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We are increasingly facing in contemporary society significant debates over the nature and purpose of our institutions. In business, its purpose is often pitted between a shareholder maximization or stakeholder balance principle. This purpose discussion, however, too often fails to get to the underlying nature of the business institution itself, which entails how we understand who is in the business (individual vs. person) and its communal character (association vs. community). This essay describes the nature of a business on a continuum between an “association of individuals” and a “community of persons” and the various shadings in between. It is accepted as compelling that the nature of business is a “community of persons” and then lays out the principle of the common good as its purpose. Recognizing the various obstacles of the principle in relationship to business, we explain how the common good views the institutional goods that are particular to a business (good goods, good work, good wealth), and how these goods are ordered to human development (ordering principles, goods held in common, virtues).

The paper examines the problematic understanding of “risk” in entrepreneurial literature that locates courage in either the loss or gain of having or in the difficulty and hardship of the doing. We argue in this paper that what is lost in this vernacular view of courage is a deeper notion of the subjective dimension of work and the social need of society. Grounded within the Catholic social and moral tradition, we find a richer notion of courage, which in part corrects and rounds out the insufficient description of the vernacular understanding of courage in entrepreneurship. What we also find in this account of the virtues and subjective dimension of work is greater explanatory power of what happens to the entrepreneur in the work that he or she does. The end result of this analysis is a more spiritual, ethical and social understanding of entrepreneurship.

This article analyses the core sources of evidence that were claimed to underpin the wide-ranging reforms of the criminal justice system under the Criminal Justice Act 2003. Drawing from Foucault’s governmentality thesis, it argues that the processes of evidence collection and deployment did not comply with the government’s theoretical and methodological dictates of ‘evidence-based-policy’ as a guiding principle in all public policymaking. On the contrary, the parameters of the exercise were framed in such a way that critical evidence that questioned the wisdom of many of the planned reforms on the grounds that they will cause miscarriages of justice was completely disregarded. It is, therefore, concluded that the Criminal Justice Act (2003) is not ‘non-ideological’ as claimed. Rather, it symbolizes a governmental technique (in the Foucauldian sense) to transform ideology into discourse, which then provides the legitimate authority to force through the intended reform agenda.

This article analyses key documents that were produced in collaboration between the Prison Service and the Prison Reform Trust. It identifies an organisational inability on the part of the Prison Service and the Parole Board to acknowledge that the courts can return incorrect verdicts and that wrongful imprisonment can, and does occur. It argues that this renders the ways in which the Prison Service and the Parole Board deal with life prisoners who maintain that they are innocent of the crimes for which they were convicted untenable. To demonstrate this, the article distinguishes two broad categories of wrongful imprisonment. It concludes that those charged with a duty of care for, and the possible release of, those given custodial sentences by the courts must, therefore, be prepared to 'think the unthinkable' and make adequate provision for the innocent victims of wrongful imprisonment that are sure to come their way.

This article confronts a perennial question raised by critical criminologists, namely, what part do critical counter-discourses play in the exercise of dominant forms of power in the sphere of criminal justice? In specific terms, it analyses some of the key sources of critical socio-legal counter-discourse that were produced and deployed in response to the most recent governmental review of the criminal justice system on the problem of miscarriages of justice in England and Wales. In so doing, it draws from Foucault’s theses on power, resistance and governmentality and suggests an alternative reading of the relations of power and the role and rationality of governmental intervention in the legislative framework of the criminal justice system. In light of this, it is argued that the reform of the criminal justice system should not only or merely be viewed as a ‘damage limitation exercise’ by a repressive state attempting to ‘betray’ the public to retain or reproduce its power. On the contrary, reform of the criminal justice system might, also, fruitfully be seen as part of a process that is initiated when the governmental conditions are right; a process which can, also, present opportunities to achieve progressive reforms.

This article confronts a question that has barely received any attention at all: What precisely constitutes a miscarriage of justice' in England and Wales? It revives two complimentary human-rights-based perspectives that have lain dormant for almost a decade and brings them into dialogue with Foucault's theoretical note on the need to unearth subjugated discourses that interrupt and disturb dominant ways of thinking. It redefines miscarriages of justice to include all successful appeals against criminal conviction, to provide a more adequate depiction of justice in error'. It emphasizes the need for future research on routine successful appeals, to unearth and give voice' to a plethora of anti-discourses' on wrongful criminal conviction that are not currently articulated.

