Unexpected perturbations training improves balance control and voluntary stepping times in older adults - a double blind randomized control trial.

PubMed

Kurz, Ilan; Gimmon, Yoav; Shapiro, Amir; Debi, Ronen; Snir, Yoram; Melzer, Itshak

2016-03-04

Falls are common among elderly, most of them occur while slipping or tripping during walking. We aimed to explore whether a training program that incorporates unexpected loss of balance during walking able to improve risk factors for falls. In a double-blind randomized controlled trial 53 community dwelling older adults (age 80.1±5.6 years), were recruited and randomly allocated to an intervention group (n = 27) or a control group (n = 26). The intervention group received 24 training sessions over 3 months that included unexpected perturbation of balance exercises during treadmill walking. The control group performed treadmill walking with no perturbations. The primary outcome measures were the voluntary step execution times, traditional postural sway parameters and Stabilogram-Diffusion Analysis. The secondary outcome measures were the fall efficacy Scale (FES), self-reported late life function (LLFDI), and Performance-Oriented Mobility Assessment (POMA). Compared to control, participation in intervention program that includes unexpected loss of balance during walking led to faster Voluntary Step Execution Times under single (p = 0.002; effect size [ES] =0.75) and dual task (p = 0.003; [ES] = 0.89) conditions; intervention group subjects showed improvement in Short-term Effective diffusion coefficients in the mediolateral direction of the Stabilogram-Diffusion Analysis under eyes closed conditions (p = 0.012, [ES] = 0.92). Compared to control there were no significant changes in FES, LLFDI, and POMA. An intervention program that includes unexpected loss of balance during walking can improve voluntary stepping times and balance control, both previously reported as risk factors for falls. This however, did not transferred to a change self-reported function and FES. ClinicalTrials.gov NCT01439451 .

Unexpected individual clinical site variation in eradication rates of group a streptococci by penicillin in multisite clinical trials.

PubMed

Kaplan, Edward L; Oakes, J Michael; Johnson, Dwight R

2007-12-01

Previously, we reported an unexpectedly large percentage of failures by penicillin to eradicate group A streptococci (GAS) from the upper respiratory tract. Because penicillin has been the recommended therapy for the treatment of GAS pharyngitis, our report prompted controversy. Data from clinical trials in which our laboratory has participated demonstrated marked variation in GAS eradication rates among clinical sites. The reasons for such variation have never been adequately examined. We performed statistical analyses of site variation in eradication rates to assess the potential effect on reported reduced penicillin efficacy. Penicillin GAS eradication rates were compared using data from 4 large multisite pharyngitis treatment trials (75 clinical sites; 1158 subjects). Variation in eradication rates among clinical sites was statistically evaluated [chi(2) tests and generalized estimating equation (GEE) regression models]. There was significant site-to-site variation in GAS eradication rates in each of the trials (range, 17-100%; P < 0.005) as well as between separate trials (mean range, 58-69%; P < 0.033). GEE modeling indicated that GAS eradication rates were significantly higher for clinical sites participating in more than one clinical trial. The statistically significant site-to-site variation in penicillin eradication rates was related to factors (dependencies) at individual sites. Such factors may affect assessment of therapeutic efficacy and indicate a necessity for considering clinical site variation before reporting pooled efficacy data from multiple sites; combined data may result in misleading clinical implications. This is the first report documenting significant variation resulting from individual clinical site-related factors and offers a possible explanation for reduced penicillin eradication.

Cataplexy as a side effect of modafinil in a patient without narcolepsy☆

PubMed Central

Lopes, Eduardo; Pereira, Danielle; da Silva Behrens, Nilce Sanny Costa; de Almeida Fonseca, Hassana; Calvancanti, Paola Oliveira; de Araújo Lima, Taís Figueiredo; Pradella-Hallinan, Marcia; Castro, Juliana; Tufik, Sergio; Coelho, Fernando Morgadinho Santos

2014-01-01

Narcolepsy is a disease in which there is diurnal excessive sleepiness with sleep attacks and a prevalence in the general population of 1/4000 individuals. Classically, it is characterized by cataplexy, sleep paralysis, hypnagogic hallucinations and fragmented sleep. The use of modafinil in the treatment of narcolepsy is the first option of treatment for diurnal excessive sleepiness. Although considered a safe drug for use in patients with narcolepsy, being utilized for more than 20 years, modafinil possesses a series of side effects, some of them still not fully researched or described. Side effects such as headache, nausea, anxiety, insomnia, lumbago, diarrhea, dyspepsia, rhinitis and vertigo are the most frequent. However, the clinical follow-up of patients under treatment with modafinil must be intensive and the side effects ought to be noted and evaluated. The under-response to treatment or the unexpected side effects must always be directed to differential diagnostics. The objective of this article is to describe an unexpected side effect of the use of modafinil in a patient with incorrect diagnosis of narcolepsy. PMID:26483900

A Systematic Review of the Unintended Consequences of Clinical Interventions to Reduce Adverse Outcomes.

PubMed

Manojlovich, Milisa; Lee, Soohee; Lauseng, Deborah

2016-12-01

This is a systematic review of the literature on unintended consequences of clinical interventions to reduce falls, catheter-related urinary tract infection, and vascular catheter-related infections in hospitalized patients. A systematic search of the literature was conducted in CINAHL and PubMed. We developed a screening tool and a two-stage screening process to identify relevant articles. Nine articles met inclusion criteria, and of those, 8 reported on interventions to reduce patient falls. Four studies reported a positive, unexpected benefit; 3 studies reported a negative, unexpected detriment; and 4 reported a perverse effect (different from what was expected). Three studies reported both positive and perverse effects arising from the intervention. In 4 of the studies, despite fall prevention interventions, patients fell while trying to get to the bathroom, suggesting that interventions to reduce one adverse outcome (i.e., CAUTI) may be associated with another outcome (i.e., patient falls). In some cases, there were positive outcomes for those who implemented and/or evaluated interventions. We encourage colleagues to collect and report data on possible unintended consequences of their interventions to allow a fuller picture of the relationship between intervention and all outcomes to emerge.

Zolpidem-Induced Sleepwalking, Sleep Related Eating Disorder, and Sleep-Driving: Fluorine-18-Flourodeoxyglucose Positron Emission Tomography Analysis, and a Literature Review of Other Unexpected Clinical Effects of Zolpidem

PubMed Central

Hoque, Romy; Chesson, Andrew L.

2009-01-01

Zolpidem is a hypnotic which acts at the GABAA receptor and is indicated for short-term insomnia. Sleep related disorders including somnambulism, sleep related eating and sleep-driving have been reported with zolpidem. A 51-year-old insomniac who used zolpidem 10 mg nightly starting at 44 years of age is described. A few weeks after starting zolpidem she began walking, eating, and had one episode of driving while asleep. Episodes of sleep related eating, sleepwalking, and sleeptalking occurred 3 nights per week, 1 to 2 h after sleep onset. After her evaluation, the patient's zolpidem was gradually discontinued, and all sleep related activities immediately ceased. An 18F-FDG-PET was obtained 2 months after discontinuation of zolpidem. The following day, FDG was administered 1 h after oral administration of 10 mg zolpidem, and then a second PET was performed. We report the results and a review of the literature regarding other unintended effects seen with zolpidem use. Citation: Hoque R; Chesson AL. Zolpidem-induced sleepwalking, sleep related eating disorder, and sleep-driving: fluorine-18-flourodeoxyglucose positron emission tomography analysis, and a literature review of other unexpected clinical effects of zolpidem. J Clin Sleep Med 2009;5(5):471-476 PMID:19961034

Incorporating uncertainty into medical decision making: an approach to unexpected test results.

PubMed

Bianchi, Matt T; Alexander, Brian M; Cash, Sydney S

2009-01-01

The utility of diagnostic tests derives from the ability to translate the population concepts of sensitivity and specificity into information that will be useful for the individual patient: the predictive value of the result. As the array of available diagnostic testing broadens, there is a temptation to de-emphasize history and physical findings and defer to the objective rigor of technology. However, diagnostic test interpretation is not always straightforward. One significant barrier to routine use of probability-based test interpretation is the uncertainty inherent in pretest probability estimation, the critical first step of Bayesian reasoning. The context in which this uncertainty presents the greatest challenge is when test results oppose clinical judgment. It is this situation when decision support would be most helpful. The authors propose a simple graphical approach that incorporates uncertainty in pretest probability and has specific application to the interpretation of unexpected results. This method quantitatively demonstrates how uncertainty in disease probability may be amplified when test results are unexpected (opposing clinical judgment), even for tests with high sensitivity and specificity. The authors provide a simple nomogram for determining whether an unexpected test result suggests that one should "switch diagnostic sides.'' This graphical framework overcomes the limitation of pretest probability uncertainty in Bayesian analysis and guides decision making when it is most challenging: interpretation of unexpected test results.

Unexpected Events Induce Motor Slowing via a Brain Mechanism for Action-Stopping with Global Suppressive Effects

PubMed Central

Aron, Adam R.

2013-01-01

When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression. PMID:24259571

Unexpected Complications of Novel Deep Brain Stimulation Treatments: Ethical Issues and Clinical Recommendations

PubMed Central

Cheeran, Binith; Pugh, Jonathan; Pycroft, Laurie; Boccard, Sandra; Prangnell, Simon; Green, Alexander L.; FitzGerald, James; Savulescu, Julian; Aziz, Tipu

2017-01-01

Background Innovative neurosurgical treatments present a number of known risks, the natures and probabilities of which can be adequately communicated to patients via the standard procedures governing obtaining informed consent. However, due to their novelty, these treatments also come with unknown risks, which require an augmented approach to obtaining informed consent. Objective This paper aims to discuss and provide concrete procedural guidance on the ethical issues raised by serious unexpected complications of novel deep brain stimulation treatments. Approach We illustrate our analysis using a case study of the unexpected development of recurrent stereotyped events in patients following the use of deep brain stimulation (DBS) to treat severe chronic pain. Examining these unexpected complications in light of medical ethical principles, we argue that serious complications of novel DBS treatments do not necessarily make it unethical to offer the intervention to eligible patients. However, the difficulty the clinician faces in determining whether the intervention is in the patient's best interests generates reasons to take extra steps to promote the autonomous decision making of these patients. Conclusion and recommendations We conclude with clinical recommendations, including details of an augmented consent process for novel DBS treatment. PMID:28557242

[Unexpected outings of Alzheimer patients living in retirement homes: Therapeutic perspectives].

PubMed

Brossard, F; Caron, R

2016-10-01

Various behavior disorders can occur during Alzheimer's disease, in particular unexpected outings. This article aims at understanding the diverse mechanisms present during a "runaway" episode, which can manifest in an acute way. The authors bring to light through clinical examples what is at work from a psychological perspective in order to create new accompaniment methods. First, the authors reviewed the literature on runaway episodes in order to point out necessary themes for reflection. Then, from a Freudian theoretical model, they brought to light four fundamental mechanisms: hallucinations, false recognition, non-recognition, and recognition. These are mainly, although not exhaustively, understood from perceptions, memory-traces, indications of quality, and memories. This theory was questioned by means of presented clinical cases. Various post-Freudian models allowed the authors to emphasize the pathological experience in the role of perceptions and the functions, which come into play in the psychic economy. By going back and forth between theory and clinical cases, the authors underline the importance of perception in the phenomenon of unexpected outings. Finally, the Lacanian psychoanalytical theories provide a framework to question clinical cases but also provide answers to the criticisms found in the diverse reserved models. Through this study the authors hypothesize that the runaway episodes are not senseless but result from the interaction between the effects of the brain damage and the anxiety, which they arouse in the subjectivity of the person suffering from Alzheimer's. Leaning on false-recognitions, hallucinations, and non-recognitions such as were described in "Project for a scientific psychology", the authors put forward the hypothesis that these mechanisms express themselves in an imaginary relation, as in psychosis. The question of whether the runaway episodes of Alzheimer's sufferers can be classified as psychotic breakouts with a loss of touch with reality, or if the runaway episodes could be prevented by offering enough reassurance and support, is open to further debate. Copyright © 2016. Published by Elsevier Masson SAS.

[Grenade splinter injury simulating thrombophlebitis].

PubMed

Gaber, Y

2003-02-01

Two patients with a grenade-splinter injury with clinical symptoms of a thrombophlebitis and periphlebitis are presented. Unexpectedly, the supposed thrombus proved to be metallic fragments. Both patients recalled to be wounded in the second world war in 1944/1945 by grenades. The splinters were not extracted. Both patients experienced more than 5 decades without any symptoms. As an after-effect caused by movement of the splinters, significant superficial inflammation could be seen now.

The congenital Zika virus infection: still a puzzle.

PubMed

Salomão, José Francisco M

2018-01-01

As a new disease, some features of the congenital Zika virus infection are not yet fully understood. The current Brazilian outbreak brought up an unexpected increase in the number of microcephaly cases as this strain is essentially neurotropic and associated with devastating effects on the developing central nervous system. This focus session aims to discuss the several issues related to the epidemiology, diagnosis, clinical features, and treatment of the congenital Zika virus infection.

Hepatic Hemangioendothelioma Presenting as Sudden Unexpected Death in Infancy: A Case Report

PubMed Central

Dempers, Johan; Wadee, Shabbir Ahmed; Boyd, Theonia; Wright, Colleen; OdendaaL, Hein J; Sens, Mary Ann

2014-01-01

The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy, death scene investigation and review of medical history to exclude known causes of death. Death from occult neoplastic disease in infancy is extremely rare but is within the broad differential of SIDS. We report the sudden and unexpected death of a one-month-old infant from a hepatic (infantile) hemangioendothelioma. The physiologic mechanism of death was likely cardiac failure induced by the circulatory demands of this large vascular tumor and respiratory compromise from diaphragmatic thoracic incursion. The clinical progression and pathology of these relatively common tumors of infant livers are extremely variable. This case dramatically illustrates the potential for fatal outcome of this tumor, as well as the need for the autopsy to determine the cause of sudden and unexpected death in an infant PMID:20465426

[Consequences of the 12th AMG amendment on the conduct of non-commercial clinical trials].

PubMed

Rossion, I

2005-12-01

In 2004, the German Drug Law was reformed substantially putting into effect the European directive 2001/20/EG on Good Clinical Practice (GCP). Investigator initiated trials have to comply with the same requirements as clinical trials for drug development. When registered drugs are used in non-commercial clinical trials some simplifications are possible.Currently, all essential elements of GCP, such as financing of the trial, laying-down of sponsor responsibilities, establishing an extensive quality assurance system as well as immediate reporting of unexpected serious drug reactions, are stipulated by law. Since regulatory authorities and ethics committees have to approve every clinical trial, surveillance is reinforced. The new requirements cannot be met without sufficient financing, qualified personnel and professional structures for clinical trials. Compared to European partners, the research location Germany is at a disadvantage due to high administrative workload and costs.

Rates of abnormalities and infectious agents in cervical smears from female inmates in Texas: comparison with private and university clinic patients.

PubMed

Logrono, R; Wong, J Y

1999-09-01

Inmates are generally considered a high-risk population for gynecologic neoplasia and sexually transmitted diseases. Cervical smears from prisoners of the Texas Department of Corrections (TDC) were expected initially to have higher rates of cellular abnormalities and infectious agents than do smears from the general population. The cytologic findings from 25,522 TDC gynecologic smears were compared with those of 6883 cases from The University of Texas Medical Branch (UTMB) affiliated physician private clinics, and with 56,178 from the UTMB hospital clinics. The period of study was from September 1995 to February 1998. This study revealed a 5.23% higher rate of abnormalities for TDC gynecologic smears as compared with that for the private clinic smears. However, the TDC rate of abnormalities was unexpectedly 1.08% lower than that for the UTMB clinic smears. These unexpected findings were probably the result of a more selected high-risk population referred to the UTMB clinics. The TDC smears showed also the highest incidence of trichomoniasis.

Abrupt and unexpected stressful life events are followed with increased disease activity in spondyloarthritis: a two years web-based cohort study.

PubMed

Luo, Guanguan; Boelle, Pierre Yves; Turbelin, Clément; Costantino, Félicie; Kerneis, Solen; Nahal, Roula Said; Breban, Maxime; Hanslik, Thomas

2018-06-05

The contribution of environmental factors to spondyloarthritis (SpA) course remains poorly characterized. We previously reported a possible triggering of disease flares by stressful life events and vaccination. The objective of the present study was to specify the types of vaccine and life event that may influence disease activity. A prospective cohort of adult SpA was followed for two years. Patients logged on to a secured website every month to complete a standardized auto-questionnaire. They reported whether they had been exposed to stressful life events, vaccinations or other environmental factors. Patients were asked to rate the distress resulting from exposure to life events on a numerical rating scale (NRS: 0-10). Primary outcome variable was the variation of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured on two consecutive connections. Months where an event occurred were compared to months without events. The cutoff value of 1 is defined as the minimal clinically important variation for the BASDAI. The 272 enrolled SpA patients returned 3,388 questionnaires. Months where an abrupt and unexpected traumatic event occurred were associated with a significant increase of BASDAI of 0.57 [95%CI: 0.29; 0.85] (p<0.001). The higher the rating of distress, the larger the impact on BASDAI, reaching a clinically meaningful increase of 0.99 [0.17; 1.82] for a VNS ≥9. The effect of stressful events on BASDAI persisted during a median of 3 months. No other environmental factor was significantly associated with BASDAI variations. Among stressful life events, abrupt and unexpected events were associated with transient worsening of disease activity in SpA, which reached a clinically meaningful increase for the highest rating of distress. Association between vaccines and disease flare was not confirmed. Copyright © 2018. Published by Elsevier Masson SAS.

Sphingosine 1-Phosphate Receptor Modulators and Drug Discovery

PubMed Central

Park, Soo-Jin; Im, Dong-Soon

2017-01-01

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P1–5. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn’s disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications. PMID:28035084

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

PubMed Central

Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

2015-01-01

Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

Clinical audit of leg ulceration prevalence in a community area: a case study of good practice.

PubMed

Hindley, Jenny

2014-09-01

This article presents the findings of an audit on venous leg ulceration prevalence in a community area as a framework for discussing the concept and importance of audit as a tool to inform practice and as a means to benchmark care against national or international standards. It is hoped that the discussed audit will practically demonstrate how such procedures can be implemented in practice for those who have not yet undertaken it, as well as highlighting the unexpected extra benefits of this type of qualitative data collection that can often unexpectedly inform practice and influence change. Audit can be used to measure, monitor and disseminate evidence-based practice across community localities, facilitating the identification of learning needs and the instigation of clinical change, thereby prioritising patient needs by ensuring safety through the benchmarking of clinical practice.

Inattentional blindness is influenced by exposure time not motion speed.

PubMed

Kreitz, Carina; Furley, Philip; Memmert, Daniel

2016-01-01

Inattentional blindness is a striking phenomenon in which a salient object within the visual field goes unnoticed because it is unexpected, and attention is focused elsewhere. Several attributes of the unexpected object, such as size and animacy, have been shown to influence the probability of inattentional blindness. At present it is unclear whether or how the speed of a moving unexpected object influences inattentional blindness. We demonstrated that inattentional blindness rates are considerably lower if the unexpected object moves more slowly, suggesting that it is the mere exposure time of the object rather than a higher saliency potentially induced by higher speed that determines the likelihood of its detection. Alternative explanations could be ruled out: The effect is not based on a pop-out effect arising from different motion speeds in relation to the primary-task stimuli (Experiment 2), nor is it based on a higher saliency of slow-moving unexpected objects (Experiment 3).

Severe excessive daytime sleepiness induced by hydroxyurea.

PubMed

Revol, Bruno; Joyeux-Faure, Marie; Albahary, Marie-Victoire; Gressin, Remy; Mallaret, Michel; Pepin, Jean-Louis; Launois, Sandrine H

2017-06-01

Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Orthographic Processing and Visual Sequential Memory in Unexpectedly Poor Spellers

ERIC Educational Resources Information Center

Holmes, Virginia M.; Malone, Aisling M.; Redenbach, Holly

2008-01-01

Does unexpectedly poor spelling in adults result from inferior visual sequential memory? In one experiment, unexpectedly poor spellers performed significantly worse than better spellers in the immediate reproduction of sequences of visual symbols, but in a second experiment, the effect was not replicated. Poor spellers were also no worse at the…

The French prospective multisite registry on sudden unexpected infant death (OMIN): rationale and study protocol

PubMed Central

Levieux, Karine; Patural, Hugues; Harrewijn, Inge; Briand Huchet, Elisabeth; de Visme, Sophie; Gallot, Géraldine; Chalumeau, Martin; Gras Le Guen, Christèle; Hanf, Matthieu; Garcia-Meric, Patricia

2018-01-01

Introduction Even after ‘back-to-sleep’ campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1 month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area. Methods and analysis This observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths. Ethics and dissemination The French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l’Informatique et des Libertés: number 915273) and by an independent ethics committee (Groupe Nantais d’Ethique dans le Domaine de la Santé: number 2015-01-27). Results will be discussed with associations of families affected by SUID, caregivers, funders of the registry, medical societies and researchers and will be submitted to international peer-reviewed journals and presented at international conferences. PMID:29666137

Attitudes toward clinical autopsy in unexpected patient deaths in Japan: a nation-wide survey of the general public and physicians.

PubMed

Kamishiraki, Etsuko; Maeda, Shoichi; Starkey, Jay; Ikeda, Noriaki

2012-12-01

Autopsy is a useful tool for understanding the cause and manner of unexpected patient death. However, the attitudes of the general public and physicians in Japan about clinical autopsy are limited. To describe the beliefs of the general public about whether autopsy should be performed and ascertain if they would actually request one given specific clinical situations where patient death occurred with the additional variable of medical error. To compare these attitudes with previously obtained attitudes of physicians practising at Japanese teaching hospitals. We conducted a cross-sectional study of the general public. We sent standardised questionnaires in 2010 to a randomly selected non-physician adult population using a survey company for participant selection. Respondents gave their opinions about the necessity of autopsy and how they might act given various clinical scenarios of patient death. We compared these results with those of a previous survey of Japanese physicians conducted in 2009. Of the 2300 eligible general adult population, 1575 (68.5%) responded. The majority of the general public indicated they believed an autopsy was necessary. However, in cases of unclear medical error or unclear cause and effect relationship of medical care and patient death, the general public were much less likely to indicate they would actually request an autopsy than were physicians (p<0.0001). Currently in Japan the debate about the role autopsy should play in the case of error related to death is underway. The results from this study will be important in informing related decisions.

Psychotic Symptomatology in a Juvenile Court Clinic Population

ERIC Educational Resources Information Center

Lewis, Dorothy Otnow; And Others

1973-01-01

This report indicating an unexpectedly high incidence of psychotic symptomatology in a population of cases referred to the Juvenile Court Psychiatric Clinic of the Second District of Connecticut, manifests the necessity for juvenile court systems to be made aware of the possibility of psychosis in our delinquent populations. (CS)

Randomized clinical trials and observational studies in the assessment of drug safety.

PubMed

Sawchik, J; Hamdani, J; Vanhaeverbeek, M

2018-05-01

Randomized clinical trials are considered as the preferred design to assess the potential causal relationships between drugs or other medical interventions and intended effects. For this reason, randomized clinical trials are generally the basis of development programs in the life cycle of drugs and the cornerstone of evidence-based medicine. Instead, randomized clinical trials are not the design of choice for the detection and assessment of rare, delayed and/or unexpected effects related to drug safety. Moreover, the highly homogeneous populations resulting from restrictive eligibility criteria make randomized clinical trials inappropriate to describe comprehensively the safety profile of drugs. In that context, observational studies have a key added value when evaluating the benefit-risk balance of the drugs. However, observational studies are more prone to bias than randomized clinical trials and they have to be designed, conducted and reported judiciously. In this article, we discuss the strengths and limitations of randomized clinical trials and of observational studies, more particularly regarding their contribution to the knowledge of medicines' safety profile. In addition, we present general recommendations for the sensible use of observational data. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Robust passive dynamics of the musculoskeletal system compensate for unexpected surface changes during human hopping

PubMed Central

van der Krogt, Marjolein M.; de Graaf, Wendy W.; Farley, Claire T.; Moritz, Chet T.; Richard Casius, L. J.; Bobbert, Maarten F.

2009-01-01

When human hoppers are surprised by a change in surface stiffness, they adapt almost instantly by changing leg stiffness, implying that neural feedback is not necessary. The goal of this simulation study was first to investigate whether leg stiffness can change without neural control adjustment when landing on an unexpected hard or unexpected compliant (soft) surface, and second to determine what underlying mechanisms are responsible for this change in leg stiffness. The muscle stimulation pattern of a forward dynamic musculoskeletal model was optimized to make the model match experimental hopping kinematics on hard and soft surfaces. Next, only surface stiffness was changed to determine how the mechanical interaction of the musculoskeletal model with the unexpected surface affected leg stiffness. It was found that leg stiffness adapted passively to both unexpected surfaces. On the unexpected hard surface, leg stiffness was lower than on the soft surface, resulting in close-to-normal center of mass displacement. This reduction in leg stiffness was a result of reduced joint stiffness caused by lower effective muscle stiffness. Faster flexion of the joints due to the interaction with the hard surface led to larger changes in muscle length, while the prescribed increase in active state and resulting muscle force remained nearly constant in time. Opposite effects were found on the unexpected soft surface, demonstrating the bidirectional stabilizing properties of passive dynamics. These passive adaptations to unexpected surfaces may be critical when negotiating disturbances during locomotion across variable terrain. PMID:19589956

Sex Differences in Pharmacokinetics and Pharmacodynamics

PubMed Central

Soldin, OP; Mattison, DR

2013-01-01

Males and females differ in their response to drug treatment. These differences can be critical in response to drug treatment. It is therefore essential to understand those differences to appropriately conduct risk assessment and to design safe and effective treatments. Even from that modest perspective, how and when we use drugs can result in unwanted and unexpected outcomes. We summarize the sex differences that impact pharmacokinetics and pharmacodynamics and include a general comparison of clinical pharmacology as it applies to men, pregnant and non-pregnant women. Since this is an area rapidly evolving, it is essential for the practitioner to review drug prescribing information and recent literature to understand fully the impact of sex differences in clinical therapeutics. PMID:19385708

[The whole world in a cup of coffee. Case reports].

PubMed

De Fiore, Luca

2009-01-01

There is a rising interest for clinical cases in medicine. Actually, they don't necessarily conflict with the evidence-based medicine approach; rather, as several authors made clear, EBM-oriented case reports and clinical trials could be complementary. Cases and case series could even represent the first line of evidence and they are extremely valuable in discovering new pathologies and monitoring unexpected drug effects. They also play a relevant role in continuing medical education. The new section of Recenti Progressi in Medicina is edited by a prominent Italian research Institute (Istituto di Fisiologia Clinica, CNR). It focuses on a single case, guiding the physicians' decision-making from differential diagnosis to the treatment options.

An analysis of possible mechanisms of unexpected death occurring in hydatid disease (echinococcosis).

PubMed

Byard, Roger W

2009-07-01

Most cases of hydatid disease in human populations are due to Echinococcus granulosus. The hydatid life cycle involves passage between definitive hosts such as dogs and intermediate hosts such as sheep. Humans become accidental intermediate hosts following ingestion of food or water contaminated with eggs or by contact with infected dogs. Although hydatid disease may remain asymptomatic, occasional cases of sudden and unexpected death present to autopsy. Causes of rapid clinical decline involve a wide range of mechanisms including anaphylaxis (with or without cyst rupture), cardiac outflow obstruction or conduction tract disturbance, pulmonary and cerebral embolism, pericarditis, cardiac tamponade, myocardial ischemia, pulmonary hypertension, peritonitis, hollow organ perforation, intracerebral mass effect, obstructive hydrocephalus, seizures, cerebral ischemia/infarction, and pregnancy complications. The autopsy assessment of cases therefore requires careful examination of all organ systems for characteristic cystic lesions, as multiorgan involvement is common, with integration of findings so that possible mechanisms of death can be determined. Measurement of serum tryptase and specific IgE levels should be undertaken for possible anaphylaxis.

An unexpected N-terminal loop in PD-1 dominates binding by nivolumab

PubMed Central

Tan, Shuguang; Zhang, Hao; Chai, Yan; Song, Hao; Tong, Zhou; Wang, Qihui; Qi, Jianxun; Wong, Gary; Zhu, Xiaodong; Liu, William J.; Gao, Shan; Wang, Zhongfu; Shi, Yi; Yang, Fuquan; Gao, George F.; Yan, Jinghua

2017-01-01

Cancer immunotherapy by targeting of immune checkpoint molecules has been a research ‘hot-spot' in recent years. Nivolumab, a human monoclonal antibody targeting PD-1, has been widely used clinically since 2014. However, the binding mechanism of nivolumab to PD-1 has not yet been shown, despite a recent report describing the complex structure of pembrolizumab/PD-1. It has previously been speculated that PD-1 glycosylation is involved in nivolumab recognition. Here we report the complex structure of nivolumab with PD-1 and evaluate the effects of PD-1 N-glycosylation on the interactions with nivolumab. Structural and functional analyses unexpectedly reveal an N-terminal loop outside the IgV domain of PD-1. This loop is not involved in recognition of PD-L1 but dominates binding to nivolumab, whereas N-glycosylation is not involved in binding at all. Nivolumab binds to a completely different area than pembrolizumab. These results provide the basis for the design of future inhibitory molecules targeting PD-1. PMID:28165004

Mandatory weight loss during the wait for bariatric surgery.

PubMed

Glenn, Nicole M; Raine, Kim D; Spence, John C

2015-01-01

Mandatory presurgical, behavior-induced weight loss, although not standard, is a relatively common practice among bariatric surgical clinics. We explore the patient's experience of this practice using phenomenology. We gathered experiential accounts from 7 individuals waiting to have the procedure at a large publically funded clinic in western Canada. In writing this article, we focused on four phenomenological themes: "just nod your head and carry on"-silencing through the ideal; waiting and weighing-promoting weight consciousness to the weight conscious; paying for surgical approval through weight loss; and presurgical weight loss and questioning the need for weight loss surgery altogether. We contrast the experiential findings with the clinical literature to question the impact and possible (unintended or unexpected) effects the practice might have, particularly on patients' lives. We situate this article within a larger discussion about the possible contribution of experiential knowledge to clinical guidelines, practices, and pedagogies. © The Author(s) 2014.

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings.

PubMed

Thom, Maria; Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W; Sisodiya, Sanjay M

2016-08-01

Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy-related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Benchmarking the perioperative process: II. Introducing anesthesia clinical pathways to improve processes and outcomes and to reduce nursing labor intensity in ambulatory orthopedic surgery.

PubMed

Williams, B A; DeRiso, B M; Engel, L B; Figallo, C M; Anders, J W; Sproul, K A; Ilkin, H; Harner, C D; Fu, F H; Nagarajan, N J; Evans, J H; Watkins, W D

1998-11-01

(1) To introduce anesthesia clinical pathways as a management tool to improve the quality of care; (2) to use the Procedural Times Glossary published by the Association of Anesthesia Clinical Directors (AACD) as a template for data collection and analysis; and (3) to determine the effects of anesthesia clinical pathways on surgical processes, outcomes, and costs in common ambulatory orthopedic surgery. Hospital database and patient chart review of consecutive patients undergoing anterior cruciate ligament reconstruction (ACLR) during academic years (AY) 1995-1996 and 1996-1997. Patient data from AY 1995-1996, during which no intraoperative anesthesia clinical pathways existed, served as historical controls. Data from AY 1996-1997, during which intraoperative anesthesia clinical pathways were used, served as the treatment group. Regional anesthesia options were routinely offered to patients in the clinical pathway. Ambulatory surgery center in a teaching hospital. The records of 503 ASA physical status I and II patients were reviewed. 1996-1997 patients underwent clinical pathway anesthesia care in which the intraoperative and postoperative anesthesia process was standardized with respect to symptom management, drugs, and equipment used. 1995-1996 patients did not have a standardized intraoperative and postoperative anesthetic course with respect to the management of common symptoms or to specific drugs and supplies used. Intervals described in the AACD Procedural Times Glossary, anesthesia drug and supply costs, and patient outcome variables (postoperative nursing interventions required and unexpected admissions), as influenced by the use of the anesthesia clinical pathway, were measured. Clinical pathway anesthesia care of ACLR in 1996-1997, which actively incorporated regional anesthesia options, reduced pharmacy and materials cost variability; slightly increased turnover time; improved intraoperative anesthesia and surgical efficiency, recovery times, and unexpected admission rates; and decreased the number of required nursing interventions for common postoperative symptoms. Clinical pathway patient management systems in anesthesia care are likely to produce useful outcome data of current practice patterns when compared with historical controls. This management tool may be useful in simultaneously containing costs and improving process efficiency and patient outcomes.

Unexpected Decrease in Milk Production after Fenbendazole Treatment of Dairy Cows during Early Grazing Season

PubMed Central

Ravinet, Nadine; Chartier, Christophe; Bareille, Nathalie; Lehebel, Anne; Ponnau, Adeline; Brisseau, Nadine; Chauvin, Alain

2016-01-01

Gastrointestinal nematodes (GIN) infection can impair milk production (MP) in dairy cows. To investigate whether MP would be optimized by spring targeted-selective anthelmintic treatment in grazing cows, we assessed (1) the effect on MP of an anthelmintic treatment applied 1.5 to 2 months after turn-out, and (2) herd and individual indicators associated with the post-treatment MP response. A randomized controlled clinical trial was conducted in 13 dairy farms (578 cows) in western France in spring 2012. In each herd, lactating cows of the treatment group received fenbendazole orally, control cows remained untreated. Daily cow MP was recorded from 2 weeks before until 15 weeks after treatment. Individual serum pepsinogen and anti-Ostertagia antibody levels (expressed as ODR), faecal egg count and bulk tank milk (BTM) Ostertagia ODR were measured at treatment time. Anthelmintic treatment applied during the previous housing period was recorded for each cow. In each herd, information regarding heifers’ grazing and anthelmintic treatment history was collected to assess the Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving. The effect of treatment on weekly MP averages and its relationships with herd and individual indicators were studied using linear mixed models with two nested random effects (cow within herd). Unexpectedly, spring treatment had a significant detrimental effect on MP (-0.92 kg/cow/day on average). This negative MP response was particularly marked in high producing cows, in cows not treated during the previous housing period or with high pepsinogen levels, and in cows from herds with a high TEC or a high BTM ODR. This post-treatment decrease in MP may be associated with immuno-inflammatory mechanisms. Until further studies can assess whether this unexpected result can be generalized, non-persistent treatment of immunized adult dairy cows against GIN should not be recommended in early grazing season. PMID:26808824

Unexpected Decrease in Milk Production after Fenbendazole Treatment of Dairy Cows during Early Grazing Season.

PubMed

Ravinet, Nadine; Chartier, Christophe; Bareille, Nathalie; Lehebel, Anne; Ponnau, Adeline; Brisseau, Nadine; Chauvin, Alain

2016-01-01

Gastrointestinal nematodes (GIN) infection can impair milk production (MP) in dairy cows. To investigate whether MP would be optimized by spring targeted-selective anthelmintic treatment in grazing cows, we assessed (1) the effect on MP of an anthelmintic treatment applied 1.5 to 2 months after turn-out, and (2) herd and individual indicators associated with the post-treatment MP response. A randomized controlled clinical trial was conducted in 13 dairy farms (578 cows) in western France in spring 2012. In each herd, lactating cows of the treatment group received fenbendazole orally, control cows remained untreated. Daily cow MP was recorded from 2 weeks before until 15 weeks after treatment. Individual serum pepsinogen and anti-Ostertagia antibody levels (expressed as ODR), faecal egg count and bulk tank milk (BTM) Ostertagia ODR were measured at treatment time. Anthelmintic treatment applied during the previous housing period was recorded for each cow. In each herd, information regarding heifers' grazing and anthelmintic treatment history was collected to assess the Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving. The effect of treatment on weekly MP averages and its relationships with herd and individual indicators were studied using linear mixed models with two nested random effects (cow within herd). Unexpectedly, spring treatment had a significant detrimental effect on MP (-0.92 kg/cow/day on average). This negative MP response was particularly marked in high producing cows, in cows not treated during the previous housing period or with high pepsinogen levels, and in cows from herds with a high TEC or a high BTM ODR. This post-treatment decrease in MP may be associated with immuno-inflammatory mechanisms. Until further studies can assess whether this unexpected result can be generalized, non-persistent treatment of immunized adult dairy cows against GIN should not be recommended in early grazing season.

Understanding the Role of P Values and Hypothesis Tests in Clinical Research.

PubMed

Mark, Daniel B; Lee, Kerry L; Harrell, Frank E

2016-12-01

P values and hypothesis testing methods are frequently misused in clinical research. Much of this misuse appears to be owing to the widespread, mistaken belief that they provide simple, reliable, and objective triage tools for separating the true and important from the untrue or unimportant. The primary focus in interpreting therapeutic clinical research data should be on the treatment ("oomph") effect, a metaphorical force that moves patients given an effective treatment to a different clinical state relative to their control counterparts. This effect is assessed using 2 complementary types of statistical measures calculated from the data, namely, effect magnitude or size and precision of the effect size. In a randomized trial, effect size is often summarized using constructs, such as odds ratios, hazard ratios, relative risks, or adverse event rate differences. How large a treatment effect has to be to be consequential is a matter for clinical judgment. The precision of the effect size (conceptually related to the amount of spread in the data) is usually addressed with confidence intervals. P values (significance tests) were first proposed as an informal heuristic to help assess how "unexpected" the observed effect size was if the true state of nature was no effect or no difference. Hypothesis testing was a modification of the significance test approach that envisioned controlling the false-positive rate of study results over many (hypothetical) repetitions of the experiment of interest. Both can be helpful but, by themselves, provide only a tunnel vision perspective on study results that ignores the clinical effects the study was conducted to measure.

Do you really represent my task? Sequential adaptation effects to unexpected events support referential coding for the joint Simon effect.

PubMed

Klempova, Bibiana; Liepelt, Roman

2016-07-01

Recent findings suggest that a Simon effect (SE) can be induced in Individual go/nogo tasks when responding next to an event-producing object salient enough to provide a reference for the spatial coding of one's own action. However, there is skepticism against referential coding for the joint Simon effect (JSE) by proponents of task co-representation. In the present study, we tested assumptions of task co-representation and referential coding by introducing unexpected double response events in a joint go/nogo and a joint independent go/nogo task. In Experiment 1b, we tested if task representations are functionally similar in joint and standard Simon tasks. In Experiment 2, we tested sequential updating of task co-representation after unexpected single response events in the joint independent go/nogo task. Results showed increased JSEs following unexpected events in the joint go/nogo and joint independent go/nogo task (Experiment 1a). While the former finding is in line with the assumptions made by both accounts (task co-representation and referential coding), the latter finding supports referential coding. In contrast to Experiment 1a, we found a decreased SE after unexpected events in the standard Simon task (Experiment 1b), providing evidence against the functional equivalence assumption between joint and two-choice Simon tasks of the task co-representation account. Finally, we found an increased JSE also following unexpected single response events (Experiment 2), ruling out that the findings of the joint independent go/nogo task in Experiment 1a were due to a re-conceptualization of the task situation. In conclusion, our findings support referential coding also for the joint Simon effect.

Recognizing and Reducing Analytical Errors and Sources of Variation in Clinical Pathology Data in Safety Assessment Studies.

