A large net carbon loss attributed to anthropogenic and natural disturbances in the Amazon Arc of Deforestation.

The Amazon forest contains globally important carbon stocks, but in recent years, atmospheric measurements suggest that it has been releasing more carbon than it has absorbed because of deforestation and forest degradation. Accurately attributing the sources of carbon loss to forest degradation and natural disturbances remains a challenge because of the difficulty of classifying disturbances and simultaneously estimating carbon changes. We used a unique, randomized, repeated, very high-resolution airborne laser scanning survey to provide a direct, detailed, and high-resolution partitioning of aboveground carbon gains and losses in the Brazilian Arc of Deforestation. Our analysis revealed that disturbances directly attributed to human activity impacted 4.2% of the survey area while windthrows and other disturbances affected 2.7% and 14.7%, respectively. Extrapolating the lidar-based statistics to the study area (544,300 km2), we found that 24.1, 24.2, and 14.5 Tg C y-1 were lost through clearing, fires, and logging, respectively. The losses due to large windthrows (21.5 Tg C y-1) and other disturbances (50.3 Tg C y-1) were partially counterbalanced by forest growth (44.1 Tg C y-1). Our high-resolution estimates demonstrated a greater loss of carbon through forest degradation than through deforestation and a net loss of carbon of 90.5 ± 16.6 Tg C y-1 for the study region attributable to both anthropogenic and natural processes. This study highlights the role of forest degradation in the carbon balance for this critical region in the Earth system.

Potential safety implications of fatty acid-binding protein inhibition.

Fatty acid-binding proteins (FABPs) are small intracellular proteins that regulate fatty acid metabolism, transport, and signalling. There are ten known human isoforms, many of which are upregulated and involved in clinical pathologies. As such, FABP inhibition may be beneficial in disease states such as cancer, and those involving the cardiovascular system, metabolism, immunity, and cognition. Recently, a potent, selective FABP5 inhibitor (ART26.12), with 90-fold selectivity to FABP3 and 20-fold selectivity to FABP7, was found to be remarkably benign, with a no-observed-adverse-effect level of 1000 mg/kg in rats and dogs, showing no genotoxicity, cardiovascular, central, or respiratory toxicity. To understand the potential implication of FABP inhibition more fully, this review systematically assessed literature investigating genetic knockout, knockdown, and pharmacological inhibition of FABP3, FABP4, FABP5, or FABP7. Analysis of the literature revealed that animals bred not to express FABPs showed the most biological effects, suggesting key roles of these proteins during development. FABP ablation sometimes exacerbated symptoms of disease models, particularly those linked to metabolism, inflammatory and immune responses, cardiac contractility, neurogenesis, and cognition. However, FABP inhibition (genetic silencing or pharmacological) had a positive effect in many more disease conditions. Several polymorphisms of each FABP gene have also been linked to pathological conditions, but it was unclear how several polymorphisms affected protein function. Overall, analysis of the literature to date suggests that pharmacological inhibition of FABPs in adults is of low risk.

Population genomics of Bronze Age Eurasia.

The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.

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.

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.

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.

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.

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.

Development of an orthopedic surgery trauma patient handover checklist.

BACKGROUND: In surgery, preoperative handover of surgical trauma patients is a process that must be made as safe as possible. We sought to determine vital clinical information to be transferred between patient care teams and to develop a standardized handover checklist. METHODS: We conducted standardized small-group interviews about trauma patient handover. Based on this information, we created a questionnaire to gather perspectives from all Canadian Orthopaedic Association (COA) members about which topics they felt would be most important on a handover checklist. We analyzed the responses to develop a standardized handover checklist. RESULTS: Of the 1106 COA members, 247 responded to the questionnaire. The top 7 topics felt to be most important for achieving patient safety in the handover were comorbidities, diagnosis, readiness for the operating room, stability, associated injuries, history/mechanism of injury and outstanding issues. The expert recommendations were to have handover completed the same way every day, all appropriate radiographs available, adequate time, all appropriate laboratory work and more time to spend with patients with more severe illness. CONCLUSION: Our main recommendations for safe handover are to use standardized checklists specific to the patient and site needs. We provide an example of a standardized checklist that should be used for preoperative handovers. To our knowledge, this is the first checklist for handover developed by a group of experts in orthopedic surgery, which is both manageable in length and simple to use.

