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There is wide variability in settings where students with intellectual disability are taught and a dearth of research related to district special education administrators, their roles and responsibilities, and their perceptions of barriers to and policies and practices that promote access to general education environments for these students. This study was designed to collect information to identify trends related to differences between districts that included no students with intellectual disabilities and those that were more inclusive. Data were collected via an online survey. We conducted descriptive analyses to identify trends among the districts and chi-square analyses to compare two types of districts. We found that there is very little diversity among administrators, who were primarily White women. We found that less inclusive districts spent more time engaged in due process and litigation activities than inclusive districts, and administrators identified external factors as barriers to more inclusive practice. We discuss administrator responsibilities in the context of student outcomes in the state and implications for policy implementation. [ABSTRACT FROM AUTHOR]

The Metacognitions Questionnaire – Short Form (MCQ-30) was designed as a parsimonious measure of the metacognitive beliefs and processes implicated in the maintenance of Generalized Anxiety Disorder (GAD). The present study sought to examine the psychometric properties and clinical utility of the MCQ-30 among people with GAD. One hundred and thirty-nine adults diagnosed with GAD and 76 non-clinical controls completed the MCQ-30 and self-report measures of worry, fear of anxiety, attempted thought suppression, distress, GAD symptoms, and interference. A five-factor structure was evaluated using confirmatory factor analysis (CFA). Among the clinical sample, CFA supported the construct validity of the scale, although the relationship between the factors differed from community samples. Evidence was found for the internal consistency, test-retest reliability, and concurrent, convergent and criterion validity of the MCQ-30 in people with GAD. The treatment sensitivity and clinical responsiveness of the scale were also demonstrated, with the Uncontrollability and Danger Beliefs subscale identified as the most accurate predictor of clinical status. This subscale also exhibited the strongest correlations with most symptom measures, highlighting the cardinal role played by negative beliefs about worry in maintaining clinical levels of GAD. This study provides the first evidence of the reliability, validity and clinical utility of the MCQ-30 with people diagnosed with GAD. [ABSTRACT FROM AUTHOR]

Purpose. To report a case of ocular involvement of Loa loa parasite. Observations. We present a rare case report of a Loiasis diagnosed in the United States from a patient presenting with subcutaneous migration of an adult worm within an eyelid who was found to have systemic disease with microfilaria in his blood. This is the second report in the United States and the eighth case in published literature worldwide. Conclusions and Importance. Due to the relatively mild disease course, Loiasis is relatively ignored in public health in low resource health districts. Understandably, the focus of public health in endemic areas must focus on basic health needs like malnutrition and diseases that entail a greater disease burden. As globalization has increased the amount of trade of physical goods, the effect of immigration also has implications for the spread of infectious disease. Medical practitioners in the United States should be aware of endemic diseases from foreign lands. [ABSTRACT FROM AUTHOR]

Providers should be aware that many women experience confusion and concern about their ductal carcinoma in situ diagnosis and treatment that persist for years. Shared decision‐making and research focusing on patient‐reported outcomes are critical. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast MRI is a valuable imaging modality that plays a critical role in the detection, diagnosis, and treatment of breast cancer. The superior sensitivity of breast MRI allows for more accurate evaluation of the extent of disease for breast cancer, which is important in an era where de-escalation of treatment is being considered and offered. In this review, we provided a detailed overview of breast MRI and its clinical utility in the management of breast cancer as a foundation for its use in the field of radiation oncology. Specifically, we describe breast MRI technique, anatomy, common breast MR imaging findings, and the role of breast MRI in assessing extent of disease and tumor response to neoadjuvant therapy. There has been increased interest in the use of MRI during radiotherapy treatment planning and delivery for patients with early-stage breast cancer as it may allow for more personalized radiotherapy. Contrast-enhanced breast MRI has an established role in aiding in the detection, evaluation, and management of breast cancer. This article discusses MRI sequences, the clinical utility of MRI, and how MRI has been evaluated for use in breast radiotherapy treatment planning. We highlight the contribution of MRI in the decision-making regarding selecting appropriate candidates for breast conservation therapy and review the emerging role of MRI-guided breast radiotherapy. [ABSTRACT FROM AUTHOR]

Lack of access to general education for students with disabilities, particularly students with extensive support needs, students of color, and students from low-income households, reflects continued educational inequities for multiply marginalized students. Here, we present findings of a geospatial analysis of the intersections of race, socioeconomic status, disability labels, and levels of inclusion for students with disabilities in an urban school district, serving primarily students of color. Findings show trends in segregated placements mirroring historical redlining practices, suggesting the persistence of racial segregation that is enacted systematically and systemically via special education placements, disability categories, and geography. Results suggest the need to examine student-level placement data in the context of race, class, disability label, and space to identify and address inequities in access to inclusive schooling. [ABSTRACT FROM AUTHOR]