PubMed

Schultze, A E; Irizarry, A R

2017-02-01

Veterinary clinical pathologists are well positioned via education and training to assist in investigations of unexpected results or increased variation in clinical pathology data. Errors in testing and unexpected variability in clinical pathology data are sometimes referred to as "laboratory errors." These alterations may occur in the preanalytical, analytical, or postanalytical phases of studies. Most of the errors or variability in clinical pathology data occur in the preanalytical or postanalytical phases. True analytical errors occur within the laboratory and are usually the result of operator or instrument error. Analytical errors are often ≤10% of all errors in diagnostic testing, and the frequency of these types of errors has decreased in the last decade. Analytical errors and increased data variability may result from instrument malfunctions, inability to follow proper procedures, undetected failures in quality control, sample misidentification, and/or test interference. This article (1) illustrates several different types of analytical errors and situations within laboratories that may result in increased variability in data, (2) provides recommendations regarding prevention of testing errors and techniques to control variation, and (3) provides a list of references that describe and advise how to deal with increased data variability.

Homozygous and compound heterozygous mutations in the FBN1 gene: unexpected findings in molecular diagnosis of Marfan syndrome.

PubMed

Arnaud, Pauline; Hanna, Nadine; Aubart, Mélodie; Leheup, Bruno; Dupuis-Girod, Sophie; Naudion, Sophie; Lacombe, Didier; Milleron, Olivier; Odent, Sylvie; Faivre, Laurence; Bal, Laurence; Edouard, Thomas; Collod-Beroud, Gwenaëlle; Langeois, Maud; Spentchian, Myrtille; Gouya, Laurent; Jondeau, Guillaume; Boileau, Catherine

2017-02-01

Marfan syndrome (MFS) is an autosomal-dominant connective tissue disorder usually associated with heterozygous mutations in the gene encoding fibrillin-1 (FBN1). Homozygous and compound heterozygous cases are rare events and have been associated with a clinical severe presentation. Report unexpected findings of homozygosity and compound heterozygosity in the course of molecular diagnosis of heterozygous MFS and compare the findings with published cases. In the context of molecular diagnosis of heterozygous MFS, systematic sequencing of the FBN1 gene was performed in 2500 probands referred nationwide. 1400 probands carried a heterozygous mutation in this gene. Unexpectedly, among them four homozygous cases (0.29%) and five compound heterozygous cases (0.36%) were identified (total: 0.64%). Interestingly, none of these cases carried two premature termination codon mutations in the FBN1 gene. Clinical features for these carriers and their families were gathered and compared. There was a large spectrum of severity of the disease in probands carrying two mutated FBN1 alleles, but none of them presented extremely severe manifestations of MFS in any system compared with carriers of only one mutated FBN1 allele. This observation is not in line with the severe clinical features reported in the literature for four homozygous and three compound heterozygous probands. Homozygotes and compound heterozygotes were unexpectedly identified in the course of molecular diagnosis of MFS. Contrary to previous reports, the presence of two mutated alleles was not associated with severe forms of MFS. Although homozygosity and compound heterozygosity are rarely found in molecular diagnosis, they should not be overlooked, especially among consanguineous families. However, no predictive evaluation of severity should be provided. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Assessment of General Education: An Unexpected (but Effective) Faculty Development Opportunity

ERIC Educational Resources Information Center

Hawthorne, Joan; Zerr, Ryan; Kelsch, Anne V.

2018-01-01

This chapter describes a collective faculty effort to administer, proctor, score, and interpret student work that created an unexpected opportunity for deep discussions of teaching, learning, and assessment.

Low-Dose Naltrexone: A New Therapy Option for Complex Regional Pain Syndrome Type I Patients.

PubMed

Sturn, Kayla M; Collin, Michael

2016-01-01

Naltrexone (an opioid antagonist) has long been used in patients overcoming alcohol and opioid dependency. However, at doses one-tenth of those commonly prescribed for the above conditions, an unexpected effect occurs that aids in alleviating pain. Although there are currently no randomized clinical trials supporting the use of low-dose naltrexone, we present a case study describing the impact of compounding low-dose naltrexone that has dramatically improved the patient's pain symptoms which were refractory to other treatments. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial.

PubMed

Rezk, Mohamed; Shaheen, Abd-Elhamid; Saif El-Nasr, Ibrahim

2018-04-01

A total of 202 patients with clomiphene citrate (CC) -resistant polycystic ovary syndrome (PCOS) were randomly allocated into two arms of induction of ovulation; the first group (n = 102) received CC 100 mg and metformin 500 mg while the second group (n = 100) received letrozole 2.5 mg with ovulation rate, clinical pregnancy rate, adverse effects, and acceptability were assessed. Patients in the letrozole arm experienced higher rate of ovulation (82% versus 43.1%, p < .001), more dominant follicles (p < .05), better endometrial thickness (p < .001), higher clinical pregnancy rate (36% versus 9.8%, p < .001), higher multiple pregnancy rate (p < .05), lesser adverse effects (p < .05) and higher acceptability (p < .001) compared to patients in the CC and metformin arm. In conclusion; letrozole is better and more acceptable than combined CC and metformin for inducing ovulation in patients with CC-resistant PCOS with higher clinical pregnancy rate and unexpectedly higher multiple pregnancy rate.

Post hoc analyses: after the facts.

PubMed

Srinivas, Titte R; Ho, Bing; Kang, Joseph; Kaplan, Bruce

2015-01-01

Prospective clinical trials are constructed with high levels of internal validity. Sample size and power considerations usually address primary endpoints. Primary endpoints have traditionally included events that are becoming increasingly less common and thus have led to growing use of composite endpoints and noninferiority trial designs in transplantation. This approach may mask real clinical benefit in one or the other domain with regard to either clinically relevant secondary endpoints or other unexpected findings. In addition, endpoints solely chosen based on power considerations are prone to misjudgment of actual treatment effect size as well as consistency of that effect. In the instances where treatment effects may have been underestimated, valuable information may be lost if buried within a composite endpoint. In all these cases, analyses and post hoc analyses of data become relevant in informing practitioners about clinical benefits or safety signals that may not be captured by the primary endpoint. On the other hand, there are many pitfalls in using post hoc determined endpoints. This short review is meant to allow readers to appreciate post hoc analysis not as an entity with a single approach, but rather as an analysis with unique limitations and strengths that often raise new questions to be addressed in further inquiries.

Expertise in Clinical Psychology. The Effects of University Training and Practical Experience on Expertise in Clinical Psychology

PubMed Central

Vollmer, Sabine; Spada, Hans; Caspar, Franz; Burri, Salome

2013-01-01

How do university training and subsequent practical experience affect expertise in clinical psychology? To answer this question we developed methods to assess psychological knowledge and the competence to diagnose, construct case conceptualizations, and plan psychotherapeutic treatment: a knowledge test and short case studies in a first study, and a complex, dynamically evolving case study in the second study. In our cross-sectional studies, psychology students, trainees in a certified postgraduate psychotherapist curriculum, and behavior therapists with more than 10 years of experience were tested (100 in total: 20 each of novice, intermediate, and advanced university students, postgraduate trainees, and therapists). Clinical knowledge and competence increased up to the level of trainees but unexpectedly decreased at the level of experienced therapists. We discuss the results against the background of expertise research and the training of clinical psychologists (in Germany). Important factors for the continuing professional development of psychotherapists are proposed. PMID:23543213

Presurgical language fMRI: Clinical practices and patient outcomes in epilepsy surgical planning.

PubMed

Benjamin, Christopher F A; Li, Alexa X; Blumenfeld, Hal; Constable, R Todd; Alkawadri, Rafeed; Bickel, Stephan; Helmstaedter, Christoph; Meletti, Stefano; Bronen, Richard; Warfield, Simon K; Peters, Jurriaan M; Reutens, David; Połczyńska, Monika; Spencer, Dennis D; Hirsch, Lawrence J

2018-03-12

The goal of this study was to document current clinical practice and report patient outcomes in presurgical language functional MRI (fMRI) for epilepsy surgery. Epilepsy surgical programs worldwide were surveyed as to the utility, implementation, and efficacy of language fMRI in the clinic; 82 programs responded. Respondents were predominantly US (61%) academic programs (85%), and evaluated adults (44%), adults and children (40%), or children only (16%). Nearly all (96%) reported using language fMRI. Surprisingly, fMRI is used to guide surgical margins (44% of programs) as well as lateralize language (100%). Sites using fMRI for localization most often use a distance margin around activation of 10mm. While considered useful, 56% of programs reported at least one instance of disagreement with other measures. Direct brain stimulation typically confirmed fMRI findings (74%) when guiding margins, but instances of unpredicted decline were reported by 17% of programs and 54% reported unexpected preservation of function. Programs reporting unexpected decline did not clearly differ from those which did not. Clinicians using fMRI to guide surgical margins do not typically map known language-critical areas beyond Broca's and Wernicke's. This initial data shows many clinical teams are confident using fMRI not only for language lateralization but also to guide surgical margins. Reported cases of unexpected language preservation when fMRI activation is resected, and cases of language decline when it is not, emphasize a critical need for further validation. Comprehensive studies comparing commonly-used fMRI paradigms to predict stimulation mapping and post-surgical language decline remain of high importance. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine.

PubMed

Wang, Rui; Yan, Han; Tang, Xi-can

2006-01-01

Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase(AChE). Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA has been found to improve cognitive deficits in a broad range of animal models. HupA possesses the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria, upregulate nerve growth factor and its receptors, and interfere with amyloid precursor protein metabolism. Antagonizing effects of HupA on N-methyl-D-aspartate receptors and potassium currents may also contribute to its neuroprotection as well. Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that HupA was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate with the property of slow and prolonged release after oral administration. Animal and clinical safety tests showed that HupA had no unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.

Media work adds a new dimension to my clinical practice.

PubMed

Wedderburn, Pete

2017-06-24

Pete Wedderburn describes his media career as 'accidental and unexpected', but having dipped his toe in the water, he found he enjoyed it. Here, he explains how it started. British Veterinary Association.

Postmarketing surveillance: perspectives of a journal editor.

PubMed

Gelenberg, A J

1993-01-01

In the absence of a systematic monitoring program for drugs newly approved by the Food and Drug Administration (FDA), reports in clinical journals provide a legitimate forum for disseminating information about unexpected pharmacologic events. A journal editor bears the responsibility for publishing educated clinical observations that meet standards of scientific rigor while not giving premature credibility to chance and dubious reports of side effects of new drugs. Often this responsibility involves overcoming the fear of bad publicity and withstanding pressures from pharmaceutical companies to print only positive information about new products. Published preliminary observations may contribute to the problem of product liability, but they also generate testable hypotheses and healthy debate. If hypotheses later prove to be incorrect, they can be refuted by systematic studies and clarified in reviews and editorials. Our goal of effective education will be reached not by self-censorship but by scientific openness.

In-situ medical simulation for pre-implementation testing of clinical service in a regional hospital in Hong Kong.

PubMed

Chen, P P; Tsui, N Tk; Fung, A Sw; Chiu, A Hf; Wong, W Cw; Leong, H T; Lee, P Sf; Lau, J Yw

2017-08-01

The implementation of a new clinical service is associated with anxiety and challenges that may prevent smooth and safe execution of the service. Unexpected issues may not be apparent until the actual clinical service commences. We present a novel approach to test the new clinical setting before actual implementation of our endovascular aortic repair service. In-situ simulation at the new clinical location would enable identification of potential process and system issues prior to implementation of the service. After preliminary planning, a simulation test utilising a case scenario with actual simulation of the entire care process was carried out to identify any logistic, equipment, settings or clinical workflow issues, and to trial a contingency plan for a surgical complication. All patient care including anaesthetic, surgical, and nursing procedures and processes were simulated and tested. Overall, 17 vital process and system issues were identified during the simulation as potential clinical concerns. They included difficult patient positioning, draping pattern, unsatisfactory equipment setup, inadequate critical surgical instruments, blood products logistics, and inadequate nursing support during crisis. In-situ simulation provides an innovative method to identify critical deficiencies and unexpected issues before implementation of a new clinical service. Life-threatening and serious practical issues can be identified and corrected before formal service commences. This article describes our experience with the use of simulation in pre-implementation testing of a clinical process or service. We found the method useful and would recommend it to others.

Impact of Exercise on Clinical Symptom Report and Neurocognition after Concussion in Children and Adolescents.

PubMed

Manikas, Vicky; Babl, Franz E; Hearps, Stephen; Dooley, Julian; Anderson, Vicki

2017-06-01

Recovery from concussion in childhood is poorly understood, despite its importance in decisions regarding return to normal activity. Resolution of post-concussive symptoms (PCS) is widely employed as a marker of recovery in clinical practice; however, it is unclear whether subtle impairments persist only to re-emerge in the context of increased physical or cognitive demands. This study aimed to examine the effect of strenuous exercise on clinical symptom report and neurocognition in children and adolescents after PCS resolution after concussion. We recruited children and adolescents with concussion (n = 30) on presentation to an Emergency Department (ED). At Day 2 and Day 10 post-self-reported symptom resolution, participants completed a strenuous exercise protocol, and pre- and post-exercise assessment of PCS and neurocognition. Results demonstrated an overall reduction in PCS from Day 2 to Day 10 post-symptom resolution, with no evidence of symptom increase after strenuous exercise at either time point. Neurocognitive performance was linked to task complexity: on less cognitively demanding tasks, processing speed was slower post-exercise and, unexpectedly, slower on Day 10 than Day 2, while for more demanding tasks (new learning), Day 2 exercise resulted in faster responses, but Day 10 processing speed post-exercise was slower. In summary, we found the expected recovery pattern for PCS, regardless of exercise, while for neurocognition, recovery was dependent on the degree of cognitive demand, and there was an unexpected reduction in performance from Day 2 to Day 10. Findings provide some suggestion that premature return to normal activities (e.g., school) may slow neurocognitive recovery.

The Prepared Mind.

PubMed

Garber, Susan L

Every day, in clinics and hospitals around the world, occupational therapists care for patients with serious problems requiring viable solutions. Each patient is unique, and his or her problem does not necessarily correspond to existing practice models. Practitioners must adapt standard approaches to provide effective outcomes, yet problems exist for which few or no beneficial approaches have been identified. Such clinical issues require solutions to be generated de novo from the practitioner's body of knowledge and past experience. Yet, no single new intervention can be used without prior validation of its efficacy. Only a therapist with a prepared mind can accept such challenges, recognize what is known and not yet known, design studies to acquire that needed knowledge, and translate it into successful clinical treatment strategies. The occupational therapist with a prepared mind is one willing to seize unexpected opportunities and construct new paradigms of practice. Innovation through scientific inquiry requires a prepared mind. Copyright © 2016 by the American Occupational Therapy Association, Inc.

A tale of two health literacies: public health and clinical approaches to health literacy.

PubMed

Pleasant, Andrew; Kuruvilla, Shyama

2008-06-01

Public health concerns underlie a considerable portion of the global burden of disease, increasing the utility and need for promoting and assessing the knowledge about public health issues. Health literacy is generally agreed upon as a means to find, understand, analyze and use information to make better decisions about health and to ultimately reduce inequities in health. A public health literacy knowledge scale was tested in China, Mexico, Ghana and India. A somewhat unexpected finding, which was that experts 'scored' less on the scale than the general public, led to consideration of differences between clinical and public health approaches to health literacy and their implications. These differences in perspective, for instance consideration of single case effects versus impacts at the societal level, pose significant challenges to developing and assessing health literacy. We suggest that a comprehensive approach to health literacy will include both clinical and public health approaches.

Clinical, pathological and sonographic characteristics of unexpected gallbladder carcinoma

PubMed Central

Wang, Jin-Huan; Liu, Bo-Ji; Xu, Hui-Xiong; Sun, Li-Ping; Li, Dan-Dan; Guo, Le-Hang; Liu, Lin-Na; Xu, Xiao-Hong

2015-01-01

Objectives: To investigate the clinical, pathological, and sonographic characteristics of unexpected gallbladder carcinoma (UGC). Methods: Of 5424 patients who had undergone cholecystectomy from December 2006 to October 2013, 54 patients with primary gallbladder carcinomas confirmed by pathological diagnosis were identified. The patients were divided into two groups: diagnosed before operation (n=34) and UGC groups (n=20), of whom the clinical, pathological, and sonographic characteristics were compared. Results: No significant differences in age, gender, location of lesion, histological type, length of the gallbladder, existence of biliary sludge, and intestinal gas interference between the two groups were found (all P>0.05). The clinical symptoms, laboratory abnormalities, tumor markers, coexisting gallbladder stones, lesion size, lesion type, degree of differentiation, and tumor staging showed statistically significant differences between the two groups (all P<0.05). On ultrasound, the width of the gallbladder, gallbladder wall thickness, vascularity on color Doppler ultrasound, and bile volume in the gallbladder showed significant differences (all P<0.05). Conclusions: UGCs are commonly found at an early stage, often well-differentiated, wall thickened, and are generally accompanied with cholelithiasis. UGCs should be taken into consideration in cases with cholelithiasis or small gallbladder on ultrasound. PMID:26379911

Adverse effects associated with the clinical use of 4% TiF₄ on teeth enamel: case report.

PubMed

Pedro, Rafael de Lima; Pomarico, Luciana; Villardi, Michele; Maia, Lucianne Cople

2011-05-01

Titanium tetrafluoride (TiF₄) has been studied in dentistry as a promissory alternative for prevention and treatment of carious lesions. However, there are few in vivo studies concerning the consequences of its use on tooth enamel. The goal of this study was to report the effects of a 4% TiF₄ application on the remineralization of an incipient carious lesion of a permanent tooth. This research found an unexpected clinical outcome. A patient with active white spots had two of these lesions treated with 4% TiF₄ associated with fluoridated dentifrice and another lesion treated with fluoridated dentifrice only, thus the remineralization of the two kinds of treatment administered could be observed and compared. An extrinsic pigment appeared in the regions that received the TiF₄ treatment, which was partially removed by professional prophylaxis. Also, regular recidivists of this pigmentation in the review consultations were noted. The authors concluded that although the use of 4% TiF₄ was effective in treating incipient carious lesions on enamel, it was also responsible for an undesired pigmented layer on the tooth to which it was applied. Beyond the varied fluoridated materials used in dentistry, titanium tetrafluoride (TiF₄) deserves attention. This compound has the common properties of fluorides, and researchers are exploring its role in carious lesion prevention, fissure sealing, and tooth erosion prevention in in vitro and in situ studies. Research is also exploring its use for microinfiltration prevention in tooth restoration and hypersensitivity treatment. However, when compared to other fluoridated products TiF₄ demonstrates additional, specific particularities, such as the formation of a titanium dioxide (TiO₂) layer, which is tough, hydrophobic, and resistant in acidic environments. Nevertheless, there are insufficient in vivo studies concerning the consequences of TiF₄-containing products affecting tooth enamel. Thus, the goals of this study were to report the effects of a 4% TiF₄ application on the remineralization of an incipient carious lesion of a permanent tooth and to show the results of a backscattered scanning electron (BSE) analysis that was performed on the primary tooth. The clinical outcome was unexpected.

Team OSCE: A Teaching Modality for Promotion of Multidisciplinary Work in Mental Health Settings.

PubMed

Sharma, Manoj Kumar; Chandra, Prabha S; Chaturvedi, Santosh K

2015-01-01

The objective structured clinical examination has been in use both as an assessment and a teaching modality within the mental health profession. It focuses on individual skill enhancement, the inter-professional understanding of role obligation is helpful in promoting competence as a team as well as role of other team members. The Team OSCE (TOSCE) is an effective way in promoting inter-professional learning. The present work assesses the trainee experience with TOSCE and its utility in clinical care. Twenty-two mental health trainees (17 male and 5 female from psychiatry, clinical psychology and psychiatric social work) got exposure to weekly OSCAF training as well as 2-3 Team OSCAFS on various aspects of clinical work as a part of their clinical training for 3 months. Rating from the trainees were taken on TOSCE feedback checklist. TOSCE was helpful in promoting the understanding role of other team members; shared decision-making, problem-solving, handling unexpected events, giving feedback and closure. The TOSCE may be introduced as a way to work on clinical performance, shared decision-making and inter-professional understanding.

Ketamine and phencyclidine: the good, the bad and the unexpected

PubMed Central

Lodge, D; Mercier, M S

2015-01-01

The history of ketamine and phencyclidine from their development as potential clinical anaesthetics through drugs of abuse and animal models of schizophrenia to potential rapidly acting antidepressants is reviewed. The discovery in 1983 of the NMDA receptor antagonist property of ketamine and phencyclidine was a key step to understanding their pharmacology, including their psychotomimetic effects in man. This review describes the historical context and the course of that discovery and its expansion into other hallucinatory drugs. The relevance of these findings to modern hypotheses of schizophrenia and the implications for drug discovery are reviewed. The findings of the rapidly acting antidepressant effects of ketamine in man are discussed in relation to other glutamatergic mechanisms. PMID:26075331

[Animal welfare and corporate welfare in pharmaceutical R&D - the future of third-party assessment].

PubMed

Suzuki, Makoto

For research and development (R&D) of new drugs, animal experimentation is indispensable, and research institutes, pharmaceutical companies, or contract research organizations routinely conduct preclinical studies of efficacy, safety, or metabolism using laboratory animals. However, animal experimentation entails some organizational risks. One is the suspension of R&D of a new drug, because in the course of clinical studies it becomes apparent that the drug has limited efficacy, unexpected side effects, and/or unexpected metabolites. Another risk is damage to the company image by development of an unfavorable reputation. Society has accepted animal experimentation as a necessary evil, but if such experimentation is not conducted with adequate concern for animal welfare, social sanctions will against that institute, company or organization will result. Once this happens, it is difficult to recover a good public image. Therefore, pharmaceutical companies must conduct animal experiments so as to obtain highly useful data without sacrificing public favor. One way to maintain a good reputation is through third-party accreditation, which verifies that the institute, company or organization and its researchers value animal welfare appropriately.

The Unexpected Effects of Inclusion on the Families of Students with Learning Disabilities: A Focus-Group Study

ERIC Educational Resources Information Center

Dyson, Lily L.

2007-01-01

This study investigated the unexpected effects of inclusion on the families of students with learning disabilities. A focus group interview was conducted with 13 parents who have children with learning disabilities. The children's ages ranged from 5 to 24 years. Findings are reported regarding participants' comments in response to two guiding…

Exploring links between greenspace and sudden unexpected death: a spatial analysis

EPA Science Inventory

Greenspace has been increasingly recognized as having numerous health benefits. However, its effects are unknown concerning sudden unexpected death (SUD), commonly referred to as sudden cardiac death, which constitutes a large proportion of mortality in the United States. Because...

A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

PubMed

Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

2018-04-25

Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

Humanization of the anti-CD18 antibody 6.7: an unexpected effect of a framework residue in binding to antigen.

PubMed

Caldas, Cristina; Coelho, Verônica; Kalil, Jorge; Moro, Ana Maria; Maranhão, Andrea Q; Brígido, Marcelo M

2003-05-01

Humanization of monoclonal antibodies by complementary determinant region (CDR)-grafting has become a standard procedure to improve the clinical usage of animal antibodies. However, antibody humanization may result in loss of activity that has been attributed to structural constraints in the framework structure. In this paper, we report the complete humanization of the 6.7 anti-human CD18 monoclonal antibody in a scFv form. We used a germline-based approach to design a humanized VL gene fragment and expressed it together with a previously described humanized VH. The designed humanized VL has only 14 mutations compared to the closest human germline sequence. The resulting humanized scFv maintained the binding capacity and specificity to human CD18 expressed on the cell surface of peripheral blood mononuclear cells (PBMC), and showed the same pattern of staining T-lymphocytes sub-populations, in comparison to the original monoclonal antibody. We observed an unexpected effect of a conserved mouse-human framework position (L37) that hinders the binding of the humanized scFv to antigen. This paper reveals a new framework residue that interferes with paratope and antigen binding and also reinforces the germline approach as a successful strategy to humanize antibodies.

The Appalachian Tri-State Node Experiences with the National Institute on Drug Abuse Clinical Trials Network.

PubMed

Kelly, Thomas M; Daley, Dennis C; Byrne, Mimmie; Demarzo, Larry; Smith, Doris; Madl, Stephanie

2011-07-01

The National Institute on Drug Abuse (NIDA)-sponsored Clinical Trial Network (CTN) recently celebrated 10 years of conducting "real world" research into the treatment of addiction. This article reviews the history and results of the most recent CTN studies and describes the experiences of one of the 13 participating research affiliates, the Appalachian Tri-State (ATS) Node. We discuss our "bidirectional" collaboration with multiple community treatment programs (CTPs) on research and dissemination activities and include their experiences as a member of our ATS Node.Results of CTN clinical trials have found unexpectedly that treatment as usual (TAU) is often almost as good as evidence-based interventions such as Motivational Interviewing (MI), possibly due to the difficulty in implementing evidence-based practices most effectively among divergent treatment sites and heterogeneous clinical populations. Some expected findings from the reviewed research are that severity of addiction and comorbidity moderate treatment outcomes and must be accounted for in future CTN-sponsored studies. Notwithstanding these results, much has been learned and recommendations are suggested for changes in CTN research designs that will address methodological limitations and increase treatment effectiveness in future CTN studies.

Obesity Paradox in Lung Cancer Prognosis: Evolving Biological Insights and Clinical Implications.

PubMed

Zhang, Xueli; Liu, Yamin; Shao, Hua; Zheng, Xiao

2017-10-01

The survival rate of lung cancer remains low despite the progress of surgery and chemotherapy. With the increasing comorbidity of obesity in patients with lung cancer, new challenges are emerging in the management of this patient population. A key issue of interest is the prognostic effect of obesity on surgical and chemotherapeutic outcomes in patients with lung cancer, which is fueled by the growing observation of survival benefits in overweight or obese patients. This unexpected inverse relationship between obesity and lung cancer mortality, called the obesity paradox, remains poorly understood. The evolving insights into the heterogeneity of obesity phenotypes and associated biological connections with lung cancer progression in recent years may help explain some of the seemingly paradoxical relationship, and well-designed clinical studies looking at the causal role of obesity-associated molecules are expected. Here, we examine potential biological mechanisms behind the protective effects of obesity in lung cancer. We highlight the need to clarify the clinical implications of this relationship toward an updated intervention strategy in the clinical care of patients with lung cancer and obesity. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Factor X activating Atractaspis snake venoms and the relative coagulotoxicity neutralising efficacy of African antivenoms.

PubMed

Oulion, Brice; Dobson, James S; Zdenek, Christina N; Arbuckle, Kevin; Lister, Callum; Coimbra, Francisco C P; Op den Brouw, Bianca; Debono, Jordan; Rogalski, Aymeric; Violette, Aude; Fourmy, Rudy; Frank, Nathaniel; Fry, Bryan G

2018-05-15

Atractaspis snake species are enigmatic in their natural history, and venom effects are correspondingly poorly described. Clinical reports are scarce but bites have been described as causing severe hypertension, profound local tissue damage leading to amputation, and deaths are on record. Clinical descriptions have largely concentrated upon tissue effects, and research efforts have focused upon the blood-pressure affecting sarafotoxins. However, coagulation disturbances suggestive of procoagulant functions have been reported in some clinical cases, yet this aspect has been uninvestigated. We used a suite of assays to investigate the coagulotoxic effects of venoms from six different Atractaspis specimens from central Africa. The procoagulant function of factor X activation was revealed, as was the pseudo-procoagulant function of direct cleavage of fibrinogen into weak clots. The relative neutralization efficacy of South African Antivenom Producer's antivenoms on Atractaspis venoms was boomslang>polyvalent>saw-scaled viper. While the boomslang antivenom was the most effective on Atractaspis venoms, the ability to neutralize the most potent Atractaspis species in this study was up to 4-6 times less effective than boomslang antivenom neutralizes boomslang venom. Therefore, while these results suggest cross-reactivity of boomslang antivenom with the unexpectedly potent coagulotoxic effects of Atractaspis venoms, a considerable amount of this rare antivenom may be needed. This report thus reveals potent venom actions upon blood coagulation that may lead to severe clinical effects with limited management strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

Erythrocyte Alloimmunization and Autoimmunization among Blood Donors and Recipients visiting a Tertiary Care Hospital.

PubMed

Kaur, Daljit; Bains, Lovenish; Kandwal, Manoj; Parmar, Indu

2017-03-01

The ultimate aim of pretransfusion testing is the acceptable survival of donor red cells in recipient's body and antibody detection plays a critical role in achieving the same. The cornerstone of antibody detection method is detecting an unexpected antibody as against the expected antibodies of ABO blood group system. Autoantibodies can also interfere with the detection of clinically significant alloantibodies. To study the frequency of alloantibodies and autoantibodies in the healthy blood donors and patient population visiting our hospital. The Column Agglutination Technology (CAT) was used for ABO RhD blood grouping, Direct Antiglobulin Test (DAT), Autocontrol (AC), Indirect Antiglobulin Test (IAT) and red cell antibody screening and the unexpected reactions in any of these tests were recorded for further evaluation. Ethylene Diamine Tetra Acetic Acid (EDTA) blood samples were used for all these tests for both blood donors and admitted patients. The CAT was exercised for the blood grouping (using ABD-Reverse Diluent cassettes) and antibody screening (using 0.8% Surgiscreen, Ortho Clinical Diagnostics Limited, USA and Low Ionic Strength Saline Ortho BLISS with AHG cassettes) on the automated immunohaematology platform ORTHO AutoVue ® Innova system (Ortho Clinical Diagnostics Limited, USA). Among all blood donors (n=6350), seven (0.11%) donors had showed unexpected reaction. Of these, four had positive antibody screen (three having naturally occuring antibodies 2=anti-M, 1=anti-Le a and 1=inconclusive) and the other three had positive DAT. Of all the patient samples (n=6136) screened for irregular red cell antibodies, four (0.06%) patients were found to have unexpected reaction revealing one (0.02%) with anti-M antibody and the other three (0.05%) had autoantibodies in their serum. The combined prevalence for both blood donor and recipient population (n=12,486) was found to be 0.11% at our center. The alloimmunisation among patient population was found to be lower than many other studies worldwide as our hospital does not cater to multitransfused or transfusion dependant patients with haematological disorders and majorly elective surgery patients with no history of previous blood transfusions visit our hospital.

Erythrocyte Alloimmunization and Autoimmunization among Blood Donors and Recipients visiting a Tertiary Care Hospital

PubMed Central

Bains, Lovenish; Kandwal, Manoj; Parmar, Indu

2017-01-01

Introduction The ultimate aim of pretransfusion testing is the acceptable survival of donor red cells in recipient’s body and antibody detection plays a critical role in achieving the same. The cornerstone of antibody detection method is detecting an unexpected antibody as against the expected antibodies of ABO blood group system. Autoantibodies can also interfere with the detection of clinically significant alloantibodies. Aim To study the frequency of alloantibodies and autoantibodies in the healthy blood donors and patient population visiting our hospital. Materials and Methods The Column Agglutination Technology (CAT) was used for ABO RhD blood grouping, Direct Antiglobulin Test (DAT), Autocontrol (AC), Indirect Antiglobulin Test (IAT) and red cell antibody screening and the unexpected reactions in any of these tests were recorded for further evaluation. Ethylene Diamine Tetra Acetic Acid (EDTA) blood samples were used for all these tests for both blood donors and admitted patients. The CAT was exercised for the blood grouping (using ABD-Reverse Diluent cassettes) and antibody screening (using 0.8% Surgiscreen, Ortho Clinical Diagnostics Limited, USA and Low Ionic Strength Saline Ortho BLISS with AHG cassettes) on the automated immunohaematology platform ORTHO AutoVue® Innova system (Ortho Clinical Diagnostics Limited, USA). Results Among all blood donors (n=6350), seven (0.11%) donors had showed unexpected reaction. Of these, four had positive antibody screen (three having naturally occuring antibodies 2=anti-M, 1=anti-Lea and 1=inconclusive) and the other three had positive DAT. Of all the patient samples (n=6136) screened for irregular red cell antibodies, four (0.06%) patients were found to have unexpected reaction revealing one (0.02%) with anti-M antibody and the other three (0.05%) had autoantibodies in their serum. Conclusion The combined prevalence for both blood donor and recipient population (n=12,486) was found to be 0.11% at our center. The alloimmunisation among patient population was found to be lower than many other studies worldwide as our hospital does not cater to multitransfused or transfusion dependant patients with haematological disorders and majorly elective surgery patients with no history of previous blood transfusions visit our hospital. PMID:28511387

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements

PubMed Central

Sprouse, Alyssa A.

2016-01-01

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug–botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John’s wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug–botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug–botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism. PMID:26438626

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements.

PubMed

Sprouse, Alyssa A; van Breemen, Richard B

2016-02-01

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug-botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John's wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug-botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug-botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Implementation of computer-based patient records in primary care: the societal health economic effects.

PubMed Central

Arias-Vimárlund, V.; Ljunggren, M.; Timpka, T.

1996-01-01

OBJECTIVE: Exploration of the societal health economic effects occurring during the first year after implementation of Computerised Patient Records (CPRs) at Primary Health Care (PHC) centres. DESIGN: Comparative case studies of practice processes and their consequences one year after CPR implementation, using the constant comparison method. Application of transaction-cost analyses at a societal level on the results. SETTING: Two urban PHC centres under a managed care contract in Ostergötland county, Sweden. MAIN OUTCOME MEASURES: Central implementation issues. First-year societal direct normal costs, direct unexpected costs, and indirect costs. Societal benefits. RESULTS: The total societal effect of the CPR implementation was a cost of nearly 250,000 SEK (USD 37,000) per GP team. About 20% of the effect consisted of direct unexpected costs, accured from the reduction of practitioners' leisure time. The main issues in the implementation process were medical informatics knowledge and computer skills, adaptation of the human-computer interaction design to practice routines, and information access through the CPR. CONCLUSIONS: The societal costs exceed the benefits during the first year after CPR implementation at the observed PHC centres. Early investments in requirements engineering and staff training may increase the efficiency. Exploitation of the CPR for disease prevention and clinical quality improvement is necessary to defend the investment in societal terms. The exact calculation of societal costs requires further analysis of the affected groups' willingness to pay. PMID:8947717

Process improvement methodologies uncover unexpected gaps in stroke care.

PubMed

Kuner, Anthony D; Schemmel, Andrew J; Pooler, B Dustin; Yu, John-Paul J

2018-01-01

Background The diagnosis and treatment of acute stroke requires timed and coordinated effort across multiple clinical teams. Purpose To analyze the frequency and temporal distribution of emergent stroke evaluations (ESEs) to identify potential contributory workflow factors that may delay the initiation and subsequent evaluation of emergency department stroke patients. Material and Methods A total of 719 sentinel ESEs with concurrent neuroimaging were identified over a 22-month retrospective time period. Frequency data were tabulated and odds ratios calculated. Results Of all ESEs, 5% occur between 01:00 and 07:00. ESEs were most frequent during the late morning and early afternoon hours (10:00-14:00). Unexpectedly, there was a statistically significant decline in the frequency of ESEs that occur at the 14:00 time point. Conclusion Temporal analysis of ESEs in the emergency department allowed us to identify an unexpected decrease in ESEs and through process improvement methodologies (Lean and Six Sigma) and identify potential workflow elements contributing to this observation.

An Aggregate of Four Anthrax Cases during the Dry Summer of 2011 in Epirus, Greece.

PubMed

Gaitanis, Georgios; Lolis, Christos J; Tsartsarakis, Antonios; Kalogeropoulos, Chris; Leveidiotou-Stefanou, Stamatina; Bartzokas, Aristidis; Bassukas, Ioannis D

2016-01-01

Human anthrax is currently a sporadic disease in Europe, without significant regional clustering. To report an unexpected aggregate of anthrax cases and correlate local climatic factors with yearly anthrax admissions. Clinical description of a geographical-temporal anthrax aggregate, correlation of disease admissions with local weather data in the period 2001-2014 and literature reports of anthrax clusters from Europe in the last 20 years. We identified 5 cases, all cutaneous: an unexpected aggregate of 4 cases in mid-summer 2011 (including a probable human-to-human transmission) and a sporadic case in August 2005, all in relatively dry periods (p < 0.05). Remarkably, 3/6 reports of human anthrax aggregates from Europe were observed in Balkan Peninsula countries in the year 2011. In the light of the predicted climatic change, unexpected anthrax aggregates during dry periods in southern Europe underscore the risk of future anthrax re-emergence on this continent. © 2015 S. Karger AG, Basel.

Does Pelvic Exam in the Emergency Department Add Useful Information?

PubMed Central

Brown, Jeremy; Fleming, Rita; Aristzabel, Jamie; Gishta, Rocksolana

2011-01-01

Objective: Physicians are taught that the pelvic exam is a key part of the evaluation of a woman presenting with abdominal pain or vaginal bleeding. However, the exam is time consuming and invasive, and its use in the emergency department (ED) has not been prospectively evaluated. We evaluated how often the findings of the pelvic exam changed management in a cohort of consecutive female patients presenting with acute abdominal pain or vaginal bleeding. Methods: We enrolled women who required a pelvic exam together with the providers caring for them in an academic ED from September 2004 to August 2005. We collected the results of the general history and physical exam. The provider was asked to predict the findings of the pelvic exam, and these were compared with the actual findings of the exam. Results: One hundred eighty-three patients were prospectively entered into the study. When compared with predicted findings, the pelvic exam was as expected in 131 patients (72%). In a further 40 patients (22%), the findings of the pelvic exam were not as predicted, but resulted in no change in the clinical plan. In 12 cases (6%) the exam revealed a finding that was both unexpected and changed the clinical plan. Only one of these patients was admitted. Of the 24 patients who were admitted, four had a pelvic exam that revealed unexpected results, but only one of these cases caused the physician to change the care planned for the patient. Conclusion: In 94% of women with acute abdominal pain or vaginal bleeding, the results of the pelvic exam were either predictable or had no effect on the clinical plan. This suggests that there may be a subset of women with abdominal pain or vaginal bleeding in whom a pelvic exam may safely be deferred. PMID:21691528

Unexpectedly high leprosy seroprevalence detected using a random surveillance strategy in midwestern Brazil: A comparison of ELISA and a rapid diagnostic test.

PubMed

Frade, Marco Andrey C; de Paula, Natália A; Gomes, Ciro M; Vernal, Sebastian; Bernardes Filho, Fred; Lugão, Helena B; de Abreu, Marilda M M; Botini, Patrícia; Duthie, Malcolm S; Spencer, John S; Soares, Rosa Castália F R; Foss, Norma T

2017-02-01

Leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. We conducted a temporary campaign to detect previously unknown leprosy cases in midwestern Brazil and to compare the performance of different serological tests. A mobile clinic was stationed at the main bus terminal in Brasília, Brazil. Volunteers were quizzed and given a clinical exam to allow categorization as either patients, known contacts of patients or non-contacts, and blood was collected to determine anti-PGL-I and anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New cases of leprosy and the impact of performing this broad random surveillance strategy were evaluated. Accuracy values and concordance between the test results were evaluated among all groups. Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were diagnosed with leprosy. Borderline forms were the most frequent presentation. Both tests presented higher positivity in those individuals with multibacillary disease. Serological tests demonstrated specificities arround 70% for anti-PGL-1 and anti-LID ELISA; and arround 40% for NDO-LID. Sensitivities ranged from 48 to 62%. A substantial agreement between NDO-LID and ELISA with concomitant positive results was found within leprosy patients (Kappa index = 0.79 CI95% 0.36-1.22). The unexpectedly high leprosy prevalence in this population indicates ongoing community-based exposure to Mycobacterium leprae antigens and high rates of subclinical infection. All tests showed low specificity and sensitivity values and therefore cannot be considered for use as stand-alone diagnostics. Rather, considering their positivity among MB patients and non-patients, these tests can be considered effective tools for screening and identifying individuals at high risk who might benefit from regular monitoring.

Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women.

