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Wet markets have been implicated in multiple zoonotic outbreaks, including COVID-19. They are also a conduit for legal and illegal trade in wildlife, which threatens thousands of species. Yet wet markets supply food to millions of people around the world, and differ drastically in their physical composition, the goods they sell, and the subsequent risks they pose. As such, policy makers need to know how to target their actions to efficiently safeguard human health and biodiversity without depriving people of ready access to food. Here, we propose a taxonomy of wet markets, oriented around the presence of live or dead animals, and whether those animals are domesticated or wild (either captive-reared or wild-caught). We assess the dimensions and levels of risk that different types of wet markets pose to people and to biodiversity. We identify six key risk factors of wet markets that can affect human health: (1) presence of high disease-risk animal taxa, (2) presence of live animals, (3) hygiene conditions, (4) market size, (5) animal density and interspecies mixing, and (6) the length and breadth of animal supply chains. We also identify key factors informing risk to biodiversity. Finally, we recommend targeted, risk-adjusted policies to more efficiently and humanely address the dangers posed by wet markets.

Aircraft can hold large numbers of persons in close proximity for long periods, which can increase the risk for transmission of infectious disease.* Current CDC guidelines recommend against travel for persons who have not been vaccinated against COVID-19, and a January 2021 CDC order requires masking for all persons while on airplanes.†,§ Research suggests that seating proximity on aircraft is associated with increased risk for infection with SARS-CoV-2, the virus that causes COVID-19 (1,2). However, studies quantifying the benefit of specific distancing strategies to prevent transmission, such as keeping aircraft cabin middle seats vacant, are limited. Using bacteriophage MS2 virus as a surrogate for airborne SARS-CoV-2, CDC and Kansas State University (KSU) modeled the relationship between SARS-CoV-2 exposure and aircraft seating proximity, including full occupancy and vacant middle seat occupancy scenarios. Compared with exposures in full occupancy scenarios, relative exposure in vacant middle seat scenarios was reduced by 23% to 57% depending upon the modeling approach. A 23% exposure reduction was observed for a single passenger who was in the same row and two seats away from the SARS-COV-2 source, rather than in an adjacent middle seat. When quantifying exposure reduction to a full 120-passenger cabin rather than to a single person, exposure reductions ranging from 35.0% to 39.4% were predicted. A 57% exposure reduction was observed under the vacant middle seat condition in a scenario involving a three-row section that contained a mix of SARS-CoV-2 sources and other passengers. Based on this laboratory model, a vacant middle seat reduces risk for exposure to SARS-CoV-2 from nearby passengers. These data suggest that increasing physical distance between passengers and lowering passenger density could help reduce potential COVID-19 exposures during air travel. Physical distancing of airplane passengers, including through policies such as middle seat vacancy, could provide additional reductions in SARS-CoV-2 exposure risk.

Serologic testing of residual blood samples from 812 children from a hospital in New Orleans, LA, between March and May 2020, demonstrated a SARS-CoV-2 seroprevalence of 6.8% based on S and N protein IgG; Black and Hispanic children, and children living in zip codes with lower household incomes were over-represented.

BACKGROUND: Circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA may represent a more reliable indicator of infection than nasal RNA, but quantitative reverse transcription PCR (RT-qPCR) lacks diagnostic sensitivity for blood samples. METHODS: A CRISPR-augmented RT-PCR assay that sensitively detects SARS-CoV-2 RNA was employed to analyze viral RNA kinetics in longitudinal plasma samples from nonhuman primates (NHPs) after virus exposure; to evaluate the utility of blood SARS-CoV-2 RNA detection for coronavirus disease 2019 (COVID-19) diagnosis in adults cases confirmed by nasal/nasopharyngeal swab RT-PCR results; and to identify suspected COVID-19 cases in pediatric and at-risk adult populations with negative nasal swab RT-qPCR results. All blood samples were analyzed by RT-qPCR to allow direct comparisons. RESULTS: CRISPR-augmented RT-PCR consistently detected SARS-CoV-2 RNA in the plasma of experimentally infected NHPs from 1 to 28 days after infection, and these increases preceded and correlated with rectal swab viral RNA increases. In a patient cohort (n = 159), this blood-based assay demonstrated 91.2% diagnostic sensitivity and 99.2% diagnostic specificity versus a comparator RT-qPCR nasal/nasopharyngeal test, whereas RT-qPCR exhibited 44.1% diagnostic sensitivity and 100% specificity for the same blood samples. This CRISPR-augmented RT-PCR assay also accurately identified patients with COVID-19 using one or more negative nasal swab RT-qPCR results. CONCLUSION: Results of this study indicate that sensitive detection of SARS-CoV-2 RNA in blood by CRISPR-augmented RT-PCR permits accurate COVID-19 diagnosis, and can detect COVID-19 cases with transient or negative nasal swab RT-qPCR results, suggesting that this approach could improve COVID-19 diagnosis and the evaluation of SARS-CoV-2 infection clearance, and predict the severity of infection. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04358211. FUNDING: Department of Defense, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the National Center for Research Resources.

Balanced fusion and fission are key for the proper function and physiology of mitochondria1,2. Remodelling of the mitochondrial inner membrane is mediated by the dynamin-like protein mitochondrial genome maintenance 1 (Mgm1) in fungi or the related protein optic atrophy 1 (OPA1) in animals3–5. Mgm1 is required for the preservation of mitochondrial DNA in yeast6, whereas mutations in the OPA1 gene in humans are a common cause of autosomal dominant optic atrophy—a genetic disorder that affects the optic nerve7,8. Mgm1 and OPA1 are present in mitochondria as a membrane-integral long form and a short form that is soluble in the intermembrane space. Yeast strains that express temperature-sensitive mutants of Mgm19,10 or mammalian cells that lack OPA1 display fragmented mitochondria11,12, which suggests that Mgm1 and OPA1 have an important role in inner-membrane fusion. Consistently, only the mitochondrial outer membrane—not the inner membrane—fuses in the absence of functional Mgm113. Mgm1 and OPA1 have also been shown to maintain proper cristae architecture10,14; for example, OPA1 prevents the release of pro-apoptotic factors by tightening crista junctions15. Finally, the short form of OPA1 localizes to mitochondrial constriction sites, where it presumably promotes mitochondrial fission16. How Mgm1 and OPA1 perform their diverse functions in membrane fusion, scission and cristae organization is at present unknown. Here we present crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum. Mgm1 consists of a GTPase (G) domain, a bundle signalling element domain, a stalk, and a paddle domain that contains a membrane-binding site. Biochemical and cell-based experiments demonstrate that the Mgm1 stalk mediates the assembly of bent tetramers into helical filaments. Electron cryo-tomography studies of Mgm1-decorated lipid tubes and fluorescence microscopy experiments on reconstituted membrane tubes indicate how the tetramers assemble on positively or negatively curved membranes. Our findings convey how Mgm1 and OPA1 filaments dynamically remodel the mitochondrial inner membrane. Crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum reveal that Mgm1 forms bent tetramers, which further assemble into helical filaments on both positively and negatively curved membranes.

