1,949 research outputs found

    Impact of radiation therapy on survival in patients with triple‑negative breast cancer

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    Triple-negative breast cancer (TNBC) has a poorer prognosis compared with other sub-groups. In the current study, survival associated with locoregional treatment of females with TNBC was investigated. Specifically, 468 patients with stage I–III TNBC treated between 2002 and 2009 were identified. Data included patient and tumor characteristics, treatment received and survival. Data were compared using χ(2) and Fisher’s exact tests, as well as MANOVA. Kaplan-Meier curves were generated. The study cohort had a mean age of 54±13 years old with a mean follow-up period of 51±21 months. Of 468 patients, 249 (53%) underwent lumpectomy, 63 (14%) underwent simple mastectomy (SM) and 156 (33%) underwent modified radical mastectomy (MRM). Overall, 263 (56%) received adjuvant radiation, including 178/249 (71%) following lumpectomy, 13/63 (21%) following SM and 72/156 (46%) following MRM (P<0.0001). Following control for potential confounders in univariate tests, adjuvant radiation was associated with improved overall survival in the total cohort (HR, 0.46; 95% CI, 0.31–0.68; P=0.0001). When comparing survival by surgical type, receipt of adjuvant radiation significantly improved survival in the lumpectomy group (HR, 0.30; 95% CI, 0.16–0.58; P=0.0004), but was not associated with improved survival in the SM group (HR, 0.38; 95% CI, 0.05–3.04; P=0.36) or in the MRM group (HR, 0.79; 95% CI, 0.46–1.34; P=0.38). The survival benefit of adjuvant radiation in these TNBC patients is attributed to those undergoing breast-conserving therapy. There was no benefit in either mastectomy group. These data warrant validation from prospective trials, in order to develop tailored locoregional treatment for patients with TNBC

    Investigating diet as the source of tetrodotoxin in Pleurobranchaea maculata

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    The origin of tetrodotoxin (TTX) is highly debated; researchers have postulated either an endogenous or exogenous source with the host accumulating TTX symbiotically or via food chain transmission. The aim of this study was to determine whether the grey side-gilled sea slug (Pleurobranchaea maculata) could obtain TTX from a dietary source, and to attempt to identify this source through environmental surveys. Eighteen non-toxic P. maculata were maintained in aquariums and twelve were fed a TTX-containing diet. Three P. maculata were harvested after 1 h, 24 h, 17 days and 39 days and TTX concentrations in their stomach, gonad, mantle and remaining tissue/fluids determined using liquid chromatography-mass spectrometry. Tetrodotoxin was detected in all organs/tissue after 1 h with an average uptake of 32%. This decreased throughout the experiment (21%, 15% and 9%, respectively). Benthic surveys at sites with dense populations of toxic P. maculata detected very low or no TTX in other organisms. This study demonstrates that P. maculata can accumulate TTX through their diet. However, based on the absence of an identifiable TTX source in the environment, in concert with the extremely high TTX concentrations and short life spans of P. maculata, it is unlikely to be the sole TTX source for this species

    Relationships and Client Protection Differences in the APA and ACA Ethical Codes

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    We present the results of a line-by-line comparison regarding relationship and client protection issues between the American Psychological Association (APA) and American Counseling Association (ACA) ethical codes. Out of 144 total differences in these ethical codes, 34 differences pertain specifically to the topics of relationships and client protection. Results from the study showed ACA to provide extensive requirements and prohibitions relating to the therapeutic relationship, compared to APA’s more general and principle-driven approach to this domain. Citing a few examples here, we note that ACA requires more extensive documentation of relationship boundary changes pertaining to romantic and/or sexual relationships, therapeutic role changes, and other redefinitions of relationships. Additionally, ACA and APA both limit the potential for multiple relationships, but ACA specifically prohibits counselors from terminating a therapeutic relationship in order to pursue a romantic relationship with someone closely related to their client. In sum regarding this domain, the ACA is more definitive, prescriptive, and limiting in what appears to be attempts at providing strengthened client protection. Similarly, the ACA is more detailed and narrow regarding client/counselor relationships and other therapeutic boundary establishments. The protections also are more fully extended to the counseling supervisor/supervisee relationship in the ACA code. In contrast, the APA is more general and/or silent in the domains which are spelled-out in detail by ACA. In the present study, we draw attention to the specific wording in the two documents and how these differences in words potentially impact clinical practice with both clients and supervisees. We also discuss how the results of the present study have implications for undergraduate students who are at the point of decision-making regarding which profession to select. Additionally, any psychologist who supervises counselors must ensure that all ethical standards—of both psychology and counseling—are upheld when counselors work under the licenses of a practicing psychologist. And finally, agencies who hire both licensed psychologist and licensed counselors must be aware of these significant differences in the APA and ACA ethical codes. We place the results of the present study into the larger context of the overall differences between the two codes

