Evaluation of the clinical impact of concomitant acid suppression therapy in colorectal cancer patients treated with capecitabine monotherapy.

BACKGROUND: Capecitabine is an oral chemotherapeutic agent used in colorectal cancer. Two prior studies found a negative impact with the concomitant use of proton pump inhibitor agents during treatment with capecitabine in patients with early colorectal and gastroesophageal cancers. OBJECTIVE: To determine if there is a clinical impact of the concomitant use of capecitabine and acid suppression therapy in patients with local and metastatic colorectal cancer. METHODS: This was a single-center retrospective cohort study of adult patients with colorectal cancer on capecitabine monotherapy between 2011 and 2017. Progression-free survival (PFS) and overall survival were compared between patients on acid suppression therapy and those not on acid suppression therapy. RESULTS: A total of 70 patients were included. Patients on acid suppression therapy at capecitabine initiation (21%) had decreased progression-free survival versus those not on acid suppression therapy (HR 2.24, 95% CI 1.06-4.41, p = 0.035), after adjusting for disease severity and age. Acid suppression therapy use was associated with a numerical decrease in overall survival (HR 1.86, 95% CI 0.81-3.91, p = 0.14). In patients on any concomitant acid suppression therapy (25%), there was a decreased rate of progression-free survival (HR 6.21, 95% CI 2.56-14.32, p = 0.0001) but not overall survival (HR 1.64, 95% CI 0.68-3.54, p = 0.25) versus those without concomitant acid suppression therapy, after adjusting for age and disease severity. CONCLUSIONS: Concurrent use of acid suppression therapy and capecitabine was associated with decreased progression-free survival, and there was a trend towards decreased overall survival. Due to the demonstrated potential of decreased efficacy, concurrent use of proton pump inhibitors or histamine 2 receptor antagonists should be avoided in colorectal cancer patients on treatment with capecitabine monotherapy.

Safety of commercial airflight in patients with brain tumors: a case series.

INTRODUCTION: Patients with intracranial masses are often advised to avoid airflight due to concerns of worsening neurological symptoms or deterioration. However, many patients often travel cross-country or internationally to tertiary care centers for definitive care. This study assesses the safety of commercial airflight for brain and skull base tumor patients without severe or progressive neurological deficits. METHODS: Patients that had traveled to our institution for surgery via commercial airflight from 2014 to 2017 were identified. An electronic survey was administered (RedCap) and flight duration, aircraft type, presenting symptoms and new or worsened peri-flight symptoms were queried. Severity was assessed using visual analogue scale (VAS). Significant change of symptoms was determined to be greater than 25%. Demographics and clinical history were obtained from electronic medical records. Providence Health System IRB: 16-168. RESULTS: Of 665 patients operated on for brain tumor, 63 (9.5%) traveled by airflight to our center for surgery and of these, 41 (65%) completed the study (mean age 48.5 ± 16.8 years, 63% female). Pathology included pituitary and other parasellar tumors (58%), meningiomas (22%), metastatic tumors (5%), gliomas (5%), pineal tumor (5%), cerebello-pontine tumor (5%). Average tumor volume was 11.4 cc and average maximal dimension was 2.7 cm. Ten (24.4%) patients developed worsened symptoms during airflight including: headaches 3/19 (15.8%), fatigue 3/14 (21.4%), dizziness 3/5 (60%) and ear pain 3/3 (100%), as well as one patient who had new onset seizures inflight. Seven patients (70%) sustained worsened symptoms after airflight. There were no permanent neurological deficits related to airflight. There was no correlation with tumor size, volume, location or flight duration with development of neurological symptoms. There was an inverse correlation between peri-flight corticosteroid usage and symptom exacerbation (p = 0.048). No patient with completely asymptomatic tumors developed new symptoms during flight. CONCLUSIONS: Most patients with brain and skull base tumors can travel safely via commercial airflight with acceptable symptom exacerbation. However, consideration should be given to administering corticosteroids and possibly anticonvulsants to patients who are symptomatic and/or have relatively large tumors with mass effect and peritumoral edema.

No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer's Disease: A Randomised Controlled Trial.

Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce the risk of cognitive decline and Alzheimer's disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer's disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.

The influence of tonality, tempo, and musical sophistication on the listener's time-duration estimates.

Music listening affects time perception, with previous studies suggesting that a variety of factors may influence this: musical, individual, and environmental. Two experiments investigated the effect of musical factors (tonality and musical tempo) and individual factors (a listener's level of musical sophistication) on subjective estimates of duration. Participants estimated the duration of different versions of newly composed instrumental music stimuli under retrospective and prospective conditions. Stimuli varied in tempo (90-120 bpm) and tonality (tonal-atonal), in a 2 × 2 factorial design, while other musical parameters remained constant. Estimates were made using written estimates of minutes and seconds in Experiment 1, and the reproduction method in Experiment 2. Two-way analyses of variance (ANOVAs) showed no main effect of tonality on estimates and no significant interactions between tempo and tonality, under any condition. Musical tempo significantly affected estimates, with the faster tempo leading to longer estimates, but only in the prospective condition, and with the use of the reproduction method. Correlation matrices using the Pearson correlation coefficient found no correlation between musical sophistication scores (measured using the Goldsmiths Musical Sophistication Index [Gold-MSI]) and verbal or reproduction estimates. In conclusion, together with the existing literature, findings suggest that (1) changes in tonality, without further changes in rhythm, metre, or melodic contour, do not significantly affect estimates; (2) small changes in musical tempo influence only prospective reproduction estimates, with larger tempo differences or longer stimuli being needed to cause changes in retrospective estimates; (3) participants' level of musical sophistication does not impact estimates of musical duration; and (4) empirical research on music listening and subjective time must consider potential method-dependent results.

Technical efficiency of the urban gas industry in china.

China's Paris Agreement Pledge and recent introduction of an Emissions Trading Scheme have created a need for information on where it makes the most economic sense to use different sources of energy. With lower carbon dioxide emissions, natural gas and liquefied petroleum gas provide cleaner sources of energy relative to coal. Although it is practically crucial to investigate the use of these two sources, empirical studies are limited due to lack of data. To fill the research gap, this paper studies the efficiency of natural gas and liquefied petroleum gas sector in China by using data from 24 major province-level divisions over the years 2006-2015. Efficiency is defined as the utility's ability to produce the highest output given fixed inputs. We find that: (1) GDP per capita and high customer density are associated with higher levels of efficiency and (2) utilities that serve higher proportions of households (as opposed to industry and firms) are associated with lower levels of efficiency. Policy makers can use this information to address China's energy needs due to rapid urbanization while also pursuing Paris Agreement goals.

Mapping Teacher Informal Advice Networks as a Tool for District Administrators: A Case Study.

With few resources and little time for professional development, science education leaders need ways to efficiently disseminate effective pedagogical practices, improve instruction, and support science teachers (Shaked and Schecter, 2016). Efficient leader strategies are especially important as teachers and districts face reforms to existing standards. One potential avenue for dissemination is leveraging the informal social networks of teachers. Therefore, it is necessary to map and interpret informal teacher networks. We describe a case study involving a partnership of university researchers and a district science curriculum specialist who collected survey data to map district teacher informal advice-seeking networks. We also describe the kinds of network analysis information that science education leaders can use to make strategic decisions about the costs and benefits of efforts directed at all teachers (e.g. workshops, annual professional development time) and those directed at highly connected teachers who can become or already are informal leaders in their communities.

Graduate nurses' capability upon entering the workforce: An integrative review.

