Serial Draws Research Articles

Sang-e-Mah (2022): Hamlet , Gendered Violence, and Female Identity on Pakistani Television

Abstract: This article analyzes the Urdu drama serial Sang-e-Mah 2022, broadcast on Pakistani television, arguing that it relocates William Shakespeare’s Hamlet within cultural, regional, and national identities in Pakistan’s Khyber Pakhtunkhwa (KPK) province. The serial draws on Shakespeare’s play to offer a social commentary on female identity and gender-based violence in relation to the cultural practice of ghag in KPK. Examining the representation of female oppression, power, and agency on Pakistani television in the context of KPK, the article argues that the serial both disrupts the power dynamics of Hamlet and challenges gender roles in KPK in its attempt to redefine attitudes towards women in Pakistan.Ultimately, this article illustrates that Sang-e-Mah “localizes” Shakespeare’s play to allow it to participate in global conversations about the violation of women’s rights, the violation of law and order, and the valorization of gun cultures.

Authoritarianism in Relation to Children: Reflections in Times of War

This article examines the impact of Ukraine’s totalitarian past on the education system and the treatment of children in the current wartime context. It analyzes the role and effects of the war on adult-child relationships, particularly how authoritarian educational and communicative styles contribute to the risk of PTSD in children. Through two clinical illustrations—group work with children displaced by the war in the “Safe Space” psychosocial support program, and individual work with a teenager affected by a rocket attack using the “serial drawing” technique—the article demonstrates the importance of open communication, respect for feelings, and free play. These case studies highlight the ongoing struggle to overcome the remnants of totalitarian control in Ukraine’s educational and familial structures, emphasizing the need for a democratic and compassionate approach to foster resilience and psychological well-being in children.

Homes and Selves in Times of War: Ukrainian Rituals and Analytic Practices with Children who are Surviving Russian Aggression; All You Have is this Small Backpack

This study introduces a method of group work with children called “serial drawing,” developed and tested by specialists from the Center for Mental Health at the National University of Kyiv-Mohyla Academy. This method is designed for children who have experienced traumatic situations and is based on the Jungian concept of the psyche’s desire for wholeness, as well as the principle of psychological resilience. It leverages the psyche’s natural ability to integrate experiences and recover from trauma, creating an environment conducive to this healing process. The program we developed examines the psychological impact of losing one’s home due to military operations and highlights traditional, cultural coping methods, such as community rituals and symbols, within communities. A case study illustrating the recovery process from traumatic experiences is also presented.

Genomic spectrum of actionable alterations in serial cell free DNA (cfDNA) analysis of patients with metastatic breast cancer

We aimed to study the incidence and genomic spectrum of actionable alterations (AA) detected in serial cfDNA collections from patients with metastatic breast cancer (MBC). Patients with MBC who underwent plasma-based cfDNA testing (Guardant360®) between 2015 and 2021 at an academic institution were included. For patients with serial draws, new pathogenic alterations in each draw were classified as actionable alterations (AA) if they met ESCAT I or II criteria of the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). A total of 344 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) MBC, 95 patients with triple-negative (TN) MBC and 42 patients with HER2-positive (HER2 + ) MBC had a baseline (BL) cfDNA draw. Of these, 139 HR+/HER2-, 33 TN and 13 HER2+ patients underwent subsequent cfDNA draws. In the HR+/HER2- cohort, the proportion of patients with new AA decreased from 63% at BL to 27–33% in the 2nd-4th draws (p < 0.0001). While some of the new AA in subsequent draws from patients with HR+/HER2- MBC were new actionable variants in the same genes that were known to be altered in previous draws, 10-24% of patients had new AA in previously unaltered genes. The incidence of new AA also decreased with subsequent draws in the TN and HER2+ cohorts (TN: 25% to 0–9%, HER2 + : 38% to 14–15%). While the incidence of new AA in serial cfDNA decreased with subsequent draws across all MBC subtypes, new alterations with a potential impact on treatment selection continued to emerge, particularly for patients with HR+/HER2- MBC.

