The effect of tibial slope on the biomechanics of cruciate-retaining TKA:a musculoskeletal simulation study

INTRODUCTION: Tibial slope can affect the outcomes of Total Knee Arthroplasty (TKA). More posterior slope potentially helps releasing a too tight flexion gap and it is generally associated with a wider range of post-operative knee flexion. However, the mechanism by which tibial slope affects the function of TKA during dynamic activities of daily living is rather complex and not well documented. The aim of this study was to investigate the effect of tibial slope on the kinematics of the tibiofemoral (TF) contact point, quadriceps muscle forces, and patellofemoral (PF) joint contact forces during squat. In addition, we studied the effect of anterior tibial cortex-referencing (ACR) versus center of tibial plateau-referencing (CPR), as two possible techniques to obtain the desired degree of tibial slope. METHODS: A previously validated musculoskeletal model of a 86-year-old male subject, having a cruciate-retaining (CR) TKA prosthesis, was used to simulate a squat activity [1]. Motion-capture data were input to a motion optimization algorithm to find the full body kinematics. Quadriceps muscle forces were then calculated using inverse-dynamics. The kinematics of the TF contact point and PF joint contact forces were simultaneously calculated using force-dependent kinematics. A baseline case with 0° tibial slope was simulated, plus four additional cases with anterior (-3°), and posterior (+3°, +6°, +9°) tibial slope using the ACR technique (Fig. 1a), and four using the CPR technique (Fig. 1b). RESULTS: Compared to the baseline, more posterior tibial slope with ACR technique resulted in a larger excursion of the TF contact point, which shifted to a more anterior position, on the lateral side, and a more posterior position, on the medial side, in extension (Fig. 2). With the CPR technique, the contact point in extension shifted gradually more posterior on both sides with more posterior slope, and in flexion it shifted gradually more posterior mainly on the lateral side. The peak quadriceps force decreased on average by 1.7 and 1.2 % BW per degree of more posterior slope, with the ACR and CPR techniques, respectively. However, due to the different relative position of patella and femur, the peak PF contact force was mainly reduced by increasing the posterior slope with the CPR technique (-3.9 % BW/degree), rather than with the ACR technique (-1.5 % BW/degree) (Fig. 3). DISCUSSION: Increasing the tibial slope using the ACR technique produced large changes in the TF kinematics: the pattern of the contact point became more unstable, with a larger AP movement observed on the lateral side, denoting increased anterior-posterior laxity. On the other hand, variations of tibial slope with CPR technique resulted in more stable TF kinematics, more posterior position of the TF contact point, and a greater reduction of the PF contact forces. It is advisable to pre-plan the desired amount of tibial slope and execute it using the CPR technique. The surgeon should be very careful applying too much tibial slope with the ACR technique in CR-TKA, as it may have devastating effects on the TF kinematics, laxity and PF forces. SIGNIFICANCE: This study provides new insights into the effect of variation of tibial slope in TKA using different surgical techniques, which were not documented before, and used a highly controlled and parameterized study design and dynamic loading conditions. Orthopedic surgeons can directly use these results as an indication for the clinical practice. The presented tool can also be very useful for educational/medical training purposes. REFERENCES: [1] Marra MA, Vanheule V, Fluit R, et al. A Subject-Specific Musculoskeletal Modeling Framework to Predict In Vivo Mechanics of Total Knee Arthroplasty. ASME. J Biomech Eng. 2015;137(2):020904-020904-12 ACKNOWLEDGEMENTS: The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 323091 awarded to N. Verdonschot

Differential survival throughout the full annual cycle of a migratory bird presents a life-history trade-off.

Long-distance migrations are among the most physically demanding feats animals perform. Understanding the potential costs and benefits of such behaviour is a fundamental question in ecology and evolution. A hypothetical cost of migration should be outweighed by higher productivity and/or higher annual survival, but few studies on migratory species have been able to directly quantify patterns of survival throughout the full annual cycle and across the majority of a species' range. Here, we use telemetry data from 220 migratory Egyptian vultures Neophron percnopterus, tracked for 3,186 bird months and across approximately 70% of the species' global distribution, to test for differences in survival throughout the annual cycle. We estimated monthly survival probability relative to migration and latitude using a multi-event capture-recapture model in a Bayesian framework that accounted for age, origin, subpopulation and the uncertainty of classifying fates from tracking data. We found lower survival during migration compared to stationary periods (β = −0.816; 95% credible interval: −1.290 to −0.318) and higher survival on non-breeding grounds at southern latitudes (<25°N; β = 0.664; 0.076-1.319) compared to on breeding grounds. Survival was also higher for individuals originating from Western Europe (β = 0.664; 0.110-1.330) as compared to further east in Europe and Asia, and improved with age (β = 0.030; 0.020-0.042). Anthropogenic mortalities accounted for half of the mortalities with a known cause and occurred mainly in northern latitudes. Many juveniles drowned in the Mediterranean Sea on their first autumn migration while there were few confirmed mortalities in the Sahara Desert, indicating that migration barriers are likely species-specific. Our study advances the understanding of important fitness trade-offs associated with long-distance migration. We conclude that there is lower survival associated with migration, but that this may be offset by higher non-breeding survival at lower latitudes. We found more human-caused mortality farther north, and suggest that increasing anthropogenic mortality could disrupt the delicate migration trade-off balance. Research to investigate further potential benefits of migration (e.g. differential productivity across latitudes) could clarify how migration evolved and how migrants may persist in a rapidly changing world