In this study, the total self-consistent field binding energy of a small ice cluster is estimated as the sum of two- and three-body interaction terms. The energy of each term is analyzed using the Morokuma method. Counterpoise calculations were performed to estimate the basis set superposition errors. Additional calculations were done to determine the correlation energy contribution to the total binding energy. Results show that the nearest-neighbor two-body components contribute most to the total binding energy, but also that the contiguous three-body terms must be included to reproduce the total binding energy of the system. [ABSTRACT FROM AUTHOR]

Multiphysics coupling presents a significant challenge in terms of both computational accuracy and performance. Achieving high performance on coupled simulations can be particularly challenging in a high-performance computing context. The US Department of Energy Exascale Computing Project has the mission to prepare mission-relevant applications for the delivery of the exascale computers starting in 2023. Many of these applications require multiphysics coupling, and the implementations must be performant on exascale hardware. In this special issue we feature six articles performing advanced multiphysics coupling that span the computational science domains in the Exascale Computing Project. [ABSTRACT FROM AUTHOR]

Purpose: To examine 10-year rates of local, regional, and distant recurrences, patterns of recurrence, and survival rates for breast cancer patients enrolled on Study NRG Oncology/Radiation Therapy Oncology Group 9517, a multi-institutional prospective trial that studied one of the earliest methods of accelerated partial breast irradiation (APBI), multicatheter brachytherapy (MCT).Methods and Materials: Eligibility included stage I/II unifocal breast cancer <3 cm in size after lumpectomy with negative surgical margins and 0 to 3 positive axillary nodes without extracapsular extension. The APBI dose delivered was 34 Gy in 10 twice-daily fractions over 5 days for high-dose-rate (HDR); and 45 Gy in 3.5 to 5 days for low-dose-rate (LDR) brachytherapy. The primary endpoint was HDR and LDR MCT reproducibility. This analysis focuses on long-term ipsilateral breast recurrence (IBR), contralateral breast cancer events (CBE), regional recurrence (RR), and distant metastases (DM), disease-free, and overall survival.Results: The median follow-up was 12.1 years. One hundred patients were accrued from 1997 to 2000; 98 were evaluable; 65 underwent HDR and 33 LDR MCT. Median age was 62 years; 88% had T1 tumors; 81% were pN0. Seventy-seven percent were estrogen receptor and/or progesterone receptor positive; 33% received adjuvant chemotherapy and 64% antiendocrine therapy. There have been 4 isolated IBRs and 1 IBR with RR, for 5.2% 10-year IBR without DM. There was 1 isolated RR, 1 with IBR, and 1 with a CBE, for 3.1% 10-year RR without DM. The 10-year CBE rate was 4.2%, with 5 total events. Eleven patients have developed DM, 8 have died of breast cancer, and 22 have died from other causes. The 10-year DFS and OS rates are 69.8% and 78.0%, respectively.Conclusion: This multi-institutional, phase 2 trial studying MCT-APBI continues to report durable in-breast cancer control rates with long-term follow-up. [ABSTRACT FROM AUTHOR]

Recent research has extended the metacognitive model of adult psychopathology to childhood anxiety, however the results have been confounded by poor comprehension of the Metacognitions Questionnaire for Children (MCQ-C) amongst 7-8 year olds. The aim of this study was to improve comprehension of the MCQ-C, to enable reliable and valid evaluation of the metacognitive model of anxiety in children. Poorly comprehended items of the MCQ-C were revised to the appropriate reading level and pilot tested with 7-8 year olds. One hundred and eighty seven children aged 7-12 years then completed an online version of the revised MCQ-C (MCQ-CR) and self-report measures of anxiety symptoms, excessive worry and externalising thoughts. The MCQ-CR was well understood by children as young as 7 years and exhibited sound psychometric properties. As predicted, children's negative beliefs about worry, thoughts in general and memories were found to be significantly positively related to symptoms of anxiety disorders. Confirmatory factor analysis supported the construct validity of the scale. Positive beliefs about worry were not associated with children's worry levels, raising questions about the relevance of this element of the metacognitive model with children. Although further validation is required with a clinical sample, these results provide support for the integral role played by metacognitions in childhood anxiety disorders, and suggest that these mechanisms may be appropriate targets for future early intervention and treatment programs. [ABSTRACT FROM AUTHOR]

Postmastectomy radiation therapy (PMRT) improves breast cancer survival in many women with lymph node-positive disease who undergo surgery followed by adjuvant chemotherapy. The role of PMRT after women receive neoadjuvant chemotherapy (NAC) is less clear. The available data suggest that clinical extent of disease at presentation before NAC, pathologic residual disease (especially pathologically involved lymph nodes) after NAC, and response to NAC are key prognostic factors for locoregional recurrence. Therefore, accurate axillary staging before the initiation of NAC and assessment of response to chemotherapy are critically important. Here, the authors review the literature addressing the radiotherapy management of patients with breast cancer who received NAC and underwent mastectomy with a special focus on the imaging modalities used to assess axillary lymph node status. Cancer 2015;121:1187-1194. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Hypofractionated radiation refers to treatment with greater than 2Gy per fraction, usually in fewer number and an overall shorter treatment period, compared to conventional radiation fractionation. Randomized prospective trials of hypofractionated whole breast irradiation (WBI) have demonstrated comparable outcomes as conventional fractionation in early stage postlumpectomy radiation in selected groups of patients. These data have changed the traditional radiobiology estimation of the alpha/beta ratio that predicted fractionation sensitivity for breast cancer, suggesting that further increase in dose per fraction is possible for early stage breast cancer without significantly increasing late effects. Many questions remain regarding hypofractionated WBI and span from optimal patient selection to radiation technique including dose planning optimization and the incorporation of a tumor bed boost. A concurrent radiation boost has been studied in a number of single institution studies and has shown to be feasible with acceptable acute and short-term late toxicity. A phase III trial by the Radiation Therapy Oncology Group (RTOG 1005) in North America and other trials in Europe are currently studying in-breast cancer control from hypofractionated WBI with a concurrent tumor bed boost. Results from these current trials could improve the acceptance and broaden the applicability of hypofractionation treatment courses for the treatment of patients with early stage breast cancer. [Copyright &y& Elsevier]