PubMed

McKeand, William

2017-09-01

Bazedoxifene is a selective estrogen receptor modulator that has estrogen agonist effects on bone and lipid metabolism while having neutral or estrogen antagonist effects on the breast and endometrium. The present report describes findings from 3 Phase I clinical studies that evaluated the single-dose pharmacokinetics (study 1; n = 84), multiple-dose pharmacokinetics (study 2; n = 23), and absolute bioavailability (study 3; n = 18) of bazedoxifene. All 3 studies enrolled healthy postmenopausal women who were either naturally postmenopausal or had undergone bilateral oophorectomy at least 6 months before the start of the study. Study 1 showed that unconjugated and total (unconjugated and conjugated) bazedoxifene levels increased proportionally with ascending oral doses of bazedoxifene (through the dose range of 5-120 mg). Evaluation with or without food intake was conducted at the 10-mg dose, with no clinically relevant effect on pharmacokinetic parameters. Study 2 showed that bazedoxifene achieved steady state in 1 week and exhibited linear pharmacokinetics in doses of 5 to 40 mg with no unexpected accumulation over the dose range. In accordance with a linear pharmacokinetic profile, mean maximum plasma concentration values increased with increasing dose, with values of 1.6, 6.2, and 12.5 ng/mL for the 5-, 20-, and 40-mg doses, respectively. In study 3, tablet and capsule formulations of bazedoxifene formulations had an estimated oral bioavailability of ~6%. The clearance of bazedoxifene was 0.4 (0.1) L/h/kg based on intravenous administration. The oral formulations had comparable exposure profiles with respect to AUC and AUC0-t, and the 90% CIs for these values were within the bioequivalence limits of 80% to 125%. Bazedoxifene was safe and well tolerated in all 3 studies. These pharmacokinetic evaluations in healthy postmenopausal women found that bazedoxifene displayed linear pharmacokinetics with doses ranging from 5 to 40 mg, with no unexpected accumulation. Food did not seem to have any clinically relevant impact on pharmacokinetic parameters. Bazedoxifene had an estimated oral bioavailability of ~6% and was safe and well tolerated in the range of doses evaluated. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Expectancy Disconfirmation and Attitude Change.

PubMed

McPeek, Robert W; Edwards, John D

1975-08-01

An experiment was conducted testing the hypothesis that sources delivering unexpected communications (long-haired males arguing against marijuana usage and seminarians arguing in its favor) would be more persuasive than communicators of expected messages (promarijuana hippies and antimarijuana seminarians). Greater attitude change for unexpected sources was found only when the message was antimarijuana. Unexpected communicators also were rated as more sincere and honest than expected sources. Possible reasons for the failure of the expectancy effect to hold for promarijuana communications were suggested, and the results were discussed in terms of a variety of social-psychological theories.

Inattentional deafness in music.

PubMed

Koreimann, Sabrina; Gula, Bartosz; Vitouch, Oliver

2014-01-01

While inattentional blindness is a modern classic in attention and perception research, analogous phenomena of inattentional deafness have been widely neglected. We here present the first investigation of inattentional deafness in and with music under controlled experimental conditions. Inattentional deafness in music is defined as the inability to consciously perceive an unexpected musical stimulus when attention is focused on a certain facet of the piece. Participants listened to a modification of the first 1'50″ of Richard Strauss' Thus Spake Zarathustra; while the control group just listened, the experimental group had to count the number of timpani beats. An e-guitar solo served as the unexpected event. In Study 1, experimental data from n = 115 participants were analyzed. Non-musicians were compared with musicians to investigate the impact of expertise. In Study 2 (n = 47), the scope of the inattentional deafness effect was investigated with a more salient unexpected stimulus. Results demonstrate an inattentional deafness effect under dynamic musical conditions. Quite unexpectedly, the effect was structurally equivalent even for musicians. Our findings clearly show that sustained inattentional deafness exists in the musical realm, in close correspondence to inattentional blindness with dynamic visual stimuli.

Multiple effects of sentential constraint on word processing

PubMed Central

Federmeier, Kara D.; Wlotko, Edward W.; De Ochoa-Dewald, Esmeralda; Kutas, Marta

2009-01-01

Behavioral and electrophysiological studies have uncovered different patterns of constraint effects on the processing of words in sentences. Whereas response time measures have indicated a reduced scope of facilitation from strongly constraining contexts, event-related brain potential (ERP) measures have instead revealed enhanced facilitation for semantically related endings in such sentences. Given this disparity, and the concomitant possibility of functionally separable stages of context effects, the current study jointly examined expectancy (cloze probability) and constraint effects on the ERP response to words. Expected and unexpected (but plausible) words completed strongly and weakly constraining sentences; unexpected items were matched for contextual fit across the two levels of constraint and were semantically unrelated to the most expected endings. N400 amplitudes were graded by expectancy but unaffected by constraint and seemed to index the benefit of contextual information. However, a later effect, in the form of increased frontal positivity from 500 to 900 ms post-stimulus-onset, indicated a possible cost associated with the processing of unexpected words in strongly constraining contexts. PMID:16901469

Striatal and midbrain connectivity with the hippocampus selectively boosts memory for contextual novelty

PubMed Central

Kafkas, Alexandros; Montaldi, Daniela

2015-01-01

The role of contextual expectation in processing familiar and novel stimuli was investigated in a series of experiments combining eye tracking, functional magnetic resonance imaging, and behavioral methods. An experimental paradigm emphasizing either familiarity or novelty detection at retrieval was used. The detection of unexpected familiar and novel stimuli, which were characterized by lower probability, engaged activity in midbrain and striatal structures. Specifically, detecting unexpected novel stimuli, relative to expected novel stimuli, produced greater activity in the substantia nigra/ventral tegmental area (SN/VTA), whereas the detection of unexpected familiar, relative to expected, familiar stimuli, elicited activity in the striatum/globus pallidus (GP). An effective connectivity analysis showed greater functional coupling between these two seed areas (GP and SN/VTA) and the hippocampus, for unexpected than for expected stimuli. Within this network of midbrain/striatal–hippocampal interactions two pathways are apparent; the direct SN–hippocampal pathway sensitive to unexpected novelty and the perirhinal–GP–hippocampal pathway sensitive to unexpected familiarity. In addition, increased eye fixations and pupil dilations also accompanied the detection of unexpected relative to expected familiar and novel stimuli, reflecting autonomic activity triggered by the functioning of these two pathways. Finally, subsequent memory for unexpected, relative to expected, familiar, and novel stimuli was characterized by enhanced recollection, but not familiarity, accuracy. Taken together, these findings suggest that a hippocampal–midbrain network, characterized by two distinct pathways, mediates encoding facilitation and most critically, that this facilitation is driven by contextual novelty, rather than by the absolute novelty of a stimulus. This contextually sensitive neural mechanism appears to elicit increased exploratory behavior, leading subsequently to greater recollection of the unexpected stimulus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25708843

An Unexpected Influence on a Quadratic

ERIC Educational Resources Information Center

Davis, Jon D.

2013-01-01

Using technology to explore the coefficients of a quadratic equation can lead to an unexpected result. This article describes an investigation that involves sliders and dynamically linked representations. It guides students to notice the effect that the parameter "a" has on the graphical representation of a quadratic function in the form…

Violence and unsafe sexual practices in adolescents under 15 years of age.

PubMed

Teixeira, Sérgio Araujo Martins; Taquette, Stella Regina

2010-01-01

To identify factors associated with unprotected sexual activity in females under the age of 15 years. Cross-sectional observational study of sexually active adolescents under the age of 15 seen at a public outpatient gynecology clinic. Data were collected by means of semi-structured interviews (personal information and data on sexuality), clinical examination, and laboratory tests for diagnosis of sexually transmitted infections. Data were analyzed by frequency testing, association of variables (with p <0.05) and multiple correspondence analysis. One hundred sexually active adolescents between the ages of 11 and 14 were interviewed and examined. Of these, 71% declared themselves black; one-third were behind in school; 80% began sexual activity before the age of 13; 58% reported having been victims of violence within the family environment, and 13% had suffered sexual abuse; 77% did not use condoms regularly; and 22% had STIs. Unprotected sexual activity was more frequent with first sexual intercourse before the age of 13, commercial sexual exploitation, multiple sexual partners, intrafamily violence and school delay, as well as black race, unexpected pregnancy, and STIs. The multiple types of violence suffered by teenagers, including structural, intrafamily, and sexual violence, increase their vulnerability to early, unprotected sexual activity and to STIs and unexpected pregnancy. The synergistic effects of poverty, low educational achievement, and low self-esteem reduces the odds that adolescents will build the tools required for self-protection and exposes them to further victimization outside the family environment.

The biasing effect of clinical history on physical examination diagnostic accuracy.

PubMed

Sibbald, Matthew; Cavalcanti, Rodrigo B

2011-08-01

Literature on diagnostic test interpretation has shown that access to clinical history can both enhance diagnostic accuracy and increase diagnostic error. Knowledge of clinical history has also been shown to enhance the more complex cognitive task of physical examination diagnosis, possibly by enabling early hypothesis generation. However, it is unclear whether clinicians adhere to these early hypotheses in the face of unexpected physical findings, thus resulting in diagnostic error. A sample of 180 internal medicine residents received a short clinical history and conducted a cardiac physical examination on a high-fidelity simulator. Resident Doctors (Residents) were randomised to three groups based on the physical findings in the simulator. The concordant group received physical examination findings consistent with the diagnosis that was most probable based on the clinical history. Discordant groups received findings associated with plausible alternative diagnoses which either lacked expected findings (indistinct discordant) or contained unexpected findings (distinct discordant). Physical examination diagnostic accuracy and physical examination findings were analysed. Physical examination diagnostic accuracy varied significantly among groups (75 ± 44%, 2 ± 13% and 31 ± 47% in the concordant, indistinct discordant and distinct discordant groups, respectively (F(2,177)  = 53, p < 0.0001). Of the 115 Residents who were diagnostically unsuccessful, 33% adhered to their original incorrect hypotheses. Residents verbalised an average of 12 findings (interquartile range: 10-14); 58 ± 17% were correct and the percentage of correct findings was similar in all three groups (p = 0.44). Residents showed substantially decreased diagnostic accuracy when faced with discordant physical findings. The majority of trainees given discordant physical findings rejected their initial hypotheses, but were still diagnostically unsuccessful. These results suggest that overcoming the bias induced by a misleading clinical history may involve two independent steps: rejection of the incorrect initial hypothesis, and selection of the correct diagnosis. Educational strategies focused solely on prompting clinicians to re-examine their hypotheses may be insufficient to reduce diagnostic error. © Blackwell Publishing Ltd 2011.

Vitamin effects on the immune system: vitamins A and D take centre stage.

PubMed

Mora, J Rodrigo; Iwata, Makoto; von Andrian, Ulrich H

2008-09-01

Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity.

Vitamin effects on the immune system: vitamins A and D take centre stage

PubMed Central

Mora, J. Rodrigo; Iwata, Makoto; von Andrian, Ulrich H.

2010-01-01

Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity. PMID:19172691

The Influence of Attention Set, Working Memory Capacity, and Expectations on Inattentional Blindness.

PubMed

Kreitz, Carina; Furley, Philip; Memmert, Daniel; Simons, Daniel J

2016-04-01

The probability of inattentional blindness, the failure to notice an unexpected object when attention is engaged on some primary task, is influenced by contextual factors like task demands, features of the unexpected object, and the observer's attention set. However, predicting who will notice an unexpected object and who will remain inattentionally blind has proven difficult, and the evidence that individual differences in cognition affect noticing remains ambiguous. We hypothesized that greater working memory capacity might modulate the effect of attention sets on noticing because working memory is associated with the ability to focus attention selectively. People with greater working memory capacity might be better able to attend selectively to target items, thereby increasing the chances of noticing unexpected objects that were similar to the attended items while decreasing the odds of noticing unexpected objects that differed from the attended items. Our study (N = 120 participants) replicated evidence that task-induced attention sets modulate noticing but found no link between noticing and working memory capacity. Our results are largely consistent with the idea that individual differences in working memory capacity do not predict noticing of unexpected objects in an inattentional blindness task. © The Author(s) 2015.

The event-related potential effects of cognitive conflict in a Chinese character-generation task.

PubMed

Qiu, Jiang; Zhang, Qinglin; Li, Hong; Luo, Yuejia; Yin, Qinging; Chen, Antao; Yuan, Hong

2007-06-11

High-density event-related potentials were recorded to examine the electrophysiologic correlates of the evaluation of possible answers provided during a Chinese character-generation task. We examined three conditions: the character given was what participants initially generated (Consistent answer), the character given was correct (Unexpected Correct answer), or it was incorrect (Unexpected Incorrect answer). Results showed that Unexpected Correct and Incorrect answers elicited a more negative event-related potential deflection (N320) than did Consistent answers between 300 and 400 ms. Dipole source analysis of difference waves (Unexpected Correct or Incorrect minus Consistent answers) localized the generator of the N320 in the anterior cingulate cortex. The N320 therefore likely reflects the cognitive change or conflict between old and new ways of thinking while identifying and judging characters.

Kinase inhibitor profiling reveals unexpected opportunities to inhibit disease-associated mutant kinases

PubMed Central

Duong-Ly, Krisna C.; Devarajan, Karthik; Liang, Shuguang; Horiuchi, Kurumi Y.; Wang, Yuren; Ma, Haiching; Peterson, Jeffrey R.

2016-01-01

Summary Small-molecule kinase inhibitors have typically been designed to inhibit wild-type kinases rather than the mutant forms that frequently arise in diseases such as cancer. Mutations can have serious clinical implications by increasing kinase catalytic activity or conferring therapeutic resistance. To identify opportunities to repurpose inhibitors against disease-associated mutant kinases, we conducted a large-scale functional screen of 183 known kinase inhibitors against 76 recombinant, mutant kinases. The results revealed lead compounds with activity against clinically important mutant kinases including ALK, LRRK2, RET, and EGFR as well as unexpected opportunities for repurposing FDA-approved kinase inhibitors as leads for additional indications. Furthermore, using T674I PDGFRα as an example, we show how single-dose screening data can provide predictive structure-activity data to guide subsequent inhibitor optimization. This study provides a resource for the development of inhibitors against numerous disease-associated mutant kinases and illustrates the potential of unbiased profiling as an approach to compound-centric inhibitor development. PMID:26776524

Challenges in transformation of the "traditional block rotation" medical student clinical education into a longitudinal integrated clerkship model.

PubMed

Heddle, William; Roberton, Gayle; Mahoney, Sarah; Walters, Lucie; Strasser, Sarah; Worley, Paul

2014-01-01

Longitudinal integrated clerkships (LIC) in the first major clinical year in medical student training have been demonstrated to be at least equivalent to and in some areas superior to the "traditional block rotation" (TBR). Flinders University School of Medicine is starting a pilot changing the traditional teaching at the major Academic Medical Centre from TBR to LIC (50% of students in other locations in the medical school already have a partial or full LIC programme). This paper summarises the expected challenges presented at the "Rendez-Vous" Conference in October 2012: (a) creating urgency, (b) training to be a clinician rather than imparting knowledge, (c) resistance to change. We discuss the unexpected challenges that have evolved since then: (a) difficulty finalising the precise schedule, (b) underestimating time requirements, (c) managing the change process inclusively. Transformation of a "block rotation" to "LIC" medical student education in a tertiary academic teaching hospital has many challenges, many of which can be anticipated, but some are unexpected.

The effect of pain on involuntary and voluntary capture of attention.

PubMed

Troche, S J; Houlihan, M E; Connolly, J F; Dick, B D; McGrath, P J; Finley, G A; Stroink, G

2015-03-01

There is converging evidence for the notion that pain affects a broad range of attentional domains. This study investigated the influence of pain on the involuntary capture of attention as indexed by the P3a component in the event-related potential derived from the electroencephalogram. Participants performed in an auditory oddball task in a pain-free and a pain condition during which they submerged a hand in cold water. Novel, infrequent and unexpected auditory stimuli were presented randomly in a series of frequent standard and infrequent target tones. P3a and P3b amplitudes were observed to novel, unexpected and target-related stimuli, respectively. Both electrophysiological components were characterized by reduced amplitudes in the pain compared with the pain-free condition. Hit rate and reaction time to target stimuli did not differ between the two conditions presumably because the experimental task was not difficult enough to exceed attentional capacities under pain conditions. These results indicate that voluntary attention serving the maintenance and control of ongoing information processing (reflected by the P3b amplitude) is impaired by pain. In addition, the involuntary capture of attention and orientation to novel, unexpected information (measured by the P3a) is also impaired by pain. Thus, neurophysiological measures examined in this study support the theoretical positions proposing that pain can reduce attentional processing capacity. These findings have potentially important implications at the theoretical level for our understanding of the interplay of pain and cognition, and at the therapeutic level for the clinical treatment of individuals experiencing ongoing pain. © 2014 European Pain Federation - EFIC®

Effects of a Structured Discharge Planning Program on Perceived Functional Status, Cardiac Self-efficacy, Patient Satisfaction, and Unexpected Hospital Revisits Among Filipino Cardiac Patients: A Randomized Controlled Study.

PubMed

Cajanding, Ruff Joseph

Cardiovascular diseases remain the leading cause of morbidity and mortality among Filipinos and are responsible for a very large number of hospital readmissions. Comprehensive discharge planning programs have demonstrated positive benefits among various populations of patients with cardiovascular disease, but the clinical and psychosocial effects of such intervention among Filipino patients with acute myocardial infarction (AMI) have not been studied. In this study we aimed to determine the effectiveness of a nurse-led structured discharge planning program on perceived functional status, cardiac self-efficacy, patient satisfaction, and unexpected hospital revisits among Filipino patients with AMI. A true experimental (randomized control) 2-group design with repeated measures and data collected before and after intervention and at 1-month follow-up was used in this study. Participants were assigned to either the control (n = 68) or the intervention group (n = 75). Intervention participants underwent a 3-day structured discharge planning program implemented by a cardiovascular nurse practitioner, which is comprised of a series of individualized lecture-discussion, provision of feedback, integrative problem solving, goal setting, and action planning. Control participants received standard routine care. Measures of functional status, cardiac self-efficacy, and patient satisfaction were measured at baseline; cardiac self-efficacy and patient satisfaction scores were measured prior to discharge, and perceived functional status and number of revisits were measured 1 month after discharge. Participants in the intervention group had significant improvement in functional status, cardiac self-efficacy, and patient satisfaction scores at baseline and at follow-up compared with the control participants. Furthermore, participants in the intervention group had significantly fewer hospital revisits compared with those who received only standard care. The results demonstrate that a nurse-led structured discharge planning program is an effective intervention in improving perceived functional health status, cardiac self-efficacy, and patient satisfaction, while reducing the number of unexpected hospital revisits, among Filipino patients with AMI. It is recommended that this intervention be incorporated in the optimal care of patients being discharged with an AMI.

Illnesses and Other Causes of Unexpected Absences from Work During Residency Training.

ERIC Educational Resources Information Center

Parker, Ruth M.; And Others

1987-01-01

Unexpected absences from work among residents cause scheduling difficulties and stress among residents. University of Rochester internal medicine and pediatric residents recorded the days they had been absent from work and provided their opinions regarding the stress these absences caused and the effectiveness for the sick-call system. (Author/MLW)

Physicians’ Perspectives on the Uncertainties and Implications of Chromosomal Microarray Testing of Children and Families

PubMed Central

Reiff, Marian; Ross, Kathryn; Mulchandani, Surabhi; Propert, Kathleen Joy; Pyeritz, Reed E.; Spinner, Nancy B.; Bernhardt, Barbara A.

2012-01-01

Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This paper explores clinicians’ perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using non-parametric statistical tests. Clinicians’ comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late-onset disease, in a hypothetical case. Many non-genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings. PMID:22989118

Safety evaluation of phytosterol-esters. Part 9: Results of a European post-launch monitoring programme.

PubMed

Lea, L J; Hepburn, P A

2006-08-01

Phytosterol-esters were developed by Unilever as a cholesterol lowering novel food ingredient for use initially in vegetable oil spreads. In addition to an extensive package of safety studies and clinical studies a programme of post-launch monitoring (PLM) was developed. PLM was used to address the following questions: (a) Is the product use as predicted/recommended? (b) Are the known effects as predicted? (c) Does the product cause unexpected health effects? The overall conclusions from the PLM programme were: the product is being bought by the target population but intakes are less than the original assumptions made in the risk assessment; long-term use of phytosterol-ester enriched spreads results in a reduction in the serum levels of the most lipophilic carotenoids but at current levels of intake this is unlikely to result in reductions in carotenoids that are of biological significance; evaluation of health related consumer complaints have not indicated any unexpected health effects associated with the use of the product in the marketplace. As part of the European approval under Regulation (EC) No. 258/97 on Novel Foods and Food Ingredients the results of the PLM programme had to be submitted to the European Commission (EC) and reviewed by the Scientific Committee on Food (SCF). They concluded that the study provided valuable information, which complemented the pre-market safety evaluation studies, and that the EC mandatory requirement had been met.

Animacy, perceptual load, and inattentional blindness.

PubMed

Calvillo, Dustin P; Jackson, Russell E

2014-06-01

Inattentional blindness is the failure to notice unexpected objects in a visual scene while engaging in an attention-demanding task. We examined the effects of animacy and perceptual load on inattentional blindness. Participants searched for a category exemplar under low or high perceptual load. On the last trial, the participants were exposed to an unexpected object that was either animate or inanimate. Unexpected objects were detected more frequently when they were animate rather than inanimate, and more frequently with low than with high perceptual loads. We also measured working memory capacity and found that it predicted the detection of unexpected objects, but only with high perceptual loads. The results are consistent with the animate-monitoring hypothesis, which suggests that animate objects capture attention because of the importance of the detection of animate objects in ancestral hunter-gatherer environments.

Evolutions of elastic-plastic shock compression waves in different materials

NASA Astrophysics Data System (ADS)

Kanel, G. I.; Zaretsky, E. B.; Razorenov, S. V.; Savinykh, A. S.; Garkushin, G. V.

2017-01-01

In the paper, we discuss such unexpected features in the wave evolution in solids as a departure from self-similar development of the wave process which is accompanied with apparent sub-sonic wave propagation, changes of shape of elastic precursor wave as a result of variations in the material structure and the temperature, unexpected peculiarities of reflection of elastic-plastic waves from free surface, effects of internal friction at shock compression of glasses and some other effects.

Flight crew exposure to ozone concentrations affecting the visual system.

PubMed

Daubs, J

1980-02-01

To estimate the potential for ozone (O3) effects on the human visual system in flight, O3 concentrations in Boeing 747-100 cockpits were measured during routine flights between London and the United States. From a review of previous reports, it appears that O3 may have both beneficial and harmful effects but that further studies of the visual system responses to O3 are needed before the present findings of 0.030 parts per million (ppm) mean O3, 0.200 ppm maximum O3, and 0.261 ppm-hours average cumulative O3 exposure can be effectively evaluated. Unexpectedly high O3 concentrations were encountered at altitudes below 18,000 feet and, at times, the O3 concentration was observed to decrease as flight level was increased. The clinical, operational, and policy implications of these findings are discussed.

Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

PubMed

Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

Progress in Understanding Autism: 2007-2010

ERIC Educational Resources Information Center

Rutter, Michael L.

2011-01-01

Scientific progress is discussed in relation to clinical issues; genetic issues; environmental issues; and the state of play on psychological treatments. It is concluded that substantial gains in knowledge have been achieved during the last 3 years, and there have been some unexpected findings, but major puzzles remain. We should be hopeful of…

Ectopic Thymic Cyst of the Subglottis: Considerations for Diagnosis and Management.

PubMed

Ahmad, Iram; Kirby, Patricia; Liming, Bryan

2018-03-01

To share the diagnostic and management challenges created by an extremely rare airway lesion-the subglottic ectopic thymic cyst. Case report and literature review. We review the presentation, management, and clinical course of an infant who presented with a subglottic mass that was histologically confirmed as a thymic cyst. A brief literature review supplements the case presentation Results: We present the third described case of an ectopic thymic cyst presenting as a subglottic mass. The differential diagnosis of subglottic masses in neonates consists primarily of subglottic hemangioma and mucous retention cysts. Otolaryngologists must be prepared for unexpected findings when dealing with critical airways. We compare the presentation and management of our patient with the 2 previously described cases. We propose an embryologic theory for the origin of these rare lesions. An ectopic thymic cyst is a rare and unexpected cause of neonatal stridor. Management of pediatric airway lesions must allow for unexpected findings at the time of diagnostic and therapeutic endoscopy. The appropriate management of subglottic thymic cysts is poorly defined, but close surveillance for recurrence is mandatory.

The role of domain expertise and judgment in dealing with unexpected events

NASA Astrophysics Data System (ADS)

Kochan, Janeen Adrion

Unexpected events, particularly those creating surprise, interrupt ongoing mental and behavioral processes, creating an increased potential for unwanted outcomes to the situation. Human reactions to unexpected events vary. One can hypothesize a number of reasons for this variation, including level of domain expertise, previous experience with similar events, emotional connotation, and the contextual surround of the event. Whereas interrupting ongoing activities and focusing attention temporarily on a surprising event may be a useful evolutionary response to a threatening situation, the same process may be maladaptive in today's highly dynamic world. The purpose of this study was to investigate how different aspects of expertise affected one's ability to detect and react to an unexpected event. It was hypothesized that there were two general types of expertise, domain expertise and judgment (Hammond, 2000), which influenced one's performance on dealing with an unexpected event. The goal of the research was to parse out the relative contribution of domain expertise, so the role of judgment could be revealed. The research questions for this study were: (a) Can we identify specific knowledges and skills which enhance one's ability to deal with unexpected events? (b) Are these skills "automatically" included in domain expertise? (c) How does domain expertise improve or deter one's reaction and response to unexpected events? (d) What role does judgment play in responding to surprise? The general hypothesis was that good judgment would influence the process of surprise at different stages and in different ways than would domain expertise. The conclusions from this research indicated that good judgment had a significant positive effect in helping pilots deal with unexpected events. This was most pronounced when domain expertise was low.

A review of the effects of some endocrinological factors on respiratory mechanics.

PubMed

Rubini, Alessandro; Frigo, Alessandro; Carniel, Emanuele Luigi

2016-12-01

Endocrinological factors have been recently described to affect respiratory mechanics. To review recent literature data, most of all obtained by the end-inflation occlusion method, describing the effects of molecules of endocrinological interest such as endothelin, erythropoietin and renin-angiotensin, on respiratory mechanics parameters. The papers considered in this review were found by inserting in Pubmed/Medline the following indexing terms: hormones, endothelin, erythropoietin, angiotensin and respiratory mechanics. It was found that the above cited molecules, beside their well known physiological main effects, exhibit influences on respiratory mechanics, most of all on the airflow resistance, which was described to be increased by endothelin and angiotensin, and decreased by erythropoietin. A number of molecules of biological interest exhibit unexpected influences on respiratory mechanics. The clinical effects depend on the consequences of modified inspiratory pressure values the respiratory muscles have to perform for a given breathing pattern.

Stories That Heal: Understanding the Effects of Creating Digital Stories With Pediatric and Adolescent/Young Adult Oncology Patients.

PubMed

Laing, Catherine M; Moules, Nancy J; Estefan, Andrew; Lang, Mike

The purpose of this philosophical hermeneutic study was to determine if, and understand how, digital stories might be effective therapeutic tools to use with children and adolescents/young adults (AYA) with cancer, thus helping mitigate suffering. Sixteen participants made digital stories with the help of a research assistant trained in digital storytelling and were interviewed following the completion of their stories. Findings from this research revealed that digital stories were a way to have others understand their experiences of cancer, allowed for further healing from their sometimes traumatic experiences, had unexpected therapeutic effects, and were a way to reconcile past experiences with current life. Digital stories, we conclude, show great promise with the pediatric and AYA oncology community and we believe are a way in which the psychosocial effects of cancer treatment may be addressed. Recommendations for incorporating digital stories into clinical practice and follow-up programs are offered.

Unexpected deaths in cardiology outpatients - what can we learn from case review?

PubMed

Kitz, Thomas Michael; Burnand, Nikki; Ortner, Astrid; Rudd, Ian G; Sampson, Rod; Rushworth, Gordon F; Leslie, Stephen James

2016-12-01

A proportion of cardiac patients managed at a cardiology outpatient clinic will die between clinic visits. This study aimed to identify the cause of death, to determine if case review occurred and if a formal review of such cases might be useful. Single-centre retrospective cohort study. A remote regional centre in the North of Scotland. All patients who had been removed from the cardiology outpatient clinic due to death in the community. Cause of death, comorbidities and treatments were collected from hospital records and the national register of deaths. Chi-squared test and Student's t -test were used with significance taken at the 5% level. Of 10,606 patients who attended the cardiology outpatient clinic, 75 (0.7%) patients died in the community. The majority (57.0%) died from a non-cardiac cause. Eleven patients (14.9%) died due to an unexpected cardiac death. A detailed case note review was undertaken. In only two (18.2%) cases was any note made as to the cause of death in the hospital records and in only one was there details of post mortem discussion between primary and secondary care. A small proportion of patients attending a cardiology outpatient clinic died in the community. Documentation of the death in the hospital notes was very poor and evidence of post mortem communication between primary and secondary care was absent in all but one case. Better documentation and communication between primary and secondary care would seem desirable.

Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.

PubMed

Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef

2018-01-01

Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.

Last resort or roll of the die? Exploring the role of metaphors in cancer clinical trials education among medically underserved populations.

PubMed

Krieger, Janice L

2014-01-01

Improving communication about cancer clinical trials may help increase patients' understanding of medical research and their interest in participating. It is unfortunate that there is little empirical research to provide guidance on how to adapt clinical trial messages to maximize cultural sensitivity. This study examines (a) how medically underserved women conceptualize clinical trials by examining the language they use to describe them and (b) how this audience interprets metaphorical language used to explain randomization in the context of Phase III cancer clinical trials. The author conducted in-depth interviews and focus groups with 41 rural, low-income older women who either had been diagnosed with cancer or were caregivers for a person with cancer. The most commonly used lay metaphors for clinical trials had strong negative connotations and included treatment by trial and error, patients are guinea pigs, and treatment of last resort. Participants also expressed strong, unfavorable responses to conventional metaphors that equate randomization with the roll of a die or use other gambling language. Low-literacy definition approaches were unexpectedly problematic, suggesting the potential effectiveness of culturally grounded metaphors for communicating about clinical trials. Ethical implications of these findings for cancer communication are discussed.

Management of post-operative Crohn's disease in 2017: where do we go from here?

PubMed

Nguyen, Vu; Kanth, Rajan; Gazo, Joshua; Sorrentino, Dario

2016-11-01

Postoperative recurrence (POR) of Crohn's disease is common after surgical resection. How to best manage POR remains uncertain. Areas covered: In this review, we will first describe the natural course and the best modalities to diagnose this surgical sequela. We will then focus on the potential risk factors for relapse and highlight the main shortcomings in the current study designs and endoscopic and clinical scoring systems, which may partly explain the unexpected outcomes of recent clinical trials. Finally, we will propose a strategy to address the management of POR. Expert commentary: Anti-tumor necrosis factor (Anti-TNF) agents are the most effective therapy to prevent POR in Crohn's disease. Patient risk stratification and active monitoring with scheduled ileocolonoscopy are cornerstones of optimal POR management. Further studies are needed to address areas of uncertainty including timing and duration of therapy and the role of therapeutic drug monitoring in this setting.

The discovery and development of HIV therapy: the new challenges.

PubMed

Perno, Carlo Federico

2011-01-01

The therapy of HIV infection has been dramatically improved over the years, and allowed the achievement of unexpected results. The availability of many drugs, and the knowledge of HIV related pathogenesis, helped in selecting highly effective antiviral therapies, yet today a major challenge stands, that is the selection of the best regimen(s) in clinical practice. In this frame, evidence-based medicine remains a cornerstone of modern medicine, but its structure needs to be adapted to the new challenges, made by an excess of information (not always fully reliable), by highly sophisticated statistical systems that may overlook the clinical practice despite their ability to define the statistical significance, and the limited number of independent controlled studies. The revision of the criteria of evidence-based medicine, and their adaptation to the new tools available, may allow a better contribution to the definition of the best therapy for each single patient.

Novel Development of Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome due to Insulin Therapy.

PubMed

Mainali, Naba Raj; Schmidt, Torrey R; Alweis, Richard; George, David L

2014-01-01

Male, 67 FINAL DIAGNOSIS: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome Symptoms: Bilateral wrist swelling Medication: - Clinical Procedure: - Specialty: Rheumatology. Unusual or unexpected effect of treatment. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is a rare clinical entity characterized by the sudden onset of inflammatory arthritis and marked pitting edema on upper and lower extremities. RS3PE is considered a rheumatic process distinct from rheumatoid arthritis, which may occasionally represent a paraneoplastic syndrome. Herein, we describe a rare case of RS3PE associated with insulin therapy in a patient with no evidence of underlying malignancy. To the best of our knowledge, this is the first case report of RS3PE associated with insulin therapy. Physicians should look at the introduction of drugs as possible triggers for the development of RS3PE.

Cattle mortality in the Thane district, India: a study of cause/effect relationships.

PubMed

Dogra, R K; Murthy, R C; Srivastava, A K; Gaur, J S; Shukla, L J; Varmani, B M

1996-02-01

An unexpected mortality of more than 300 cattle was investigated near a metal recovery factory located in a rural area of the Thane district of India. The factory was engaged in reclaiming lead, aluminum, tin, and zinc from discarded lead storage batteries and soft drink cans. The environmental samples (soil, leaves, grass, slag, water, and sediment), human blood and hair and animal samples (blood, urine, peritoneal fluid, liver, kidney, cow dung, ribs, and femur), collected for analysis revealed toxic levels of lead, cadmium, and chromium. Clinical examination of factory workers and school children revealed cough, fever, gastric problems, abdominal pain, skin lesions (scabies), and blue line on gums. Histopathological examination of animal tissues revealed chronic pathology with lead inclusion bodies in hepatocytes and renal tubules. Based on environmental, clinical, analytical, and histopathological observations, the mortality has been attributed to toxic levels of metals in the body and the malnourished status of the animals.

Unique topics and issues in rheumatology and clinical immunology.

PubMed

Selmi, Carlo

2014-08-01

Clinicians are facing unexpected issues in everyday practice, and these may become counterintuitive or challenging. Illustrative examples are provided by the hypersensitivity to universally used immunosuppressants such as corticosteroids or antibiotics such as beta-lactam. Secondly, additional issues are represented by the discovery of new pathogenetic mechanisms involved in rheumatoid and psoriatic arthritis or other chronic inflammatory diseases, genomic susceptibility to enigmatic diseases such as giant cell arteritis, or the shared role of specific mediators such as semaphorins. Third, the therapeutic armamentarium has dramatically changed over the past decade following the introduction of biotechnological drugs, and new mechanisms are being proposed to reduce adverse events or increase the drug effectiveness, particularly on cardiovascular comorbidities. Finally, rare diseases continue to represent difficult cases, as for Cogan's syndrome, with limited literature available for clinical recommendations. For these reason, the present issue of Clinical Reviews in Allergy and Immunology is timely and dedicated to these and other unique topics in clinical immunology and allergy. The aim of this issue is thus to help clinicians involved in internal medicine as well as allergists and clinical immunologists while discussing new pathways that will prove important in the near future.

Data sets for manuscript titled Unexpected benefits of reducing aerosol cooling effects

EPA Pesticide Factsheets

These data sets were created using extensive model simulation results from the WRF-CMAQ model, population distributions, and through the use of an health impact assessment model - see manuscript for details.This dataset is associated with the following publication:Xing, J., J. Wang, R. Mathur , J. Pleim , S. Wang, C. Hogrefe , C. Gan, D. Wong , and J. Hao. Unexpected Benefits of Reducing Aerosol Cooling Effects. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 50(14): 7527–7534, (2016).

The Obesity-Breast Cancer Conundrum: An Analysis of the Issues

PubMed Central

Matthews, Shawna B.; Thompson, Henry J.

2016-01-01

Breast cancer develops over a timeframe of 2–3 decades prior to clinical detection. Given this prolonged latency, it is somewhat unexpected from a biological perspective that obesity has no effect or reduces the risk for breast cancer in premenopausal women yet increases the risk for breast cancer in postmenopausal women. This conundrum is particularly striking in light of the generally negative effects of obesity on breast cancer outcomes, including larger tumor size at diagnosis and poorer prognosis in both pre- and postmenopausal women. This review and analysis identifies factors that may contribute to this apparent conundrum, issues that merit further investigation, and characteristics of preclinical models for breast cancer and obesity that should be considered if animal models are used to deconstruct the conundrum. PMID:27338371

Ivermectin treatment of free-ranging endangered Australian sea lion (Neophoca cinerea) pups: effect on hookworm and lice infection status, haematological parameters, growth, and survival.

PubMed

Marcus, Alan D; Higgins, Damien P; Gray, Rachael

2015-07-01

A placebo-controlled study was used to investigate the effectiveness of ivermectin to treat hookworm (Uncinaria sanguinis) and lice (Antarctophthirus microchir) infections in free-ranging Australian sea lion (Neophoca cinerea) pups and to test the hypotheses that these parasitic infections cause anaemia, systemic inflammatory responses, and reduced growth, and contribute towards decreased pup survival. Ivermectin was identified as an effective and safe anthelmintic in this species. Pups administered ivermectin had significantly higher erythrocyte counts and significantly lower eosinophil counts compared to controls at 1-2 months post-treatment, confirming that U. sanguinis and/or A. microchir are causatively associated with disease and demonstrating the positive effect of ivermectin treatment on clinical health parameters. Higher growth rates were not seen in ivermectin-treated pups and, unexpectedly, relatively older pups treated with ivermectin demonstrated significantly reduced growth rates when compared to matched saline-control pups. Differences in survival were not identified between treatment groups; however, this was attributed to the unexpectedly low mortality rate of recruited pups, likely due to the unintended recruitment bias towards pups >1-2 months of age for which mortality due to hookworm infection is less likely. This finding highlights the logistical and practical challenges associated with treating pups of this species shortly after birth at a remote colony. This study informs the assessment of the use of anthelmintics as a tool for the conservation management of free-ranging wildlife and outlines essential steps to further the development of strategies to ensure the effective conservation of the Australian sea lion and its parasitic fauna.

High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death.

PubMed

Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Hall, Kathi; Stein, C Michael

2017-02-01

Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline. The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011. The mean age was 47 years, and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of proarrhythmic effects. The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% CI, 0.40-1.75), 1.24 (95% CI, 0.75-2.05), 0.75 (95% CI, 0.45-1.24), and 1.53 (95% CI, 0.91-2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥ 60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study end point. We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline. © Copyright 2016 Physicians Postgraduate Press, Inc.

High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death

PubMed Central

Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Hall, Kathi; Stein, C. Michael

2018-01-01

Objective Studies demonstrating higher doses of citalopram (>40mg) and escitalopram (>20mg) prolong the QTc interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these SSRIs to that for equivalent doses of fluoxetine, paroxetine, and sertraline. Method The Tennessee Medicaid retrospective cohort study included 54,220 persons 30–74 years of age without cancer or other life-threatening illness prescribed high-dose SSRIs. The mean age was 47 years and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of pro-arrhythmic effects. Results The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% confidence interval [CI], 0.40–1.75), 1.24 (0.75–2.05), 0.75 (0.45–1.24), and 1.53 (0.91–2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study endpoint. Conclusions We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline. PMID:27736049

Pirate Stealth or Inattentional Blindness? The Effects of Target Relevance and Sustained Attention on Security Monitoring for Experienced and Naïve Operators

PubMed Central

Näsholm, Erika; Rohlfing, Sarah; Sauer, James D.

