Use of multiple pharmacodynamic measures to deconstruct the Nix-TB regimen in a short-course murine model of tuberculosis.

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen [bedaquiline-pretomanid-linezolid (BPaL)] during the first 3 weeks of treatment at human equivalent doses. The rRNA synthesis (RS) ratio, an exploratory pharmacodynamic (PD) marker of ongoing Mycobacterium tuberculosis rRNA synthesis, together with solid culture CFU counts and liquid culture time to positivity (TTP) were used as PD markers of treatment response in lung tissue; and their time-course profiles were mathematically modeled using rate equations with pharmacologically interpretable parameters. Antimicrobial interactions were quantified using Bliss independence and Isserlis formulas. Subadditive (or antagonistic) and additive effects on bacillary load, assessed by CFU and TTP, were found for bedaquiline-pretomanid and linezolid-containing pairs, respectively. In contrast, subadditive and additive effects on rRNA synthesis were found for pretomanid-linezolid and bedaquiline-containing pairs, respectively. Additionally, accurate predictions of the response to BPaL for all three PD markers were made using only the single-drug and pairwise effects together with an assumption of negligible three-way drug interactions. The results represent an experimental and PD modeling approach aimed at reducing combinatorial complexity and improving the cost-effectiveness of in vivo systems for preclinical TB regimen development.

Land-based climate solutions for the United States.

Meeting end-of-century global warming targets requires aggressive action on multiple fronts. Recent reports note the futility of addressing mitigation goals without fully engaging the agricultural sector, yet no available assessments combine both nature-based solutions (reforestation, grassland and wetland protection, and agricultural practice change) and cellulosic bioenergy for a single geographic region. Collectively, these solutions might offer a suite of climate, biodiversity, and other benefits greater than either alone. Nature-based solutions are largely constrained by the duration of carbon accrual in soils and forest biomass; each of these carbon pools will eventually saturate. Bioenergy solutions can last indefinitely but carry significant environmental risk if carelessly deployed. We detail a simplified scenario for the United States that illustrates the benefits of combining approaches. We assign a portion of non-forested former cropland to bioenergy sufficient to meet projected mid-century transportation needs, with the remainder assigned to nature-based solutions such as reforestation. Bottom-up mitigation potentials for the aggregate contributions of crop, grazing, forest, and bioenergy lands are assessed by including in a Monte Carlo model conservative ranges for cost-effective local mitigation capacities, together with ranges for (a) areal extents that avoid double counting and include realistic adoption rates and (b) the projected duration of different carbon sinks. The projected duration illustrates the net effect of eventually saturating soil carbon pools in the case of most strategies, and additionally saturating biomass carbon pools in the case of forest management. Results show a conservative end-of-century mitigation capacity of 110 (57-178) Gt CO2 e for the U.S., ~50% higher than existing estimates that prioritize nature-based or bioenergy solutions separately. Further research is needed to shrink uncertainties, but there is sufficient confidence in the general magnitude and direction of a combined approach to plan for deployment now.

A new open-path eddy covariance method for nitrous oxide and other trace gases that minimizes temperature corrections.

Low-power, open-path gas sensors enable eddy covariance (EC) flux measurements in remote areas without line power. However, open-path flux measurements are sensitive to fluctuations in air temperature, pressure, and humidity. Laser-based, open-path sensors with the needed sensitivity for trace gases like methane (CH4 ) and nitrous oxide (N2 O) are impacted by additional spectroscopic effects. Corrections for these effects, especially those related to temperature fluctuations, often exceed the flux of gases, leading to large uncertainties in the associated fluxes. For example, the density and spectroscopic corrections arising from temperature fluctuations can be one or two orders of magnitude greater than background N2 O fluxes. Consequently, measuring background fluxes with laser-based, open-path sensors is extremely challenging, particularly for N2 O and gases with similar high-precision requirements. We demonstrate a new laser-based, open-path N2 O sensor and a general approach applicable to other gases that minimizes temperature-related corrections for EC flux measurements. The method identifies absorption lines with spectroscopic effects in the opposite direction of density effects from temperature and, thus, density and spectroscopic effects nearly cancel one another. The new open-path N2 O sensor was tested at a corn (Zea mays L.) field in Southwestern Michigan, United States. The sensor had an optimal precision of 0.1 ppbv at 10 Hz and power consumption of 50 W. Field trials showed that temperature-related corrections were 6% of density corrections, reducing EC random errors by 20-fold compared to previously examined lines. Measured open-path N2 O EC fluxes showed excellent agreement with those made with static chambers (m = 1.0 ± 0.3; r2  = .96). More generally, we identified absorption lines for CO2 and CH4  flux measurements that can reduce the temperature-related corrections by 10-100 times compared to existing open-path sensors. The proposed method provides a new direction for future open-path sensors, facilitating the expansion of accurate EC flux measurements.