    Efficient targeted mutagenesis in the monarch butterfly using zinc finger nucleases

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    The development of reverse-genetic tools in non-model insect species with distinct biology is critical to establish them as viable model systems. The eastern North American monarch butterfly (Danaus plexippus), whose genome is sequenced, has emerged as a model to study animal clocks, navigational mechanisms and the genetic basis of long-distance migration. Here, we developed a highly efficient gene-targeting approach in the monarch using zinc-finger nucleases (ZFNs), engineered nucleases that generate mutations at targeted genomic sequences. We focused our ZFN approach on targeting the type 2 vertebrate-like cryptochrome gene of the monarch (designated cry2), which encodes a putative transcriptional repressor of the monarch circadian clockwork. Co-injections of mRNAs encoding ZFNs targeting the second exon of monarch cry2 into one nucleus stage embryos led to high frequency non-homologous end-joining-mediated, mutagenic lesions in the germline (up to 50%). Heritable ZFN-induced lesions in two independent lines produced truncated, nonfunctional CRY2 proteins, resulting in the in vivo disruption of circadian behavior and the molecular clock mechanism. Our work genetically defines CRY2 as an essential transcriptional repressor of the monarch circadian clock and provides a proof of concept for the use of ZFNs for manipulating genes in the monarch butterfly genome. Importantly, this approach could be used in other lepidopterans and non-model insects, thus opening new avenues to decipher the molecular underpinnings of a variety of biological processes

    Prevalence of drug-drug interactions in oncology patients enrolled on National Clinical Trials Network oncology clinical trials

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    Abstract Background Drug-drug interactions (DDIs) in subjects enrolling in clinical trials can impact not only safety of the patient but also study drug outcomes and data validity. This makes it critical to adequately screen and manage DDIs. The study objective was to determine the prevalence of DDIs involving study medications in subjects enrolling in National Clinical Trials Network (NCTN) clinical trials at a single institution. DDIs were evaluated based on study protocol recommendations for concomitant medication use (i.e. exclude, avoid or use caution), screening via DDI tool, and pharmacist review. Methods Subjects enrolled in NCTN trials of commercially available agents between January 2013 and August 2017 were included if a complete medication list was available. Complete medication lists were collected from the date of enrollment or the next available date then screened utilizing protocol guidance and the DDI screening tool, Lexicomp® Drug Interactions (Wolters Kluwer, Hudson, OH). Interactions were reviewed for clinical relevance: defined as a DDI that would require a medication change to ensure study agent safety and efficacy at enrollment. Results One hundred and twenty-eight subjects enrolled in 35 clinical trials were included. Protocol guidance detected 15 unique DDI pairs that should be avoided or used with caution in 10.2% (13/128) of subjects. The majority of these subjects did not have a clinically relevant DDI (69.2%, 9/13) based on pharmacist review. Lexicomp® detected moderate to major DDIs in 24.2% (31/128) of subjects, with 9.4% (12/128) having a clinically relevant DDI. Conclusions This study confirms a high prevalence of DDIs present in subjects enrolling in oncology clinical trials. Further efforts should be made to improve methods to detect and manage DDIs in patients enrolling on clinical trials to ensure patient safety and trial data validity.https://deepblue.lib.umich.edu/bitstream/2027.42/146516/1/12885_2018_Article_5076.pd

    The Next Generation Virgo Cluster Survey. IX. Estimating the Efficiency of Galaxy Formation on the Lowest-Mass Scales

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    The Next Generation Virgo Cluster Survey has recently determined the luminosity function of galaxies in the core of the Virgo cluster down to unprecedented magnitude and surface brightness limits. Comparing simulations of cluster formation to the derived central stellar mass function, we attempt to estimate the stellar-to-halo-mass ratio (SHMR) for dwarf galaxies, as it would have been before they fell into the cluster. This approach ignores several details and complications, e.g., the contribution of ongoing star formation to the present-day stellar mass of cluster members, and the effects of adiabatic contraction and/or violent feedback on the subhalo and cluster potentials. The final results are startlingly simple, however; we find that the trends in the SHMR determined previously for bright galaxies appear to extend down in a scale-invariant way to the faintest objects detected in the survey. These results extend measurements of the formation efficiency of field galaxies by two decades in halo mass, or five decades in stellar mass, down to some of the least massive dwarf galaxies known, with stellar masses of 105M\sim 10^5 M_\odot.Comment: 18 pages, 12 figures; published in ApJ July 1st 201