ПСИХОЛОГИЧЕСКИЙ СТАТУС ГИПЕРТЕНЗИВНЫХ ЛИЦ ПРИЗЫВНОГО ВОЗРАСТА И ВЗАИМОСВЯЗЬ ОТДЕЛЬНЫХ СТРЕССОГЕННЫХ ФАКТОРОВ С ПАРАМЕТРАМИ СУТОЧНОГО МОНИТОРИНГА АРТЕРИАЛЬНОГО ДАВЛЕНИЯ

The aim of the research was to study the psychological status of young men of military age with hypertension (AH) and to identify relationships with clinical data and the results of 24-hour blood pressure monitoring (DBPM). Materials and methods: 181 young men aged 18 to 27 years inclusive (average 21.3±0.2 years) with a confirmed diagnosis of primary AH were examined. Comprehensive psychological testing was carried out among 26 volunteers using questionnaires recommended by the Ministry of Defense of the Russian Federation for psychological testing of persons called up for military service (Khanin-Spielberg scale (situational (ST) and personal anxiety (LT), “Prognosis” scale (nervous-psychic resistance (NPR), PSM-25 (experience of stress) and the HADS scale (anxiety and depression), studied the relationship between test results among themselves and with DBPM parameters, the value of the level of statistical significance was taken equal to 0.05. Results. A simple interpretation of a complex of psychological tests showed the psychological well-being of the examined hypertensive individuals. A correlation analysis of scores scored on various psychological scales among themselves confirmed the validity and informativeness of the selected methods. A statistically significant moderate negative correlation was found between the number of points assessing the NS of an individual with the duration of AH, estimated in years, which indicates the protective nature of psychological discharge in relation to AH. Thus, our data showed that NS is the main psychological resource of conscripts and determines the development of AH among military personnel. As one of the methods of safe psychological relaxation, the method of serial drawing was proposed (Sysoeva, Korneeva, 2018). In addition, moderate positive correlations were found between the scores scored on the scales assessing the experience of stress (PSM-25) and the level of depression (HADS) with the average daily and daily DBP values and the average daily heart rate. Conclusions. 1. Among the persons of military age with primary hypertension, there was revealed the predominance of low levels of situational, personal anxiety and stress, normal indicators of anxiety and depression, a high degree of neuropsychic stability, which negatively correlated with the duration of hypertensive anamnesis. 2. The results of psychological tests positively correlate with the DBPM parameters that characterize DBP, which allows us to consider the methods of psychological correction among young men of military age as additional non-drug measures.

The Relationship of Serial Storytelling Activities in Stimulating Early Reading Ability in Kindergarten

The purpose of the study was to find out how storytelling activities relate to using series image media in improving initial reading skills. The formulation of the problem stated in this study is the low initial reading ability in children of Al-Karomah Kindergarten PGRI 4 Pujon. The type of research used is quantitative, using a correlation approach. The subject to be studied is a child, which amounts to 15 children. The required data collected through observation sheets, documentation, and data acquisition of relationships of two or more variables will be analyzed using descriptive and inferential statistics. The coefficient results obtained from the regression test analysis showed that the constant value was 1.975. In contrast, the serialized image storytelling value received a value of 0.902, so the regression model equation above can be described as Y = a + bX or 1.957 + 0.902X. Following the results described, it can be concluded that there is a significant relationship between serial drawing storytelling activities and children's initial reading ability.

Abstract P4-01-14: Changes in the Genomic Spectrum of Actionable Alterations in HER2 Negative Metastatic Breast Cancer in Serial Cell Free DNA (cfDNA) Analysis