2014-01-01

Closed Circuit Television (CCTV) operators are responsible for maintaining security in various applied settings. However, research has largely ignored human factors that may contribute to CCTV operator error. One important source of error is inattentional blindness – the failure to detect unexpected but clearly visible stimuli when attending to a scene. We compared inattentional blindness rates for experienced (84 infantry personnel) and naïve (87 civilians) operators in a CCTV monitoring task. The task-relevance of the unexpected stimulus and the length of the monitoring period were manipulated between participants. Inattentional blindness rates were measured using typical post-event questionnaires, and participants' real-time descriptions of the monitored event. Based on the post-event measure, 66% of the participants failed to detect salient, ongoing stimuli appearing in the spatial field of their attentional focus. The unexpected task-irrelevant stimulus was significantly more likely to go undetected (79%) than the unexpected task-relevant stimulus (55%). Prior task experience did not inoculate operators against inattentional blindness effects. Participants' real-time descriptions revealed similar patterns, ruling out inattentional amnesia accounts. PMID:24465932

Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

PubMed

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-07-09

There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

Unexpected Rift Valley Fever Outbreak, Northern Mauritania

PubMed Central

El Mamy, Ahmed B. Ould; Baba, Mohamed Ould; Barry, Yahya; Isselmou, Katia; Dia, Mamadou L.; Hampate, Ba; Diallo, Mamadou Y.; El Kory, Mohamed Ould Brahim; Diop, Mariam; Lo, Modou Moustapha; Thiongane, Yaya; Bengoumi, Mohammed; Puech, Lilian; Plee, Ludovic; Claes, Filip; Doumbia, Baba

2011-01-01

During September–October 2010, an unprecedented outbreak of Rift Valley fever was reported in the northern Sahelian region of Mauritania after exceptionally heavy rainfall. Camels probably played a central role in the local amplification of the virus. We describe the main clinical signs (hemorrhagic fever, icterus, and nervous symptoms) observed during the outbreak. PMID:22000364

Melanoma in situ and syringoma: a rare collision tumor. Clinical-pathological report of a case*

PubMed Central

Umbert-Millet, Pablo; Quintana-Codina, Monica; Salleras-Redonnet, Montse

2017-01-01

Collision or contiguous tumors, defined as two or more distinct tumors occurring at one site, are often an unexpected finding and may represent a diagnostic challenge, as clinical and histological presentations do not always coincide. Various combinations of collision tumors have been described with respect to melanocytic lesions, with the most frequently reported being the combination of nevus and basal cell carcinoma. We present an unusual case on the nose involving a melanoma in situ and a clinically-inapparent syringoma, which, to the best of our knowledge, is the first report of this combination. PMID:29267461

Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy.

PubMed

Leung, H; Kwan, P; Elger, C E

2006-08-01

Basic science studies of the human brain have supported the cortical representation of cardiovascular responses, including heart rate variability. Clinical observations of ictal bradyarrhythmia may be mechanistically explained by the influence of the central autonomic network, although the localization and lateralization issues need to be considered in the light of patterns of seizure spread, hand dominance, and presence of lesions. Ictal bradyarrhythmia also offers a mechanistic explanation of sudden unexpected death in epilepsy (SUDEP), though it may explain only some but not all cases of SUDEP. The missing links are (1) clinical evidence of common factors shared by patients with ictal bradyarrhythmia and patients who die from SUDEP, (2) evidence of arrhythmia as a risk factor for SUDEP from epidemiological studies, and, (3) determination of the importance of ictal bradyarrhythmia in SUDEP with respect to other proposed mechanisms including apnea and intrinsic cardiac abnormalities. There remains a need to review the seizure mechanisms in cases of SUDEP and to step up the amount of concurrent ECG/intracranial EEG analysis in both ictal bradyarrhythmia and SUDEP cases.

Unexpected case of pneumomediastinum and subcutaneous emphysema: primary or secondary aetiology?

PubMed

Cheng, Amanda J L; Sadler, Timothy J

2018-04-19

A 77-year-old man was admitted with a relapse of antineutrophil cytoplasmic antibody-positive vasculitis with pulmonary involvement and acute kidney injury. There was a background of pulmonary fibrosis (non-specific interstitial pneumonia type pattern) and superadded pulmonary haemorrhage, acute pulmonary oedema and sepsis. The patient was intubated for 4 days and remained dependent on high flow oxygen and continuous positive airway pressure after extubation. A chest radiograph performed 2 weeks after extubation demonstrated unexpected, extensive pneumomediastinum and subcutaneous emphysema. This was confirmed on CT which raised the possibility of a tracheal defect at the level of the prior endotracheal tube cuff position. Tracheal injury was considered clinically unlikely due to the considerable interval since extubation and a short, uneventful intubation period. The cardiothoracic team recommended a diagnostic bronchoscopy but this was felt too high risk by the clinical team. The cause of pneumomediastinum and subcutaneous emphysema remained indeterminate. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Copy number variations of six and seven α-globin genes in a family with intermedia and major thalassemia phenotypes.

PubMed

Farashi, Samaneh; Vakili, Shadi; Faramarzi Garous, Negin; Ashki, Mehri; Imanian, Hashem; Azarkeivan, Azita; Najmabadi, Hossein

2015-10-01

Copy number variations in α-globin genes are results of unequal crossover between homologous segments in the α-globin gene cluster that misalign during the meiosis phase of the gametogenesis process. Reduction or augmentation of α-globin genes leads to imbalance of α/β chains in hemoglobin tetramer and consequently attenuate or worsen the β-thal clinical symptoms, respectively. Multiplications in α-globin genes have been found in some populations, justifying unexpected severe phenotype of β-thal carriers. Unexpected severe phenotype in the family members may result from coexistence of extra α-globin genes, which is an important factor in the causation of thalassemia intermedia and major in heterozygous β-thalassemia. We described different multiplications in α-globin locus in an Iranian family with one, two or three extra α-globin genes (ααα/αα, αααα/αα and αααα/ααα). The excess α-globin gene/genes cause increment in β/α chain imbalance and leads to worsening pathophysiology and clinical severity of β-thalassemia carriers.

An unexpected tetanus case.

PubMed

Ergonul, Onder; Egeli, Demet; Kahyaoglu, Bulent; Bahar, Mois; Etienne, Mill; Bleck, Thomas

2016-06-01

1 million cases of tetanus are estimated to occur worldwide each year, with more than 200 000 deaths. Tetanus is a life-threatening but preventable disease caused by a toxin produced by Clostridium tetani-a Gram-positive bacillus found in high concentrations in soil and animal excrement. Tetanus is almost completely preventable by active immunisation, but very rarely unexpected cases can occur in individuals who have been previously vaccinated. We report a case of generalised tetanus in a 22-year-old woman that arose despite the protective antitoxin antibody in her serum. The patient received all her vaccinations in the USA; her last vaccination was 6 years ago. The case was unusual because the patient had received all standard vaccinations, had no defined port of entry at disease onset, and had symptoms lasting for 6 months. Tetanus can present with unusual clinical forms; therefore, the diagnosis and management of this rare but difficult disease should be updated. In this Grand Round, we review the clinical features, epidemiology, treatment, and prognosis of C tetani infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mineralocorticoid before glucocorticoid deficiency in a dog with primary hypoadrenocorticism and hypothyroidism.

PubMed

McGonigle, Kathryn M; Randolph, John F; Center, Sharon A; Goldstein, Richard E

2013-01-01

A dog with an unexpected presentation of primary hypoadrenocorticism was evaluated for clinical signs and electrolyte abnormalities characteristic of Addison's disease. Although the initial adrenocorticotropic hormone (ACTH) stimulation test documented serum cortisol concentrations within the reference range, subsequent assessments confirmed hypoaldosteronism. Mineralocorticoid replacement promptly normalized electrolytes and transiently improved clinical illness. Six weeks after initial ACTH stimulation testing, the dog became glucocorticoid deficient. Concurrent primary hypothyroidism was also documented. Hypoaldosteronism preceding hypocortisolemia is a unique presentation of canine Addison's disease.

Obsessive-compulsive personality disorder and behavioral disinhibition.

PubMed

Villemarette-Pittman, Nicole R; Stanford, Matthew S; Greve, Kevin W; Houston, Rebecca J; Mathias, Charles W

2004-01-01

Although obsessive-compulsive personality disorder (OCPD) is an Axis II diagnosis that is not commonly associated with behavioral disinhibition, the literature contains reports of occasional explosive aggressive outbursts. Existing explanations of OCPD etiology do not address the coexistence of compulsive and impulsive features witnessed in some subpopulations of patients. In this study, the authors present a compensatory theory of OCPD in an effort to explain clinical observations of an unexpectedly large number of OCPD diagnoses among patients clinic referred and self-referred for aggression problems.

Characterization of Clinically Attenuated Burkholderia mallei by Whole-Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists

DTIC Science & Technology

2008-04-01

symptoms may have been related to endotoxin . Clinical signs in the ponies and the mule were either minimal (fever) or nonexistent. All 6 equids produced ...ponies, 1 mule, 1 donkey), natural hosts, for purposes of producing antibodies. Multiple high inocula were used in some cases. Unexpectedly SAVP1 appeared...that was experimentally infected in 6 equids (4 ponies, 1 mule, 1 donkey), natural hosts, for purposes of producing antibodies. Multiple high inocula

Anomalous Shocks on the Measured Near-Field Pressure Signatures of Low-Boom Wind-Tunnel Models

NASA Technical Reports Server (NTRS)

Mack, Robert J.

2006-01-01

Unexpected shocks on wind-tunnel-measured pressure signatures prompted questions about design methods, pressure signature measurement techniques, and the quality of measurements in the flow fields near lifting models. Some of these unexpected shocks were the result of component integration methods. Others were attributed to the three-dimension nature of the flow around a lifting model, to inaccuracies in the prediction of the area-ruled lift, or to wing-tip stall effects. This report discusses the low-boom model wind-tunnel data where these unexpected shocks were initially observed, the physics of the lifting wing/body model's flow field, the wind-tunnel data used to evaluate the applicability of methods for calculating equivalent areas due to lift, the performance of lift prediction codes, and tip stall effects so that the cause of these shocks could be determined.

Unexpected molecular weight effect in polymer nanocomposites

DOE PAGES

Cheng, Shiwang; Holt, Adam P.; Wang, Huiqun; ...

2016-01-22

Here, the properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp constrast to theoretical predictions. Further analyses reveal amore » reduction in mass density of the interfacial layer with increasing MW, which can explain these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties.« less

Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial.

PubMed

Leoutsakos, Jeannie-Marie S; Muthen, Bengt O; Breitner, John C S; Lyketsos, Constantine G

2012-04-01

We examined the effects of non-steroidal anti-inflammatory drugs on cognitive decline as a function of phase of pre-clinical Alzheimer disease. Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer disease. We fit growth mixture models of Modified Mini-Mental State (3MS) Examination trajectories with data from 2388 participants in the Alzheimer's Disease Anti-inflammatory Prevention Trial and included class-specific effects of naproxen and celecoxib. We identified three classes: "no decline", "slow decline", and "fast decline", and examined the effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (-2 log likelihood difference: 369.23; p < 0.001) but resulted in reversal of effects over time. Over 4 years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, whereas those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), whereas those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Our results appeared statistically robust but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then attenuated change in fast decliners. Copyright © 2011 John Wiley & Sons, Ltd.

An international study of how laboratories handle and evaluate patient samples after detecting an unexpected APTT prolongation.

PubMed

Ajzner, Éva; Rogic, Dunja; Meijer, Piet; Kristoffersen, Ann Helen; Carraro, Paolo; Sozmen, Eser; Faria, Ana Paula; Sandberg, Sverre

2015-09-01

An unexpectedly detected prolonged activated partial thromboplastin time (APTT) can be a harmless laboratory finding, but can also reflect a thrombotic tendency or a bleeding disorder. The assistance of laboratory professionals in the interpretation of an unexpectedly detected prolonged APTT (uAPTT) is often required. The way in which uAPTTs are evaluated in laboratories was assessed in this international study with the aim of determining whether laboratory professionals are able to fulfill this need. Postanalytical practices after uAPTT were investigated and the mixing study methodology (if used) was studied by circulating a case report with a questionnaire to staff in the invited laboratories. In addition, the interpretations of those staff regarding the presence or absence of inhibitors in three APTT mixing study scenarios were examined. Large within- and between-country variations were detected in both postanalytical practices and mixing study methodologies among the 990 responding laboratories, 90% of which were in 13 countries. Shortcomings regarding the investigation of uAPTTs leading to potentially incorrect or delayed clinical diagnoses were found in 88% of the laboratories. Of the laboratories to which the interpretative questions were sent, 49% interpreted all mixing study scenarios correctly. uAPTTs were investigated appropriately and all mixing study scenarios interpreted correctly in parallel in only 9.6% of the participating laboratories. The clinical requirement for the assistance of laboratory professionals in the interpretation of uAPTTs cannot be met at most of the participating laboratories. Laboratory professionals should be trained in the evaluation of ordinary laboratory tests, such as that for uAPTTs.

[Development of the unexpected reality scale for childcare training].

PubMed

Matsuda, Yuko; Shitara, Saeko; Hamada, Shoko

2016-10-01

This study aimed to develop a scale for unexpected reality for childcare training (Study 1) and examine the change and influence it exerts on the efficacy of preschool teachers (Study 2). In Study 1, the sample consisted of 571 university and junior college students enrolled in a childcare course. After exploratory factor analysis, four factors were extracted: “actual feelings for childcare as a field of study,” “difficulties faced during involvement with children,” “negative aspects of the childcare worker,” and “severity of work.” The study’s scale was shown to be internally consistent and valid. In Study 2, the sample consisted of 122 junior college students enrolled in a childcare course. The results showed that the high-scoring groups of each unexpected reality subscales experienced less unexpected reality in the subsequent training session. Moreover, the results of multiple regression showed that preschool teacher efficacy was predicted positively by “actual feelings for childcare as a field of study” and negatively by “difficulties faced during involvement with children.” Thus, we suggest that for effective pre- and post-guidance of childcare training, unexpected realities should be considered.

Sudden Unexpected Death in Fetal Life Through Early Childhood

PubMed Central

Kinney, Hannah C.; Willinger, Marian

2016-01-01

In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled “Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities.” Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term “SIDS” in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and “omics” approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of “SIDS” as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. PMID:27230764

Manufacturing Affordability

DTIC Science & Technology

2011-10-01

Effective planning early in and throughout program develop - ment is critical to enabling manufacturing affordability. There is no silver bullet and no...unexpected lessons. “Gee, this stove is hot” may be an unexpected lesson for the toddler but should not be so for the adult. All production programs...in program design efforts from day 1 of Engineer- ing and Manufacturing Development , you should be seriously worried. A program that includes the

ERP correlates of unexpected word forms in a picture–word study of infants and adults

PubMed Central

Duta, M.D.; Styles, S.J.; Plunkett, K.

2012-01-01

We tested 14-month-olds and adults in an event-related potentials (ERPs) study in which pictures of familiar objects generated expectations about upcoming word forms. Expected word forms labelled the picture (word condition), while unexpected word forms mismatched by either a small deviation in word medial vowel height (mispronunciation condition) or a large deviation from the onset of the first speech segment (pseudoword condition). Both infants and adults showed sensitivity to both types of unexpected word form. Adults showed a chain of discrete effects: positivity over the N1 wave, negativity over the P2 wave (PMN effect) and negativity over the N2 wave (N400 effect). Infants showed a similar pattern, including a robust effect similar to the adult P2 effect. These observations were underpinned by a novel visualisation method which shows the dynamics of the ERP within bands of the scalp over time. The results demonstrate shared processing mechanisms across development, as even subtle deviations from expected word forms were indexed in both age groups by a reduction in the amplitude of characteristic waves in the early auditory evoked potential. PMID:22483072

Clinical Effectiveness and Cost of a Hospital-Based Fall Prevention Intervention: The Importance of Time Nurses Spend on the Front Line of Implementation.

PubMed

Nuckols, Teryl K; Needleman, Jack; Grogan, Tristan R; Liang, Li-Jung; Worobel-Luk, Pamela; Anderson, Laura; Czypinski, Linda; Coles, Courtney; Walsh, Catherine M

2017-11-01

The aim of this study is to evaluate the clinical effectiveness and incremental net cost of a fall prevention intervention that involved hourly rounding by RNs at 2 hospitals. Minimizing in-hospital falls is a priority, but little is known about the value of fall prevention interventions. We used an uncontrolled before-after design to evaluate changes in fall rates and time use by RNs. Using decision-analytical models, we estimated incremental net costs per hospital per year. Falls declined at 1 hospital (incidence rate ratio [IRR], 0.47; 95% confidence interval [CI], 0.26-0.87; P = .016), but not the other (IRR, 0.83; 95% CI, 0.59-1.17; P = .28). Cost analyses projected a 67.9% to 72.2% probability of net savings at both hospitals due to unexpected declines in the time that RNs spent in fall-related activities. Incorporating fall prevention into hourly rounds might improve value. Time that RNs invest in implementing quality improvement interventions can equate to sizable opportunity costs or savings.

The value of 'binder-off' imaging to identify occult and unexpected pelvic ring injuries.

PubMed

Fagg, James A C; Acharya, Mehool R; Chesser, Tim J S; Ward, Anthony J

2018-02-01

To determine the effectiveness of 'binder-off' plain pelvic radiographs in the assessment of pelvic ring injuries. All patients requiring operative intervention at our tertiary referral pelvic unit/major trauma centre for high-energy pelvic injuries between April 2012 and December 2014 were retrospectively identified. Pre-operative pelvic imaging with and without pelvic binder was reviewed with respect to fracture pattern and pelvic stability. The frequency with which the imaging without pelvic binder changed the opinion of the pelvic stability and need for operative intervention, when compared with the computed tomography (CT) scans and anteroposterior (AP) radiographs with the binder on, was assessed. Seventy-three percent (71 of 97) of patients had initial imaging with a pelvic binder in situ. Of these, 76% (54 of 71) went on to have 'binder-off' imaging. Seven percent (4 of 54) of patients had unexpected unstable pelvic ring injuries identified on 'binder-off' imaging that were not identified on CT imaging in binder. Trauma CT imaging of the pelvis with a pelvic binder in place is inadequate at excluding unstable pelvic ring injuries, and, based on the original findings in this paper, we recommend additional plain film 'binder-off' radiographs, when there is any clinical concern. Copyright © 2017 Elsevier Ltd. All rights reserved.

The bizzare phenomenon of smokers' paradox in the immediate outcome post acute myocardial infarction: an insight into the Malaysian National Cardiovascular Database-Acute Coronary Syndrome (NCVD-ACS) registry year 2006-2013.

PubMed

Venkatason, Padmaa; Salleh, Norsabihin Mohd; Zubairi, Yong; Hafidz, Imran; Ahmad, Wan Azman Wan; Han, Sim Kui; Zuhdi, Ahmad Syadi Mahmood

2016-01-01

'Smoker's paradox' is a controversial phenomenon of an unexpected favourable outcome of smokers post acute myocardial infarction. There are conflicting evidences from the literature so far. We investigate for the existence of this phenomenon in our post acute myocardial infarction patients. We analysed 12,442 active smokers and 10,666 never-smokers diagnosed with STEMI and NSTEMI from the Malaysian National Cardiovascular Database-Acute Coronary Syndrome (NCVD-ACS) year 2006-2013 from 18 hospitals across Malaysia. Comparisons in the baseline characteristics, clinical presentation, in-hospital treatment and short term clinical outcome were made between the two groups. To compare the clinical outcome, an extensive multivariate adjustment was made to estimate the allcause mortality risk ratios for both groups. The active smokers were younger (smokers 53.7 years vs non-smokers 62.3 years P < 0.001) and had lower cardiovascular risk burden and other co-morbidities. STEMI is more common in smokers and intravenous thrombolysis was the main reperfusion therapy in both groups. Smokers had a higher rate of in-hsopital coronary revascularisation in NSTEMI group (21.6 % smokers vs 16.7 % non-smokers P < 0.001) but similar to non-smokers in the STEMI group. Multivariate adjusted mortality risk ratios showed significantly lower mortality risks of smokers at both in-hospital (RR 0.510 [95 % CI 0.442-0.613]) and 30-day post discharge (RR 0.534 [95 % CI 0.437-0.621]). Smoking seems to be associated with a favourable outcome post myocardial infarction. The phenomenon of 'smoker's paradox' is in fact a reality in our patients population. The definitive explanation for this unexpected protective effect of smoking remains unclear.

Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children.

PubMed

Gonzalez Ballesteros, Luisa F; Ma, Nina S; Gordon, Rebecca J; Ward, Leanne; Backeljauw, Philippe; Wasserman, Halley; Weber, David R; DiMeglio, Linda A; Gagne, Julie; Stein, Robert; Cody, Declan; Simmons, Kimber; Zimakas, Paul; Topor, Lisa Swartz; Agrawal, Sungeeta; Calabria, Andrew; Tebben, Peter; Faircloth, Ruth; Imel, Erik A; Casey, Linda; Carpenter, Thomas O

2017-04-01

Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop. Copyright © 2017 Elsevier Inc. All rights reserved.

Unexpectedly high leprosy seroprevalence detected using a random surveillance strategy in midwestern Brazil: A comparison of ELISA and a rapid diagnostic test

PubMed Central

Bernardes Filho, Fred; de Abreu, Marilda M. M.; Botini, Patrícia; Duthie, Malcolm S.; Spencer, John S.; Soares, Rosa Castália F. R.

2017-01-01

Background Leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. We conducted a temporary campaign to detect previously unknown leprosy cases in midwestern Brazil and to compare the performance of different serological tests. Methods A mobile clinic was stationed at the main bus terminal in Brasília, Brazil. Volunteers were quizzed and given a clinical exam to allow categorization as either patients, known contacts of patients or non-contacts, and blood was collected to determine anti-PGL-I and anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New cases of leprosy and the impact of performing this broad random surveillance strategy were evaluated. Accuracy values and concordance between the test results were evaluated among all groups. Results Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were diagnosed with leprosy. Borderline forms were the most frequent presentation. Both tests presented higher positivity in those individuals with multibacillary disease. Serological tests demonstrated specificities arround 70% for anti-PGL-1 and anti-LID ELISA; and arround 40% for NDO-LID. Sensitivities ranged from 48 to 62%. A substantial agreement between NDO-LID and ELISA with concomitant positive results was found within leprosy patients (Kappa index = 0.79 CI95% 0.36–1.22). Conclusions The unexpectedly high leprosy prevalence in this population indicates ongoing community-based exposure to Mycobacterium leprae antigens and high rates of subclinical infection. All tests showed low specificity and sensitivity values and therefore cannot be considered for use as stand-alone diagnostics. Rather, considering their positivity among MB patients and non-patients, these tests can be considered effective tools for screening and identifying individuals at high risk who might benefit from regular monitoring. PMID:28231244

Effect of Phenylephrine on the Accommodative System

PubMed Central

Del Águila-Carrasco, Antonio J.; Bernal-Molina, Paula; Ferrer-Blasco, Teresa; López-Gil, Norberto; Montés-Micó, Robert

2016-01-01

Accommodation is controlled by the action of the ciliary muscle and mediated primarily by parasympathetic input through postganglionic fibers that originate from neurons in the ciliary and pterygopalatine ganglia. During accommodation the pupil constricts to increase the depth of focus of the eye and improve retinal image quality. Researchers have traditionally faced the challenge of measuring the accommodative properties of the eye through a small pupil and thus have relied on pharmacological agents to dilate the pupil. Achieving pupil dilation (mydriasis) without affecting the accommodative ability of the eye (cycloplegia) could be useful in many clinical and research contexts. Phenylephrine hydrochloride (PHCl) is a sympathomimetic agent that is used clinically to dilate the pupil. Nevertheless, first investigations suggested some loss of functional accommodation in the human eye after PHCl instillation. Subsequent studies, based on different measurement procedures, obtained contradictory conclusions, causing therefore an unexpected controversy that has been spread almost to the present days. This manuscript reviews and summarizes the main research studies that have been performed to analyze the effect of PHCl on the accommodative system and provides clear conclusions that could help clinicians know the real effects of PHCl on the accommodative system of the human eye. PMID:28053778

[Education Program of Kampo-medicine for Undergraduates in Preparation for Clinical Setting].

PubMed

Homma, Masato

2016-01-01

Kampo-medicine has become popular in Japanese medical practice combined with western medicine. For example, Daikenchu-To for intestinal obstruction after surgical operation, Shakuyakukanzo-To and Goshajinki-Gan for anti-cancer agents-induced neuropathy, and Yokkan-San for behavioral psychological symptoms of dementia are alternatively used in addition to conventional treatments in Japan. However, combined use of Kampo-medicine and western medicine may cause unexpected adverse events including undesirable drug-drug interactions because Kampo-medicine was not originally developed to be used with western medicine. Although adverse effects of Kampo-medicine are rare compared with those of western medicine, severe events such as liver dysfunction and interstitial pneumonia have been reported in increasing trends. Medical staff including pharmacists, therefore, should be aware of the onset of adverse events before the patients' symptoms become severe. Several adverse effects are caused by chemical constituents such as glycyrrhizin in licorice for pseudoaldosteronism and geniposide in Gardeniae fructus for mesenteric phlebosclerosis. To understand the adverse effects of Kampo-medicine, pharmacists should learn trends in current medication as well as pharmacology and toxicology of the chemical constituents in pharmacognosy. These issues should also be addressed in educational materials for students of clinical pharmacy and pharmacy practice.

Unexpected results in Chernozem soil respiration while measuring the effect of a bio-fertilizer on soil microbial activity.

PubMed

Bautista, Gabriela; Mátyás, Bence; Carpio, Isabel; Vilches, Richard; Pazmino, Karina

2017-01-01

The number of studies investigating the effect of bio-fertilizers is increasing because of their importance in sustainable agriculture and environmental quality. In our experiments, we measured the effect of different fertilizers on soil respiration. In the present study, we were looking for the cause of unexpected changes in CO2 values while examining Chernozem soil samples. We concluded that CO2 oxidizing microbes or methanotrophs may be present in the soil that periodically consume CO2 . This is unusual for a sample taken from the upper layer of well-ventilated Chernozem soil with optimal moisture content.

Unexpected results in Chernozem soil respiration while measuring the effect of a bio-fertilizer on soil microbial activity

PubMed Central

Bautista, Gabriela; Mátyás, Bence; Carpio, Isabel; Vilches, Richard; Pazmino, Karina

2017-01-01

The number of studies investigating the effect of bio-fertilizers is increasing because of their importance in sustainable agriculture and environmental quality. In our experiments, we measured the effect of different fertilizers on soil respiration. In the present study, we were looking for the cause of unexpected changes in CO2 values while examining Chernozem soil samples. We concluded that CO2 oxidizing microbes or methanotrophs may be present in the soil that periodically consume CO2 . This is unusual for a sample taken from the upper layer of well-ventilated Chernozem soil with optimal moisture content. PMID:29333243

Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects.

PubMed

Berlanga-Acosta, Jorge; Abreu-Cruz, Angel; Herrera, Diana García-Del Barco; Mendoza-Marí, Yssel; Rodríguez-Ulloa, Arielis; García-Ojalvo, Ariana; Falcón-Cama, Viviana; Hernández-Bernal, Francisco; Beichen, Qu; Guillén-Nieto, Gerardo

2017-01-01

Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. GHRPs bind to two different receptors (GHS-R1a and CD36), which redundantly or independently exert relevant biological effects. GHRPs' binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS) spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of "drugable" peptides awaits for a definitive clinical niche.

Effects of Unexpected Chords and of Performer's Expression on Brain Responses and Electrodermal Activity

PubMed Central

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-01-01

Background There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. Methodology/Principal Findings This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. Conclusions/Significance These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music. PMID:18612459

Trip-specific training enhances recovery after large postural disturbances for which there is NO expectation.

PubMed

Oludare, Simisola O; Pater, Mackenzie L; Rosenblatt, Noah J; Grabiner, Mark D

2018-03-01

Informed consent usually provides foreknowledge of experimental methods that can potentially increase expectation of stimuli and, therefore, influence the response. We determined the effects of increased expectation and trip-specific training on the recovery response following a treadmill-delivered, trip-specific disturbance. To deliver unexpected disturbances, subjects were deceived during the informed consent process. The primary hypothesis was that the recovery response following an expected postural disturbance would be characterized by trunk kinematics that have been shown to decrease the likelihood of a fall, compared to following an unexpected postural disturbance. We further hypothesized that following an unexpected postural disturbance, the recovery response of the subjects who had completed a trip-specific training protocol would be more biomechanically favorable to recovery compared to those of subjects who had not received the training. Young adults were randomized into Untrained or Trained groups. During the informed consent process, the purpose of the study was explained to subjects in both groups as being to determine the effect of trip-specific training on postural sway while performing an attention-demanding task. Untrained subjects completed two trials during which they minimized their postural sway. During the second trial, an unexpected disturbance was delivered while they performed the attention-demanding task. Trained subjects performed a pre-training postural sway trial, followed by the delivery of a series of expected, training disturbances. Finally, an unexpected disturbance was delivered while they minimized postural sway and performed the attention-demanding task. Expectation significantly improved trunk kinematics (p < .05). In addition, participation in the trip-specific training protocol following the unexpected disturbance the trunk kinematics of the Trained subjects were more biomechanically favorable to recovery than those of the Untrained subjects (p < .01). Improved trunk kinematics following trip-specific training may be independent of the extent to which the disturbance is expected. Copyright © 2018 Elsevier B.V. All rights reserved.

Is There a Relationship between Zinc and the Peculiar Comorbidities of Down Syndrome?

ERIC Educational Resources Information Center

Romano, Corrado; Pettinato, Rosa; Ragusa, Letizia; Barone, Concetta; Alberti, Antonino; Failla, Pinella

2002-01-01

A comparison was made between a range of clinical and biochemical variables and zinc levels in 120 individuals with Down syndrome. No significant differences were found between the normal-zinc and low-zinc groups, except for IgG4 which was, unexpectedly, significantly decreased in the group with normal zinc levels. (Contains references.)…

Bridging the boundaries between scientists and clinicians-mechanistic hypotheses and patient stories in risk assessment of drugs.

PubMed

Rocca, Elena

2017-02-01

The cultural divide between scientists and clinicians has been described as undermining the advance of medical science, by hindering the production of practice-relevant research and of research-informed clinical decisions. Here, I consider the field of post-marketing risk assessment of drugs as an example of strict interdependence between basic biomedical research, clinical research, and clinical evaluation and show how it would benefit from a closer collaboration between scientists and clinicians. The risk assessment of drugs after their marketing relies on spontaneous adverse effect reports to drug agencies and on peer-reviewed case reports. I emphasize the importance of qualitative analysis of such reports for the improvement of mechanistic understanding of harmful effects of drugs. I argue that mechanistic explanations of drug effects are at least as important as determination of their frequency, in order to establish causation. An ideal risk assessment, then, verifies not only the frequency of undesired effects but also why and how the harm happens. For this purpose, the frequency or novelty of the unintended outcome, although contextually indicative, should not determine the epistemic value of a report. Details about the context that generated an unexpected outcome, instead, can offer the chance of improving causal understanding about how the intervention works. This is illustrated through examples from medical research. Mechanistic understanding is a domain of joint collaboration among (1) clinicians, in charge of detailed, qualitative reporting of patient stories about side effects, (2) qualitative clinical researchers, in charge of analyzing clinical contexts or harmful effects and formulating explanatory hypotheses, and (3) basic biomedical researchers, in charge of verifying such hypotheses. In addition, direct information flow can on one side focus clinicians' attention on knowledge gaps about drugs/effects where more research is needed, while on the other side create a more contextualized concept of mechanism among scientists. © 2016 John Wiley & Sons, Ltd.

Homeopathic Treatment of Vitiligo: A Report of Fourteen Cases

PubMed Central

Mahesh, Seema; Mallappa, Mahesh; Tsintzas, Dionysios; Vithoulkas, George

2017-01-01

Case series Patient: — Final Diagnosis: — Symptoms: Skin lesions Medication: — Clinical Procedure: — Specialty: Dermatology Objective: Unusual or unexpected effect of treatment Background: Vitiligo, also known as leukoderma, is an autoimmune skin condition that results in the loss of melanin pigment. Vitiligo is not a rare condition but is difficult to treat and is associated with psychological distress. Case Reports: A series of 14 cases of vitiligo are presented that were treated with individualized homeopathic remedies that were based on plant, animal, or mineral compounds. There were 13 women and one man in the case series, with a mean age 29.8 years, and a mean follow-up from treatment of 58 months. The mean time between the onset of the appearance of vitiligo and the first consultation at our clinic was 96 months. Homeopathic treatment for patients is holistic and was performed on an individualized basis as described in this case series. Photographic images of the skin are presented before and after treatment. Conclusions: In 14 patients with vitiligo treated with individualized homeopathy, the best results were achieved in the patients who were treated in the early stages of the disease. We believe that homeopathy may be effective in the early stages of vitiligo, but large controlled clinical studies are needed in this area. PMID:29196612

Vortex breakdown in simple pipe bends

NASA Astrophysics Data System (ADS)

Ault, Jesse; Shin, Sangwoo; Stone, Howard

2016-11-01

Pipe bends and elbows are one of the most common fluid mechanics elements that exists. However, despite their ubiquity and the extensive amount of research related to these common, simple geometries, unexpected complexities still remain. We show that for a range of geometries and flow conditions, these simple flows experience unexpected fluid dynamical bifurcations resembling the bubble-type vortex breakdown phenomenon. Specifically, we show with simulations and experiments that recirculation zones develop within the bends under certain conditions. As a consequence, fluid and particles can remain trapped within these structures for unexpectedly-long time scales. We also present simple techniques to mitigate this recirculation effect which can potentially have impact across industries ranging from biomedical and chemical processing to food and health sciences.

Reduction of Blood Pressure Following After Renal Artery Adventitia Stripping During Total Nephroureterectomy: Potential Effect of Renal Sympathetic Denervation

PubMed Central

Okamura, Keisuke; Satou, Shunsuke; Setojima, Keita; Shono, Shinjiro; Miyajima, Shigero; Ishii, Tatsu; Shirai, Kazuyuki; Urata, Hidenori

2018-01-01

Case series Patients: Male, 85 • Male, 89 Final Diagnosis: Essential hypertension Symptoms: High blood pressure Medication: Anti-hypertensive agents Clinical Procedure: Operation Specialty: Cardiology and Hypertension Objective: Unusual or unexpected effect of treatment Background: Catheter-based renal sympathetic denervation has been reported to be effective for treatment resistance hypertension in Australia and Europe. However, in the blinded SYMPLICITY HTN-3 trial, renal denervation did not achieve a significant decrease in blood pressure (BP) in comparison to sham controls. There have been various discussions on the factors that influenced this result. Case Reports: Two men on antihypertensive therapy underwent unilateral radical nephroureterectomy for cancer of the renal pelvis. When the renal artery adventitia was stripped and cauterized just before renal artery ligation, the measured BP of the 2 men increased after stripping adventitia and decreased gradually after cauterization of the renal artery. This was presumably due to removal of renal artery sympathetic nerves, similar to the mechanism of catheter-based renal sympathetic denervation, although anesthesia, fluid infusion, and/or mesenteric traction may have had an influence. Conclusions: A similar strategy involving thoracolumbar sympathectomy was reported about 50 years ago. The clinically significant blood pressure reduction in these patients suggests renal denervation is effective. PMID:29765015

Ground reaction vector re-adjustment-the secret of success in treatment of medial compartment knee osteoarthritis by novel high fibular osteotomy.

PubMed

Xie, Wenjun; Zhang, Yu; Qin, Xiaodong; Song, Lijun; Chen, Qun

2018-03-01

High fibular osteotomy has been preliminarily proved to be an effective treatment of knee osteoarthritis by excising a segment of bone at the proximal part of fibula. This imaginative procedure is clinical validated by its instant and explicit knee pain resorption and eventually deformity correction. The rationale of this treatment is named non-uniform settlement of the tibial plateau and used to elucidate the cause of knee joint degeneration, but cannot illuminate the reason of prompt postoperative pain resorption faithfully. To assist in better understanding of this therapeutic method and raising alert to possible unexpected complications, we proposed a new theory to elucidate the pain relief mechanism.

Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

PubMed

Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher; Bagnall, Richard D; Sisodiya, Sanjay; Cooper, Paul N

2016-01-01

Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

All about the Money - External Performance Monitoring is Affected by Monetary, but Not by Socially Conveyed Feedback Cues in More Antisocial Individuals.

PubMed

Pfabigan, Daniela Melitta; Alexopoulos, Johanna; Bauer, Herbert; Lamm, Claus; Sailer, Uta

2011-01-01

This study investigated the relationship between feedback processing and antisocial personality traits measured by the PSSI questionnaire (Kuhl and Kazén, 1997) in a healthy undergraduate sample. While event-related potentials [feedback related negativity (FRN), P300] were recorded, participants encountered expected and unexpected feedback during a gambling task. As recent findings suggest learning problems and deficiencies during feedback processing in clinical populations of antisocial individuals, we performed two experiments with different healthy participants in which feedback about monetary gains or losses consisted either of social-emotional (facial emotion displays) or non-social cues (numerical stimuli). Since the FRN and P300 are both sensitive to different aspects of feedback processing we hypothesized that they might help to differentiate between individuals scoring high and low on an antisocial trait measure. In line with previous evidence FRN amplitudes were enhanced after negative and after unexpected feedback stimuli. Crucially, participants scoring high on antisocial traits displayed larger FRN amplitudes than those scoring low only in response to expected and unexpected negative numerical feedback, but not in response to social-emotional feedback - irrespective of expectancy. P300 amplitudes were not modulated by antisocial traits at all, but by subjective reward probabilities. The present findings indicate that individuals scoring high on antisociality attribute higher motivational salience to monetary compared to emotional-social feedback which is reflected in FRN amplitude enhancement. Contrary to recent findings, however, no processing deficiencies concerning social-emotional feedback stimuli were apparent in those individuals. This indicates that stimulus salience is an important aspect in learning and feedback processes in individuals with antisocial traits which has potential implications for therapeutic interventions in clinical populations.

Estrogen, aging and the cardiovascular system

PubMed Central

Stice, James P.; Lee, Jennifer S.; Pechenino, Angela S.; Knowlton, Anne A.

2014-01-01

Estrogen is a powerful hormone with pleiotropic effects. Estrogens have potent antioxidant effects and are able to reduce inflammation, induce vasorelaxation and alter gene expression in both the vasculature and the heart. Estrogen treatment of cultured cardiac myocytes and endothelial cells rapidly activates NFκB, induces heat-shock protein (HSP)-72, a potent intracellular protective protein, and protects cells from simulated ischemia. In in vivo models, estrogens protect against ischemia and trauma/hemorrhage. Estrogens may decrease the expression of soluble epoxide hydrolase, which has deleterious effects on the cardiovascular system through metabolism of epoxyeicosatrienoic acids. Natural (endogenous) estrogens in premenopausal women appear to protect against cardiovascular disease and yet controlled clinical trials have not indicated a benefit from estrogen replacement postmenopause. Much remains to be understood in regards to the many properties of this powerful hormone and how changes in this hormone interact with aging-associated changes. The unexpected negative results of trials of estrogen replacement postmenopause probably arise from our lack of understanding of the many effects of this hormone. PMID:19371207

Adapting the Forms of Yesterday to the Functions of Today and the Needs of Tomorrow: A Genealogical Case Study of Clinical Teaching Units in Canada

ERIC Educational Resources Information Center

Schrewe, Brett; Pratt, Daniel D.; McKellin, William H.

2016-01-01

Emergent discourses of social responsibility and accountability have in part fuelled the expansion of distributed medical education (DME). In addition to its potential for redressing physician maldistribution, DME has conferred multiple unexpected educational benefits. In several countries, its recent rise has occurred around the boundaries of…

Molecular and cellular insights into Zika virus-related neuropathies.

