Quantitative Feedback Referencing for Improved Kinetic Fitting of Scanning Electrochemical Microscopy Measurements.

Scanning electrochemical microscopy (SECM) has matured as a technique for studying local electrochemical processes. The feedback mode is most commonly used for extracting quantitative kinetic information. However, approaching individual regions of interest, as is commonly done, does not take full advantage of the spatial resolution that SECM has to offer. Moreover, fitting of experimental approach curves remains highly subjective due to the manner of estimating the tip-to-substrate distance. We address these issues using negative or positive feedback currents as a reference to calculate the tip-to-substrate distance directly for quantitative kinetic fitting of approach curves and line profiles. The method was first evaluated by fitting simulated data and then tested experimentally by resolving negative feedback and intermediate kinetics behavior in a spatially controlled fashion using (i) a flat, binary substrate composed of Au and SiO2 segments and (ii) a dual-mediator system for live-cell measurements. The methodology developed herein, named quantitative feedback referencing (QFR), improves fitting accuracy, removes fitting subjectivity, and avoids substrate-microelectrode contact.

Super-resolution Scanning Electrochemical Microscopy.

To achieve super-resolution scanning electrochemical microscopy (SECM), we must overcome the theoretical limitation associated with noncontact electrochemical imaging of surface-generated species. This is the requirement for mass transfer to the electrode, which gives rise to the diffusional broadening of surface features. In this work, a procedure is developed for overcoming this limitation and thus generating "super-resolved" images using point spread function (PSF)-based deconvolution, where the point conductor plays the same role as the point emitter in optical imaging. In contrast to previous efforts in SECM towards this goal, our method uses a finite element model to generate a pair of corresponding blurred and sharp images for PSF estimation, avoiding the need to perform parameter optimization for effective deconvolution. It can therefore be used for retroactive data treatment and an enhanced understanding of the structure-property relationships that SECM provides.

Evaluating the Use of Edge Detection in Extracting Feature Size from Scanning Electrochemical Microscopy Images.

The edge of a reactive or topographical feature is hard to estimate from feedback-based scanning electrochemical microscopy due to diffusional blurring, but is crucial to determining the accurate size and shape of these features. In this work, numerical simulations are used to demonstrate that the inflection point in a 1D line scan corresponds well to the true feature edge. This approach is then applied in 2D using the Canny algorithm to experimental images of two model substrates and a biological sample. This approach circumvents the need for aligning the imaged region between separate microscopy techniques, reveals hidden details embedded in SECM images, and allows individual features to be separated from their background more effectively.

Simultaneous Electrochemical and Emission Monitoring of Electrogenerated Chemiluminescence through Instrument Hyphenation.

One of the long-standing challenges to performing electrogenerated chemiluminescence (ECL) research is the need for dedicated instrumentation or highly customized cells to achieve reproducibility. This manuscript describes an approach to designing ECL systems through the hyphenation of existing laboratory instruments, which provide innate time correlation of electrochemical and emission data. This design methodology lowers the entry barrier required to obtaining reproducible ECL measurements and provides flexibility in the scope of applications. Uniquely, the simplicity of this system's experimental interface, a spectrochemical quartz cuvette, readily enables collaboration with finite element modeling that simulates ECL occurring in the cuvette-based cell. This combination of empirical and simulation data allowed for the investigation of the intertwined kinetics behind the coreactant ECL mechanism of tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)32+) and tripropylamine (TPA). The complexity of the system measurable via the hyphenation methodology was further scaled though the addition of tris[2-(4,6-difluorophenyl)pyridinato-C2, N] iridium(III) (Ir(dFppy)3) and the observation of real time multiplexing.

Altered Spatial Resolution of Scanning Electrochemical Microscopy Induced by Multifunctional Dual-Barrel Microelectrodes.

The nonuniform diffusion profile to the edge of many multifunctional microelectrodes has the potential to give rise to distortions in its imaging capability, reducing the spatial accuracy of the techniques they are used in. In this work, numerical simulations are used to predict these distortions for dual-barrel electrodes used in the combined feedback/generation-collection mode of scanning electrochemical microscopy imaging a model substrate. The sensitivity of this distortion to tip-substrate distance, electrolyte composition, and size and shape of a reactive substrate feature are discussed.

What happens during early outpatient palliative care consultations for persons with newly diagnosed advanced cancer? A qualitative analysis of provider documentation.