Abstract: Background: Despite the high efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) in preventing pregnancy, uptake of the intrauterine devices remains low in the United States. Decreasing pain at the time of intrauterine device insertion may be one way to increase interest in this method of contraception. Study Design: We conducted a double-blind, placebo-controlled trial, randomizing women to 800 mg ibuprofen or placebo 45 min prior to LNG-IUS insertion to determine effect of ibuprofen on the pain of LNG-IUS insertion. Results: Eighty-one women completed the study: 44 received ibuprofen, and 37 received placebo. Women in the ibuprofen and placebo groups had similar mean scores for anticipated pain (4.07 and 3.91, respectively; p=.79), pain with tenaculum placement (3.86 and 3.81, respectively; p=.90) and pain with insertion (3.69 and 3.34, respectively; p=.91). Conclusion: Administration of ibuprofen prophylaxis for LNG-IUS insertion does not decrease pain at the time of insertion. [Copyright &y& Elsevier]

Abstract: Purpose: Low α/β ratio for breast cancer has drawn a growing interest for exploring hypofractionation for breast irradiation. This work is to confirm the low α/β ratio based on large randomized clinical trials of breast irradiation. Methods and materials: A model based on the generalized linear-quadratic (LQ) model and Poisson statistical model was developed to calculate disease-free survival with consideration of clonogen proliferation during the course of radiation treatment and exponential behavior of survival rate with follow-up time. Outcome data from a series of randomized clinical trials of early-stage breast radiotherapy were fitted to estimate the model parameters. Other clinical outcomes, including treatments with surgery alone or radiotherapy alone were used to validate the model and the estimated parameters. Hypofractionation regimens were proposed based on the newly estimated LQ parameters. Results: Plausible population averaged radiobiologic parameters for breast cancer (95% confidence level) are α/β =2.88 (0.75–5.01) Gy; α =0.08±0.02Gy−1; potential doubling time T d =14.4±7.8day. The analysis of the radiation-alone data suggested an α/β ratio of 3.89±6.25Gy, verifying the low α/β ratio based on the post-lumpectomy irradiation data. The hypofractionation regimens that are equivalent to the conventional regimen of 2.0Gy×25 in 5weeks include 2.26Gy×20, 3.34Gy×10, 4.93Gy×5 or 3.39Gy×10 (BID). Conclusions: The analysis of the available clinical data from multiple institutions support that breast cancer has a low ratio of α/β, encouraging hypofractionated radiotherapy regimens for breast cancer. [Copyright &y& Elsevier]

Purpose: To examine the respiratory motion for target and normal structures during whole breast and nodal irradiation and the resulting dosimetric impact. Methods and Materials: Four-dimensional CT data sets of 18 patients with early-stage breast cancer were analyzed retrospectively. A three-dimensional conformal dosimetric plan designed to irradiate the breast was generated on the basis of CT images at 20% respiratory phase (reference phase). The reference plans were copied to other respiratory phases at 0% (end of inspiration) and 50% (end of expiration) to simulate the effects of breathing motion on whole breast irradiation. Dose–volume histograms, equivalent uniform dose, and normal tissue complication probability were evaluated and compared. Results: Organ motion of up to 8.8mm was observed during free breathing. A large lung centroid movement was typically associated with a large shift of other organs. The variation of planning target volume coverage during a free breathing cycle is generally within 1%–5% (17 of 18 patients) compared with the reference plan. However, up to 28% of V45 variation for the internal mammary nodes was observed. Interphase mean dose variations of 2.2%, 1.2%, and 1.4% were observed for planning target volume, ipsilateral lung, and heart, respectively. Dose variations for the axillary nodes and brachial plexus were minimal. Conclusions: The doses delivered to the target and normal structures are different from the planned dose based on the reference phase. During normal breathing, the dosimetric impact of respiratory motion is clinically insignificant with the exception of internal mammary nodes. However, noticeable degradation in dosimetric plan quality may be expected for the patients with large respiratory motion. [Copyright &y& Elsevier]