BACKGROUND: The current neuroblastoma (NBL) staging system employs image-defined risk factors (IDRFs) to assess numerous anatomic features, but the impact of IDRFs on surgical and oncologic outcomes is unclear. METHODS: The Vanderbilt Cancer Registry identified children treated for NBL from 2002 to 2017. Tumor volume (TV) and IDRFs were measured radiographically at diagnosis and before resection. Perioperative and oncologic outcomes were evaluated. RESULTS: At diagnosis of 106 NBL, 61% were IDRF positive. MYCN-amplified and undifferentiated NBL had more IDRFs than nonamplified and more differentiated tumors (p = 0.001 and p = 0.01). Of 86 NBLs resected, 43% were IDRF positive, which associated with higher stage, risk, and TV (each p < 0.001). The presence of IDRF at resection was also associated with increased blood loss (p < 0.001), longer operating times (p < 0.001), greater incidence of intraoperative complications (p = 0.03), more frequent ICU admissions postoperatively (p < 0.001), and longer hospital stays (p < 0.001). IDRF negative and positive tumors did not have significantly different rates of gross total resection (p = 0.2). Five-year relapse-free and overall survival was similar for IDRF negative and positive NBL (p = 0.9 and p = 0.8). CONCLUSIONS: IDRFs at diagnosis were associated with larger, less differentiated, advanced stage, and higher risk NBL and at resection with increased operative difficulty and perioperative morbidity. However, the frequency of gross total resection and patient survival after resection were not associated with the presence of IDRFs. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level III.

Background: Despite the paucity of evidence supporting chemotherapy in the treatment of node-negative, HER2-positive breast cancer measuring

BACKGROUNDChildren (≤18 years) account for ∼20% of the US population but currently represent METHODSDuring the March 18th-May 15th 2020 Louisiana Stay At Home Order, 1690 blood samples from 812 individuals from a Children’s Hospital were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Demographics, COVID-19 testing, and clinical presentation abstracted from medical records were compared with local COVID-19 cases.RESULTSIn total, 62 subjects (7.6%) were found to be seropositive. The median age was 11 years with 50.4% female. The presenting complaint of seropositive patients was chronic illness (43.5%). Only 18.2% had a previous positive COVID-19 PCR or antibody test. Seropositivity was significantly associated with parish (counties), race, and residence in a low-income area. Importantly, seropositivity was linearly correlated with cumulative COVID-19 case number for all ages by parish.CONCLUSIONIn a large retrospective study, the seropositivity prevalence for SARS-CoV-2 in children in Louisiana during the mandated Stay At Home Order was 7.6%. Residence location, race, and lower socioeconomic factors were linked to more frequent seropositivity in children and correlated to regional COVID-19 case rates. Thus, a significant number of children in Louisiana had SARS-CoV-2 infections that went undetected and unreported and may have contributed to virus transmission.

1. Monika L. Dietrich, MD* 2. Russell W. Steele, MD†,‡ 1. *Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 2. †Department of Pediatrics, Ochsner Health Center for Children, New Orleans, LA 3. ‡University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA * Abbreviations: ANF: : acute necrotizing fasciitis ARF: : acute rheumatic fever GAS: : group A Streptococcus IVIG: : intravenous immunoglobulin MRSA: : methicillin-resistant Staphylococcus aureus MSSA: : methicillin-susceptible S aureus PANDAS: : pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections PSGN: : poststreptococcal glomerulonephritis STSS: : streptococcal toxic shock syndrome 1. Clinical prediction rules for group A Streptococcus pharyngitis are unreliable in children, and unless viral etiology is strongly suspected, throat swab with a rapid antigen detection test should be performed. 2. Avoid “proof of cure” cultures when treating pharyngitis. 3. Clindamycin is important in invasive group A Streptococcus infection for toxin mediation but should not be used alone secondary to possible resistance. After completing this article, readers should be able to: 1. Understand the epidemiology, transmission, and major virulence factors of group A Streptococcus (GAS) infections. 2. Plan the appropriate diagnostic evaluation of suspected GAS infection. 3. Recognize the clinical features of, and major complications associated with, invasive and noninvasive GAS infections. 4. Plan appropriate management for a patient with a GAS infection. In 1933, Rebecca Lancefield changed our understanding of β-hemolytic streptococci by developing a system of serologic classification based on the carbohydrate composition of cell wall antigens. Of these organisms, the most significant in human pathogenicity is group A Streptococcus (GAS), otherwise known as Streptococcus pyogenes . (1) GAS is responsible for an impressively wide variety of clinical manifestations, from noninvasive infections, such as pharyngitis, scarlet fever, erysipelas, and cellulitis, to invasive disease, including sepsis, streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis (Table 1). It has also been linked to multiple nonsuppurative complications including acute rheumatic fever (ARF), poststreptococcal glomerulonephritis (PSGN), and the controversial pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Globally, an estimated 18 million people are suffering from a serious GAS-related illness, with about 1.78 million new cases annually. Hundreds of millions of people develop less serious GAS infection every year, placing a massive burden on healthcare systems. The …

BACKGROUND: Embryonal tumors arise typically in infants and young children and are often massive at presentation. Operative resection is a cornerstone in the multimodal treatment of embryonal tumors but potentially disrupts therapeutic timelines. When used appropriately, minimally invasive surgery can minimize treatment delays. The oncologic integrity and safety attainable with minimally invasive resection of embryonal tumors, however, remains controversial. METHODS: Query of the Vanderbilt Cancer Registry identified all children treated for intracavitary, embryonal tumors during a 15-year period. Tumors were assessed radiographically to measure volume (mL) and image-defined risk factors (neuroblastic tumors only) at time of diagnosis, and at preresection and postresection. Patient and tumor characteristics, perioperative details, and oncologic outcomes were compared between minimally invasive surgery and open resection of tumors of comparable size. RESULTS: A total of 202 patients were treated for 206 intracavitary embryonal tumors, of which 178 were resected either open (n = 152, 85%) or with minimally invasive surgery (n = 26, 15%). The 5-year, relapse-free, and overall survival were not significantly different after minimally invasive surgery or open resection of tumors having a volume less than 100 mL, corresponding to the largest resected with minimally invasive surgery (P = .249 and P = .124, respectively). No difference in margin status or lymph node sampling between the 2 operative approaches was detected (p = .333 and p = .070, respectively). Advantages associated with minimally invasive surgery were decreased blood loss (P < .001), decreased operating time (P = .002), and shorter hospital stay (P < .001). Characteristically, minimally invasive surgery was used for smaller volume and earlier stage neuroblastic tumors without image-defined risk factors. CONCLUSION: When selected appropriately, minimally invasive resection of pediatric embryonal tumors, particularly neuroblastic tumors, provides acceptable oncologic integrity. Large tumor volume, small patient size, and image-defined risk factors may limit the broader applicability of minimally invasive surgery.

