Climate change drives migratory range shift via individual plasticity in shearwaters.

How individual animals respond to climate change is key to whether populations will persist or go extinct. Yet, few studies investigate how changes in individual behavior underpin these population-level phenomena. Shifts in the distributions of migratory animals can occur through adaptation in migratory behaviors, but there is little understanding of how selection and plasticity contribute to population range shift. Here, we use long-term geolocator tracking of Balearic shearwaters (Puffinus mauretanicus) to investigate how year-to-year changes in individual birds' migrations underpin a range shift in the post-breeding migration. We demonstrate a northward shift in the post-breeding range and show that this is brought about by individual plasticity in migratory destination, with individuals migrating further north in response to changes in sea-surface temperature. Furthermore, we find that when individuals migrate further, they return faster, perhaps minimizing delays in return to the breeding area. Birds apparently judge the increased distance that they will need to migrate via memory of the migration route, suggesting that spatial cognitive mechanisms may contribute to this plasticity and the resulting range shift. Our study exemplifies the role that individual behavior plays in populations' responses to environmental change and highlights some of the behavioral mechanisms that might be key to understanding and predicting species persistence in response to climate change.

Clinical Pharmacy Practice Patterns Among North Carolina Rural Hospitals.

INTRODUCTION: Rural hospitals are isolated without adequate funding needed to provide for clinical services offered at larger health systems. The purpose of this study is to determine the clinical pharmacy services available and desired by rural hospitals in North Carolina. METHODS: This prospective, cross-sectional, survey was distributed to a cohort of rural pharmacy directors and managers at rural hospitals across North Carolina. Data collected pertained to characteristics of the hospital and pharmacy, pharmacy director, clinical services, and responder impressions on their ability to maintain or enhance clinical services. Responses were summarized utilizing descriptive statistics and free-responses were coded for similar themes. RESULTS: Seventeen respondents (32.6%) completed the survey. Clinical activities varied, as did characteristics of the hospitals and staff. Improved patient care is the primary reason why hospital pharmacies expand their clinical participation (46.7%). Pharmacy directors believed growth of clinical activities was a long-term goal while reporting regulations, staff, and finances as barriers to growth. CONCLUSION: Clinical pharmacy services vary in NC rural hospitals. Directors exhibit a willingness to expand clinical responsibilities. Rural hospital pharmacy directors desire pharmacists to be active clinically in patient care, but face barriers in reaching that goal.

Discovery of Chemicals to Either Clear or Indicate Amyloid Aggregates by Targeting Memory-Impairing Anti-Parallel Aß Dimers.

Amyloid-ß (Aß) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of their explicit role in AD progression, impeding the development of tools targeting soluble Aß oligomers. Herein parallel and anti-parallel variants of Aß(1-40) dimers were designed and synthesized, and their pathogenic properties in AD models characterized. Anti-parallel dimers induced cognitive impairments with increased amyloidogenesis and cytotoxicity, and this dimer was then used in a screening platform. Through screening, two FDA-approved drugs, Oxytetracycline and Sunitinib, were identified to dissociate Aß oligomers and plaques to monomers in 5XFAD transgenic mice. In addition, fluorescent Astrophloxine was shown to detect aggregated Aß in brain tissue and cerebrospinal fluid samples of AD mice. This screening platform provides a stable and homogeneous environment for observing Aß interactions with dimer-specific molecules.

Description of Pharmacist Recommendations in the Caring for Older Adults and Caregivers at Home (COACH) Program.

