Search

The opportunity to benefit from climate prediction arises from the intersection of human vulnerability, climate predictability, and decision capacity. Climate forecasts, like other technical innovations, are not an unambiguous boon to growers. Florida's tomato industry was shown vulnerable to predictable climate variability. This industry is characterized by a small number of decision makers who may have profound influence on aggregate supply, prices, grower's decision capacity, and potential benefits of climate predictions. The objective of this study is to evaluate the potential benefits of ENSO forecast information as a function of the scale of adoption. Using a participatory approach, biophysical modeling, and economic modeling, we estimated the value of ENSO forecasts at the field, farm, and regional scales for Florida's fresh tomato production. Simulated yield reductions in El Niño years relative to neutral years (∼20%) compared closely with historical results (∼23%). At the field scale, we showed that growers can adjust planting dates to reduce negative impacts of El Niño on yields and increase productivity during La Niña years. Adoption of climate forecast can help growers increase income and reduce costs at the farm scale. At the regional scale, the aggregate forecast value to producers increased with increasing adoption. However, our simulation results suggest that widespread forecast adoption can offset and perhaps eliminate the benefits of forecast adoption to individual tomato growers. Climate forecasts are an emerging technical innovation that may improve productive efficiency for Florida's tomato growers. However, if tomato growers' responses to ENSO forecasts will affect agricultural markets, then growers should consider those market changes when deciding whether to adopt these forecasts. Future development of technology to apply climate forecasts in the tomato industry should focus on strategies to reduce costs rather than to increase tomato production. [ABSTRACT FROM AUTHOR]

Osteochondromas, the most common benign bone tumor, often go undetected and seldom cause significant clinical sequelae. Rarely they present as an arterial pseudoaneurysm, usually of the popliteal or superficial femoral artery. The authors present the case of a 14-year-old male with a distal superficial femoral artery pseudoaneurysm accompanied by distal embolization from a femoral exostosis. [ABSTRACT FROM AUTHOR]

The objective of this study was to quantify the coacti vation patterns of the knee flexor and extensor muscles as part of continued efforts to identify the role of the antagonist muscles in maintaining joint stability.The simultaneous EMG from the flexor and extensor muscles of the knee were recorded during maximal effort, slow isokinetic contractions (15 deg/sec) on the plane parallel to the ground to eliminate the effect of gravity. The processed EMG from the antagonist mus cle was normalized with respect to its EMG as agonist at maximal effort for each joint angle. The plots of normalized antagonist EMG versus joint angle for each muscle group were shown to relate inversely to their moment arm variations over the joint range of motion. Additional calculations demonstrated that the antago nist exerts nearly constant opposing torque throughout joint range of motion. Comparison of data recorded from normal healthy subjects with that of high perform ance athletes with hypertrophied quadriceps demon strated strong inhibitory effects on the hamstrings coac tivations. Athletes who routinely exercise their ham strings, however, had a coactivation response similar to that of normal subjects.We concluded that coactivation of the antagonist is necessary to aid the ligaments in maintaining joint stability, equalizing the articular surface pressure dis tribution, and regulating the joint's mechanical imped ance. The reduced coactivation pattern of the unexer cised antagonist to a hypertrophied muscle increases the risk of ligamentous damage, as well as demon strates the adaptive properties of the antagonist muscle in response to exercise. It was also concluded that reduced risk of knee injuries in high performance ath letes with muscular imbalance could result from com plementary resistive exercise of the antagonist muscle. [ABSTRACT FROM PUBLISHER]

This study illustrates the potential synergies and conflicts of interest between farmers and insurers in the selection of an optimal crop insurance contract. Special attention is given to how climate information influences this decision-making process. To do so, we consider a representative 40 ha, rainfed, cotton-peanut farm located in Jackson County, Florida. Our results show that year-to-year El Niño Southern Oscillation (ENSO) based climate variability affects farmers' and insurers' net returns according to crop insurance contracts. Introduction of ENSO-based climate forecasts presents a significant impact on the selection of a particular contract to both the farmer and the insurer. We conclude that insurers and farmers can bridge their divergent interests by improving their understanding of the effect of climate conditions on the development of sustainable business plans. [ABSTRACT FROM AUTHOR]

