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Purpose In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures. Methods and Materials Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an IMRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan was optimized for target coverage and normal tissue sparing. Results Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11–70 months). Median follow-up was 27 months (10–90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p = 0.03), testes (0.0 CGE vs. 0.6 Gy; p = 0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p = 0.016), growth plates (21.7 CGE vs. 32.4 Gy; p = 0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p = 0.016) compared to IMRT. Conclusions This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies incorporating extended follow-up, objective outcome measures, and quality-of-life analyses.

A 4-year-old boy was admitted to this hospital because of a 1-week history of back pain, with sleepiness, constipation, and refusal to walk. The serum calcium level was elevated. Initial radiographs and MRI studies were interpreted as normal. Diagnostic tests were performed.

Although numerous quantitative trait loci (QTL) mapping studies involving milk protein percent (PP), milk yield (MY), and protein yield (PY) have been carried out, there has not been any systematic evaluation of the effects of individual QTL on these 3 interrelated traits. Consequently, the aim of the present study was to investigate the effects on MY and PY of QTL for PP previously mapped in various laboratories. The study, based on selective DNA pooling of milk samples, included 10 Israeli Holstein artificial insemination bulls, each the sire of 1,800 or more milk-recorded daughters. For each sire-trait combination across the 10 sires, milk samples of the highest and lowest daughters with respect to estimated breeding values for PP, PY, and MY were collected for pooling. A total of 134 dinucleotide microsatellites distributed over 25 bovine autosomes were used. An empirical standard error for marker-QTL linkage testing was calculated based on the variation among split samples within the same tail. Threshold comparison-wise error rate P-values were set to control proportion of false positives at P = 0.10 level for declaring significant effects at the marker-trait level. Estimates of the number of true null hypotheses for each trait were obtained from the histogram of marker comparison-wise error rate P-values. Based on these estimates, effective power of the experiment at the marker-trait level was estimated as 0.75, 0.41, and 0.73 for PP, PY, and MY. The proportion of heterozygosity at the QTL was estimated as 0.46, 0.39, and 0.40, respectively. After correcting for incomplete power and proportion of false positives, it was estimated that 38.7 and 37.5% of the markers affecting PP and MY, respectively, also affected PY. Of the markers affecting PY, 68.9 and 76.5%, respectively, also affected PP and MY. Apparently, none of the significant markers affected PY exclusively, and only 6.5 and 16.0%, respectively, affected PP or MY exclusively. Thus, almost all significant markers, and by inference almost all QTL, had effects on at least 2 of the 3 traits.

1. Alison M. Friedmann, MD, MSc* 1. *Department of Hematology/Oncology, Massachusetts General Hospital, Boston, Mass After completing this article, readers should be able to: 1. Define lymphadenopathy. 2. Develop a systematic approach to the evaluation and management of lymphadenopathy. 3. Discuss the differential diagnosis of localized and generalized lymphadenopathy. 4. Recognize worrisome features of lymphadenopathy that should prompt a referral for a biopsy. Examining the lymph nodes is an important aspect of the general physical examination of both well and ill children and adolescents. Lymph nodes are normal structures, and certain lymph nodes may be palpable in a healthy patient, particularly in a young child. Conversely, the presence of abnormally enlarged lymph nodes (“lymphadenopathy”) can be a clue to a serious underlying systemic disease, and the differential diagnosis of lymphadenopathy can be broad. Thus, the challenge for the general pediatrician is to learn how to distinguish pathologic from nonpathologic lymph nodes and to develop a rational approach to the evaluation of lymphadenopathy. Because of its association with malignancy, lymphadenopathy can be a major source of parental anxiety. Therefore, it is crucial to know when to provide reassurance and to recognize when concern is sufficient to warrant referral to a subspecialist. The lymphatic system is an open circulatory system that is a component of the immune system. It includes lymph, lymphatic vessels, lymph nodes, spleen, tonsils, adenoids, Peyer patches, and the thymus. Lymph contains lymphocytes and is an ultrafiltrate of blood that is collected in lymphatic capillaries present throughout the body in all organs except the brain and heart. Lymph moves slowly, without a central pump and under low pressure, via peristalsis and through the milking action of skeletal muscles. Lymph is transported from the head and extremities to progressively larger lymphatic vessels and ultimately into either the right lymphatic duct (lymph from the right upper body) or the thoracic duct (lymph from the rest of the body). These ducts …

Quantitative trait loci (QTL) mapping projects have been implemented mainly in the Holstein dairy cattle breed for several traits. The aim of this study is to map QTL for milk yield (MY) and milk protein percent (PP) in the Brown Swiss cattle populations of Austria, Germany, and Italy, considered in this study as a single population. A selective DNA pooling approach using milk samples was applied to map QTL in 10 paternal half-sib daughter families with offspring spanning from 1,000 to 3,600 individuals per family. Three families were sampled in Germany, 3 in Italy, 1 in Austria and 3 jointly in Austria and Italy. The pools comprised the 200 highest and 200 lowest performing daughters, ranked by dam-corrected estimated breeding value for each sire-trait combination. For each tail, 2 independent pools, each of 100 randomly chosen daughters, were constructed. Sire marker allele frequencies were obtained by densitometry and shadow correction analyses of 172 genome-wide allocated autosomal markers. Particular emphasis was placed on Bos taurus chromosomes 3, 6, 14, and 20. Marker association for MY and PP with a 10% false discovery rate resulted in nominal P-values of 0.071 and 0.073 for MY and PP, respectively. Sire marker association tested at a 20% false discovery rate (within significant markers) yielded nominal P-values of 0.031 and 0.036 for MY and PP, respectively. There were a total of 36 significant markers for MY, 33 for PP, and 24 for both traits; 75 markers were not significant for any of the traits. Of the 43 QTL regions found in the present study, 10 affected PP only, 8 affected MY only, and 25 affected MY and PP. Remarkably, all 8 QTL regions that affected only MY in the Brown Swiss, also affected MY in research reported in 3 Web-based QTL maps used for comparison with the findings of this study (http://www.vetsci.usyd.edu.au/reprogen/QTL_Map/; http://www.animalgenome.org/QTLdb/cattle.html; http://bovineqtl.tamu.edu/). Similarly, all 10 QTL regions in the Brown Swiss that affected PP only, affected only PP in the databases. Thus, many QTL appear to be common to Brown Swiss and other breeds in the databases (mainly Holstein), and an appreciable fraction of QTL appears to affect MY or PP primarily or exclusively, with little or no effect on the other trait. Although QTL information available today in the Brown Swiss population can be utilized only in a within family marker-assisted selection approach, knowledge of QTL segregating in the whole population should boost gene identification and ultimately the implementation and efficiency of an individual genomic program.