OBJECTIVE: To describe recommendations made by geriatric clinical pharmacists within an innovative care model focusing on patients with dementia living at home. DESIGN: Retrospective chart review. SETTING: Outpatients in a tertiary care Veterans Affairs health care system. PARTICIPANTS: Veterans who underwent a Caring for Older Adults and Caregivers at Home (COACH) Program assessment and had at least one medicationrelated recommendation made by a geriatric clinical pharmacist. MAIN OUTCOME MEASURES: The primary endpoint was the number and category of medication-related recommendations made by a geriatric clinical pharmacist at the initial COACH program assessment. Secondary endpoints were recommendation acceptance rates and change in potentially inappropriate medications (PIMs) at six months. RESULTS: There were 104 patients included. The mean age was 81 years and the majority of patients were male and Caucasian. At baseline, patients were receiving a mean of 12 medications/person, and 59% of patients were receiving at least one PIM. There were 248 total medication recommendations made, with a mean of 2.4 recommendations/person (range 1-5). The three most common recommendation categories were to discontinue a drug, decrease the dose, and switch to a potentially safer alternative. Providers accepted 110 (44%) recommendations within six months. Patients were receiving a mean of one PIM/person at baseline, and no change was observed at six months.CONCLUSION: This study describes recommendations made through medication reviews by geriatric clinical pharmacists within an innovative care model for patients with dementia living at home. These data may provide information to other clinical pharmacists implementing consult services in similar settings.

An Interdisciplinary Academic Detailing Approach to Decrease Inappropriate Medication Prescribing by Physician Residents for Older Veterans Treated in the Emergency Department.

OBJECTIVE: To evaluate the impact of an academic detailing intervention delivered as part of a quality improvement project by a physician-pharmacist pair on (1) self-reported confidence in prescribing for older adults and (2) rates of potentially inappropriate medications (PIMs) prescribed to older adults by physician residents in a Veteran Affairs emergency department (ED). METHODS: This quality improvement project at a single site utilized a questionnaire that assessed knowledge of Beers Criteria, self-perceived barriers to appropriate prescribing in older adults, and self-rated confidence in ability to prescribe in older adults which was administered to physician residents before and after academic detailing delivered during their emergency medicine rotation. PIM rates in the resident cohort who received the academic detailing were compared to residents who did not receive the intervention. RESULTS: Sixty-three residents received the intervention between February 2013 and December 2014. At baseline, approximately 50% of the residents surveyed reported never hearing about nor using the Beers Criteria. A significantly greater proportion of residents agreed or strongly agreed in their abilities to identify drug-disease interactions and to prescribe the appropriate medication for the older adult after receiving the intervention. The resident cohort who received the educational intervention was less likely to prescribe a PIM when compared to the untrained resident cohort with a rate ratio of 0.73 ( P < .0001). CONCLUSION: Academic detailing led by a physician-pharmacist pair resulted in improved confidence in physician residents' ability to prescribe safely in an older adult ED population and was associated with a statistically significant decrease in PIM rates.

Diagnosing and treating postpartum uterine artery pseudoaneurysm.

Uterine artery pseudoaneurysm (UAP) is an uncommon cause of postpartum hemorrhage. We present a case of a 19-year-old woman 6 weeks postpartum after low transverse cesarean delivery with recurrent heavy vaginal bleeding requiring a blood transfusion. Transvaginal sonogram revealed a UAP. Embolization of the uterine artery was performed, with resolution of her symptoms.

Evaluation of Hypoglycemia and Potential Risk Factors in a Veterans Affairs Community Living Center.

OBJECTIVES: To describe hypoglycemic events in a Veterans Affairs (VA) community living center (CLC) population and to determine predictive risk factors associated with hypoglycemia. DESIGN: Retrospective, exploratory, observational chart review. SETTING: Tertiary-care VA Healthcare System CLC. PATIENTS: Residents residing in a VA CLC with at least one active order for insulin between June 1, 2009, and June 30, 2013, were evaluated over a 90-day study period. MAIN OUTCOME MEASURES: The primary outcome was the number of days to the first hypoglycemic event as described by the survival curve analysis. The secondary outcomes included the overall incidence of hypoglycemia, the association of potential risk factors on the proportion of hypoglycemic events, and the association of potential risk factors on the development of an additional hypoglycemic event. RESULTS: There was a 49% incidence of a hypoglycemic event in the 90-day study period with a 24% incidence within the first 7 days of resident admission, representing approximately half of all events that occurred. The only statistically significant risk factor for having a hypoglycemic event was the number of units of insulin/kg/day (hazard ratio = 1.008, 95% confidence interval 1.001, 1.015; P = 0.0317) that a resident was prescribed. CONCLUSIONS: Residents are at increased risk for hypoglycemia within the first seven days of admission to a CLC. It is imperative that providers closely monitor and reevaluate antidiabetic regimens at this time of transition.