Predictability of seasonal climate variability associated with the El Niño Southern Oscillation (ENSO) suggests a potential to reduce farm risk by selecting crop insurance products with the purpose of increasing farm income stability. A hypothetical 50% peanut, 50% cotton, non-irrigated, 40 ha (100 ac) north Florida farm was used to study the interactions of different crop insurance products with ENSO-based climate information and levels of risk aversion under uncertain conditions of climate and prices. Crop yields simulated by the DSSAT suite of crop models using multiyear weather data combined with historical series of prices were used to generate long series of stochastic income distributions in a whole-farm model portfolio. The farm model optimized planting dates and simulated uncertain incomes for 50 alternative crop insurance combinations for different levels of risk aversion under different planning horizons. Results suggested that incomes are greatest and most stable for low risk-averse farmers when catastrophic (CAT) insurance for cotton and 70% or 75% actual production history (APH) for peanut are selected in all ENSO phases. For high risk-averse farmers, the best strategy depends on the ENSO phase: (1) 70% crop revenue coverage (CRC) or CAT for cotton and 65% APH for peanut during EL Niño years; (2) CAT for cotton and 65%, 70%, or 75% APH for peanut during neutral years; and (3) 65% to 70% APH, or CAT for cotton and 70% APH for peanut during La Niña years. Optimal planting dates varied for all ENSO phases, risk aversion levels, and selected crop insurance products. [ABSTRACT FROM AUTHOR]

Background: Impending and complete pathologic fractures of the distal humerus are rare complications of metastatic cancer. Surgical treatment aims to quickly restore function and minimize pain. Plate and screw fixation (PSF) is a common method for addressing these lesions, but unlike in orthopaedic trauma, there are no clear guidelines for best management. While dual PSF theoretically provides better support and reduces the chance of reoperation due to tumor progression, single PSF is currently the more common choice., Materials and Methods: Between March 2008 and September 2021, 35 consecutive patients who underwent PSF for distal humerus metastasis or multiple myeloma were retrospectively reviewed. The proportion of patients who developed various postoperative complications, including infection, nonunion, deep vein thrombosis, tumor progression, and radial nerve palsy, as well as those requiring reoperation, was calculated. Mann-Whitney U test, Pearson's chi-squared, and Fisher's exact test were used to investigate differences between the single and dual PSF groups with statistical significance defined as p ≤ 0.05., Results: There was no significant difference (p = 0.259) in revision rate, although 3 of 21 (14.3 %) single PSF patients required reoperation compared to 0 of 14 (0.0 %) dual PSF patients. The revisions were performed in one patient due to refracture and in two patients due to tumor progression. Although not statistically significant, a larger percentage of single PSF patients developed a postoperative complication compared to dual PSF patients [odds ratio 0.42 (95 % confidence interval 0.071 to 2.5); p = 0.431]. Single PSF did lead to shorter operative time compared to dual PSF [p < 0.001]., Conclusion: Dual PSF is non-inferior to single PSF and potentially results in fewer reoperations and postoperative complications in distal humerus pathologic lesions, although it leads to longer operative time. The current study is limited by small sample size due to the rarity of distal humerus metastatic lesions., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Soft-tissue sarcomas (STS) are heterogeneous with variable response to radiation therapy (RT). Utilizing the radiosensitivity index (RSI) we estimated the radiobiologic ratio of lethal to sublethal damage (α/β), genomic-adjusted radiation dose(GARD), and in-turn a biological effective radiation dose (BED)., Methods: Two independent cohorts of patients with soft-tissue sarcoma were identified. The first cohort included 217 genomically-profiled samples from our institutional prospective tissue collection protocol; RSI was calculated for these samples, which were then used to dichotomize the population as either highly radioresistant (HRR) or conventionally radioresistant (CRR). In addition, RSI was used to calculate α/β ratio and GARD, providing ideal dosing based on sarcoma genomic radiosensitivity. A second cohort comprising 399 non-metastatic-STS patients treated with neoadjuvant RT and surgery was used to validate our findings., Results: Based on the RSI of the sample cohort, 84% would historically be considered radioresistant. We identified a HRR subset that had a significant difference in the RSI, and clinically a lower tumor response to radiation (2.4% vs. 19.4%), 5-year locoregional-control (76.5% vs. 90.8%), and lower estimated α/β (3.29 vs. 5.98), when compared to CRR sarcoma. Using GARD, the dose required to optimize outcome in the HRR subset is a BED α/β= 3.29 of 97 Gy., Conclusions: We demonstrate that on a genomic scale, that although STS is radioresistant overall, they are heterogeneous in terms of radiosensitivity. We validated this clinically and estimated an α/β ratio and dosing that would optimize outcome, personalizing dose., (Copyright © 2021. Published by Elsevier Inc.)