This short article details the birth of the Innocence Network UK, outlining the circumstances of its launch, and identifying the need for the establishment of innocence projects within universities in the UK. We examine potential benefits to students, (in addition to the wrongfully convicted and their supporters), and the impact to date of Innocence Networks in the US and Australia. We conclude with an invitation to the legal educational fraternity to support this essential, timely, and highly beneficial initiative.

Entrepreneurship is a critical need in society, and an entrepreneur's life can be a life wonderfully lived. However, most of the literature examining entrepreneurship takes an overly narrow financial viewpoint when examining entrepreneurship and entrepreneurial success. Our paper surveys the current entrepreneurial literature on what constitutes successful entrepreneurship. We then engage key conceptual ideas within the Catholic social tradition to analyze what we see as an undeveloped notion of success. We then move to construct a richer notion of success through the framework of virtue.

The detailed mechanism behind the processes of DNA-dependent RNA transcription initiation is largely unknown. When transcription initiation factors bind DNA, a significant change in the electrostatic state of the complex can result. Using electrical capacitance measurements of solutions of the YY1 zinc finger transcription initiation factor and the adeno-associated viral P5 promoter DNA, we observed a specific dielectric change when a protein-DNA complex was formed. We propose that complexation results in electrostatic changes that may trigger the markedly different electrical behavior, and offer a possible explanation for our results.

Rectally administered medications are essential in palliative medicine, particularly in the last days of life. They are underutilized. The pharmacology of rectally administered medications relates not only to the medication but also to the suppository base, additives, drug ionization, pK a, absorptive surface of the rectum, and rectal health. The pharmacokinetics may differ from those of orally administered medications owing to reduced hepatic first-pass clearance. In this review the pharmacology of rectally administered palliative medications is reviewed and the use of individual drugs is outlined.

Prostate cancer is the second leading cause of cancer death in men. Screening and advances in the treatment of localized disease may help reduce the burden of this disease. Unfortunately, despite progress in these areas, a significant number of men continue to present with advanced disease or to develop advanced disease at some time after treatment for their local disease. The treatment of advanced or metastatic prostate cancer is systemic therapy. The mainstay of systemic therapy for prostate cancer has been hormonal therapy for many years. Orchiectomy and estrogens were the initial hormonal therapies used. Over the past several years a number of agents have been shown to produce similar rates of disease control with improved tolerability profiles. The luteinizing hormone releasing hormone (LHRH) agonists are the most frequently used hormonal agents in prostate cancer. Antiandrogens have also been used as single agents, or in combination with LHRH agonists. Soon LHRH antagonists may come into clinical practice. When hormone therapy fails to control this disease, chemotherapy is the next line of treatment. Over the past several years, several newer chemotherapy agents have renewed enthusiasm for this avenue of treatment in prostate cancer. Novel agents utilizing a variety of recently identified mechanisms of action are likely to become clinically relevant in the treatment of prostate cancer over the next few years. This review seeks to address the major issues relating to the pharmacological treatment of advanced prostate cancer.