Objectives To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. Study design The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. Results Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/μL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. Conclusions Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown about the neurobiological consequences of Foxy use. In addition, research into the long-term neuropsychological repercussions associated with these two compounds remains incomplete. The goal of the present research was to explore the effects of MDMA or Foxy on cognitive processes associated with adolescent exposure considered over much of the lifespan. Here we investigated whether the reported effects following adolescent exposure resolved in early adulthood or continued throughout life. The protocol involved repeated doses of either MDMA or Foxy during the period defined as mid-adolescence (postnatal days 34 - 46) in rats, followed by the use of four series of learning and memory tasks repeated at different points in the rodent lifespan. At four time points in adulthood, the animals were trained and tested on a on a series of spatial and non-spatial memory tasks designed to assess the impact and severity of Foxy and MDMA. Oddly, MDMA-treated rats were impaired on a step down passive avoidance task. The performance of the drug-treated rats was markedly inferior to that of the control animals on more demanding water maze tasks, with some results suggesting a lack of flexibility in adapting to changing task demands. MDMA rats were the most impaired. While some persistent cognitive deficits were found, no significant group differences in serotonin or dopamine levels were found in any of the measured regions of the brain changes, cortical or subcortical. These results provide evidence for compromised neurocognition that continues long after drug exposure in the absence of any discernable changes in neurotransmitter levels. Several possible physiological and neurochemical mechanisms associated with these compounds requiring further study are also outlined.

Background: Congenital cytomegalovirus (cCMV) is the leading cause of nongenetic congenital hearing loss in much of the world and a leading cause of neurodevelopmental disabilities. Infected babies can be born to women who are seropositive and seronegative prior to pregnancy, and the incidence is approximately 0.6%-0.7% in the United States. Symptoms vary from mild to severe, and hearing loss can be delayed in onset and progressive. Methods: We reviewed the literature to summarize the epidemiology, clinical manifestations, diagnosis, treatment, and future directions of cCMV. Results: The best way to diagnose the infection is with polymerase chain reaction of urine or saliva within 3 weeks after birth, followed by a repeat confirmatory test if positive. Moderately to severely symptomatic neonates should be treated for 6 months with valganciclovir, and some practitioners also choose to treat infants who have isolated hearing loss only. Treatment is not recommended for asymptomatic infants. All infected infants should be screened for hearing loss and neurodevelopmental sequelae. Universal and targeted screening may be cost effective. Currently, no vaccine is commercially available, although multiple candidates are under study. Conclusion: Congenitally acquired cytomegalovirus is found in all communities around the world with a disease burden that is greater than many other well-known diseases. Advances are being made in prevention and treatment; however, improved awareness of the disease among clinicians and patients is needed.

Recent observational studies are concerning because they document rising mastectomy rates coinciding with more than a dozen reports that lumpectomy has better overall survival (OS) than mastectomy. Our aim was to determine if there were differences in OS of matched breast cancer patients undergoing lumpectomy versus mastectomy in the National Cancer Database (NCDB).A retrospective cohort of patients with stage I-III breast cancer in the NCDB (2004-2013) was identified. Propensity score matching (PSM), Kaplan-Meier, and multivariate Cox proportional hazards models were used to examine OS by type of surgery.Of 845,136 patients, 464,052 (54.9%) underwent lumpectomy and 381,084 (45.1%) underwent mastectomy. After PSM, the hazard ratio (HR) and confidence interval (CI) for OS in all patients comparing lumpectomy with mastectomy was 1.02 (CI, 1.00-1.04; P = .002). In patients with stage I, II, and III, they were HR 1.27 (CI, 1.23-1.36; P .001), HR 0.98 (CI, 0.95-1.01; P = .21), and HR 0.83 (CI, 0.80-0.86; P .001), respectively. In subgroup analyses of all patients by estrogen receptor (ER) status, they were HR 1.05 (CI, 1.03-1.07; P .001) and HR 1.00 (CI, 0.96-1.03; P = .65) in ER+ and ER- patients.In our primary model of all stage I-III matched patients, using the most recent NCDB data and the largest observational sample size to date, the OS after mastectomy was not inferior to lumpectomy. This finding can be reassuring to patients and providers. In subgroup analyses, the association between type of surgery and OS differed by cancer stage and hormone receptor status.

The purpose of this study was to determine if receipt of chemotherapy was associated with utilization of the 21-gene recurrence score assay (RS assay) or with recurrence score (RS) in eligible patients. Using the National Cancer Data Base (NCDB), we identified female patients eligible for RS assay based on National Comprehensive Cancer Network (NCCN) guidelines: age 18–70, ER-positive and HER2-negative early-stage breast cancer diagnosed during 2010–2013. We excluded patients not meeting testing guidelines. Inclusion required result of RS in patients who underwent RS assay and status for receipt of chemotherapy. Multivariable logistic regression models and propensity matched analysis were used to determine associations between RS assay and RS with receipt of chemotherapy. Among 129,765 patients who were eligible, 74,778 underwent RS assay and had results available. Of these, 59.5 % (44,505) had low-risk, 32.0 % (23,920) had intermediate-risk, and 8.5 % (6353) had high-risk RS. Patients with intermediate- and high-risk RS were more likely to receive chemotherapy [OR 12.9 (CI 12.2–13.6), p

Background Estrogen receptor beta (ERβ) is expressed by 50% to 80% of triple-negative breast cancers (TNBC). Agonism of ERβ has antiproliferative effects in TNBC cells expressing ERβ. This phase 2 study evaluated single-agent high-dose estradiol in patients with advanced TNBC. Patients and Methods Adult women with measurable advanced TNBC were treated with estradiol 10 mg oral 3 times daily provided continuously for 28-day cycles. A Simon optimal 2-stage design was used. The primary end point was objective response (OR). Secondary end points included progression-free survival (PFS), clinical benefit (CB), and safety. OR, CB, and PFS by ERβ status were also examined. Results Seventeen evaluable women were enrolled. Median age was 58 years (range, 34-90 years); the median number of prior systemic therapies was 2 (range, 0-6). One patient had a confirmed partial response (OR rate, 5.9%) and remained on the study for > 24 weeks. Three patients had stable disease, with one lasting more than 16 weeks. ERβ expression was detected in 77% (13 patients). The CB rate at 16 weeks was 15% (2 of 13) in ERβ-positive patients and 0% (0 of 4) in ERβ-negative patients ( P = 1). PFS was poor (median, 1.9 months) and not statistically significantly different between ERβ-positive versus -negative patients. No new adverse events from estradiol were identified. The study closed after the first stage as a result of limited responses in these unselected patients. Conclusion In unselected TNBC, high-dose estradiol has limited efficacy. However, further evaluation of ERβ selective agonists in TNBC selected by ERβ expression may be warranted.