Climate-smart soils.

Soils are integral to the function of all terrestrial ecosystems and to food and fibre production. An overlooked aspect of soils is their potential to mitigate greenhouse gas emissions. Although proven practices exist, the implementation of soil-based greenhouse gas mitigation activities are at an early stage and accurately quantifying emissions and reductions remains a substantial challenge. Emerging research and information technology developments provide the potential for a broader inclusion of soils in greenhouse gas policies. Here we highlight 'state of the art' soil greenhouse gas research, summarize mitigation practices and potentials, identify gaps in data and understanding and suggest ways to close such gaps through new research, technology and collaboration.

Management of Gustilo-Anderson IIIB open tibial fractures in adults-a systematic review.

INTRODUCTION: Open tibial fractures are the most common open long bone fracture, despite this, the management of these complex injuries still remains a topic of discussion amongst orthopaedic surgeons. SOURCES OF DATA: We searched the EMBASE, MEDLINE and Google Scholar and a systematic review of 7500 articles, leaving 23 after exclusion criteria were applied, in order to analyse the management of open tibial fractures. AREAS OF AGREEMENT AND CONTROVERSY: Infection was noted to be the most significant concern amongst authors, with definitive external fixation having a high rate of superficial pin-site infection and internal fixation having a high deep infection rate. GROWING POINTS: It is essential to have a combined ortho-plastic approach to the management of these fractures as muscle flaps were the most common form of soft tissue coverage. AREAS TIMELY FOR DEVELOPING RESEARCH: A national pragmatic trial into the management of open tibial fractures is required looking at fixation methods and soft tissue coverage, with at least a 2-year follow-up in order to ascertain the most appropriate management of these fractures and patient-related outcomes.

Nitrification is a minor source of nitrous oxide (N2 O) in an agricultural landscape and declines with increasing management intensity.

The long-term contribution of nitrification to nitrous oxide (N2 O) emissions from terrestrial ecosystems is poorly known and thus poorly constrained in biogeochemical models. Here, using Bayesian inference to couple 25 years of in situ N2 O flux measurements with site-specific Michaelis-Menten kinetics of nitrification-derived N2 O, we test the relative importance of nitrification-derived N2 O across six cropped and unmanaged ecosystems along a management intensity gradient in the U.S. Midwest. We found that the maximum potential contribution from nitrification to in situ N2 O fluxes was 13%-17% in a conventionally fertilized annual cropping system, 27%-42% in a low-input cover-cropped annual cropping system, and 52%-63% in perennial systems including a late successional deciduous forest. Actual values are likely to be <10% of these values because of low N2 O yields in cultured nitrifiers (typically 0.04%-8% of NH3 oxidized) and competing sinks for available NH4+ in situ. Most nitrification-derived N2 O was produced by ammonia-oxidizing bacteria rather than archaea, who appeared responsible for no more than 30% of nitrification-derived N2 O production in all but one ecosystem. Although the proportion of nitrification-derived N2 O production was lowest in annual cropping systems, these ecosystems nevertheless produced more nitrification-derived N2 O (higher Vmax ) than perennial and successional ecosystems. We conclude that nitrification is minor relative to other sources of N2 O in all ecosystems examined.

Long-term research avoids spurious and misleading trends in sustainability attributes of no-till.

Agricultural management recommendations based on short-term studies can produce findings inconsistent with long-term reality. Here, we test the long-term environmental sustainability and profitability of continuous no-till agriculture on yield, soil water availability, and N2 O fluxes. Using a moving window approach, we investigate the development and stability of several attributes of continuous no-till as compared to conventional till agriculture over a 29-year period at a site in the upper Midwest, US. Over a decade is needed to detect the consistent effects of no-till. Both crop yield and soil water availability required 15 years or longer to generate patterns consistent with 29-year trends. Only marginal trends for N2 O fluxes appeared in this period. Relative profitability analysis suggests that after initial implementation, 86% of periods between 10 and 29 years recuperated the initial expense of no-till implementation, with the probability of higher relative profit increasing with longevity. Importantly, statistically significant but misleading short-term trends appeared in more than 20% of the periods examined. Results underscore the importance of decadal and longer studies for revealing consistent dynamics and emergent outcomes of no-till agriculture, shown to be beneficial in the long term.

