Early Diagnostic Marker Panel Determination for Microarray Based Clinical Studies

We present a novel, cost efficient two-phase design for predictive clinical gene expression studies: early marker panel determination (EMPD). In Phase-1, genome-wide microarrays are used only for a small number of individual patient samples. From this Phase-1 data a panel of marker genes is derived. In Phase-2, the expression values of these marker panel genes are measured for a large group of patients and a predictive classification model is learned from this data. Phase-2 does not require the use of expensive whole genome microarrays, thus making EMPD a cost efficient alternative for current trials. The expected performance loss of EMPD is compared to designs which use genome-wide microarrays for all patients. We also examine the trade-off between the number of patients included in Phase-1 and the number of marker genes required in Phase-2. By analysis of five published datasets we find that in Phase-1 already 16 patients per group are sufficient to determine a suitable marker panel of 10 genes, and that this early decision compromises the final performance only marginally.

Download Full-text

Endometrial Adenocarcinoma in SurePath™ Cervical Samples: Cytological Features Revisited

Acta Cytologica ◽

10.1159/000444043 ◽

2016 ◽

Vol 60 (1) ◽

pp. 46-52 ◽

Cited By ~ 1

Author(s):

Nalini Gupta ◽

John Crossley ◽

Nick Dudding ◽

John H.F. Smith

Keyword(s):

Phase 1 ◽

Endometrial Adenocarcinoma ◽

Nuclear Chromatin ◽

Phase 2 ◽

Cervical Lesions ◽

Two Phase ◽

Endometrial Cells ◽

Phase Study ◽

Cytological Features ◽

Liquid Based Cytology

Objective: The cytomorphological criteria of malignant endometrial lesions in cervical samples are less well described than those of cervical lesions. We wished to investigate if there were features in SurePath™ liquid-based cytology samples that would facilitate more accurate differentiation between benign and malignant endometrial cells. Study Design: This was a two-phase study, with a review of all SurePath™ samples reported as endometrial adenocarcinoma (n = 42) evaluating 12 cytological features in the first phase. In phase 2 (test set), all initial cases plus an additional 83 cases were reviewed using these 12 cytological features to predict the outcome. Results: Out of 12 cytological features evaluated in phase 1 (training set), nuclear chromatin pattern, apoptotic bodies and tingible body macrophages were found to be the most significant features determining malignant histological outcome. These 12 cytological features were re-evaluated in phase 2 (n = 125). Of 125 cases, 54 had a benign and 71 had a malignant or premalignant histological outcome, with a positive predictive value of 56.8%. Conclusion: Granular nuclear chromatin, tingible body macrophages and apoptosis in the background are the most significant factors in determining whether endometrial cells present in cervical samples represent malignancy or are benign. Using these features, relatively accurate predictions of endometrial pathology can be made.

Download Full-text

Developing a realist theory of psychosocial rehabilitation: the Clubhouse model

10.32920/14639136 ◽

2021 ◽

Author(s):

Christina Mutschler ◽

Jen Rouse ◽

Kelly McShane ◽

Criss Habal-Brosek

Keyword(s):

Phase 1 ◽

Psychosocial Rehabilitation ◽

Theory Development ◽

Realist Evaluation ◽

Self Determination ◽

Phase 2 ◽

Two Phase ◽

Realist Theory ◽

Clubhouse Model ◽

Two Phases

Background Psychosocial rehabilitation is a service that supports recovery from mental illness by providing opportunities for skill development, self-determination, and social interaction. One type of psychosocial rehabilitation is the Clubhouse model. The purpose of the current project was to create, test, and refine a realist theory of psychosocial rehabilitation at Progress Place, an accredited Clubhouse. Method Realist evaluation is a theory driven evaluation that uncovers contexts, mechanisms, and outcomes, in order to develop a theory as to how a program works. The current study involved two phases, encompassing four steps: Phase 1 included (1) initial theory development and (2) initial theory refinement; and Phase 2 included (3) theory testing and (4) refinement. Results The data from this two-phase approach identified three demi-regularities of recovery comprised of specific mechanisms and outcomes: the Restorative demi-regularity, the Reaffirming demi-regularity, and the Re-engaging demi-regularity. The theory derived from these demi-regularities suggests that there are various mechanisms that produce outcomes of recovery from the psychosocial rehabilitation perspective, and as such, it is necessary that programs promote a multifaceted, holistic perspective on recovery. Conclusions The realist evaluation identified that Progress Place promotes recovery for members. Additional research on the Clubhouse model should be conducted to further validate that the model initiates change and promotes recovery outcomes.