Introduction: MutHER is a phase II trial that demonstrated the anti-tumor activity of the pan-HER inhibitor neratinib in HER2mut, non-amplified MBC. The major challenges to accrue to this trial were the large number of pts to screen for the 2-3% HER2mut population and the high rate (24%) of poor quality tumor DNA for sequencing. The goals of this ctDNA study were: 1) the concordance of HER2mut detected by ctDNA versus tumor testing; 2) the incidence of ctDNA HER2mut in HER2 non-amplified MBC; 3) changes in HER2mut variant allele frequency (VAF) on neratinib therapy. Methods: A sample size of 30 negative (neg) controls was needed to ensure 90% confidence if ctDNA testing has >90% specificity in detecting HER2mut. Thus, plasma from MBC pts obtained at screening for MutHER trial (Neg control: 40 pts without HER2mut on tumor testing; Positive (pos) control: 14 pts with known HER2mut who received neratinib) were subjected to Guardant360 ctDNA 70-gene panel sequencing (all exons of HER2 included). ctDNA from the 14 neratinib treated pts were also analyzed at week (wk) 4 and upon progression. ctDNA data from MBC pts clinically tested at Guardant Health were interrogated for HER2mut incidence. Results: Among the 14 pts with tumor pos for HER2mut, ctDNA sequencing identified the same HER2mut in 11, discrepant HER2mut in 1, and neg in 2. The 2 pts with ctDNA neg for HER2mut had progressive disease (PD) and stable disease (SD > 6 months) on neratinib, respectively. Among the 40 neg controls, 8 were not evaluable (no detectable ctDNA or assay unsuccessful) and all 32 successfully sequenced cases were neg for HER2mut. The sensitivity and specificity of ctDNA for HER2mut detection was 11/14 (79%, 90% CI: 53-94%) and 32/32 (100%, 90% CI: 91-100%), respectively. Among the 11 paired baseline and wk 4 samples, 9 (82%) had lower HER2mut VAFs at wk 4 than at baseline, with 1 complete response (CR), 1 partial response (PR), 5 SD, and 4 PD at wk 8 as best tumor response. Two pts had higher wk 4 ctDNA HER2mut VAFs and both had radiographic PD at wk 8. The absolute HER2mut VAF levels at wk 4 were significantly associated with TTP (Spearman rho=-0.69, p=0.02) and tumor size change (rho=0.67, p=0.05). The HER2mut VAFs were significantly higher at progression than wk 4 in all pts (p Conclusions: ctDNA sequencing is sensitive and highly specific in detecting HER2mut, offering a non-invasive method to identify pts for trials of HER2mut-targeted therapy. Decreased HER2mut VAFs at wk 4 was observed in 82% of cases, consistent with the on-target effect of neratinib. Increased HER2mut VAFs at wk 4 is a potential early marker of progression. Citation Format: Cynthia Ma, Ron Bose, Feng Gao, Rachel Freedman, Melinda Telli, Gretchen Kimmick, Eric Winer, Michael Naughton, Matthew Goetz, Christy Russell, Debu Tripathy, Melody Cobleigh, Andres Forero, Timothy Pluard, Carey Anders, Shana Thomas, Jill Anderson, Caroline Bumb, Kimberly Banks, Richard Lanman, Richard Bryce, Alshad Lalani, John Pfeifer, Daniel Hays, Mark Pegram, Kimberly Blackwell, Philippe Bedard, Hussam Al-Kateb, Matthew Ellis. Circulating tumor DNA (ctDNA) sequencing for HER2 mutation (HER2mut) screening and response monitoring to neratinib in metastatic breast cancer (MBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT011. doi:10.1158/1538-7445.AM2017-CT011

Purpose: Mammaglobin-A (MAM-A) is overexpressed in 40% to 80% of primary breast cancers. We initiated a phase I clinical trial of a MAM-A DNA vaccine to evaluate its safety and biologic efficacy. Experimental Design: Patients with breast cancer with stable metastatic disease were eligible for enrollment. Safety was monitored with clinical and laboratory assessments. The CD8 T-cell response was measured by ELISPOT, flow cytometry, and cytotoxicity assays. Progression-free survival (PFS) was described using the Kaplan–Meier product limit estimator. Results: Fourteen subjects have been treated with the MAM-A DNA vaccine and no significant adverse events have been observed. Eight of 14 subjects were HLA-A2+, and the CD8 T-cell response to vaccination was studied in detail. Flow cytometry demonstrated a significant increase in the frequency of MAM-A–specific CD8 T cells after vaccination (0.9% ± 0.5% vs. 3.8% ± 1.2%; P < 0.001), and ELISPOT analysis demonstrated an increase in the number of MAM-A–specific IFNγ-secreting T cells (41 ± 32 vs. 215 ± 67 spm; P < 0.001). Although this study was not powered to evaluate progression-free survival (PFS), preliminary evidence suggests that subjects treated with the MAM-A DNA vaccine had improved PFS compared with subjects who met all eligibility criteria, were enrolled in the trial, but were not vaccinated because of HLA phenotype. Conclusion: The MAM-A DNA vaccine is safe, capable of eliciting MAM-A–specific CD8 T-cell responses, and preliminary evidence suggests improved PFS. Additional studies are required to define the potential of the MAM-A DNA vaccine for breast cancer prevention and/or therapy. Clin Cancer Res; 20(23); 5964–75. ©2014 AACR.

Purpose: Veliparib, a PARP inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase I trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase II trial to determine the response rate of veliparib in combination with cyclophosphamide compared with cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC). Experimental Design: Adult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the combination was allowed at disease progression. Results: Seventy-five patients were enrolled and 72 were evaluable for response; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen. Treatment was well tolerated. One complete response was observed in each arm, with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm. Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair; none of the detected genetic alterations were significantly associated with treatment benefit. Conclusion: This is the first trial that evaluated single-agent, low-dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression-free survival. Clin Cancer Res; 21(7); 1574–82. ©2015 AACR.