Purpose: This study assesses the effectiveness of a single institution’s breast cancer survivorship program on patient perceptions, quality of life (QOL), and compliance with National Comprehensive Cancer Network (NCCN) guidelines for follow-up. Methods: Sampled patients completed all their breast cancer treatment at a single tertiary center. Surveys designed to evaluate QOL were obtained, and retrospective medical record review was conducted to assess NCCN compliance. Survivorship clinic (SC) attendees and nonattendees were matched for age and disease stage for comparison of the outcomes (QOL, NCCN compliance, and overall effectiveness). Results: SC patients (n = 63) tended to perceive their concerns in various categories to be addressed more adequately than did nonattendees (n = 54), with significant differences in the areas of practical concerns (P = .03) and late-term adverse effects (P = .03). There was a significant difference in compliance with three NCCN guidelines (history and physical every 3 to 6 months, annual mammography, and a pelvic examination if on tamoxifen) between survivorship attendees and nonattendees (P < .001, P = .02, and P < .001, respectively). Women who attended an SC used other survivorship support resources more often. Conclusion: Survivorship programs can be time and resource consuming, but our study is one of the first to show that a survivorship program effectively changes patient behavior in important ways. Patients who attended an SC were more likely to be compliant with NCCN-recommended follow-up and to use other survivorship resources and felt their concerns were better addressed. These measures can be used to help us improve our survivorship services and by other institutions to measure the quality and effectiveness of their programs.

Adjuvant therapy for breast cancer can be improved by increasing dose density. We tested the feasibility of delivering dose-dense docetaxel-cyclophosphamide (TC) in a single-arm phase II trial of 42 patients via the Wisconsin Oncology Network. Treatment was safe, tolerable, and most patients completed therapy as plan- ned. Thus, this commonly used regimen can be delivered in 8 weeks. Introduction: Dose-dense therapies have had a major effect on reducing toxicity and improving outcomes in breast cancer. A combination of TC every 3 weeks has emerged as a common chemotherapy regimen used for treatment of node-negative or lower-risk node-positive breast cancer. We tested whether it is feasible to deliver TC on a dose- dense schedule, with therapy completed within 10 weeks. Patients and Methods: We enrolled women with early stage breast cancer on a single-arm phase II study of adjuvant dose-dense TC through a regional oncology network. All women completed primary surgery before accrual, and subsequent therapy with TC was deemed appropriate by the treating physician. Planned treatment was docetaxel 75 mg/m 2 plus cyclophosphamide 600 mg/m 2 every 2 weeks for 4 cycles with subcutaneous pegfilgrastim 6 mg administered 24 to 48 hours after the administration of each chemotherapy cycle. Results: Of 42 women enrolled, 41 were evaluable using prespecified criteria. Of these, 37 (90.2%) completed therapy within 10 weeks and 34 (83%) completed therapy at 8 weeks without dose modification. Rates of neuropathy were similar to that reported previously. The rate of neutropenic fever was low (2.5%). Rash and plantar-palmar erythrodythesia were common and reached grade 3 in 4 subjects (9.8%). Conclusion: Dose-dense TC is feasible with tolerability profiles similar to standard TC and a low likelihood of neutropenic fever. This study supports further clinical development of this 8-week adjuvant chemotherapy regimen.

Background: Dose-dense therapies have had a major impact on reducing toxicity and improving outcomes in breast cancer. A combination of docetaxel plus cyclophosphamide (TC) every 3 weeks has emerged as a common chemotherapy regimen used for treatment of node-negative or lower-risk node-positive breast cancer. We tested whether it is feasible to deliver TC on a dose-dense schedule. Patients and Methods: We enrolled women with early stage breast cancer on a single-arm phase II study of adjuvant dose-dense TC (ddTC) through a regional oncology network (WON). All women completed primary surgery; subsequent therapy with TC was deemed appropriate by the treating physician. Planned treatment was docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 every 2 weeks for 4 cycles with subcutaneous pegfilgrastim 6 mg administered 24-48 hours after the administration of each chemotherapy cycle. The primary endpoint was feasibility of administering therapy within 10 weeks. A Simon Optimal 2-Stage design was employed for the study design. Results: Of 42 women enrolled, 41 were evaluable by prespecified criteria. Median age was 54 (28-73). Most subjects had node negative (73%) or hormone receptor positive (71%) tumors. Of the 41 subjects, 37 (90.2%) completed therapy within 10 weeks and 34 (83%) completed therapy at 8 weeks without dose modification. Rates of grade 2 neuropathy were similar to that reported previously (15%) and there were no cases of grade 3 or higher neuropathy. The rate of neutropenic fever was low (2.5%). Rash and plantar/palmar erythrodythesia were common and reached grade 3 in four subjects (9.8%). Conclusion: Dose-dense TC is feasible with tolerability profiles similar to standard TC and a low likelihood of neutropenic fever. This study supports further clinical development of this 8-week adjuvant chemotherapy regimen. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-10.

Background: Sialophorin is a transmembrane sialoglycoprotein. Normally, the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signalling, apoptosis, migration and proliferation. Methods: Normal breast tissue and primary breast tumours were analysed by immunohistochemistry for sialophorin expression. The sialophorin-positive breast cancer cell line MCF7 was engineered to stably express either non-targeted or sialophorin-targeted small interfering RNA (siRNA). Assays were then performed in vitro to assess apoptosis, intracellular adhesion, transendothelial migration and cytotoxicity. An orthotopic mouse model assayed ability to produce tumours in vivo. Results: Normal breast epithelial cells exhibit expression of the N-terminal domain of sialophorin in the cytoplasm but not the nucleus. The majority of these normal cells are also negative for expression of the C-terminal domain. In contrast, malignant breast epithelial cells exhibit N-terminal expression both in the cytoplasm and nucleus and the majority express the C-terminus in the nucleus. Using differential patterns of intracellular expression of the N and C termini of sialophorin, we define six subtypes of breast cancer that are independent of histological and receptor status classification. Targeting sialophorin with siRNA resulted in the MCF7 breast cancer cell line exhibiting increased homotypic adhesion, decreased transendothelial migration, increased susceptibility to apoptosis, increased vulnerability to lysis by natural killer cells and decreased ability to produce tumours in mice. Conclusion: Our results indicate that intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and that sialophorin represents a novel therapeutic target.