Empirical Evidence for the Potential Climate Benefits of Decarbonizing Light Vehicle Transport in the U.S. with Bioenergy from Purpose-Grown Biomass with and without BECCS.

Climate mitigation scenarios limiting global temperature increases to 1.5 °C rely on decarbonizing vehicle transport with bioenergy production plus carbon capture and storage (BECCS), but climate impacts for producing different bioenergy feedstocks have not been directly compared experimentally or for ethanol vs electric light-duty vehicles. A field experiment at two Midwest U.S. sites on contrasting soils revealed that feedstock yields of seven potential bioenergy cropping systems varied substantially within sites but little between. Bioenergy produced per hectare reflected yields: miscanthus > poplar > switchgrass > native grasses ≈ maize stover (residue) > restored prairie ≈ early successional. Greenhouse gas emission intensities for ethanol vehicles ranged from 20 to -179 g CO2e MJ-1: maize stover ≫ miscanthus ≈ switchgrass ≈ native grasses ≈ poplar > early successional ≥ restored prairie; direct climate benefits ranged from ∼80% (stover) to 290% (restored prairie) reductions in CO2e compared to petroleum and were similar for electric vehicles. With carbon capture and storage (CCS), reductions in emission intensities ranged from 204% (stover) to 416% (restored prairie) for ethanol vehicles and from 329 to 558% for electric vehicles, declining 27 and 15%, respectively, once soil carbon equilibrates within several decades of establishment. Extrapolation based on expected U.S. transportation energy use suggests that, once CCS potential is maximized with CO2 pipeline infrastructure, negative emissions from bioenergy with CCS for light-duty electric vehicles could capture >900 Tg CO2e year-1 in the U.S. In the future, as other renewable electricity sources become more important, electricity production from biomass would offset less fossil fuel electricity, and the advantage of electric over ethanol vehicles would decrease proportionately.

Field-scale experiments reveal persistent yield gaps in low-input and organic cropping systems.

Knowledge of production-system performance is largely based on observations at the experimental plot scale. Although yield gaps between plot-scale and field-scale research are widely acknowledged, their extent and persistence have not been experimentally examined in a systematic manner. At a site in southwest Michigan, we conducted a 6-y experiment to test the accuracy with which plot-scale crop-yield results can inform field-scale conclusions. We compared conventional versus alternative, that is, reduced-input and biologically based-organic, management practices for a corn-soybean-wheat rotation in a randomized complete block-design experiment, using 27 commercial-size agricultural fields. Nearby plot-scale experiments (0.02-ha to 1.0-ha plots) provided a comparison of plot versus field performance. We found that plot-scale yields well matched field-scale yields for conventional management but not for alternative systems. For all three crops, at the plot scale, reduced-input and conventional managements produced similar yields; at the field scale, reduced-input yields were lower than conventional. For soybeans at the plot scale, biological and conventional managements produced similar yields; at the field scale, biological yielded less than conventional. For corn, biological management produced lower yields than conventional in both plot- and field-scale experiments. Wheat yields appeared to be less affected by the experimental scale than corn and soybean. Conventional management was more resilient to field-scale challenges than alternative practices, which were more dependent on timely management interventions; in particular, mechanical weed control. Results underscore the need for much wider adoption of field-scale experimentation when assessing new technologies and production-system performance, especially as related to closing yield gaps in organic farming and in low-resourced systems typical of much of the developing world.

Sustainable bioenergy production from marginal lands in the US Midwest.