BACKGROUND: Early outpatient palliative care consultations are recommended by clinical oncology guidelines globally. Despite these recommendations, it is unclear which components should be included in these encounters. AIM: Describe the evaluation and treatment recommendations made in early outpatient palliative care consultations. DESIGN: Outpatient palliative care consultation chart notes were qualitatively coded and frequencies tabulated. SETTING/PARTICIPANTS: Outpatient palliative care consultations were automatically triggered as part of an early versus delayed randomized controlled trial (November 2010 to April 2013) for patients newly diagnosed with advanced cancer living in the rural Northeastern US. RESULTS: In all, 142 patients (early = 70; delayed = 72) had outpatient palliative care consultations. The top areas addressed in these consultations were general evaluations-marital/partner status (81.7%), spirituality/emotional well-being (80.3%), and caregiver/family support (79.6%); symptoms-mood (81.7%), pain (73.9%), and cognitive/mental status (68.3%); general treatment recommendations-counseling (39.4%), maintaining current medications (34.5%), and initiating new medication (23.9%); and symptom-specific treatment recommendations-pain (22.5%), constipation (12.7%), depression (12.0%), advanced directive completion (43.0%), identifying a surrogate (21.8%), and discussing illness trajectory (21.1%). Compared to the early group, providers were more likely to evaluate general pain ( p = 0.035) and hospice awareness ( p = 0.005) and discuss/recommend hospice ( p = 0.002) in delayed group participants. CONCLUSION: Outpatient palliative care consultations for newly diagnosed advanced cancer patients can address patients' needs and provide recommendations on issues that might not otherwise be addressed early in the disease course. Future prospective studies should ascertain the value of early outpatient palliative care consultations that are automatically triggered based on diagnosis or documented symptom indicators versus reliance on oncologist referral.

Adaptation by the collecting duct to an exogenous acid load is blunted by deletion of the proton-sensing receptor GPR4.

We previously reported that the deletion of the pH sensor GPR4 causes a non-gap metabolic acidosis and defective net acid excretion (NAE) in the GPR4 knockout mouse (GPR4-/-) (Sun X, Yang LV, Tiegs BC, Arend LJ, McGraw DW, Penn RB, and Petrovic S. J Am Soc Nephrol 21: 1745-1755, 2010). Since the major regulatory site of NAE in the kidney is the collecting duct (CD), we examined acid-base transport proteins in intercalated cells (ICs) of the CD and found comparable mRNA expression of kidney anion exchanger 1 (kAE1), pendrin, and the a4 subunit of H(+)-ATPase in GPR4-/- vs. +/+. However, NH4Cl loading elicited adaptive doubling of AE1 mRNA in GPR4+/+, but a 50% less pronounced response in GPR4-/-. In GPR4+/+, NH4Cl loading evoked a cellular response characterized by an increase in AE1-labeled and a decrease in pendrin-labeled ICs similar to what was reported in rabbits and rats. This response did not occur in GPR4-/-. Microperfusion experiments demonstrated that the activity of the basolateral Cl(-)/HCO3(-) exchanger, kAE1, in CDs isolated from GPR4-/- failed to increase with NH4Cl loading, in contrast to the increase observed in GPR4+/+. Therefore, the deficiency of GPR4 blunted, but did not eliminate the adaptive response to an acid load, suggesting a compensatory response from other pH/CO2/bicarbonate sensors. Indeed, the expression of the calcium-sensing receptor (CaSR) was nearly doubled in GPR4-/- kidneys, in the absence of apparent disturbances of Ca(2+) homeostasis. In summary, the expression and activity of the key transport proteins in GPR4-/- mice are consistent with spontaneous metabolic acidosis, but the adaptive response to a superimposed exogenous acid load is blunted and might be partially compensated for by CaSR.

Medical management of a patent urachus in a southern white rhinoceros (Ceratotherium simum simum) calf.

A female southern white rhinoceros (Ceratotherium simum simum) calf presented with a patent urachus at 5 days of age. It was immobilized for examination and medical treatment was elected over surgical repair. Systemic antibiotics and topical treatment of the site by cleaning with chlorhexidine solution were followed by silver nitrate cautery. This animal required no further treatment and has reached 1 yr of age with no other medical problems. Although patent urachus is relatively common in domestic animals, especially horses, neither the problem nor its resolution are well documented in exotic animals and surgical intervention is more commonly performed.

Interprofessional Post-Graduate Training Model for Nurse Practitioners and Physician Trainees.