PubMed

Zhou, Kai; Wang, Long; Yu, Di; Huang, Hesuyuan; Ji, Hong; Mo, Xuming

2017-06-01

Zika virus (ZIKV), a relatively elusive Aedes mosquito-transmitted flavivirus, had been brought into spotlight until recent widespread outbreaks accompanied by unexpectedly severe clinical neuropathies, including fetal microcephaly and Guillain-Barré syndrome (GBS) in the adult. In this review, we focus on the underlying cellular and molecular mechanisms by which vertically transmitted microorganisms reach the fetus and trigger neuropathies.

Structural and Functional Survey of Environmental Aminoglycoside Acetyltransferases Reveals Functionality of Resistance Enzymes.

PubMed

Xu, Zhiyu; Stogios, Peter J; Quaile, Andrew T; Forsberg, Kevin J; Patel, Sanket; Skarina, Tatiana; Houliston, Scott; Arrowsmith, Cheryl; Dantas, Gautam; Savchenko, Alexei

2017-09-08

Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al. Nature 2014 , 509 , 612 ). These enzymes are new members of the Gcn5-Related-N-Acetyltransferase superfamily and confer resistance to the aminoglycosides gentamicin C, sisomicin, and tobramycin. Moreover, the meta-AAC0020 enzyme demonstrated activity comparable with an AAC(3)-I enzyme that serves as a model AAC enzyme identified in a clinical bacterial isolate. The crystal structure of meta-AAC0020 in complex with sisomicin confirmed an unexpected AAC(6') regiospecificity of this enzyme and revealed a drug binding mechanism distinct from previously characterized AAC(6') enzymes. Together, our data highlights the presence of highly active antibiotic-modifying enzymes in the environmental microbiome and reveals unexpected diversity in substrate specificity. These observations of additional AAC enzymes must be considered in the search for novel aminoglycosides less prone to resistance.

Effects of Monoclonal Antibodies against Nerve Growth Factor on Healthy Bone and Joint Tissues in Mice, Rats, and Monkeys: Histopathologic, Biomarker, and Microcomputed Tomographic Assessments.

PubMed

Gropp, Kathryn E; Carlson, Cathy S; Evans, Mark G; Bagi, Cedo M; Reagan, William J; Hurst, Susan I; Shelton, David L; Zorbas, Mark A

2018-01-01

Tanezumab, an anti-nerve growth factor (NGF) antibody, is in development for management of chronic pain. During clinical trials of anti-NGF antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a partial clinical hold on all NGF inhibitors. Three nonclinical toxicology studies were conducted to evaluate the effects of tanezumab or the murine precursor muMab911 on selected bone and joint endpoints and biomarkers in cynomolgus monkeys, Sprague-Dawley rats, and C57BL/6 mice. Joint and bone endpoints included histology, immunohistochemistry, microcomputed tomography (mCT) imaging, and serum biomarkers of bone physiology. Responses of bone endpoints to tanezumab were evaluated in monkeys at 4 to 30 mg/kg/week for 26 weeks and in rats at 0.2 to 10 mg/kg twice weekly for 28 days. The effects of muMab911 at 10 mg/kg/week for 12 weeks on selected bone endpoints were determined in mice. Tanezumab and muMab911 had no adverse effects on any bone or joint parameter. There were no test article-related effects on bone or joint histology, immunohistochemistry, or structure. Reversible, higher osteocalcin concentrations occurred only in the rat study. No deleterious effects were observed in joints or bones in monkeys, rats, or mice administered high doses of tanezumab or muMab911.

Multi-channel metabolic imaging, with SENSE reconstruction, of hyperpolarized [1- 13C] pyruvate in a live rat at 3.0 tesla on a clinical MR scanner

NASA Astrophysics Data System (ADS)

Tropp, James; Lupo, Janine M.; Chen, Albert; Calderon, Paul; McCune, Don; Grafendorfer, Thomas; Ozturk-Isik, Esin; Larson, Peder E. Z.; Hu, Simon; Yen, Yi-Fen; Robb, Fraser; Bok, Robert; Schulte, Rolf; Xu, Duan; Hurd, Ralph; Vigneron, Daniel; Nelson, Sarah

2011-01-01

We report metabolic images of 13C, following injection of a bolus of hyperpolarized [1-13C] pyruvate in a live rat. The data were acquired on a clinical scanner, using custom coils for volume transmission and array reception. Proton blocking of all carbon resonators enabled proton anatomic imaging with the system body coil, to allow for registration of anatomic and metabolic images, for which good correlation was achieved, with some anatomic features (kidney and heart) clearly visible in a carbon image, without reference to the corresponding proton image. Parallel imaging with sensitivity encoding was used to increase the spatial resolution in the SI direction of the rat. The signal to noise ratio in was in some instances unexpectedly high in the parallel images; variability of the polarization among different trials, plus partial volume effects, are noted as a possible cause of this.

Novel Development of Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome due to Insulin Therapy

PubMed Central

Mainali, Naba Raj; Schmidt, Torrey R.; Alweis, Richard; George, David L.

2014-01-01

Patient: Male, 67 Final Diagnosis: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome Symptoms: Bilateral wrist swelling Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Unusual or unexpected effect of treatment Background: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is a rare clinical entity characterized by the sudden onset of inflammatory arthritis and marked pitting edema on upper and lower extremities. RS3PE is considered a rheumatic process distinct from rheumatoid arthritis, which may occasionally represent a paraneoplastic syndrome. Case Report: Herein, we describe a rare case of RS3PE associated with insulin therapy in a patient with no evidence of underlying malignancy. Conclusions: To the best of our knowledge, this is the first case report of RS3PE associated with insulin therapy. Physicians should look at the introduction of drugs as possible triggers for the development of RS3PE. PMID:24696753

Patients with difficult intubation may need referral to sleep clinics.

PubMed

Chung, Frances; Yegneswaran, Balaji; Herrera, Francisco; Shenderey, Alex; Shapiro, Colin M

2008-09-01

Upper airway abnormalities carry the risk of obstructive sleep apnea (OSA) and difficult tracheal intubations. Both conditions contribute to significant clinical problems and have increased perioperative morbidity and mortality. We hypothesized that patients who presented with difficult intubation would have a very high prevalence of OSA and that those with unexpected difficult intubation may require referral to sleep clinics for polysomnography (PSG). Patients classified as a grade 4 Cormack and Lehane on direct laryngoscopic view, and who required more than two attempts for successful endotracheal intubation, were referred to the study by consultant anesthesiologists at four hospitals. Apnea-hypopnea index (AHI) data and postoperative events were collected. Patients with AHI >5/h were considered positive for OSA. Clinical and PSG variables were compared using t-tests and chi(2) test. Over a 20-mo period, 84 patients with a difficult intubation were referred into the study. Thirty-three patients agreed to participate. Sixty-six percent (22 of 33) had OSA (AHI >5/h). Of the 22 OSA patients, 10 patients (64%) had mild OSA (AHI 5-15), 6 (18%) had moderate OSA (AHI >15/h), and 6 (18%) had severe OSA (AHI >30/h). Of the 33 patients, 11 patients (33%) were recommended for continuous positive airway pressure treatment. Between the OSA group and the non-OSA group, there were significant differences in gender, neck size, and the quality of sleep, but there were no significant differences in age and body mass index. Sixty-six percent of patients with unexpected difficult intubation who consented to undergo a sleep study were diagnosed with OSA by PSG. Patients with difficult intubation are at high risk for OSA and should be screened for signs and symptoms of sleep apnea. Screening for OSA should be considered by referral to a sleep clinic for PSG.

Leflunomide counter akt s cardiac hypertrophy.

PubMed

Pescatore, Luciana A; Laurindo, Francisco R M

2018-05-31

Cardiac hypertrophy (CH) is a major independent risk factor for heart failure and mortality. However, therapeutic interventions that target hypertrophy signaling in a load-independent way are unavailable. In a recent issue of Clinical Science (vol. 132, issue 6, 685-699), Ma et al. describe that the anti-inflammatory drug leflunomide markedly antagonized CH, dysfunction, and fibrosis induced by aortic banding or angiotensin-II in mice or by agonists in cultured cells. Unexpectedly, this occurred not via anti-inflammatory mechanisms but rather via inhibtion of Akt (protein kinase B, PKB) signaling. We further discuss the mechanisms underlying Akt activation and its effects on CH and review possible mechanisms of leflunomide effects. Despite some caveats, the availability of such a newly repurposed compound to treat CH can be a relevant advance. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings.

PubMed

Celik, I; Duda, D; Stinner, B; Kimura, K; Gajek, H; Lorenz, W

2003-10-01

The perioperative use of colloidal plasma substitutes is still under discussion. We therefore conducted a prospective randomised study with three commonly used plasma substitutes to examine their histamine releasing effects in 21 volunteers. MATERIAL OR SUBJETS: 21 male volunteers were enrolled in this prospective, randomised, controlled clinical study. Endpoints were the incidence of early and late histamine release and the time course of the release kinetics. Normovolemic hemodilution technique was used with hydroxyethyl starch (n = 6), human albumin (n = 6) and polygeline (n = 9). Measurement and observation period was 240 min after the start of the plasma substitute infusion. Heart rate, blood pressure, SaO(2), clinical symptoms/signs and plasma histamine were measured during the observation period. The incidence of histamine release over the whole observation period in all three groups was 100%. Histamine release occurred frequently in all three groups until 30 min (50%-78%) and up to 240 min (late release reaction: 67%-83%) after the start of infusion. Surprisingly even hydroxyethyl starch, which is regarded as a generally safe and effective plasma substitute, caused high incidences of late histamine release (67%). Histamine release is a well known side effect of polygeline and - to a lesser extent - also of albumin, but was a novel finding for hydroxyethyl starch. We demonstrated for the first time histamine releasing effects of hydroxyethyl starch over a long period of time after administration. This perioperatively and for intensive care possibly relevant finding should make clinicians aware of late side effects not yet connected with the clinical use of these colloidal plasma substitutes.

Effects of automobile steering characteristics on driver/vehicle system performance in discrete maneuvers

NASA Technical Reports Server (NTRS)

Klein, R. H.; Mcruer, D. T.

1975-01-01

A series of discrete maneuver tasks were used to evaluate the effects of steering gain and directional mode dynamic parameters on driver/vehicle responses. The importance and ranking of these parameters were evaluated through changes in subjective driver ratings and performance measures obtained from transient maneuvers such as a double lane change, an emergency lane change, and an unexpected obstacle. The unexpected obstacle maneuver proved more sensitive to individual driver differences than to vehicle differences. Results were based on full scale tests with an experienced test driver evaluating many different dynamic configurations plus seventeen ordinary drivers evaluating six key configurations.

Intraday LeBaron effects

PubMed Central

Bianco, Simone; Corsi, Fulvio; Renò, Roberto

2009-01-01

We study the relation at intraday level between serial correlation and volatility of the Standard and Poor (S&P) 500 stock index futures returns. At daily and weekly levels, serial correlation and volatility forecasts have been found to be negatively correlated (LeBaron effect). After finding a significant attenuation of the original effect over time, we show that a similar but more pronounced effect holds by using intraday measures, by such as realized volatility and variance ratio. We also test the impact of unexpected volatility, defined as the part of volatility which cannot be forecasted, on the presence of intraday serial correlation in the time series by employing a model for realized volatility based on the heterogeneous market hypothesis. We find that intraday serial correlation is negatively correlated to volatility forecasts, whereas it is positively correlated to unexpected volatility.

Sudden death in Lesch-Nyhan disease.

PubMed

Neychev, Vladimir Kostadinov; Jinnah, H A

2006-11-01

To increase awareness of sudden and unexpected death in Lesch-Nyhan disease (LND) and to explore its potential causes, we report the anteceding clinical features and laboratory evaluations of five males with LND who ultimately experienced sudden and unexpected death, along with three additional males who suffered serious respiratory events during life. The ages of patients ranged from 2 to 45 years. The cause of sudden death in LND appears to have a respiratory rather than a cardiogenic basis. All cases cannot be linked readily with a single respiratory process. Instead, different respiratory processes appear to operate in different cases. These may include aspiration, laryngospasm, central apnea, cyanotic breath-holding spells, and high cervical spine damage. Better recognition of these processes will help to guide appropriate workup and management that could include chest imaging, endoscopy of the airways, polysomnography, electroencephalogram, and brain and/or spine imaging.

Long-range DHPS mutations unexpectedly increase Mycobacterium chimaera susceptibility to sulfonamides.

PubMed

Gotthard, Guillaume; Muhammed Ameen, Sirwan; Drancourt, Michel; Chabriere, Eric

2013-12-01

The two closely related mycobacteria, Mycobacterium intracellulare and Mycobacterium chimaera, exhibit a more than two-fold difference in their in vitro susceptibility to sulfonamides. Sulfonamides are antibiotics targeting the 6-hydroxymethyl-7,8-dihydropteroate synthase (DHPS) enzyme involved in the folate synthesis pathway. Comparing the DHPS gene sequence in six M. intracellulare and M. chimaera types trains and clinical isolates yielded only four amino acid changes. In silico structural modelling surprisingly indicated that these amino acids are not located in the active site of DHPS and do not interact directly with sulfonamides. Unexpectedly, these amino acids in distal positions may play a key role in the increased sulfonamide susceptibility observed in M. chimaera compared with M. intracellulare. This example illustrates how three-dimensional models could help to identify distal mutations capable of modulating enzymatic activity. Copyright © 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy.

PubMed

Awada, A; Dirix, L; Manso Sanchez, L; Xu, B; Luu, T; Diéras, V; Hershman, D L; Agrapart, V; Ananthakrishnan, R; Staroslawska, E

2013-01-01

Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor with clinical activity in patients with ErbB2/HER2-positive breast cancer. Phase I of this open-label, phase I/II study investigated the maximum tolerated dose (MTD) of oral neratinib (160 or 240 mg/day) plus vinorelbine (25 mg/m2; days 1 and 8 of each 21-day cycle) in patients with solid tumors. Phase II assessed the safety, clinical activity, and pharmacokinetics of the combination in patients with HER2-positive metastatic breast cancer; the primary efficacy end point was objective response (OR). In phase I (n=12), neratinib (240 mg) plus vinorelbine (25 mg/m2) was established as the MTD. In phase II, 79 patients with HER2-positive metastatic breast cancer were treated at the MTD. The most common treatment-related adverse events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients discontinued treatment due to diarrhea. No clinically important skin side-effects were observed. The OR rate in assessable phase II patients was 41% (no prior lapatinib) and 8% (prior lapatinib). There was no evidence of pharmacokinetic interaction between neratinib and vinorelbine. Neratinib plus vinorelbine showed promising antitumor activity and no unexpected toxic effects in HER2-positive metastatic breast cancer patients. Trial registration ClinicalTrials.gov #NCT00706030.

Transdermal fentanyl: pharmacology and toxicology.

PubMed

Nelson, Lewis; Schwaner, Robert

2009-12-01

To evaluate the underlying pharmacology, safety, and misuse/abuse of transdermal fentanyl, one of the cornerstone pharmacotherapies for patients with chronic pain. Literature was identified through searches of Medline (PubMed) and several textbooks in the areas of pharmacology, toxicology, and pain management. A bibliographical review of articles identified by these searches was also performed. Search terms included combinations of the following: fentanyl, transdermal, patch, pharmacology, kinetics, toxicity, and poisoning. All pertinent clinical trials, retrospective studies, and case reports relevant to fentanyl pharmacology and transdermal fentanyl administered by any route and published in English were identified. Each was reviewed for data regarding the clinical pharmacology, abuse, misuse, and safety of transdermal fentanyl. Data from these studies and information from review articles and pharmaceutical prescribing information were included in this review. Fentanyl is a high-potency opioid that has many uses in the treatment of both acute and chronic pain. Intentional or unintentional misuse, as well as abuse, may lead to significant clinical consequences, including death. Both the US Food and Drug Administration (FDA) and Health Canada have warned of potential pitfalls associated with transdermal fentanyl, although these have not been completely effective in preventing life-threatening adverse events and fatalities related to its inappropriate use. Clinically consequential adverse effects may occur unexpectedly with normal use of transdermal fentanyl, or if misused or abused. Misuse and therapeutic error may be largely preventable through better education at all levels for both the prescriber and patient. The prevention of intentional misuse or abuse may require regulatory intervention.

Minimally invasive corticotomy in orthodontics using a three-dimensional printed CAD/CAM surgical guide.

PubMed

Cassetta, M; Giansanti, M; Di Mambro, A; Calasso, S; Barbato, E

2016-09-01

The aim of this prospective study was to evaluate the effectiveness of an innovative, minimally invasive, flapless corticotomy procedure in orthodontics. The STROBE guidelines were followed. Ten patients with severe dental crowding and a class I molar relationship were selected to receive orthodontic treatment with clear aligners and corticotomy-facilitated orthodontics. The mean age of these patients was 21 years (range 17-28, standard deviation 6.08 years); the male to female ratio was 2:1. The main outcome was a reduction in the total treatment time to correct dental crowding. The secondary outcomes were periodontal index changes, the degree of root resorption, and patient perceptions of the method used, assessed using the short-form Oral Health Impact Profile (OHIP-14). The occurrence of early surgical complications or unexpected events was also recorded. All patients completed the treatment to correct dental crowding. The average treatment time was reduced by two-thirds. The procedure did not significantly modify the periodontal indices or oral health-related quality of life. No early surgical complications or unexpected events were observed. In short, the results indicate that this new procedure is safe and accelerates tooth movement without periodontal complications or discomfort. However, the efficacy of this procedure must be confirmed in controlled clinical trials. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Expected and Unexpected Consequences of the Affordable Care Act: The Impact on Patients and Surgeons-Pro and Con Arguments.

PubMed

Rudnicki, Marek; Armstrong, John H; Clark, Clancy; Marcus, Stuart G; Sacks, Lee; Moser, A James; Reid-Lombardo, K Marie

2016-02-01

The Patient Protection and Affordable Care Act (PPACA), called the Affordable Care Act (ACA) or "ObamaCare" for short, was enacted in 2010. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract (SSAT) hosted a debate with an expert panel to discuss the ACA and its impact on surgical care after the first year of patient enrollment. The purpose of this debate was to focus on the impact of ACA on the public and surgeons. At the core of the ACA are insurance industry reforms and expanded coverage, with a goal of improved clinical outcomes and reduced costs of care. We have observed supportive and opposing views on ACA. Nonetheless, we will witness major shifts in health care delivery as well as restructuring of our relationship with payers, institutions, and patients. With the rapidly changing health care landscape, surgeons will become key members of health systems and will likely need to lead transition from solo-practice to integrated care systems. The full effects of the ACA remain unrealized, but its implementation has begun to change the map of the American health care system and will surely impact the practice of surgery. Herein, we provide a synopsis of the "pro" and "con" arguments for the expected and unexpected consequences of the ACA on society and surgeons.

Socio-professional handicap and accidental risk in patients with hypersomnias of central origin.

PubMed

Bayon, Virginie; Léger, Damien; Philip, Pierre

2009-12-01

Narcolepsy and idiopathic hypersomnia profoundly affect quality of life, education and work. Young patients are very handicapped by unexpected sleep episodes during lessons. Professionals frequently complain about sleepiness at work. Motor discomfort (i.e., cataplectic attacks) surprisingly is less handicapping in narcoleptics than sleepiness but only a few studies clearly assess the problem. Quality of life is also largely impaired in its physical and emotional dimensions. Sleepiness is the major factor explaining a decrease of quality of life and unexpectedly cataplectic attacks have little impact on patients. Another potential problem for these patients is the risk of accidents at work or when driving. Narcoleptic and hypersomniac patients have a higher risk of accidents than apneic or insomniac subjects. But, confounding factors such as duration of driving, number of cataplectic attacks or even objective level of alertness are not always entered in the analytic models mainly because of small samples of patients. Unlike in apneic patients, the effect of treatment on accidental risk has not been studied in narcoleptics or in hypersomniacs. Epidemiological data are needed to improve knowledge concerning these areas. Clinical trials assessing the impact of treatment on driving and work are also urgently needed. Finally, medical treatment does not seem to be completely efficient and physicians should pay more attention to the education, work, life and social environment of their patients.

Simulation modeling analysis of sequential relations among therapeutic alliance, symptoms, and adherence to child-centered play therapy between a child with autism spectrum disorder and two therapists.

PubMed

Goodman, Geoff; Chung, Hyewon; Fischel, Leah; Athey-Lloyd, Laura

2017-07-01

This study examined the sequential relations among three pertinent variables in child psychotherapy: therapeutic alliance (TA) (including ruptures and repairs), autism symptoms, and adherence to child-centered play therapy (CCPT) process. A 2-year CCPT of a 6-year-old Caucasian boy diagnosed with autism spectrum disorder was conducted weekly with two doctoral-student therapists, working consecutively for 1 year each, in a university-based community mental-health clinic. Sessions were video-recorded and coded using the Child Psychotherapy Process Q-Set (CPQ), a measure of the TA, and an autism symptom measure. Sequential relations among these variables were examined using simulation modeling analysis (SMA). In Therapist 1's treatment, unexpectedly, autism symptoms decreased three sessions after a rupture occurred in the therapeutic dyad. In Therapist 2's treatment, adherence to CCPT process increased 2 weeks after a repair occurred in the therapeutic dyad. The TA decreased 1 week after autism symptoms increased. Finally, adherence to CCPT process decreased 1 week after autism symptoms increased. The authors concluded that (1) sequential relations differ by therapist even though the child remains constant, (2) therapeutic ruptures can have an unexpected effect on autism symptoms, and (3) changes in autism symptoms can precede as well as follow changes in process variables.

Electrocatalytic Hydrogenation of Phenol over Platinum and Rhodium: Unexpected Temperature Effects Resolved

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Nirala; Song, Yang; Gutiérrez, Oliver Y.

2016-11-04

Both electrocatalytic hydrogenation (ECH) and thermal hydrogenation (TH) of phenol by Pt and Rh show a roll-over in rate with increasing temperature without changing the principal reaction pathways. The negative effect of temperature for aqueous-phase phenol H2 and electrocatalytic hydrogenation on Pt and Rh is deduced to be due to the unexpected buildup of dehydrogenated phenol adsorbates, which block active sites. Rates of ECH and TH increase similarly with increasing hydrogen chemical potential whether induced by applied potential or H2 pressure, both via increasing H coverage, and indirectly by removing site blockers, a very strong effect at high temperature. Thismore » enables unprecedented rates in the TH of phenol at these temperatures.« less

Potential for Enhanced Therapeutic Activity of Biological Cancer Therapies with Doxycycline Combination

PubMed Central

Tang, Hui; Sampath, Padma; Yan, Xinmin; Thorne, Stephen H

2012-01-01

Despite significant strides made in the clinical translation of adoptive immune cell therapies, it is apparent that many tumors incorporate strategies to avoid recognition by receptors expressed on the immune cells, such as NKG2D. Strategies that stabilize the expression of ligands for these receptors may enhance the therapeutic potential of these and related therapies. Doxycycline inhibits matrix metalloproteinases (MMPs) that act to cleave the extracellular domain of MICA/B, ligands for the NKG2D receptor. Doxycycline treatment blocked shedding of MICA/B from a panel of human tumor cells, but also acted to increase their expression and cell surface translocation, possibly through its action on ATM. This meant that many tumor cells displayed increased MICA/B expression and enhanced susceptibility to CIK cells. Interestingly, doxycycline also selectively enhanced the replication of oncolytic vaccinia in many tumor cell lines, leading to increased sensitivity to these therapies. Combination (CIK-oncolytic vaccinia) therapies used in conjunction with doxycyline led to increased anti-tumor effects. The unexpected and pleiotropic beneficial anti-tumor effects of doxycycline on both immune cell and oncolytic viral therapies make it an excellent candidate for rapid clinical testing. PMID:23282955

Culturally targeted patient navigation for increasing african americans' adherence to screening colonoscopy: a randomized clinical trial.

PubMed

Jandorf, Lina; Braschi, Caitlyn; Ernstoff, Elizabeth; Wong, Carrie R; Thelemaque, Linda; Winkel, Gary; Thompson, Hayley S; Redd, William H; Itzkowitz, Steven H

2013-09-01

Patient navigation has been an effective intervention to increase cancer screening rates. This study focuses on predicting outcomes of screening colonoscopy for colorectal cancer among African Americans using different patient navigation formats. In a randomized clinical trial, patients more than 50 years of age without significant comorbidities were randomized into three navigation groups: peer-patient navigation (n = 181), pro-patient navigation (n = 123), and standard (n = 46). Pro-patient navigations were health care professionals who conducted culturally targeted navigation, whereas peer-patient navigations were community members trained in patient navigation who also discussed their personal experiences with screening colonoscopy. Two assessments gathered sociodemographic, medical, and intrapersonal information. Screening colonoscopy completion rate was 75.7% across all groups with no significant differences in completion between the three study arms. Annual income more than $10,000 was an independent predictor of screening colonoscopy adherence. Unexpectedly, low social influence also predicted screening colonoscopy completion. In an urban African American population, patient navigation was effective in increasing screening colonoscopy rates to 15% above the national average, regardless of patient navigation type or content. Because patient navigation successfully increases colonoscopy adherence, cultural targeting may not be necessary in some populations.

SGLT2 inhibitors in the pipeline for the treatment of diabetes mellitus in Japan.

PubMed

Ito, Hiroyuki; Shinozaki, Masahiro; Nishio, Shinya; Abe, Mariko

2016-10-01

Sodium glucose cotransporter 2 (SGLT2) inhibitors have been available for the treatment of type 2 diabetes (T2DM) in Japan since April 2014. The prescription rate in Japan is low in comparison to Western countries. We summarize the results obtained from the phase 3 clinical trials and clinical studies involving Japanese T2DM patients. We also discuss the current situation and the future prospects of SGLT2 inhibitors in Japan. Unexpected adverse events, such as cerebral infarction and diabetic ketoacidosis have been reported from clinics shortly after the initiation of SGLT2 inhibitor treatment. However, the reductions in blood glucose levels and body weight have been demonstrated in phase 3 trials using 6 types of SGLT2 inhibitors, while observational studies of Japanese T2DM patients, which were performed in the clinical setting, showed that the incidence of adverse drug reactions, such as severe hypoglycemia, was low. SGLT2 inhibitors are also considered to be effective for treating Japanese patients with T2DM. When prescribing SGLT2 inhibitors, it is necessary to ensure that they are used appropriately because the Japanese T2DM patient population has a high proportion of elderly individuals and a high incidence of cerebrovascular disease.

Mapping Brain Metals to Evaluate Therapies for Neurodegenerative Disease

PubMed Central

Popescu, Bogdan Florin Gh; Nichol, Helen

2013-01-01

The brain is rich in metals and has a high metabolic rate, making it acutely vulnerable to the toxic effects of endogenously produced free radicals. The abundant metals, iron and copper, transfer single electrons as they cycle between their reduced (Fe2+, Cu1+) and oxidized (Fe3+, Cu2+) states making them powerful catalysts of reactive oxygen species (ROS) production. Even redox inert zinc, if present in excess, can trigger ROS production indirectly by altering mitochondrial function. While metal chelators seem to improve the clinical outcome of several neurodegenerative diseases, their mechanisms of action remain obscure and the effects of long-term use are largely unknown. Most chelators are not specific to a single metal and could alter the distribution of multiple metals in the brain, leading to unexpected consequences over the long-term. We show here how X-ray fluorescence will be a valuable tool to examine the effect of chelators on the distribution and amount of metals in the brain. PMID:20553312

Zolpidem efficacy and safety in disorders of consciousness.

PubMed

Machado, Calixto; Estévez, Mario; Rodriguez-Rojas, Rafael

2018-01-01

Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

Clinical efficacy of subgingivally delivered simvastatin gel in chronic periodontitis patients.

PubMed

Agarwal, Swati; Chaubey, Krishna Kumar; Chaubey, Abhinav; Agarwal, Vikas; Madan, Ellora; Agarwal, Manvi Chandra

2016-01-01

Simvastatin (SMV), a new locally delivered drug of class statins, is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. Statins, besides having lipid-lowering abilities, also have pleiotropic effects like host modulation and bone regeneration. The present study was designed to investigate the effectiveness of SMV, 1.2 mg, in an indigenously prepared biodegradable controlled-release gel as an adjunct to scaling and root planing (SRP). A total of 60 sites, with pocket depth ≥5 mm, two from each of 30 patients after SRP, were categorized into two treatment groups, for subgingival placement of placebo (Gp 1) or SMV (Gp 2). Clinical parameters were recorded at baseline and at 1, 3 and 6 months comprising plaque index, gingival index, probing pocket depth (PPD) and clinical attachment level (CAL). The osseous changes were evaluated radiographically by measuring vertical gain, INFRA 1 and angle of the defect, INFRA 2 from baseline to 6 months. All subjects tolerated the drug, without any post-application complication. The treatment improved the periodontal condition in both the groups but significant reductions in PPD (p= 0.04), and INFRA 1 (p= 0.000), along with gain in CAL (p= 0.02) and INFRA 2 (p= 0.000) were observed in Gp 2. In one site, an unexpected 5 mm decrease in INFRA 1 was found. Local drug delivery of SMV enhanced the beneficial effect of SRP, in pocket reduction, gain in CAL and bone fill.

Clinical efficacy of subgingivally delivered simvastatin gel in chronic periodontitis patients

PubMed Central

Agarwal, Swati; Chaubey, Krishna Kumar; Chaubey, Abhinav; Agarwal, Vikas; Madan, Ellora; Agarwal, Manvi Chandra

2016-01-01

Background: Simvastatin (SMV), a new locally delivered drug of class statins, is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. Statins, besides having lipid-lowering abilities, also have pleiotropic effects like host modulation and bone regeneration. The present study was designed to investigate the effectiveness of SMV, 1.2 mg, in an indigenously prepared biodegradable controlled-release gel as an adjunct to scaling and root planing (SRP). Materials and Methods: A total of 60 sites, with pocket depth ≥5 mm, two from each of 30 patients after SRP, were categorized into two treatment groups, for subgingival placement of placebo (Gp 1) or SMV (Gp 2). Clinical parameters were recorded at baseline and at 1, 3 and 6 months comprising plaque index, gingival index, probing pocket depth (PPD) and clinical attachment level (CAL). The osseous changes were evaluated radiographically by measuring vertical gain, INFRA 1 and angle of the defect, INFRA 2 from baseline to 6 months. Results: All subjects tolerated the drug, without any post-application complication. The treatment improved the periodontal condition in both the groups but significant reductions in PPD (p= 0.04), and INFRA 1 (p= 0.000), along with gain in CAL (p= 0.02) and INFRA 2 (p= 0.000) were observed in Gp 2. In one site, an unexpected 5 mm decrease in INFRA 1 was found. Conclusion: Local drug delivery of SMV enhanced the beneficial effect of SRP, in pocket reduction, gain in CAL and bone fill. PMID:28298823

Financial Burden of Pediatric Cancer for Patients and Their Families.

PubMed

Warner, Echo L; Kirchhoff, Anne C; Nam, Gina E; Fluchel, Mark

2015-01-01

Cancer treatment may cause financial stress for pediatric oncology patients and their families. We evaluated pediatric cancer caregivers' perceived financial burden related to socioeconomic factors (eg, parental employment) and health care use factors (eg, unexpected hospitalizations). A single-site, cross-sectional survey of primary caretakers of patients with childhood cancer was performed from July 2010 to July 2012. Eligible patients were treated at a pediatric cancer hospital, diagnosed at age ≤ 21 years and were ≤ 5 years from diagnosis (N = 254). Financial burden was rated on a visual analog scale of 0 to 100. Multivariable linear regression models were used to calculate coefficients and 95% CIs of financial burden by time since diagnosis. Mean age at diagnosis was 6.8 years (SD = 5.5 years), and average time since diagnosis was 1.6 years (SD = 1.4 years). The most common diagnosis was leukemia (41.9%). When adjusted for sex, age at diagnosis, insurance status, and rural residence, caregivers whose child was 1 to 5 years from diagnosis with ≥ 5 unexpected hospitalizations experienced 24.9 (95% CI, 9.1 to 40.7; P < .01) points higher financial burden than those with no unexpected hospitalizations. In addition, when compared with families without employment disruptions, families of children 1 to 5 years from diagnosis in which a caregiver had quit or changed jobs reported 13.4 (95% CI, 3.2 to 23.6; P = .01) points higher financial burden. Efforts to reduce unexpected hospitalizations and employment disruptions by providing more comprehensive supportive care for pediatric patients with cancer could help ease families' financial burden. Copyright © 2015 by American Society of Clinical Oncology.

Risk factors and consequences of unexpected trapping for ruptured anterior communicating artery aneurysms

PubMed Central

Fukuda, Hitoshi; Iwasaki, Koichi; Murao, Kenichi; Yamagata, Sen; Lo, Benjamin W.Y.; Macdonald, R. Loch

2014-01-01

Background: While clipping cerebral aneurysms at the neck is optimal, in some cases this is not possible and other strategies are necessary. The purpose of this study was to describe the incidence, risk factors, and outcomes for inability to clip reconstruct ruptured anterior communicating artery (ACoA) aneurysms. Methods: Of the 70 cases of ruptured ACoA aneurysms between January 2006 and December 2013, our institutional experience revealed four cases of small ACoA aneurysms that had been considered clippable prior to operation but required trapping. When a unilateral A2 segment of anterior cerebral artery (ACA) was compromised by trapping, revascularization was performed by bypass surgery. Clinical presentation, angiographic characteristics, operative approach, intraoperative findings, and treatment outcomes were assessed. Results: Very small aneurysm under 3 mm was a risk factor for unexpected trapping. The reason for unexpected trapping was laceration of the aneurysmal neck in two cases, and lack of clippaple component due to disintegration of entire aneurysmal wall at the time of rupture in the others. Aneurysms with bilateral A1 were treated with sole trapping through pterional approach in two cases. The other two cases had hypoplastic unilateral A1 segment of ACA and were treated with combination of aneurysm trapping and revascularization of A2 segment of ACA through interhemispheric approach. No patients had new cerebral infarctions of cortical ACA territory from surgery. Cognitive dysfunction was observed in three cases, but all patients became independent at 12-month follow up. Conclusions: Unexpected trapping was performed when ruptured ACoA aneurysms were unclippable. Trapping with or without bypass can result in reasonable outcomes, with acceptable risk of cognitive dysfunction. PMID:25101201

[Perioperative onset of sarcoidosis : Rare differential diagnosis of a difficult airway].

PubMed

Jansen, G; Nowak, A

2018-05-01

Sarcoidosis is a rare multisystemic chronic inflammatory condition. Typically, there is a big discrepancy between the patient's subjectively perceived symptoms and the presence of clinical signs. Due to the high number of potential sites of onset (e. g. larynx, lungs, heart, liver, kidneys) the affected organs may show functional restrictions that are relevant for decisions related to anesthesia. Therefore, an anesthetists working in a clinical setting should be familiar with the special needs of this patient collective. This article describes the onset of sarcoidosis in a case of an unexpected difficult airway.

Some comments on clinical studies in orthodontics and their applications to orthodontic treatment.

PubMed

Baumrind, S

1999-06-01

This article indicates the origins and background of the current series of National Institute of Dental and Craniofacial Research-funded, university-based clinical studies of orthodontic treatment. It suggests that future studies should be less focused on refining our estimates of mean changes during treatment and concentrate research on the systematic analysis of individual differences among patients' responses to treatment, and study how skilled clinicians make in-course corrections in response to unexpected changes in treatment conditions. Finally, some suggestions are made concerning optimization of decision making in the presence of uncertainty.

Chronic disease management at Intermountain Healthcare.

PubMed

Towner, Steven

2008-01-01

The care of patients with chronic disease is a significant challenge for any healthcare system. Intermountain Healthcare is trying a variety of approaches to chronic disease management. There are five general areas that have been organized centrally. These areas are provider education, patient education, outcomes data, clinical support (ideas that make it easier to do the right thing), and multidisciplinary coordination of care. Typically within each area a variety of tools are developed. The clinical application of the tools varies from provider to provider and from patient to patient. Innovative tools have come from unexpected sources. Significant improvement in measured outcomes has been demonstrated.

[Identifying children at risk for cardiorespiratory arrest].

PubMed

Carrillo Alvarez, A; Martínez Gutiérrez, A; Salvat Germán, F

2004-08-01

Cardiorespiratory arrest in children with severe disease does not usually present suddenly or unexpectedly but is often the result of a progressive deterioration of respiratory and/or circulatory function. Before failure of these functions occurs, there is a series of clinical signs that serve as a warning. Health professionals should not only evaluate clinical signs of respiratory and/or circulatory insufficiency but should also be able to identify these warning signs as early as possible, preferably in the compensation phase, given that the possibility that this process can be reversed by therapeutic measures decreases as the process progresses.

Mothering: an unacknowledged aspect of undergraduate clinical teachers' work in nursing.

PubMed

McKenna, Lisa; Wellard, Sally

2009-05-01

Clinical education is an important component of undergraduate nurse education, in which clinical teachers facilitate students' application of theoretical classroom knowledge into the clinical practice setting. Mothering as part of clinical teachers' work was a major finding from a larger study exploring clinical teaching work to identify what shaped their work and barriers to their work in clinical settings. The study used semi-structured interviews, informed by the work of Foucault. Maternal discourses emerged as a predominant one as participants presented their relationships with students describing examples of nurturing, protecting, supporting, guiding and providing discipline. The unexpected finding contradicted the dominant view of students as adult learners, and potentially positions them as dependent in their learning in clinical environments. Exploration of this discourse in the context of the study forms the basis of this paper. It is argued that the overall impact of maternal discourses on clinical teaching and learning is unclear but warrants more detailed investigation.

A journey from basic stem cell discovery to clinical application: the case of adventitial progenitor cells.

PubMed

Spencer, Helen L; Slater, Sadie C; Rowlinson, Jonathan; Morgan, Tom; Culliford, Lucy A; Guttridge, Martin; Emanueli, Costanza; Angelini, Gianni; Madeddu, Paolo

2015-01-01

Ischemia is a leading cause of death in the western world. Regenerative medicine aims to improve healing of ischemic injury by complementing pharmacologic/interventional treatments. Navigating regenerative therapies from 'bench-to-bedside' is a multistep time-consuming process, balancing cell expansion, purity, safety and efficacy while complying with regulatory guidelines. Studies started in academic laboratories unused to long-term planning often fail because of poor strategy design, lack of contingency plans or funding. We provide a strategic insight into our translation of saphenous vein-derived adventitial progenitor cells into a clinical grade product to treat angina. We discuss discovery phases, introduction of standard operating procedures and upgrade to clinical standards. We also examine contractual aspects of transferring to GMP-accredited facilities for clinical production and unexpected hurdles.

The treatment of human cancer with agents prepared from bovine cartilage.

PubMed

Prudden, J F

1985-12-01

Oral and subcutaneous administration of specific preparations of bovine tracheal cartilage rings (Catrix), a nontoxic agent, has resulted in a high response rate in 31 cases of a variety of clinical malignancies (response rate 90%, 61% complete). The demonstrated responder include present therapeutic disasters such as glioblastoma multiforme and cancers of the pancreas and lung. Other types which were treated with success included cancers of the ovary, rectum, prostate, cervix, thyroid, and an inoperable squamous cancer of the nose. These responses were observed when full dose therapy was given over prolonged courses of treatment (years). This wide range of Catrix efficacy now invites investigation by others to confirm the effectiveness of the material and to isolate the molecular entities responsible for these unexpectedly favorable results.

Clinical utility of transthoracic two-dimensional and Doppler echocardiography.

