Ariel - Volume 11 Number 3

Executive Editors Ellen Feldman Leonardo S. Nasca, Jr. Business Managers Barbara L. Davies Martin B. Getzow News Editor Hugh A. Gelabert Features Editor Aaron D. Bleznak CAHS Editor Joan M. Greco Editorial Page Editor Samuel Markind Photography Editor Todd Demmy Sports Editor Paul F. Mansfiel

Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors

PURPOSE: Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T-cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune-related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD-L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD-L1 in pituitary adenomas. METHODS: PD-L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non-functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. RESULTS: Pituitary tumors express variable levels of PD-L1 transcript and protein. PD-L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin-expressing) pituitary adenomas compared to non-functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD-L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD-L1 expression, particularly in the functional subtypes. CONCLUSIONS: Human pituitary adenomas harbor PD-L1 across subtypes, with significantly higher expression in functioning adenomas compared to non-functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management

Reconfigurable Asynchronous Logic Automata (RALA)

Computer science has served to insulate programs and programmers from knowledge of the underlying mechanisms used to manipulate information, however this fiction is increasingly hard to maintain as computing devices decrease in size and systems increase in complexity. Manifestations of these limits appearing in computers include scaling issues in interconnect, dissipation, and coding. Reconfigurable Asynchronous Logic Automata (RALA) is an alternative formulation of computation that seeks to align logical and physical descriptions by exposing rather than hiding this underlying reality. Instead of physical units being represented in computer programs only as abstract symbols, RALA is based on a lattice of cells that asynchronously pass state tokens corresponding to physical resources. We introduce the design of RALA, review its relationships to its many progenitors, and discuss its benefits, implementation, programming, and extensions.National Science Foundation (U.S.) Center for Bits and AtomsUnited States. Army Research Office (Grant number W911NF-08-1-0254)United States. Army Research Office (Grant number W911NF-09-1-0542

A scoping review of the unassisted physical exam conducted over synchronous audio-video telemedicine

Background This scoping review aims to provide a broad overview of the research on the unassisted virtual physical exam performed over synchronous audio-video telemedicine to identify gaps in knowledge and guide future research. Methods Searches for studies on the unassisted virtual physical exam were conducted in 3 databases. We included primary research studies in English on the virtual physical exam conducted via patient-to-provider synchronous, audio-video telemedicine in the absence of assistive technology or personnel. Screening and data extraction were performed by 2 independent reviewers. Results Seventy-four studies met inclusion criteria. The most common components of the physical exam performed over telemedicine were neurologic (38/74, 51%), musculoskeletal (10/74, 14%), multi-system (6/74, 8%), neuropsychologic (5/74, 7%), and skin (5/74, 7%). The majority of the literature focuses on the telemedicine physical exam in the adult population, with only 5% of studies conducted specifically in a pediatric population. During the telemedicine exam, the patients were most commonly located in outpatient offices (28/74, 38%) and homes and other non-clinical settings (25/74, 34%). Both patients and providers in the included studies most frequently used computers for the telemedicine encounter. Conclusions Research evaluating the unassisted virtual physical exam is at an early stage of maturity and is skewed toward the neurologic, musculoskeletal, neuropsychologic, and skin exam components. Future research should focus on expanding the range of telemedicine exam maneuvers studied and evaluating the exam in the most relevant settings, which for telemedicine is trending toward exams conducted through mobile devices and in patients’ homes

Love is the triumph of the imagination: daydreams about significant others are associated with increased happiness, love and connection

Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others

Highly nonlinear transport across single-molecule junctions via destructive quantum interference

To rival the performance of modern integrated circuits, single-molecule devices must be designed to exhibit extremely nonlinear current–voltage (I–V) characteristics1,2,3,4. A common approach is to design molecular backbones where destructive quantum interference (QI) between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) produces a nonlinear energy-dependent tunnelling probability near the electrode Fermi energy (EF)5,6,7,8. However, tuning such systems is not straightforward, as aligning the frontier orbitals to EF is hard to control9. Here, we instead create a molecular system where constructive QI between the HOMO and LUMO is suppressed and destructive QI between the HOMO and strongly coupled occupied orbitals of opposite phase is enhanced. We use a series of fluorene oligomers containing a central benzothiadiazole10 unit to demonstrate that this strategy can be used to create highly nonlinear single-molecule circuits. Notably, we are able to reproducibly modulate the conductance of a 6-nm molecule by a factor of more than 104

Rationale and design of the Multicenter Medication Reconciliation Quality Improvement Study (MARQUIS)

Background: Unresolved medication discrepancies during hospitalization can contribute to adverse drug events, resulting in patient harm. Discrepancies can be reduced by performing medication reconciliation; however, effective implementation of medication reconciliation has proven to be challenging. The goals of the Multi-Center Medication Reconciliation Quality Improvement Study (MARQUIS) are to operationalize best practices for inpatient medication reconciliation, test their effect on potentially harmful unintentional medication discrepancies, and understand barriers and facilitators of successful implementation. Methods: Six U.S. hospitals are participating in this quality improvement mentored implementation study. Each hospital has collected baseline data on the primary outcome: the number of potentially harmful unintentional medication discrepancies per patient, as determined by a trained on-site pharmacist taking a “gold standard” medication history. With the guidance of their mentors, each site has also begun to implement one or more of 11 best practices to improve medication reconciliation. To understand the effect of the implemented interventions on hospital staff and culture, we are performing mixed methods program evaluation including surveys, interviews, and focus groups of front line staff and hospital leaders. Discussion At baseline the number of unintentional medication discrepancies in admission and discharge orders per patient varies by site from 2.35 to 4.67 (mean=3.35). Most discrepancies are due to history errors (mean 2.12 per patient) as opposed to reconciliation errors (mean 1.23 per patient). Potentially harmful medication discrepancies averages 0.45 per patient and varies by site from 0.13 to 0.82 per patient. We discuss several barriers to implementation encountered thus far. In the end, we anticipate that MARQUIS tools and lessons learned have the potential to decrease medication discrepancies and improve patient outcomes. Trial registration Clinicaltrials.gov identifier NCT0133706