We report the discovery of a planet --- OGLE-2014-BLG-0676Lb --- via gravitational microlensing. Observations for the lensing event were made by the MOA, OGLE, Wise, RoboNET/LCOGT, MiNDSTEp and $\mu$FUN groups. All analyses of the light curve data favour a lens system comprising a planetary mass orbiting a host star. The most favoured binary lens model has a mass ratio between the two lens masses of $(4.78 \pm 0.13)\times 10^{-3}$. Subject to some important assumptions, a Bayesian probability density analysis suggests the lens system comprises a $3.09_{-1.12}^{+1.02}$ M_jup planet orbiting a $0.62_{-0.22}^{+0.20}$ M_sun host star at a deprojected orbital separation of $4.40_{-1.46}^{+2.16}$ AU. The distance to the lens system is $2.22_{-0.83}^{+0.96}$ kpc. Planet OGLE-2014-BLG-0676Lb provides additional data to the growing number of cool planets discovered using gravitational microlensing against which planetary formation theories may be tested. Most of the light in the baseline of this event is expected to come from the lens and thus high-resolution imaging observations could confirm our planetary model interpretation., Comment: 10 pages, 5 figures, MNRAS accepted

The building of complex systems from basic logic gates is one of the hallmarks of circuit design in electrical engineering. The question arises whether a similar strategy can be adopted for the design of artificial biological systems. In this paper, we present the design of two logic gates, a biological AND and a biological XOR. They can be combined to produce a half-adder, one of the fundamental elements of complex systems engineering, and represent a promising basis for the design of more complex genetic circuits. Design space exploration allowed us to screen gate variants, while sensitivity analysis of refined models contributed to the specific implementation of the gates at the DNA level. The XOR gate is based on two specific proteases, which reciprocally inactivate co-synthesised transcription factors. The AND gate is designed such that, in the presence of two signals, a tRNA suppresses the premature termination of T7 RNA polymerase translation. Computer models confirmed that both designs allow gate behaviour that is reasonably close to idealised gates.

Background Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. Methods We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 Gy RBE (50.4-55.8 Gy RBE ). Tumor size was measured before initial CT and before RT. Results With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm 3 vs 43 cm 3 , P =.9) but a greater median volume before RT (pre-RT) (40 cm 3 vs 7 cm 3 , P =.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P P =.05), larger pre-RT tumor volume ( P =.03), and smaller RPVR ( P =.003) were significantly associated with actuarial LF on univariate Cox analysis. Conclusions Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS.

Purpose To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. Patients and Methods From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or “B” symptoms and all stage III and IV. Results Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% ± 2.5% and 75.6% ± 4.1%, respectively. Conclusion Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.

Background. Prevalence of hypertension is greater in older adults, and increased intake of fruits, vegetables, and dairy—good sources of potassium, calcium, and magnesium—can reduce blood pressure. This study examined the hypertension-related dietary patterns of older adults. Methods. A cohort of 180 Pennsylvania adults (aged ≥65), 90 with hypertension, were randomly selected from the Geisinger Rural Aging Study (GRAS). Data were collected by trained interviewers at a home visit. Dietary assessment used five 24-h recalls. We compared the characteristics and dietary intake of people with hypertension to those without hypertension and compared their intakes to current recommendations. Results. Mean intakes of all participants were less than two thirds of the DRI for calcium and magnesium and fell far short of the 3,500 mg of potassium recommended for prevention and treatment of hypertension. Participants with hypertension consumed less sodium than controls. Both groups ate fewer fruits and vegetables than recommended but reached the dairy recommendation. Calcium intake was mainly from high-fat dairy products, beans were the top source of potassium and magnesium. Conclusions. Older adults with hypertension should be guided to choose more low-fat dairy products and other low-fat calcium sources and to increase intakes of beans, dark green leafy vegetables, and other potassium and magnesium sources.

From the Division of Pediatric Hematology–Oncology, Pediatric Service (A.M.F.), and the Departments of Radiation Oncology (N.J.T.), Radiology (P.W.S.), and Pathology (B.L.H.), Massachusetts General Hospital; and the Departments of Pediatrics (A.M.F.), Radiation Oncology (N.J.T.), Radiology (P.W.S.), and Pathology (B.L.H.), Harvard Medical School.

Presentation of Case An 18-year-old man was admitted to the hospital because of back and leg pain and a nondiagnostic biopsy specimen from a paravertebral mass. The patient had been well until eight months earlier, when the back pain began. Despite the use of ibuprofen and local application of ice, the pain increased, and three months before admission, pain developed in the right lower leg. A chiropractor obtained a radiograph of the spine, which revealed a compression fracture at the L3 vertebra. About one month before admission, a computed tomographic (CT) scan of the lumbosacral spine, obtained at another facility, . . .

