Functional Longevity Research Articles

Genetic evaluation for longevity of Croatian Simmental bulls using a piecewise Weibull model

Abstract. Genetic evaluation of sires for functional longevity was conducted using survival analysis techniques. The data set consisted of 49 659 Simmental cows with first calving from 1997 to 2008. A piecewise Weibull sire model was used to estimate breeding values of 251 bulls for functional length of productive life of their daughters. The model was stratified by parity i.e. a separate baseline hazard was computed for each stratum. Besides the random sire effect, the model included the fixed time independent effects of age at first calving, herd size and region as well as the time dependent effects of relative milk production and year*season of first calving. The highest impact on longevity was found for relative milk production. Cows with the lowest milk yields were at approximately 2.7 times higher risk of culling compared to cows with average milk production. Effects of age at first calving, herd size and country region had lower impact on longevity. Sire variance was 0.023 which results in a heritability of 0.06 for functional length of productive life. The average approximate reliability of estimated breeding values was 0.49. Genetic trend showed no clear tendency by year of birth of bulls.

ELASTOMERS IN THE OIL FIELD

ABSTRACT Even before Spindletop “gushered” in the great Texas oil boom in 1901, rubber chemistry and technology played a key role in the pressure and flow control of hydrocarbons from petroleum reservoirs. This key role for rubber in the oil field continues today, where the cost of construction of an oil or gas well can exceed a billion dollars. Almost all equipment used in downhole drilling and completion operations currently depends on elastomers and other sealing materials to provide steady, reliable performance during service. Although the cost of the individual seals used downhole in a well represents only a fraction of the total well cost, the seals are critical to well performance and safety. Sealing mechanisms are at the heart of any drilling, completion, or production system and are the primary components on which the functional success and longevity of the system rests. Modern drilling systems, with their significant use of onboard electronic components and sensors, rely heavily on nonmetallic seals to prevent well environmental contamination while withstanding sustained dynamic loadings throughout service. Well completion systems can be categorized by either relatively short-term applications, after which seals can be changed or maintained, or long-term applications, in which seals are expected to perform without change or maintenance for 20 years or longer. The assurance of these systems' continued performance throughout the life of the well, whether the expected life is short or long, is of vital importance.

Impact of health disorders and culling reasons on functional and biological longevity in Warmblood breeding stallions

The objective of this study was to compare the impact of health disorders and reasons for culling on the functional and biological longevity of warmblood breeding stallions using semi-parametric survival analysis accounting for competing risks. Complete breeding records were collected from 455 warmblood stallions serving between 1975 and 2010 at Marbach State Stud in Germany. The median length of life (18.0years) was twice as long as the median length of service (9.0years). However, both figures increased significantly over the time period examined (e.g., functional longevity increased from 5years in the 1970s to 8years in the 1980s to 12years in the 1990s).Compared to disorders of the musculoskeletal system, hazards for termination of functional life were higher for infectious diseases with a hazard ratio (HR) of 3.5, and for dissatisfaction with performance (HR, 2.0). Hazards were lower for disorders of the respiratory system (HR, 0.78), followed by accidents (HR, 0.58), disorders of the reproductive system (HR, 0.51), sale for non-breeding purposes (HR, 0.40), disorders of the gastrointestinal system (HR, 0.36), unknown reasons (HR, 0.32) and disorders of the cardiovascular system (HR, 0.25). For biological life, the relative importance of these disorders was similar.Factors linked to demand for stallions such as coat colour and several parameters of the stallions’ genetic merit (negative influence) and own performance (positive influence) in dressage and particularly in show-jumping influenced (P<0.05) or tended to influence (P<0.1) functional, but not biological longevity. Furthermore, hazards for both functional and biological life declined with rising stud fees (both HR, 0.99; P<0.0001). A more direct consideration of both functional and biological longevity in breeding programmes might help to further enhance both figures, and therefore welfare of the horses.

