications are described. We describe the advantages of full holographic serialization and the requirements in terms of materials and techniques for mass production of true serialized holograms. These requirements having been met, we report for the first time the mass production of fully serialized holograms. The novelty of the approach consists of the direct use of the product manufacturer's information as the object in a holographic recording system along with a self-processing photopolymer and modular optical system to facilitate mass production of truly serialized volume holograms. Various types of serialized holograms for overt and covert authentication are described. We discuss briefly the application of Optrace's manufacturing methods for future generation holographic devices.

Communities in charge of alcohol (CICA): a protocol for a stepped-wedge randomised control trial of an alcohol health champions programme.

BACKGROUND: Communities In Charge of Alcohol (CICA) takes an Asset Based Community Development (ABCD) approach to reducing alcohol harm. Through a cascade training model, supported by a designated local co-ordinator, local volunteers are trained to become accredited 'Alcohol Health Champions' to provide brief opportunistic advice at an individual level and mobilise action on alcohol availability at a community level. The CICA programme is the first time that a devolved UK region has attempted to coordinate an approach to building health champion capacity, presenting an opportunity to investigate its implementation and impact at scale. This paper describes the protocol for a stepped wedge randomised controlled trial of an Alcohol Health Champions programme in Greater Manchester which aims to strengthen the evidence base of ABCD approaches for health improvement and reducing alcohol-related harm. METHODS: A natural experiment that will examine the effect of CICA on area level alcohol-related hospital admissions, Accident and Emergency attendances, ambulance call outs, street-level crime and anti-social behaviour data. Using a stepped wedged randomised design (whereby the intervention is rolled out sequentially in a randomly assigned order), potential changes in health and criminal justice primary outcomes are analysed using mixed-effects log-rate models, differences-in-differences models and Bayesian structured time series models. An economic evaluation identifies the set-up and running costs of CICA using HM Treasury approved standardised methods and resolves cost-consequences by sector. A process evaluation explores the context, implementation and response to the intervention. Qualitative analyses utilise the Framework method to identify underlying themes. DISCUSSION: We will investigate: whether training lay people to offer brief advice and take action on licensing decisions has an impact on alcohol-related harm in local areas; the cost-consequences for health and criminal justice sectors, and; mechanisms that influence intervention outcomes. As well as providing evidence for the effectiveness of this intervention to reduce the harm from alcohol, this evaluation will contribute to broader understanding of asset based approaches to improve public health. TRIAL REGISTRATION: ISRCTN 81942890 , date of registration 12/09/2017.

Evaluating the Utility of the Lateral Elbow Radiograph in Central Articular Olecranon Reduction: An Anatomic and Radiographic Study.

OBJECTIVES: The surgical reduction of intra-articular olecranon fractures is judged primarily on the lateral elbow radiograph, as orthogonal imaging of the articular surface is not obtainable. We sought to determine surgeon accuracy in identifying intra-articular olecranon malreductions on the lateral elbow radiograph. METHODS: Six human fresh-frozen cadaveric elbow specimens were sagittally sectioned in 5-mm increments after olecranon dissection, preservation of soft tissue envelope, and rigid fixation of the elbow in an external fixator. Three patterns of central intra-articular olecranon malreduction were created in each elbow using a ruler and bone saw. Perfect lateral elbow radiographs were taken of each malreduction, and these images were randomized along with x-rays of normal cadaveric olecranons. The image series was presented to 4 masked trauma-trained surgeons to determine whether the olecranon was malreduced or anatomic. Surgeons interpreted the same image series on 2 separate occasions separated by 6 weeks. Percent correct was recorded, and the interobserver and intraobserver reliability was calculated. RESULTS: Orthopedic trauma surgeons correctly identified olecranon malreductions only 73% of the time on the lateral elbow radiograph. Interobserver agreement was moderate for the first review of images and fair for the second review, with respective Fleiss Kappa values of 0.43 and 0.28. Intrarater reliability revealed moderate agreement with Cohen's Kappa value ranging from 0.56 to 0.66. CONCLUSIONS: Intra-articular olecranon malreductions are inconsistently recognized by trauma surgeons on the lateral elbow radiograph. Therefore, articular incongruity may still be present after surgical fixation of comminuted olecranon fractures. We must further define the radiographic anatomic representation of the articular olecranon to improve surgical reduction and clinical outcomes.

Historical and projected trends in landscape drivers affecting carbon dynamics in Alaska.