PubMed

Krumholz, H M; Douglas, P S; Goldman, L; Waksmonski, C

1994-07-01

The purpose of this study was to determine the value of contemporary echocardiography for patient diagnosis and management in clinical practice. Although the use of echocardiography is growing rapidly, there is little information about its clinical utility. A prospective observational study was performed at a community-based, tertiary care teaching hospital. Physicians were interviewed before and after learning the result of their patients' echocardiographic examination. Chart reviews were performed to confirm reports of new diagnoses and treatments that resulted from echocardiography. Physician interviews were successfully completed for 244 (49%) of 497 inpatients and 101 (30%) of 336 outpatients. Among patients with moderate or greater mitral regurgitation, the diagnosis of "clinically significant" mitral regurgitation was unsuspected in 5 (31%) of 16 outpatients and 28 (60%) of 47 inpatients. Among the patients with left ventricular wall motion abnormalities, the result was unsuspected in 7 (50%) of 14 outpatients and 18 (22%) of 81 inpatients. As assessed by chart review, echocardiography produced a definite new diagnosis in 25 inpatients (10%) and 5 outpatients (5%) and was responsible for changes in pharmacologic treatment in at least 16 inpatients (7%) and 2 outpatients (2%). The echocardiogram commonly provided information that was unexpected. This information provided a definite new diagnosis or treatment in a smaller proportion of the patients. Further research is necessary to define the appropriate yield that would warrant echocardiography on the basis of both clinical and cost-effectiveness criteria.

What is stereoscopic vision good for?

NASA Astrophysics Data System (ADS)

Read, Jenny C. A.

2015-03-01

Stereo vision is a resource-intensive process. Nevertheless, it has evolved in many animals including mammals, birds, amphibians and insects. It must therefore convey significant fitness benefits. It is often assumed that the main benefit is improved accuracy of depth judgments, but camouflage breaking may be as important, particularly in predatory animals. In humans, for the last 150 years, stereo vision has been turned to a new use: helping us reproduce visual reality for artistic purposes. By recreating the different views of a scene seen by the two eyes, stereo achieves unprecedented levels of realism. However, it also has some unexpected effects on viewer experience. The disruption of established mechanisms for interpreting pictures may be one reason why some viewers find stereoscopic content disturbing. Stereo vision also has uses in ophthalmology. Clinical stereoacuity tests are used in the management of conditions such as strabismus and amblyopia as well as vision screening. Stereoacuity can reveal the effectiveness of therapy and even predict long-term outcomes post surgery. Yet current clinical stereo tests fall far short of the accuracy and precision achievable in the lab. At Newcastle University, we are exploiting the recent availability of autostereo 3D tablet computers to design a clinical stereotest app in the form of a game suitable for young children. Our goal is to enable quick, accurate and precise stereoacuity measures which will enable clinicians to obtain better outcomes for children with visual disorders.

Quantitative appraisal of the Amyloid Imaging Taskforce appropriate use criteria for amyloid-PET.

PubMed

Altomare, Daniele; Ferrari, Clarissa; Festari, Cristina; Guerra, Ugo Paolo; Muscio, Cristina; Padovani, Alessandro; Frisoni, Giovanni B; Boccardi, Marina

2018-04-18

We test the hypothesis that amyloid-PET prescriptions, considered appropriate based on the Amyloid Imaging Taskforce (AIT) criteria, lead to greater clinical utility than AIT-inappropriate prescriptions. We compared the clinical utility between patients who underwent amyloid-PET appropriately or inappropriately and among the subgroups of patients defined by the AIT criteria. Finally, we performed logistic regressions to identify variables associated with clinical utility. We identified 171 AIT-appropriate and 67 AIT-inappropriate patients. AIT-appropriate and AIT-inappropriate cases did not differ in any outcomes of clinical utility (P > .05). Subgroup analysis denoted both expected and unexpected results. The logistic regressions outlined the primary role of clinical picture and clinical or neuropsychological profile in identifying patients benefitting from amyloid-PET. Contrary to our hypothesis, also AIT-inappropriate prescriptions were associated with clinical utility. Clinical or neuropsychological variables, not taken into account by the AIT criteria, may help further refine criteria for appropriateness. Copyright © 2018. Published by Elsevier Inc.

Home Videophones Improve Direct Observation in Tuberculosis Treatment: A Mixed Methods Evaluation

PubMed Central

Wade, Victoria A.; Karnon, Jonathan; Eliott, Jaklin A.; Hiller, Janet E.

2012-01-01

Background The use of direct observation to monitor tuberculosis treatment is controversial: cost, practical difficulties, and lack of patient acceptability limit effectiveness. Telehealth is a promising alternative delivery method for improving implementation. This study aimed to evaluate the clinical and cost-effectiveness of a telehealth service delivering direct observation, compared to an in-person drive-around service. Methodology/Principal Findings The study was conducted within a community nursing service in South Australia. Telehealth patients received daily video calls at home on a desktop videophone provided by the nursing call center. A retrospective cohort study assessed the effectiveness of the telehealth and traditional forms of observation, defined by the proportion of missed observations recorded in case notes. This data was inputted to a model, estimating the incremental cost-effectiveness ratio (ICER) of telehealth. Semi-structured interviews were conducted with current patients, community nursing and Chest Clinic staff, concerning service acceptability, usability and sustainability. The percentage of missed observations for the telehealth service was 12.1 (n = 58), compared to 31.1 for the in-person service (n = 70). Most of the difference of 18.9% (95% CI: 12.2 – 25.4) was due to fewer pre-arranged absences. The economic analysis calculated the ICER to be AUD$1.32 (95% CI: $0.51 – $2.26) per extra day of successful observation. The video service used less staff time, and became dominant if implemented on a larger scale and/or with decreased technology costs. Qualitative analysis found enabling factors of flexible timing, high patient acceptance, staff efficiency, and Chest Clinic support. Substantial technical problems were manageable, and improved liaison between the nursing service and Chest Clinic was an unexpected side-benefit. Conclusions/Significance Home video observation is a patient-centered, resource efficient way of delivering direct observation for TB, and is cost-effective when compared with a drive-around service. Future research is recommended to determine applicability and effectiveness in other settings. PMID:23226243

Concept maps and nursing theory: a pedagogical approach.

PubMed

Hunter Revell, Susan M

2012-01-01

Faculty seek to teach nursing students how to link clinical and theoretical knowledge with the intent of improving patient outcomes. The author discusses an innovative 9-week concept mapping activity as a pedagogical approach to teach nursing theory in a graduate theory course. Weekly concept map building increased student engagement and fostered theoretical thinking. Unexpectedly, this activity also benefited students through group work and its ability to enhance theory-practice knowledge.

Specific Language Impairment, Nonverbal IQ, Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Cochlear Implants, Bilingualism, and Dialectal Variants: Defining the Boundaries, Clarifying Clinical Conditions, and Sorting Out Causes

PubMed Central

2016-01-01

Purpose The purpose of this research forum article is to provide an overview of a collection of invited articles on the topic “specific language impairment (SLI) in children with concomitant health conditions or nonmainstream language backgrounds.” Topics include SLI, attention-deficit/hyperactivity disorder, autism spectrum disorder, cochlear implants, bilingualism, and dialectal language learning contexts. Method The topic is timely due to current debates about the diagnosis of SLI. An overarching comparative conceptual framework is provided for comparisons of SLI with other clinical conditions. Comparisons of SLI in children with low-normal or normal nonverbal IQ illustrate the unexpected outcomes of 2 × 2 comparison designs. Results Comparative studies reveal unexpected relationships among speech, language, cognitive, and social dimensions of children's development as well as precise ways to identify children with SLI who are bilingual or dialect speakers. Conclusions The diagnosis of SLI is essential for elucidating possible causal pathways of language impairments, risks for language impairments, assessments for identification of language impairments, linguistic dimensions of language impairments, and long-term outcomes. Although children's language acquisition is robust under high levels of risk, unexplained individual variations in language acquisition lead to persistent language impairments. PMID:26502218

A Method for Functional Task Alignment Analysis of an Arthrocentesis Simulator.

PubMed

Adams, Reid A; Gilbert, Gregory E; Buckley, Lisa A; Nino Fong, Rodolfo; Fuentealba, I Carmen; Little, Erika L

2018-05-16

During simulation-based education, simulators are subjected to procedures composed of a variety of tasks and processes. Simulators should functionally represent a patient in response to the physical action of these tasks. The aim of this work was to describe a method for determining whether a simulator does or does not have sufficient functional task alignment (FTA) to be used in a simulation. Potential performance checklist items were gathered from published arthrocentesis guidelines and aggregated into a performance checklist using Lawshe's method. An expert panel used this performance checklist and an FTA analysis questionnaire to evaluate a simulator's ability to respond to the physical actions required by the performance checklist. Thirteen items, from a pool of 39, were included on the performance checklist. Experts had mixed reviews of the simulator's FTA and its suitability for use in simulation. Unexpectedly, some positive FTA was found for several tasks where the simulator lacked functionality. By developing a detailed list of specific tasks required to complete a clinical procedure, and surveying experts on the simulator's response to those actions, educators can gain insight into the simulator's clinical accuracy and suitability. Unexpected of positive FTA ratings of function deficits suggest that further revision of the survey method is required.

Malaria's contribution to World War One - the unexpected adversary.

PubMed

Brabin, Bernard J

2014-12-16

Malaria in the First World War was an unexpected adversary. In 1914, the scientific community had access to new knowledge on transmission of malaria parasites and their control, but the military were unprepared, and underestimated the nature, magnitude and dispersion of this enemy. In summarizing available information for allied and axis military forces, this review contextualizes the challenge posed by malaria, because although data exist across historical, medical and military documents, descriptions are fragmented, often addressing context specific issues. Military malaria surveillance statistics have, therefore, been summarized for all theatres of the War, where available. These indicated that at least 1.5 million solders were infected, with case fatality ranging from 0.2 -5.0%. As more countries became engaged in the War, the problem grew in size, leading to major epidemics in Macedonia, Palestine, Mesopotamia and Italy. Trans-continental passages of parasites and human reservoirs of infection created ideal circumstances for parasite evolution. Details of these epidemics are reviewed, including major epidemics in England and Italy, which developed following home troop evacuations, and disruption of malaria control activities in Italy. Elsewhere, in sub-Saharan Africa many casualties resulted from high malaria exposure combined with minimal control efforts for soldiers considered semi-immune. Prevention activities eventually started but were initially poorly organized and dependent on local enthusiasm and initiative. Nets had to be designed for field use and were fundamental for personal protection. Multiple prevention approaches adopted in different settings and their relative utility are described. Clinical treatment primarily depended on quinine, although efficacy was poor as relapsing Plasmodium vivax and recrudescent Plasmodium falciparum infections were not distinguished and managed appropriately. Reasons for this are discussed and the clinical trial data summarized, as are controversies that arose from attempts at quinine prophylaxis (quininization). In essence, the First World War was a vast experiment in political, demographic, and medical practice which exposed large gaps in knowledge of tropical medicine and unfortunately, of malaria. Research efforts eventually commenced late in the War to address important clinical questions which established a platform for more effective strategies, but in 1918 this relentless foe had outwitted and weakened both allied and axis powers.

Nonclinical and clinical pharmacology evidence for cardiovascular safety of saxagliptin.

PubMed

Pollack, Pia S; Chadwick, Kristina D; Smith, David M; Billger, Martin; Hirshberg, Boaz; Iqbal, Nayyar; Boulton, David W

2017-09-13

In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial in patients with type 2 diabetes mellitus (T2D) at high risk of cardiovascular (CV) disease, saxagliptin did not increase the risk for major CV adverse events. However, there was an unexpected imbalance in events of hospitalization for heart failure (hHF), one of six components of the secondary CV composite endpoint, with a greater number of events observed with saxagliptin. Here, we examined findings from nonclinical safety and clinical pharmacology studies of saxagliptin with the aim of identifying any potential signals of myocardial injury. In vitro and in vivo (rat, dog, monkey) safety pharmacology and toxicology studies evaluating the potential effects of saxagliptin and its major active metabolite, 5-hydroxy saxagliptin, on the CV system are reviewed. In addition, results from saxagliptin clinical studies are discussed: one randomized, 2-period, double-blind, placebo-controlled single-ascending-dose study (up to 100 mg); one randomized, double-blind, placebo-controlled, sequential, multiple-ascending-high-dose study (up to 400 mg/day for 14 days); and one randomized, double-blind, 4-period, 4-treatment, cross-over thorough QTc study (up to 40 mg/day for 4 days) in healthy volunteers; as well as one randomized, placebo-controlled, sequential multiple-ascending-dose study in patients with T2D (up to 50 mg/day for 14 days). Neither saxagliptin nor 5-hydroxy saxagliptin affected ligand binding to receptors and ion channels (e.g. potassium channels) or action potential duration in in vitro studies. In animal toxicology studies, no changes in the cardiac conduction system, blood pressure, heart rate, contractility, heart weight, or heart histopathology were observed. In healthy participants and patients with T2D, there were no findings suggestive of myocyte injury or fluid overload. Serum chemistry abnormalities indicative of cardiac injury, nonspecific muscle damage, or fluid homeostasis changes were infrequent and balanced across treatment groups. There were no QTc changes associated with saxagliptin. No treatment-emergent adverse events suggestive of heart failure or myocardial damage were reported. The saxagliptin nonclinical and clinical pharmacology programs did not identify evidence of myocardial injury and/or CV harm that may have predicted or may explain the unexpected imbalance in the rate of hHF observed in SAVOR.

Theory of mind for processing unexpected events across contexts.

PubMed

Dungan, James A; Stepanovic, Michael; Young, Liane

2016-08-01

Theory of mind, or mental state reasoning, may be particularly useful for making sense of unexpected events. Here, we investigated unexpected behavior across both social and non-social contexts in order to characterize the precise role of theory of mind in processing unexpected events. We used functional magnetic resonance imaging to examine how people respond to unexpected outcomes when initial expectations were based on (i) an object's prior behavior, (ii) an agent's prior behavior and (iii) an agent's mental states. Consistent with prior work, brain regions for theory of mind were preferentially recruited when people first formed expectations about social agents vs non-social objects. Critically, unexpected vs expected outcomes elicited greater activity in dorsomedial prefrontal cortex, which also discriminated in its spatial pattern of activity between unexpected and expected outcomes for social events. In contrast, social vs non-social events elicited greater activity in precuneus across both expected and unexpected outcomes. Finally, given prior information about an agent's behavior, unexpected vs expected outcomes elicited an especially robust response in right temporoparietal junction, and the magnitude of this difference across participants correlated negatively with autistic-like traits. Together, these findings illuminate the distinct contributions of brain regions for theory of mind for processing unexpected events across contexts. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Antiepileptic treatment in paediatric oncology--an interdisciplinary challenge.

PubMed

Tibussek, D; Distelmaier, F; Schönberger, S; Göbel, U; Mayatepek, E

2006-01-01

Epileptic seizures are a common and clinically relevant problem in paediatric oncology. Attributable to the heterogeneity of this group of patients and a number of possible comorbidities antiepileptic treatment in paediatric oncology poses a number of diagnostic and therapeutic challenges. This requires a close interdisciplinary approach to the seizing child or adolescent. A prompt and detailed diagnostic work-up is needed in every case in order to establish the diagnosis and, equally important, to detect secondary aetiological factors, e. g. epileptogenic drugs or any acute underlying pathology, such as metabolic or toxic encephalopathies, CNS-infections or cerebrovascular events. This might offer the opportunity for a specific causative treatment and thus prevent unnecessary long-term antiepileptic drug (AED) treatment. If AED treatment is initiated several aspects have to be taken into account. Most importantly, AEDs and chemotherapeutic drugs (CTDs) may interact. Depending on the comedication this may result in reduced tumour or seizure control or unexpected toxicity of AEDs or CTDs. Understanding these interactions will allow to anticipate clinically relevant adverse effects. AED may be further complicated by side-effects, some of them of particular concern for children or adolescents, such as cognitive effects, myelotoxicity, serious rashes, endocrinological disturbances, and many more. Beside critically questioning the need for AED treatment it is therefore important to prefer AED with a good safety-profile in this population. Enzyme-inducing and inhibiting AED should be avoided if possible. Preliminary studies indicate that gabapentin and levetiracetam may provide good options in terms of efficacy and safety. However, more properly designed clinical studies are warranted to raise the level of evidence for robust clinical recommendations. Until that time, clinicians will need to continue to question current policies and adapt their daily practice to evolving scientific data.

Do Rare Stimuli Evoke Large P3s by Being Unexpected? A Comparison of Oddball Effects Between Standard-Oddball and Prediction-Oddball Tasks

PubMed Central

Verleger, Rolf; Śmigasiewicz, Kamila

2016-01-01

The P3 component of event-related potentials increases when stimuli are rarely presented. It has been assumed that this oddball effect (rare-frequent difference) reflects the unexpectedness of rare stimuli. The assumption of unexpectedness and its link to P3 amplitude were tested here. A standard- oddball task requiring alternative key-press responses to frequent and rare stimuli was compared with an oddball-prediction task where stimuli had to be first predicted and then confirmed by key-pressing. Oddball effects in the prediction task depended on whether the frequent or the rare stimulus had been predicted. Oddball effects on P3 amplitudes and error rates in the standard oddball task closely resembled effects after frequent predictions. This corroborates the notion that these effects occur because frequent stimuli are expected and rare stimuli are unexpected. However, a closer look at the prediction task put this notion into doubt because the modifications of oddball effects on P3 by expectancies were entirely due to effects on frequent stimuli, whereas the large P3 amplitudes evoked by rare stimuli were insensitive to predictions (unlike response times and error rates). Therefore, rare stimuli cannot be said to evoke large P3 amplitudes because they are unexpected. We discuss these diverging effects of frequency and expectancy, as well as general differences between tasks, with respect to concepts and hypotheses about P3b’s function and conclude that each discussed concept or hypothesis encounters some problems, with a conception in terms of subjective relevance assigned to stimuli offering the most consistent account of these basic effects. PMID:27512527

B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design.

PubMed

Reddy, Venkat; Jayne, David; Close, David; Isenberg, David

2013-01-01

B cells are believed to be central to the disease process in systemic lupus erythematosus (SLE), making them a target for new therapeutic intervention. In recent years there have been many publications regarding the experience in SLE of B-cell depletion utilising rituximab, an anti-CD20 mAb that temporarily depletes B cells,reporting promising results in uncontrolled open studies and in routine clinical use. However, the two large randomised controlled trials in extra-renal lupus (EXPLORER study) and lupus nephritis (LUNAR study) failed to achieve their primary endpoints. Based on the clinical experience with rituximab this failure was somewhat unexpected and raised a number of questions and concerns, not only into the true level of benefit of B-cell depletion in a broad population but also how to test the true level of effectiveness of an investigational agent as we seek to improve the design of therapeutic trials in SLE. A better understanding of what went wrong in these trials is essential to elucidate the underlying reasons for the disparate observations noted in open studies and controlled trials. In this review, we focus on various factors that may affect the ability to accurately and confidently establish the level of treatment effect of the investigational agent, in this case rituximab, in the tw studies and explore hurdles faced in the randomised controlled trials investigating the efficacy of ocrelizumab, the humanised anti-CD20 mAb, in SLE. Further, based on the lessons learned from the clinical trials, we make suggestions that could be implemented in future clinical trial design to overcome the hurdles faced.

Percutaneous transvenous mitral commissurotomy in patients with mitral stenosis and coexistent hyperthyroidism.

PubMed

Wang, P W; Hung, J S; Fu, M; Yeh, K H; Wu, J J

1996-01-01

Percutaneous transvenous mitral commissurotomy (PTMC) was performed successfully without complications in 3 patients with severe mitral stenosis and hyperthyroidism. All 3 patients had pliable, noncalcified mitral valves. One patient who had been treated with methimazole for 6 months was still in a hyperthyroid state when she presented with intractable congestive heart failure and was found to have severe mitral stenosis. The heart failure improved immediately after PTMC, but the patient remained in New York Heart Association functional class 2 until a euthyroid state was achieved with I131 therapy. In the other 2 patients, hyperthyroidism was unsuspected at the time of PTMC. Unexpectedly suboptimal symptom improvement led to the diagnosis of hyperthyroidism 1 month after the intervention. In all 3 patients, PTMC resulted in an immediate hemodynamic and clinical improvement. However, complete clinical improvement occurred only when euthyroid state was achieved after antithyroid treatment. The present study suggests that PTMC is a safe and effective intervention modality in patients with coexisting hyperthyroidism and severe mitral stenosis. The procedure may be considered a therapeutic option in patients with hyperthyroidism and severe mitral stenosis.

The approach to patients with possible cardiac chest pain.

PubMed

Parsonage, William A; Cullen, Louise; Younger, John F

2013-07-08

Chest pain is a common reason for presentation in hospital emergency departments and general practice. Some patients presenting with chest pain to emergency departments and, to a lesser extent, general practice will be found to have a life-threatening cause, but most will not. The challenge is to identify those who do in a safe, timely and cost-effective manner. An acute coronary syndrome cannot be excluded on clinical grounds alone. In patients with ongoing symptoms of chest pain, without an obvious other cause, ST-segment-elevation myocardial infarction should be excluded with a 12-lead electrocardiogram at the first available opportunity. Significant recent advances in the clinical approach to patients with acute chest pain, including better understanding of risk stratification, increasingly sensitive cardiac biomarkers and new non-invasive tests for coronary disease, can help clinicians minimise the risk of unexpected short-term adverse cardiac events. An approach that integrates these advances is needed to deliver the best outcomes for patients with chest pain. All hospital emergency departments should adopt such a strategic approach, and general practitioners should be aware of when and how to access these facilities.

Clinical nutrition and drug interactions

PubMed Central

Ekincioğlu, Aygin Bayraktar; Demirkan, Kutay

2013-01-01

A drug’s plasma level, pharmacological effects or side effects, elimination, physicochemical properties or stability could be changed by interactions of drug-drug or drug-nutrition products in patients who receive enteral or parenteral nutritional support. As a result, patients might experience ineffective outcomes or unexpected effects of therapy (such as drug toxicity, embolism). Stability or incompatibility problems between parenteral nutrition admixtures and drugs might lead to alterations in expected therapeutic responses from drug and/or parenteral nutrition, occlusion in venous catheter or symptoms or mortality due to infusion of composed particles. Compatibilities between parenteral nutrition and drugs are not always guaranteed in clinical practice. Although the list of compatibility or incompatibilities of drugs are published for the use of clinicians in their practices, factors such as composition of parenteral nutrition admixture, drug concentration, contact time in catheter, temperature of the environment and exposure to light could change the status of compatibilities between drugs and nutrition admixtures. There could be substantial clinical changes occurring in the patient’s nutritional status and pharmacological effects of drugs due to interactions between enteral nutrition and drugs. Drug toxicity and ineffective nutritional support might occur as a result of those predictable interactions. Although administration of drugs via feeding tube is a complex and problematic route for drug usage, it is possible to minimise the risk of tube occlusion, decreased effects of drug and drug toxicity by using an appropriate technique. Therefore, it is important to consider pharmacological dosage forms of drugs while administering drugs via a feeding tube. In conclusion, since the pharmacists are well-experienced and more knowledgeable professionals in drugs and drug usage compared to other healthcare providers, it is suggested that provision of information and drug counselling by pharmacists in terms of detection and prevention of problems (such as interactions, stability, incompatibility) related with enteral/parenteral nutrition and drugs are invaluable in clinical practice. PMID:25931873

Small bowel obstruction by an anomalous congenital band.

PubMed

Nouira, F; Sarrai, N; Charieg, A; Jlidi, S; Chaouachi, B

2012-01-01

We report a case of a 3-year-old boy who presented with symptoms and signs of intestinal obstruction. The patient reported no previous history of abdominal surgery or trauma while clinical and radiographic examinations were not diagnostic. An open laparotomy was subsequently performed and the intraoperative findings were consistent with a congenital band extending from the antimesenteric wall of the jejunum to the root of mesentery. The band was ligated and divided with an uneventful postoperative course. Congenital bands are extremely rare. Their exact incidence is still unknown. This case, therefore, represents an unusual surgical problem in a child in which the diagnosis was clinically unexpected.

Hypoxia Induced Factor in Chronic Kidney Disease: Friend or Foe?

PubMed

Li, Weiying; Zhao, Yuliang; Fu, Ping

2017-01-01

Many studies have shown evidence that erythropoiesis-stimulating agents (ESAs), as a classic treatment for chronic kidney disease (CKD)-related anemia, have several disadvantages and may trigger various adverse events with long-term use. The hypoxia-induced factor (HIF) pathway has been intensively investigated in kidney disease, especially in CKD, as research has shown that HIF-mediated erythropoiesis might work as a potential therapeutic strategy for managing CKD-related anemia. Development of prolyl hydroxylase domain inhibitors (PHIs), as an effective HIF activator, is a valuable step toward finding a replacement for ESAs, which showed an effective erythropoiesis through a comprehensive and physiological approach by promoting erythropoietin production, increasing iron bioavailability and improving chronic inflammatory status. Heretofore no adverse events or obvious off-target effects have been reported in clinical trials of PHIs. Nevertheless, a cautious inspection with extended follow-up period is warranted to validate the safety of prolonged HIF elevation, especially considering its ambiguous role in fibrogenesis and inflammation responses and possible risks in accelerating vascular calcification and tumorigenesis. A weighed dosing strategy might be the key to circumvent the unexpected side-effect brought by pleotropic effects of HIF elevation and achieve a selective augmentation of HIF-mediated signaling pathway. New studies with longer follow-up period and adequate analysis about the risks for proinflammation, vascular calcification and tumorigenesis are needed to ensure the drugs are safe for long-term use before being widely accepted in daily clinical practice.

Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?

PubMed

Otten, Henny G; Brummelhuis, Walter J; Fritsch-Stork, Ruth; Leavis, Helen L; Wisse, Bram W; van Laar, Jacob M; Derksen, Ronald H W M

2017-01-01

The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients. In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes). Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation. We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

A review of the evidence of zolpidem efficacy in neurological disability after brain damage due to stroke, trauma and hypoxia: A justification of further clinical trials.

PubMed

Sutton, J A; Clauss, R P

2017-01-01

During 15 years, 23 clinical reports and 6 studies have demonstrated associations between sub-sedative doses of zolpidem and recoveries from brain damage due to strokes, trauma and hypoxia. Clinical findings include unexpected awakenings from vegetative states and regressions of stroke symptoms after dosing that disappear during elimination and reappear on repeat dosing. Initially single-photon emission computed tomography scans showed improved perfusion within, around and distant from infarctions. Then positron emission tomography scans and electroencephalography detected renewed metabolic and neuronal activity. Placebo or a similar, gamma-aminobutyric acid (GABA)-ergic, sedative zopiclone has no such effect. The effect appears only several months after the injury, reflecting recent evidence in mice of substantial differences between the states of GABA receptors in acute and chronic repair phases of recovery. Zolpidem's good safety record and rapid absorption further indicate a need for more clinical trials. List of acronyms: BOLD, Blood-Oxygen-Level Dependent contrast imaging in MRI; CRS, Coma Recovery Scale; CRS-R, Coma Recovery Scale Revised; CSI, Cerebral State Index; CSM, Cerebral State Monitor; DOC, Disorder of Consciousness; EEG, Electro Encephalography; FDG-PET, FluoroDeoxyGlucose-Positron Emission Tomography; FTD, Frontotemporal dementia; GABA, Gamma-Aminobutyric Acid; MCS, Minimally Conscious State; M-EEG, Magneto-Encephalography; MRI, Magnetic Resonance Image; MSN, Median Spiny Neurones; PET, Positron Emission Tomography; PVS, Persistent Vegetative Sate; RLAC, Rancho Los Amigos Cognitive scores; SPECT, Single-photon emission computed tomography; TFES, Tinetti Falls Efficacy Scale; 99mTc HMPAO, Technetium hexamethylpropyleneamine oxime.

[A unique case of secondary takotsubo syndrome].

PubMed

Arcari, Luca; Limite, Luca Rosario; Autore, Camillo; Volpe, Massimo; Musumeci, Maria Beatrice

2018-04-01

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by transient systolic left ventricular dysfunction frequently preceded by stressful events. It typically affects postmenopausal women without angiographic evidence of obstructive coronary artery disease. We report here an uncommon occurrence of secondary TTS in a male with coronary artery disease after exogenous catecholamine administration and pacemaker implantation. This unexpected case suggests that, in such clinical scenario, a TTS diagnosis might be considered even in unsuspected individuals.

Administration of Probiotic Kefir to Mice with Clostridium difficile Infection Exacerbates Disease

PubMed Central

Spinler, Jennifer K.; Brown, Aaron; Ross, Caná L.; Boonma, Prapaporn; Conner, Margaret E.; Savidge, Tor C.

2016-01-01

Lifeway® kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI. PMID:27180007

Release of inattentional blindness by high working memory load: elucidating the relationship between working memory and selective attention.

PubMed

de Fockert, Jan W; Bremner, Andrew J

2011-12-01

An unexpected stimulus often remains unnoticed if attention is focused elsewhere. This inattentional blindness has been shown to be increased under conditions of high memory load. Here we show that increasing working memory load can also have the opposite effect of reducing inattentional blindness (i.e., improving stimulus detection) if stimulus detection is competing for attention with a concurrent visual task. Participants were required to judge which of two lines was the longer while holding in working memory either one digit (low load) or six digits (high load). An unexpected visual stimulus was presented once alongside the line judgment task. Detection of the unexpected stimulus was significantly improved under conditions of higher working memory load. This improvement in performance prompts the striking conclusion that an effect of cognitive load is to increase attentional spread, thereby enhancing our ability to detect perceptual stimuli to which we would normally be inattentionally blind under less taxing cognitive conditions. We discuss the implications of these findings for our understanding of the relationship between working memory and selective attention. Copyright © 2011 Elsevier B.V. All rights reserved.

Body Weight Gain and Hyperphagia After Administration of SGLT-2 Inhibitor: A Case Report

PubMed Central

Hamamoto, Hiromi; Noda, Mitsuhiko

2015-01-01

Patient: Male, 44 Final Diagnosis: Type 2 diabetes Symptoms: Hunger • increased appetite Medication: GLP-1 receptor agonist • SGLT-2 inhibitor Clinical Procedure: — Specialty: Internal Medicine/Diabetology Objective: Unusual or unexpected effect of treatment Background: A detailed description is given of a case we encountered in which unexpectedly marked weight gain occurred following a treatment switch from a GLP-1 receptor agonist to an SGLT-2 inhibitor. Case Report: The patient, a 44-year-old man with type 2 diabetes mellitus, had gained about 10 kg in weight in the previous year. Therefore, metformin was replaced with liraglutide to obtain reduction of body weight. Although the patient lost about 8 kg (7%), during the 18-month period on the medication, the weight loss stabilized; therefore, the treatment was again switched to tofogliflozin to obtain further reduction of body weight. However, the patient reported increasing hunger and an exaggerated appetite from week 3 onward after the start of tofogliflozin, and gained about 9 kg in weight within 2 weeks, associated with a tendency towards increased HbA1c; therefore, tofogliflozin was discontinued. Immediate reinstitution of liraglutide resulted in reduction of the increased appetite, weight, and HbA1c level. Conclusions: Caution should be exercised against hyperphagia and weight gain due to hunger that may occur following discontinuation of a GLP-1 receptor agonist and/or initiation of an SGLT-2 inhibitor. PMID:26638727

Compressive cervical pannus formation in a patient after 2-level disc arthroplasty: a rare complication treated with posterior instrumented fusion.

PubMed

Brophy, Carl M; Hoh, Daniel J

2018-06-01

Cervical disc arthroplasty (CDA) has received widespread attention as an alternative to anterior fusion due to its similar neurological and functional improvement, with the advantage of preservation of segmental motion. As CDA becomes more widely implemented, the potential for unexpected device-related adverse events may be identified. The authors report on a 48-year-old man who presented with progressive neurological deficits 3 years after 2-level CDA was performed. Imaging demonstrated periprosthetic osteolysis of the vertebral endplates at the CDA levels, with a heterogeneously enhancing ventral epidural mass compressing the spinal cord. Diagnostic workup for infectious and neoplastic processes was negative. The presumptive diagnosis was an inflammatory pannus formation secondary to abnormal motion at the CDA levels. Posterior cervical decompression and instrumented fusion was performed without removal of the arthroplasty devices or the ventral epidural mass. Postoperative imaging at 2 months demonstrated complete resolution of the compressive pannus, with associated improvement in clinical symptoms. Follow-up MRI at > 6 months showed no recurrence of the pannus. At 1 year postoperatively, CT scanning revealed improvement in periprosthetic osteolysis. Inflammatory pannus formation may be an unexpected complication of abnormal segmental motion after CDA. This rare etiology of an epidural mass associated with an arthroplasty device should be considered, in addition to workup for other potential infectious or neoplastic mass lesions. In symptomatic individuals, compressive pannus lesions can be effectively treated with fusion across the involved segment without removal of the device.

Unravelling the mysteries of sudden unexpected death in epilepsy.

PubMed

Hampel, K G; Rocamora Zuñiga, R; Quesada, C M

2017-04-18

Sudden unexpected death in epilepsy (SUDEP) is the most frequent cause of premature death in epileptic patients. Most SUDEP events occur at night and frequently go unnoticed; the exact pathophysiological mechanisms of this phenomenon therefore remain undetermined. Nevertheless, most cases of SUDEP are attributed to an infrequent yet extremely severe complication of epileptic seizures. We conducted a systematic literature search on PubMed. Our review article summarises scientific evidence on the classification, pathophysiological mechanisms, risk factors, biomarkers, and prevention of SUDEP. Likewise, we propose new lines of research and critically analyse findings that are relevant to clinical practice. Current knowledge suggests that SUDEP is a heterogeneous phenomenon caused by multiple factors. In most cases, however, SUDEP is thought to be due to postictal cardiorespiratory failure triggered by generalised tonic-clonic seizures and ultimately leading to cardiac arrest. The underlying pathophysiological mechanism involves multiple factors, ranging from genetic predisposition to environmental factors. Risk of SUDEP is higher in young adults with uncontrolled generalised tonic-clonic seizures. However, patients apparently at lower risk may also experience SUDEP. Current research focuses on identifying genetic and neuroimaging biomarkers that may help determine which patients are at high risk for SUDEP. Antiepileptic treatment is the only preventive measure proven effective to date. Night-time monitoring together with early resuscitation may reduce the risk of SUDEP. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.

PubMed

McKenney, James; Bays, Harold; Gleim, Gilbert; Mitchel, Yale; Kuznetsova, Olga; Sapre, Aditi; Sirah, Waheeda; Maccubbin, Darbie

2015-01-01

The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets. We examined the safety profile of ERN-LRPT vs the comparators ERN alone and statins in the ERN-LRPT development program to assess whether similar safety signals were observed to those seen in HPS-THRIVE and whether these might be attributed to ERN or LRPT. Postrandomization safety data from 12 clinical studies, 12 to 52 weeks in duration and involving 11,310 patients, were analyzed across 3 treatments: (1) ERN-LRPT; (2) ERN-NSP (ERN, Merck & Co, Inc or Niaspan [NSP], Abbott Laboratories); and (3) statin-PBO (statin or PBO). The safety profiles of ERN-LRPT and ERN-NSP were similar, except for less flushing with ERN-LRPT. Nonflushing AEs reported more frequently with ERN-LRPT or ERN-NSP than with statin-PBO were mostly nonserious and typical of niacin (nausea, diarrhea, and increased blood glucose). There was no evidence for an increased risk of serious AEs related to diabetes, muscle, infection, or bleeding. Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN. The inability to replicate the unexpected AE findings in HPS2-THRIVE could be because of the smaller sample size and substantially shorter duration of these studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Neural responses to negative outcomes predict success in community-based substance use treatment

PubMed Central

Forster, Sarah E.; Finn, Peter R.; Brown, Joshua W.

2017-01-01

Background and aims Activation in some specific brain regions has demonstrated promise as prognostic indicators in substance dependent individuals (SDIs) but this issue has not yet been explored in SDIs attending typical of community-based treatment. We used a data-driven, exploratory approach to identify brain-based predictors of treatment outcome in a representative community sample of SDIs. The predictive utility of brain-based measures was evaluated against clinical indicators, cognitive-behavioral performance, and self-report assessments. Design Prospective clinical outcome design, evaluating baseline functional magnetic resonance imaging data from the Balloon Analogue Risk Task (BART) as a predictor of 3-month substance use treatment outcomes. Setting Community-based substance use programs in Bloomington, Indiana, USA. Participants Twenty-three SDIs (17 male, ages 18–43) in an intensive outpatient or residential treatment program; abstinent 1–4 weeks at baseline. Measurements Event-related brain response, BART performance, and self-report scores at treatment onset, substance use outcome measure (based on days of use) Findings Using voxel-level predictive modeling and leave-one-out cross-validation, an elevated response to unexpected negative feedback in bilateral amygdala and anterior hippocampus (Amyg/aHipp) at baseline successfully predicted greater substance use over the 3-month study interval (p ≤ 0.006, cluster-corrected). This effect was robust to inclusion of significant non-brain-based covariates. A larger response to negative feedback in bilateral Amyg/aHipp was also associated with faster reward-seeking responses after negative feedback (r(23) = −0.544, p = 0.007; r(23) = −0.588, p = 0.003). A model including Amyg/aHipp activation, faster reward-seeking after negative feedback, and significant self-report scores accounted for 45% of the variance in substance use outcomes in our sample. Conclusions An elevated response to unexpected negative feedback in bilateral amygdala and anterior hippocampus (Amyg/aHipp) appears to predict relapse to substance use in people attending community-based treatment. PMID:28029198

Effects of Inconsistent Behaviors on Person Impressions: A Multidimensional Study.

ERIC Educational Resources Information Center

Vonk, Roos

1995-01-01

Examined effects of unexpected behavioral information on person impressions. Inconsistency was manipulated with respect to Implicit Personality Theory. Found that behaviors with inconsistent evaluation implications did not affect impressions and that effects of inconsistent information depended on dimension of contrast, valence of initial…

Preparing for the unexpected: special considerations and complications after sugammadex administration.

PubMed

Iwasaki, Hajime; Renew, J Ross; Kunisawa, Takayuki; Brull, Sorin J

2017-10-17

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.

Quality of healing of gastric ulcers: Natural products beyond acid suppression

PubMed Central

Kangwan, Napapan; Park, Jong-Min; Kim, Eun-Hee; Hahm, Ki Baik

2014-01-01

Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H2-receptor antagonists, and proton pump inhibitors (PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suffered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing (QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products. PMID:24891974

Quality of healing of gastric ulcers: Natural products beyond acid suppression.

PubMed

Kangwan, Napapan; Park, Jong-Min; Kim, Eun-Hee; Hahm, Ki Baik

2014-02-15

Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H2-receptor antagonists, and proton pump inhibitors (PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suffered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing (QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products.

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

PubMed

Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

Stem cells catalyze cartilage formation by neonatal articular chondrocytes in 3D biomimetic hydrogels.

PubMed

Lai, Janice H; Kajiyama, Glen; Smith, Robert Lane; Maloney, William; Yang, Fan

2013-12-19

Cartilage loss is a leading cause of disability among adults and effective therapy remains elusive. Neonatal chondrocytes (NChons) are an attractive allogeneic cell source for cartilage repair, but their clinical translation has been hindered by scarce donor availability. Here we examine the potential for catalyzing cartilage tissue formation using a minimal number of NChons by co-culturing them with adipose-derived stem cells (ADSCs) in 3D hydrogels. Using three different co-culture models, we demonstrated that the effects of co-culture on cartilage tissue formation are dependent on the intercellular distance and cell distribution in 3D. Unexpectedly, increasing ADSC ratio in mixed co-culture led to increased synergy between NChons and ADSCs, and resulted in the formation of large neocartilage nodules. This work raises the potential of utilizing stem cells to catalyze tissue formation by neonatal chondrocytes via paracrine signaling, and highlights the importance of controlling cell distribution in 3D matrices to achieve optimal synergy.