    Association of Exposure to Phthalates with Endometriosis and Uterine Leiomyomata: Findings from NHANES, 1999-2004

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    BACKGROUND. Phthalates are ubiquitous chemicals used in consumer products. Some phthalates are reproductive toxicants in experimental animals, but human data are limited. OBJECTIVE. We conducted a cross-sectional study of urinary phthalate metabolite concentrations in relation to self-reported history of endometriosis and uterine leiomyomata among 1,227 women 20-54 years of age from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999-2004. METHODS. We examined four phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monobenzyl phthalate (MBzP). From the last two NHANES cycles, we also examined mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS. Eighty-seven (7%) and 151 (12%) women reported diagnoses of endometriosis and leiomyomata, respectively. The ORs comparing the highest versus lowest three quartiles of urinary MBP were 1.36 (95% CI, 0.77-2.41) for endometriosis, 1.56 (95% CI, 0.93-2.61) for leiomyomata, and 1.71 (95% CI, 1.07-2.75) for both conditions combined. The corresponding ORs for MEHP were 0.44 (95% CI, 0.19-1.02) for endometriosis, 0.63 (95% CI, 0.35-1.12) for leiomyomata, and 0.59 (95% CI, 0.37-0.95) for both conditions combined. Findings for MEHHP and MEOHP agreed with findings for MEHP with respect to endometriosis only. We observed null associations for MEP and MBzP. Associations were similar when we excluded women diagnosed > 7 years before their NHANES evaluation. CONCLUSION. The positive associations for MBP and inverse associations for MEHP in relation to endometriosis and leiomyomata warrant investigation in prospective studies

    ESTABLISHING TRAINING PARAMETERS FOR A DEEP NEURAL NETWORK TO ASSESS 2D, FRONTAL PLANE KINEMATICS

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    The purpose of this study was to establish the optimal training parameters to assess frontal plane, 2D kinematics using DeepLabCut. DeepLabCut is an open-source platform that allows the user to train neural networks for customized feature detection in 2D videos. Deep neural networks were trained using frontal plane videos from 41 participants who completed single- and double-leg drop landings. Networks were trained with an increasing number of training iterations (25-250k) and training frames (200-800). Our results indicate that a minimum of 175k training iterations and 400 training frames were adequate for stable network performance (training/test errors= 2.8/3.7 pixels)

    Mild postoperative acute kidney injury and outcomes after surgery for congenital heart disease

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    ObjectiveThe effect of mild acute kidney injury (AKI) on outcomes after heart surgery in children is unclear. We sought to characterize the epidemiology of mild AKI associated with surgery for congenital heart disease (CHS-AKI) in children.MethodsWe conducted a single-center, retrospective cohort study of 693 patients (aged 6 days-18 years) who underwent heart surgery in 2009. The prevalence of AKI within 72 hours of surgery was determined using the 3-stage Acute Kidney Injury Network criteria. Factors associated with both hospital length of stay and AKI were used in a proportional hazards model to test the association of stage 1 AKI with hospital length of stay.ResultsThe median age of the patients was 11.5 months (interquartile range, 3-54 months). Eighteen percent of the cohort had single ventricle heart disease and 54% underwent RACHS-1 category 3 or higher surgery. The prevalence of stages 1, 2, and 3 AKI in this cohort was 11% (n = 77), 3% (n = 19), and 1% (n = 8), respectively. Factors independently associated with AKI were prematurity, single ventricle physiology, peak postoperative lactic acid concentration, cardiopulmonary bypass time, and a history of heart surgery. Stage 2 or greater CHS-AKI was associated with hospital length of stay (adjusted hazard ratio [AHR], 0.53; 95% confidence interval [CI], 0.33-0.87; P = .01), but stage 1 was not (AHR, 0.85; 95% CI, 0.66-1.10; P = .22).ConclusionsAKI occurs after surgery for congenital heart disease but may be less common than previously reported. Although moderate to severe CHS-AKI is independently associated with prolonged recovery after heart surgery, mild disease does not appear to be
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