Abstract Background: Serial cell free DNA (cfDNA) analysis in metastatic breast cancer (MBC) is a noninvasive method for tracking tumor evolution and the emergence of new somatic alterations through the course of the disease. The detection of new actionable alterations may impact treatment selection; thus, serial cfDNA collection is increasingly being performed in the clinic. However, it is not well-understood how often serial cfDNA testing identifies new actionable alterations. We evaluated changes in the genomic spectrum of actionable alterations in serial cfDNA analysis of HER2 negative (HER2-) MBC. Method: Patients with HER2- MBC who underwent plasma-based cfDNA testing (Guardant360, 74-gene assay) between February 2015 and February 2021 at an academic institution were included. A retrospective review of records was conducted to identify subtype, demographics, lines of therapy, and cfDNA results. At baseline cfDNA testing, all cfDNA alterations were considered new. For patients with serial draws, new cfDNA alterations in each draw, compared to previous draws, were quantified and characterized. The pathogenicity of new alterations was determined using the OncoKB precision oncology database. New pathogenic alterations were further classified as actionable alterations (AA) using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). Alterations that met the ESCAT I (alteration-drug match was associated with improved outcomes in clinical trials) or ESCAT II (alteration-drug match was associated with antitumor activity) criteria were considered as AA. Results: 344 patients with hormone receptor positive (HR+) MBC and 95 patients with triple negative (TN) MBC had a baseline cfDNA draw. Among the HR+ cohort, 139, 79 and 48 patients had 2nd, 3rd, and 4th serial cfDNA draws, respectively. Among the TN cohort, 33 and 18 patients had 2nd and 3rd serial cfDNA draws, respectively. Table 1 depicts the prevalence of AA found in each of these draws, as well as the median number of prior therapies at each point of collection and the mean time between serial draws. The median number of new genomic alterations was lower in subsequent draws compared to the baseline, regardless of subtype (HR+: 4 vs. 2, TN: 4 vs. 1.5-3, at baseline vs. subsequent draws, respectively). In the HR+ cohort the proportion of patients with new AA (ESCAT I/II) decreased from 63% at baseline to 27-33% in the 2nd-4th draws. While some of the new AA in subsequent draws were new actionable variants in the same genes that were known to be altered in previous draws (in 19%, 68% and 57% of patients with new AA in the 2nd, 3rd and 4th draws, respectively), the remainder were new AA in previously unaltered genes. In the TN cohort 25% of patients had new AA at baseline and this proportion of TN patients with new AA continued to decrease in subsequent draws (9% and 0% in the 2nd and 3rd draws, respectively). PIK3CA and ESR1 were the most frequent genes with new AA in the ER+ cohort, regardless of draw number. In the TN cohort, PIK3CA was the most frequent gene with new AA in the first draw, and in the second draw, new AA in PIK3CA, BRCA2, and ERBB2 were present at an equal frequency. Conclusion: While the proportion of patients with HER2- MBC identified to have new AA in serial cfDNA decreased with time for both HR+ and TNBC, new alterations continue to emerge, particularly for patients with HR+ MBC. Further research is needed to determine the impact of serial cfDNA testing on the selection of genotype-matched therapy and outcomes. Table 1. Citation Format: Yael Bar, Jennifer C. Keenan, Lianne Ryan, Dejan Juric, Jennifer Shin, Seth A. Wander, Laura M. Spring, Beverly Moy, Leif Ellisen, Steven J. Isakoff, Aditya Bardia, Neelima Vidula. Changes in the Genomic Spectrum of Actionable Alterations in HER2 Negative Metastatic Breast Cancer in Serial Cell Free DNA (cfDNA) Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-14.

Circulating tumor cells (CTCs) as liquid biopsies in patients with metastatic colorectal cancer versus other GI malignancies.

192 Background: Most of the focus on liquid biopsies for patients with colorectal cancers and other solid tumors has been on circulating tumor DNA (ctDNA). Circulating Tumor Cells (CTCs) are the other less talked about liquid biopsies. This is due to need for real-time processing and handling of CTCs, and is less conducive on previously banked samples. We took this prospective discovery endeavor to report in real-time CTC analyses using 2 very different platforms in patients with colorectal and other GI cancers. Methods: CTCs were evaluated using 2 platforms: RareCyte, which is simplistically based on density of CTCs and unbiased selection/identification for enumeration/biomarker analyses, and Parsortix, which is based on size/compressibility of CTCs. All patients signed written informed consent. Up to 4 serial draws were done for each patient (Total = 150 draws; 281 test results). CTCs were identified using standard definitions of nuclear/epithelial markers. À la carte we selected PD-L1, HER2, EGFR, Ki-67, and where adequate, confirmation with panel based single cell sequencing was also performed. Cell cultures were attempted for the Parsortix collections. Results: Patients with colorectal cancer (CRC) had the highest number of CTCs (Mean: 15.8; Median: 7.5). This was in sharp contrast to the number of CTCs in patients with pancreatic cancer (PC) (Mean: 4.2; Median: 3). At least a third of patients with CRC had at least 3 CTCs. Another 17.4% and 11.4% had at least 10, and at least 20 CTCs in CRC; while no patients with PC had more than 20 CTCs. CTCs in clusters were also common at baseline. In addition, we detected a significantly lower number of CTCs from patients receiving treatment versus those were not (Median 2.7 versus 0.7). Striking differences were also observed in CTCs for those with untreated/progressive disease versus those who had responding/stable disease (Median of 2.7 versus 0). Biomarker analyses on HER2/PD-L1/Ki-67/EGFR were feasible when CTCs were detected. There was overall agreement on CTCs detected on either platform. Where available, single cell sequencing data was concordant with clonal aberrations on sequencing. Conclusions: This is one of the largest prospective real-time endeavors in patients with colorectal and other GI cancers providing data on CTCs as liquid biopsies using 2 very different platforms. The descriptive insights gained from processing, enumeration, kinetics, timing of collection, biomarker analysis, costs, comparison across tumor types, attempts at cell culture, and single cell sequencing are of value for studies and investigators considering the use of CTCs in patients with colorectal and other GI cancers. While most of the focus is on ctDNA-based platforms, CTCs offer a different lens from a liquid biopsy standpoint that is complimentary and worth developing further.