OBJECTIVES: To clarify capability for work readiness in newly graduated registered nurses as viewed from the perspective of clinicians in practice, educators in tertiary institutions, and graduates. DESIGN: Integrative review. DATA SOURCES: Databases searched for peer-reviewed studies included PubMed, MEDLINE, ERIC, Campbell collaboration, Google Scholar, and Cochrane databases. REVIEW METHODS: Pragmatism informed this integrative review. The five-stage method described by Whittemore and Knafl was used to enable rigorous examination of the expected capability of graduate nurses. A comprehensive database search was conducted using PRISMA guidelines. Eighteen articles were appraised and analysed for this review. The capability concept was used as a framework for analysis. RESULTS: Eighteen articles met the inclusion criteria. Findings revealed that although there is no definition for graduate nurses' work readiness, there is a common theme. Graduate nurses are expected to have broad theoretical knowledge (knowing) along with practical knowledge (doing). They are also expected to demonstrate integrity, honesty, respect, compassion, and a moral compass. A list of personal attributes and organisational acumen was also reflective of graduate readiness upon entering the workforce and identified as necessary capabilities for graduates. CONCLUSIONS: A picture of the perfect employee is illustrated in the definition of work readiness by the participants of the original studies. Yet there is a lack of stakeholder consensus on the capabilities expected from a graduate nurse.

Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by heterogeneous lesions containing CD207(+) Langerhans cells (LCs) and lymphocytes that can arise in almost any tissue and cause significant morbidity and mortality. After decades of research, the cause of LCH remains speculative. A prevailing model suggests that LCH arises from malignant transformation and metastasis of epidermal LCs. In this study, CD207(+) cells and CD3(+) T cells were isolated from LCH lesions to determine cell-specific gene expression. Compared with control epidermal CD207(+) cells, the LCH CD207(+) cells yielded 2113 differentially expressed genes (false discovery rate < 0.01). Surprisingly, the expression of many genes previously associated with LCH, including cell-cycle regulators, proinflammatory cytokines, and chemokines, were not significantly different from control LCs in our study. However, several novel genes whose products activate and recruit T cells to sites of inflammation, including SPP1 (osteopontin), were highly overexpressed in LCH CD207(+) cells. Furthermore, several genes associated with immature myeloid dendritic cells were overexpressed in LCH CD207(+) cells. Compared with the peripheral CD3(+) cells from LCH patients, the LCH lesion CD3(+) cells yielded only 162 differentially regulated genes (false discovery rate < 0.01), and the expression profile of the LCH lesion CD3(+) cells was consistent with an activated regulatory T cell phenotype with increased expression of FOXP3, CTLA4, and SPP1. Results from this study support a model of LCH pathogenesis in which lesions do not arise from epidermal LCs but from accumulation of bone marrow-derived immature myeloid dendritic cells that recruit activated lymphocytes.

Lower omega-3 fatty acid intake and status are associated with poorer cognitive function in older age: A comparison of individuals with and without cognitive impairment and Alzheimer's disease.

OBJECTIVES: Various strands of evidence suggest that low intake of omega-3 fatty acids increases risk of cognitive decline and dementia. The present study investigated differences in dietary intake and blood plasma content of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in individuals with cognitive impairment no dementia (CIND), individuals with Alzheimer's disease (AD), and healthy volunteers (HV). METHODS: A total of 135 individuals aged between 55 and 91 years (19 AD, 55 CIND, and 61 HV) were assessed predominantly within a hospital setting. RESULTS: Compared with age and sex-matched HV, individuals with AD or CIND performed poorly on a majority of tests of cognitive function. Impairment was greatest for delayed and verbal recognition memory. CIND individuals were less impaired than AD individuals. Omega-3 intake and the percentage of EPA and DHA in plasma phosphatidylcholine (PC) showed a similar pattern (AD < HV, with intermediate scores for CIND). Across the whole sample, and after controlling for age, years of education, level of socio-economic deprivation, and gender, omega-3 intake, plasma PC DHA, and plasma PC EPA were all significant positive predictors of memory functioning. DISCUSSION: These results are consistent with the possibility that omega-3 fatty acid nutrition has an impact on cognitive decline, but could equally be explained by dietary changes that occurred after onset of cognitive decline. It is also possible that the results could be explained by unknown confounding factors.

Levelling the Playing Field: The Role of Workshops to Explore How People With Parkinson's Use Music for Mood and Movement Management as Part of a Patient and Public Involvement Strategy.

