A preliminary study of the probitive value of personality assessment in medical school admissions within the United States.

BACKGROUND: Allopathic medicine faces a daunting challenge of selecting the best applicants because of the very high applicant / matriculant ratio. The quality of graduates ultimately reflects the quality of medical practice. Alarming recent trends in physician burnout, misconduct and suicide raise questions of whether we are selecting the right candidates. The United States (US) lags far behind the United Kingdom (UK) and Europe in the study of non-cognitive tests in medical school admissions. Although more recently, medical schools in both the UK, Europe and the US have begun to use situational judgement tests such as the Computer-Based Assessment for Sampling Personal Characteristics (CASPer) and the situational judgement test (SJT), recently developed by the Association of American Medical Colleges (AAMC) and that these tests are, in a sense non-cognitive in nature, direct personality tests per se have not been utilized. We have historically used, in the admissions process within the US, knowledge, reasoning and exam performance, all of which are largely influenced by intelligence and also improved with practice. Personality, though also undoubtedly influenced by intelligence, is fundamentally different and subject to different kinds of measurements. METHODS: A popular personality measurement used over the past two decades within the US in business and industry, but not medical school has been the Neo Personality Inventory - Revised (NEO-PI-R) Test. This test has not been utilized regularly in allopathic medicine probably because of the paucity of exploratory retrospective and validating prospective studies. The hypothesis which we tested was whether NEO-PI-R traits exhibited consistency between two institutions and whether their measurements showed probative value in predicting academic performance. RESULTS: Our retrospective findings indicated both interinstitutional consistencies and both positive and negative predictive values for certain traits whose correlative strengths exceeded traditional premed metrics: medical college admission test (MCAT) scores, grade point average (GPA), etc. for early academic performance. CONCLUSIONS: Our exploratory studies should catalyze larger and more detailed confirmatory studies designed to validate the importance of personality traits not only in predicting early medical school performance but also later performance in one's overall medical career.

The virtues of the virtual medical school interview.

The COVID-19 pandemic has mandated the use of virtual interactions in medical school. Although this falls mainly in the area of didactic instruction, of necessity, it has extended to the critical Admissions Process and the Medical School Interview itself. The California University of Science and Medicine (CUSM) with their flipped classroom approach had previously entered a virtual space of instruction even before COVID-19. Because CUSM was, in a sense, already committed to 'virtual' education, in the face of the COVID-19 pandemic, CUSM focused not on what it might lose but what it might gain and what their applicants to medical school might gain with the virtual format. The COVID-19 pandemic provided a unique opportunity to initially compare the Virtual Interview with the traditional On-Campus (In-Person) Interview during the hybrid 2020 year when the COVID-19 pandemic began. The Virtual Interview was patterned after the On-Campus Interview with some modifications. The same faculty conducted both interviews. A number of inherent advantages of the Virtual Interview surfaced to these faculty interviewers based on their subjective observations and conclusions. The overall interviewee satisfaction with the Virtual Interview was very positive based on their subjective observations and conclusions. The objective data from the Virtual Interviews compared to the On-Campus Interviews in the hybrid year resulted in a greater percentage of both offers of acceptance (p = .001) and matriculations (p = .001). In order to strengthen our initial observations, we expanded our study to include 2 pre-COVID-19 years (2018, 2019) of exclusively On-Campus interviews (n = 743) and 1 additional COVID-19 year (2021) of exclusively Virtual Interviews (n = 529). In this expanded study, interviewee demographics were not confounding and the Virtual Interview gave rise to overall greater interviewee satisfaction (p = .001), a trend to greater interviewer satisfaction and a greater percentage of both offers of acceptance (p = .047) and matriculations (p = .036).

Use of constitutive and inducible oncogene-containing iPSCs as surrogates for transgenic mice to study breast oncogenesis.

BACKGROUND: Powerful constitutive and inducible transgenic / bitransgenic / tritransgenic murine models of breast cancer have been used over the past two decades to shed light on the molecular mechanisms by which the given transgenic oncogenes have interacted with other cellular genes and set in motion breast cancer initiation and progression. However, these transgenic models, as in vivo models only, are expensive and restrictive in the opportunities they provide to manipulate the experimental variables that would enable a better understanding of the molecular events related to initial transformation and the target cell being transformed. METHODS: To overcome some of these limitations, we derived oncogene-containing induced pluripotent stem cell (iPSC) clones from tail vein fibroblasts of these transgenic mice and manipulated them both in vitro and in vivo in non-transgenic background mice. We created the iPSC clones with a relatively low M.O.I, producing retroviral integrations which averaged only 1 to 2 sites per retroviral plasmid construct used. RESULTS: Most iPSC clones derived from each group displayed an essentially normal murine karyotype, strong expression of the exogenous reprogrammable genes and significant expression of characteristic endogenous murine surface stem cell markers including SSEA-1 (CD15), PECAM-1 (CD31), Ep-Cam (CD326), and Nectin (CD112), but no expression of their transgene. A majority (75%) of iPSC clones displayed a normal murine karyotype but 25% exhibited a genomically unstable karyotype. However, even these later clones exhibited stable and characteristic iPSC properties. When injected orthotopically, select iPSC clones, either constitutive or inducible, no longer expressed their exogenous pluripotency reprogramming factors but expressed their oncogenic transgene (PyVT or ErbB2) and participated in both breast ontogenesis and subsequent oncogenesis. When injected non-orthotopically or when differentiated in vitro along several different non-mammary lineages of differentiation, the iPSC clones failed to do so. Although many clones developed anticipated teratomas, select iPSC clones under the appropriate constitutive or inducible conditions exhibited both breast ontogenesis and oncogenesis through the same stages as exhibited by their transgenic murine parents and, as such, represent transgenic surrogates. CONCLUSIONS: The iPSC clones offer a number of advantages over transgenic mice including cost, the ability to manipulate and tag in vitro, and create an in vitro model of breast ontogeny and oncogenesis that can be used to gain additional insights into the differentiated status of the target cell which is susceptible to transformation. In addition, the use of these oncogene-containing iPSC clones can be used in chemopreventive studies of breast cancer.