Modern climate change in Alaska has resulted in widespread thawing of permafrost, increased fire activity, and extensive changes in vegetation characteristics that have significant consequences for socioecological systems. Despite observations of the heightened sensitivity of these systems to change, there has not been a comprehensive assessment of factors that drive ecosystem changes throughout Alaska. Here we present research that improves our understanding of the main drivers of the spatiotemporal patterns of carbon dynamics using in situ observations, remote sensing data, and an array of modeling techniques. In the last 60 yr, Alaska has seen a large increase in mean annual air temperature (1.7°C), with the greatest warming occurring over winter and spring. Warming trends are projected to continue throughout the 21st century and will likely result in landscape-level changes to ecosystem structure and function. Wetlands, mainly bogs and fens, which are currently estimated to cover 12.5% of the landscape, strongly influence exchange of methane between Alaska's ecosystems and the atmosphere and are expected to be affected by thawing permafrost and shifts in hydrology. Simulations suggest the current proportion of near-surface (within 1 m) and deep (within 5 m) permafrost extent will be reduced by 9-74% and 33-55% by the end of the 21st century, respectively. Since 2000, an average of 678 595 ha/yr was burned, more than twice the annual average during 1950-1999. The largest increase in fire activity is projected for the boreal forest, which could result in a reduction in late-successional spruce forest (8-44%) and an increase in early-successional deciduous forest (25-113%) that would mediate future fire activity and weaken permafrost stability in the region. Climate warming will also affect vegetation communities across arctic regions, where the coverage of deciduous forest could increase (223-620%), shrub tundra may increase (4-21%), and graminoid tundra might decrease (10-24%). This study sheds light on the sensitivity of Alaska's ecosystems to change that has the potential to significantly affect local and regional carbon balance, but more research is needed to improve estimates of land-surface and subsurface properties, and to better account for ecosystem dynamics affected by a myriad of biophysical factors and interactions.

Incidence, Risk Factors, and Location of Articular Malreductions of the Tibial Plateau.

OBJECTIVES: To define the incidence, risk factors, and anatomic location of articular malreductions in operatively treated lateral tibial plateau fractures. DESIGN: Prospective Cohort Study. SETTING: Academic Level 1 Trauma Centre. PATIENTS/PARTICIPANTS: Study subjects were patients entered into a prospective cohort study of tibial plateau fractures. INTERVENTIONS: Surgical fixation of tibial plateau fractures and postoperative computed tomographies (CTs). MAIN OUTCOME MEASURES: The primary outcome was incidence of articular malreduction. Secondary outcomes included risk factors for malreduction and a descriptive analysis of malreduction location. RESULTS: Sixty-five postoperative CTs were reviewed. Twenty-one reductions (32.3%) had a step or gap more than 2 mm. The frequency of malreductions in patients undergoing submeniscal arthrotomy or fluoroscopic-assisted reduction alone was 16.6% and 41.4%, respectively (P = 0.0021). Age, body mass index, OTA/AO fracture type, operative time, use of bone graft or bone graft substitute, and use of locking plates were not predictive of malreduction. Malreductions were heavily weighted to the posterior quadrants of the lateral tibial plateau. CONCLUSIONS: When examined using cross-sectional imaging the rate of articular malreductions was high at 32.3%. Fluoroscopic reduction alone was a predictor for articular malreduction. Most malreductions were located in the posterior quadrants of the lateral plateau. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Target organ profiles in toxicity studies supporting human dosing: Does severity progress with longer duration of exposure?

We have previously reported the profile of target organs (defined as organs showing histopathological changes) in rodent and non-rodent toxicity studies conducted prior to first-time-in-man (FTiM) for 77 AstraZeneca candidate drugs (CDs). Here, we test the assumption that toxicity is exacerbated by dosing duration by comparing the incidence and severity of target organ toxicities in these ≤ 6 week FTiM studies with those observed in subsequent subchronic/chronic (≥ 3 month) studies. Looking at the effect of dosing duration on severity (pathological score) and incidence (percentage of animals within the group) for the 39 CDs that met the criteria for inclusion (comparable doses between FTiM and subchronic/chronic studies), new toxicities appeared for 31 target organs but existing ones resolved for 29 target organs. Increased severity was more frequent for rodent (16 target organs) than for non-rodent (4 target organs). Most notable changes were a large increase in severity/incidence in liver and in non-rodent lung in contrast to a large decrease in severity and incidence for kidneys/ureter and for the non-rodent thymus. Overall this analysis shows that, even with continued exposure, target organ toxicities of CDs are as likely to show partial or complete recovery as they are to progress in severity.