Direct interaction between E47 and p21 controls LT-HSC proliferation and functional longevity (P4471)

Abstract Long-term hematopoietic stem cells (LT-HSCs) are important multipotent cells that replenish all immune cells lost due to natural turnover, infection or injury. LT-HSC proliferation is controlled by cell cycle regulators and upstream transcription factors but direct links between the two have not been established. Here, we demonstrate a mechanistic link between the transcription factor E47 and the major cell cycle regulator p21 in controlling LT-HSC proliferation, self-renewal, and functional competence. Gain-of-function and loss-of-function studies show that E47 directly regulates p21 transcription in HSCs. Using E47/p21 compound heterozygotes, a powerful approach for analyzing HSC activity in vivo, we show a 2-fold increase in BrdU+ LT-HSCs compared to WT or single HET controls in both steady state conditions and under transplantation stress. E47HETp21HET HSCs are also more sensitive to mitotoxic challenge with 5-FU resulting in a 45% decrease in HSC numbers compared to treated controls. In serial adoptive transfer assays, a rigorous challenge to HSC self-renewal, E47HETp21HET HSCs were decreased by 40% and 60% in secondary and tertiary recipients, respectively. In addition to hyperproliferation and poor self-renewal, E47HETp21HET adoptive transfer recipients had selective myeloid bias indicating HSC skewing. Together, these data suggest a developmental stage-specific, cell-intrinsic collaboration between E47 and p21 in the regulation of LT- HSC competence in vivo.

Estimation of genetic parameters for longevity traits in dairy cattle: A review with focus on the characteristics of analytical models

Longevity is an economically important trait of dairy cattle for increasing the profitability of dairy management. The reasons for culling can be either voluntary (primarily productivity) or involuntary (primarily health and fertility). Longevity characteristics include: (i) true longevity (all culling reasons, including productivity); and (ii) functional longevity (all culling reasons, except productivity). Improvements to longevity are made to decrease the rate of involuntary culling rather than extend the herd life (HL). The proportional hazard model is useful for evaluating genetic ability for HL. However, the differences between estimates made using the proportional hazard model and those made using linear single or multiple-trait animal models are not clear. The model commonly used for evaluation differs among countries. Productive traits, udder traits, and feet and legs traits are genetically correlated with longevity, and consequently these traits are used to indirectly evaluate longevity. The reliability of estimates of genetic ability for longevity is increased by combining direct and indirect estimates. In Japan, HL is evaluated using the multiple-traits model. The genetic correlations between HL and other traits vary with the birth year. Therefore, these genetic correlations need to be reviewed regularly.

The impact of chronic blood–brain barrier breach on intracortical electrode function

Brain-computer interfaces (BCIs) have allowed control of prosthetic limbs in paralyzed patients. Unfortunately, the electrodes of the BCI that interface with the brain only function for a short period of time before the signal quality on these electrodes becomes substantially diminished. To truly realize the potential of BCIs, it is imperative to have electrodes that function chronically. In order to elucidate the physiological determinants of a chronically functional neural interface, we studied the role of the blood–brain barrier (BBB) in electrode function, because it is a key mediator of neuronal hemostasis. We monitored the status of the BBB and the consequences of BBB breach on electrode function using non-invasive imaging, electrophysiology, genomic, and histological analyses. Rats implanted with commercially available intracortical electrodes demonstrated an inverse correlation between electrode performance and BBB breach over a period of 16 weeks. Genomic analysis showed that chronically functional electrodes elicit an enhanced wound healing response. Conversely, in poorly functioning electrodes, chronic BBB breach led to local accumulation of neurotoxic factors and an influx of pro-inflammatory myeloid cells, which negatively affect neuronal health. These findings were further verified in a subset of electrodes with graded electrophysiological performance. In this study, we determine the mechanistic link between intracortical electrode function and failure. Our results indicate that BBB status is a critical physiological determinant of intracortical electrode function and can inform future electrode design and biochemical intervention strategies to enhance the functional longevity of BCIs.

Understanding the genetics of survival in dairy cows

Premature mortality and culling causes great wastage in the dairy industry, as a large number of heifers born never become productive or are culled before their full lactation potential is reached. The objectives of this study were to characterize survival and estimate genetic parameters for alternative longevity traits that considered (1) the survival of replacement heifers and (2) functional longevity of milking cows in the UK Holstein Friesian population, using combined information from the British Cattle Movement Service and milk recording organizations. Mortality of heifers was highest in the first month of life and was proportionately highest in calves born during winter months. Heifer mortality tended to decrease with age until about 16mo onward; it then gradually increased, expected to be associated with culls due to reproductive failure or problems during pregnancy and calving. In milking cows, days of productive life (DPL) was analyzed as an alternative to the current trait lifespan score. Cows that died in 2009 on average lived for 6.8yr with an average production of 4.3yr. Heritability estimates were low for both heifer and cow survival and were ~0.01 and ~0.06, respectively. The positive genetic correlation between heifer survival with lifespan score (0.31) indicates that bulls that sire daughters with longer productive lives are also likely to have calves that survive and become replacement heifers. However, the magnitude of the genetic correlation suggests that survival in the rearing period and the milking herd are different traits. Genetic correlations were favorable between DPL with somatic cell count and fertility traits indicating that animals with a longer productive life tend to have lower somatic cell count, a shorter calving interval, fewer days to first service, and require fewer inseminations. However, an antagonistic relationship existed between DPL with milk and fat yield traits.