Encountering unexpected difficult airway: relationship with the intubation difficulty scale

PubMed Central

Koh, Wonuk; Kim, Hajung; Kim, Kyongsun; Ro, Young-Jin

2016-01-01

Background An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. Methods We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. Results For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack-Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. Conclusions Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation. PMID:27274369

Nurses' Experiences With Patients Who Die From Failure to Rescue After Surgery.

PubMed

Bacon, Cynthia Thornton

2017-05-01

To describe the lived experiences of hospital nurses caring for surgical patients who died from failure to rescue (FTR). A qualitative phenomenologic approach was used. Methods to ensure rigor and trustworthiness were incorporated into the design. The investigator conducted one-on-one semistructured interviews with 14 nurses, and data were analyzed using Colaizzi's methods. Six themes were identified: (a) the environment surrounding the FTR was unexpected; (b) FTR was unexpected but not preventable; (c) nurses were emotionally ill-prepared for the FTR; (d) nurse outcomes are different in unexpected versus expected death; (e) nurses' roles as protectors are important; and (f) FTR effects future nursing practice. Nurses' reactions after an FTR surgical death may be different when there is no identified nursing error contributing to the event. There may be key differences between deaths that are simply unexpected and those that involve FTR. The importance of mentoring junior nurses in protective surveillance skills is vital. Developing an understanding of nurses' experiences with FTR can assist nurse leaders to better support nurses who experience FTR deaths. Insight into the environment surrounding FTR deaths provides a foundation for future research aimed at improving patient safety and quality through an improved working environment for nurses. © 2017 Sigma Theta Tau International.

Euro-Esli: a European audit of real-world use of eslicarbazepine acetate as a treatment for partial-onset seizures.

PubMed

Villanueva, Vicente; Holtkamp, Martin; Delanty, Norman; Rodriguez-Uranga, Juan; McMurray, Rob; Santagueda, Patricia

2017-11-01

The Euro-Esli study was an exploratory pooled analysis of data from 14 European clinical practice studies, which was conducted to audit the real-world effectiveness, safety, and tolerability of eslicarbazepine acetate (ESL) as an adjunctive treatment for partial-onset seizures. Retention and effectiveness were assessed after 3, 6, and 12 months of ESL treatment, and at the final visit. Safety and tolerability were assessed throughout ESL treatment by evaluating adverse events (AEs) and ESL discontinuation due to AEs. Data from 2058 patients (52.1% male; mean age 44.0 years) were included. All 2058 patients were assessed for safety and 1975 (96.0%) patients were assessed for effectiveness. After 12 months, retention, responder (≥50% seizure frequency reduction), and seizure freedom rates were 73.4, 75.6, and 41.3%, respectively. AEs were reported for 34.0% of patients and led to discontinuation in 13.6% of patients. The most frequently reported AEs were dizziness (6.7% of patients), fatigue (5.4%), and somnolence (5.1%). No unexpected safety signals emerged over a median duration of follow-up of >5 years. Subgroup analyses revealed that ESL was significantly more effective in patients aged ≥65 versus <65 years, in patients who were not receiving treatment with other sodium channel blockers versus those who were receiving treatment with other sodium channel blockers, and in patients who were receiving <2 versus ≥2 concomitant antiepileptic drugs at baseline. Euro-Esli is the largest ESL clinical practice study conducted to date. This study provides strong and reassuring evidence of ESL's safety profile, and complements the data from clinical trials.

Long-term efficacy and safety of lamotrigine monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures: An open-label extension study.

PubMed

Yasumoto, Sawa; Ohtsuka, Yoko; Sato, Katsuaki; Kurata, Atsuyo; Numachi, Yotaro; Shimizu, Masahiro

2018-05-31

To investigate the efficacy and safety of long-term lamotrigine (LTG) monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures. Six Japanese patients and one South Korean patient were enrolled in the extension phase of the study after completing the 12-week maintenance phase of an open-label clinical study of LTG monotherapy. During the extension phase, patients underwent efficacy and safety evaluation every 12 weeks. Of the seven patients, six patients completed the extension phase. The seizure-free rate confirmed by hyperventilation (HV)-electroencephalography ranged from 71.4% to 100.0% at each visit up to Week 168 of the extension phase. Similar effects were confirmed by HV-clinical signs and seizure diaries. Although no unexpected adverse events were observed, one Japanese patient was withdrawn from the extension phase due to mild drug-related rash developed 842 days after the start of LTG. Although the number of patients is limited, long-term LTG monotherapy appeared to be effective and generally well tolerated in Japanese and South Korean pediatric patients with typical absence seizures. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Introduction to the Special Issue on Neuropsychology Practices in Integrated Care Teams.

PubMed

Festa, Joanne R

2018-05-01

This special issue on neuropsychology practices in integrated healthcare teams demonstrates how neuropsychologists have transformed their practices in an evolving healthcare landscape. These contributions are an overview of the many ways in which neuropsychologists function in integrated care teams. The experiences of integrated neuropsychologists serve as a model for those seeking new practice opportunities by providing highly practical, clinically relevant information. Included in this volume are articles on education and reimbursement issues, information about clinical practices that address diagnostic issues, prognostics and clinical management, as well as surgical treatment planning and outcome prediction. Authors highlight the value of their services, their contribution to improving team and patient communication, as well as the biopsychosocial understanding of the patient. Several unexpected challenges are detailed among the pearls and pitfalls of these practices.

Evolution of structural abnormalities in the rat brain following in utero exposure to maternal immune activation: A longitudinal in vivo MRI study.

PubMed

Crum, William R; Sawiak, Stephen J; Chege, Winfred; Cooper, Jonathan D; Williams, Steven C R; Vernon, Anthony C

2017-07-01

Genetic and environmental risk factors for psychiatric disorders are suggested to disrupt the trajectory of brain maturation during adolescence, leading to the development of psychopathology in adulthood. Rodent models are powerful tools to dissect the specific effects of such risk factors on brain maturational profiles, particularly when combined with Magnetic Resonance Imaging (MRI; clinically comparable technology). We therefore investigated the effect of maternal immune activation (MIA), an epidemiological risk factor for adult-onset psychiatric disorders, on rat brain maturation using atlas and tensor-based morphometry analysis of longitudinal in vivo MR images. Exposure to MIA resulted in decreases in the volume of several cortical regions, the hippocampus, amygdala, striatum, nucleus accumbens and unexpectedly, the lateral ventricles, relative to controls. In contrast, the volumes of the thalamus, ventral mesencephalon, brain stem and major white matter tracts were larger, relative to controls. These volumetric changes were maximal between post-natal day 50 and 100 with no differences between the groups thereafter. These data are consistent with and extend prior studies of brain structure in MIA-exposed rodents. Apart from the ventricular findings, these data have robust face validity to clinical imaging findings reported in studies of individuals at high clinical risk for a psychiatric disorder. Further work is now required to address the relationship of these MRI changes to behavioral dysfunction and to establish thier cellular correlates. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cardio-Oncology: How New Targeted Cancer Therapies and Precision Medicine Can Inform Cardiovascular Discovery

PubMed Central

Bellinger, Andrew M.; Arteaga, Carlos L.; Force, Thomas; Humphreys, Benjamin D.; Demetri, George D.; Druker, Brian J.; Moslehi, Javid

2016-01-01

Cardio-Oncology (the cardiovascular care of cancer patients) has developed as a new translational and clinical field based on the expanding repertoire of mechanism-based cancer therapies. While these therapies have changed the natural course of many cancers, several may also lead to cardiovascular complications. Many new anti-cancer drugs approved over the past decade are “targeted” kinase inhibitors that interfere with intracellular signaling contributing to tumor progression. Unexpected cardiovascular and cardio-metabolic effects following patient treatment with these inhibitors have provided unique insights into the role of kinases in human cardiovascular biology. Today, an ever-expanding number of cancer therapies targeting novel kinases as well as other specific cellular and metabolic pathways are being developed and tested in oncology clinical trials. Some of these drugs may impact the cardiovascular system in detrimental and others perhaps in beneficial ways. We propose that the numerous ongoing oncology clinical trials are an opportunity for closer collaboration between cardiologists and oncologists to study the cardiovascular and cardio-metabolic changes due to modulation of these pathways in patients. In this regard, cardio-oncology represents an opportunity and a novel platform for basic and translational investigation and can serve as a potential avenue for optimization of anti-cancer therapies as well as for cardiovascular research and drug discovery. PMID:26644247

Is anybody doing it? An experimental study of the effect of normative messages on intention to do physical activity.

PubMed

van Bavel, René; Esposito, Gabriele; Baranowski, Tom

2014-07-31

The study explores whether messages about the physical activity levels of the majority (i.e. normative messages) affect young adults' intention to engage in regular physical activity. An experimental survey among 16 to 24 year-olds in Bulgaria, Croatia and Romania (n = 1200) was conducted in March 2013. A control group received no message; one treatment group was told that the majority was physically active (positive message); and another treatment group was told that the majority was not physically active (negative message). Both the positive and (unexpectedly) the negative normative messages showed a significant and positive effect on intention to be physically active. There was no difference between the effects of the messages. Normative messages affect intention, which is encouraging for public health campaigns. The effect of the positive message confirms previous findings on conformity to the norm; the effect of the negative message is unexpected and requires further research to be understood.

Hydrogen effects on Ni-Ti fatigue performance by self -heating method

NASA Astrophysics Data System (ADS)

Rokbani, M.; Saint-Sulpice, L.; Arbab Chirani, S.; Bouraoui, T.

2017-10-01

Ni-Ti superelastic alloys are extensively used in manufacturing biomedical devices because of their high mechanical performance, good fatigue durability and biocompatibility compared to traditional metallic materials. During clinical use, most of these devices are intended to work under cyclic or repetitive loadings and may be in contact with corrosive environments leading to unexpected failures. It is however recognized that the fatigue-environment interaction, especially fatigue-hydrogen absorption, can be the main cause of these failures. The aim of this work is to investigate the fatigue behavior of superelastic Ni-Ti intended for manufacturing medical devices at high number of cycles (HCF) with a particular emphasis to the effect of hydrogen on fatigue properties. Fatigue tests were analyzed using self-heating measurements based on observing thermal effects during cyclic loadings. The results obtained with self-heating approach showed a trend of a decrease in the fatigue life of Ni-Ti alloys after hydrogen absorption and the fatigue limit extrapolated will be compared with the results obtained with the classical S-N curves method.

Sudden Unexpected Death in Epilepsy: A Retrospective Autopsy Study of 112 Epileptic Patients.

PubMed

Esen Melez, İpek; Arslan, Murat Nihat; Melez, Deniz Oğuzhan; Şanli, Ahmet Necati; Koç, Sermet

2017-09-01

Sudden unexpected deaths comprise the most important and worthy investigation case profiles in both neurology and forensic medicine. Epilepsy, which is one of the neuropathological causes of sudden unexpected deaths, is an important disorder having mysterious aspects. The aim of this study is to make common the points of view between neurology and forensic medicine experts and to discuss the features of the findings together with the related clinical hypotheses, leading to the differential diagnosis of sudden unexpected death in epilepsy (SUDEP) by presenting autopsy findings and available medical data of patients who had a prior diagnosis of epilepsy. In Istanbul, the cases of 20334 autopsied patients who were referred to The Ministry of Justice Council of Forensic Medicine between 2007 and 2011 were identified from the complete forensic autopsy data of the city and were retrospectively reviewed. Patients who had a prior diagnosis of epilepsy were included. Both descriptive and inferential statistical analyses were performed through the parameters of demographical data, physical properties, incident features, macroscopic-microscopic autopsy findings, and cause of death initially for all cases and then separately for SUDEP cases. Among the 20334 patients, 112 were determined to have a prior diagnosis of epilepsy. A possible macroscopic and/or microscopic epileptic focus was present in 23 (20.5%) of these 112 cases. The cause of death was determined to be SUDEP in 40 (35.7%) cases, while it could not be determined in 28 (25%) cases. Among patients whose death cause was considered as SUDEP, the male-to-female ratio was 1.1:1, while the mean age was 31.5±13.9 years in males and 29.6±12.9 years in females. The presence of hypertrophy and myocardial scar tissue findings in the microscopic examination were significantly more frequent among patients determined to have died from cardiovascular diseases compared to patients in the SUDEP group (p=0.001 for each finding). Besides, in 40 SUDEP cases, 38 (95%) patients underwent toxicological analysis and no antiepileptic agent was detected in 21 (55.3%) of these. It can be concluded that there is equality in gender distribution among SUDEP patients, that the young adult population has a slightly increased risk for SUDEP, and that the inconsistent use of antiepileptic medicines is a greater risk factor for SUDEP than polytherapy. Besides, it is important to emphasize that all clinical and postmortem parameters together should be considered for the differential diagnosis of SUDEP, particularly with cardiovascular diseases.

[Lung infection by Mycobacterium terrae].

PubMed

Díaz Ricomá, N; González Vargas, F; Casado Moreno, I; Galán Antoñanza, L; Rojas Sierra, M; Alado Arboleda, J C

2001-02-01

Mycobacterium terrae complex encompasses three species of microbacteria that are usually saprophytic and that may occasionally cause disease in humans, particularly in joints and synovial fluid. The literature includes slightly over a dozen cases of pulmonary infection, although none has been described in Spain. We report a case of infection by M. terrae in an immunodepressed patient with no other risk factor. Microbial identification by culture was unexpected and clinical management was difficult due to the absence of an established treatment protocol.

Autophagy and TGF-Beta Antagonist Signaling in Breast Cancer at Premetastatic Sites

DTIC Science & Technology

2015-06-01

dormant legions. These inhibitors will be the drug leads for further medicinal chemistry and preclinical/clinical studies. 4 Body Overview Over the...autophagy, largely due to unexpected half-year delay of the official approval of our ACURO animal protocol . Below we report our progress, starting with...sections taken at various times after tail vein injection will enable us to verify that the anti-Coco MAb does not affect extravasation or homing but

Writing Case Reports: Contributing to Practice and Research.

PubMed

Bavdekar, Sandeep B; Save, Sushma

2015-04-01

Case reports describe a patient with unusual or unexpected features. They represent the oldest type of medical publication. They are about generating a new hypothesis and not about proving a hypothesis. Hence, despite being considered as the lowest level of evidence; they continue to be relevant for clinical practice, research and medical education. This article intends to provide guidance regarding writing a case report to those wishing to make a foray in scientific writing through reporting an interesting case.

Mifepristone in Italy: the case of a drug trapped between ethics and clinical practice.

PubMed

Banfi, Roberto; Pavone, Eleonora; Cerri, Rita; Menichetti, Monica

2007-08-01

In Italy mifepristone is not yet marketed. Gynaecologists in our hospital asked to use this medication as a less traumatic method for voluntary abortions. We followed the standard procedure defined by the Italian Health Ministry (IMH) for purchasing drugs from abroad but encountered several unexpected barriers. Starting from this case, this paper is aimed at identifying these barriers which we found to be not only professional, but also ethical, religious and moral.

Rickets: case series and diagnostic review of hypovitaminosis D in swine.

PubMed

Madson, Darin M; Ensley, Steve M; Gauger, Phil C; Schwartz, Kent J; Stevenson, Greg W; Cooper, Vickie L; Janke, Bruce H; Burrough, Eric R; Goff, Jesse P; Horst, Ronald L

2012-11-01

Rickets can be attributed to nutritional, genetic, hormonal, or toxic disturbances and is classified as a metabolic bone disease. Rickets is most often associated with inappropriate dietary levels of calcium, phosphorus, and/or vitamin D. During a 27-month period (January 2010 through March 2012), the Iowa State University Veterinary Diagnostic Laboratory investigated causes of sudden, unexpected death and lameness in growing pigs throughout the Midwestern United States. Clinical observations from 17 growing pig cases included weakness, lameness, reluctance to move, muscle fasciculations and/or tremors, tetany, and death. Ribs were weak, soft, and bent prior to breaking; rachitic lesions were apparent at costochondral junctions in multiple cases. Acute and/or chronic bone fractures were also noted in multiple bones. Failure of endochondral ossification, expanded physes, infractions, thin trabeculae, and increased osteoclasts were noted microscopically. Decreased bone ash and serum 25(OH)D(3), combined with clinical and microscopic evaluation, confirmed a diagnosis of vitamin D-dependent rickets in all cases. In 3 cases, disease was linked to a specific nutrient supplier that ultimately resulted in a voluntary feed recall; however, most cases in the current investigation were not associated with a particular feed company. The present report describes vitamin D-associated rickets and its importance as a potential cause of weakness, lameness, muscle fasciculations, recumbency or sudden unexpected death in swine, and describes appropriate samples and tests for disease diagnosis.

Conducting experimental research in marginalised populations: clinical and methodological implications from a mixed-methods randomised controlled trial in Kenya.

PubMed

Lowther, Keira; Harding, Richard; Ahmed, Aabid; Gikaara, Nancy; Ali, Zippy; Kariuki, Hellen; Sherr, Lorraine; Simms, Victoria; Selman, Lucy

2016-01-01

Experimental studies to test interventions for people living with HIV in low- and middle-income countries are essential to ensure appropriate and effective clinical care. The implications of study participation on outcome data in such populations have been discussed theoretically, but rarely empirically examined. We aimed to explore the effects of participating in a randomised controlled trial conducted in an HIV clinic in Mombasa, Kenya. We report qualitative data from the Treatment Outcomes in Palliative Care trial, which evaluated the impact of a nurse-led palliative care intervention for HIV positive adults on antiretroviral therapy compared to standard care. Participants in both arms attended five monthly quantitative data collection appointments. Post-trial exit, 10 control and 20 intervention patients participated in semi-structured qualitative interviews, analysed using thematic analysis. We found benefit attributed to the compassion of the research team, social support, communication, completion of patient reported outcome measures (PROMs) and material support (transport reimbursement). Being treated with compassion and receiving social support enabled participants to build positive relationships with the research team, which improved mental health and well-being. Open and non-judgmental communication made participants feel accepted. Participants described how repeated completion of the PROMs was a prompt for reflection, through which they began to help themselves and self-care. Participant reimbursements relieved financial hardship and enabled them to fulfil their social responsibilities, enhancing self-worth. These findings emphasise the importance of compassion, support and effective communication in the clinical encounter, particularly in stigmatised and isolated populations, and the potential of the integration of simple PROMs to improve patient outcomes. Participation in research has unexpected positive benefits for participants, which should be taken into account when designing research in similar populations. Researchers should be aware of the effects of financial reimbursement and contact with researchers in isolated and impoverished communities.

Cardiac and electro-cortical concomitants of social feedback processing in women

PubMed Central

van der Molen, Melle J. W.; Gunther Moor, Bregtje; van der Veen, Frederik M.; van der Molen, Maurits W.

2015-01-01

This study provides a joint analysis of the cardiac and electro-cortical—early and late P3 and feedback-related negativity (FRN)—responses to social acceptance and rejection feedback. Twenty-five female participants performed on a social- and age-judgment control task, in which they received feedback with respect to their liking and age judgments, respectively. Consistent with previous reports, results revealed transient cardiac slowing to be selectively prolonged to unexpected social rejection feedback. Late P3 amplitude was more pronounced to unexpected relative to expected feedback. Both early and late P3 amplitudes were shown to be context dependent, in that they were more pronounced to social as compared with non-social feedback. FRN amplitudes were more pronounced to unexpected relative to expected feedback, irrespective of context and feedback valence. This pattern of findings indicates that social acceptance and rejection feedback have widespread effects on bodily state and brain function, which are modulated by prior expectancies. PMID:25870439

Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity in the first sarin gas terrorism.

PubMed

Okudera, H; Morita, H; Iwashita, T; Shibata, T; Otagiri, T; Kobayashi, S; Yanagisawa, N

1997-09-01

This report describes the rescue activities and the exposure of rescue and hospital personnel from the first unexpected nerve gas terrorist attack using sarin (isopropyl methylphophonofluoridate) in the city of Matsumoto at midnight on June 27, 1994. The details of the emergency activities in the disaster were studied based on the records from emergency departments of the affiliated hospitals and records from the firehouse. About 600 people, including residents and rescue staff, were exposed to sarin gas. Fifty-eight residents were admitted to hospitals, and 7 died. Among 95 rescuers and the duty doctor from the doctor car, 8 had mild symptoms of poisoning. All the rescue activity took place without gas masks or decontamination procedures. In this case of unexpected mass exposure to sarin gas, the emergency rescue system for a large disaster in Matsumoto city, which had been established for a conflagration or a local earthquake, was effective.

Making psycholinguistics musical: Self-paced reading time evidence for shared processing of linguistic and musical syntax

PubMed Central

Robert Slevc, L.; Rosenberg, Jason C.; Patel, Aniruddh D.

2009-01-01

Linguistic processing–especially syntactic processing–is often considered a hallmark of human cognition, thus the domain-specificity or domain-generality of syntactic processing has attracted considerable debate. These experiments address this issue by simultaneously manipulating syntactic processing demands in language and music. Participants performed self-paced reading of garden-path sentences in which structurally unexpected words cause temporary syntactic processing difficulty. A musical chord accompanied each sentence segment, with the resulting sequence forming a coherent chord progression. When structurally unexpected words were paired with harmonically unexpected chords, participants showed substantially enhanced garden-path effects. No such interaction was observed when the critical words violated semantic expectancy, nor when the critical chords violated timbral expectancy. These results support a prediction of the shared syntactic integration resource hypothesis (SSIRH, Patel, 2003), which suggests that music and language draw on a common pool of limited processing resources for integrating incoming elements into syntactic structures. PMID:19293110

A pharmacy student's role as a teaching assistant in an undergraduate medicinal chemistry course - Implementation, evaluation, and unexpected opportunities for educational outreach.

PubMed

DellaVecchia, Matthew J; Claudio, Alyssa M; Fairclough, Jamie L

2017-11-01

To describe 1) a pharmacy student's teaching assistant (TA) role in an undergraduate medicinal chemistry course, 2) an active learning module co-developed by the TA and instructor, and 3) the unexpected opportunities for pharmacy educational outreach that resulted from this collaboration. Medicinal Chemistry (CHM3413) is an undergraduate course offered each fall at Palm Beach Atlantic University (PBA). As a TA for CHM3413, a pharmacy student from the Gregory School of Pharmacy (GSOP) at PBA co-developed and implemented an active learning module emphasizing foundational medicinal chemistry concepts as they pertain to performance enhancing drugs (PEDs). Surveys assessed undergraduate students' perceived knowledge of medicinal chemistry concepts, PEDs, and TA involvement. Students' (total n = 60, three fall semesters) perceived confidence in knowledge of medicinal chemistry concepts and PEDs increased significantly (p < 0.001) after the TA's module. Nearly 93% of students acknowledged this was their first interaction with a TA at PBA, ~ 82% "agreed/strongly agreed" that the TA provided effective instruction, and ~ 62% "agreed/strongly agreed" that TA availability raised overall confidence in CHM3413. Unexpected "side-effects" of this collaboration included opportunities for the TA and instructor to discuss health risks associated with PED usage with student-athletes and coaches at PBA. This collaboration developed the pharmacy student's teaching skills and reinforced knowledge of foundational pharmaceutical science concepts for both the TA and undergraduate students. Unexpected "side-effects" that resulted from this collaboration included opportunities for the TA and instructor to discuss health risks associated with PED usage with student-athletes in PBA's athletic department. Educational/interprofessional outreach opportunities resulted from a pharmacy student TA's involvement in an undergraduate medicinal chemistry course. An advanced pharmacy practice experience elective in sports pharmacy (based on Ambrose's model) begins Fall 2017. Copyright © 2017 Elsevier Inc. All rights reserved.

Dark Adaptation at High Altitude: An Unexpected Pupillary Response to Chronic Hypoxia in Andean Highlanders.

PubMed

Healy, Katherine; Labrique, Alain B; Miranda, J Jaime; Gilman, Robert H; Danz, David; Davila-Roman, Victor G; Huicho, Luis; León-Velarde, Fabiola; Checkley, William

2016-09-01

Healy, Katherine, Alain B. Labrique, J. Jaime Miranda, Robert H. Gilman, David Danz, Victor G. Davila-Roman, Luis Huicho, Fabiola León-Velarde, and William Checkley. Dark adaptation at high altitude: an unexpected pupillary response to chronic hypoxia in Andean highlanders. High Alt Med Biol. 17:208-213, 2016.-Chronic mountain sickness is a maladaptive response to high altitude (>2500 m above sea level) and is characterized by excessive erythrocytosis and hypoxemia resulting from long-term hypobaric hypoxia. There is no known early predictor of chronic mountain sickness and the diagnosis is based on the presence of excessive erythrocytosis and clinical features. Impaired dark adaptation, or an inability to visually adjust from high- to low-light settings, occurs in response to mild hypoxia and may serve as an early predictor of hypoxemia and chronic mountain sickness. We aimed to evaluate the association between pupillary response assessed by dark adaptometry and daytime hypoxemia in resident Andean highlanders aged ≥35 years living in Puno, Peru. Oxyhemoglobin saturation (SpO 2 ) was recorded using a handheld pulse oximeter. Dark adaptation was quantitatively assessed as the magnitude of pupillary contraction to light stimuli of varying intensities (-2.9 to 0.1 log-cd/m 2 ) using a portable dark adaptometer. Individual- and stimulus-specific multilevel analyses were conducted using mixed-effect models to elicit the relationship between SpO 2 and pupillary responsiveness. Among 93 participants, mean age was 54.9 ± 11.0 years, 48% were male, 44% were night blind, and mean SpO 2 was 89.3% ± 3.4%. The magnitude of pupillary contraction was greater with lower SpO 2 (p < 0.01), and this dose relationship remained significant in multiple variable analyses (p = 0.047). Pupillary responsiveness to light stimuli under dark-adapted conditions was exaggerated with hypoxemia and may serve as an early predictor of chronic mountain sickness. This unexpected association is potentially explained as an excessive and unregulated sympathetic response to hypoxemia at altitude.

Misleading Gastrointestinal Symptoms: The Ongoing Story of Chronic Lead Intoxication.

PubMed

Macedo, Guilherme; Lopes, Susana; Peixoto, Armando

2016-10-01

Inorganic lead intoxication has emerged as an important and challenging clinical problem owing to increased awareness of lead and enhanced surveillance of exposed individuals. However, recognition may not be very difficult when there is an obvious history of exposure. Our interest began a few years ago when we could trace an outbreak, following a patient who was admitted with colickly abdominal pain, convulsions, and coma. After that, 16 more cases were identified and characterized. All patients recovered completely after adequate chelation therapy. Although the clinical picture of lead intoxication is pleomorphic, the increased awareness of gastroenterologists in this subject may possibly bring chronically complaining difficult patients to an earlier, unexpected, and fairly treatable disease.

Intestinal obstruction caused by omphalomesenteric duct remnant: usefulness of laparoscopy.

PubMed

Bueno Lledó, J; Serralta Serra, A; Planeéis Roig, M; Dobón Giménez, F; Ibáñez Palacín, F; Rodero Rodero, R

2003-10-01

The anomalies related to omphalomesenteric duct remnant constitute an uncommon cause of intestinal obstruction, of which Meckel"s diverticulum and its variants represent the most important clinical presentation. In most cases they are asymptomatic and usually affect young patients. When symptomatic, they usually present episodes of gastrointestinal bleeding or acute abdomen syndromes caused by strangulation of intestinal loops as a result of fibrous intraabdominal remnants or inflammation produced by the diverticulum. In most cases, the unexpected presence of these alterations makes intraoperative diagnosis necessary. Treatment is surgical and consists in exeresis of the diverticulum or the fibrous band causing the clinical picture. We report two cases of persistence of the vitelline duct resolved by laparoscopic approach.

Quality Control Practices for Chemistry and Immunochemistry in a Cohort of 21 Large Academic Medical Centers.

PubMed

Rosenbaum, Matthew W; Flood, James G; Melanson, Stacy E F; Baumann, Nikola A; Marzinke, Mark A; Rai, Alex J; Hayden, Joshua; Wu, Alan H B; Ladror, Megan; Lifshitz, Mark S; Scott, Mitchell G; Peck-Palmer, Octavia M; Bowen, Raffick; Babic, Nikolina; Sobhani, Kimia; Giacherio, Donald; Bocsi, Gregary T; Herman, Daniel S; Wang, Ping; Toffaletti, John; Handel, Elizabeth; Kelly, Kathleen A; Albeiroti, Sami; Wang, Sihe; Zimmer, Melissa; Driver, Brandon; Yi, Xin; Wilburn, Clayton; Lewandrowski, Kent B

2018-05-29

In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program. We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing. We observed significant variation and unexpected similarities in practice across laboratories, including QC frequency, cutoffs, number of levels analyzed, and other features. This variation in practice indicates an opportunity exists to establish an evidence-based approach to QC that can be generalized across institutions.

The drug-induced degradation of oncoproteins: an unexpected Achilles' heel of cancer cells?

PubMed

Ablain, Julien; Nasr, Rihab; Bazarbachi, Ali; de Thé, Hugues

2011-07-01

Many targeted therapies against cancer are aimed at inhibiting the enzymatic activity of kinases. Thus far, this approach has undoubtedly yielded significant clinical improvements, but has only rarely achieved cures. Other drugs, which selectively elicit proteasome-dependent degradation of oncoproteins, induce the loss of cancer cell self-renewal and promote cell differentiation and/or apoptosis. In acute promyelocytic leukemia, the cooperative degradation of PML/RARA by arsenic and retinoic acid cures most patients. In this condition and others, drug-induced proteolysis of oncoproteins is feasible and underlies improved clinical outcome. Several transcription factors, nuclear receptors, or fusion proteins driving cancer growth could be candidates for proteolysis-based drug-discovery programs.

The N400 and the P300 are not all that independent.

PubMed

Arbel, Yael; Spencer, Kevin M; Donchin, Emanuel

2011-06-01

This study assessed whether two ERP components that are elicited by unexpected events interact. The conditions that are known to elicit the N400 and the P300 ERP components were applied separately and in combination to terminal-words in sentences. Each sentence ended with a terminal-word that was highly expected, semantically unexpected, physically deviant, or both semantically unexpected and physically deviant. In addition, we varied the level of semantic relatedness between the unexpected terminal-words and the expected exemplars. Physically deviant words elicited a P300, whereas semantically unexpected words elicited an N400, whose amplitude was sensitive to the level of semantic relatedness. Words that were both semantically unexpected and physically deviant elicited both an N400 with enhanced amplitude, and a P300 with reduced amplitude. These results suggest an interaction between the processes manifested by the two components. Copyright © 2010 Society for Psychophysiological Research.

Out of place, out of mind: Schema-driven false memory effects for object-location bindings.

PubMed

Lew, Adina R; Howe, Mark L

2017-03-01

Events consist of diverse elements, each processed in specialized neocortical networks, with temporal lobe memory systems binding these elements to form coherent event memories. We provide a novel theoretical analysis of an unexplored consequence of the independence of memory systems for elements and their bindings, 1 that raises the paradoxical prediction that schema-driven false memories can act solely on the binding of event elements despite the superior retrieval of individual elements. This is because if 2, or more, schema-relevant elements are bound together in unexpected conjunctions, the unexpected conjunction will increase attention during encoding to both the elements and their bindings, but only the bindings will receive competition with evoked schema-expected bindings. We test our model by examining memory for object-location bindings in recognition (Study 1) and recall (Studies 2 and 3) tasks. After studying schema-relevant objects in unexpected locations (e.g., pan on a stool in a kitchen scene), participants who then viewed these objects in expected locations (e.g., pan on stove) at test were more likely to falsely remember this object-location pairing as correct, compared with participants that viewed a different unexpected object-location pairing (e.g., pan on floor). In recall, participants were more likely to correctly remember individual schema-relevant objects originally viewed in unexpected, as opposed to expected locations, but were then more likely to misplace these items in the original room scene to expected places, relative to control schema-irrelevant objects. Our theoretical analysis and novel paradigm provide a tool for investigating memory distortions acting on binding processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Repeat testing of low-level HIV-1 RNA: assay performance and implementation in clinical trials.

PubMed

White, Kirsten; Garner, Will; Wei, Lilian; Eron, Joseph J; Zhong, Lijie; Miller, Michael D; Martin, Hal; Plummer, Andrew; Tran-Muchowski, Cecilia; Lindstrom, Kim; Porter, James; Piontkowsky, David; Light, Angela; Reiske, Heinz; Quirk, Erin

2018-05-15

Assess the performance of HIV-1 RNA repeat testing of stored samples in cases of low-level viremia during clinical trials. Prospective and retrospective analysis of randomized clinical trial samples and reference standards. To evaluate assay variability of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, v2.0, three separate sources of samples were utilized: the World Health Organization (WHO) HIV reference standard (assayed using 50 independent measurements at six viral loads <200 copies/ml), retrospective analysis of four to six aliquots of plasma samples from four clinical trial participants, and prospective repeat testing of 120 samples from participants in randomized trials with low-level viremia. The TaqMan assay on the WHO HIV-1 RNA standards at viral loads <200 copies/ml performed within the expected variability according to assay specifications. However, standards with low viral loads of 36 and 18 copies/ml reported values of ≥ 50 copies/ml in 66 and 18% of tests, respectively. In participants treated with antiretrovirals who had unexpected viremia of 50-200 copies/ml after achieving <50 copies/ml, retesting of multiple aliquots of stored plasma found <50 copies/ml in nearly all cases upon retesting (14/15; 93%). Repeat testing was prospectively implemented in four clinical trials for all samples with virologic rebound of 50-200 copies/ml (n = 120 samples from 92 participants) from which 42% (50/120) had a retest result of less than 50 copies/ml and 58% (70/120) retested ≥ 50 copies/ml. The TaqMan HIV-1 RNA assay shows variability around 50 copies/ml that affects clinical trial results and may impact clinical practice. In participants with a history of viral load suppression, unexpected low-level viremia may be because of assay variability rather than low drug adherence or true virologic failure. Retesting a stored aliquot of the same sample may differentiate between assay variability and virologic failure as the source of viremia. This retesting strategy could save time, money, and anxiety for patients and their providers, as well as decrease follow-up clinic visits without increasing the risk of virologic failure and resistance development.

On the anatomy of a chain shift1

PubMed Central

Dinnsen, Daniel A.; Green, Christopher R.; Gierut, Judith A.; Morrisette, Michele L.

2012-01-01

Phonological chain shifts have been the focus of many theoretical, developmental, and clinical concerns. This paper considers an overlooked property of the problem by focusing on the typological properties of the widely attested ‘s > θ > f’ chain shift involving the processes of Labialization and Dentalization in early phonological development. Findings are reported from a cross-sectional study of 234 children (ages 3 years; 0 months–7;9) with functional (nonorganic) phonological delays. The results reveal some unexpected gaps in the predicted interactions of these processes and are brought to bear on the evaluation of recent optimality theoretic proposals for the characterization of phonological interactions. A developmental modification to the theory is proposed that has the desired effect of precluding certain early-stage grammars. The proposal is further evaluated against the facts of another widely cited developmental chain shift known as the ‘puzzle > puddle > pickle’ problem (Smith 1973). PMID:22389522

A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome.

PubMed

Doyle, Jefferson J; Doyle, Alexander J; Wilson, Nicole K; Habashi, Jennifer P; Bedja, Djahida; Whitworth, Ryan E; Lindsay, Mark E; Schoenhoff, Florian; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Ehsan, Hamid; Huso, David; Thomas, Craig J; Caulfield, Mark J; Van Eyk, Jennifer E; Judge, Daniel P; Dietz, Harry C

2015-10-27

Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.

What is the reward? Medical students' learning and personal development during a research project course.

PubMed

Möller, Riitta; Shoshan, Maria; Heikkilä, Kristiina

2015-01-01

Until recently, the outcome of medical students' research projects has mainly been assessed in terms of scientific publications, whereas other results important for students' development have been less studied. The aim of this study was to investigate medical students' experiences of learning as an outcome of the research project course. Written reflections of 50 students were analyzed by manifest inductive content analysis. Three categories emerged: 'thinking as a scientist', 'working as a scientist', and 'personal development'. Students became more aware about the nature of knowledge, how to generate new knowledge, and developed skills in scientific thinking and critical appraisal. Unexpectedly, effects on personal characteristics, such as self-confidence, self-discipline, independence, and time management skills were also acknowledged. We conclude that individual research projects enhance research-specific skills and competencies needed in evidence-based clinical work and are beneficial for personal and professional development.

Interactions between mood and the structure of semantic memory: event-related potentials evidence

PubMed Central

Pinheiro, Ana P.; del Re, Elisabetta; Nestor, Paul G; McCarley, Robert W.; Gonçalves, Óscar F.

2013-01-01

Recent evidence suggests that affect acts as modulator of cognitive processes and in particular that induced mood has an effect on the way semantic memory is used on-line. We used event-related potentials (ERPs) to examine affective modulation of semantic information processing under three different moods: neutral, positive and negative. Fifteen subjects read 324 pairs of sentences, after mood induction procedure with 30 pictures of neutral, 30 pictures of positive and 30 pictures of neutral valence: 108 sentences were read in each mood induction condition. Sentences ended with three word types: expected words, within-category violations, and between-category violations. N400 amplitude was measured to the three word types under each mood induction condition. Under neutral mood, a congruency (more negative N400 amplitude for unexpected relative to expected endings) and a category effect (more negative N400 amplitude for between- than to within-category violations) were observed. Also, results showed differences in N400 amplitude for both within- and between-category violations as a function of mood: while positive mood tended to facilitate the integration of unexpected but related items, negative mood made their integration as difficult as unexpected and unrelated items. These findings suggest the differential impact of mood on access to long-term semantic memory during sentence comprehension. PMID:22434931

Interactions between mood and the structure of semantic memory: event-related potentials evidence.

PubMed

Pinheiro, Ana P; del Re, Elisabetta; Nestor, Paul G; McCarley, Robert W; Gonçalves, Óscar F; Niznikiewicz, Margaret

2013-06-01

Recent evidence suggests that affect acts as modulator of cognitive processes and in particular that induced mood has an effect on the way semantic memory is used on-line. We used event-related potentials (ERPs) to examine affective modulation of semantic information processing under three different moods: neutral, positive and negative. Fifteen subjects read 324 pairs of sentences, after mood induction procedure with 30 pictures of neutral, 30 pictures of positive and 30 pictures of neutral valence: 108 sentences were read in each mood induction condition. Sentences ended with three word types: expected words, within-category violations, and between-category violations. N400 amplitude was measured to the three word types under each mood induction condition. Under neutral mood, a congruency (more negative N400 amplitude for unexpected relative to expected endings) and a category effect (more negative N400 amplitude for between- than to within-category violations) were observed. Also, results showed differences in N400 amplitude for both within- and between-category violations as a function of mood: while positive mood tended to facilitate the integration of unexpected but related items, negative mood made their integration as difficult as unexpected and unrelated items. These findings suggest the differential impact of mood on access to long-term semantic memory during sentence comprehension.

