Different Perspectives of Psychiatry Within Two Neighboring Residency Training Programs

This paper arises out of my fortunate opportunity to observe two very different psychiatric residency training programs. While a fourth-year resident at a large, psycho dynamically-oriented private psychiatric hospital, I was able to do a consultation liaison rotation at a neighboring academic institution at the vanguard of biological psychiatry. I left the familiar, we ll-manicured suburban grounds for the inner city of Baltimore to be one of the first experiments in cross-fertilization between these residency training programs. Although the two institutions are located in the same city and stem from the early history of American psychiatry, they have been worlds apart in their approach. The hospitals have distinct development histories. The private hospital was originally founded by a philanthropic Quaker, Moses Sheppard, before the Civil War. He wished to provide a humane asylum for treatment of the mentally disturbed. In the context of the en lightened ideas of Pineal and The Moral Treatment, he believed that separating the patients from chaotic family and social influences and providing a respectful and humane environment would help restore sanity. Sheppard instructed that all cells for patients were to be above ground and have windows. Enoch Pratt, a successful businessman, later made a large contribution to what is now known as The Sheppard and Enoch Pratt Hospital. The academic center was established out of a growing interest in research, training, and in returning psychiatry to the field of medicine . Under the direction of Adolf Meyer in 19I3, the Henry Phipps Psychiatric Clinic at Johns Hopkins Hospital was founded. Many advances in psychosocial theory and biological research continue to be achieved at this internationally renowned medical center

Utilization of a multimodal preoperative pain regimen prior to gynecologic oncology exploratory laparotomies

Objective: The aim of this study was to evaluate the use of a combination of non-opioid preoperative pain medications including Tylenol, Lyrica, and Celecoxib (TLC) in patients undergoing gynecologic oncologic exploratory laparotomies. We evaluated postoperative narcotic use in morphine equvalents (ME) as well as pain scores, anti-emetic use, and length of stay.https://jdc.jefferson.edu/patientsafetyposters/1055/thumbnail.jp

DeepAPT: Nation-State APT Attribution Using End-to-End Deep Neural Networks

In recent years numerous advanced malware, aka advanced persistent threats (APT) are allegedly developed by nation-states. The task of attributing an APT to a specific nation-state is extremely challenging for several reasons. Each nation-state has usually more than a single cyber unit that develops such advanced malware, rendering traditional authorship attribution algorithms useless. Furthermore, those APTs use state-of-the-art evasion techniques, making feature extraction challenging. Finally, the dataset of such available APTs is extremely small. In this paper we describe how deep neural networks (DNN) could be successfully employed for nation-state APT attribution. We use sandbox reports (recording the behavior of the APT when run dynamically) as raw input for the neural network, allowing the DNN to learn high level feature abstractions of the APTs itself. Using a test set of 1,000 Chinese and Russian developed APTs, we achieved an accuracy rate of 94.6%

Microcystic, Elongated, and Fragmented (MELF) Pattern Invasion in Ovarian Endometrioid Carcinoma: Immunohistochemical Profile and Prognostic Implications

BACKGROUND •Microcystic, Elongated and Fragmented (MELF) is a well-recognized pattern of uterine endometrioid carcinoma (UEC) associated with lymphovascular space invasion and occult lymph node metastasis •MELF in UEC may be seen with Lynch Syndrome •MELF in UEC is hypothesized to be histologic evidence of an epithelial mesenchymal transition •MELF pattern invasion in ovarian endometrioid carcinoma (OEC) was first described at USCAP 2015 • Current study evaluates MELF in OEC for •Prognostic implications •Immunohistochemical (IHC) profile related to •Lynch Syndrome •Epithelial mesenchymal transition DESIGN •42 consecutive cases of OEC without concurrent UEC (1996-2014) evaluated by 2 pathologists •MELF defined as at least three glands fulfilling histologic criteria •32 cases had blocks available for staining •MLH1, PMS2, MSH2 and MSH6 for mismatch repair (MMR) protein expression •Graded as “retained” or “lost” •β-catenin, e-cadherin, CK19 and cyclin D1 for evidence of epithelial mesenchymal transition •Graded as “rare” (75% cells stain) •Retrospective chart review of clinical and demographic features and overall survival •Data analyzed using Fisher exact test analysis •Survival analyzed using Kaplan-Meier metho

Drug treatment program patients' hepatitis C virus (HCV) education needs and their use of available HCV education services

BACKGROUND: In spite of the disproportionate prevalence of hepatitis C virus (HCV) infection among drug users, many remain uninformed or misinformed about the virus. Drug treatment programs are important sites of opportunity for providing HCV education to their patients, and many programs do, in fact, offer this education in a variety of formats. Little is known, however, about the level of HCV knowledge among drug treatment program patients, and the extent to which they utilize their programs' HCV education services. METHODS: Using data collected from patients (N = 280) in 14 U.S. drug treatment programs, we compared patients who reported that they never injected drugs (NIDUs) with past or current drug injectors (IDUs) concerning their knowledge about HCV, whether they used HCV education opportunities at their programs, and the facilitators and barriers to doing so. All of the programs were participating in a research project that was developing, implementing, and evaluating a staff training to provide HCV support to patients. RESULTS: Although IDUs scored higher on an HCV knowledge assessment than NIDUs, there were many gaps in HCV knowledge among both groups of patients. To address these knowledge gaps, all of the programs offered at least one form of HCV education: all offered 1:1 sessions with staff, 12 of the programs offered HCV education in a group format, and 11 of the programs offered this education through pamphlets/books. Only 60% of all of the participating patients used any of their programs' HCV education services, but those who did avail themselves of these HCV education opportunities generally assessed them positively. In all, many patients were unaware that HCV education was offered at their programs through individual sessions with staff, group meetings, and books/pamphlets, (42%, 49%, and 46% of the patients, respectively), and 22% were unaware that any HCV education opportunities existed. CONCLUSION: Efforts especially need to focus on ensuring that all drug treatment program patients are made aware of and encouraged to use HCV education services at their programs