Automated intraretinal segmentation of SD-OCT images in normal and age-related macular degeneration eyes.

This work introduces and evaluates an automated intra-retinal segmentation method for spectral-domain optical coherence (SD-OCT) retinal images. While quantitative assessment of retinal features in SD-OCT data is important, manual segmentation is extremely time-consuming and subjective. We address challenges that have hindered prior automated methods, including poor performance with diseased retinas relative to healthy retinas, and data smoothing that obscures image features such as small retinal drusen. Our novel segmentation approach is based on the iterative adaptation of a weighted median process, wherein a three-dimensional weighting function is defined according to image intensity and gradient properties, and a set of smoothness constraints and pre-defined rules are considered. We compared the segmentation results for 9 segmented outlines associated with intra-retinal boundaries to those drawn by hand by two retinal specialists and to those produced by an independent state-of-the-art automated software tool in a set of 42 clinical images (from 14 patients). These images were obtained with a Zeiss Cirrus SD-OCT system, including healthy, early or intermediate AMD, and advanced AMD eyes. As a qualitative evaluation of accuracy, a highly experienced third independent reader blindly rated the quality of the outlines produced by each method. The accuracy and image detail of our method was superior in healthy and early or intermediate AMD eyes (98.15% and 97.78% of results not needing substantial editing) to the automated method we compared against. While the performance was not as good in advanced AMD (68.89%), it was still better than the manual outlines or the comparison method (which failed in such cases). We also tested our method's performance on images acquired with a different SD-OCT manufacturer, collected from a large publicly available data set (114 healthy and 255 AMD eyes), and compared the data quantitatively to reference standard markings of the internal limiting membrane and inner boundary of retinal pigment epithelium, producing a mean unsigned positioning error of 6.04 ± 7.83µm (mean under 2 pixels). Our automated method should be applicable to data from different OCT manufacturers and offers detailed layer segmentations in healthy and AMD eyes.

Application of the Layered Learning Practice Model in an Academic Medical Center.

The layered learning practice model (LLPM) is a teaching strategy designed to train residents to precept students and other residents with the oversight of a seasoned clinical pharmacist. This model serves as a tool for residency programs to implement quality precepting opportunities and learning experiences as they look for new ways to integrate multiple learners into the practice setting. The levels of the LLPM include a senior preceptor, resident, and student. It is best implemented through utilization of 4 steps: orientation to the LLPM, preexperience planning, implementation, and postexperience evaluation. Orientation introduces preceptors and residents to the LLPM and outlines expectations for each precepting level. Preexperience planning allows the resident to take a leadership role in developing calendars, rotation activities, rubrics, and activities that match goals and objectives. For implementation, the senior preceptor maintains an active role with all learners; the resident serves as the student's primary preceptor and is responsible for incorporating the student into clinical activities, evaluating student work, and providing feedback. Postexperience evaluation is designed to solicit and provide feedback to the resident and student and to identify recommendations for improvement of the LLPM. Overall, the LLPM is a multilayered model incorporating the expertise and unique learning positions of the senior preceptor, resident, and student. Redistributing components of the senior preceptor's responsibility amongst learners may result in expansion of patient care and clinical services and help satisfy the increasing demands placed on pharmacists.

Fine-needle aspiration biopsy of prostate synovial sarcoma: A case report and review of the literature.

We describe a case of synovial sarcoma originating from prostate gland. The diagnosis was confirmed by fluorescent in situ hybridization analysis (FISH) for SYT rearrangement on the cell block. Synovial sarcoma is a high grade soft tissue malignancy with exceedingly rare involvement of genitourinary tract. However this entity should be considered in the differential diagnosis when dealing with aspiration biopsies of particularly deep seated lesions with spindle cell or small round blue cell cytomorphology. Diagn. Cytopathol. 2017;45:168-172. © 2016 Wiley Periodicals, Inc.

Evaluating the Impact of Medication Safety Alerts on Prescribing of Potentially Inappropriate Medications for Older Veterans in an Ambulatory Care Setting.