Why is cancer so common a disease in people yet so rare at a cellular level?

Cancers are common diseases in people and yet, on a cellular level, are quite rare. The vast majority of both sporadic, spontaneous cancers and inherited germline cancers arise in single foci from singly transformed cells despite the fact that, in the former, carcinogenic factors bathe fields of millions of potential target cells and, in the latter, the predisposing germline mutations are present in every cell of a given organ and, in fact, every cell of the body. Although the multi-hit theory of carcinogenesis has been invoked to explain such things as cancer latency, which is the period between cancer initiation and emergence and the cancer-aging relationship where an accumulation of "hits" over a period of time are necessary for cancer emergence, the multi-hit theory falls short in explaining the rareness of transformation at a cellular level. This is so because many cancers are not due to multiple hits, and even for those that are, it would be expected that many cells would be exposed to those factors inducing the hits. Although the tumor stem/progenitor cell compartmental theory of tumorigenesis characterizes a tumor compartment that is capable of self-renewal and multipotency, accounting for cancer relapses and recurrences, this compartmental theory alone cannot account for the rareness of initial transformation at a cellular level as the cancer stem/progenitor cell compartment is already transformed and considerable in size. This study advances a different and novel hypothesis that oncogenesis is regulated and ultimately determined by a cell of origin's critical state of differentiation. Before and after this critical state of differentiation has been reached, target cells cannot transform and give rise to cancer even when they receive the necessary carcinogenic insults or have the requisite transforming tumor suppressor genes or oncogenes. As support for this hypothesis, the study cites preliminary evidence using oncogene-containing transgenic mice that develop mammary carcinomas, to derive tail vein fibroblasts converted to iPSCs which, when left undifferentiated, and injected into the cleared fat pads of non-transgenic background mice give rise to mammary gland ontogeny and mammary gland carcinogenesis. However, when first differentiated in vitro into multiply different non-mammary lineages prior to injection, they fail to do so. The hypothesis has widespread implications for chemopreventive strategies.

Regulation of breast cancer oncogenesis by the cell of origin's differentiation state.

Human breast cancer which affects 1/8 women is rare at a cellular level. Even in the setting of germline BRCA1/BRCA2, which is present in all breast cells, solitary cancers or cancers arising at only several foci occur. The overwhelming majority of breast cells (109-1012 cells) resist transformation. Our hypothesis to explain this rareness of transformation is that mammary oncogenesis is regulated by the cell of origin's critical window of differentiation so that target cells outside of this window cannot transform. Our novel hypothesis differs from both the multi-hit theory of carcinogenesis and the stem/progenitor cell compartmental theory of tumorigenesis and utilizes two well established murine transgenic models of breast oncogenesis, the FVB/N-Tg (MMTV-PyVT)634Mul/J and the FVB-Tg (MMTV-ErbB2) NK1Mul/J. Tail vein fibroblasts from each of these transgenics were used to generate iPSCs. When select clones were injected into cleared mammary fat pads, but not into non-orthotopic sites of background mice, they exhibited mammary ontogenesis and oncogenesis with the expression of their respective transgenes. iPSC clones, when differentiated along different non-mammary lineages in vitro, were also not able to exhibit either mammary ontogenesis or oncogenesis in vivo. Therefore, in vitro and in vivo regulation of differentiation is an important determinant of breast cancer oncogenesis.

Does wastewater treatment plant upgrading with activated carbon result in an improvement of fish health?

In the present study, the efficiency of a wastewater treatment plant (WWTP) upgraded with a powdered activated carbon unit for the reduction of micropollutants and the related advantages for fish health have been analyzed by means of different biomarkers, i.e. histopathological investigations, analyses of glycogen content and stress proteins, as well as by chemical analyses in different matrices. Comparative analyses were conducted prior and subsequent to the installation of the additional purification unit. Chemical analyses revealed a significant reduction of several pharmaceuticals, including diclofenac, carbamazepine and metoprolol, in samples of effluent and surface water downstream of the WWTP after its upgrade. In addition, diminished concentrations of diclofenac and PFOS were detected in tissues of analyzed fish. Histopathological investigations of fish liver, gills, and kidney revealed improved tissue integrity in fish after improved wastewater treatment. In parallel, biochemical measurements of glycogen revealed increased energy resources in fish liver and, furthermore, hsp70 levels in livers of exposed rainbow trout and in kidneys of exposed brown trout were lower after than before the WWTP upgrade. In summary, additional treatment with powdered activated carbon led to a reduction of potentially hazardous chemicals in the effluent and the adjacent river and, consequently, to an improvement of fish health in the receiving water course.