Objective To test the feasibility of two models of home meal delivery with Meals-on-Wheels (MOW) applicants who were identified as being malnourished or ″at-risk" as determined by the validated Mini Nutritional Assessment (MNA). Design A 6-month, prospective comparative study of two nutrition intervention models with data collection at baseline, 3 months, and 6 months. Randomized treatment assignment was followed, with a few exceptions linked to particular client circumstances. Subjects A total of 203 older adults (age range=60 to 90 years) newly applying for homebound meal service were enrolled. At baseline, the body mass index (BMI) was 26.3±7.2 (mean±SD) in the ″Traditional" MOW model (101 subjects including 30 malnourished), and the BMI was 27.6±9.0 in the ″New" MOW model (102 subjects including 26 malnourished) (P = ns). Intervention Study participants received either the Traditional MOW program of five hot meals per week, meeting 33% of the Daily Reference Intake (DRI) or the restorative, comprehensive New MOW program of three meals and two snacks per day, 7 days a week, meeting 100% of the DRI. Assessments were conducted in the home of the participants. Main outcome measures The MNA was used to evaluate nutritional risk and status of participants at baseline, 3 months, and 6 months. Standardized functional impairment scales, Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) evaluated limitations in activities of daily living and life management skills. Statistical analysis Comparisons between treatment groups were calculated with t tests or Wilcoxon rank-sum tests when appropriate. Comparisons among time periods between treatment groups were conducted with repeated measures analysis of variance. A general linear model was used to evaluate the relationship between change in functional status and BMI, controlling for sex. Results The New MOW group gained significantly more weight between baseline and 3 months than did the Traditional MOW group (2.78 lb vs −1.46 lb, respectively, P=.0120) and again between baseline and 6 months (4.30 lb vs −1.72 lb, respectively, P=.0004). MNA improved faster in the New MOW group. Functional change appeared to be related more to BMI and age than to treatment intervention. The malnourished participants in both groups took longer to affect positive change in nutrition measurements, with the New MOW group showing the most improvement over the 6-month measurement period. Both delivery models were well accepted. Conclusions Applicants for home meal delivery have varying nutrition needs. By addressing nutritional risk, interventions can be targeted to meet these needs. A new, restorative, comprehensive meal program improved nutritional status and decreased nutritional risk and can possibly impact independence and functionality. J Am Diet Assoc. 2003;103:329-336.

This study was designed to determine if low doses of oral sodium phenylbutyrate (SPB) induce hemoglobin F (HbF) synthesis in children with hemoglobin SS (HbSS). We treated 8 children with HbSS over a period of 5-30 weeks. The initial dose (1.0 g/d) was increased weekly (by 1.0 g/d) until F-reticulocytes doubled. All patients showed an increase in F-reticulocytes (P = 0.002) that was dose-dependent (P = 0.001). Three of 5 patients who continued oral SPB for more than 10 weeks had substantial increases in HbF. We conclude that lower dose SPB is effective in inducing HbF synthesis in some children with HbSS. Further trials are warranted to determine the optimal treatment regimen.

PURPOSE: Between January 1990 and April 1993, 56 pediatric patients with Hodgkin’s disease were treated on a single-arm trial at three institutions with a regimen designed to maintain high cure rates while minimizing the potential late effects of treatment, such as infertility, second malignant neoplasms, and cardiopulmonary injury. PATIENTS AND METHODS: The regimen used combined-modality therapy with six cycles of vinblastine, etoposide, prednisone, and doxorubicin (VEPA) chemotherapy and low-dose, involved-field radiation. Unfavorable features comprised bulky presentations of localized (stage I or II) disease or advanced (stage III or IV) Hodgkin’s disease. RESULTS: Of 56 patients enrolled, 26 (46%) had unfavorable presentations of stage I/II disease and 30 (54%) had advanced (stage III/IV) disease. Seventy-nine percent of the patients are alive without disease at a median follow-up time of 8.9 years from diagnosis. Nineteen patients had events at a median of 1.5 years (range, 0.4 to 7.9 years) from diagnosis; 17 patients relapsed, one died of cardiomyopathy, and one died of accidental injuries. Survival and event-free survival (EFS) estimates at 5 years for the entire cohort were 81.9% (SE, 5.2%) and 67.8% (SE, 6.3%), respectively. Five-year EFS by stage was 100% for stage I, 79.2% (SE, 8.3%) for stage II, 70% (SE, 14.5%) for stage III, and 49.5% (SE, 11.3%) for stage IV patients. CONCLUSION: Combined-modality therapy with VEPA chemotherapy and low-dose, involved-field radiation is adequate for disease control of early-stage patients with unfavorable features, but it is inferior to other standard regimens for advanced-stage patients.

OBJECTIVE: The purpose of this study was to determine whether energy expenditure estimated from physical activity and energy intake were equivalent to total daily energy expenditure in an elderly rural population. METHODS: Twenty-seven elderly male ( n = 14) and female ( n = 13) subjects (mean age, 74 y) were recruited from a rural Pennsylvania population. Over a 2-wk period, total daily energy expenditure was measured by doubly labeled water (TEE) and estimated from 7-d physical activity recall factors multiplied by weight (PA WT ), estimated basal metabolic rate (PA BMR ) and resting energy expenditure from indirect calorimetry (PA REE ), and energy intake from 3-d self-reported diet records (EI). Analysis of variance was used to determine significant within-subject differences in physical activity, energy intake, and energy expenditure. RESULTS: PA REE (men: 13.69 ± 3.23 MJ, women: 9.51 ± 2.40 MJ) and PA BMR (men: 13.69 ± 2.99 MJ, women: 10.15 ± 2.21 MJ) were not significantly different from TEE (men: 12.43 ± 1.63 MJ, women: 9.44 ± 0.90 MJ). EI (men: 8.66 ± 2.34 MJ, women: 7.12 ± 0.93 MJ) was significantly less than TEE, and PA WT (men: 17.03 ± 4.07 MJ, women: 12.86 ± 3.41 MJ) was significantly greater than TEE. CONCLUSIONS: Whereas 7-d physical activity recall determined with an age- and gender-specific estimate of resting metabolic rate or measured using indirect calorimetry accurately estimated TEE for this group of rural elderly, self-reported diet records consistently underestimated and physical activity recall determined with weight alone consistently overestimated energy expenditure measured by doubly labeled water.