Potentially inappropriate medications (PIMs) have been associated with poor outcomes in older adults. Electronic health record (EHR)-based interventions may be an effective way to reduce PIM prescribing. The main objective of this study was to evaluate changes in PIM prescribing to older adult veterans ≥65 years old in the ambulatory care setting preimplementation and postimplementation of medication alert messages at the point of computerized provider order entry (CPOE). Additional exploratory objectives included evaluating provider type and patient-provider relationship as a factor for change in PIM prescribing. A total of 1539 patients prealert and 1490 patients postalert were prescribed 1952 and 1897 PIMs, respectively. End points were reported as the proportion of new PIM orders of total new prescriptions. There was no significant difference in the rate of new PIMs prealert and postalert overall, 12.6% to 12.0% ( P = .13). However, there was a significant reduction in the rate of the top 10 most common newly prescribed PIMs, 9.0% to 8.3% ( P = .016), and resident providers prescribed fewer PIMs during both time periods. A simple, age-specific medication alert message during CPOE decreased the incidence of the most frequently prescribed PIMs in older adults receiving care in an ambulatory care setting.

Impact of Clinical Pharmacy Specialists on the Design and Implementation of a Quality Improvement Initiative to Decrease Inappropriate Medications in a Veterans Affairs Emergency Department.

BACKGROUND: As the proportion of older adult patients who interface with the health care system grows, clinical pharmacy specialists (CPS) have a pivotal role in reducing potentially inappropriate medication (PIM) use in this population. OBJECTIVES: To (a) describe CPS involvement in the design and implementation of a quality improvement (QI) initiative to decrease PIM prescribing in a Veterans Affairs (VA) emergency department (ED) and (b) report on changes in PIM prescribing before and after the initiative. METHODS: Enhancing Quality of Prescribing Practices for Veterans Discharged from the Emergency Department (EQUiPPED) is an ongoing multisite QI project that aims to decrease ED PIM prescribing. We used a mixed-method approach that applied qualitative and quantitative measures in describing the CPS role and evaluating PIM rates. PIMs were defined using the 2012 Beers Criteria. We reported monthly PIM rates in patients aged 65 years and older who were discharged from the ED from January 2012 to November 2014. A piecewise, nonlinear regression model evaluated the pattern in PIM prescriptions over time. RESULTS: At the Durham, North Carolina, VA Medical Center, a total of 4 CPS were involved with tailoring the design and implementation of the EQUiPPED intervention for local use. CPS input led to 3 key innovations: academic detailing performed by a physician-CPS pair, medication alert messages identifying medications as PIMs in the computerized patient record system, and automated reports describing the frequency and type of PIMs prescribed by each ED provider. Between February 2013 and November 2014, 73 ED providers received the academic detailing. The ED facility experienced a relative reduction of 47.5% in the rate of PIM prescribing over the observation period. CONCLUSIONS: This QI project resulted in a meaningful decrease in PIM prescribing in older ED adults. CPS contributions to QI can extend beyond pharmacotherapy and provider education to also include information technology tools using formulary management expertise.

Inhaler misuse in an older adult population.

OBJECTIVE: To determine the prevalence of inhaler misuse in an older adult population. DESIGN: Prospective observational study. SETTING: Two primary care outpatient clinics in a Veterans Affairs Medical Center in North Carolina. PARTICIPANTS: Male veterans 65 years of age and older (N = 24) prescribed a pressurized metered dose inhaler (pMDI) or a dry powder inhaler (DPI). MEASUREMENTS: Inhaler technique was evaluated using placebo inhaler devices and a standardized technique assessment form that included critical steps. Potential risk factors for misuse were obtained from the medical record, and the time for technique evaluation was collected. MAIN RESULTS: Study participants yielded 44 unique device observations. Patients were male with an average age of 82 years. All patients made at least one error, with a mean error rate of 2.5 errors/patient/inhaler, while 20 of 24 (83%) patients made at least one critical error with a mean error rate of 1.2 critical errors/patient/inhaler. Assessment of inhaler technique required 2.3 minutes/inhaler. Critical errors were made during 15 of 19 (79%) pMDI observations and 22 of 25 (88%) DPI observations. Patients with multiple inhalers or a history of stroke committed errors more often, although no risk factors demonstrated meaningful differences in error rates. CONCLUSIONS: Inhaler misuse in older adults is common, including committing critical errors that have been shown to reduce drug delivery. The time necessary for technique evaluation is relatively small. The high rate of misuse observed should serve as motivation for increased vigilance, individualized technique education, and routine re-assessment in the highly heterogeneous older adult population.