Background: Breast cancer is the most common cancer and second cause of death in women worldwide. Patients with breast cancer are classified into subgroups based on the presence or absence of hormone receptors and the human epidermal growth factor 2-neu (HER-2) marker, the different molecular profiles come with an associated prognosis and variety of possible treatment options. Patients with triple negative cancer have a worse prognosis, a more aggressive behavior, higher likelihood of spreading, a higher risk of recurrence and a poorer outcome overall. Intramedullary rod fixation has proven to provide a good outcome and function in patients with metastatic breast cancer, but no study has addressed the receptor-status potential outcome differences that may affect disease progression at an orthopaedic surgery site., Questions/purposes: (1) Do patients with triple negative breast cancer have a higher revision rate of intramedullary rod fixation of bone metastases? (2) Do patients with metastatic triple negative breast cancer have a higher revision rate of intramedullary rod fixation due to local disease progression?, Methods: This was a single-center, observational, retrospective cohort study. Fifty-seven patients with a diagnosis of breast cancer metastatic to long bones who underwent surgical fixation with an intramedullary rod for a pathological fracture or an impending fracture due to a bone metastasis with a Mirels' score equal or above 8 between January 2004 and December 2016 at our institution were included. All implants used were from the same manufacturer (Stryker Corp., Mahwah, NJ, USA). Patients were divided into two groups based on the receptor status of the tumor and were classified either as triple negative, when the tumor lacked progesterone, estrogen and HER-2 receptors, or as receptor-positive when the presence of one or a combination of either three was proven. In the triple-negative tumor group the mean follow up time was 26 months (SD 29) and median follow up time was 16 months. In the receptor-positive tumor group mean follow up was 27 months (SD 24) with a median follow up of 19 months. To assess possible associations between different factors and the outcomes of interest, we used either the chi-square test or Fisher's exact test for categorical variables and the ANOVA test for continuous variables. For the survival assessment, a Kaplan-Meier analysis was performed and for the cumulative incidence a competing risk analysis was utilized., Results: The intramedullary rod revision rate for patients in the triple-negative tumor group was 17%, while for the receptor-positive group it was 12%, this was not statistically different for our sample size. The mean time for revision of the intramedullary rod in the whole sample was 19 months (SD 11, range 6-40). The causes of revision were disease progression (43%), nonunion (29%) and surgeon error (29%). The cumulative incidence of revision surgery was 6% (CI 95%, 2-14%) at 12 months and 20% (CI 95%, 8-36%) at 60 months., Conclusions: Intramedullary rodding can be considered for the treatment of long bones metastases in breast cancer patients for an impending or actual pathological fracture. There is no difference in the intramedullary rod revision rate among patients with different receptor-status when comparing triple-negative tumor patients and receptor-positive ones., Level of Evidence: Level III, therapeutic study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: Aseptic loosening is one of the most common causes of revision of distal femoral endoprostheses and is considered a mid- to long-term complication. There are not many reports of 10-year survivorship free from aseptic loosening and all-cause survivorship in cemented stems. To our knowledge, there are no reports on radiographic features that are associated with aseptic loosening of these implants., Questions/purposes: (1) What is the 5- and 10-year survivorship free from aseptic loosening in patients undergoing reconstruction with a cemented distal femoral endoprosthesis after a tumor resection? (2) What is the all-cause 5- and 10-year survivorship at in these patients? (3) What radiographic features are associated with aseptic loosening at long-term follow-up?, Methods: We performed a multicenter retrospective study reviewing aseptic loosening in cemented prostheses to determine radiographic features associated with long-term implant survivorship. Patients who underwent a cemented distal femoral reconstruction with a modular endoprosthesis after resection of a musculoskeletal tumor between 1997 and 2017 were reviewed. A total of 246 patients were identified from five institutions and met initial inclusion criteria. Of those, 21% (51) were lost to follow-up before 2 years, leaving 195 patients available for us to evaluate and analyze the survivorship and radiologic features associated with long-term implant survival. The mean (range) follow-up was 78 months (22 to 257). At the time of this analysis, 69% (135 of 195) of the patients were alive. Osteosarcoma was the most common diagnosis in 43% of patients (83 of 195), followed by metastatic carcinoma 13% (25 of 195). Fifty-six percent (110 of 195) of patients received chemotherapy; 15% (30 of 195) had radiation therapy. Aseptic loosening was diagnosed radiographically and was defined as a circumferential radiolucent line on all views, or subsidence around the stem in the absence of infection. We present 5- and 10-year Kaplan-Meier survivorship free from aseptic loosening, 5- and 10-year all-cause survivorship, and a qualitative assessment of radiographic features potentially associated with aseptic loosening (including the junctional radiolucent area, and cortical expansion remodeling). The junctional radiolucent area was defined as a radiolucent area of the bone starting at the bone-endoprosthesis junction to the tip of the femoral stem, and cortical expansion remodeling was defined as an increased cortical thickness at the stem tip. Although we wished to statistically analyze radiographic factors potentially associated with aseptic loosening, we did not have enough clinical material to do so (only nine patients developed loosening). Instead, we will report a few preliminary qualitative observations, which necessarily are preliminary, and which will need to be confirmed or refuted by future studies. We urge caution in interpreting these findings because of the very small numbers involved., Results: Kaplan-Meier survivorship free from aseptic loosening of the femoral component at 5 and 10 years were 95% (95% CI 89 to 98) and 93% (95% CI 86 to 97), respectively. Kaplan-Meier survivorship free from revision for any cause at 5 and 10 years were 74% (95% CI 65 to 79) and 64% (95% CI 49 to 70), respectively. Although the numbers were too small to analyze statistically, all patients with aseptic loosening had a junctional radiolucent area more than 20% of the total length of the stem without cortical expansion remodeling at the stem tip. No aseptic loosening was observed if there was cortical ex remodeling, a junctional radiolucent area less than 20%, or curved stems that were 13 mm or greater in diameter. The numbers of patients with aseptic loosening in this series were too small to analyze statistically., Conclusions: Cemented distal femoral endoprostheses have a relatively low rate of aseptic loosening and acceptable projected first-decade survivorship. The presence of a radiolucent area more than 20% without cortical expansion remodeling at the stem tip may lead to aseptic loosening in patients with these implants. Close radiographic surveillance and revision surgery may be considered for progressive lucencies and clinical symptoms of pain. If revision is contemplated, we recommend using larger diameter curved cemented stems. These are preliminary and provisional observations based on a low number of patients with aseptic loosening; future studies with greater numbers of patients are needed to validate or refute these findings., Level of Evidence: Level III, therapeutic study.