The purpose of this study was to determine which clinical and laboratory features correlate with serious hemorrhage in thrombocytopenic oncology patients. A retrospective review was conducted of all thrombocytopenic adult patients admitted to the Johns Hopkins Oncology Center, Baltimore, MD, over the last 10 years. We performed multiple logistic regression analysis on 2942 patients looking at the frequency of serious bleeding as a function of platelet count and numerous features that may correlate with hemorrhage. Multivariate analyses showed no relationship between either the first morning platelet count or the lowest platelet count of the day and the risk of hemorrhage. Of the other features we examined, several correlated independently with bleeding, including uremia (odds ratio [OR] 1.64; 95% confidence interval [CI], 1.40 to 1.92), hypoalbuminemia (OR 1.54; 95% CI, 1.33 to 1.79), recent bone marrow transplantation (OR 1.32; 95% CI, 1.22 to 1.43), and recent hemorrhage (OR 6.72; 95% CI, 5.53 to 8.18). Leukopenia was associated with a decreased risk of bleeding (OR 0.70; 95% CI, 0.60 to 0.82). Although this large study identified a number of clinical and laboratory features that correlated significantly with bleeding, the ORs of these factors were not large and all were much less than previous bleeding. These findings suggest that the major goal of transfusion support should be the aggressive therapeutic use of blood products rather than prophylactic use based on such weak clinical correlates and on the platelet count, which was not a correlate at all in multivariate analysis.

Purpose This prospective phase II study was designed to assess disease control and to describe acute and late adverse effects of treatment with proton radiotherapy in children with rhabdomyosarcoma (RMS). Patients and Methods Fifty-seven patients with localized RMS (age 21 years or younger) or metastatic embryonal RMS (age 2 to 10 years) were enrolled between February 2005 and August 2012. All patients were treated with chemotherapy based on either vincristine, actinomycin, and cyclophosphamide or vincristine, actinomycin, and ifosfamide–based chemotherapy and proton radiation. Surgical resection was based on tumor site and accessibility. Common Terminology Criteria for Adverse Events, Version 3.0, was used to assess and grade adverse effects of treatment. Concurrent enrollment onto Children's Oncology Group or European Pediatric Sarcoma Study Group protocols was allowed. All pathology and imaging were reviewed at the treating institution. Results Median follow-up was 47 months (range, 14 to 102 months) for survivors. Five-year event-free survival (EFS), overall survival (OS), and local control (LC) were 69%, 78%, and 81%, respectively, for the entire cohort. The 5-year LC by risk group was 93% for low-risk and 77% for intermediate-risk disease. There were 13 patients with grade 3 acute toxicity and three patients with grade 3 late toxicity. There were no acute or late toxicities higher than grade 3. Conclusion Five-year LC, EFS, and OS rates were similar to those observed in comparable trials that used photon radiation. Acute and late toxicity rates were favorable. Proton radiation appears to represent a safe and effective radiation modality for pediatric RMS.

BACKGROUND: Esthesioneuroblastoma (EN) of the paranasal sinus comprises less than 3% of tumors of in pediatric and adolescent patients [1]. The collective adult literature indicates a critical role for radiotherapy in attaining a cure [2], yet pediatric outcome data is limited. Radiation in pediatric EN patients can cause significant morbidity due to the proximity of critical structures. Proton radiotherapy offers a potential dosimetric benefit that may improve long-term survival and toxicity outcomes in the pediatric population [3]. METHODS: We retrospectively identified 8 patients treated for EN with proton radiotherapy from 2000-2013. Times to event clinical endpoints are summarized using the Kaplan Meier methods and are from the date of radiotherapy completion. Toxicities are reviewed and graded according to CTCAE v. 4.0. RESULTS: Median follow up was 4.6 years for survivors (range 0.8-9.4 years). The 4 year overall survival was 87.5%. Four of eight patients (one elective) had comprehensive neck radiotherapy. No local or regional failures were observed. Two patients failed distantly with diffuse leptomeningeal disease and intraparenchymal brain metastases respectively, at 0.6 and 1.3 months. Four patients developed radiation related late toxicities including endocrine dysfunction, two cases of grade 2 retinopathy and one case of grade 3 optic neuropathy. CONCLUSIONS: In a limited cohort, proton radiotherapy appears to provide excellent locoregional disease control even in those patients with locally advanced disease and intracranial extension. Distant failure determined overall survival in our cohort. Toxicities were acceptable given disease location and extent.

Background The potential for the use of nutritional screening to identify older persons at risk of hospitalization has not been contrasted with the use of tools developed for predicting hospital admissions. Objective Our goal was to compare the associations of items from the Level II Nutrition Screen (LII) and the Probability of Repeated Admissions (P(ra)) questionnaire with the outcome of hospitalization. Design This was a cohort study of participants in a Medicare managed-risk health plan who completed both the LII and P(ra) (n = 386). All hospitalizations within 1 y of screening were recorded. Hierarchical multivariate logistic regression was used to model associations with hospitalization. Results P(ra) items that retained significant associations with hospitalization were self-reported health, hospitalization in the past year, and >6 doctor visits in the past year (positive predictive value: 20%; sensitivity: 53.1; specificity: 69.7). LII items that retained significant associations with hospitalization were eating problems and polypharmacy (positive predictive value: 17.9%; sensitivity: 58.0; specificity: 56.3). Those persons designated by the P(ra) score as being at high risk of hospitalization (P(ra) > or = 0.30, 75th percentile) were also more likely to report weight loss, polypharmacy, consumption of a special diet, and functional limitation on the LII. Conclusions Retained items from the P(ra) and the LII were comparable in identifying participants at risk of hospitalization. These observations suggest that nutritional risk factors such as eating problems, weight loss, and consumption of special diets should be considered in the management of older persons at risk of hospitalization, irrespective of the screening approach selected.