HERMES: Towards an Integrated Toolbox to Characterize Functional and Effective Brain Connectivity

The analysis of the interdependence between time series has become an important field of research in the last years, mainly as a result of advances in the characterization of dynamical systems from the signals they produce, the introduction of concepts such as generalized and phase synchronization and the application of information theory to time series analysis. In neurophysiology, different analytical tools stemming from these concepts have added to the ‘traditional’ set of linear methods, which includes the cross-correlation and the coherency function in the time and frequency domain, respectively, or more elaborated tools such as Granger Causality. This increase in the number of approaches to tackle the existence of functional (FC) or effective connectivity (EC) between two (or among many) neural networks, along with the mathematical complexity of the corresponding time series analysis tools, makes it desirable to arrange them into a unified-easy-to-use software package. The goal is to allow neuroscientists, neurophysiologists and researchers from related fields to easily access and make use of these analysis methods from a single integrated toolbox. Here we present HERMES (http://hermes.ctb.upm.es), a toolbox for the Matlab® environment (The Mathworks, Inc), which is designed to study functional and effective brain connectivity from neurophysiological data such as multivariate EEG and/or MEG records. It includes also visualization tools and statistical methods to address the problem of multiple comparisons. We believe that this toolbox will be very helpful to all the researchers working in the emerging field of brain connectivity analysis

NMDA and Dopamine Converge on the NMDA-Receptor to Induce ERK Activation and Synaptic Depression in Mature Hippocampus

The formation of enduring internal representation of sensory information demands, in many cases, convergence in time and space of two different stimuli. The first conveys the sensory input, mediated via fast neurotransmission. The second conveys the meaning of the input, hypothesized to be mediated via slow neurotransmission. We tested the biochemical conditions and feasibility for fast (NMDA) and slow (dopamine) neurotransmission to converge on the Mitogen Activated Protein Kinase signaling pathways, crucial in several forms of synaptic plasticity, and recorded its effects upon synaptic transmission. We detected differing kinetics of ERK2 activation and synaptic strength changes in the CA1 for low and high doses of neurotransmitters in hippocampal slices. Moreover, when weak fast and slow inputs are given together, they converge on ERK2, but not on p38 or JNK, and induce strong short-term synaptic depression. Surprisingly, pharmacological analysis revealed that a probable site of such convergence is the NMDA receptor itself, suggesting it serves as a detector and integrator of fast and slow neurotransmission in the mature mammalian brain, as revealed by ERK2 activation and synaptic function

α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas

BACKGROUND: Checkpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools to circumvent resistance. In human patients, responses to checkpoint blockade therapy correlate with tumor mutation load, and intrinsic resistance associates with pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis and TGFβ signaling. METHODS: To facilitate studies on mechanisms of squamous cell carcinoma (SCC) evasion of checkpoint blockade immunotherapy, we sought to develop a novel panel of murine syngeneic SCC lines reflecting the heterogeneity of human cancer and its responses to immunotherapy. We characterized six Kras-driven cutaneous SCC lines with a range of mutation loads. Following implantation into syngeneic FVB mice, we examined multiple tumor responses to α-PD-1, α-TGFβ or combinatorial therapy, including tumor growth rate and regression, tumor immune cell composition, acquired tumor immunity, and the role of cytotoxic T cells and Tregs in immunotherapy responses. RESULTS: We show that α-PD-1 therapy is ineffective in establishing complete regression (CR) of tumors in all six SCC lines, but causes partial tumor growth inhibition of two lines with the highest mutations loads, CCK168 and CCK169. α-TGFβ monotherapy results in 20% CR and 10% CR of established CCK168 and CCK169 tumors respectively, together with acquisition of long-term anti-tumor immunity. α-PD-1 synergizes with α-TGFβ, increasing CR rates to 60% (CCK168) and 20% (CCK169). α-PD-1 therapy enhances CD4 + Treg/CD4 + Th ratios and increases tumor cell pSmad3 expression in CCK168 SCCs, whereas α-TGFβ antibody administration attenuates these effects. We show that α-TGFβ acts in part through suppressing immunosuppressive Tregs induced by α-PD-1, that limit the anti-tumor activity of α-PD-1 monotherapy. Additionally, in vitro and in vivo, α-TGFβ acts directly on the tumor cell to attenuate EMT, to activate a program of gene expression that stimulates immuno-surveillance, including up regulation of genes encoding the tumor cell antigen presentation machinery. CONCLUSIONS: We show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFβ-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFβ combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFβ/α-PD-1 combination therapy (NCT02947165)