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Equations for the estimation of strong ground motions from shallow crustal earthquakes using data from Europe and the Middle East : vertical peak ground acceleration and spectral acceleration

This article presents equations for the estimation of vertical strong ground motions caused by shallow crustal earthquakes with magnitudes M w 5 and distance to the surface projection of the fault less than 100km. These equations were derived by weighted regression analysis, used to remove observed magnitude-dependent variance, on a set of 595 strong-motion records recorded in Europe and the Middle East. Coefficients are included to model the effect of local site effects and faulting mechanism on the observed ground motions. The equations include coefficients to model the observed magnitude-dependent decay rate. The main findings of this study are that: short-period ground motions from small and moderate magnitude earthquakes decay faster than the commonly assumed 1/r, the average effect of differing faulting mechanisms is similar to that observed for horizontal motions and is not large and corresponds to factors between 0.7 (normal and odd) and 1.4 (thrust) with respect to strike-slip motions and that the average long-period amplification caused by soft soil deposits is about 2.1 over those on rock sites

Types of Stroke among People Living with HIV in the United States

Background: Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes.Setting: CNICS, a U.S. multisite clinical cohort of PLWH in care.Methods: We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort.Results: Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes.Conclusion: Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH

Phylogenomic analysis of a 55.1 kb 19-gene dataset resolves a monophyletic Fusarium that includes the Fusarium solani Species Complex

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user¿s needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option availabl

State of the climate in 2013

In 2013, the vast majority of the monitored climate variables reported here maintained trends established in recent decades. ENSO was in a neutral state during the entire year, remaining mostly on the cool side of neutral with modest impacts on regional weather patterns around the world. This follows several years dominated by the effects of either La Niña or El Niño events. According to several independent analyses, 2013 was again among the 10 warmest years on record at the global scale, both at the Earths surface and through the troposphere. Some regions in the Southern Hemisphere had record or near-record high temperatures for the year. Australia observed its hottest year on record, while Argentina and New Zealand reported their second and third hottest years, respectively. In Antarctica, Amundsen-Scott South Pole Station reported its highest annual temperature since records began in 1957. At the opposite pole, the Arctic observed its seventh warmest year since records began in the early 20th century. At 20-m depth, record high temperatures were measured at some permafrost stations on the North Slope of Alaska and in the Brooks Range. In the Northern Hemisphere extratropics, anomalous meridional atmospheric circulation occurred throughout much of the year, leading to marked regional extremes of both temperature and precipitation. Cold temperature anomalies during winter across Eurasia were followed by warm spring temperature anomalies, which were linked to a new record low Eurasian snow cover extent in May. Minimum sea ice extent in the Arctic was the sixth lowest since satellite observations began in 1979. Including 2013, all seven lowest extents on record have occurred in the past seven years. Antarctica, on the other hand, had above-average sea ice extent throughout 2013, with 116 days of new daily high extent records, including a new daily maximum sea ice area of 19.57 million km2 reached on 1 October. ENSO-neutral conditions in the eastern central Pacific Ocean and a negative Pacific decadal oscillation pattern in the North Pacific had the largest impacts on the global sea surface temperature in 2013. The North Pacific reached a historic high temperature in 2013 and on balance the globally-averaged sea surface temperature was among the 10 highest on record. Overall, the salt content in nearsurface ocean waters increased while in intermediate waters it decreased. Global mean sea level continued to rise during 2013, on pace with a trend of 3.2 mm yr-1 over the past two decades. A portion of this trend (0.5 mm yr-1) has been attributed to natural variability associated with the Pacific decadal oscillation as well as to ongoing contributions from the melting of glaciers and ice sheets and ocean warming. Global tropical cyclone frequency during 2013 was slightly above average with a total of 94 storms, although the North Atlantic Basin had its quietest hurricane season since 1994. In the Western North Pacific Basin, Super Typhoon Haiyan, the deadliest tropical cyclone of 2013, had 1-minute sustained winds estimated to be 170 kt (87.5 m s-1) on 7 November, the highest wind speed ever assigned to a tropical cyclone. High storm surge was also associated with Haiyan as it made landfall over the central Philippines, an area where sea level is currently at historic highs, increasing by 200 mm since 1970. In the atmosphere, carbon dioxide, methane, and nitrous oxide all continued to increase in 2013. As in previous years, each of these major greenhouse gases once again reached historic high concentrations. In the Arctic, carbon dioxide and methane increased at the same rate as the global increase. These increases are likely due to export from lower latitudes rather than a consequence of increases in Arctic sources, such as thawing permafrost. At Mauna Loa, Hawaii, for the first time since measurements began in 1958, the daily average mixing ratio of carbon dioxide exceeded 400 ppm on 9 May. The state of these variables, along with dozens of others, and the 2013 climate conditions of regions around the world are discussed in further detail in this 24th edition of the State of the Climate series. © 2014, American Meteorological Society. All rights reserved

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017