This study aimed to determine the maximum-tolerated dose and dose-limiting toxicities of pegylated liposomal doxorubicin (PLD) in combination with temsirolimus (T) in patients with refractory solid tumors. Using a standard “3+3” dose escalation design, 23 patients were enrolled in three dosing cohorts in this phase I study. The starting dose level was PLD at 30 mg/m2 every 4 weeks and T at 20 mg weekly. Pharmacokinetics (PK) of doxorubicin were evaluated for patients in the expansion cohort. The most common treatment-related adverse events of all grades were mucositis/stomatitis (69.6 %), anorexia (52.2 %), thrombocytopenia (52.2 %), and fatigue (47.8 %). The recommended doses of this combination for phase II studies are 25 mg/m2 PLD and 25 mg T. PK analyses suggested increased exposure of doxorubicin in this combination regimen compared to doxorubicin administered as a single agent, possibly due to PK drug interactions. Out of 18 patients evaluable for a treatment response, two had partial responses (PR) (breast cancer and hepatocellular carcinoma) and six had stable disease (SD). Two patients remained on treatment for more than 1 year. The combination of PLD and T is tolerable, and the treatment resulted in clinical benefit. The combination regimen should be further explored in appropriate tumor types. Electronic supplementary material The online version of this article (doi:10.1007/s00280-014-2493-x) contains supplementary material, which is available to authorized users.

Purpose: Scatter factor (SF), also known as hepatocyte growth factor (HGF), has been shown to induce proliferation, scattering and invasiveness in human prostate cancer cell lines. In this study we determined the serum level of SF-HGF in men with metastatic prostate cancer compared to those with localized prostate cancer and without prostate cancer.Materials and Methods: Serum samples were obtained from men with biopsy proved adenocarcinoma of the prostate and radiographic evidence of metastatic disease, those with biopsy proved adenocarcinoma of the prostate and clinically localized disease, and those with negative sextant prostate biopsies. Serum SF-HGF was determined using a commercially available enzyme-linked immunosorbent assay kit.Results: Of the 108 men enrolled in our study 52 had negative sextant biopsies, 36 had clinically localized cancer and 20 had metastatic disease. The serum level in men with metastatic disease was significantly elevated (mean 2,117 pg./ml., range 820 to 6,403) compared to...

Background BKM120, an oral pan-Phosphatidylinositol-3-kinase (PI3K) inhibitor, plus fulvestrant (F) induced synergistic anti-tumor effect in preclinical studies of estrogen receptor positive (ER+) breast cancer. We therefore conducted a phase I trial of BKM120 and F in postmenopausal women with ER+ metastatic breast cancer (MBC) to determine the maximum tolerated dose (MTD), tolerability and preliminary efficacy. Methods A 3+3 phase I design was chosen for phase IA with BKM120 administered orally to define MTD [Table 1]. Cycle (C) length was 28 days. F 500mg was administered intramuscularly on C1 day (D)1 and D15 then on D1 of each subsequent cycles. Two expansion cohorts, phase IB (intermittent dosing: 5 days on and 2 days off) and Cohort C (continuous dosing: daily) of BKM120 at MTD, was initiated to further assess the tolerability and efficacy. Patients (pts) with ER+ MBC with measurable disease were eligible. No more than 3 lines of systemic therapy in the metastatic setting were allowed in phase 1B or Cohort C. Tumor measurement occurred every 3 cycles. Adverse events (AEs) were assessed by CTCAE 4.0 and response by RECIST 1.1. Results Thirty one pts, with median age of 58 (range: 34-71) years, prior exposure to a median of 1 (range: 0-9) endocrine and 0 (range: 0-2) chemo regimens, were enrolled. Majority of pts (83%) had visceral metastasis. Thirty, 25, and 22 pts were evaluable for AE, response and clinical benefit (CB), respectively. Most C1 AEs were grade (G)1 or 2, except 1 G3 diarrhea. No DLT occurred in C1. However, G2/3 AEs required BKM120 interruption and/or reduction in C2 or beyond occurred in 16 (53%) pts, including 9 ALT/AST elevation (G2 10%, G3 17%, G4 3%), 7 rash (G3 23%), and 1 pt each with G2 confusion, G3 hyperglycemia, G2 pneumonitis, and G3 tremor. As of June 3, 2014, 1 pt withdrew consent, 19 pts discontinued therapy due to progressive disease (PD) (n=15) or AE (n=4), 11 pts continue to receive BKM120/F. Fourteen (63.6%, 95% CI: 43.0 - 80.3%) of the 22 evaluable pts derived CB, including 7 partial response (PR) and 7 prolonged stable disease (SD) > 6 months. Archival tumor and circulating tumor DNA are being analyzed for presentation. Data will be updated. Table 1 Study enrollment and resultsCohortNBKM120N pt BKM120 interrupted/reduced (AE)*PDPR (Cycle completed)SD (Cycle completed)NE1A DL1380 mg daily2 (confusion, ALT)101 (22)1 (a)1A DL26100 mg daily3 (ALT, rash)22 (13,3 (a))2 (9, 7)01A DL2b2100 mg intermittent0002 (6, 6)01B10100 mg intermittent6 (AST, ALT, rash Hyperglycemia)02 (15+, 12)5 (16+, 9+, 9, 6, 6)3 (a, a, b)C10100 mg daily5 (rash, ALT, diarrhea, tremor)23 (9+, 8+, 4+)3 (3+, 3+, 3+)#2 (1+, 2+)Total (N)31 1657136*All occurred in C2+ except the diarrhea, CBR: 63%, NE: Not evaluable, a: off due to AE, b: withdrew consent, # NE for CBR Conclusion BKM120 100mg, administered daily or intermittently, plus F was tolerable without DLT during C1. Grade 2/3 AST/ALT and rash were common in both dosing schedules in subsequent cycles resulting in BKM120 interruption/reduction. Promising activity observed in this trial warrants further development of this combination in ER+ BC. Phase III studies are ongoing in pts with ER+ MBC progressed on aromoatase inhibitor. Citation Format: Cynthia X Ma, Jingqin Luo, Michael Naughton, Foluso Ademuyiwa, Rama Suresh, Timothy Pluard, Gayathri Nagaraj, Kaitlin Arnold, Craig Lockhart, Matthew J Ellis. A phase I study of BKM120 and fulvestrant in postmenopausal women with estrogen receptor positive metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD5-6.

Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy.Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypTcT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls.76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%).This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.

Purpose To prospectively examine quality of life (QOL) of patients with early stage breast cancer treated with accelerated partial breast irradiation (APBI) using high-dose-rate (HDR) interstitial brachytherapy. Methods and Materials Between March 2004 and December 2008, 151 patients with early stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients included those with Tis-T2 tumors measuring ≤3 cm excised with negative surgical margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. QOL was measured using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, version 3.0, and QLQ-BR23 questionnaires. The QLQ-C30 and QLQ-BR23 questionnaires were evaluated during pretreatment and then at 6 to 8 weeks, 3 to 4 months, 6 to 8 months, and 1 and 2 years after treatment. Results The median follow-up was 55 months. Breast symptom scores remained stable in the months after treatment, and they significantly improved 6 to 8 months after treatment. Scores for emotional functioning, social functioning, and future perspective showed significant improvement 2 years after treatment. Symptomatic fat necrosis was associated with several changes in QOL, including increased pain, breast symptoms, systemic treatment side effects, dyspnea, and fatigue, as well as decreased role functioning, emotional functioning, and social functioning. Conclusions HDR multicatheter interstitial brachytherapy was well tolerated, with no significant detrimental effect on measured QOL scales/items through 2 years of follow-up. Compared to pretreatment scores, there was improvement in breast symptoms, emotional functioning, social functioning, and future perspective 2 years after treatment.

Business education at a Catholic university should engage students and faculty across the university in critically examining the purpose of business in society. Following the best practices of leading business schools, the Catholic business curriculum has mostly focused on the shareholder and stakeholder approaches - with the shareholder approach being the predominant view. Creatively engaging the Catholic Social Tradition (especially the “community of persons”) can bring a richer appreciation of the purpose of business in our contemporary society than either the shareholder or stakeholder approaches. We argue that far more discretion to pursue various corporate purposes in manifold ways exists than is frequently appreciated by business managers and those who educate them. This article examines how, given this legal and moral discretion, the Catholic Social Tradition is a rich resource for teaching corporate purpose, and reveals how tapping into a religious tradition with a long philosophical discourse can shape a rich dialogue in the curriculum as to a company’s moral direction. We contrast two philosophies of business: an Association of Individuals (the shareholder and stakeholder approaches) and a Community of Persons (mission-centric approach), and their respective views of corporate purpose. While business scholars tend not to question their underlying anthropological presuppositions because of the desire to be “practical,” a business education grounded in the liberal arts must engage the first principles of its discourse.