Effect of age at first calving on longevity and fertility traits for Holstein cattle

Effects of age at first calving (AFC) on functional longevity of Czech Holstein cows and their reproduction traits in the first lactation were analyzed using the first lactation data of 605 538 Holstein cows first calved from 1993 to 2008. Three classes were formed for AFC: low age class (16&amp;ndash;24 months), average age class (25&amp;ndash;30 months), and high age class (33&amp;ndash;46 months). Effects of AFC on length of productive life (LPL), days open (DO), days between calving and first service (CTFS), and days between first service and conception in the first lactation (FSTC) were estimated by survival and linear model analyses. It was found that LPL was on average slightly shorter for cows with higher AFC who showed also a lower proportion of higher lactations and tended to longer DO and longer CTFS in the first parity. The results of survival analysis indicate that cows with higher AFC had a tendency to shorter LPL (risk of culling 1.118) and to longer DO (risk of conception 0.758), CTFS (risk of conception 0.757), and FSTC (risk of conception 0.754) in comparison with cows with lower AFC. When the effect of fertility traits on LPL was analyzed, it was found that longer DO, CTFS, and FSTC were connected with a lower risk of culling (0.132, 0.183, 0.206) regardless of the particular AFC group. In linear model analysis, the effects of AFC group were estimated from two datasets, where the second dataset included also the missing values of fertility traits. It was found that the cows group with the highest AFC showed worse values of fertility traits (16.75, 19.69, 20.46 days) than the cows groups with lower AFC. Results of all analyses showed that a high AFC is connected with worse cow&amp;rsquo;s fertility at the first lactation and with lower cow&amp;rsquo;s LPL. &amp;nbsp; &amp;nbsp;

Comparison of piecewise Weibull baseline survival models for estimation of true and functional longevity in Brown cattle raised in small herds

Piecewise Weibull proportional hazard models were used to investigate the effect of genetic and nongenetic factors on functional and true longevity traits of the Slovenian Brown cattle breed. Records of 37 908 Brown cows from 2401 Slovenian herds were used. As these herds were characterised by a relatively small average herd size starting from 6.7 in 1999 and increasing to 8.7 Brown cows per herd in 2008, milk yield classification was made within different herd size groups. The hazard rate was the lowest in the first part of each lactation and was increasing for later stages. Culling risk was lower for cows from herds increasing in size, for cows with higher milk production and for cows from a region with smaller herd sizes and tougher conditions for cattle breeding. The latter result is surprising and may be related to better attention to maintain the animals, despite their lower milk production. The introduction of the milk quota system and drought was found to have an important effect on culling policy between the last seasons of the years 2001 and 2003. Seasonal effects were not related to the milk quota year (from April to March), but to the effect of shortage in fodder during the winter time. The effect of age at first calving and the interaction between year and milk yield class were not found to be significant. Heritability for functional and for true longevity were similar at around 10% each. Inclusion of a correction for class of milk yield to approximate functional longevity increased the herd-year random effect variance by 53%, whereas the sire variance increased by only 14%. The correlation coefficient between ranks of breeding values for functional and true longevity was high (0.91), whereas genetic trends were not found to be significant. To assess their predictive ability, models were compared looking at the survival rate of 4212 second-crop daughters not included in the initial models. The average correlation between estimated breeding values and survival at different stages was 0.39 for true longevity and 0.43 for functional longevity. Results showed that ranking milk yield at population level is appropriate to correct for voluntary culling on low production in small herds.