Background The prevalence of congenital cytomegalovirus infection (cCMV) at birth is 0.5%–1% in the United States. Most cCMV newborns are asymptomatic at birth with 10%–15% subsequently developing sequelae, such as hearing loss. Higher cCMV prevalence (2.5%–11.4%) is reported in infants born to HIV-infected women, associated with maternal immune suppression and lack of antiretroviral therapy (ART), with few studies addressing neurodevelopmental (ND) outcomes in their offspring. We report birth prevalence of cCMV in a cohort of HIV-exposed, uninfected infants (HEU) born to women on combination ART with well-controlled HIV and describe ND outcomes through age 5 years. Methods The Surveillance Monitoring for ART Toxicities (SMARTT) study is an ongoing NICHD-funded observational multi-centered cohort study (United States and Puerto Rico) of growth and development of HEU children that commenced in 2007. As of August 1, 2017, participants with stored blood pellets collected ≤3 weeks after birth and at least 1 ND assessment ≥1 year of age had pellets tested by DNA PCR to establish cCMV. Comparisons of ND outcomes (defined in figure) at ages 1, 2, and 5 by cCMV status were made using Wilcoxon and Fisher’s Exact tests. Results Of 895 children meeting study criteria (55% black; 32% white; 40% Latino), 8 had cCMV, yielding a birth prevalence of 0.89% (95% CI 0.39–1.75%). All were asymptomatic and similar to CMV-uninfected infants in gestational age and anthropometric measurements at birth. The last HIV viral load prior to delivery was undetectable in 88% of women. The last available CD4% was Conclusion Birth prevalence of cCMV in HEU children born within the last decade approaches national US prevalence. Preschool HEU children with asymptomatic cCMV at birth did not show poorer language, hearing, and developmental outcomes compared with CMV-uninfected HEU children. Disclosures All authors: No reported disclosures.

We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point.In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2.Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).

An item-by-item comparison of states’ certification standards and/or competencies for Early Childhood Special Education (ECSE) with those of national professional association standards (i.e., Council for Exceptional Children [CEC] Common Core, Division for Early Childhood [DEC] of CEC ECSE, and the National Association for the Education of Young Children personnel standards when relevant) is reported in this article. Results of the content analysis are reported specific to the percentage of national standards met by states’ policies overall and the percentage of national standards met for each of the five major certification models found to be used by states for certifying personnel to work with young children with delays and disabilities. Descriptive information is also provided as to the professional association standards most and least likely to be included in state standards. Implications for state and professional association policy are provided, as well as recommendations for further research.

Foxy or Methoxy Foxy (5-methoxy- N , N -di(iso)propyltryptamine hydrochloride; 5-MeO-DIPT) is rapidly gaining popularity among recreational users as a hallucinogenic “designer drug.” Unfortunately, much remain unknown about the consequences of its use on neuropsychological development or behavior. During one of two adolescent periods, the rats were given repeated injections of 5 mg/kg or 20 mg/kg of 5-MeO-DIPT or a corresponding volume of isotonic saline. After the animals reached adulthood, they were trained and tested on a number of tasks designed to assess the impact of 5-MeO-DIPT, if any, on spatial memory, presumably involving declarative memory systems as well as a nonspatial task that is considered sensitive to disruptions in nondeclarative memory. Both the 5-MeO-DIPT- and saline-treated rats were able to master spatial navigation tests where the task included a single goal location and all groups performed comparably on these phases of training and testing. Regardless of exposure level during adolescence, the performance of the drug-treated rats was markedly inferior to that of the control animals on a task where the goal was moved to a new location and on a response learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. Detected reductions in serotonin activity in the forebrain similar to the effects of extensively investigated compounds such as methylenedioxymethamphetamine (MDMA), suggest that 5-MeO-DIPT may produce its adverse effects by compromising serotonergic systems in the brain.

Measurement of quality indicators and peer comparison has been demonstrated to improve quality of care. The goal of this study was to determine whether a community breast center, in collaboration with the National Consortium of Breast Centers (NCBC), could voluntarily audit the quality of breast cancer care, confidentially transmit quality information to the NCBC, and receive peer performance comparisons. Quality indicator metrics from consecutive breast cancer patients undergoing care at a community interdisciplinary breast center were entered into a prospective database of quality measures that were defined by the NCBC. Retrospective review of patients from 2004 to 2006 was performed and subsequent quality indicator data was submitted electronically to the NCBC National Quality Measures for Breast Centers (NQMBC(TM) ) program. The percentage of new cancer diagnoses made by needle biopsy techniques was 94%, 95% and 96% from 2004 to 2006. Sentinel lymph node utilization in eligible patients was 93%, 96% and 91% from 2004 to 2006 and the immediate intraoperative pathologic frozen section false negative rate of the sentinel lymph node was 6.5%, 4.7% and 4%. Chart documentation of "patient participation in shared decision making for breast conserving therapy versus mastectomy" improved from 74% to 99% (p

49 Background: The 2005 Institute of Medicine report recommended providing a cancer TSCP, but barriers including time needed to complete these documents led to limited implementation. In 2014, in order to facilitate delivery, ASCO released a streamlined version of a TSCP. The current prospective, randomized study compares a Breast Cancer ASCO 2014 derived template (concise TSCP) with a facility derived Breast Cancer TSCP template based on the “old” ASCO version and NCCN guideline recommended elements (detailed TSCP). Methods: Female breast cancer survivors who completed therapy at Gundersen Health System were randomized between a concise TSCP and a detailed TSCP. Subjects received a survey prior to their survivorship visit assessing their baseline knowledge of their breast cancer diagnosis and treatment (pre visit knowledge). After the visit, participants completed the same survey (post visit knowledge) and a satisfaction survey. Pre and post visit knowledge survey scores, patient satisfaction scores and time needed to complete the TSCP were compared between the two study groups. Results: Both TSCP groups showed significant improvement in patient-specific disease and treatment knowledge scores (% of applicable knowledge questions answered correctly) after their survivorship visit. There was no significant difference between the concise and detailed groups’ pre-visit knowledge score (mean 78% vs. 79%, p=0.88). Calculated difference between the groups’ post knowledge scores met the pre-determined threshold for non-inferiority (p=0.013). Conclusions: Our study demonstrates the value of a cancer TSCP and Survivorship visit in improving breast cancer survivors’ knowledge of their disease characteristics and treatment. The concise version was found to be non-inferior to the detailed TSCP in terms of patient knowledge and satisfaction and required less time to complete. These results assist us and other institutions in choosing a more streamlined version of TSCP without compromising patient knowledge or satisfaction. [Table: see text]

PURPOSE Symptoms of gastroesophageal reflux disease (GERD) occur in 2% to 7% of children. The manifestations of GERD can be limited to symptoms (eg, heartburn, regurgitation) or can be more complicated, such as erosive esophagitis, esophageal strictures, or Barrett esophagus. The prevalence of such GERD complications in children is unknown. The purpose of this study was to determine the prevalence of endoscopic findings of erosive esophagitis in children. PATIENTS AND METHODS All children ages 0 to 17 years, 11 months who underwent upper endoscopy that was recorded in the Pediatric Endoscopic Database System-Clinical Outcomes Research Initiative between 1999 and 2002 were included. Endoscopic reports that were incomplete or that did not include demographic features, indications for endoscopy, or endoscopic findings were excluded. Erosive esophagitis was defined either descriptively or by the Los Angeles classification. Esophageal biopsy was not evaluated. RESULTS A total of 7188 children who underwent upper endoscopy fulfilled the inclusion and exclusion criteria. Of those, 888 (12.4%) had erosive esophagitis. The median age of children with erosive esophagitis was 12.7 +/- 4.9 years versus 10.0 +/- 5.1 years in those without erosive esophagitis (P

61 Patients with caput obstipum musculare were operated on our clinic between 1968 to 1985. 45 patients were examined after cosmetic and functional criteria (Manitz 1974, Stein et al., 1985). We found 28 "very good", 10 "good", 6 "satisfactory" and 1 "insufficient" results after the criteria established by Leuschner (1967).