OBJECTIVES: To determine whether there is a gender difference in how body mass index (BMI) relates to self-reported functional limitation. Also, to evaluate whether the method of categorizing BMI changes the observed results. DESIGN: Cross-sectional cohort study. SETTING: Rural Pennsylvania. PARTICIPANTS: A total of 7,120 male (n = 3,312) and female (n = 3,808) community-dwelling older adults enrolled in a Medicare managed-risk contract. MEASUREMENTS: All subjects completed a modified Level II Nutrition Risk Screen upon enrollment in the health plan. Height and weight were obtained by nursing personnel during an enrollment clinic visit. Subjects who reported 10 or more pounds weight loss in the previous 6 months were excluded. Logistic regression was used to evaluate the relationship between BMI and self-reported functional limitation separately for each sex, adjusting for age, depression, and polypharmacy. Two schemes were used to categorize BMI: equally distributed sex-specific quintiles and arbitrary division based on National Institutes of Health (NIH) Obesity Guidelines. RESULTS: How BMI relates to functional limitation depends upon both sex and method of categorizing BMI. When BMI was considered in gender-specific quintiles, women in the highest quintile of BMI had increased risk of functional impairment; there was no relationship between BMI and functional limitation for men. When BMI was categorized by the NIH obesity guidelines, both men and women with BMI >40 had significantly increased risk of functional limitation. CONCLUSIONS: The mechanisms behind gender discrepancy in self-reported functional limitation remain unclear. Studies may need to consider men and women separately, because how BMI relates to function depends on gender. Further research is needed to evaluate how changes in weight and body composition during middle and old age affect functional status.

The mechanisms of cadmium (Cd)-dependent nephrotoxicity were studied in a rat proximal tubule (PT) cell line. CdCl(2) (5 microM) increased the production of reactive oxygen species (ROS), as determined by oxidation of dihydrorhodamine 123 to fluorescent rhodamine 123. The levels of ubiquitin-conjugated cellular proteins were increased by Cd in a time-dependent fashion (maximum at 24-48 h). This was prevented by coincubation with the thiol antioxidant N-acetylcysteine (NAC, 15 mM). Cd also increased apoptosis (controls: 2.4+/-1.6%; Cd: 8.1+/-1.9%), but not necrosis (controls: 0.5 +/- 0.3%; Cd: 1.4+/- 2.5%). Exposure of PT cells with Cd decreased protein levels of the catalytic subunit (alpha1) of Na+/K(+)-ATPase, a long-lived membrane protein (t(1/2)>48 h) that drives reabsorption of ions and nutrients through Na(+)-dependent transporters in PT. Incubation of PT cells for 48 h with Cd decreased Na+/K(+)-ATPase alpha1-subunit, as determined by immunoblotting, by approximately 50%, and NAC largely prevented this effect. Inhibitors of the proteasome such as MG-132 (20 microM) or lactacystin (10 microM), as well as lysosomotropic weak bases such as chloroquine (0.2 mM) or NH(4)Cl (30 mM), significantly reduced the decrease of Na(+)/K(+)-ATPase alpha1-subunit induced by Cd, and in combination abolished the effect of Cd on Na+/K(+)-ATPase. Immunofluorescence labeling of Na+/K(+)-ATPase showed a reduced expression of the protein in the plasma membrane of Cd-exposed cells. After addition of lactacystin and chloroquine to Cd-exposed PT cells, immunoreactive material accumulated into intracellular vesicles. The data indicate that micromolar concentrations of Cd can increase ROS production and exert a toxic effect on PT cells. Oxidative damage increases the degradation of Na+/K(+)-ATPase through both the proteasomal and endo-/lysosomal proteolytic pathways. Degradation of oxidatively damaged Na+/K(+)-ATPase may contribute to the 'Fanconi syndrome'-like Na(+)-dependent transport defects associated with Cd-nephrotoxicity.

The mass of the lenses giving rise to Galactic microlensing events can be constrained by measuring the relative lens-source proper motion and lens flux. The flux of the lens can be separated from that of the source, companions to the source, and unrelated nearby stars with high-resolution images taken when the lens and source are spatially resolved. For typical ground-based adaptive optics (AO) or space-based observations, this requires either inordinately long time baselines or high relative proper motions. We provide a list of microlensing events toward the Galactic Bulge with high relative lens-source proper motion that are therefore good candidates for constraining the lens mass with future high-resolution imaging. We investigate all events from 2004 -- 2013 that display detectable finite-source effects, a feature that allows us to measure the proper motion. In total, we present 20 events with mu >~ 8 mas/yr. Of these, 14 were culled from previous analyses while 6 are new, including OGLE-2004-BLG-368, MOA-2005-BLG-36, OGLE-2012-BLG-0211, OGLE-2012-BLG-0456, MOA-2012-BLG-532, and MOA-2013-BLG-029. In, Comment: 10 pages, 8 figures, 6 tables, submitted to ApJ. For a brief video explaining the key results of this paper, please visit: https://www.youtube.com/watch?v=i_dzT8NydJI