From a humanistic perspective, participatory processes in research find support on both ethical and moral grounds. In practical terms however, it is often difficult to establish protocols that best honour (i.e., elicit, capture, and integrate) the opinions of individuals and groups that represent the various specific stakeholders (e.g., from allied health, scientific, and academic disciplines) needed to investigate complex phenomena. Here, we describe a consultation process (funded by Parkinson's UK) devised to explore use of music among people with Parkinson's in relation to potential applications to enhance quality of life. People with Parkinson's were paired with researchers in order to discuss music on an equal footing so as to enable participant empowerment. We describe outcomes that demonstrate avenues of success as a result of this approach and additional insights gained through these processes in the hope of informing future practise. It has been our experience that researchers must establish a balance between (a) ensuring methodological rigour within an appropriate framework, and (b) facilitating informal "playtime" that develops connectivity between participants and enables both creative thinking and reflexive practise amongst stakeholders. We encourage researchers not to underestimate "playtime" as an important vehicle to foster this social interactivity and fuel the good will required to conduct inclusive and relevant research.

Replicating or franchising a STEM afterschool program model: core elements of programmatic integrity.

BACKGROUND: Designed in 2012 with a first implementation in 2013, NE STEM 4U is a professional development program for post-secondary students/undergraduates, and serves as a source of outreach, content knowledge generation, and STEM literacy for youth in grades kindergarten through 8th grade (ages 5-14). The model empowers post-secondary students as facilitators of inquiry-based learning within the context of an out-of-school time program. This study investigated the potential for replicating or 'franchising' this model by evaluating on the following: (1) Is the model replicable? And, if so, (2) what core elements are necessary for program fidelity? And (3) is there a dependency on a particular setting/participant type (e.g., a more rural or urban setting)? RESULTS: Strategic expansion of the program to different institutional types (i.e., Research 1, Research II, and a predominantly undergraduate institution), different geographical locations (i.e., rural and urban), and with various school district partners (i.e., large and small) determined that program fidelity and replicability required 4 core elements or criteria: (i) intentional programming, (ii) staff quality, (iii) effective partnerships, and (iv) program evaluation and continuous improvement. Importantly, we examined emergent themes by each site, as well as in combination (n = 16 focus group participants, n = 12 reflection surveys). These data indicated that Flexibility (21.22%), Student Engagement (i.e., Youth) (19.53%), Classroom Management (i.e., also pertaining to youth) (19.31%), and Communication (15.71%) were the themes most referenced by the post-secondary student mentors in the NE STEM 4U program, regardless of site. Finally, the YPQA results demonstrate general replication of program quality in a "franchise" location. CONCLUSIONS: These results highlight the core elements of the NE STEM 4U program for consideration of expansion (through strategic replication or 'franchising') as a possible international model. The findings and voices highlight the program's trajectory toward success into environments that expand professional development for post-secondary students, and for delivering STEM opportunities for youth. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40594-021-00320-0.

Holistic aboveground ecological productivity efficiency modeling using data envelopment analysis in the southeastern U.S.

Aboveground net primary productivity (ANPP) of an ecosystem is among the most important metrics of valued ecosystem services. Measuring the efficiency scores of ecological production (ESEP) based on ANPP using relevant variables is valuable for identifying inefficient sites. The efficiency scores computed by the Data Envelopment Analysis (DEA) may be influenced by the number of input variables incorporated into the models and two DEA settings-orientations and returns-to-scales (RTSs). Therefore, the objectives were threefold to: (1) identify soil-environmental variables relevant to ANPP, (2) assess the sensitivity of ESEP to the number of input variables and DEA settings, and (3) assess local management relations with ESEP. The ANPP rates were calculated for pine forests in the southeastern U.S. where 10 management types were used. This was followed by an all-relevant variable selection technique based on 696 variables that cover biotic, pedogenic, climatic, geological, and topographical factors. Five minimal-optimal variable selection techniques were further applied to create five parsimonious sets that contain a different number of variables used as DEA inputs. After setting ANPP as the output variable, two DEA orientations (input/output) and six RTS were applied to compute ESEP. The variable selection methods succeeded in objectively identifying the major factors relevant to ANPP variation. The site index showed the highest correlation with ANPP (r = 0.39), while various precipitation factors were negatively correlated (r = - 0.15~ - 0.29, p < 0.01). Parsimonious ESEP models observed a decrease in score variances as the number of input variables increased. Various RTS produced similar scores across orientations. Of the DEA settings, an output orientation with decreasing RTS produced the most progressive ESEP with large variation. Results also suggested that macro- and micronutrient fertilization is the best combination of management strategies to achieve high ESEP. This holistic benchmark approach can be applied to other ecological functions in diverse regions.