Purpose: To investigate whether helical tomotherapy can provide conformal, uniform target-dose coverage for partial-breast irradiation (PBI) of patients positioned prone while achieving organ-at-risk sparing compliant with National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 guidelines; and to report our initial experience with the delivery of prone-breast PBI treatments using tomotherapy. Methods and Materials: For our pilot study, we generated helical tomotherapy plans upon the images of 10 prone-positioned patients previously treated using conventional techniques. We also generated plans for 4 left-breast prone-positioned PBI patients who were treated using helical tomotherapy, and recalculated the planned sinograms upon the pretreatment megavoltage computed tomographic images. Of the planning target volume (PTV), 95% was prescribed to receive 38.5 Gy, administered twice daily for 5 days. Results: For our pilot study, on average the maximum point dose to the PTV was 41.3 Gy, and 99% or more of the PTV received 90% or more of the prescribed dose. RTOG 0413 dose–volume histogram objectives were fulfilled for all organs at risk except the contralateral breast, which received a maximum point dose as high as 3.2 Gy in 1 case. For the prospective prone-positioned tomotherapy PBI plans, all objectives were met except the contralateral-breast maximum dose, which was 3.7 Gy on average. Dose calculation using the planned sinogram upon the pretreatment megavoltage computed tomographic images indicated consistency with the planned dose distributions. Conclusions: Helical tomotherapy can provide conformal and uniform target-dose coverage simultaneous with adequate sparing of critical structures; in this study only the contralateral breast dose exceeded RTOG 0413 guidelines. Dosimetric results for our 4 prospective patient cases were consistent with those for our 10-case pilot study. [Copyright &y& Elsevier]

Background: Pharmacy board certification provides pharmacists with formal recognition of their careers and their involvement in direct and comprehensive patient care. Credentialing as a board-certified pharmacist demonstrates that the pharmacist has specialized expertise and is able to provide advanced level patient care in a specific pharmacy practice specialty. There is currently not a community pharmacy board certification available in the United States. With the expanding role and clinical expectations of community pharmacists nationwide, perspectives regarding the utility of a community pharmacy specialty board certification are necessary. Methods: A cross-sectional survey with demographic and perception questions (5-point Likert scale) was distributed electronically via Qualtrics. A random sample of pharmacists registered in Rhode Island, Ohio, and Nebraska were selected and surveyed. Results: 53 survey responses were collected. There was a statistically significant difference in board certification history (P =.001) and history of post-graduate training (P <.001) between community pharmacists and non-community pharmacists. Community pharmacists were more likely to simultaneously see community pharmacists as general practitioners (P =.030) and as pharmacy practice specialists (P =.001). Non-community pharmacists were more likely to be familiar with current maintenance requirements for pharmacy board certifications (P <.001) and to feel that a board certification is an appropriate indicator of experience in a pharmacy specialty area (P =.016). Conclusion: Views regarding community pharmacy and board certification differed between community and non-community pharmacists. There was not a statistically significant difference in the perceived value of community pharmacy board certification between community and non-community pharmacist. [ABSTRACT FROM AUTHOR]

Purpose: The Patterns of Care Study performed this first known practice survey to establish a national profile of the delivery of postmastectomy radiotherapy (RT) in operable breast cancer.Methods and materials: A Patterns of Care Study research associate collected data from 55 randomly selected institutions. The survey data included 132 items describing the patient, pathologic features, and treatment course for patients with clinical Stage I, II, and IIIA breast cancer undergoing postmastectomy RT in 1998 and 1999. A multivariate analysis was performed to determine the impact of tumor factors and type of treatment facility on the radiation fields used.Results: A weighted sample size of 13,720 was obtained from a sampling of 405 patient records. The mean tumor size was 3.5 cm, and the mean number of axillary nodal metastases was 4.55. Lymphatic vascular invasion was noted in 34%, microscopic skin or dermal lymphatic invasion in 16%, positive or close margins in 36%, and extracapsular nodal extension in 23%. Radiotherapy included the chest wall in all cases and the regional nodes in 78%. When nodal RT was delivered, it included a supraclavicular field, supplemental axillary field, and/or an internal mammary field in 98%, 46%, and 23% of cases, respectively. Chest wall and supraclavicular RT was delivered in >90% of instances with 6-MV photons to doses between 45 and 50 Gy. More variation was seen in the delivery of the axillary and internal mammary RT. On multivariate analysis, the presence of four or more positive nodes and treatment at a large-volume facility were the factors most frequently associated with the use of regional radiation fields.Conclusion: This Patterns of Care Study survey has demonstrated that breast cancer patients undergoing postmastectomy RT in 1998 and 1999 had a high proportion of factors associated with an increased risk of locoregional failure. The practice patterns established in this study provide a baseline for comparison with future survey results. [Copyright &y& Elsevier]

A major goal of molecular biology is to understand protein interactions and how interaction networks form the functional circuitry of cells. This goal is also relevant to drug development, as molecular target discovery and validation require an understanding of the function and disease relevance of proteins. One of the best approaches available to achieve this goal is the yeast two-hybrid system and its variants. This powerful tool can be used not only to identify and characterize individual drug targets, but also to dissect whole pathways and map protein interactions on a proteomic scale. [Copyright &y& Elsevier]