Legislation on biofuels production in the USA and Europe is directing food crops towards the production of grain-based ethanol, which can have detrimental consequences for soil carbon sequestration, nitrous oxide emissions, nitrate pollution, biodiversity and human health. An alternative is to grow lignocellulosic (cellulosic) crops on 'marginal' lands. Cellulosic feedstocks can have positive environmental outcomes and could make up a substantial proportion of future energy portfolios. However, the availability of marginal lands for cellulosic feedstock production, and the resulting greenhouse gas (GHG) emissions, remains uncertain. Here we evaluate the potential for marginal lands in ten Midwestern US states to produce sizeable amounts of biomass and concurrently mitigate GHG emissions. In a comparative assessment of six alternative cropping systems over 20 years, we found that successional herbaceous vegetation, once well established, has a direct GHG emissions mitigation capacity that rivals that of purpose-grown crops (-851 ± 46 grams of CO(2) equivalent emissions per square metre per year (gCO(2)e m(-2) yr(-1))). If fertilized, these communities have the capacity to produce about 63 ± 5 gigajoules of ethanol energy per hectare per year. By contrast, an adjacent, no-till corn-soybean-wheat rotation produces on average 41 ± 1 gigajoules of biofuel energy per hectare per year and has a net direct mitigation capacity of -397 ± 32 gCO(2)e m(-2) yr(-1); a continuous corn rotation would probably produce about 62 ± 7 gigajoules of biofuel energy per hectare per year, with 13% less mitigation. We also perform quantitative modelling of successional vegetation on marginal lands in the region at a resolution of 0.4 hectares, constrained by the requirement that each modelled location be within 80 kilometres of a potential biorefinery. Our results suggest that such vegetation could produce about 21 gigalitres of ethanol per year from around 11 million hectares, or approximately 25 per cent of the 2022 target for cellulosic biofuel mandated by the US Energy Independence and Security Act of 2007, with no initial carbon debt nor the indirect land-use costs associated with food-based biofuels. Other regional-scale aspects of biofuel sustainability, such as water quality and biodiversity, await future study.

The greenhouse gas cost of agricultural intensification with groundwater irrigation in a Midwest U.S. row cropping system.

Groundwater irrigation of cropland is expanding worldwide with poorly known implications for climate change. This study compares experimental measurements of the net global warming impact of a rainfed versus a groundwater-irrigated corn (maize)-soybean-wheat, no-till cropping system in the Midwest US, the region that produces the majority of U.S. corn and soybean. Irrigation significantly increased soil organic carbon (C) storage in the upper 25 cm, but not by enough to make up for the CO2 -equivalent (CO2 e) costs of fossil fuel power, soil emissions of nitrous oxide (N2 O), and degassing of supersaturated CO2 and N2 O from the groundwater. A rainfed reference system had a net mitigating effect of -13.9 (±31) g CO2 e m-2  year-1 , but with irrigation at an average rate for the region, the irrigated system contributed to global warming with net greenhouse gas (GHG) emissions of 27.1 (±32) g CO2 e m-2  year-1 . Compared to the rainfed system, the irrigated system had 45% more GHG emissions and 7% more C sequestration. The irrigation-associated increase in soil N2 O and fossil fuel emissions contributed 18% and 9%, respectively, to the system's total emissions in an average irrigation year. Groundwater degassing of CO2 and N2 O are missing components of previous assessments of the GHG cost of groundwater irrigation; together they were 4% of the irrigated system's total emissions. The irrigated system's net impact normalized by crop yield (GHG intensity) was +0.04 (±0.006) kg CO2 e kg-1 yield, close to that of the rainfed system, which was -0.03 (±0.002) kg CO2 e kg-1 yield. Thus, the increased crop yield resulting from irrigation can ameliorate overall GHG emissions if intensification by irrigation prevents land conversion emissions elsewhere, although the expansion of irrigation risks depletion of local water resources.

Legacy effects of land use on soil nitrous oxide emissions in annual crop and perennial grassland ecosystems.

Land use conversions into and out of agriculture may influence soil-atmosphere greenhouse gas fluxes for many years. We tested the legacy effects of land use on cumulative soil nitrous oxide (N2 O) fluxes for 5 yr following conversion of 22-yr-old Conservation Reserve Program (CRP) grasslands and conventionally tilled agricultural fields (AGR) to continuous no-till corn, switchgrass, and restored prairie. An unconverted CRP field served as a reference. We assessed the labile soil C pool of the upper 10 cm in 2009 (the conversion year) and in 2014 using short-term soil incubations. We also measured in situ soil N2 O fluxes biweekly from 2009 through 2014 using static chambers except when soils were frozen. The labile C pool was approximately twofold higher in soils previously in CRP than in those formerly in tilled cropland. Five-year cumulative soil N2 O emissions were approximately threefold higher in the corn system on former CRP than on former cropland despite similar fertilization rates (~184 kg N·ha-1 ·yr-1 ). The lower cumulative emissions from corn on former cropland were similar to emissions from switchgrass that was fertilized less (~57 kg N·ha-1 ·yr-1 ), regardless of former land use, and lowest emissions were observed from the unfertilized restored prairie and reference systems. Findings support the hypothesis that soil labile carbon levels modulate the response of soil N2 O emissions to nitrogen inputs, with soils higher in labile carbon but otherwise similar, in this case reflecting land use history, responding more strongly to added nitrogen.