Chronic toxicity of fluorotelomer acids to Daphnia magna and Chironomus dilutus.

Saturated and unsaturated fluorotelomer carboxylic acids (fluorotelomer acids: FTAs) represent important intermediates in the degradation of fluorotelomer alcohols to perfluorinated carboxylic acids (PFCAs). Recent studies have detected FTAs at low concentrations (ng/L) in precipitation and surface waters; however, information regarding chronic toxicity is lacking. The present study assessed the chronic toxicity of the 8:2 saturated fluorotelomer carboxylic acid (8:2 FTCA) to Chironomus dilutus and the 10:2 saturated and unsaturated fluorotelomer carboxylic acids (10:2 FTCA and 10:2 fluorotelomer unsaturated carboxylic acid [FTuCA]) to Daphnia magna in separate life-cycle tests. In D. magna tests the FTCA was consistently more toxic than the FTuCA. Lethal concentrations (LC50s) were 150 and >60 microg/L for FTuCA and FTCA, respectively. Reproduction was significantly reduced relative to the controls, with respective median effective concentrations (EC50s) for time to first brood and mean number of offspring/female of 287 and 214 microg/L for FTuCA and 50 and 48 microg/L for FTCA. In tests with C. dilutus, EC50s for survival and growth at 20 d were 2,610 and 1,250 microg/L. Total emergence and time to first emergence, the most sensitive endpoints, yielded EC50s of 440 and 890 microg/L. Few adults emerged and no reproduction occurred at the two highest concentrations (600 and 1540 microg/L). Mean number of eggs/female was not affected. These results represent the first chronic toxicity data for FTCAs and additional evidence that FTCAs are more toxic than some PFCAs. While the results indicate that current environmental concentrations of FTAs likely pose negligible risk to aquatic biota, additional quantification of FTAs in surface waters and assessment of their toxicity is needed before meaningful assessments of potential risks to aquatic biota are possible.

What Determines the Perception of Segmentation in Contemporary Music?

BACKGROUND: This study concerns the perception of musical segmentation during listening to live contemporary classical music. Little is known about how listeners form judgments of musical segments, particularly when typical section markers, such as cadences and fermatas, are absent [e.g., Sears et al. (2014)] or when the music is non-tonal (e.g., in much contemporary classical music). AIMS: The current study aimed to examine the listeners' segmentation decisions in a piece of contemporary music, Ligeti's "Fanfares"? METHODS: Data were gathered using a smartphone application [Practice & Research in Science & Music (PRiSM) Perception App] designed for this study by the Royal Northern College of Music (RNCM) Centre for PRiSM and the Oxford e-Research Centre. A total of 259 audience participants were asked to "tap" when they felt that a section had ended. Subjective responses were captured, as well as contextual data about the participants. RESULTS: The audience members demonstrated high levels of agreement regarding segmentation, mostly at places in the music involving breaks in the musical texture (one piano hand resting), changes in dynamic (volume), and changes in register/pitch. A sense of familiarity with contemporary repertoire did seem to influence the responses-the participants who self-reported being familiar with contemporary music used a wider range of cues to make their segmentation decisions. The self-report data analysis suggested that the listeners were not always aware of how they made decisions regarding segmentation. The factors which may influence their judgment of musical segmentation are, to some extent, similar to those identified by music analysis (Steinitz, 2011) but different in other ways. The effect of musical training was found to be quite small. CONCLUSION: Whether musically trained and/or familiar with contemporary classical music or not, the listeners demonstrate commonalities in segmentation, which they are not always aware of. This study has implications for contemporary composers, performers, and audiences and how they engage with new music in particular.

Comparison of FDG-PET scans to conventional radiography and bone scans in management of Langerhans cell histiocytosis.