Background: Rising health care costs, physician shortages, and an aging patient population have increased the demand and utilization of advanced practice providers (APPs). Despite their expanding role in care delivery, little research has evaluated the care delivered by APPs compared with physicians., Methods: We used clinical patient simulations to measure and compare the clinical care offered by APPs and physicians, collecting data from 4 distinct health care systems/hospitals in the United States between 2013 and 2017. Specialties ranged from primary care to hospital medicine and oncology. Primary study outcomes were to 1) measure any differences in practice patterns between APPs and physicians, and 2) determine whether the use of serial measurement and feedback could mitigate any such differences., Results: At baseline, we found no major differences in overall performance of APPs compared with physicians (P = .337). APPs performed 3.2% better in history taking (P = .013) and made 10.5% fewer unnecessary referrals (P = .025), whereas physicians ordered 17.6% fewer low-value tests per case (P = .042). Regardless of specialty or site, after 4 rounds of serial measurement and provider-specific feedback, APPs and physicians had similar increases in average overall scores-7.4% and 7.6%, respectively (P < .001 for both). Not only did both groups improve, but practice differences between the groups disappeared, leading to a 9.1% decrease in overall practice variation., Conclusions: We found only modest differences in quality of care provided by APPs and physicians. Importantly, both groups improved their performance with serial measurement and feedback so that after 4 rounds, the original differences were mitigated entirely and overall variation significantly reduced. Our data suggest that APPs can provide high quality care in multiple clinical settings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Interdisciplinary research is increasingly called upon to find solutions to complex sustainability problems, yet co-creating usable knowledge can be challenging. This article offers broad lessons for conducting interdisciplinary science from the South Florida Water, Sustainability, and Climate Project (SFWSC), a 5-year project funded by the U.S. National Science Foundation (NSF). The goal was to develop a holistic decision-making framework to improve understanding of the complex natural-social system of South Florida water allocation and its threats from climate change, including sea level rise, using a water resources optimization model as an integration mechanism. The SFWSC project faced several challenges, including uncertainty with tasks, high task interdependence, and ensuring communication among geographically dispersed members. Our hypothesis was that adaptive techniques would help overcome these challenges and maintain scientific rigor as research evolved. By systematically evaluating the interdisciplinary management approach throughout the project, we learned that integration can be supported by a three-pronged approach: (1) Build a well-defined team and leadership structure for collaboration across geographic distance and disciplines, ensuring adequate coordination funding, encouraging cross-pollination, and allowing team structure to adapt; (2) intentionally design a process and structure for facilitating collaboration, creating mechanisms for routine analysis, and incorporating collaboration tools that foster communication; and (3) support integration within the scientific framework, by using a shared research output, and encouraging team members to adapt when facing unanticipated constraints. These lessons contribute to the international body of knowledge on interdisciplinary research and can assist teams attempting to develop sustainable solutions in complex natural-social systems.