Perennialization and Cover Cropping Mitigate Soil Carbon Loss from Residue Harvesting.

While the US Midwest is expected to serve as a primary feedstock source for cellulosic biofuel production, the impacts of residue harvesting on soil organic carbon (SOC) may greatly limit sustainable production capacity. However, viable feedstock production could be realized through adoption of management practices and cropping systems that offset residue-harvest-induced SOC losses. Sequestration of SOC can be enhanced by increasing the duration of crop soil cover through cover or double cropping or cultivation of dedicated perennials. However, assessing the efficacy of such options across sites and over long periods is experimentally challenging. Hence, we use the Environmental Productivity Integrated Climate (EPIC) model to provide such an assessment. Model-data integration was used to calibrate and evaluate model suitability, which exhibited reasonable effectiveness through of 0.97 and 0.63 for SOC stock and yield, respectively. Long-term simulations indicate considerable capacity for offsetting SOC loss. Incorporating rye ( L.) into continuous corn ( L.) and corn-soybean [ (L.) Merr.] systems offset the SOC losses induced by harvesting 21.2 and 38.3% of available stover, respectively. Similarly, converting 20.4% of corn-soybean land to miscanthus ( × J.M. Greef & Deuter ex Hodkinson & Renvoize) or 27.5% of land to switchgrass ( L.) offset the SOC impacts of harvesting 60% of stover from the remaining corn-soybean lands. These responses indicate that adoption of such measures would sizably affect the life cycle consequences of residue-derived biofuels and expand estimates of sustainable cellulosic feedstock production capacity from the US Midwest.

Advancing the Sustainability of US Agriculture through Long-Term Research.

Agriculture in the United States must respond to escalating demands for productivity and efficiency, as well as pressures to improve its stewardship of natural resources. Growing global population and changing diets, combined with a greater societal awareness of agriculture's role in delivering ecosystem services beyond food, feed, fiber, and energy production, require a comprehensive perspective on where and how US agriculture can be sustainably intensified, that is, made more productive without exacerbating local and off-site environmental concerns. The USDA's Long-Term Agroecosystem Research (LTAR) network is composed of 18 locations distributed across the contiguous United States working together to integrate national and local agricultural priorities and advance the sustainable intensification of US agriculture. We explore here the concept of sustainable intensification as a framework for defining strategies to enhance production, environmental, and rural prosperity outcomes from agricultural systems. We also elucidate the diversity of factors that have shaped the past and present conditions of cropland, rangeland, and pastureland agroecosystems represented by the LTAR network and identify priorities for research in the areas of production, resource conservation and environmental quality, and rural prosperity. Ultimately, integrated long-term research on sustainable intensification at the national scale is critical to developing practices and programs that can anticipate and address challenges before they become crises.

Return to sport following stress fractures of the great toe sesamoids: a systematic review.

Introduction: This review aims to provide information on return rates and times to sport following stress fractures of the great toe sesamoids (SFGTSs). Sources of data: A systematic search of CINAHAL, Cochrane, EMBASE, Google Scholar, Medline, PEDro, Scopus, SPORTDiscus and Web of Science was performed using the keywords 'stress', 'fractures', 'great', 'toe', 'sesamoid', 'athletes', 'sports', 'non-operative', 'conservative', 'operative' and 'return to sport'. Areas of agreement: Fourteen studies were included: three studies reported on the outcome of conservatively-managed SFGTSs; thirteen studies reported on the outcome of surgically-managed SFGTSs. The management principles were to attempt conservative management for 2-6 months using activity modification, analgesia, orthotics and physiotherapy; if symptoms persisted following this, surgical management was to be recommended, either with internal fixation or sesamoidectomy. Areas of controversy: The optimal treatment modalities for SFGTSs remain to be defined. Growing points: Internal fixation shows the best return to full-level sport rates with low rates of complications. Areas timely for developing research: Future prospective studies should aim to establish the optimal treatment modalities for SFGTSs.