BACKGROUND: We evaluated the effectiveness of FDG-PET scans in identifying sites of active disease and assessing response to therapy in patients with Langerhans cell histiocytosis (LCH). Changes in standardized uptake value (SUV) indicated increased or decreased disease activity before changes are evident by plain films or bone scans. METHODS: One hundred and two PET scans for 44 patients (41 children, 3 adults) with biopsy-proven LCH were compared with 83 corollary imaging modalities and were rated for overall clinical utility: false positive or negative ("inferior"), confirming lesions identified by another imaging modality ("confirmatory"), or showing additional lesions, response to therapy or recurrence of disease activity ("superior"), in comparison to bone scans, MRI, CT or plain films. RESULTS: FDG-PET was rated superior in that 90/256 (35%) new, recurrent, or lesions responding to therapy were identified via change in standard uptake value (SUV) before other radiographic changes. PET scans confirmed active LCH in 146/256 (57%). FDG-PET was superior to bone scans in that 8/23 (34%) lesions, 11/53 (21%) comparisons to lesions found by MRI, 13/64 (20%) CT, and 58/116 (50%) plain films. PET scans confirmed lesions found by: 14/23 (61%) bone scans, 33/53 (62%) MRI, 45/64 (65%) CT, and 54/116 (46%) of plain films. CONCLUSIONS: Whole body FDG-PET scans can detect LCH activity and early response to therapy with greater accuracy than other imaging modalities in patients with LCH lesions in the bones and soft tissues. Whole-body FDG-PET scanning is an important and informative study at diagnosis and for following disease course in patients with LCH.

Event-related potential (ERP) evidence for varied recollection during source monitoring.

The source monitoring framework (SMF; M. K. Johnson, S. Hashtroudi, & D. S. Lindsay, 1993) posits that source monitoring can be supported by varying degrees of recollection. Source judgments were made for words heard at study (male or female voice) followed by remember/know (RK) judgments in order to assess differences in degrees of recollection during source monitoring (J. L. Hicks, R. L. Marsh, & L. Ritschel, 2002). The neural correlate of recollection was examined by contrasting event-related potentials (ERPs) for R and K responses that followed accurate source judgments. The recollection ERP effect was greater for R than K responses but greater for K responses than correct rejections, which reinforces the behavioral evidence that indicates source monitoring can be supported by varying degrees of recollection. A robust late posterior negativity ERP effect was present and began earlier for accurate source judgments given subsequent R than K responses. This is interpreted as reflecting systematic decision processes that are described by the SMF.

Measuring Information Processing Speed in Mild Cognitive Impairment: Clinical Versus Research Dichotomy.

A substantial body of research evidence is indicative of disproportionately slowed information processing speed in a wide range of multi-trial, computer-based, neuroimaging- and electroencephalography-based reaction time (RT) tests in Alzheimer's disease and mild cognitive impairment (MCI). However, in what is arguably a dichotomy between research evidence and clinical practice, RT associated with different brain functions is rarely assessed as part of their diagnosis. Indeed, often only the time taken to perform a single, specific task, commonly the Trail making test (TMT), is measured. In clinical practice therefore, there can be a failure to assess adequately the integrity of the rapid, serial information processing and response, necessary for efficient, appropriate, and safe interaction with the environment. We examined whether a typical research-based RT task could at least match the TMT in differentiating amnestic MCI (aMCI) from cognitively healthy aging at group level. As aMCI is a heterogeneous group, typically containing only a proportion of individuals for whom aMCI represents the early stages of dementia, we examined the ability of each test to provide intra-group performance variation. The results indicate that as well as significant slowing in performance of the operations involved in TMT part B (but not part A), individuals with aMCI also experience significant slowing in RT compared to controls. The results also suggest that research-typical RT tests may be superior to the TMT in differentiating between cognitively healthy aging and aMCI at group level and in revealing the performance variability one would expect from an etiologically heterogeneous disorder such as aMCI.

Supporting Graduate Nurse Transition: Collaboration Between Practice and University.