Seeing Serially: Harman’s Object-Oriented Ontology Encountering Serial Drawing

ABSTRACT Graham Harman’s Object-Oriented Ontology prioritises aesthetics as first philosophy, and finds increasing interest from those working across art, architecture and the humanities in general. This article tests the application of Harman’s ideas by applying them to a thorny issue related to the domain of serial art, and serially developed drawing in particular. The issue concerns the productive role of the beholder in constituting the serial artwork as a unified thing, wherein it appears manifestly deeper than the sum of its physical parts. Referring to an artwork produced by contemporary artist Stefana McClure, I build upon prior propositions on serial art put forward by Christy Mag Uidhir and Nicolas de Warren to make the case for seeing serially. This uses Harman’s understanding of aesthetics to claim that imagined iterations constitute an integral element to serial drawing, brought into play when the beholder reflects upon the loose relationship between the array of qualities the artwork palpably presents and its withdrawn reality as a unified object.

Recent Advances in Bedside Device-Based Early Detection of Sepsis.

Early detection of sepsis is challenging to achieve with current diagnostic methods, leading to expenditures of $27 billion annually in the United States with significant associated mortality. Various scoring systems have been proposed such as the sequential organ failure assessment (SOFA) and systemic inflammatory response syndrome (SIRS) criteria for identification of sepsis, but their sensitivities range from 60% to 70% when used in the emergency department triage. Other methods for the recognition of sepsis may rely on laboratory work, in addition to vitals monitoring, and are often outpaced by the development of sepsis. Automated alerts have not shown any reduction in mortality thus far. New technology may fill a critical gap in the early detection of sepsis. The ideal bedside screening device for would demonstrate rapid time to result, high portability, and high sensitivity to not miss cases, but also reasonable specificity to prevent provider fatigue from excessive false alerts. Non-invasive end-organ perfusion devices analyzing lactate and capillary refill time (CRT) tend to perform well in speed and portability, but may be less sensitive. Biomarker devices demonstrate a wider array of performance metrics. Those analyzing a single biomarker tend to be more sensitive but are less specific to the diagnosis of sepsis than technologies that assess multiple biomarkers, which in turn have lower sensitivity. Additionally, biomarker devices are generally invasive requiring blood samples, which may or may not be feasible in all patients especially when serial draws are needed. Sepsis is a complex disease process and most likely will require a combination of improved technology in addition to vital signs and high-risk patient history for better recognition. This review examines recent advances in the device-based early detection of sepsis between 2017 and 2020 with emphasis on bedside diagnostics, divided into markers of perfusion and biomarkers commonly implicated in sepsis.

Microstructure and mechanical properties of low carbon steel wires with serial and reverse-direction cold drawing

Low carbon steel wires were prepared by two processes, serial drawing (SD) and reverse-direction drawing (RD). Effects of the two processes on microstructure and mechanical properties in steel wires were investigated by field emission-scanning electron microscopy, electron backscatter diffraction (EBSD), X-ray diffraction and transmission electron microscopy (TEM). Residual compressive stress and more low-angle grain boundaries were introduced into the steel wire by the RD. As a result, the RD wires exhibited a greater tensile strength when drawing strain e < 1.18. The SD encouraged grain refinement and texture formation in the wire. The SD wires exhibited a smaller average width of the elongated ferrite grain and a higher intensity of 〈110〉 fiber texture at all drawing strains. Therefore, the SD wires showed a bit greater tensile strength and 20% greater torsion performance than the RD wires at e = 2.51. TEM and EBSD analysis indicated that dislocation tangle was formed easily in RD wires, and it transformed into twist boundary. This twist boundary impeded the grain refinement in the RD wires, and there were still non-fibrous grains in the RD wires even after heavy drawing.