Several lines of evidence suggested that the first γ-aminobutyric acid B receptor to be cloned required an additional factor for functional expression. GABAB1 was retained within the endoplasmic reticulum and failed to couple to signal transduction pathways on stimulation with agonists. In radioligand binding experiments it was found that although the affinity of antagonists showed a close agreement between rat brain membranes and membranes expressing the cloned receptor, agonist ligands were significantly weaker at recombinant receptors. Using the C-terminal tail as bait, a yeast two-hybrid screen was run against a human brain cDNA library and identified a second receptor, GABAB2, as a major interacting protein. This interaction was confirmed by coimmunoprecipitation as well as extensive colocalization studies. Coexpression of the two seven-transmembrane proteins generated a fully functional receptor, which was expressed at the cell surface confirming the importance of receptor heterodimerization for GABAB receptor activity. [Copyright &y& Elsevier]

Examines the theoretical capacity of G-protein-coupled receptors (GPCR) to interact with a wide range of proteins. GPCR structure; Interactions between GPCR and ion channels; GPCR signalling, internalization and desensitization.

Presents an analysis of the gamma-aminobutyric acid type B, GABA [sub B] receptor and associated transcription factors. Distribution of CREB2 within the cytosol and nucleus when expressed either in Chinese hamster ovary cells together with the GABA [sub B] receptor or in primary neuronal cultures.

Examines the role of tube/pelle death domain complexes in the regulation of postreceptor signalling in Drosophila. Molecular cloning for gene product functions; Death domain content of postreceptor activation complex; Usage of yeast two-hybrid system; Pelle death domains and wild-type tube binding.

Reports the cloning of a complementary DNA encoding a subtype of the gamma-aminobutyric acid B (GABAB) receptor (GABABR2), which was identified by mining expressed-sequence-tag databases. The indication that, in vivo, functional brain GABAB receptors may be heterodimers composed of GABABR1 and GABABR2; GABA being the main inhibitory neurotransmitter in the mammalian central nervous system.

Discusses the importance of addressing the psychosocial needs of adolescents confined in hospitals for medical intervention. Case of Monash Medical Centre in Melbourne, Victoria; Recognition of adolescence as a transition period; Effect of hospitalization on a child's emotional status; Myths and theories about adolescents and their psychosocial needs.

We have sequenced a 4200-base-pair fragment of Schizosaccharomyces pombe DNA which encompasses the entire DNA ligase gene, CDCI 7. S1 mapping has enabled us to identify two small introns (40 and 62 nucleotides) at the 5' end of the coding region of the gene and their 3' internal conserved sequences match the CTRAY consensus found in other S. pombe introns. The major transcription initiation and 3' polyadenylation sites have been mapped and are preceded by higher eukaryotic-like TATA and AATAAA sequences respectively. Furthermore, the CDC17 mRNA carries a poly(A) tail whose length (approximately 250 nucleotides) is typical of that found in higher eukaryotic mRNAs, and is in contrast to the much shorter polyadenylated sequences found for the mRNAs of the budding yeast, Saccharomyces cerevisiae. The deduced amino acid sequence of the S. pombe DNA ligase predicts a protein of 86182 daltons, and an overall 53% homology with the same enzyme from S. cerevisiae. In particular, a stretch of 24 amino acids with 100% sequence homology spans the putative ATP-binding region which is also conserved in T4 and T7 bacteriophage DNA ligases. [ABSTRACT FROM AUTHOR]

Reports on the identification of three cellular proteins that bind to the adenovirus E1B 19K proteins. Ability of E1B 19K to inhibit apoptosis; Use of the yeast two-hybrid system to identify the binding proteins; Effect of the overexpression of the bak protein.

Simple Summary: There is paucity of data on the optimal management of brain metastases in older women ≥65 years old with breast cancer. In this single-institutional retrospective study, we assessed the survival outcomes and treatment patterns of breast cancer patients ≥65 years old with brain metastases and compared them to younger patients. A total of 112 patients were included. Treatment-related adverse events were similar in both groups. Although older women had a poorer median overall survival compared to younger women (9.5 vs. 14.5 months), survival was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and leptomeningeal disease in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with brain metastases and personalized decision-making including a comprehensive geriatric assessment should be considered. Background: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution. Methods: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan–Meier estimates and Cox proportional hazard regression method were used for survival analyses. Results: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were <65 years old. Median age at RT was 72 years (range 65–84) compared to 52 years (31–64) in younger patients. There were significantly higher number of older women with ER/PR positive disease (75% vs. 49%, p = 0.036), while younger patients were more frequently triple negative (32% vs. 12%, p = 0.074) and HER2 positive (42% vs. 29%, p = 0.3). Treatment-related adverse events were similar in both groups. Overall, 14.3% patients had any grade radiation necrosis (RN) (older vs. young: 8.3% vs. 16%, p = 0.5) while 5.4% had grade 3 or higher RN (0% vs. 6.8%, p = 0.7). Median OS after RT was poorer in older patients compared to younger patients (9.5 months vs. 14.5 months, p = 0.037), while intracranial PFS from RT was similar between the two groups (9.7 months vs. 7.1 months, p = 0.580). On univariate analysis, significant predictors of OS were age ≥65 years old (hazard risk, HR = 1.70, p = 0.048), KPS ≤ 80 (HR = 2.24, p < 0.001), HER2 positive disease (HR = 0.46, p < 0.001), isolated CNS metastatic disease (HR = 0.29, p < 0.001), number of brain metastases treated with RT (HR = 1.06, p = 0.028), and fractionated SRS (HR = 0.53, p = 0.013). On multivariable analysis, KPS ≤ 80, HER2 negativity and higher number of brain metastases predicted for poorer survival, while age was not a significant factor for OS after adjusting for other variables. Patients who received systemic therapy after SRS had a significantly improved OS on univariate and multivariable analysis (HR = 0.32, p < 0.001). Number of brain metastases treated was the only factor predictive of worse PFS (HR = 1.06, p = 0.041), which implies a 6% additive risk of progression for every additional metastasis treated. Conclusions: Although older women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with BMs and personalized decision-making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in older patients. [ABSTRACT FROM AUTHOR]