Current concepts of elbow-joint disorders and their treatment

BackgroundRecently, many studies have emphasized the importance of the comprehension of detailed functional anatomy and biomechanics of the elbow and its significant contribution in facilitating good functional outcomes of conservative and surgical treatment in the field of elbow disorders. MethodsThe most common disease of elbow disorders and their treatment was reviewed. ResultsLateral epicondylitis of the elbow, is defined as a microscopic tear of extensor carpi radialis brevis tendon, and microscopic findings show immature reparative tissue (angiofibroblastic hyperplasia). The patient needs coordinated rehabilitation, range-of motion-exercise, stretching, and bracing in the second phase. Ninety-five percent of patients with lateral epicondylitis heal spontaneously or conservatively. The medial collateral ligament injury of the elbow is most common in the overhead-throwing athlete. Jobe’s procedure, the original reconstruction technique, and its modifications in bone-tunnel creation, allow a tendon graft to be wound in a figure-eight configuration through the tunnels. Further modification of Jobe’s procedure in bone-tunnel configuration reduced the total number of tunnels and facilitates easier graft tensioning. Outcomes with these reconstruction techniques have proven effective in returning high-level throwing athletes back to their sport. Arthroscopic surgery for the elbow in the throwing athlete has evolved and has proven successful results. Arthroscopic treatment includes debridement of posteromedial synovitis, loose-body removal, and excision of the olecranon spur. Posteromedial elbow impingement is also a source of disability in the overhead-throwing athlete. Twenty-five percent of these patients require a medial collateral ligament reconstruction after removal of a posteromedial bony spur. Linked and unlinked total elbow arthroplasty are successful treatment procedures for patients with rheumatoid arthritis, posttraumatic osteoarthritis, and elderly patients with comminuted distal humeral fractures and the salvage of distal humeral nonunion. Proper selection and implantation of prostheses are also important to achieve good functional outcome and longevity. ConclusionThe success of treatment of elbow disorders depends greatly on surgical design and technique, both of which require comprehensive knowledge of detailed anatomy and biomechanics of the elbow.

Comparison of Conventional Polyethylene Wear and Signs of Cup Failure in Two Similar Total Hip Designs

Multiple factors have been identified as contributing to polyethylene wear and debris generation of the acetabular lining. Polyethylene wear is the primary limiting factor in the functional behavior and consequent longevity of a total hip arthroplasty (THA). This retrospective study reviewed the clinical and radiographic data of 77 consecutive THAs comparing in vivo polyethylene wear of two similar acetabular cup liners. Minimum follow-up was 7 years (range 7–15). The incidence of measurable wear in a group of machined liners sterilized with ethylene oxide and composed of GUR 1050 stock resin was significantly higher (61%) than the compression-molded, GUR 1020, O2-free gamma irradiation sterilized group (24%) (P = 0.0004). Clinically, at a 9-year average followup, both groups had comparable HHS scores and incidence of thigh or groin pain, though the machined group had an increased incidence of osteolysis and annual linear wear rate.

The Molecular Chaperone GRP78/BiP as a Therapeutic Target for Neurodegenerative Disorders: A Mini Review

The glucose regulated protein 78 (GRP78), also known as BiP, is the endoplasmatic reticulum (ER) homologue of HSP70, which plays a dual role in the ER by controlling protein folding, in order to prevent aggregation, and by regulating the signaling of the unfolded protein response (UPR). Most neurodegenerative disorders including Parkinson's, Alzheimer's diseases and progressive retinal degeneration are characterized by activation of the UPR and modified expression of GRP78. The expression levels and activity of GRP78 are altered with age raising the question of whether the lack of GRP78 could be a predisposing factor for many neurodegenerative disorders associated with age including PD, Alzheimer and Age-related macular degeneration. Attempts to induce or upregulate GRP78 in animal models of neurodegeneration have recently been made with the help of pharmacological BiP protein Inducer X (BIX) and GRP78 cDNA delivery via adeno-associated virus (AAV) vectors. The results of these studies validate GRP78 as a new therapeutic target for treatments of forebrain ischemia, Parkinson disease and retinal degeneration. These data, together with the results from age-related studies, highlight the importance for developing drugs to induce elevation of endogenous GRP78 in order to increase cellular survival and extend functional longevity.