APPLICATION OF ART THERAPY FOR CORRECTION OF PERSONAL DISORDERS OF PSYCHOEMOTIONAL STATE OF CHILDREN - INHABITANTS OF RADIATION POLLUTED TERRITORIES AND CHILDREN DISPLACED FROM THE ARMED CONFLICT ON THE SOUTHERN EAST OF UKRAINE.

to identify the psycho-emotional state of children - residents of radioactively contaminated territories and children displaced from the zone of armed conflict in the south-east of Ukraine, and evaluate the effectiveness of art therapy application to correct its disturbances. The psycho-emotional state was determined in 113 children, of which 57 children from radioactively contaminated territories with 137Cs content in the body from 269 Bq to 7024 Bq (group I) and 56 chil- dren displaced from the zone of military conflict in the Southeast of Ukraine (group II). The age of children ranged from 10 to 17 years. The children were hospitalized to the childrens' clinics of the NRCRM because of functional dis- orders and chronic somatic pathology. The psycho-emotional state of children was evaluated using the «non-exis- tent animal» test. It was analyzed for three symptoms - anxiety, aggressiveness and neuropsychiatric exhaustion and was evaluated by scoring points. Correction of the psychoemotional condition was carried out by the method of art therapy in the form of a serial drawing. Psychological testing was performed twice: at admission to the hospital and after the end of the art therapy. The results of the primary examination of the psycho-emotional state of children by the «non-existent ani- mal» test showed that in children - residents of radioactively contaminated territories the state of anxiety was reg- istered in all 57 children (100 %), the state of aggression - in 38 children (66.7%); exhaustion - in 37 children (64.9 %). In children who have been displaced from the zone of armed conflict in the south-east of Ukraine, the state of anxiety was also registered in all 56 children (100 %), the status of aggression was determined in 53 chil- dren (94.6 %), and the state of exhaustion - in 44 children (78.6 %). It was established that in children displaced from the combat zone in the Southeast of Ukraine, the quantitative indices of anxiety and aggression states were sig- nificantly higher than in children living in radioactively contaminated territories (p < 0.001), whereas nor by frequen- cy, nor by the degree of severity of exhaustion state they did not clearly differ (p > 0.05). Correlation analysis with the definition of Spearman's criterion did not reveal likely association between the content of 137Cs in the body of children - residents of radioactively contaminated territories and the peculiarities of their psycho-emotional state. The use of the art therapy method in the form of a serial drawing for children - residents of radioac- tively contaminated territories and children moved from the combat zone in the south-east of Ukraine, led to a sig- nificant positive effect, which was characterized by a decrease in the manifestations of symptoms of anxiety and aggressiveness. The state of exhaustion was less well corrected and its indices only had a tendency to improve. Thus, the method of art therapy in the form of a serial drawing is characterized by efficiency, simplicity of execution, low cost, it can be widely used in children's teams to correct disorders of the psycho-emotional state.

Drawing with words

Abstract

Nine Drawings: seriality, postphenomenology and the force of time

ABSTRACTThis article describes a piece of practice-led drawing research titled: Nine Drawings (2016). Treated as a first-person investigation combining serial drawing, Bergsonian philosophy and a postphenomenological methodology, the purpose is to test the idea of research through drawing by seeking to represent the enigmatic Bergsonian notion that time acts as a force. The methodology employs serially developed drawing to ‘record’ (represent) the drawers experience of time ‘passing’. Treated as a form of praxis which is reflected upon in the drafting of this paper, the process of drawing centres around the effort to draw biro lines ‘in time’ to a ticking metronome. The metronome is set ticking at various increasing tempos, each represented by a different coloured biro ink, and the results displayed across a series of nine graph paper sheets. In conceptual terms, time is interpreted according to Bergson’s philosophy of la durée (duration), while the series is largely assessed using the phenomenological method of variations. Considered in terms of research, the assessment seeks both an invariant and a multistable understanding of the phenomenon under consideration – the experientially derived idea that time acts as a force. The nine drawings are presented individually after the conclusion for the reader to refer to, whilst being presented once as a full series. The results of this multifaceted investigation are reported at the end, and offer potential insights into the way in which research through drawing might operate when art and philosophy are combined.