Breast cancer–related lymphedema (BCRL) is a treatment complication that significantly reduces patient quality of life. Regional nodal irradiation (RNI) may increase the risk of BCRL. Recently, a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) was identified as a potential organ at risk (OAR). Here, we set out to validate whether radiation dose to the ALTJ is associated with BCRL. We identified patients with stage II-III breast cancer treated with adjuvant RNI from 2013 to 2018, excluding those with BCRL preradiation. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb >2.5 cm at any 1 encounter or ≥2 cm on ≥2 visits. All patients suspected of having BCRL at routine follow-up visits were referred to physical therapy for confirmation. The ALTJ was retrospectively contoured and dose metrics were collected. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. The study population included 378 patients with a median age of 53 years, median body mass index of 28.4 kg/m2, and median of 18 axillary nodes removed; 71% underwent mastectomy. Median follow-up was 70 months (interquartile range, 55-89.7 months). BCRL developed in 101 patients at a median of 18.9 months (interquartile range, 9.9-32.4 months), with a corresponding 5-year cumulative incidence BCRL of 25.8%. On multivariate analysis, none of the ALTJ metrics were associated with BCRL risk. Only increasing age, increasing body mass index, and increasing number of nodes were associated with a higher risk of developing BCRL. The 6-year locoregional recurrence rate was 3.2%, the axillary recurrence rate was 1.7%, and the isolated axillary recurrence rate was 0%. The ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL. [ABSTRACT FROM AUTHOR]

Background: Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation.Methods: We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181.Findings: Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group.Interpretation: APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women.Funding: National Cancer Institute, US Department of Health and Human Services. [ABSTRACT FROM AUTHOR]

Federal laws mandate students with disabilities, including students with complex instructional needs (SWCIN), be involved and progress in the general education curriculum and that schools be accountable for continuous and substantial improvement of academic achievement for all students. The limited research on teaching academic content to SWCIN indicates that they achieve more positive outcomes when standards aligned instruction occurs within general education contexts. However, long-term change for instruction in general education contexts typically seems to be personality dependent rather than embedded within a sustainable system. We present content analysis findings of an expert panel concerning one state's initiative to address these issues, organized around four themes: (a) defining inclusive practices, (b) rethinking instruction for SWCIN, (c) rethinking the individualized education program (IEP), and (d) building sustainable inclusive practices across a system. Finally, we extend the panelists' conclusions to provide implications for professional development, practice, policy and administrative procedures, monitoring the quality of services, and research. [ABSTRACT FROM AUTHOR]

Addresses concerns raised by Newton Morton in the November 1998 issue of 'Nature Genetics,' regarding gene nomenclature. Effects of problems in nomenclature on map integration in human genetics; Arguments against proposals to sort out nomenclature in one species before any cross-species collaboration.