How one structures an organization is not only important from the perspective of productivity and efficiency, but primarily how it affects the moral formation of those who are employed in that organization. Organizational structures whether in the manufacturing, service or non-profit sector have moral dimensions that cannot be escaped. Papal social tradition has been concerned about the moral formation of all workers within the organization. This tradition has maintained that an essential component to a humane organizational structure is participation of those involved in the organization, and consequently that participation must be understood primarily in terms of the formation of employees. This article explores the papal social tradition's understanding of participation and examines its significance in today's organizational environment, particularly in reference to work-teams.

This paper is an insighful critique of the shareholder and stakeholder models of organizational purpose. The authors emphasize that both these models fail to serve as an adequate basis for explaining the purpose of an organization and are unable to capture a fuller meaning of living in an organizational community. The paper thus endeavours to introduce into the mainstream of discussion a third model, based on the idea of the common good which draws inspiration from the communitarian Catholic tradition. The first part of this paper traces the idea of common good as it relates to organizations. The second part engages the common good tradition with the shareholder and stake holder models. The paper goes on to describe common good within the organization through three propositions: fundamentality, excellence and integration. The authors reiterate, however, that the idea of the common good does not provide a micro-blueprint for managers, but rather an orientation or moral compass that directs organizational activity towards human development.

Background: Patients with TNBC who do not achieve a pathologic complete response (pCR) or near pCR have high rates of relapse, due to chemotherapy resistance, within the first few years after their diagnosis. Molecular biomarkers predictive for chemotherapy sensitivity are lacking. This ongoing trial is evaluating carboplatin and docetaxel in the neoadjuvant setting to determine whether these drugs will increase the pCR rate compared to historical controls. Correlative studies include exome and transcriptome sequencing on samples acquired from patients as a means to decipher the genomic architecture and clonal evolution of those who achieved a pCR compared to those who did not. The simultaneous development of patient derived xenografts (PDX) from host tumors is also planned. Methods: Patients with clinical stage 2 or 3 histologically confirmed TNBC will receive six cycles of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 every 3 weeks, followed by definitive surgery. Forty-one eligible patients will be treated according to this protocol, permitting us to attain a power of 83% to detect our expected pCR rate of 54% compared to the historical 35% rate, based on a two-sided exact binomial test at the 4.8% significance level. Eligibility: tumor size at least 2 cm, adequate organ and bone marrow function, no bilateral or inflammatory breast cancer, no invasive cancer within 5 years, ECOG performance status of ? 2, no prior sentinel lymph node biopsy. Tissue collection for xenografting and correlative studies will occur at baseline, at cycle 1 day 3, and at surgery. The primary objective is to determine the pCR rate, defined as the absence of invasive cancer in breast or nodes at definitive surgery. Secondary and exploratory objectives include xenografting rates, evaluation of mutational signatures of chemotherapy resistance and response, and comparison of chemotherapy responses between patients and their xenografts. The study was activated on 7/7/2014 and is still recruiting. Twenty (48.8% of planned 41) patients have been enrolled and have had baseline tissue banked. Fourteen patients have completed protocol therapy. Three patients have tissue at all 3 time points (9 samples), and are presently being studied by exome and transcriptome sequencing. Citation Format: Foluso O. Ademuyiwa, Shunqiang Li, Jingqin Luo, Tracy Skinner, Jason Hoshower, Cynthia X. Ma, Katherine Weilbaecher, Michael Naughton, Leonel Hernandez-Aya, Elaine R. Mardis, Matthew J. Ellis. A neoadjuvant co-clinical trial in triple-negative breast cancer patients with genomic discovery analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT091.

TPS1099Background: Patients with TNBC who do not achieve a pathologic complete response (pCR) or near pCR have high rates of relapse, due to chemotherapy resistance, within the first few years afte...

516Background: HER2 mutation occurs in ~2% of breast cancer (BC). Preclinical models suggested neratinib, an irreversible HER2/EGFR tyrosine kinase inhibitor, could be an effective treatment. This trial was conducted to assess the clinical benefit rate (CBR), defined as complete response (CR), partial response (PR) or stable disease (SD) ≥ 6 months (mo.), for neratinib in patients (pts) with HER2mutMBC (NCT01670877). Methods: This single arm phase II trial employed the Simon’s Optimal 2-stage design (1st stage: n=10, 2nd stage: n=19) to detect CBR of 20% versus the null hypothesis of 5% (80% power, 1-sided alpha 0.05). The primary endpoint is met if ≥ 4 CB is observed. Eligibility required the presence of somatic HER2mut and absent HER2 amplification. Activating HER2mut by in vitro study was required in the 2nd stage. Pts received neratinib 240 mg PO daily (28-day cycle) with prophylactic loperamide. Response was assessed every 2 cycles by RECIST 1.1. Enrollment was stopped early due to a protocol amendme...