CONTEXT: People living with serious illness and their care partners rely on team-based specialty hospice and palliative care (HPC) in order to achieve high quality end of life outcomes. In HPC, physician and nurse practitioner (NP) scope of practice has significant overlap so training together may offer benefits to clinicians and patients. OBJECTIVES: Assessment of clinical competencies in a post-graduate training program consisting of NPs and physicians training and learning side-by-side. METHODS: A crosswalk assured NP and physician HPC clinical competencies were captured in evaluation questions used by interprofessional program faculty to observe and assess trainees. Six clinical competencies were calculated based on aggregated evaluations for each physician and NP HPC post-graduate trainee at 3, 6, 9, and 12 months annually for 3 years. For NPs and physicians, the mean slopes of the best fit lines, the final numeric score, and the mean net change between 12 and three month competencies were compared. Learner experience was captured qualitatively. RESULTS: There was no statistical difference in the change of competency scores, the final competency scores, or the trajectory of improvement in the six competencies between physician to NP trainees. Adding NP trainees was considered by post-graduate trainees as a strength of the program, and did not detract from physician competence achievement. CONCLUSION: Assessing an IPE post-graduate training program in HPC was possible using a shared clinical competency framework, and revealed similar clinical gains for NPs and physicians enrolled in the program.

Validating Whole Slide Imaging Systems for Diagnostic Purposes in Pathology.

CONTEXT.­: The original guideline, "Validating Whole Slide Imaging for Diagnostic Purposes in Pathology," was published in 2013 and included 12 guideline statements. The College of American Pathologists convened an expert panel to update the guideline following standards established by the National Academies of Medicine for developing trustworthy clinical practice guidelines. OBJECTIVE.­: To assess evidence published since the release of the original guideline and provide updated recommendations for validating whole slide imaging (WSI) systems used for diagnostic purposes. DESIGN.­: An expert panel performed a systematic review of the literature. Frozen sections, anatomic pathology specimens (biopsies, curettings, and resections), and hematopathology cases were included. Cytology cases were excluded. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, the panel reassessed and updated the original guideline recommendations. RESULTS.­: Three strong recommendations and 9 good practice statements are offered to assist laboratories with validating WSI digital pathology systems. CONCLUSIONS.­: Systematic review of literature following release of the 2013 guideline reaffirms the use of a validation set of at least 60 cases, establishing intraobserver diagnostic concordance between WSI and glass slides and the use of a 2-week washout period between modalities. Although all discordances between WSI and glass slide diagnoses discovered during validation need to be reconciled, laboratories should be particularly concerned if their overall WSI-glass slide concordance is less than 95%.

National Society for Histotechnology and Digital Pathology Association Online Self-Paced Digital Pathology Certificate of Completion Program.

The field of digital pathology has rapidly expanded within the last few years with increasing adoption and growth in popularity. As digital pathology matures, it is apparent that we need well-trained individuals to manage our whole-slide imaging systems. This editorial introduces the joint National Society for Histotechnology and Digital Pathology Association online self-paced digital pathology certificate program which was launched in May 2018 that was established to meet this demand. An overview of how this program was developed, the content of the educational modules, and the way that this program is being offered is discussed.

Evaluation of T cell infiltration in matched biopsy and nephrectomy samples in renal cell carcinoma.

T cell infiltration in tumors has been investigated as a biomarker of response to checkpoint inhibitors. Neo-adjuvant studies in renal cell carcinoma (RCC) may provide a unique opportunity to compare T cell infiltration in a pretreatment renal mass biopsy to a posttreatment nephrectomy specimen, and thus evaluate the effects of immune checkpoint inhibitors. However, there are no data regarding the association of T cell infiltration in matched biopsy and nephrectomy samples without intervening treatment. Understanding this association will inform investigation of this potential biomarker in future studies.Matched biopsy and nephrectomy samples (without intervening systemic therapy) were identified from patients with nonmetastatic RCC. Selected tissue sections from biopsy and nephrectomy samples were reviewed and marked for intratumoral lymphocytes by a pathologist. Immunohistochemistry (IHC) was utilized to stain for T cell markers (CD3, CD4, and CD8). Intratumoral staining was then quantified in the tissue sections as counts per total tumor area surveyed. Spearman correlation (r) was used to measure associations.Thirty matched pairs were investigated. The median interval between biopsy and nephrectomy was 2.8 (0.2-87.7) months. Clear cell was the most common histology (29/30; 97%). There was a statistically significant positive correlation between the frequency of CD3 and CD8 T cells between matched biopsy and nephrectomy samples (r = 0.39; P = .036 and r = 0.38; P = .041, respectively).The frequencies of CD8+ T cells in matched biopsy and nephrectomy samples in RCC in the absence of intervening treatment have been characterized and show a positive correlation between matched biopsy and nephrectomy samples.

Acceptability and Impact of a Required Palliative Care Rotation with Prerotation and Postrotation Observed Simulated Clinical Experience during Internal Medicine Residency Training on Primary Palliative Communication Skills.