Use of serial multi-template liquid biopsies in triple negative breast cancer monitoring.

1091 Background: Triple negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer in which up to 1/3 of all patients will relapse early and distantly. There remains no proven method to monitor and detect early recurrence. This study examines the utility of serial liquid biopsies using a multi-template approach (identification and analysis of cell-free DNA (cfDNA) and circulating tumor cells (CTCs)) as a solution. Methods: 210 patients (average 53 yrs.) with confirmed diagnosis of TNBC, within 3 years of completion of therapy (mean 25 mos.), and in full remission were enrolled. Liquid biopsies were performed quarterly to look for cancer specific genomic mutations not seen in germ line controls, but in cfDNA and CTCs using a custom 27-gene breast cancer panel. Prior validation of our gene panel demonstrated a false positive rate of 0.001-0.0007% in normal cfDNA and cell-based controls. Results: Each subject had on average 3.0 serial samples collected to date. 169 patients (80.4%) had evidence of mutations in at least one sample. Seventy-five percent of cfDNA and 36% of CTC samples examined have been found to bear mutations. The total number of samples with orthogonally (either between template or between draws) confirmed signal was 16.9%. Seven patients (3.3%) have developed documented evidence of recurrence, one in the axilla and the others with visceral/distant metastases. Of the patients that have recurred, all had a persistent mutation on consecutive blood draws or evidence of genomic mutations in both cfDNA and CTCs. Conclusions: The majority of TNBC patients in our study post-treatment were found to have genomic mutations on at least one liquid biopsy sample – either cfDNA or CTC. But, very few had a persistent presence of mutations in subsequent samples and 96.7% of our patients have remained NED. Unlike patients who remained NED, patients who recurred displayed persistent evidence of mutations on serial draws or in both cfDNA and CTC samples. To date our recurrence rate is lower than predicted. This study highlights the need for serial monitoring using a multi-template approach to better fully understand patient specific tumor biology and kinetics. The trial is ongoing. Clinical trial information: NCT02639832.

Abstract P6-03-06: Circulating tumor DNA (ctDNA) for detection of molecular residual disease (MoRD) in breast cancer

Abstract Background Metastatic breast cancer (BC) is an incurable condition and treated with palliative intent. Standard diagnostic imaging and serum markers have limited sensitivity and are not recommended in clinical practice. Micrometastatic disease in the bone marrow (DTC) and peripheral blood (CTCs) is a recognized prognostic marker but with limited clinical utility. The detection of asymptomatic disease using a sensitive, reproducible and robust blood-based molecular test, or molecular residual disease (MoRD) could potentially represents a tool with the capability to design early therapeutic interventions and improve outcome. Circulating tumor DNA (ctDNA) has the potential to reflect residual tumor burden with higher diagnostic accuracy. We performed a pilot study in patients with high-risk primary BC. Methods This is a prospective study of 30 patients with either locally advanced BC who had completed primary therapy (21 patients) and had no evidence of disease (NED), or were metastatic but treated with curative intent and currently NED or stable (9 patients). Plasma was analyzed for ctDNA either after completing neo-adjuvant therapy (NAT), for recurrence monitoring after surgery, or when there was a clinical suspicion of recurrence. Guardant360™(Guardant Health) is a ctDNA next generation sequencing panel which produces a quantitative measurement of the mutant allele fraction for single nucleotide variants in 54 genes and copy number variants in 3 genes (panel was expanded to 68 genes in Feb '15) using digital sequencing technology. Results Baseline ctDNA analysis was done for 30 patients and 25 (83%) had serial draws for a total of 76 samples. All patients were stage 3-4 except for two stage 2 patients. ctDNA or MoRD was detected in 17 (57%) of patients and in 39 (51%) of the samples. Of the 18 patients treated with NAT, 11 achieved pCR or had minimal residual disease. Of these 11, six had no ctDNA detected after surgery, 3 had mixed results of no ctDNA and low volume ctDNA alterations on different draws, and 2 had persistent mutations on 2 draws. Ten of these 11 patients remain NED with median follow up of 24 months, while the one patient who recurred had persistent low volume missense ctDNA alterations on serial draws, first detected 6 months before clinically evident recurrence. Of the 7 patients with significant residual disease (less than PR) after NAT, 6 had post-surgical ctDNA detected and 5 have recurred at a median of 13 months after surgery. Four of those patients had ctDNA tested prior to recurrence and all had alterations detected in the blood prior to clinical recurrence. Lastly, one HER2+ metastatic patient treated with curative intent with a subsequent negative PET scan and no ctDNA detected after HER2-targeted therapy progressed on CT 2 months later and repeat ctDNA revealed EGFR mutant allele fraction of 51% and ERBB2 amplification. Conclusions The evaluation of ctDNA in high-risk BC patients can identify MoRD and predict for clinical recurrence. Patients with no or low volume ctDNA after primary treatment remained NED longer than those with multiple or high volume alterations. Future studies will validate these early observations and aid in selecting patients for additional systemic therapy with the hope of improving outcome. Citation Format: Austin L, Jaslow R, Fortina P, Nagy R, Zill O, Talasaz A, Cristofanilli M. Circulating tumor DNA (ctDNA) for detection of molecular residual disease (MoRD) in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-06.