Background ER+ BC is associated with activated CDK4/6. The CDK4/6 inhibitor palbociclib (P) markedly improves time to progression in advanced ER+HER2- BC. We conducted a neoadjuvant phase II trial to determine the activity of P in primary breast cancer as a prelude to adjuvant studies. Methods To assess molecular changes induced by anastrozole (A) or P+A, patients (pts) were treated initially with A alone (1mg PO daily) for 28 days in cycle 0 (C0) before the addition of P (125mg PO daily on D1-21 each cycle) on C1D1. P+A was administered for 4 28-day cycles followed by C5 with A alone for 2-4 weeks (wks) before surgery. P was added in C5 for 10-12 days immediately prior to surgery in the last 20 pts enrolled to assess molecular changes induced by A, either alone or in combination with P immediately prior to surgery, in resected tumor. Goserelin was added in premenopausal pts. Research tumor biopsies were obtained at baseline, C1D1, and C1D15. Central Ki67 analysis was performed at all timepoints, those with Ki67 >10% at C1D15 went off study treatment. The primary endpoint was complete cell cycle arrest (CCA), defined as Ki67 50% improvement over A in CCA rate on C1D15 biopsy (44% with A alone based on historical data, vs 66% with P+A, power = 0.8, alpha=0.05). The primary endpoint is met if >20 pts achieved CCA in this cohort. Correlative endpoints included assessment of markers of proliferation, apoptosis, senescence, Rb, gene expression microarray, intrinsic subtype, and next generation sequencing of 83-gene panels, which will be reported at the meeting. Results Between 4/23/2013 and 4/24/2015, 50 pts (33 PIK3CA WT, 11 PIK3CA Mut, 2 pending, 4 tissue quantity or quality not sufficient for sequencing (QNS)) were enrolled to the study. Median age was 57.5 (range: 34.1–79.6) years. Four pts, all with WT PIK3CA, went off study due to Ki67 >10% on C1D15 biopsy, 26 pts completed treatment and surgery, 1 refused surgery, 3 withdrew study treatment in C1, and 16 continued to receive study drug (2 in C0, 3 in C1, 4 in C2, 5 in C3, 1 in C4, and 1 in C5). Among the 40 pts currently evaluable for the primary endpoint (C1D15 Ki67), CCA occurred in 34 (85%) pts, including 9 of 9 (100%) PIK3CA Mut, 22 of 28 (78.5%) WT, and 3 of 3 QNS pts. Preliminary analysis of available data indicated a significantly lower Ki67 value after 2 wks of P+A (C1D15) compared to that on A alone (C1D1) (p=0.034, n=18). Conclusion This study met the primary endpoint demonstrating that P+A is a highly effective anti-proliferative combination. The sequential biopsy design clearly demonstrated that P+A increased cell cycle control over A alone. P+A was effective regardless of PIK3CA mutation status and these results support the evaluation of this combination in the adjuvant setting for ER+HER2- BC. Citation Format: Ma CX, Gao F, Northfelt D, Goetz M, Forero A, Naughton M, Ademuyiwa F, Suresh R, Anderson KS, Margenthaler J, Aft R, Hobday T, Moynihan T, Gillanders W, Cyr A, Eberlein TJ, Hieken T, Krontiras H, Hoog J, Han J, Guo Z, Vij K, Mardis E, Al-Kateb H, Sanati S, Ellis MJ. A phase II trial of neoadjuvant palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with anastrozole for clinical stage 2 or 3 estrogen receptor positive HER2 negative (ER+HER2-) breast cancer (BC). [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 S6-05.

The Faith at Work Scale (FWS) is a 15-item measure of faith and work integration, inspired by Judaeo-Christian thought. The valid and reliable single-factor scale draws on five dimensions of work and faith—relationship, meaning, community, holiness, and giving. Recently released, the FWS is being employed in multiple studies exploring the intersection of work and faith. The scale, its development, and its approach to workplace spirituality are described in this chapter, along with the findings of research employing the scale and potential directions for future research in workplace faith.