This study determined predictors of early nonelective hospital readmission in 92 (49 women and 43 men) nutritionally compromised Medicare patients. Subjects ranged in age from 65 to 92 y and represented patients hospitalized previously for medical or surgical services. The study used a repeated-measures design of multiple variables representing demographics, anthropometric and clinical values, and functional status. Data were collected during hospitalization and during home visits at 1 and 3 mo postdischarge. There were 26 readmissions, making the 4-mo nonelective readmission rate 26%. Subjects who were readmitted nonelectively were compared with those not readmitted. Univariate analyses suggested strong relations between readmission outcome and serum albumin, total lymphocyte count, change in weight, and change in white blood cell count. Sociodemographic variables were less useful in predicting readmission than were measurements of patients' clinical status. Measurements of change in clinical variables were generally more predictive of readmission than was any one single measurement. Multivariate-logistic-regression analyses suggested a model consisting of change in weight and change in serum albumin from hospitalization to 1 mo after discharge as being highly predictive of early nonelective readmission. Individuals with any amount of weight loss and no improvement in albumin concentrations during the first month after hospitalization were at a much higher risk of readmission than were those who maintained or increased their postdischarge weight and had repleted their serum albumin concentrations. More study is warranted to clarify whether routine monitoring of changes in weight and serum albumin after hospitalization is appropriate in older adults.

The outcome of treatment for pediatric Hodgkin lymphoma (HL) is excellent using chemotherapy and radiation. However, a minority of patients will relapse after treatment, but additional therapy achieves durable second remission in many cases. The optimal surveillance strategy after modern therapy for HL has not been well defined.We reviewed the outcomes of pediatric patients with HL treated between 1990 and 2006 to determine the primary event that led to the detection of relapse. We determined the probability of relapse detection by routine follow-up procedures, including history, physical examination, laboratory tests, and imaging, and determined the impact of each of these screening methods on the likelihood of survival after relapse.Relapse occurred in 64 of 402 evaluable patients (15.9%) at a median of 1.7 years from the time of diagnosis. The majority of relapses (60%) were diagnosed at a routine visit, and patient complaint was the most common initial finding that led to a diagnosis of relapse (47% of relapses). An abnormal finding on physical examination was the primary event in another 17% of relapses, and imaging abnormalities led to the diagnosis in the remaining 36%. Laboratory abnormalities were never the primary finding. The method of detection of relapse and timing (whether detected at a routine visit or an extra visit) did not impact survival.In pediatric HL, most relapses are identified through history and physical examination. Frequent imaging of asymptomatic patients does not appear to impact survival and is probably not warranted.

Survival for childhood acute lymphoblastic leukemia (ALL) now approaches 90% with risk adapted therapy based on National Cancer Institute risk group (NCI RG) at diagnosis, somatic lymphoblast genetics, and early response to therapy as measured by minimal residual disease (MRD). The Children's Oncology Group AALL03B1 ALL Classification trial enrolled 11,145 children, adolescents, and young adults less than 31 years of age with newly diagnosed B- or T-lineage ALL between December 2003 and September 2011. Companion therapeutic trials for B-lineage ALL included AALL0331 (n= 5226) for NCI standard risk (SR-ALL)(age 1-10 years and white blood cell count (WBC) < 50,000/uL) and AALL0232 (n=2907] for NCI high risk (HR) ALL (age > 10 years or presenting WBC > 50,000/uL). Assessing outcome by lymphoblast genetics revealed statistically significant distributions of genotype and NCI RG, as well as differences in event-free and overall-survival (EFS, OS) (Table 1). Not surprisingly, favorable genetic groups of Trisomy 4/10/17 (TT) and ETV6/RUNX1 were significantly more common in NCI SR patients (p< 0.0001 for each) while those with unfavorable characteristics (MLL rearranged [MLLr], intrachromosomal amplification of chromosome 21 [iAMP21], BCR/ABL1 and hypodiploidy [n A subset of consecutively enrolled (N=605) AALL0232 NCI HR patients underwent additional genomic interrogation, including assessment of Ph-like status, ABL1 class fusions, CRLF2r, JAK mutations (JAKm), and IKZF1 alterations. Based on sample availability, patients studied were younger (p < 0.0001) and had a higher WBC (p < 0.0001) compared to the remainder of AALL0232. There were 85/605 (14.0%) Ph-like patients defined using PAM clustering algorithms and Ph-like status was significantly associated with an IKZF1 alteration (75%) (p < 0.0001) and day 29 MRD > .01% (p < 0.0001). Five-year EFS for Ph-like versus non Ph-like was 62.3±5.8% vs. 83.9±1.7% (p < 0.0001). Outcomes of Ph-like ALL with or without CRLF2r were similar (60.6±8.3% versus 65.4±8.0%, p =0.86). Similarly, 5-year EFS of Ph-like ALL was no different with or without IKZF1 alterations (61.5±7.0% vs. 64.6 ±11.1%). There were 155 (27.1%) IKZF1 alterations, 60 of which occurred in Ph-like ALL with a trend towards concomitant CRLF2r/JAKm (p=0.055). Five-year EFS for patients with IKZF1 alterations was 66.8±4.0% (p < 0.0001) versus 86.4±1.8% for those without IKZF1 lesions. Multivariable analysis demonstrated age, WBC and day 29 MRD as independent risk factors for sustained CR while only Ph-like status, IKZF1 alteration, BCR/ABL1 and ETV6/RUNX1retained independent prognostic significance when added to the model individually. In summary, somatic sentinel cytogenetic alterations are independently prognostic in childhood ALL and are strongly associated with NCI RG and outcome, supporting continued incorporation into risk stratification algorithms. Notably, >44% of all patients have favorable blast cytogenetics with 5-year overall survival rates approaching 100%. In contrast, NCI HR patients with Ph-like ALL have poor outcomes with currently available therapy and this subtype is associated with CRLF2 r and IKZF1 alterations, which do not confer an inferior EFS within the Ph-like subgroup. Novel therapies for genomicallydefined Ph-like ALL may improve outcomes. Disclosures Loh: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding. Borowitz:HTG Molecular: Consultancy; Bristol-Myers Squibb: Research Funding; MedImmune: Research Funding; BD Biosciences: Research Funding.