BACKGROUND: Improving communication training for primary palliative care using a required palliative care rotation for internal medicine (IM) residents has not been assessed. OBJECTIVE: To assess skills acquisition and acceptability for IM residents not selecting an elective. DESIGN: A consecutive, single-arm cohort underwent preobjective structured clinical examination (OSCE) with learner-centric feedback, two weeks of clinical experience, and finally a post-OSCE to crystallize learner-centric take home points. SETTING/SUBJECTS: IM second year residents from Dartmouth-Hitchcock were exposed to a required experiential palliative care rotation. MEASUREMENTS: Pre- and post-OSCE using a standardized score card for behavioral skills, including patient-centered interviewing, discussing goals of care/code status, and responding to emotion, as well as a confidential mixed qualitative and quantitative evaluation of the experience. RESULTS: Twelve residents were included in the educational program (two were excluded because of shortened experiences) and showed statistically significant improvements in overall communication and more specifically in discussing code status and responding to emotions. General patient-centered interviewing skills were not significantly improved, but prerotation scores reflected pre-existing competency in this domain. Residents viewed the observed simulated clinical experience (OSCE) and required rotation as positive experiences, but wished for more opportunities to practice communication skills in real clinical encounters. CONCLUSIONS: A required palliative care experiential rotation flanked by OSCEs at our institution improved the acquisition of primary palliative care communication skills similarly to other nonclinical educational platforms, but may better meet the needs of the resident and faculty as well as address all required ACGME milestones.

Developing successful models of cancer palliative care services.

OBJECTIVES: This article describes successful institutionally based programs for providing high-quality palliative care to persons with cancer and their family members. Challenges and opportunities for program development are also described. DATA SOURCES: Published literature from 2000 to present describing concurrent oncology palliative care clinical trials, standards, and guidelines were reviewed. CONCLUSION: Clinical trials have shown feasibility and positive outcomes and formed the basis for consensus guidelines that support concurrent oncology palliative care models. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses should advocate for all patients with advanced cancer and their families to have access to concurrent oncology palliative care from the time of diagnosis with a life-limiting cancer.

Medication kits for managing symptomatic emergencies in the home: a survey of common hospice practice.

INTRODUCTION: Alleviation of symptoms associated with advanced illness and dying is a fundamental goal and core principle of palliative care. Little research exists regarding hospice programs' practices for prescribing, dispensing, and utilizing medication kits in the home for management of uncontrolled symptoms. METHODS: We conducted a telephone survey of all 22 agencies in New Hampshire providing home hospice care. The survey inquired about the timing of medication kit ordering and availability, characteristics of prescribers and pharmacies, kit contents, costs, frequency of use, and perceived impact of kits. RESULTS: All programs' kits contained medications to treat pain and dyspnea, 81% for nausea and vomiting, and 76% for seizures. Eighty-six percent of agencies (18/21) reported that a medication within the kits was used in more than 50% of cases. Eighty-six percent reported the kits often averted hospital or emergency department visits. Oral, sublingual, and rectal routes of administration were common as was topical preparations of combination medications. Three programs included parenteral morphine in kits. Kits cost less than $50 for the majority of programs. CONCLUSION: Hospice programs commonly utilize kits containing prescription medications for the purpose of managing uncontrolled symptoms in the home. There is considerable variation in kit contents and practice. Programs believe that kits diminish emergency department visits and hospitalizations. Research is needed to more fully describe and study the outcomes of these practices.

Case cancellations on the day of surgery: an investigation in an Australian paediatric hospital.

BACKGROUND: This study investigates case cancellations on the intended day of surgery (DOS) at a paediatric hospital in Melbourne, Australia. The hospital in Melbourne treats over 32 000 inpatients annually and handles both elective and emergency cases. METHODS: The data for this paper were collected over a period of 12 months, from June 2004 to June 2005. The data were extracted retrospectively from the theatre computer system. A nurse researcher reviewed the full written details of all cancellations to clarify their cause and confirm the reasons for cancellation; the reasons for cancellation were then sorted into one of 14 groups. RESULTS: There were 16 559 theatre bookings, and of these, 1198 (7.2%) were cancelled on the DOS. There was a mean of 3.28 cancellations of surgery on the intended day. The hospital-initiated postponements accounted for 18.5% of DOS cancellations. The top four reasons for cancellation accounted for 65% of all cancelled surgeries and were all patient initiated. CONCLUSIONS: There was also evidence that some specialties were more susceptible to DOS cancellation than others. The paper ends with proposals to reduce patient-initiated cancellations and directions for future research.