Covalently grafted BMP‐7 peptide to reduce macrophage/monocyte activity: An in vitro study on cobalt chromium alloy

Cobalt chromium (CoCr) alloy is widely used in orthopedic implants but its functional longevity is susceptible to inflammation related complications. Reduction of the development of chronic inflammation on the biomaterial surface would enhance direct bone-implant bonding and improve implant survival and long-term results. The BMP-7 peptide was derived from the knuckle epitope of bone morphogenic protein-7 (BMP-7) and was conjugated via a cysteine amino acid at the N-terminus. Mouse RAW 264.7 monocytes/macrophages were seeded on the CoCr substrates and inflammation was induced via lipopolysaccharide (LPS) challenge. The effects of BMP-7 peptide on inflammation were evaluated by measuring the expression of inflammatory markers like toll-like receptor-4 (TLR-4), tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1). ELISA and qPCR assays were used to study the inflammatory signals. BMP-7 signaling pathway activation was shown by the presence of phosphorylation of Smad1/5/8. Utilizing the reactivity of polydopamine films to immobilize BMP-7 peptide onto metal substrates may provide a promising approach for applications in situations where reduction of inflammation around implants would be beneficial in improving surgical outcome, bone healing, and implant integration.

Curcumin is an early-acting stage-specific inducer of extended functional longevity in Drosophila

Larval feeding with curcumin induces an extended health span with significantly increased median and maximum longevities in the adult fly. This phenotype is diet insensitive and shows no additive effect on longevity when combined with an adult dietary restriction (DR) diet, suggesting that curcumin and DR operate via the same or overlapping pathways for this trait. This treatment significantly slows the aging rate so that it is comparable with that of genetically selected long lived animals. The larval treatment also enhances the adult animal's geotactic activity in an additive manner with DR, suggesting that curcumin and DR may use different pathways for different traits. Feeding the drug to adults during only the health span also results in a significantly extended health span with increased median and maximum life span. This extended longevity phenotype is induced only during these stage-specific periods. Feeding adults with the drug over their whole life results in a weakly negative effect on median longevity with no increase in maximum life span. There are no negative effects on reproduction, although larval curcumin feeding increases development time, and also apparently accelerates the normal late-life neuromuscular degeneration seen in the legs. Gene expression data from curcumin-fed larvae shows that the TOR pathway is inhibited in the larvae and the young to midlife adults, although several other genes involved in longevity extension are also affected. These data support the hypothesis that curcumin acts as if it is a DR mimetic nutraceutical. These data also suggest that the search for DR mimetics may be enhanced by the use of stage-specific screening of candidate molecules.

Toward Adaptive Sleep Schedules for Balancing Energy Consumption in Wireless Sensor Networks

In this work, we assume a geographic area populated by tiny sensors, each perhaps no larger than a dime. In order to save their energy, the sensors spend most of their lifetime in sleep mode and wake up for short periods of time to participate in various tasks supportive of the overall mission of the network. We assume that the tasks to be performed stipulate QoS parameters expressed in terms of the minimum number of sensors that need to monitor their sensing area. Since only awake sensors participate in tasks, the Effective Sensor Density (ESD), defined as the density of awake sensors, is an important network parameter that obviously depends on the sleep schedules adopted in the network. The first main contribution of this work is to provide a mathematical analysis of ESD from the perspective of the monitored events. We also provide design guidelines to determine deployment-time sensor density and an associated sleep schedule that probabilistically keeps the ESD at a level needed by QoS requirements. We also propose a fully distributed sleep schedule which adaptively adjusts the duty cycles of sensors within the same sensing area based on the relative difference in their remaining energy budget. The main advantage of the proposed adaptive scheme is to balance energy consumption among sensors, thus promoting the functional longevity of the sensor network without adversely affecting the ESD.

Research regarding reproduction capacity at dairy cows and the ways of improvement by application of biotechnologies