Download Full-text

Whole system approaches to health in higher education

Health Education ◽

10.1108/he-02-2019-0010 ◽

2019 ◽

Vol 119 (4) ◽

pp. 246-258

Author(s):

Mark Dooris ◽

Alan Farrier ◽

Susan Powell ◽

Maxine Holt

Keyword(s):

Higher Education ◽

Phase 1 ◽

International Perspective ◽

Phase 2 ◽

Structured Interviews ◽

Two Phase ◽

Content Type ◽

Key Issues ◽

Strategic Influence ◽

The Uk

Purpose The purpose of this paper is to report on an evaluation of the UK Healthy Universities Network (UKHUN), which explored engagement of network members; identified what members value about the network; examined facilitators and barriers to engagement; and informed the network’s future development. Design/methodology/approach The study was a two phase mixed-method study, with participants being staff from Higher Education institutions. Phase 1 involved a documentary review and an online 14-question survey (n=32). Phase 2 comprised follow-up semi-structured interviews and focus groups, conducted using Skype (n=11). These were audio recorded and transcripts were thematically analysed in a two-stage process. Findings A number of key themes emerged from the thematic analysis: value of network meetings and events; popularity of the network website; increased communication and collaboration; sense of leadership offered by the network; interest and inclusion of an international perspective; importance of institutional support. Research limitations/implications Only six universities who are involved in the network took part in Phase 2. Although a range of organisations were chosen purposively, it is possible that additional key issues at other universities were excluded. Originality/value The UKHUN is valued by its membership, particularly its biannual meetings, online presence, leadership, ethos and communication methods. Key barriers include the capacity of staff to attend meetings and contribute to the network, influenced by a lack of institutional commitment and prioritisation. Findings from the evaluation have informed a “refresh” of the network’s website and a revision of its membership structure, as well as guiding its positioning to achieve greater strategic influence.

Download Full-text

A computationally fast approach to maximum‐likelihood deconvolution

Geophysics ◽

10.1190/1.1441690 ◽

1984 ◽

Vol 49 (5) ◽

pp. 550-565 ◽

Cited By ~ 48

Author(s):

Chong‐Yung Chi ◽

Jerry M. Mendel ◽

Dan Hampson

Keyword(s):

Maximum Likelihood ◽

Initial Conditions ◽

Phase 1 ◽

Real Data ◽

Phase 2 ◽

Statistical Parameters ◽

Two Phase ◽

Nonminimum Phase ◽

Fast Approach ◽

Fine Adjustment

In this paper we derive and implement a maximum‐likelihood deconvolution (MLD) algorithm, based on the same channel and statistical models used by Kormylo and Mendel (1983a), that leads to many fewer computations than their MLD algorithm. Both algorithms can simultaneously estimate a nonminimum phase wavelet and statistical parameters, detect locations of significant reflectors, and deconvolve the data. Our MLD algorithm is implemented by a two‐phase block component method (BCM). The phase‐1 block functions like a coarse adjustment of unknown quantities and provides a set of good initial conditions for the phase‐2 block, which functions like a fine adjustment of unknown quantities. We demonstrate good performance of our algorithm for both synthetic and real data.

Download Full-text

Phase 1/2 study of safety/efficacy using trabectedin, ipilimumab, and nivolumab as first-line treatment of advanced soft tissue sarcoma (STS).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.tps46 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. TPS46-TPS46 ◽

Cited By ~ 2

Author(s):

Erlinda Maria Gordon ◽

Victoria S. Chua-Alcala ◽

Katherine Kim ◽

William W. Tseng ◽

Doris M Quon ◽

...