More than 90% of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects.To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone (VAMP) in patients with favorable-risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy.Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012.The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy.Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low.Two-year event-free survival was 90.8% (95% CI, 84.7%-96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P = .61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed.Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival.clinicaltrials.gov Identifier: NCT00145600.

Purpose To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS). Methods and Materials Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest. Results Median patient age at diagnosis was 3.4 years (range, 0.4–17.6). Embryonal ( n = 11), alveolar ( n = 4), and undifferentiated ( n = 2) histologies were represented. Ten patients (59%) had intracranial extension. Median prescribed dose was 50.4 cobalt gray equivalents (GyRBE) (range, 50.4–56.0 GyRBE) delivered in 1.8–2.0-GyRBE daily fractions. Median follow-up was 5.0 years for survivors. The 5-year failure-free survival estimate was 59% (95% confidence interval, 33–79%), and overall survival estimate was 64% (95% confidence interval, 37–82%). Among the 7 patients who failed, sites of first recurrence were local only ( n = 2), regional only ( n = 2), distant only ( n = 2), and local and distant ( n = 1). Late effects related to proton radiotherapy in the 10 recurrence-free patients (median follow-up, 5 years) include failure to maintain height velocity ( n = 3), endocrinopathies ( n = 2), mild facial hypoplasia ( n = 7), failure of permanent tooth eruption ( n = 3), dental caries ( n = 5), and chronic nasal/sinus congestion ( n = 2). Conclusions Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts.

A 10-year-old boy was referred to our clinic for tonsillectomy and was found to have a large mass within his oropharynx. Intraoperative biopsies confirmed Burkitt lymphoma. Further imaging and biopsy revealed pancreatic involvement. He was treated with multiagent chemotherapy. He remains disease-free 6 years later. Review of the literature demonstrates other cases of non-Hodgkin lymphoma with pancreatic involvement with good outcomes. Pancreatic involvement is a relatively rare occurrence in childhood lymphoma.

Primary pulmonary rhabdomyosarcoma (RMS) in the pediatric population is a rare entity. A 5-month-old boy initially treated for pneumonia was proven to have a primary pulmonary RMS, which was resected via thoracotomy. After a course of chemotherapy following the Children's Oncology Group low-risk RMS protocol (ARST0331), a restaging chest computerized tomography scan showed local recurrence, which was also resected by open thoracotomy. The patient is currently undergoing local radiotherapy and salvage chemotherapy regimen. This patient is the youngest reported to date with this entity. The prognostic significance of his young age and the morphologic findings of his tumor are unclear.

To describe our preliminary experience with simultaneous whole body (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and magnetic resonance imaging (PET-MRI) in the evaluation of pediatric oncology patients.This prospective, observational, single-center study was Health Insurance Portability and Accountability Act-compliant, and institutional review board approved. To be eligible, a patient was required to: (1) have a known or suspected cancer diagnosis; (2) be under the care of a pediatric hematologist/oncologist; and (3) be scheduled for clinically indicated (18)F-FDG positron emission tomography-computed tomography (PET-CT) examination at our institution. Patients underwent PET-CT followed by PET-MRI on the same day. PET-CT examinations were performed using standard department protocols. PET-MRI studies were acquired with an integrated 3 Tesla PET-MRI scanner using whole body T1 Dixon, T2 HASTE, EPI diffusion-weighted imaging (DWI) and STIR sequences. No additional radiotracer was given for the PET-MRI examination. Both PET-CT and PET-MRI examinations were reviewed by consensus by two study personnel. Test performance characteristics of PET-MRI, for the detection of malignant lesions, including FDG maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin), were calculated on a per lesion basis using PET-CT as a reference standard.A total of 10 whole body PET-MRI exams were performed in 7 pediatric oncology patients. The mean patient age was 16.1 years (range 12-19 years) including 6 males and 1 female. A total of 20 malignant and 21 benign lesions were identified on PET-CT. PET-MRI SUVmax had excellent correlation with PET-CT SUVmax for both benign and malignant lesions (R = 0.93). PET-MRI SUVmax2.5 had 100% accuracy for discriminating benign from malignant lesions using PET-CT reference. Whole body DWI was also evaluated: the mean ADCmin of malignant lesions (780.2 + 326.6) was significantly lower than that of benign lesions (1246.2 + 417.3; P = 0.0003; Student's t test). A range of ADCmin thresholds for malignancy were evaluated, from 0.5-1.5 × 10(-3) mm(2)/s. The 1.0 × 10(-3) ADCmin threshold performed best compared with PET-CT reference (68.3% accuracy). However, the accuracy of PET-MRI SUVmax was significantly better than ADCmin for detecting malignant lesions compared with PET-CT reference (P0.0001; two-tailed McNemar's test).These results suggest a clinical role for simultaneous whole body PET-MRI in evaluating pediatric cancer patients.