Time taken and time told: Serial drawing as the becoming of now

Abstract This article presents a brief report of a first-person investigation through drawing, discussing how serially developed drawing can be understood to express the becoming of now – the present moment in time. By employing a phenomenological approach, the notion that drawing expresses the becoming of now is treated as an assumption, meaning a hypothesis to be tested through practice and theory combined. This occurs as part of my developing research practice, where I look to ‘perform philosophy in a non-philosophical way’ (Emoe 2014). Rather than treat art as an object for philosophy, I use philosophy to question a thought that I, as a practitioner, believe is immanent to drawing as form of art – that drawing itself is a form of becoming, based on the intentionality underpinning the temporal experience of drawing. I employ a largely Husserlian ([1931] 2012) approach to my research, using the methods of variational practice and ‘bracketing’ to actively suspend my assumptions for the duration of each test. Deploying it here means I stand back from my uncritical ‘lived experience’ of time to establish how phenomenological theory renders the now an aporia, or puzzle, difficult to express in conventional terms. I then use this theory to develop an alternative mode of expression through drawing, developing the now as a rhythm with a fixed temporal duration, which then ‘becomes’ a spatial extension through drawing serially developed lines. In my analysis I seek the invariant understanding – meaning I ask the series what it expresses beyond the individual variation each drawing presents. I emerge from this process better able to articulate how drawing operates, but also with some reservations, leading towards some suggestions for potential development of the research.

The method of serial drawings and stories in psychological counseling to resolve disputes between parents about the child's upbringing

The urgency to develop new approaches to psychological counseling families in situations of settling disputes between the parents on the upbringing of the child is determined by the increasing frequency of such requests to clinical psychologists. Such consultations suggest the need for a rapid assessment of the psychological state, characteristics and relationships of experiencing parental divorce children. The aim of the article - to provide a description of I. M. Nikolskaya method of serial drawings and stories; to demonstrate the possibilities of its use in psychological counseling for resolution of the dispute between parents about parenting and procedure of meetings with the child on a clinical example. The method of serial drawings and stories is the integrative art therapeutic technology based on the projective approach. The method simultaneously solves the problem of psychological research and counseling in the specific situation of the child and his parents appeal to the psychologist. The article presents the short description of the method procedure, its stages and aims, the order of drawings topics. The techniques of art therapeutic interview and its advantages (concrete, detachment, structured, therapeutic effect) and showed. The information obtained through the application of the method in the form of images and texts can serve as an objective material to draw conclusions about the child’s subjective family situation view and well-being in the family. To illustrate the possibilities of the method of serial drawings and stories the clinical case of 7 years girl’s psychological counseling, conducted at the request of her mother in connection with the judicial review of the order of father and daughter meetings after a divorce, is analyzed.