Keyword(s):

Checkpoint Inhibitors ◽

Phase 1 ◽

Objective Response ◽

Progression Free Survival ◽

Maximum Tolerated Dose ◽

Categorical Variables ◽

Phase 2 ◽

First Line ◽

First Line Therapy ◽

Number Of Patients

TPS46 Background: Sarcoma cells are most immunogenic at the onset of cancer when the immune system can recognize and destroy them. Hence, immune checkpoint inhibitors would be most effective when given as first line therapy. Objectives: (1) To investigate the maximum tolerated dose of trabectedin, an alkylating agent, when given sequentially with ipilimumab, a CTLA4 inhibitor, and nivolumab, a PD-1 inhibitor, in advanced STS, (2) To investigate the objective response rate (ORR), progression free survival (PFS) and overall survival (OS) , and (3) To correlate PFS with PD-L1 and other biomarker expression in patients’ tumors. Methods: Forty patients ≥18 years of age with advanced STS will be enrolled. This is a phase 1/2 study using a defined dose of ipilimumab (1 mg/kg i.v. q 12 weeks), nivolumab (3 mg/kg i.v. q 2 weeks), and escalating doses of trabectedin (1.0, 1.3, 1.5 mg/m2 i.v. q 3 weeks). I. Dose Escalation Phase 1 (previously treated patients): The study will employ the standard “cohort of three” design. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. II. Expansion Phase 2 (previously untreated patients): An additional 22-28 patients will receive trabectedin at the MTD and defined doses of ipilimumab and nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients may continue treatment until significant disease progression or unacceptable toxicity occurs. Statistical Considerations: NIH CTCAE v4.03 and RECIST v1.1 will be used. Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. The analyses of all study objectives will be descriptive and hypothesis generating, for planning Phase 2/3 studies. Clinical trial information: NCT 03138161.

Download Full-text

Stem cell factor amplifies newborn and sickle erythropoiesis in liquid cultures

Blood ◽

10.1182/blood.v81.10.2591.bloodjournal81102591 ◽

1993 ◽

Vol 81 (10) ◽

pp. 2591-2599 ◽

Cited By ~ 1

Author(s):

RS Weinberg ◽

JC Thomson ◽

R Lao ◽

G Chen ◽

BP Alter

Keyword(s):

Stem Cell ◽

Progenitor Cells ◽

Stem Cell Factor ◽

Mononuclear Cells ◽

Phase 1 ◽

Newborn Infants ◽

Cell Number ◽

Phase 2 ◽

Two Phase ◽

Erythroid Progenitor

A two-phase liquid-culture system was used to substantially amplify and differentiate erythroblasts, starting with mononuclear cells from the blood of normal adults, newborn infants, and patients with sickle cell anemia. After the first 7 days (phase 1), in medium plus fetal bovine serum (FBS) alone, or in combination with stem cell factor (SCF) or conditioned medium (CM), the cell number was unchanged, and the cells all looked like lymphocytes. These cells were then diluted into medium with erythropoietin (Ep) alone, with Ep and either SCF or CM, or in methylcellulose with the same factors (phase 2). After 14 days in liquid phase 2 with SCF and Ep, the cell numbers increased an average of 30-fold in the sickle, 24-fold in the newborn, and 4-fold in the normal adult cultures; almost all the cells were erythroblasts and erythrocytes. SCF in phase 1 increased the number of late progenitors (CFU-E) assayed in methylcellulose, with the largest number in sickle, followed by newborn cultures and then adult cultures. We conclude that erythroid progenitor cells survive for at least 7 days without Ep (but with FBS). Progenitor cells are amplified, particularly with SCF. Later in culture, SCF with Ep increases the final number of differentiated erythroid cells. Both the early and the late effects of SCF are most effective in sickle, followed by newborn cultures and then adult cultures.