Background Variations exist in compliance with NCCN Guidelines. Prior reports of adherence to NCCN Guidelines contain limitations because of lack of contemporary review and incomplete listing of reasons for noncompliance. Purpose To assess institutional compliance and assist national quality improvement strategies through identifying valid reasons for noncompliance. Methods Compliance with NCCN Guidelines was recorded prospectively using electronic synoptic templates for patients with newly diagnosed breast cancer treated at a single institution between January 2010 and December 2011. Compliance with NCCN Guidelines was recorded. The accuracy of real-time synoptic auditing methods compared with retrospective chart review and reasons for noncompliance was assessed. SAS 9.3 software was used for data analysis. Results Compliance with NCCN Guidelines among 395 patients was 94% for initial staging evaluation, 97% for surgery, 91% for chemotherapy, 89% for hormone therapy, 91% for radiation therapy, 85% for follow-up, and 100% for determination of estrogen receptor/progesterone receptor and HER2 status. Age, comorbidities, and stage influenced guideline compliance. The most common reasons for noncompliance were patient refusal, patient choice after shared decision-making, and overuse of testing. Synoptic templated reporting was accurate in 97% patients. Conclusions High compliance with NCCN Guidelines was demonstrated. Reasons for noncompliance were identifiable. Compliance and nonadherence can be evaluated quickly with electronic synoptic reporting. This allows real-time action plans to address quality concerns and aids national risk adjustment for comparison and benchmarking.

This paper presents an investigation into the sooting characteristics of isolated droplets (for fuel n -decane) burning in heated ambients in microgravity. A backlit video view of the droplet was taken to determine the soot shell size and to judge the transient soot generation according to qualitative amount of soot. The independent experiment variables were the ambient temperature and initial droplet diameter. Soot generation was higher for initially larger droplets when compared at the same burning time normalized with the initial droplet diameter squared (called normalized burning time). At the same absolute burning time there existed an obvious initial transient period after ignition in which the stated relationship was not satisfied. This transient time increased with increasing the ambient temperature. There was a peak in the soot generation at about 1000 K throughout the lifetime of the droplet. The soot shell size was generally larger for an initially bigger droplet at the same instantaneous droplet diameter or normalized burning time. At the same absolute burning time, however, an initially smaller droplet exhibited larger relative soot shell sizes (the soot shell size normalized with the initial droplet diameter). The soot shell size increased monotonically with increasing ambient temperature. This is due to the increase in the Stefan flow drag with the larger burning rate at the higher temperature. The consequent result is that the soot shell sizes are much larger for droplets burning in heated ambients than for droplets burning in room-temperature ambients.

Background & aims: Surgical fundoplication has been recommended for children with persistent GERD. The purpose of this study was to determine the frequency of postoperative symptoms requiring medical evaluation and/or treatment after fundoplication in children with or without associated medical disorders. Methods: In a retrospective cohort study, we reviewed the medical records of all children who underwent fundoplication during 1996–1999. Data were collected to analyze the following: (1) postoperative complications, (2) postoperative symptoms, (3) procedures performed to evaluate postoperative symptoms, (4) medical treatment, and (5) repeat surgery. Results: A total of 198 children underwent fundoplication, and 176 (89%) came for follow-up evaluation within 2 months after surgery. The median age at the time of surgery was 2.1 y (range, 6 mo–18 y) and the median duration of follow-up was 2.0 y (range, 1.2–4.8 y). A total of 130 (74%) children had one or more associated medical disorders including neurodevelopmental delay (70%), cystic fibrosis (8%), tracheoesophageal anomalies (8%), bronchopulmonary dysplasia (8%), and reactive airway disease (35%). Postoperatively, children with associated medical disorders had a higher frequency of lung infections (52% vs. 22%, P = .03) and dumping syndrome (2% vs. 0%, P = .05). Most children (63%) received evaluation and treatment for symptoms suggestive of recurrent reflux despite fundoplication. Conclusions: Nearly two thirds of children who received fundoplication and were followed-up within 2 months after surgery either have symptoms or receive medical therapy for reflux. Fundoplication for the control of GERD in children needs further evaluation.

Summary. Objective: The main objective of this study was to examine factors associated with utilization and costs for persons with haemophilia. Study design: Utilization data and patient characteristics were collected through medical record review of 336 patients receiving treatment for at least 90% of their haemophilia care at one of five comprehensive haemophilia treatment centres in California. Principal findings: The range of factor VIII deficiency in our sample was similar to the distribution among haemophilic patients in the Western United States; 215 (64%) had severe FVIII deficiency. The mean age in our sample was 21.4 (SD ¼ 16.2) years old and 114 (34%) were HIV-positive. In the multivariate model predicting the total cost of health care during 1995 (adjusted R 2 ¼ 0.40), total annual costs were significantly (P < 0.05) associated with being HIV-seropositive, infusing FVIII concentrate through a port vs. i.v. infusion, the number of comorbidities, moderate arthropathy (compared with no arthropathy), mild arthropathy, history of inhibitor to FVIII, and current prophylactic FVIII concentrate infusion. Conclusion: As expected, total health-care costs were correlated with comorbid medical conditions, such as HIV and sequelae of haemophilia such as arthropathy. Health policy should consider risk adjustment for the presence of complications such as arthropathy and HIV infection in the financing of haemophilia treatment to promote more equitable delivery of these services.