[Graphic][1] Overall improvements in ALL outcomes have been attributed in part to refinements in risk classification that affect treatment intensity. The COGdeveloped a real-time disease classification protocol utilizing clinical, biologic and early disease response measures from local and central reference laboratories. Patients between 1-30 years were enrolled on the COG AALL03B1 classification study at the time of B-ALL diagnosis and subsequently initiated a 3-drug (standard risk; SR) or 4-drug induction (HR) based on NCI risk group. All patients underwent standardized testing at approved or central laboratories to detect favorable (triple trisomies of chromosomes 4, 10 and 17 [TT] or ETV6-RUNX1 fusion) and unfavorable (hypodiploidy [DNA index 1 year of age with B-ALL were classified into low, standard, high or very high risk groups for treatment allocation. Variables used for risk classification included age, initial WBC, extramedullary disease status, blast cytogenetics and early treatment response based on bone marrow morphology and day 29 marrow minimal residual disease (MRD). Rapid early response (RER) was defined as M1 (

To move one step forward toward a Galactic distribution of planets, we present the first planet sensitivity analysis for microlensing events with simultaneous observations from space and the ground. We present this analysis for two such events, OGLE-2014-BLG-0939 and OGLE-2014-BLG-0124, which both show substantial planet sensitivity even though neither of them reached high magnification. This suggests that an ensemble of low to moderate magnification events can also yield significant planet sensitivity and therefore probability to detect planets. The implications of our results to the ongoing and future space-based microlensing experiments to measure the Galactic distribution of planets are discussed., 10 pages, 5 figures, 1 table; ApJ in press

10035 Background: COG AALL0331 administered PEG IM in induction (IND) and Delayed intensification (DI) whereas AALL0932 administers the same dose IV. We compared grade 3/4 toxicities resulting from...

Background: Over 85% of pediatric orbital rhabdomyosarcoma (RMS) are cured with combined chemotherapy and radiation. However, the late effects of photon radiation compromise function and cosmetic outcome. Proton radiation can provide excellent tumor dose distributions while sparing normal tissues better than photon irradiation. Methods and Materials: Conformal 3D photon and proton radiotherapy plans were generated for children treated with proton irradiation for orbital RMS at Massachusetts General Hospital. Dose–volume histograms (90%, 50%, 10%) were generated and compared for important orbital and central nervous system structures. Average percentages of total dose prescribed were calculated based on the 3 dose–volume histogram levels for normal orbital structures for both the proton and photon plans. The percent of normal tissue spared by using protons was calculated. Results: Seven children were treated for orbital rhabdomyosarcoma with proton irradiation and standard chemotherapy. The median follow-up is 6.3 years (range, 3.5–9.7 years). Local and distant controls compare favorably to those in other published accounts. There was an advantage in limiting the dose to the brain, pituitary, hypothalamus, temporal lobes, and ipsilateral and contralateral orbital structures. Tumor size and location affect the degree of sparing of normal structures. Conclusions: Fractionated proton radiotherapy is superior to 3D conformal photon radiation in the treatment of orbital RMS. Proton therapy maintains excellent tumor coverage while reducing the radiation dose to adjacent normal structures. Proton radiation therapy minimizes long-term side effects.

We compared clinical outcomes with a standard (Ensure) or a high-protein (Boost HP) liquid nutritional supplement for older adults recovering from hip fracture surgery in a rehabilitation hospital.This randomized, double-blind, parallel-group study compared the clinical effectiveness of a standard (Ensure) with a high-protein (Boost HP) liquid nutritional supplement among patients (n = 46) 60 y or older who recently underwent surgical repair of a hip fracture. Patients were encouraged to drink at least two 8-oz cans (17.8 g/d protein for Ensure versus 30 g/d protein for Boost HP) per day for 28 d. Study measurements included change in Functional Independence Measure between rehabilitation admission and discharge, length of rehabilitation stay, laboratory measures (i.e., serum albumin, prealbumin, and C-reactive protein), physical activity energy expenditure by 7-d triaxial accelerometry, and dietary intake by three random, telephonic, 24-h dietary recalls.There were no significant group differences with respect to age, sex, acute hospital days, hip fracture assessment parameters, or surgical treatment. Consumption of supplement (260 oz/28 d of Ensure versus 239 oz/28 d of Boost HP) was comparable. There were no differences in complication or adverse event rates during the study. The Boost HP group consumed more protein than the Ensure group (63 versus 50 g, P0.048) and had a greater improvement in serum albumin over the 28-d supplementation period (+0.7 versus +0.2 g/dL, P0.019). The Boost HP group also consumed more fiber (12 versus 8 g), calcium (821 versus 639 mg), vitamin K (66 versus 45 microg), and phosphorus (1035 versus 833 mg) than did the Ensure group. Rehabilitation length of stay was shorter in the Boost HP than in the Ensure group, although this trend did not reach statistical significance (23 versus 28 d, P = 0.27). Outcome differences were not detected in the Functional Independence Measure.Supplementation was well tolerated in this population and contributed significantly to total dietary intake. Consumption of a high-protein liquid nutritional supplement may offer some benefits by improving visceral protein status.

Vegetables and fruits contain numerous bioactive and potentially anticarcinogenic substances including carotenes, dithiolthiones, flavoids, indoles, isothiocyanates, phenols, folic acid and vitamins C and E.1 There are many possible mechanisms by which the above substances might inhibit carcinogenesis, such as antioxidant effects, increases in cell-to-cell communication, activation of enzymes involved in carcinogen detoxification, alteration of estrogen metabolism, effects on DNA methylation and repair and antiproliferative effects.1,2 Epidemiologic studies on the relationships of intake of vegetables and fruit with breast cancer risk, however, have not been consistent. Several studies reported an inverse association with vegetable3–15 or fruit intake.3,4,8,10 –12, 14, 16,17 Other studies reported a non-significant inverse association of fruit and vegetable intake with breast cancer.12,23,33 The results from previous studies on micronutrients such as vitamin A, C and E and carotene have also been inconsistent.3,4,12–14,16,18 –26 A recent pooled analysis of 8 cohort studies showed no significant association between fruit and vegetable intake and breast cancer risk.27 Virtually all the above studies, however, were conducted among Caucasian women. Many studies evaluated only a limited number of food items. One of the primary aims of the study is to examine whether intake of certain fruits and vegetables may be related to a reduction of breast cancer risk. During 1996 –98 we conducted a large population-based case– control study among Chinese women in Shanghai, where the incidence rate of breast cancer is about one-third the rate in US Caucasian women28 and the dietary practices and foods are not represented by previous studies conducted in western society.