Purpose To derive a prescriptive sex-specific fetal growth standard and assess clinical management and outcomes according to sex-specific growth status. Materials and methods This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective observational study of 10,038 nulliparas from eight U.S. centers who underwent ultrasounds at 14–20 and 22–29 weeks with outcomes ascertained after delivery. From these, we selected a nested cohort of lower risk participants (excluded those with chronic hypertension, pre-gestational diabetes, suspected aneuploidy, and preterm delivery) to derive a sex-specific equation for expected fetal growth using fetal weights by ultrasound and at birth. We compared the male-female discrepancy in the rate of weight <10th (small for gestational age [SGA]) and >90th (large for gestational age [LGA]) percentiles between the sex-specific and sex-neutral (Hadlock) standards. Using the full unselected cohort, we then assessed outcomes and clinical management according to sex-specific SGA and LGA status. Results Overall, 7280 infants in the lower risk nested cohort were used to derive a sex-specific equation with fetal sex included as an equation intercept. The sex-neutral standard diagnosed SGA more often in female newborns (21% vs. 13%, p < .001) and LGA more often in male newborns (5% vs. 3%, p < .001). The sex-specific standard resolved these disparities (SGA: 9% vs. 10%, p = .23; LGA: 13% vs. 13%, p = .58). To approximate an unselected population, 1059 participants initially excluded for risk factors for abnormal growth were then included for our secondary objective (N = 8339). In this unselected cohort, 39% (95% CI 37.0–42.0%) of the 1498 newborns classified as SGA by the sex-neutral standard were reclassified as appropriate for gestational age (AGA) by the sex-specific standard. These reclassified newborns were more likely to be delivered for growth restriction despite having lower risk of morbidity (females) or comparable risk of morbidity (males) compared to newborns considered AGA by both methods. Of the 6485 newborns considered AGA by the sex-neutral standard, 737 (11.4%, 95% CI 10.6–12.2%) were reclassified as LGA by the sex-specific standard. These reclassified newborns had higher rates of cesarean for arrest of descent, cesarean for arrest of dilation, and shoulder dystocia than newborns considered AGA by both methods. None were reclassified from LGA to AGA by the sex-specific standard. Conclusion The Hadlock sex-neutral standard generates sex disparities in SGA and LGA at birth. Our sex-specific standard resolves these disparities and has the potential to improve accuracy of growth pathology risk stratification. [ABSTRACT FROM AUTHOR]

The TASH Inclusive Education National Committee responded to Horner and Dunlap’s call to ensure that future research integrates inclusive values with strong science by developing an inclusive education national research advocacy agenda. Qualitative methods were implemented to answer three questions: (a) What is the state of inclusive education research? (b) What research still must be done? and (c) What are recommendations for a national inclusive education research advocacy agenda? The findings include 15 areas organized within three domains advocating for continued research across systems-level capacity building, building and classroom capacity, and student learning and development. Implications for research and policy reform are discussed. [ABSTRACT FROM AUTHOR]

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volume parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms of gene regulation have a profound role in normal development and disease processes. An integral part of this mechanism occurs through lysine acetylation of histone tails which are recognized by bromodomains. While the biological and structural characterization of many bromodomain containing proteins has advanced considerably, the therapeutic tractability of this protein family is only now becoming understood. This paper describes the discovery and molecular characterization of potent (nM) small molecule inhibitors that disrupt the function of the BET family of bromodomains (Brd2, Brd3, and Brd4). By using a combination of phenotypic screening, chemoproteomics, and biophysical studies, we have discovered that the protein–protein interactions between bromodomains and acetylated histones can be antagonized by selective small molecules that bind at the acetylated lysine recognition pocket. X-ray crystal structures of compounds bound into bromodomains of Brd2 and Brd4 elucidate the molecular interactions of binding and explain the precisely defined stereochemistry required for activity. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To demonstrate and examine the ability of a newly developed software tool to estimate and analyze consensus contours from manually created contours by expert radiation oncologists. Material and methods: Several statistical methods and a graphical user interface were developed. For evaluation purposes, we used three breast cancer CT scans from the RTOG Breast Cancer Atlas Project. Specific structures were contoured before and after the experts’ consensus panel meeting. Differences in the contours were evaluated qualitatively and quantitatively by the consensus software tool. Estimates of consensus contours were analyzed for the different structures and Dice-similarity and Dice-Jaccard coefficients were used for comparative evaluation. Results: Based on kappa statistics, highest levels of agreement were seen in the left-breast, lumpectomy, and heart. Significant improvements between pre- and post-consensus contours were seen in delineation of the chestwall and breasts while significant variations were noticed in the supraclavicular and internal mammary nodes. Dice calculations for all pre-consensus STAPLE estimations and final consensus panel structures reached 0.80 or greater for the heart, left/right-breast, case-A lumpectomy, and chestwall. Conclusions: Using the consensus software tool incorporating STAPLE estimates provided the ability to create contours similar to the ones generated by expert physicians. [Copyright &y& Elsevier]

The article focuses on the film representation of characters with disabilities in the English classroom. It presents an active reading of the film "The Mighty," which portrays friendships between disabled and non-disabled characters. It mentions the summary of the film which features middle school students Max Kane and Kevin Dillon. Furthermore, the film aims to help English teachers consider and expose students for a broader examination of disability representations in popular culture.