In the long term, resilient animals are able to maintain their normal biological processes when confronted with environmental perturbations, reducing their risk of being culled. Therefore, longevity can be proposed as an indicator of long-term resilience. Decisions to remove a given dairy cow from the herd are mainly related to low milk production (i.e., voluntary culling) or to reasons other than production (i.e., involuntary culling). The aptitude of animals to delay any culling is defined as true longevity (TL), whereas functional longevity (FL) is the ability to avoid involuntary culling. The aim of the study was to investigate the influence of production, reproduction, morphology, and health traits on TL and FL, to identify risk factors for culling. Data included 278,217 lactations from 122,461 Holstein Friesian cows reared in 640 herds. The length of productive life, calculated as the time between first calving and culling, or censoring, was used as the measure of longevity. Survival analysis was performed using proportional hazards models assuming a piecewise Weibull distribution of the baseline hazard function, with or without adjustment for milk production to evaluate FL and TL. Insemination status, calving ease, mastitis, somatic cell count, displaced abomasum, and udder depth had significant relationships with TL and FL. Differences in estimates of relative risk between TL and FL showed that milk production often influenced culling decisions: farmers are more prone to cull animals with low production even when they had good other characteristics. The culling risk factors identified in the present study can be used to study resilience in dairy cattle and to improve genetic evaluations of functional or total longevity.

Analysis of longevity in Holstein Friesian cattle using proteomic approaches

The aim of the present study was to determine marker proteins those are associated with functional longevity of dairy cattle. Holstein-Friesian cows were grouped based on their performance as follows: group 1) individuals with good longevity traits; group 2) short production life because of poor reproduction traits; group 3) short production life with low milk yield. Twelve individuals were sampled in each group, blood and milk samples were collected from cows. Blood samples were analysed with two dimensional polyacrylamide gel electrophoresis (2D PAGE), MALDI TOF/TOF and nanoLCMS/MS. The milk samples were analysed with MALDI TOF/TOF and nanoLC-MS/MS. Using the optimized gel based proteomic approach,we have succesfully separated 143 proteins in the group1, 139 proteins in the group2 and 136 proteins in the group3, but we could not find significant differences between groups in the expression pattern. Using MALDI TOF/TOF and nanoLC-IonTrap MS, we have found eleven protein sequences those were expressed only in the samples of good longevity group.

Cruciate-Retaining vs Posterior-Substituting Inserts in Total Knee Arthroplasty: Functional Outcome Comparison

Despite clinical success, it is unclear which one, posterior-substituting (PS) or cruciate-retaining (CR) insert, has superior functional outcomes or longevity. We compared the collected results from 2 institutional review board–approved, multicenter, prospective observational studies following CR (412) and PS inserts (328). Participants were evaluated preoperatively, at 6 weeks, at 3 months, and at 1 and 2 years regarding pain, motion, function (Knee Society Score, Krackow Activity Score, Short Form–36), and procedure variables such as anesthesia and preoperative/perioperative/postoperative complications. Implant longevity was recorded at the 2-year follow-up. Improvement was observed within each group; however, there was no difference between groups in terms of pain, motion, or function at any end point. Two-year survival rate was higher than 95%. A higher incidence of wound hematoma was observed in the PS group. Both inserts can be used expecting satisfactory outcomes and high survival rates at 2 years.

Relationship between conformation traits and longevity in Polish Holstein Friesian cattle

A Weibull proportional hazard model was applied to examine the impact of conformation on true and functional longevity of Polish HF cattle. Lifetime records of 592,639 cows from 2369 herds calving from 1995 to 2008 were used. Conformation data available for 236,137 cows consisted of phenotypic scores for 14 linear traits. True longevity (LPL) was defined as the number of days from first calving to culling or censoring, and functional longevity (FLPL) as LPL adjusted for production. Linear type traits were added into the reference model, which included random effect of herd–year–season, and fixed effects of age at first calving, year–season, parity-stage of lactation, annual change in herd size, and (for FLPL) fat and protein yield. The strongest and positive influence on true longevity was found for udder traits. Capacity traits, rump traits, teat length and rear leg set displayed intermediate optima with respect to LPL. The highest impacts on functional longevity were from udder depth, body depth, chest width, and dairy character. Those traits can be considered early predictors. In respect to FLPL, udder depth had a positive impact, body depth showed an intermediate optimum, and the influences of chest width and dairy character were negative.

Current concepts in surgical treatment of osteosarcoma.

Osteosarcoma is the most common malignant primary neoplasm of bone. For an optimal oncological outcome, surgical removal of tumor is an essential component of its multidisciplinary treatment. Limb salvage surgery has long been established as the standard of care for osteosarcoma. While limb-salvaging techniques have acceptable rates of disease control, amputation remains a valid procedure in selected cases. In current orthopedic oncology practice, the focus is on optimizing the balance between preservation of form and function of the limb and adequate oncological clearance at the same time. Improving the functional outcome and longevity of reconstructive procedures also remains a challenge.