Download Full-text

Enhancing Label Representations with Relational Inductive Bias Constraint for Fine-Grained Entity Typing

Proceedings of the Thirtieth International Joint Conference on Artificial Intelligence ◽

10.24963/ijcai.2021/529 ◽

2021 ◽

Author(s):

Jinqing Li ◽

Xiaojun Chen ◽

Dakui Wang ◽

Yuwei Li

Keyword(s):

State Of The Art ◽

Phase 1 ◽

Phase 2 ◽

Two Phase ◽

Inductive Bias ◽

Fine Grained ◽

Wide Range ◽

Dynamic Experiments ◽

Novel Method ◽

Public Datasets

Fine-Grained Entity Typing (FGET) is a task that aims at classifying an entity mention into a wide range of entity label types. Recent researches improve the task performance by imposing the label-relational inductive bias based on the hierarchy of labels or label co-occurrence graph. However, they usually overlook explicit interactions between instances and labels which may limit the capability of label representations. Therefore, we propose a novel method based on a two-phase graph network for the FGET task to enhance the label representations, via imposing the relational inductive biases of instance-to-label and label-to-label. In the phase 1, instance features will be introduced into label representations to make the label representations more representative. In the phase 2, interactions of labels will capture dependency relationships among them thus make label representations more smooth. During prediction, we introduce a pseudo-label generator for the construction of the two-phase graph. The input instances differ from batch to batch so that the label representations are dynamic. Experiments on three public datasets verify the effectiveness and stability of our proposed method and achieve state-of-the-art results on their testing sets.

Download Full-text

Gastrointestinal Symptoms in Children With Life-Limiting Conditions Receiving Palliative Home Care

Frontiers in Pediatrics ◽

10.3389/fped.2021.654531 ◽

2021 ◽

Vol 9 ◽

Author(s):

Holger Hauch ◽

Peter Kriwy ◽

Andreas Hahn ◽

Reinhard Dettmeyer ◽

Klaus-Peter Zimmer ◽

...

Keyword(s):

Palliative Care ◽

Home Care ◽

Phase 1 ◽

Gastrointestinal Symptoms ◽

Phase 2 ◽

Palliative Home Care ◽

Asymptomatic Children ◽

Number Of Patients ◽

Gi Symptoms ◽

At Home

Context: Children with life-limiting diseases suffer from gastrointestinal (GI) symptoms. Since the introduction of specialized palliative home care (SPHC) in Germany, it is possible to care for these children at home. In phase 1 of care the aim is to stabilize the patient. In phase 2, terminal support is provided.Objectives: Analysis were performed of the differences between these phases. The causes and modalities/outcome of treatment were evaluated.Methods: A retrospective study was performed from 2014 to 2020. All home visits were analyzed with regard to the abovementioned symptoms, their causes, treatment and results.Results: In total, 149 children were included (45.9% female, mean age 8.17 ± 7.67 years), and 126 patients were evaluated. GI symptoms were common in both phases. Vomiting was more common in phase 2 (59.3 vs. 27.1%; p < 0.001). After therapy, the proportion of asymptomatic children in phase 1 increased from 40.1 to 75.7%; (p < 0.001). Constipation was present in 52.3% (phase 1) and 54.1% (phase 2). After treatment, the proportion of asymptomatic patients increased from 47.3 to 75.7% in phase 1 (p < 0.001), and grade 3 constipation was reduced from 33.9 to 15% in phase 2 (p < 0.05).Conclusion: Painful GI symptoms occur in both palliative care phases but are more common in phase 2. The severity and frequency can usually be controlled at home. The study limitations were the retrospective design and small number of patients, but the study had a representative population, good data quality and a unique perspective on the reality of outpatient pediatric palliative care in Germany.

Download Full-text

Sample study protocol for adapting and/or translating the 5C scale to assess the psychological antecedents of vaccination

10.31234/osf.io/we2zb ◽

2019 ◽

Author(s):

Cornelia Betsch ◽

Katrine Habersaat ◽

Sergei Deshevoi ◽

Dorothee K. Heinemeier ◽

Natalia Kostenko ◽

...