Isolated droplet burning were conducted in microgravity ambiences of different temperatures to test the initial diameter influence on droplet burning rate that shows a flame scale effect and represents an overall thermal action of flame in balance with heat loss. The coldest ambience examined was room air, which utilized a heater wire to ignite the droplet. All other ambiences hotter than 633 K were acquired through an electrically heated air chamber in a stainless steel can. An inverse influence of initial droplet diameter on burning rate was demonstrated for the cold and hot ambiences. That is, the burning rate respectively decreased and increased in the former and latter cases with raising the initial droplet diameter. The reversion between the two influences appeared gradual. In the hot ambiences the burning rate increase with increasing the initial droplet diameter was larger at higher temperatures. A “net heat” of flame that denotes the difference between “heat gain” by the droplet and “heat loss” to the flame surrounding was suggested responsible for the results. In low-temperature ambiences there is a negative net heat, and it turns gradually positive as the ambience temperature gets higher and the heat loss becomes less. Relating to luminous flame sizes and soot generation of differently sized droplets clarified that the flame radiation, both non-luminous and luminous, is determinative to the net heat in microgravity conditions. In addition, the work identified two peak values of soot generation during burning, which appeared respectively at the room temperature and at about 1000 K. The increase in ambience temperature made also bigger soot shells. The heat contribution of flame by both radiation and conduction was demonstrated hardly over 40% in the total heat required for droplet vaporization during burning in a hot ambience of 773 K.

The purpose of this study was to assess the relationship between health care and utilization of that health care, and to provide a base measurement of health status in patients with haemophilia. Provider interview and retrospective chart review of 336 patients with haemophilia treated during 1995 at one of five comprehensive haemophilia treatment centres was conducted to measure patient health status characteristics and utilization of health care. Two health status scales were included. The first, the Self-Care Measure, was a four-point single item scale measuring the patient's ability for basic self-care, which was scored by a chart review and an interview with the health-care provider. The second, the Haemophilia Utilization Group Study (HUGS) Functional Status Measure, is a four-item, 10-point scale developed specifically for patients with haemophilia. Our sample represents 27% of actively treated patients in region IX. The mean score on the HUGS Functional Status Measure was 8.7 (SD=2.4). The HUGS scale exhibited a ceiling effect across all four scales: attitude (n=269, 80.1%), overall wellbeing (n=263, 78.3%), working (n=254, 75.6%) and orthopaedic status (n=195, 58.0%). Both higher total health-care costs and factor VIII annual costs were significantly associated with lower scores on the HUGS Functional Status Measure. Health status is a critical component in the assessment of the utilization and outcomes of care. In the absence of the availability of a patient interview, the HUGS Functional Status Measure can be used as one characteristic that explains the variation in the utilization of health care by patients with haemophilia.

Burning of single droplets composed of a light cycle oil (LCO) and a diesel light oil (LO) was investigated in normal and micro gravity conditions, with the intention of developing technologies burning these oils in gas turbines. While the normal gravity test used a hot-air chamber to simulate the burning condition that occurs in actual burners, the microgravity test employed an igniter, set beneath the droplet, to make the burning free of extra radiation. The result showed that the burning of the LCO droplet had higher soot yield, while that of the LO droplet was more disruptive. In the conditions tested, coke formation was negligible for both the oils. The LCO droplets exhibited lower ignition delay times, but the burning times between ignition and extinction of equi-sized droplets were slightly larger for LO. A burning rate constant, which was an explicit value when microexplosions were present, could be defined according to the d2-law. The constant, however, was closely related to the initial droplet ...

10063 Background: The Commission on Cancer (CoC) standard 3.3 became effective in 1/2015 requiring the delivery of a survivorship care plan (SCP) at the completion of curative treatment. Both the CoC and ASCO have recommended minimum requirements for SCPs, which should include both a treatment summary and follow up care plan. Many cancer patients use social media (SM) as a way to obtain support and information. We have shown previously that the majority of SM savvy cancer survivors (88.2%) do not receive SCPs ( J Clin Oncol 35, 2017 suppl 5S; abstr 104). We sought to determine the contents of the SCPs received. Methods: An IRB-approved survey was conducted via the online tool SurveyMonkey from 3/21/2016 to 4/2/2016. Patients were invited to participate via SM outlets reaching cancer-related communities including Twitter chats, Facebook groups, blogs, and targeted emails. Results: A total of 312 patients responded. 63% (194) had completed curative treatment (excluding endocrine therapy). Of these 11.8% (23) reported receiving an SCP at the end of treatment. Of 22 patients who responded, 9/22 (40.9%) found the SCP helpful, 11/22 (50.0%) somewhat helpful, and 2/22 (9.1%) not helpful. The table below shows the components of those SCPs received. Conclusions: Not only did a small percentage of patients receive SCPs but also no patient received a complete SCP per the CoC and ASCO recommendations. Particularly deficient was a description of late/long-term effects of treatment—only 36% received such information. Challenges exist in the delivery of complete SCPs. [Table: see text]

57 Background: Patients treated for cancer are surviving their disease in increasing numbers. The 2005 Institute of Medicine (IOM) report From Cancer Patient to Cancer Survivor - Lost in Transition resulted in a call to develop survivorship programs. The Commission on Cancer (CoC) standard 3.3 became effective in 1/2015 requiring the delivery of a survivorship care plan (SCP) at the completion of treatment. Many cancer patients use social media (SM) as a way to obtain support and information. We sought to determine if SM savvy patients have received a SCP. Methods: An IRB-approved survey was conducted via the online tool SurveyMonkey between 3/21/2016 and 4/2/2016. Patients were invited to participate via SM outlets reaching cancer-related communities including Twitter chats, Facebook groups, blogs, and targeted emails. Cochran-Armitage Trend test, exact version, was performed by year for % of survivors receiving a SCP. Results: A total of 312 patients responded. 63% had completed their treatment (excluding endocrine therapy). Of a total of 194 individuals only 11.8% (23) were given a SCP at the end of treatment. A breakdown by treatment completion year is given below. Of those who did not receive a care plan 65% (112/172) answered that it would still be helpful to receive one. Most SCPs (86%) were supplied in paper form. However, patient-reported preferences for SCP delivery were paper (50%), online patient portal (41%), and email (9%). Conclusions: Despite the IOM report and CoC standard 3.3, the majority of SM savvy cancer survivors (88.2%) do not receive SCPs. In the respondents to this survey, there was no significant increase from 2015 onwards, p = 0.11, confirming an Advisory Board survey that just over 1/3 of programs felt confident that they could implement 3.3 by 2015. The CoC has updated its standard such that 25% of eligible patients should receive a plan by 12/31/2016. According to these data, that goal of 25% may not be achieved. [Table: see text]

The Grand Canyon, located in Northern Arizona, is one of the seven natural wonders of the world, and has been set aside as a National Park to preserve its unique character. Several million visitors from all over the world travel to the Grand Canyon each year to witness its awesome beauty, As a natural preserve, the area protects numerous values such as genetic diversity, solitude, non-mechanized recreation, etc, but the majority of visitors travel to the Grand Canyon for one reason: to view the scenery.There have been reports in the general press (and even in the United States Congressional Hearings) that visual conditions at the Grand Canyon have been seriously degraded by air pollution. Over the past nine years, a vast array of visibility-related research and monitoring has been conducted to determine the extent and probable cause of this visible degradation. Studies have included optical measurements, pollution characterization, source-receptor relationship analysis, and human perception of visual air quality. The resulting data document the visual air quality of the Grand Canyon and provide a basis to qualitatively and quantitatively evaluate significant events and trends.This poster comprehensively assembles, updates, analyzes and summarizes these various studies to report what has happened to air clarity at the Grand Canyon. The authors examine: - the extent and variation of optical conditions through an examination of reported standard visual range data and a qualitative review of standard photographic monitoring record; - the scientific basis and measurement techniques used to quantify optical conditions; - the probable causes of visual degradation by analyzing the chemical properties of collected aerosols, and through investigation of air mass trajectories; - how visitors to the Grand Canyon perceive and value visual air quality; - the implications study results have for control of air pollutants outside protected natural areas. By examining the situation at the Grand Canyon, managers of other natural preserves may gain insights into ways to determine the extent and causes of visual degradation in all lands afforded special protection.