Purpose To prospectively evaluate cosmetic outcomes in women treated with accelerated partial breast irradiation using high-dose-rate interstitial brachytherapy for early-stage breast cancer. Methods and Materials Between 2004 and 2008, 151 patients with early-stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients had stage Tis-T2 tumors of ≤3 cm that were excised with negative margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. Both the patients and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA). Patients also reported their satisfaction with treatment over time. Results Median follow-up was 55 months. The rates of excellent-to-good cosmesis reported by patients and the treating radiation oncologist were 92% and 97% pretreatment, 91% and 97% at 3 to 4 months' follow-up, 87% and 94% at 2 years, and 92% and 94% at 3 years, respectively. Breast infection and adjuvant chemotherapy were independent predictors of a fair-to-poor cosmetic outcome at 3 years. Compared to pretreatment pBRA (7.35), there was no significant change in pBRA over time. The volume receiving more than 150 Gy (V150) was the only significant predictor of pBRA. The majority of patients (86.6%) were completely satisfied with their treatment. Conclusions Patients and the treating physician reported a high rate of excellent-to-good cosmetic outcomes at all follow-up time points. Acute breast infection and chemotherapy were associated with worse cosmetic outcomes. Multicatheter interstitial brachytherapy does not significantly change breast size as measured by pBRA.

Background Brachytherapy as adjuvant treatment for early-stage breast cancer has become widely available and offers patients an expedited treatment schedule. Given this, many women are electing to undergo brachytherapy in lieu of standard fractionation radiotherapy. We compare outcomes between patients treated with accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy versus patients who were also eligible for and offered APBI but who chose whole breast radiation (WBI). Methods Patients treated from December 2002 through May 2007 were reviewed. Selection criteria included patients with pTis-T2N0 disease, ≤ 3 cm unifocal tumors, and negative margins who underwent breast conservation surgery. Local control (LC), cause-specific (CSS) and overall survival (OS) were analyzed. Results 202 patients were identified in the APBI cohort and 94 patients in the WBI cohort. Median follow-up for both groups exceeded 60 months. LC was 97.0% for the APBI cohort and 96.2% for the WBI cohort at 5 years (ns). Classification by 2010 ASTRO APBI consensus statement categories did not predict worse outcomes. Conclusion APBI via multicatheter interstitial brachytherapy provides similar local failure rates compared to WBI at 5 years for properly selected patients. Excellent results were seen despite the high fraction of younger patients (< 60 years old) and patients with DCIS.

If you were to ask the ‘person in the street’ what he or she wants from the criminal justice system, the reply is more than likely going to be that it should convict the guilty and acquit the innocent; and, if it should happen that an innocent person is convicted in ‘error’, then most people would probably think that the appeals system should operate to overturn the conviction in a speedy fashion to reduce the harm that was caused to the victim and his or her family and friends and restore the legitimacy of the criminal justice system. The idea that the criminal justice system should be about convicting the guilty and acquitting the innocent is reflected in political statements about how the system should function and it is transmitted in portrayals of wrongful convictions and wrongful acquittals in the media. Perhaps most significantly, the history of the criminal justice system is peppered with high profile media campaigns for alleged victims of wrongful convictions who were believed to be innocent, which have helped to shape some of the most significant changes to the structures that govern how the system operates.

Preclinical models suggested that activating mutations of the PIK3CA gene are associated with sensitivity to inhibitors of the mammalian target of rapamycin (mTOR). In breast cancers, PIK3CA mutations are associated with estrogen receptor (ER) positivity. We therefore performed an open-label single arm phase II study of the rapamycin analog, temsirolimus, at a dose of 25 mg weekly, in women with pretreated breast cancers that were positive for ER, PR, or HER2. Archived formalin-fixed paraffin embedded tumor was collected for immunohistochemical evaluation of components of the PI3K/Akt/mTOR pathway and PIK3CA mutation analysis. Thirty-one patients were enrolled. There were no major objective responses; however, three patients had stable disease for over 24 weeks. Twenty-three tumor samples were available for mutational analysis. There were five tumors with PIK3CA mutations; no association was found between prolonged stable disease and PIK3CA mutation or any immunohistochemical marker. There was a trend toward improved progression free survival (PFS) for patients with positive nuclear staining for phospho-Akt308. One patient remains on study four and a half years after starting therapy; her tumor did not have a PIK3CA mutation. We conclude that single agent temsirolimus has minimal activity in a population of women with heavily pretreated breast cancer. We found no evidence that either absence of immunohistochemical staining for PTEN or mutations in the hotspot domains of PIK3CA in the primary tumor were associated with clinical benefit.

This article draws upon 100 years of writings which are referred to as the Catholic Social Tradition (CST). Using this tradition as a guide, the nature of work is explored along with the principles and virtues which vitalize the deepest dimension of work — how it affects the dignity of the human person. It develops five operational ethical principles which can be applied to questions of workplace ethics. Organizational policies and programs that seem consistent with CST are also discussed.