Purpose: Intra- and interfractional errors for breast cancer patients undergoing breast irradiation in the prone position were analyzed. Methods and Materials: To assess intrafractional error resulting from respiratory motion, four-dimensional computed tomography scans were acquired for 3 prone and 3 supine patients, and the respiratory motion was compared for the two positions. To assess the interfractional error caused by daily set-up variations, daily electronic portal images of one of the treatment beams were taken for 15 prone-positioned patients. Portal images were then overlaid with images from the planning system that included the breast contour and the isocenter, treatment beam portal, and isocenter. The shift between the planned and actual isocenter was recorded for each portal image, and descriptive statistics were collected for each patient. The margins were calculated using the 2Sigma + 0.7sigma recipe, as well as 95% confidence interval based on the pooled standard deviation of the datasets. Results: Respiratory motion of the chest wall is drastically reduced from 2.3 +/- 0.9 mm in supine position to -0.1 +/- 0.4 mm in prone position. The daily set-up errors vary in magnitude from 0.0 cm to 1.65 cm and are patient dependent. The margins were defined by considering only the standard deviation to be 1.1 cm, and 2.0 cm when the systematic errors were considered using the 2Sigma + 0.7sigma recipe. Conclusions: Prone positioning of patients for breast irradiation significantly reduces the uncertainty introduced by intrafractional respiratory motion. The presence of large systematic error in the interfractional variations necessitates a large clinical target volume-to-planning target volume margin and indicates the importance of image guidance for partial breast irradiation in the prone position, particularly using imaging modality capable of identifying the lumpectomy cavity. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Accelerated partial breast irradiation (APBI) is being studied in a phase III randomized trial as an alternative to whole breast irradiation (WBI) for early stage breast cancer patients. There are three methods for APBI: multi-catheter brachytherapy (MCT), MammoSite® brachytherapy (MST), or 3D conformal (3DCRT). There is a paucity of data comparing among methods. Using a linear–quadratic (LQ) model, we evaluated the anticipated efficacy among the APBI methods for equivalent uniform dose (EUD), Tumor Control Probability (TCP), and Normal Tissue Complication Probability (NTCP). Materials and methods: Treatment plans from five patients treated by each APBI modality were retrospectively selected. Dose-volume-histograms (DVH) for planning target volume (PTV), breast, and lung were generated. The LQ parameters α =0.3Gy−1 and α/β =10Gy were used for calculations. The values of EUD, TCP, and NTCP were calculated based on DVHs. Results: The average EUD (normalized to 3.4Gy BID) for the MCT, MST, and 3DCRT APBI was 35, 37.2, and 37.6Gy. When normalized to 2Gy fractionation these become, 42.2, 46.4, and 46.9Gy. Average TCP for MCT, MST, and 3DCRT PBI was 94.8%, 99.1%, and 99.2%. The NTCP values for breast and lung were low for all three methods. Conclusions: The EUD for PTV and TCP were most similar in MST and 3DCRT APBI and were lower in MCT APBI. This questions the equivalence of the three APBI modalities that are currently being evaluated in the NSABP-B39/RTOG 0413 protocol. [Copyright &y& Elsevier]

We present the case of a 52-year-old woman who underwent lumpectomy and radiation therapy for breast carcinoma and 2 years later presented with changes limited to the breast radiation field including hyperpigmentation, retraction, and skin thickening. These clinical features, along with pathologic findings, were diagnostic of postirradiation morphea. It is important to be aware of this rare complication of radiation therapy because it clinically presents with symptoms mimicking malignancy and may be misinterpreted as recurrent carcinoma or even angiosarcoma. [ABSTRACT FROM AUTHOR]

Purpose: The Patterns of Care Study survey process evaluation has been an effective means of assessing the evaluation and treatment practices used by radiation oncologists in the United States for Stage I-II breast cancer. The current 1998¿1999 report updates the previous 1989 and 1993¿1994 analyses and reflects the recent changes in surgery and systemic therapy observed nationally in the management of early-stage disease. Methods and Materials: A weighted sample size of 71,877 patient records of women treated with breast-conserving surgery and radiotherapy (RT) was obtained from a stratified two-stage sampling of 353 patient records. These cases were centrally reviewed from academic and private radiation oncology practices across the United States. The data collected included patient characteristics, clinical and pathologic factors, and surgical and RT details. The results were compared with those of previous Patterns of Care Study survey reports. Results: Of the patients in the current survey, 97% had undergone mammography before biopsy. A review of the primary tumor pathologic findings indicated improved quantification of an intraductal component from 7.0% in 1993¿1994 to 20.4% in 1998¿1999 (p = 0.01). The tumor characteristics were better defined, with estrogen and progesterone receptor measurement performed in 91.4% and 91.3% in the 1998¿1999 survey vs. 83.7% and 80.3% in the 1989 survey, respectively (p = 0.03 and p = 0.002, respectively). Axillary dissection was performed in 82.2% in the present survey compared with 93.6% in the 1993¿1994 survey (p = 0.0004); sentinel node biopsy was performed in 20.1% of the present cases. The use of CT for planning was increased in the current survey, with 22.9% cases CT planned vs. 9% in 1993¿1994 (p = 0.10). In the present survey, 100% had received whole breast RT. When a supraclavicular field was added, the dose was prescribed to a specified depth in 67.5% of cases, most commonly 3 cm. When an axillary field was added, the dose was generally prescribed to the mid-plane. Chemotherapy and tamoxifen was used in 36% and 55.8% of patients, respectively, in the 1998¿1999 survey, representing a statistically significant increase compared with the 1993¿1994 survey, despite comparable pathologic tumor size and nodal involvement. Conclusion: The present results demonstrate a high level of compliance of the sampled radiation oncology practices with current breast conservation standards and continued improvement in many categories compared with prior patterns of care study surveys. The estimates in the current survey after whole breast RT will serve as a benchmark against newer trends in breast cancer RT, such as partial breast RT. [Copyright &y& Elsevier]