An association between auto-immune disorders and interferon (IFN) has been reported. High levels of natural IFNalpha are present in the blood of patients with auto-immune disease and correlate with disease activity. In addition, IFNalpha treatment of humans has resulted in multiple reports of associated auto-immune phenomena. We describe a patient who underwent resection of regionally metastatic melanoma, was given adjuvant high-dose IFNalpha2b, and subsequently developed dermatomyositis. To the authors' knowledge this is the first report of dermatomyositis in association with IFNalpha treatment. We review the literature reporting associations between IFNalpha and auto-immune disease and discuss possible mechanisms by which IFNalpha may contribute to the development of auto-immune disease. High dose IFNalpha2b is more commonly prescribed since it was approved as an adjuvant treatment for patients with surgically resected high-risk melanoma. The potential for cases of IFN-associated auto-immune disease is therefore a clinical concern. Standard side effects of high-dose IFN therapy resemble symptoms of auto-immune diseases, which may make prompt diagnosis difficult. Therefore, it is important that auto-immune diseases such as dermatomyositis are recognized as potential side effects of treatment with high-dose IFNalpha.

Background National Comprehensive Cancer Network (NCCN) guideline compliance for breast cancer was determined in a breast center. Methods A retrospective study of 200 new breast cancer patients seen in 2004 was performed. Results NCCN guideline compliance rates for preoperative evaluation, breast surgery, lymph node surgery, radiation treatment, and systemic adjuvant therapy were 87%, 97%, 97%, 77%, and 63%, respectively. The most common reasons for noncompliance were partial breast radiation, no radiation, limited life expectancy, and patient choice to defer systemic treatment. Conclusions The investigation of quality of breast cancer care requires measurement of compliance and reasons for noncompliance with established guidelines. A review that focuses only on percentage compliance has the potential to penalize institutions that (1) practice informed consent detailing absolute risks of survival with and without systemic therapy, (2) practice evidence-based medicine before the standardized guideline is changed to reflect it, and (3) serve populations with limited life expectancy.

The noradrenergic system of the locus coeruleus has been implicated in a variety of processes including reinforcement, attention, and acquisition and retention of learned behaviors. Its dense projections, some of which are shared by the cholinergic system, provide an ideal network within which to study the cognitive impairments related to aging. The current investigation explored the effects of piperoxane, an a2 noradrenergic receptor antagonist, on the performance of 18-and 24-month-old rats in the Morris water maze and a step-down passive avoidance task. Piperoxane injections (3 mg/kg, IP) facilitated the performance of the 18-month-old animals to levels comparable to those of the 8-month-old saline controls in constant-start, novel-start, and goal rotation testing variations of the Morris water maze. With the exception of the 24-month-old saline control group, all rats displayed retention on the step-down passive-avoidance task when tested 24 hours after training.

Individual droplets with diameters ranging from about 2 mm to 5 mm were burned under microgravity conditions in air at 1 bar with an ambient temperature of 300 K. Each droplet was tethered by a silicon carbide fiber of 80 μm or 150 μm diameter to keep it in view of video recording, and, in some tests, a forced air flow was applied in a direction parallel to the fiber axis. Methanol, two methanol-water mixtures, two methanol-dodecanol mixtures, and two heptane-hexadecane mixtures were the fuels. Droplet diameters were measured as functions of time, and they are compared here with existing theoretical predictions. The prediction that methanol droplets extinguish at diameters that increase with increasing initial droplet diameter is verified by these experiments. In addition, the quasi-steady burning-rate constant of the heptane-hexadecane mixtures appears to decrease with increasing droplet diameter; obscuration consistent with very heavy sooting, but without the formation of soot shells, is observed for the largest of these droplets. Forced convective flow around methanol droplets was found to increase the burning rate and to produce a ratio of downstream to upstream flame radius that remained constant as the droplet size decreased, a trend in agreement with earlier results obtained at higher convective velocities for smaller droplets having larger flame standoff ratios. Implications of the experimental results regarding droplet-combustion theory are discussed.

CERVICAL epidural steroid injections (CESIs) are generally used for the treatment of radiculopathy and pain. Other reasons cited for using CESIs include postlaminectomy syndrome, bulging cervical disc, and brachial plexitis. 1 Side effects of CESIs include stiff neck, flushing, wet tap, failed block, vomiting, upper extremity motor weakness, and transient paresthesia. 1-2 Rare but potentially catastrophic complications of CESI can occur, such as arachnoiditis, hematoma, meningitis, and quadraplegia. 3,4 We present a case of cervical epidural granuloma and intracranial hypotension after administration of epidural triamcinolone acetonide (Kenalog; Bristol-Myers Squibb, Princeton, NJ).

The present experiment examined the effects of unilateral or bilateral locus coeruleus lesions on general activity, acquisition of a non-monotonic serial pattern (14-0-3-7 food pellets, respectively), and response learning acquisition in a Greek cross version of the Morris water maze. Sham-operated control rats were capable of tracking the elements of the serial pattern while rats with a unilateral locus coeruleus lesion were moderately impaired, and those with bilateral locus coeruleus lesions were severely impaired. A similar pattern of working memory deficits emerged in an analysis of the response-learning data in the Greek cross. The results are discussed in terms of the current understanding of norepinephrine and the locus coeruleus in learning and memory processes.

Age differences among risk groups may account for rate differences in progression of human immunodeficiency virus type 1 (HIV-1) infection to AIDS. Institutions in 6 US cities used a common protocol to study infected homosexual blood donors, recipients of blood components, and factor VIII-treated hemophiliacs. Follow-up was every 6 months. Actuarial risk for AIDS 8 years after infection was 51% among blood recipients, 36% among homosexual donors, and 24% among hemophiliacs. Significant risk group differences were explained by age differences among cohorts (medians of 61, 29, and 22 years, respectively). When age was adjusted for and both CD4 cell value and zidovudine treatment were used as time-dependent covariates, homosexual donors had more rapid progression than the other groups. Omitting Kaposi's sarcoma as an AIDS-defining condition removed any significant differences among risk groups except CD4 cell count and age. Thus, major factors in AIDS progression are age-related.