Keyword(s):

Study Protocol ◽

Cultural Context ◽

Phase 1 ◽

Collective Responsibility ◽

Phase 2 ◽

Two Phase ◽

Cultural Setting ◽

Original Group ◽

Vaccination Confidence ◽

Item Scale

Background: Published in 2018, the 5C scale is psychometrically validated to assess five psychological antecedents of vaccination (confidence, complacency, constraints, calculation, and collective responsibility). The original version offers a validated English and German scale to assess these determinants with a short 5-item scale (1 item per antecedent) and a long 15-item scale (3-items per antecedent). As the original group of authors has received several requests about how to adapt the scale to another country, language, or cultural context, this sample study protocol provides guidance for this process. Here, we propose a two-phase process of how to adapt the 5C scale to a new country, language, or cultural setting. Methods: Phase 1 comprises the translation and the adaptation to a specific cultural context (if necessary). Phase 2 involves the validation of the translated and potentially expanded scale. Discussion: Following the suggested study protocol will allow better comparability across the data obtained from the scale when used in different countries, languages, and contexts—even if slight changes in the wording of the items are necessary. The data obtained from the 5C scale allows monitoring the antecedents of vaccination, and detecting potentially early warning signals. Consequently, data obtained from the 5C scale can support developing, implementing, and evaluating an intervention. The materials and the syntax for data analysis to support the process described in this protocol are available in https://osf.io/2agxe/.

Download Full-text

Multi-institutional quality care initiative (QCI) to improve the care of patients with invasive bladder cancer (BlCa).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.298 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 298-298 ◽

Cited By ~ 2

Author(s):

Bernard H. Bochner ◽

Andrew Feifer ◽

Dahlia Sperling ◽

Joseph W Mashni ◽

Dean F. Bajorin ◽

...

Keyword(s):

Bladder Cancer ◽

Neoadjuvant Chemotherapy ◽

Phase 1 ◽

Quality Care ◽

Data Entry ◽

Background Level ◽

Fold Increase ◽

Phase 2 ◽

Two Phase ◽

Survey System

298 Background: Level 1 evidence supports a survival benefit for BlCa pts that receive periop cisplatin chemotherapy in addition to radical cystectomy (RC). Underutilization of multimodal therapy has been reported nationally. We instituted a multicenter QCI to improve the use of periop chemotherapy. Methods: A two phase effort was initiated at 16 academic institutions. Phase 1 was initiated in 2010 and designed to evaluate baseline patterns of periop chemotherapy use for T2-4N0M0 BlCa pts that underwent RC between 2003-2008. Phase 2 was a prospective QCI. The quality indicators included (1) referral to medical oncology for consideration of multimodality therapy, (2) neoadjuvant, if recommended, be cisplatin based and at least 3 cycles, (3) adjuvant, if recommended, be cisplatin based and at least 3 cycles, (4) all treatment be completed within 6 months. Data on all eligible pts were collected prospectively for 12 months on a web-based survey system. Results: All 16 centers participated in phase 1. Of 4,344 pts on whom data was available, 34% received periop chemotherapy. Neoadjuvant and adjuvant therapy use was 14% and 20%, respectively. 65% of pts receiving periop chemotherapy were treated with a cisplatin-based regimen. Of those treated neoadjuvantly, cisplatin was received in 70% of cases. Nine of the 16 institutions completed phase 2 data collection. Over 700 pts that underwent RC were evaluated. 395 pts with T2-4N0M0 disease were deemed eligible for data entry. Fifty-six percent of eligible pts received periop systemic chemotherapy. Of this 56%, 47% received neoadjuvant cisplatin chemotherapy and 9% received adjuvant cisplatin chemotherapy. This represented a 64.7% increase in the use of any periop chemotherapy and a 3.4 fold increase in neoadjuvant chemotherapy compared to baseline data. Conclusions: We have successfully completed a multi-institutional QCI to improve the use of periop chemotherapy in pts undergoing RC for resectable, non-metastatic bladder cancer. Our data demonstrates that significant improvements can be achieved in not only overall use of periop chemotherapy but most notably in the use of neoadjuvant chemotherapy.

Download Full-text