Making the transition from student to RN is challenging and demanding. In Australia, where nurses commonly graduate after 3 years in a Bachelor of Nursing program, graduate transition programs have been established in the workplace to support and socialize new graduates to nursing practice. These programs vary in content, rigor, and available support mechanisms, and no nationally agreed upon standards of expected graduate performance exist. Providing a structured, evidence-based, and clinically focused education and support program specific to the needs of graduate nurses contributes to quality care and patient safety and has significant benefits for the individual graduate, the employing organizations, and health care. This article presents the development and implementation of the Bachelor of Nursing With Clinical Honors (Transition to Practice) program offered by the University of Tasmania, in collaboration with St. Vincent's Private Hospital, Sydney, Australia.

Use of a physostigmine continuous infusion for the treatment of severe and recurrent antimuscarinic toxicity in a mixed drug overdose.

INTRODUCTION: Physostigmine was once a widely used antidote for the treatment of antimuscarinic toxicity. However, reports describing the association of physostigmine with asystole and seizures in severe tricyclic antidepressant poisoning resulted in a decrease in use. Recent literature has demonstrated that physostigmine is a safe and effective antidote for the treatment of antimuscarinic toxicity. There are only two previously published articles regarding the use of physostigmine administered as a continuous intravenous infusion for persistent antimuscarinic toxicity. We present a case of physostigmine continuous infusion for the treatment of antimuscarinic symptoms in a polydrug overdose due to the ingestion of diphenhydramine along with bupropion, citalopram, acetaminophen, and naproxen. CASE PRESENTATION: A 13-year-old female presented with hyperthermia, myoclonus and rigidity, hallucinations, severe agitation, and antimuscarinic toxicity including inability to sweat after a polydrug overdose. Several doses of lorazepam were administered followed by physostigmine which produced resolution of hallucinations and attenuation of the antimuscarinic symptoms including perspiration, temperature improvement, and decreased agitation. After periods of improvement and recurrence of antimuscarinic effects, a continuous infusion of physostigmine was administered at 2 mg/h and continued for almost 8 h to maintain attenuation of symptoms. GABAergic agents including lorazepam and phenobarbital were used later in the hospital course for presumed symptoms of serotonergic and adrenergic toxicity after resolution of antimuscarinic effects. The patient did not experience any adverse effects of physostigmine administration. DISCUSSION: Physostigmine administered as a continuous infusion may be a reasonable treatment option for severe and recurrent symptoms related to antimuscarinic toxicity.

Abnormal inhibition of return in mild cognitive impairment: is it specific to the presence of prodromal dementia?

Although there is some evidence that amnestic mild cognitive impairment (aMCI) can be characterized by significant deficits in visuospatial function, the cross-sectional design of the majority of these studies renders it impossible to determine whether such deficits occur in aMCI as a result of, or accompany, amnestic dysfunction per se or whether they are the result of disproportionately poorer performance in a sub-group of patients for whom aMCI represents prodromal dementia. Similarly, whether the absence of aMCI-related functional deficit stems from the masking of dementia-specific abnormality by the preserved performance of those with a different cause of aMCI cannot be ascertained. Here we report the outcome of a cross-sectional and 2.5-year longitudinal evaluation follow-up, computer-based study of visuospatial attention, specifically attentional disengagement and inhibition of return and the mean (RTSPEED) and intra-individual variability (IIVRT) of their component reaction times, in 45 patients with aMCI and 31 cognitively healthy older adults. Reduced inhibition of return (p = 0.01 and p = 0.037 in response to 400 and 800 ms cue to target interval conditions), slowed RTSPEED (p = 0.038 and p = 0.03 in response to 400 and 800 ms cue), and raised IIVRT at baseline testing (p = 0.003, p = 0.026, p = 0.013 in response to 200, 400 and 800 ms cue) were associated with the development of dementia within the 2.5-year follow-up period, whereas the performance of patients with aMCI who did not develop dementia did not differ significantly from that of the cognitively healthy controls. Attentional disengagement appeared insensitive to the presence of prodromal dementia or amnestic dysfunction per se. The results indicate that those patients for whom aMCI represents prodromal dementia may experience, in addition to amnestic dysfunction, a decline in the functional integrity of some fundamental aspects of visual information processing, an effect potentially capable of increasing disease burden and reducing quality of life.