Combination of inhaled corticosteroid and bronchodilator-induced delirium in an elderly patient with lung disease.

Steroid psychosis has been well described with oral glucocorticoids, however, our search of the literature did not identify an association between delirium and the combination of inhaled glucocorticoids and long-acting beta-agonists. We describe the occurrence of delirium with the combination of an inhaled glucocorticoid and bronchodilator. An elderly male described confusion and hallucinations within 1 week after initiation of budesonide/formoterol for chronic obstructive pulmonary disease. The combination inhaler was discontinued with resolution of symptoms. Several weeks later, the patient was hospitalized and restarted on the combination inhaler. The patient was alert and oriented on admission, however, confusion and hallucinations progressed throughout his hospital stay. The combination inhaler was discontinued and his confusion and hallucinations resolved by discharge. The temporal relationship of these events and a probable Naranjo association allows for reasonable assumption that the use of the budesonide/formoterol combination inhaler caused or contributed to the occurrences of delirium in this elderly patient. The onset of delirium was likely due to the systemic absorption of the glucocorticoid from lung deposition, complicated in an individual with several predisposing risk factors for delirium. Health care providers should be aware of this potential adverse drug reaction when prescribing inhaled medications to older patients at risk for delirium.

Galantamine-associated nightmares and anxiety.

BACKGROUND: This case report describes recurrent nightmares and anxiety possibly caused by the administration and rapid dose titration of galantamine. CASE SUMMARY: A 90-year-old male with Alzheimer's disease was initiated on galantamine 4 mg twice daily for 10 days, followed by 8 mg twice daily thereafter. On followup to the geriatric clinic, the patient reported complaints of nightmares and associated anxiety. The occurrences of nightmares developed after initiating galantamine and temporally increased with galantamine titration. After discontinuation of galantamine, the patient reported no further occurrences of nightmares or anxiety and memory function remained stable. CONCLUSION: Galantamine-associated nightmares are an uncommon adverse event and may have been exacerbated by rapid titration. Although such adverse events are unlikely to cause harm in the patient, such sleep abnormalities have the potential to decrease a patient's quality of life and may require the need for alternative therapy.

Respiratory sinus arrhythmia as a measure of cognitive workload.

The current standard for measuring cognitive workload is the NASA Task-load Index (TLX) questionnaire. Although this measure has a high degree of reliability, diagnosticity, and sensitivity, a reliable physiological measure of cognitive workload could provide a non-invasive, objective measure of workload that could be tracked in real or near real-time without interrupting the task. This study investigated changes in respiratory sinus arrhythmia (RSA) during seven different sub-sections of a proposed selection test for Navy aviation and compared them to changes reported on the NASA-TLX. 201 healthy participants performed the seven tasks of the Navy's Performance Based Measure. RSA was measured during each task and the NASA-TLX was administered after each task. Multi-level modeling revealed that RSA significantly predicted NASA-TLX scores. A moderate within-subject correlation was also found between RSA and NASA TLX scores. The findings support the potential development of RSA as a real-time measure of cognitive workload.

Characteristics of head-mounted displays and their effects on simulator sickness.

OBJECTIVE: We examined the effects of several display characteristics of head-mounted displays (HMDs) on simulator sickness (SS). BACKGROUND: Technological limitations, such as display delay and reduced field of view (FOV), affect perception when using an HMD and are often thought to be related to SS. Few studies have examined the relationship between FOV and geometric FOV (image scale factor) or how HMD characteristics may interact. METHOD: Participants made active head movements to locate objects when viewing a live video via an HMD. RESULTS: Compared with no added delay, an additional 200 ms of display delay did not result in increased SS, as measured by the Simulator Sickness Questionnaire. Furthermore, an effect of image scale factor on SS was not revealed. However, SS was greater when peripheral vision was occluded than when it was not. Peripheral vision moderated the effects of image scale factor and delay on head movement velocity. CONCLUSION: Occluding peripheral vision may subject HMD users to the potential detrimental consequences of HMD characteristics more than when peripheral vision of the external environment is available, resulting in more SS. Future research should investigate to what extent peripheral vision can be occluded without increasing SS and without sacrificing realism and presence. APPLICATION: To reduce the occurrence of SS, a degree of peripheral vision of the external world should be provided. Furthermore, users and designers should be aware that head movement behavior may be affected by HMD characteristics.