CONTEXTE: En chirurgie, le transfert préopératoire des polytraumatisés nécessitant une chirurgie est un processus que l'on doit rendre aussi sécuritaire que possible. Nous avons voulu déterminer quels renseignements cliniques vitaux doivent être transmis aux équipes de soins et préparer une liste de vérification standardisée à cette fin. MÉTHODES: Nous avons réalisé des entrevues standardisées par petits groupes au sujet du transfert des polytraumatisés. À partir des renseignements recueillis, nous avons élaboré un questionnaire pour obtenir le point de vue de tous les membres de l'Association canadienne d'orthopédie (ACO) au sujet des éléments jugés les plus importants sur une liste de vérification en vue du transfert. Nous avons analysé les réponses pour dresser une liste de vérification standardisée. RÉSULTATS: Sur les 1106 membres de l'ACO, 247 ont répondu au questionnaire. Les 7 éléments jugés les plus importants pour assurer la sécurité des patients lors du transfert ont été : comorbidités, diagnostic, état de préparation pour le bloc opératoire, stabilité, blessures connexes, histoire et mécanisme du traumatisme et questions en suspens. Les recommandations des experts ont été les suivantes : que les transferts s'effectuent de la même façon chaque jour, qu'on obtienne toutes les radiographies appropriées disponibles, qu'on dispose de temps suffisant, qu'on obtienne toute les analyses de laboratoire appropriées et qu'on aie plus de temps à consacrer aux patients plus grièvement blessés. CONCLUSION: Nos principales recommandations pour un transfert sécuritaire sont d'utiliser des listes de vérification standardisées spécifiques aux besoins des patients et des sites. Nous fournissons un modèle type de liste de vérification pour les transferts qui devrait être utilisée pour le transfert en chirurgie des polytraumatisés. À notre connaissance, il s'agit de la première liste de vérification rapide et simple mise au point à cette fin par un groupe d'experts en chirurgie orthopédique.

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.

The nature of methadone diversion in England: a Merseyside case study.

BACKGROUND: Methadone maintenance treatment (MMT) is a key element in treatment for opiate addiction; however concerns about the diversion of methadone remain. More current empirical data on methadone diversion are required. This research investigated the market for diverted methadone in Merseyside, UK, in order to provide a case study which can be transferred to other areas undertaking methadone maintenance treatment on a large scale. METHODS: Questionnaires were completed (in interview format) with 886 past year users of methadone recruited both in and out of prescribing agencies. Topic areas covered included current prescribing, obtaining and providing methadone, reasons for using illicit methadone and other drug use. RESULTS: Large proportions of participants had obtained illicit methadone for use in the past year with smaller proportions doing so in the past month. Proportions of participants buying and being given methadone were similar. Exchange of methadone primarily took place between friends and associates, with 'dealers' rarely involved. Gender, age, whether participant's methadone consumption was supervised and whether the aims of their treatment had been explained to them fully, influenced the extent to which participants were involved in diverting or using diverted methadone. CONCLUSION: Methadone diversion is widespread although drug users generally do not make use of illicit methadone regularly (every month). The degree of altruism involved in the exchange of methadone does not negate the potential role of this action in overdose or the possibility of criminal justice action against individuals. Treatment agencies need to emphasise these risks whilst ensuring that treatment aims are effectively shared with clients to ensure adherence to treatment.

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.

Experiences of drug use and ageing: health, quality of life, relationship and service implications.

AIM: This paper is a report of an exploration of older people's experiences of substance use in the context of ageing, and its impact on health, quality of life, relationships and service use. BACKGROUND: Use of illicit drugs by older people is a neglected policy, research and service provision and is generally perceived as a lifestyle of younger populations. METHOD: A convenience sample of 11 people aged 49-61 years (mean 57 years) in contact with voluntary sector drug treatment services participated in qualitative semi-structured tape-recorded interviews and thematic content analysis was performed. The data were collected in 2008. FINDINGS: Drug use can have negative impacts on health status, quality of life, family relationships and social networks that accrue with age. Participants were identified as early or later onset users of drugs due to the impact of life events and relationships. A range of substances had been used currently and throughout their lives, with no single gateway drug identified as a prelude to personal drug careers. Life review and reflection were common, in keeping with ageing populations, along with regret of ever having started to use drugs. Living alone and their accommodation made them more susceptible to social isolation, and they reported experiences of death and dying of their contemporaries and family members earlier than usual in the life course. CONCLUSION: Older people who continue to use drugs and require the support of services for treatment and care are an important emerging population and their specific needs should recognized.

Adherence to perioperative antibiotic prophylaxis among orthopedic trauma patients.

BACKGROUND: The goal of this study was to assess whether patients receive their antibiotic prophylaxis as prescribed. We also investigated what doses and durations of antibiotics are typically ordered, which patients actually receive antibiotics and factors causing the ordered antibiotic regimen to be altered. METHODS: We performed a retrospective review of 205 patient charts and sent a national survey to all surgeon members of the Canadian Orthopaedic Trauma Society (COTS) about antibiotic prophylaxis in the setting of surgical treatment for closed fractures. RESULTS: In all, 93% (179 of 193) of patients received an appropriate preoperative dose of antibiotics, whereas less than 32% (58 of 181) of patients received their postoperative antibiotics as ordered. The most commonly stated reason for patients not receiving their postoperative antibiotics as ordered was patients being discharged before completing 3 postoperative doses. There was a 70% (39 of 56) response rate to the survey sent to COTS surgeons. A single dose of a first-generation cephalosporin preoperatively followed by 3 doses postoperatively is the most common practice among orthopedic trauma surgeons across Canada, but several surgeons give only preoperative prophylaxis. CONCLUSION: Adherence to multidose postoperative antibiotic regimens is poor. Meta-analyses have failed to demonstrate the superiority of multidose regimens over single-dose prophylaxis. Single-dose preoperative antibiotic prophylaxis may be a reasonable choice for most orthopedic trauma patients with closed fractures.