Abstract 4928: Clinical utility of circulating tumor DNA (ctDNA) in advanced and metastatic breast cancer

Abstract Background MBC is an incurable disease characterized by genomic abnormalities including somatic mutations, amplifications and gene rearrangements. It is believed that treatment resistance and disease progression is related to genomic instability making “molecular monitoring” and consequent therapeutic management a dynamic and potentially more effective approach. The detection of circulating DNA fragments with tumor-specific sequence alterations (ctDNA) found in the blood of patients is the ideal diagnostic tool for non-invasive molecular monitoring. Methods This is a retrospective evaluation of 75 patients with advanced or MBC who both completed primary therapy and were NED (stage 1-3), or failed standard therapies and had baseline plasma analyzed for ctDN before starting new therapy (stage 4). For patients with progression, selection criteria included: progression of disease after standard therapies, need to detect novel molecular abnormalities for possible therapeutic targeting, or confirmation of persistence of genomic abnormalities already demonstrated in tissue or blood analysis. Guardant360™(Guardant Health) involves ctDNA isolation from plasma using a Qiagen circulating nucleic acid kit, then a panel of 54 gene mutations associated with solid tumors as reported in the COSMIC database sequenced using single-molecule digital sequencing technology. Results Most of the patients have metastatic disease (95%), but four patients had stage III disease and are now NED after neo-adjuvant therapy and surgery. According to subtype, 41% ER+/HER2-, 17% ER+/HER2+, 11% ER-/HER2+, and 31% TNBC. ctDNA was detected in 84% (63) of all patients; however, only 20% of patients who are now NED had ctDNA detected. Of patients with detected mutations, 52% had an actionable mutation that was incorporated into treatment planning. The most common mutations were TP53 (65%), PIK3CA (38%), ALK (21%) and NOTCH1 (17%). One patient with ER+/HER2- disease had ctDNA drawn at progression demonstrating a PIK3CA mutation, started on clinical trial with Letrozole/Palbociclib with clinical response and no ctDNA detected on two serial draws. Another patient with ER+/HER2- disease with 11 alterations noted in her blood, including PIK3CA and ATM, was started on targeted therapy with Trastuzumab based on HER2+ CTCs with clinical response but upon progression, ctDNA showed a dramatic increase in the resistant ATM clone, increasing from 1.1% to 27.8%. Conclusions ctDNA can be detected in the majority of patients with MBC irrespective of disease subtype. Actionable mutations can be identified and used for selection of targeted therapies. Longitudinal monitoring can accurately predict treatment response but also detect the onset of new mutations likely related to resistant clones. The real-time molecular monitoring and therapeutic implications hold the promise to significantly change our approach to the management of MBC with survival benefit. Citation Format: Laura K. Austin, Rebecca Jaslow, Tiffany Avery, Paolo Fortina, Dragan Sebisanovic, LaiMun Siew, Aubrey Zapanta, AmirAli Talasaz, Massimo Cristofanilli. Clinical utility of circulating tumor DNA (ctDNA) in advanced and metastatic breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4928. doi:10.1158/1538-7445.AM2015-4928

Comparison of Pharmacokinetics of Dapsone in Male Sprague Dawley Rats Following Retro Orbital, Jugular Vein and Saphenous Vein Blood Sampling

Pharmacokinetic (PK) studies play an important role in identifying lead compounds for further development. Typically rats are used for PK screening of New Chemical Entities (NCEs) as the compound requirements are minimal (<10 mg), multiple blood sampling (up to 10 samples) can be performed from the same animal and in small volumes (5-25μL) for sample analysis. Blood sampling site is critical in obtaining multiple blood samples of good quality and in small volumes with minimal stress to animals. However, it is not known whether PK parameters can be influenced by sampling site. Thus, in this study, we evaluated the effect of different blood sampling sites like retro-orbital plexus, jugular vein and saphenous vein on PK parameters of Dapsone. Dapsone was administered both orally and intravenously at a dose of 12 mg/kg to a group of 4 male Sprague Dawley rats and blood samples were collected up to 24 h. Samples were analyzed by LC/MS/MS and PK parameters were calculated. With all the sampling techniques, PK parameters like clearance, volume of distribution, half-life and bioavailability were similar. Due to the control on the blood volume withdrawn at each time point, quick sampling with minimal hemolysis and minimal animal handling stress during sampling, Jugular Vein (JV) or Saphenous Vein (SV) sampled rats can be used for PK studies. Further for saphenous sampling no pre-study preparation like cannulation is required before dosing the animals therefore sampling of rats through saphenous vein is recommended for pharmacokinetic and toxicokinetic studies. To summarize, SV sampling reduce the number of animals in different Pharmacokinetic (PK) (mouse) and Toxicokinetic (TK) (mouse and rat) studies by using serial draws, offers reduction and refinement over the othersampling techniques with minimal preparation upfront and with a potential to replace them.