South Florida's water infrastructure and ecosystems are under pressure from socio-economic growth. Understanding the region's water resources management tradeoffs is essential for developing effective adaptation strategies to cope with emerging challenges such as climate change and sea level rise, which are expected to affect many other regions in the future. We describe a network-based hydro-economic optimization model of the system to investigate the tradeoffs, incorporating the economic value of water in urban and agricultural sectors and economic damages due to urban flooding while also accounting for water supply to sustain fragile ecosystems such as the Everglades and coastal estuaries. Results illustrate that maintaining high reliability of urban water supply under scenarios of reduced water availability (i.e., drier climate conditions) may trigger economic losses to the Everglades Agricultural Area, which will likely become more vulnerable as competition over scarce water resources increases. More pronounced economic losses are expected in urban and agricultural areas when flows to the Everglades are prioritized. Flow targets for coastal estuaries are occasionally exceeded under optimal flow allocations to various demand nodes, indicating that additional storage may be needed to maintain the environmental integrity of the estuarine ecosystems. Wetter climate conditions, on the other hand, generally lead to increased flows throughout the system with positive effects on meeting water demands, although flood mitigation efforts will necessitate additional releases to the estuaries. Strengths and limitations of the hydro-economic model are discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Prior studies illustrated a reduction in wound complications with the use of staged reconstruction (SR) and negative pressure wound therapy when treating soft tissue sarcoma (STS) with surgical resection followed by high-dose-rate adjuvant brachytherapy. The purpose of this study is to compare the outcomes of SR and immediate reconstruction (IR) brachytherapy in recurrent STS., Methods and Materials: A retrospective review of 40 patients with recurrent STS of the local extremity and trunk treated with resection followed by adjuvant brachytherapy alone. Margin status was defined as positive (SM(+)) if there was microscopic involvement (R1) or ≤1 mm margin and negative (SM(-)) if >1 mm margin was obtained. SR and IR were compared regarding toxicity, local control, and limb preservation., Results: Median followup was 27 months. When comparing the SR (n = 22) and IR (n = 18) cohorts, there was a significantly lower final SM(+) rate in SR (32% vs. 83%, p < 0.01). A 2-year local control benefit seen with SR (80% vs. 34%; p = 0.012) and a final SM(-) (81% vs. 39%; p = 0.023). SR was associated with less toxicity on multivariate analysis, including a 90% decrease in persistent edema, an 80% decrease in wound dehiscence, and a 94% decrease in nonhealing wounds, when compared to IR. Ten of 31 (32%) extremity cases required eventual amputation from either chronic wound complications (n = 4) or local recurrence (n = 6). SR predicted for a benefit in 2-year limb preservation (88% vs. 50%; p = 0.008)., Conclusion: In our series, the treatment with SR brachytherapy resulted in less morbidity and an improved final SM(-) rate. This technique translated to an improvement in both local control and limb preservation of recurrent STS., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Primary bone lymphoma (PBL) is a rare disease. The literature is inconsistent in regard to definition, stage and prognostic factors. We examined the PBL cases seen at the Moffitt Cancer Center between 1998 and 2013 using the 2013 World Health Organization criteria for bone/soft tissue tumours. Seventy PBL patients were included, of whom 53 (75.7%) patients were histologically classified as primary bone diffuse large B-cell lymphoma (PB-DLBCL). Femur was the most commonly involved site in PBLs with unifocal bone lesions, whereas PBLs with multifocal bone lesions most frequently presented with spine disease. Further analysis of the PB-DLBCL subgroup showed that these patients had 3- and 5-year progression-free survival (PFS) of 61.2% and 46.9%, respectively and 5- and 10-year overall survival (OS) of 81.1% and 74.7%, respectively. Multivariate analysis identified soft tissue extension and International Prognostic Index (IPI) score as the most important unfavourable prognostic factors for both PFS and OS. Multifocality was also highly significantly associated with a worse PFS (P = 0.002) and OS (P < 0.001), although it was not identified in multivariate analysis due to its incorporation into the IPI. The results warrant further investigation regarding whether PBL with multifocal bone lesions could be considered as a systemic and more aggressive disease rather than a conventional PBL., (© 2014 John Wiley & Sons Ltd.)