Global metaanalysis of the nonlinear response of soil nitrous oxide (N2O) emissions to fertilizer nitrogen.

Nitrous oxide (N2O) is a potent greenhouse gas (GHG) that also depletes stratospheric ozone. Nitrogen (N) fertilizer rate is the best single predictor of N2O emissions from agricultural soils, which are responsible for ∼ 50% of the total global anthropogenic flux, but it is a relatively imprecise estimator. Accumulating evidence suggests that the emission response to increasing N input is exponential rather than linear, as assumed by Intergovernmental Panel on Climate Change methodologies. We performed a metaanalysis to test the generalizability of this pattern. From 78 published studies (233 site-years) with at least three N-input levels, we calculated N2O emission factors (EFs) for each nonzero input level as a percentage of N input converted to N2O emissions. We found that the N2O response to N inputs grew significantly faster than linear for synthetic fertilizers and for most crop types. N-fixing crops had a higher rate of change in EF (ΔEF) than others. A higher ΔEF was also evident in soils with carbon >1.5% and soils with pH <7, and where fertilizer was applied only once annually. Our results suggest a general trend of exponentially increasing N2O emissions as N inputs increase to exceed crop needs. Use of this knowledge in GHG inventories should improve assessments of fertilizer-derived N2O emissions, help address disparities in the global N2O budget, and refine the accuracy of N2O mitigation protocols. In low-input systems typical of sub-Saharan Africa, for example, modest N additions will have little impact on estimated N2O emissions, whereas equivalent additions (or reductions) in excessively fertilized systems will have a disproportionately major impact.

Perennial grasslands enhance biodiversity and multiple ecosystem services in bioenergy landscapes.

Agriculture is being challenged to provide food, and increasingly fuel, for an expanding global population. Producing bioenergy crops on marginal lands--farmland suboptimal for food crops--could help meet energy goals while minimizing competition with food production. However, the ecological costs and benefits of growing bioenergy feedstocks--primarily annual grain crops--on marginal lands have been questioned. Here we show that perennial bioenergy crops provide an alternative to annual grains that increases biodiversity of multiple taxa and sustain a variety of ecosystem functions, promoting the creation of multifunctional agricultural landscapes. We found that switchgrass and prairie plantings harbored significantly greater plant, methanotrophic bacteria, arthropod, and bird diversity than maize. Although biomass production was greater in maize, all other ecosystem services, including methane consumption, pest suppression, pollination, and conservation of grassland birds, were higher in perennial grasslands. Moreover, we found that the linkage between biodiversity and ecosystem services is dependent not only on the choice of bioenergy crop but also on its location relative to other habitats, with local landscape context as important as crop choice in determining provision of some services. Our study suggests that bioenergy policy that supports coordinated land use can diversify agricultural landscapes and sustain multiple critical ecosystem services.

Return to sport following clavicle fractures: a systematic review.

INTRODUCTION: This review aims to provide information on the return rates and return times to sport following clavicle fractures. SOURCES OF DATA: A systematic search of Medline, EMBASE, CINAHAL, Cochrane, Web of Science, PEDro, SPORTDiscus, Scopus and Google Scholar was performed using the keywords 'clavicle', 'clavicular', 'fractures', 'athletes', 'sports', 'non-operative', 'conservative', 'operative', 'return to sport'. AREAS OF AGREEMENT: Twenty-three studies were included: 10 reported on mid-shaft fractures, 14 on lateral fractures. The management principles for athletic patients were to attempt non-operative management for undisplaced fractures to undertake operative intervention for displaced lateral fractures and to recommend operative intervention for displaced mid-shaft fractures. AREAS OF CONTROVERSY: The optimal surgical modality for mid-shaft and lateral clavicle fractures. GROWING POINTS: Operative management of displaced mid-shaft fractures offers improved return rates and times to sport compared to non-operative management. Suture fixation and non-acromio-clavicular joint (ACJ)-spanning plate fixation of displaced lateral fractures show promising results. AREAS TIMELY FOR DEVELOPING RESEARCH: Future prospective studies should aim to establish the optimal treatment modalities for clavicle fractures.