Lymphocytic host response to oral squamous cell carcinoma: an adaptive T-cell response at the tumor interface.

Lymphocytic host response (LHR) in the Risk Model is histologically quantified as the density of lymphocytes at the tumor interface (Brandwein-Gensler in Am J Surg Pathol, 34:676-688, 1; in, Am J Surg Pathol 29:167-178, 2). It is classified as strong, intermediate or weak, and is inversely associated with the risk of decreased time to disease progression. In this study, we test the hypothesis that strong LHR corresponds to a greater degree of adaptive cytotoxic T cell response as compared to moderate LHR. We studied resection specimens of primary oral squamous carcinoma classified as having either strong (n = 16), intermediate (n = 20) or weak (n = 4) LHR. CD20+, CD4+, & CD8+ cells were detected by immunohistochemistry and quantified at 40× with a grid; counting the 10 fields with the most lymphocytes at the tumor interface and within tumors. Mean counts/tumor were analyzed by the 2-sided T-test. Statistically significant differences were observed for interface CD8 cells with respect to strong versus moderate LHR, strong versus weak LHR, and moderate versus weak LHR, and tumor infiltrating CD8 cells with respect to strong versus weak LHR. Statistically significant differences were also observed for interface CD4 cells with respect to strong versus weak LHR, and moderate versus weak LHR. Statistically significant differences in interface B cell counts were seen with respect to strong versus weak LHR, and moderate versus weak LHR. Decreased CD8+ T cells were significantly associated with higher stage at presentation (P = 0.005); a direct, but nonsignificant correlation was seen between decreased CD8+ T cells and decreased survival time. Immune response at the tumor interface correlates with an adaptive T cell response; the degree of cytotoxic CD8+ cells infiltrate can distinguish between strong and intermediate LHR at the interface of oral carcinomas.

Design and synthesis of Hsp90 inhibitors: exploring the SAR of Sansalvamide A derivatives.

Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative.

Antibiotic susceptibility patterns of ocular bacterial flora in patients undergoing intravitreal injections.

PURPOSE: To determine the antibiotic susceptibility patterns of conjunctival flora in patients undergoing intravitreal (IVT) injection. DESIGN: Prospective, observational study. PARTICIPANTS: Patients (n = 85) scheduled to undergo 136 IVT injections at California Vitreoretinal Center at Stanford University. METHODS: Conjunctival cultures were obtained on the day of the IVT injection from the injection site bulbar conjunctiva before the application of povidone-iodine or antibiotics. MAIN OUTCOME MEASURES: Bacterial isolates were identified and tested for antibiotic susceptibility using either the Kirby-Bauer disc-diffusion technique or MicroScan-WalkAway system. RESULTS: Our analysis included 136 samples collected from 90 eyes of 85 patients. Of those with positive cultures (n = 65), the most common bacterial isolates were coagulase-negative staphylococci (CNS), comprising 59 (83%) of the 71 bacterial strains. Among the CNS, all were susceptible to vancomycin and >80% were susceptible to gentamicin, chloramphenicol, tetracycline, and imipenem. Between 60% and 80% of the CNS were susceptible to the cephalosporins and newer generation fluoroquinolones. Fewer than 60% were susceptible to the penicillin analogs, erythromycin, and the earlier generation fluoroquinolones. Nearly half of the CNS (47%) were resistant to oxacillin/methicillin. CONCLUSIONS: Bacteria isolated from the injection site of patients undergoing IVT injections were mostly CNS. Most are sensitive to vancomycin, gentamicin, and chloramphenicol. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.