Sarcomas are rare and heterogeneous mesenchymal tumors affecting both pediatric and adult populations with more than 70 recognized histologies. Doxorubicin and ifosfamide have been the main course of therapy for treatment of sarcomas; however, the response rate to these therapies is about 10-20% in metastatic setting. Toxicity with the drug combination is high, response rates remain low, and improvement in overall survival, especially in the metastatic disease, remains negligible and new agents are needed. Wee1 is a critical component of the G2/M cell cycle checkpoint control and mediates cell cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by MK1775 has been reported to enhance the cytotoxic effect of DNA damaging agents in different types of carcinomas. In this study we investigated the therapeutic efficacy of MK1775 in various sarcoma cell lines, patient-derived tumor explants ex vivo and in vivo both alone and in combination with gemcitabine, which is frequently used in the treatment of sarcomas. Our data demonstrate that MK1775 treatment as a single agent at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death in all sarcomas tested. Additionally, MK1775 significantly enhances the cytotoxic effect of gemcitabine in sarcoma cells lines with different p53 mutational status. In patient-derived bone and soft tissue sarcoma samples we showed that MK1775 alone and in combination with gemcitabine causes significant apoptotic cell death. Magnetic resonance imaging (MRI) and histopathologic studies showed that MK1775 induces significant cell death and terminal differentiation in a patient-derived xenograft mouse model of osteosarcoma in vivo. Our results together with the high safety profile of MK1775 strongly suggest that this drug can be used as a potential therapeutic agent in the treatment of both adult as well as pediatric sarcoma patients.

Wee1 is a critical component of the G(2)-M cell-cycle checkpoint control and mediates cell-cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by a selective small molecule inhibitor MK1775 can abrogate G(2)-M checkpoint, resulting in premature mitotic entry and cell death. MK1775 has recently been tested in preclinical and clinical studies of human carcinoma to enhance the cytotoxic effect of DNA-damaging agents. However, its role in mesenchymal tumors, especially as a single agent, has not been explored. Here, we studied the cytotoxic effect of MK1775 in various sarcoma cell lines and patient-derived tumor explants ex vivo. Our data show that MK1775 treatment at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death in all sarcomas tested. In MK1775-treated cells, CDC2 activity was enhanced, as determined by decreased inhibitory phosphorylation of tyrosine-15 residue and increased expression of phosphorylated histone H3, a marker of mitotic entry. The cytotoxic effect of Wee1 inhibition on sarcoma cells seems to be independent of p53 status as all sarcoma cell lines with different p53 mutation were highly sensitive to MK1775 treatment. Finally, in patient-derived sarcoma samples, we showed that MK1775 as a single agent causes significant apoptotic cell death, suggesting that Wee1 inhibition may represent a novel approach in the treatment of sarcomas., (©2011 AACR.)

We describe four individuals of an African-American family with a predominantly diaphyseal bone disease associated with familial gigantiform cementoma (FGC), a disorder typically seen in Caucasians. The mother and her children presented with deformities of the jaws, abnormalities of the long bones, and pre-pubertal pathologic fractures. The index patient carried the diagnosis of osteosarcoma (OS). In addition, we provide a possible explanation for the jaw abnormalities of King Tutankhamen's father in the 18th dynasty in Egypt around 1350 BC.