Unexpected angular or rotational deformity after corrective osteotomy

PubMed Central

2014-01-01

Background Codman’s paradox reveals a misunderstanding of geometry in orthopedic practice. Physicians often encounter situations that cannot be understood intuitively during orthopedic interventions such as corrective osteotomy. Occasionally, unexpected angular or rotational deformity occurs during surgery. This study aimed to draw the attention of orthopedic surgeons toward the concepts of orientation and rotation and demonstrate the potential for unexpected deformity after orthopedic interventions. This study focused on three situations: shoulder arthrodesis, femoral varization derotational osteotomy, and femoral derotation osteotomy. Methods First, a shoulder model was generated to calculate unexpected rotational deformity to demonstrate Codman’s paradox. Second, femoral varization derotational osteotomy was simulated using a cylinder model. Third, a reconstructed femoral model was used to calculate unexpected angular or rotational deformity during femoral derotation osteotomy. Results Unexpected external rotation was found after forward elevation and abduction of the shoulder joint. In the varization and derotation model, closed-wedge osteotomy and additional derotation resulted in an unexpected extension and valgus deformity, namely, under-correction of coxa valga. After femoral derotational osteotomy, varization and extension of the distal fragment occurred, although the extension was negligible. Conclusions Surgeons should be aware of unexpected angular deformity after surgical procedure involving bony areas. The degree of deformity differs depending on the context of the surgical procedure. However, this study reveals that notable deformities can be expected during orthopedic procedures such as femoral varization derotational osteotomy. PMID:24886469

New product trial, use of edibles, and unexpected highs among marijuana and hashish users in Colorado.

PubMed

Allen, Jane A; Davis, Kevin C; Duke, Jennifer C; Nonnemaker, James M; Bradfield, Brian R; Farrelly, Matthew C

2017-07-01

This study examines the relationships between trial of new marijuana or hashish products and unexpected highs, and use of edible products and unexpected highs. We conducted an online survey of 634 adult, past-year marijuana users in Colorado. We used logistic regression models to examine the relationship between new product trial or edible use and unexpected highs. In the first year that recreational marijuana was legal in Colorado, 71.4% of respondents tried a new marijuana or hashish product, and 53.6% used an edible product. Trial of new products was associated with greater odds of experiencing an unexpected high after controlling for age, gender, education, mental health status, current marijuana or hashish use, and mean amount of marijuana or hashish consumed in the past month (OR=2.13, p<0.001). Individuals who reported having used edibles had greater odds of experiencing an unexpected high, after controlling for the same set of variables (OR=1.56, p<0.05). People who try new marijuana or hashish products, or use edible marijuana or hashish products, are at greater risk for an unexpected high. It is possible that some negative outcomes associated with marijuana use and unexpected highs may be averted through a better understanding of how to use product packaging to communicate with consumers. Copyright © 2017 Elsevier B.V. All rights reserved.

Hunting for unexpected post-translational modifications by spectral library searching with tier-wise scoring.

PubMed

Ma, Chun Wai Manson; Lam, Henry

2014-05-02

Discovering novel post-translational modifications (PTMs) to proteins and detecting specific modification sites on proteins is one of the last frontiers of proteomics. At present, hunting for post-translational modifications remains challenging in widely practiced shotgun proteomics workflows due to the typically low abundance of modified peptides and the greatly inflated search space as more potential mass shifts are considered by the search engines. Moreover, most popular search methods require that the user specifies the modification(s) for which to search; therefore, unexpected and novel PTMs will not be detected. Here a new algorithm is proposed to apply spectral library searching to the problem of open modification searches, namely, hunting for PTMs without prior knowledge of what PTMs are in the sample. The proposed tier-wise scoring method intelligently looks for unexpected PTMs by allowing mass-shifted peak matches but only when the number of matches found is deemed statistically significant. This allows the search engine to search for unexpected modifications while maintaining its ability to identify unmodified peptides effectively at the same time. The utility of the method is demonstrated using three different data sets, in which the numbers of spectrum identifications to both unmodified and modified peptides were substantially increased relative to a regular spectral library search as well as to another open modification spectral search method, pMatch.

Systems pharmacology augments drug safety surveillance

PubMed Central

Lorberbaum, Tal; Nasir, Mavra; Keiser, Michael J.; Vilar, Santiago; Hripcsak, George; Tatonetti, Nicholas P.

2014-01-01

Small molecule drugs are the foundation of modern medical practice yet their use is limited by the onset of unexpected and severe adverse events (AEs). Regulatory agencies rely on post-marketing surveillance to monitor safety once drugs are approved for clinical use. Despite advances in pharmacovigilance methods that address issues of confounding bias, clinical data of AEs are inherently noisy. Systems pharmacology– the integration of systems biology and chemical genomics – can illuminate drug mechanisms of action. We hypothesize that these data can improve drug safety surveillance by highlighting drugs with a mechanistic connection to the target phenotype (enriching true positives) and filtering those that do not (depleting false positives). We present an algorithm, the modular assembly of drug safety subnetworks (MADSS), to combine systems pharmacology and pharmacovigilance data and significantly improve drug safety monitoring for four clinically relevant adverse drug reactions. PMID:25670520

A mutation in the neurofibromatosis type 2 tumor-suppressor gene, giving rise to widely different clinical phenotypes in two unrelated individuals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourn, D.; Carter, S.A.; Goodship, J.

The authors have sought mutations in the recently identified neurofibromatosis type 2 (NF2) tumor-suppressor gene in a large panel of NF2 patients, using PCR-based SSCP and heteroduplex analysis, followed by cloning and sequencing of appropriate PCR products. Two unrelated NF2 patients were found to have identical nonsense mutations caused by a C-to-T transition in a CpG dinucleotide that is a potential mutational hot spot in the NF2 tumor-suppressor gene. Unexpectedly, the two individuals had widely different clinical phenotypes, representing the severe Wishart and mild Gardner clinical subtypes. Analysis of DNA samples from different tissues of the mildly affected patient suggestsmore » that he is a somatic mosaic for the mutation. 26 refs., 3 figs.« less

Unwitting Exposure of the Therapist

PubMed Central

Ulman, Kathleen Hubbs

2001-01-01

The unwitting exposure of the therapist's private life creates an unexpected rupture in the frame and puts both the therapist and the patient off balance. The exposure introduces into the therapy a moment of human sharing of vulnerability that has the potential to enrich the treatment. Clinical vignettes are presented to help therapists anticipate possible exposures and their consequences. The discussion encourages therapists to predict their reactions, obtain needed professional support, and make the most of opportunities for full exploration of patients' material. PMID:11121003

[Preclinical birth of an extremely premature infant - a case report].

PubMed

Pöhlmann, Tobias; Schmidt, Armin; Pohl, Wolfgang

2016-11-01

Obstetrical emergencies requiring emergency medical service are very rare. An extremely premature birth in a preclinical setting is certainly exceptional. In the following case report, the emergency medical team was unexpectedly faced with the home birth of a fetus at the 23 rd week of gestation. Prematurity at the edge of viability poses a challenge to first care, equipment, infrastructure, expertise and clinical ethics. To the authors' knowledge, there is no comparable case report published so far. © Georg Thieme Verlag Stuttgart · New York.

Diabetes insipidus, diabetes mellitus, optic atrophy and deafness. A clinical and genetic study.

PubMed Central

Nagi, N. A.

1979-01-01

Two Iraqi sisters and a female cousin developed diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and deafness (D), (the 'DIDMOAD' syndrome) before the age of 12 years. One girl exhibited all the features of this disease complex only 3 months after an unusually late onset of recognizable symptoms at 11 years 9 months. Another girl died suddenly and unexpectedly. This family study illustrates the recessive inheritance pattern of the syndrome. Images Fig. 2 Fig. 3 PMID:482181

An unexpected cause for aplastic anaemia in an elderly woman.

PubMed

Phua, C K; Marimuthu, K; Teo, H Y; Ong, K H; Leo, Y S

2013-02-01

Aplastic anaemia is a rare clinical syndrome associated with diminished or absent precursors in the bone marrow. Acquired aplastic anaemia secondary to human immunodeficiency virus (HIV) is very rare. We present a 71-year-old woman with severe aplastic anaemia secondary to HIV infection, which was after extensive exclusion of other causes. She achieved undetectable viral load after 5 months of combination antiretroviral therapy but remains profoundly pancytopenic, complicated by recurrent infectious and bleeding complications. HIV infection should be considered in patients with pancytopenia.

Administration of probiotic kefir to mice with Clostridium difficile infection exacerbates disease.

PubMed

Spinler, Jennifer K; Brown, Aaron; Ross, Caná L; Boonma, Prapaporn; Conner, Margaret E; Savidge, Tor C

2016-08-01

Lifeway(®) kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Will oncotype DX DCIS testing guide therapy? A single-institution correlation of oncotype DX DCIS results with histopathologic findings and clinical management decisions.

PubMed

Lin, Chieh-Yu; Mooney, Kelly; Choy, Winward; Yang, Soo-Ryum; Barry-Holson, Keegan; Horst, Kathleen; Wapnir, Irene; Allison, Kimberly

2018-04-01

Given the increased detection rates of ductal carcinoma in situ (DCIS) and the limited overall survival benefit from adjuvant breast irradiation after breast-conserving surgery, there is interest in identifying subsets of patients who have low rates of ipsilateral breast tumor recurrence such that they might safely forgo radiation. The Oncotype DCIS score is a reverse transcription-PCR (RT-PCR)-based assay that was validated to predict which DCIS cases are most likely to recur. Clinically, these results may be used to assist in selecting which patients with DCIS might safely forgo radiation therapy after breast-conserving surgery; however, little is currently published on how this test is being used in practice. Our study examines traditional histopathologic features used in predicting DCIS risk with Oncotype DCIS results and how these results affect clinical decision-making at our academic institution. Histopathologic features and management decisions for 37 cases with Oncotype DCIS results over the past 4 years were collected. Necrosis, high nuclear grade, biopsy site change, estrogen receptor and progesterone receptor positivity <90% on immunohistochemistry, and Van Nuys Prognostic Index score of 8 or greater were significant predictors of an intermediate-high recurrence score on multivariate regression analysis (P<0.02). Low Oncotype DCIS scores and low nuclear grade were associated with lower rate of radiation therapy (P<0.008). There were seven cases (19%) with Oncotype DCIS results that we considered unexpected in relation to the histopathologic findings (ie, high nuclear grade with comedonecrosis and a low Oncotype score, or hormone receptor discrepancies). Overall, pathologic features correlate with Oncotype DCIS scores but unexpected results do occur, making individual recommendations sometimes challenging.

Unexpected finite size effects in interfacial systems: Why bigger is not always better—Increase in uncertainty of surface tension with bulk phase width

NASA Astrophysics Data System (ADS)

Longford, Francis G. J.; Essex, Jonathan W.; Skylaris, Chris-Kriton; Frey, Jeremy G.

2018-06-01

We present an unexpected finite size effect affecting interfacial molecular simulations that is proportional to the width-to-surface-area ratio of the bulk phase Ll/A. This finite size effect has a significant impact on the variance of surface tension values calculated using the virial summation method. A theoretical derivation of the origin of the effect is proposed, giving a new insight into the importance of optimising system dimensions in interfacial simulations. We demonstrate the consequences of this finite size effect via a new way to estimate the surface energetic and entropic properties of simulated air-liquid interfaces. Our method is based on macroscopic thermodynamic theory and involves comparing the internal energies of systems with varying dimensions. We present the testing of these methods using simulations of the TIP4P/2005 water forcefield and a Lennard-Jones fluid model of argon. Finally, we provide suggestions of additional situations, in which this finite size effect is expected to be significant, as well as possible ways to avoid its impact.

Gastrointestinal causes of sudden unexpected death: A review.

PubMed

Menezes, Ritesh G; Ahmed, Saba; Pasha, Syed Bilal; Hussain, Syed Ather; Fatima, Huda; Kharoshah, Magdy A; Madadin, Mohammed

2018-01-01

Gastrointestinal conditions are a less common cause of sudden unexpected death when compared to other conditions such as cardiovascular conditions, but they are equally important. Various congenital and acquired gastrointestinal conditions that have resulted in sudden unexpected death are discussed. The possible lethal mechanisms behind each condition, along with any associated risk factors or secondary diseases, have been described. Through this article, we aim to highlight the need for physicians to prevent death in such conditions by ensuring that subclinical cases are diagnosed correctly before it is too late and by providing timely and efficacious treatment to the patient concerned. In addition, this review would certainly benefit the forensic pathologist while dealing with cases of sudden unexpected death due to gastrointestinal causes. This article is a review of the major gastrointestinal causes of sudden unexpected death. In addition, related fatal cases encountered occasionally in forensic autopsy practice are also included. There are several unusual and rare causes of life-threatening gastrointestinal bleeding that may lead to sudden unexpected death to cover all the entities in detail. Nevertheless, this article is a general guide to the topic of gastrointestinal causes of sudden unexpected death.

CRISPR-mediated targeting of HER2 inhibits cell proliferation through a dominant negative mutation.

PubMed

Wang, Huajing; Sun, William

2017-01-28

With the discovery of the CRISPR/Cas9 technology, genome editing could be performed in a rapid, precise and effective manner. Its potential applications in functional interrogation of cancer-causing genes and cancer therapy have been extensively explored. In this study, we demonstrated the use of the CRISPR/Cas9 system to directly target the oncogene HER2. Directing Cas9 to exons of the HER2 gene inhibited cell growth in breast cancer cell lines that harbor amplification of the HER2 locus. The inhibitory effect was potentiated with the addition of PARP inhibitors. Unexpectedly, CRISPR-induced mutations did not significantly affect the level of HER2 protein expression. Instead, CRISPR targeting appeared to exert its effect through a dominant negative mutation. This HER2 mutant interfered with the MAPK/ERK axis of HER2 downstream signaling. Our work provides a novel mechanism underlying the anti-cancer effects of HER2-targeting by CRISPR/Cas9, which is distinct from the clinical drug Herceptin. In addition, it opens up the possibility that incomplete CRISPR targeting of certain oncogenes could still have therapeutic value by generation of dominant negative mutants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Radiobiology of Proton Therapy: Challenges and Opportunities Around Relative Biological Effectiveness.

PubMed

Jones, B; McMahon, S J; Prise, K M

2018-05-01

With the current UK expansion of proton therapy there is a great opportunity for clinical oncologists to develop a translational interest in the associated scientific base and clinical results. In particular, the underpinning controversy regarding the conversion of photon dose to proton dose by the relative biological effectiveness (RBE) must be understood, including its important implications. At the present time, the proton prescribed dose includes an RBE of 1.1 regardless of tissue, tumour and dose fractionation. A body of data has emerged against this pragmatic approach, including a critique of the existing evidence base, due to choice of dose, use of only acute-reacting in vivo assays, analysis methods and the reference radiations used to determine the RBE. Modelling systems, based on the best available scientific evidence, and which include the clinically useful biological effective dose (BED) concept, have also been developed to estimate proton RBEs for different dose and linear energy transfer (LET) values. The latter reflect ionisation density, which progressively increases along each proton track. Late-reacting tissues, such as the brain, where α/β = 2 Gy, show a higher RBE than 1.1 at a low dose per fraction (1.2-1.8 Gy) at LET values used to cover conventional target volumes and can be much higher. RBE changes with tissue depth seem to vary depending on the method of beam delivery used. To reduce unexpected toxicity, which does occasionally follow proton therapy, a more rational approach to RBE allocation, using a variable RBE that depends on dose per fraction and the tissue and tumour radiobiological characteristics such as α/β, is proposed. Copyright © 2018. Published by Elsevier Ltd.

L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer

PubMed Central

Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

2016-01-01

Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients. PMID:27152244

Efficacy of magnesium chloride in the treatment of Hailey-Hailey disease: from serendipity to evidence of its effect on intracellular Ca(2+) homeostasis.

PubMed

Borghi, Alessandro; Rimessi, Alessandro; Minghetti, Sara; Corazza, Monica; Pinton, Paolo; Virgili, Annarosa

2015-01-01

Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited intraepidermal blistering genodermatosis. Mutations in the ATP2C1 gene encoding for the Golgi secretory pathway Ca(2+) /Mn(2+) -ATPasi protein 1 (SPCA1) affect the processing of desmosomal components and the epidermal suprabasal cell-cell adhesion by deregulating the keratinocyte cytosolic Ca(2+) concentration. We report the unexpected, dramatic, and persistent clinical improvement of the skin lesions of a patient affected with longstanding HHD with daily intake of a solution containing magnesium chloride hexahydrate (MgCl2 ). We investigated the effect of MgCl2 on the intracellular Ca(2+) homeostasis and on the activity of particular Ca(2+) -effectors in HeLa cells transfected with chimeric aequorins (cytAEQ, mtAEQ, erAEQ and GoAEQ) targeted to different subcellular compartments (cytosol, mitochondria, endoplasmic reticulum, and Golgi, respectively). Experimental investigations on HeLa cells showed the effect of MgCl2 on the function of Ca(2+) -extrusor systems, resulting in increased cytosolic and mitochondrial Ca(2+) levels, without altering the mechanisms of intraluminal Ca(2+) -filling and Ca(2+) -release of stores. Based on our clinical observation and experimental results, it can be hypothesized that MgCl2 could act as an inhibitor of the Ca(2+) -extruding activity in keratinocytes favoring intracellular Ca(2+) -disponibility and Ca(2+) -dependent mechanisms in desmosome assembly. This may represent the molecular basis of the good response of the HHD clinical features with MgCl2 solution in the patient described. © 2014 The International Society of Dermatology.

Incidence and clinical characteristics of unexpected uterine sarcoma after hysterectomy and myomectomy for uterine fibroids: a retrospective study of 10,248 cases.

PubMed

Zhao, Wan-Cheng; Bi, Fang-Fang; Li, Da; Yang, Qing

2015-01-01

Uterine fibroids often require a hysterectomy or myomectomy via laparotomy or laparoscopy. Morcellation is often necessary to perform a laparoscopic surgery. The objective of this study is to determine the incidence of unexpected uterine sarcomas (UUSs) after hysterectomy and myomectomy for uterine fibroids and to reduce the occurrence and avoid the morcellation of UUSs by analyzing their characteristics. Women who had a hysterectomy or myomectomy for uterine fibroids in Shengjing Hospital of China Medical University between November 2008 and November 2014 were selected for the study, and their clinical characteristics were analyzed. During the period, 48 UUSs were found in 10,248 cases, and the overall incidence was 0.47%. There was no statistical difference (P=0.449) regarding the incidence (0.50% vs 0.33%) between 42 UUSs in 8,456 cases undergoing laparotomy and six UUSs in 1,792 cases undergoing laparoscopy. Most of the UUSs were stage I (89.58%), which occurred more commonly (56.25%) in women aged 40-49. Abnormal uterine bleeding (39.58%) was the main clinical manifestation. Rapidly growing pelvic masses (12.5%), rich blood flow signals (18.75%), and degeneration of uterine fibroids (18.75%) prompted by ultrasonography may suggest the possibility of UUSs. The margins of most UUSs (93.75%) were regular, which may cause UUSs to be misdiagnosed as uterine fibroids. Fifteen cases underwent magnetic resonance imaging examinations. Approximately 73.33% showed heterogeneous and hypointense signal intensity on T1-weighted images, and 80% showed intermediate-to-high signal intensity on T2-weighted images, with necrosis and hemorrhage in 40% of cases. After contrast administration, 80% presented early heterogeneous enhancement. The incidence of UUSs after hysterectomy and myomectomy for uterine fibroids was low, and their clinical characteristics are atypical. It is necessary and very critical to make a complete and cautious preoperative evaluation to reduce the occurrence and avoid the morcellation of UUSs.

Post-licensure safety surveillance of 23-valent pneumococcal polysaccharide vaccine in the Vaccine Adverse Event Reporting System (VAERS), 1990-2013.

PubMed

Miller, Elaine R; Moro, Pedro L; Cano, Maria; Lewis, Paige; Bryant-Genevier, Marthe; Shimabukuro, Tom T

2016-05-27

23-Valent pneumococcal polysaccharide vaccine, trade name Pneumovax(®)23 (PPSV23), has been used for decades in the Unites States and has an extensive clinical record. However, limited post-licensure safety assessment has been conducted. To analyze reports submitted to the Vaccine Adverse Event Reporting System (VAERS) following PPSV23 from 1990 to 2013 in order to characterize its safety profile. We searched the VAERS database for US reports following PPSV23 for persons vaccinated from 1990 to 2013. We assessed safety through: automated analysis of VAERS data, crude adverse event (AE) reporting rates based on PPSV23 doses distributed in the US market, clinical review of death reports and reports involving vaccine administered to pregnant women, and empirical Bayesian data mining to assess for disproportional reporting. During the study period, VAERS received 25,168 PPSV23 reports; 92% were non-serious, 67% were in females and 86% were in adults aged ≥19 years. When PPSV23 was administered alone, fever (43%), injection site erythema (28%) and injection site pain (25%) were the most commonly reported non-serious AEs in children. Injection site erythema (32%), injection site pain (27%) and injection site swelling (23%) were the most commonly reported non-serious AEs in adults. Of serious reports (2129, 8% of total), fever was most commonly reported in both children (69%) and adults (39%). There were 66 reports of death, four in children and 62 in adults. Clinical review of death reports did not reveal any concerning patterns that would suggest a causal association with PPSV23. No disproportional reporting of unexpected AEs was observed in empirical Bayesian data mining. We did not identify any new or unexpected safety concerns for PPSV23. The VAERS data are consistent with safety data from pre-licensure clinical trials and other post-licensure studies. Published by Elsevier Ltd.

Confronting the unexpected: temporal, situational, and attributive dimensions of distressing symptom experience for breast cancer survivors.

PubMed

Rosedale, Mary; Fu, Mei R

2010-01-01

To describe women's unexpected and distressing symptom experiences after breast cancer treatment. Qualitative and descriptive. Depending upon their preference, participants were interviewed in their homes or in a private office space in a nearby library. Purposive sample of 13 women 1-18 years after breast cancer treatment. Secondary analysis of phenomenologic data (constant comparative method). Breast cancer symptom distress, ongoing symptoms, and unexpected experiences. Women described experiences of unexpected and distressing symptoms in the years following breast cancer treatment. Symptoms included pain, loss of energy, impaired limb movement, cognitive disturbance, changed sexual experience, and lymphedema. Four central themes were derived: living with lingering symptoms, confronting unexpected situations, losing precancer being, and feeling like a has-been. Distress intensified when women expected symptoms to disappear but symptoms persisted instead. Increased distress also was associated with sudden and unexpected situations or when symptoms elicited feelings of loss about precancer being and feelings of being a has been. Findings suggest that symptom distress has temporal, situational, and attributive dimensions. Breast cancer survivors' perceptions of ongoing and unexpected symptoms have important influences on quality of life. Understanding temporal, situational, and attributive dimensions of symptom distress empowers nurses and healthcare professionals to help breast cancer survivors prepare for subsequent ongoing or unexpected experiences in the years after breast cancer treatment. Follow-up care for breast cancer survivors should foster dialogue about ways that symptoms might emerge and that unexpected situations might occur. Prospective studies are needed to examine symptom distress in terms of temporal, situational, and attributive dimensions and explore the relationship between symptom distress and psychological distress after breast cancer treatment.

The Unexpected Side-Effects of Dissonance

ERIC Educational Resources Information Center

Bodner, Ehud; Gilboa, Avi; Amir, Dorit

2007-01-01

The effects of dissonant and consonant music on cognitive performance were examined. Situational dissonance and consonance were also tested and determined as the state where one's opinion is contrasted or matched with the majority's opinion, respectively. Subjects performed several cognitive tasks while listening to a melody arranged dissonantly,…

Gradual electronic health record implementation: new insights on physician and patient adaptation.

PubMed

Shield, Renée R; Goldman, Roberta E; Anthony, David A; Wang, Nina; Doyle, Richard J; Borkan, Jeffrey

2010-01-01

Although there is significant interest in implementation of electronic health records (EHRs), limited data have been published in the United States about how physicians, staff, and patients adapt to this implementation process. The purpose of this research was to examine the effects of EHR implementation, especially regarding physician-patient communication and behaviors and patients' responses. We undertook a 22-month, triangulation design, mixed methods study of gradual EHR implementation in a residency-based family medicine outpatient center. Data collection included participant observation and time measurements of 170 clinical encounters, patient exit interviews, focus groups with nurses, nurse's aides, and office staff, and unstructured observations and interviews with nursing staff and physicians. Analysis involved iterative immersion-crystallization discussion and searches for alternate hypotheses. Patient trust in the physician and security in the physician-patient relationship appeared to override most patients' concerns about information technology. Overall, staff concerns about potential deleterious consequences of EHR implementation were dispelled, positive anticipated outcomes were realized, and unexpected benefits were found. Physicians appeared to become comfortable with the "third actor" in the room, and nursing and office staff resistance to EHR implementation was ameliorated with improved work efficiencies. Unexpected advantages included just-in-time improvements and decreased physician time out of the examination room. Strong patient trust in the physician-patient relationship was maintained and work flow improved with EHR implementation. Gradual EHR implementation may help support the development of beneficial physician and staff adaptations, while maintaining positive patient-physician relationships and fostering the sharing of medical information.

Angular dependence of DRAM upset susceptibility

NASA Technical Reports Server (NTRS)

Guertin, S. M.; Swift, G. M.; Edmonds, L. D.

2000-01-01

Heavy ion irradiations of two types of commercial DRAMs reveal unexpected angular responses. One device's cross section varied by two orders of magnitude with azimuthal angle. Accurate prediction of space rates requires accommodating this effect.

Detecting the unexpected: a research framework for ocean acidification.

PubMed

Pfister, Catherine A; Esbaugh, Andrew J; Frieder, Christina A; Baumann, Hannes; Bockmon, Emily E; White, Meredith M; Carter, Brendan R; Benway, Heather M; Blanchette, Carol A; Carrington, Emily; McClintock, James B; McCorkle, Daniel C; McGillis, Wade R; Mooney, T Aran; Ziveri, Patrizia

2014-09-02

The threat that ocean acidification (OA) poses to marine ecosystems is now recognized and U.S. funding agencies have designated specific funding for the study of OA. We present a research framework for studying OA that describes it as a biogeochemical event that impacts individual species and ecosystems in potentially unexpected ways. We draw upon specific lessons learned about ecosystem responses from research on acid rain, carbon dioxide enrichment in terrestrial plant communities, and nitrogen deposition. We further characterize the links between carbon chemistry changes and effects on individuals and ecosystems, and enumerate key hypotheses for testing. Finally, we quantify how U.S. research funding has been distributed among these linkages, concluding that there is an urgent need for research programs designed to anticipate how the effects of OA will reverberate throughout assemblages of species.

A Sociotechnical Approach to Evaluating the Impact of ICT on Clinical Care Environments

PubMed Central

Li, Julie

2010-01-01

Introduction: Process-supporting information technology holds the potential to increase efficiency, reduce errors, and alter professional roles and responsibilities in a manner which allows improvement in the delivery of patient care. However, clashes between the model of health care work inscribed in these tools with the actual nature of work has resulted in staff resistance and decreased organisational uptake of ICT, as well as the facilitation of unexpected and negative effects in efficiency and patient safety. Sociotechnical theory provides a paradigm against which workflow and transfusion of ICT in healthcare could be better explored and understood. Design: This paper will conceptualise a formative, multi-method longitudinal evaluation process to explore the impact of ICT with an appreciation of the relationship between the social and technical systems within a clinical department. Method: Departmental culture, including clinical work processes and communication patterns will be thoroughly explored before system implementation using both quantitative and qualitative research methods. Findings will be compared with post implementation data, which will incorporate measurement of safety and workflow efficiency indicators. Discussion: Sociotechnical theory provides a paradigm against which workflow and transfusion of ICT in healthcare could be better explored and understood. However, sociotechnical and multimethod approaches to evaluation do not exist without criticism. Inherent in the protocol are limitations of sociotechnical theory and criticism of the multimethod approach; testing of the methodology in real clinical settings will serve to verify efficacy and refine the process. PMID:21594005

Clinical and histologic evaluation of non-surgical periodontal therapy with enamel matrix derivative: a report of four cases.

PubMed

Mellonig, James T; Valderrama, Pilar; Gregory, Holly J; Cochran, David L

2009-09-01

Enamel matrix derivative (EMD) is a composite of proteins that was demonstrated histologically to work as an adjunct to periodontal regenerative surgical therapy. The purpose of this study was to evaluate the clinical and histologic effects of EMD as an adjunct to scaling and root planing. Four patients with severe chronic periodontitis and scheduled to receive complete dentures were accrued. Probing depth and clinical attachment levels were obtained. Unlimited time was allowed for hand and ultrasonic instrumentation. A notch was placed in the root >or=1 to 2 mm from the apical extent of root planing. EMD was inserted into the pocket, and a periodontal dressing was placed. Patients were seen every 2 weeks for plaque control. At 6 months post-treatment, soft tissue measurements were repeated, and the teeth were removed en bloc and prepared for histomorphologic analysis. Probing depth reduction and clinical attachment level gain were obtained in three-fourths of the specimens. Three of the four specimens analyzed histologically demonstrated new cementum, bone, periodontal ligament, and connective tissue attachment coronal to the notch. In one specimen, the gingival margin had receded below the notch. The results were unexpected and may represent an aberration. However, the substantial reduction in deep probing depths and clinical attachment level gain in three of four specimens, in addition to the histologic findings of new cementum, new bone, a new periodontal ligament, and a new connective tissue attachment, suggest that EMD may be useful as an adjunct to scaling and root planing in single-rooted teeth.

The Nrf2 pathway in the progression of renal disease.

PubMed

Zoja, Carlamaria; Benigni, Ariela; Remuzzi, Giuseppe

2014-02-01

The Nrf2/Keap1 system regulates the transcription of antioxidant and cytoprotective genes through direct Nrf2 binding to responsive elements in the promoter region of target genes or via Keap1-induced NF-kB inhibition. The association between oxidative stress and inflammation with progression of chronic kidney diseases (CKDs) directed attention towards bardoxolone methyl and its analogues, potent Nrf2/Keap1 inducers, as a potential modality of renoprotective intervention. In a phase II clinical trial (BEAM), bardoxolone methyl was shown to increase the estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes. The study generated great interest but raised concerns as well, on the adverse event profile of the drug. Experiments in rats with type 2 diabetic nephropathy treated with bardoxolone methyl analogues reproduced some drawbacks of bardoxolone methyl therapy in humans. Despite these warnings, a long-term phase III trial (BEACON) was started that was prematurely terminated because of an excess serious adverse events and mortality. Lessons from the above studies suggest that before jumping into use in clinical practice, adequately designed experiments in animal models are needed to provide insights into pathogenetic mechanisms as well as unexpected side effects.

The clinical implications of high levels of autism spectrum disorder features in anorexia nervosa: a pilot study.

PubMed

Huke, Vanessa; Turk, Jeremy; Saeidi, Saeideh; Kent, Andrew; Morgan, John F

2014-03-01

This study examined autism spectrum disorder (ASD) features in relation to treatment completion and eating disorder psychopathology in anorexia nervosa (AN). Thirty-two adult women were recruited from specialist eating disorder services. Features of ASD and disordered eating were measured. Premature termination of treatment was recorded to explore whether ASD traits had impact on early discharge. A healthy control group was also recruited to investigate ASD traits between clinical and nonclinical samples. Significant differences were found between the AN group and the healthy control group in obsessive-compulsive disorder traits, depression and anxiety and ASD traits, with significant differences between groups in Social Skill and Attention Switching. The AN group reported no significant relationship between disordered eating severity and ASD traits. No significant effect was found between ASD features and treatment completion. Raw data on premature termination of treatment, despite no statistic impact, showed that seven out of the eight participants with high features of ASD completed treatment as planned compared with 50% of those with low ASD traits. Unexpectedly, this suggests enhanced treatment adherence in ASD. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation.

PubMed

Link, C S; Teipel, R; Heidenreich, F; Rücker-Braun, E; Schmiedgen, M; Reinhardt, J; Oelschlägel, U; von Bonin, M; Middeke, J M; Muetherig, A; Trautmann-Grill, K; Platzbecker, U; Bornhäuser, M; Schetelig, J

2016-06-01

Ibrutinib, a recently approved inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT.

Growing organizational capacity through a systems approach: one health network's experience.

PubMed

MacKenzie, Richard; Capuano, Terry; Durishin, Linda Drexinger; Stern, Glen; Burke, James B

2008-02-01

Hospitals are reporting unexpected surges in demand for services. Lehigh Valley Hospital challenged its clinical and administrative staff to increase capacity by at least 4% per year using an interdepartmental, systemwide initiative, Growing Organizational Capacity (GOC). Following a systemwide leadership retreat that yielded more than 1,000 ideas, the initiative's principal sponsor convened a cross-functional improvement team. During a two-year period, 17 projects were implemented. Using a complex systems approach, improvement ideas "emerged" from microsystems at the points of care. Through rigorous reporting and testing of process adaptations, need, data, and people drove innovation. Hundreds of multilevel clinical and administrative staff redesigned processes and roles to increase organizational capacity. Admissions rose by 6.1%, 5.5 %, 8.7%, 5.0%, and 3.8% in fiscal years 2003 through 2007, respectively. Process enhancements cost approximately $1 million, while increased revenues attributable to increased capacity totaled $2.5 million. Multiple, coordinated, and concurrent projects created a greater impact than that possible with a single project. GOC and its success, best explained in the context of complex adaptive systems and microsystem theories, are transferrable to throughput issues that challenge efficiency and effectiveness in other health care systems.

Cancer hyperthermia using magnetic nanoparticles.

PubMed

Kobayashi, Takeshi

2011-11-01

Magnetic-nanoparticle-mediated intracellular hyperthermia has the potential to achieve localized tumor heating without any side effects. The technique consists of targeting magnetic nanoparticles to tumor tissue followed by application of an external alternating magnetic field that induces heat through Néel relaxation loss of the magnetic nanoparticles. The temperature in tumor tissue is increased to above 43°C, which causes necrosis of cancer cells, but does not damage surrounding normal tissue. Among magnetic nanoparticles available, magnetite has been extensively studied. Recent years have seen remarkable advances in magnetite-nanoparticle-mediated hyperthermia; both functional magnetite nanoparticles and alternating-magnetic-field generators have been developed. In addition to the expected tumor cell death, hyperthermia treatment has also induced unexpected biological responses, such as tumor-specific immune responses as a result of heat-shock protein expression. These results suggest that hyperthermia is able to kill not only local tumors exposed to heat treatment, but also tumors at distant sites, including metastatic cancer cells. Currently, several research centers have begun clinical trials with promising results, suggesting that the time may have come for clinical applications. This review describes recent advances in magnetite nanoparticle-mediated hyperthermia. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laundry detergent "pod" ingestions: a case series and discussion of recent literature.

PubMed

Beuhler, Michael C; Gala, Payal K; Wolfe, Heather A; Meaney, Peter A; Henretig, Fred M

2013-06-01

The objectives of this study were to present and explore the clinical presentation of the increasingly common pediatric exposure to the widely available single-use laundry packets or "laundry pods." This is a case report of 4 pediatric patients with significant toxicity due to laundry pod detergent exposure and a review of the available literature including abstract-only publications. An unexpectedly severe clinical pattern was noted; 3 of the 4 children required intubation for management, airway injury was noted in 1 of them, and 2 of them had hospital courses of at least 1 week. The literature suggests that laundry pod exposures are associated with increased morbidity compared to traditional laundry detergent exposures. To date, no specific contaminant or component has been identified as being responsible for the injury, although some evidence points to the surfactant component. A different approach to the triage and management of pediatric exposures to laundry detergent pod ingestions is required compared with nonpod ingestions. Although the exact cause is not known, practitioners should be vigilant for rapid onset of neurological impairment and inability to protect the airway in addition to its caustic effects.

Attention-deficit/hyperactivity disorder, joint hypermobility-related disorders and pain: expanding body-mind connections to the developmental age.

PubMed

Baeza-Velasco, Carolina; Sinibaldi, Lorenzo; Castori, Marco

2018-02-14

Attention-deficit/hyperactivity disorder (ADHD) and generalized joint hypermobility (JH) are two separated conditions, assessed, and managed by different specialists without overlapping interests. Recently, some researchers highlighted an unexpected association between these two clinical entities. This happens in a scenario of increasing awareness on the protean detrimental effects that congenital anomalies of the connective tissue may have on human health and development. To review pertinent literature to identify possible connections between ADHD and GJH, special emphasis was put on musculoskeletal pain and syndromic presentations of GJH, particularly the hypermobile Ehlers-Danlos syndrome. A comprehensive search of scientific databases and references lists was conducted, encompassing publications based on qualitative and quantitative research. Impaired coordination and proprioception, fatigue, chronic pain, and dysautonomia are identified as potential bridges between ADHD and JH. Based on these findings, a map of the pathophysiological and psychopathological pathways connecting both conditions is proposed. Although ADHD and JH are traditionally separated human attributes, their association may testify for the dyadic nature of mind-body connections during critical periods of post-natal development. Such a mixed picture has potentially important consequences in terms of disability and deserves more clinical and research attention.

What is the role of imaging in the clinical diagnosis of osteoarthritis and disease management?

PubMed

Wang, Xia; Oo, Win Min; Linklater, James M

2018-05-01

While OA is predominantly diagnosed on the basis of clinical criteria, imaging may aid with differential diagnosis in clinically suspected cases. While plain radiographs are traditionally the first choice of imaging modality, MRI and US also have a valuable role in assessing multiple pathologic features of OA, although each has particular advantages and disadvantages. Although modern imaging modalities provide the capability to detect a wide range of osseous and soft tissue (cartilage, menisci, ligaments, synovitis, effusion) OA-related structural damage, this extra information has not yet favourably influenced the clinical decision-making and management process. Imaging is recommended if there are unexpected rapid changes in clinical outcomes to determine whether it relates to disease severity or an additional diagnosis. On developing specific treatments, imaging serves as a sensitive tool to measure treatment response. This narrative review aims to describe the role of imaging modalities to aid in OA diagnosis, disease progression and management. It also provides insight into the use of these modalities in finding targeted treatment strategies in clinical research.

Shared risk aversion in spontaneous and induced abortion.

PubMed

Catalano, Ralph; Bruckner, Tim A; Karasek, Deborah; Adler, Nancy E; Mortensen, Laust H

2016-05-01

Does the incidence of spontaneous abortion correlate positively over conception cohorts with the incidence of non-clinically indicated induced abortion as predicted by shared risk aversion? We find that the number of spontaneous and non-clinically indicated induced abortions correlates in conception cohorts, suggesting that risk aversion affects both the conscious and non-conscious mechanisms that control parturition. Much literature speculates that natural selection conserved risk aversion because the trait enhanced Darwinian fitness. Risk aversion, moreover, supposedly influences all decisions including those that individuals can and cannot report making. We argue that these circumstances, if real, would manifest in conscious and non-conscious decisions to invest in prospective offspring, and therefore affect incidence of induced and spontaneous abortion over time. Using data from Denmark, we test the hypothesis that monthly conception cohorts yielding unexpectedly many non-clinically indicated induced abortions also yield unexpectedly many spontaneous abortions. The 180 month test period (January 1995 through December 2009), yielded 1 351 800 gestations including 156 780 spontaneous as well as 233 280 induced abortions 9100 of which were clinically indicated. We use Box-Jenkins transfer functions to adjust the incidence of spontaneous and non-clinically indicated induced abortions for autocorrelation (including seasonality), cohort size, and fetal as well as gestational anomalies over the 180-month test period. We use cross-correlation to test our hypothesized association. We find a positive association between spontaneous and non-clinically indicated induced abortions. This suggests, consistent with our theory, that mothers of conception cohorts that yielded more spontaneous abortions than expected opted more frequently than expected for non-clinically indicated induced abortion. Limitations of our work include that even the world's best registration system will not capture all spontaneous abortions and that results may not generalize beyond Denmark. Our findings imply that abortion, intentional or 'spontaneous,' follows from a woman's estimate, made consciously or otherwise, of the costs and benefits of extending gestation given characteristics of the prospective offspring, likely environmental circumstances at birth, and maternal resources. The Robert Wood Johnson Health and Society Scholars Program funded the research described in this manuscript. None of the authors has any conflict of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

L-DOPA: a scapegoat for accelerated neurodegeneration in Parkinson's disease?

PubMed

Lipski, Janusz; Nistico, Robert; Berretta, Nicola; Guatteo, Ezia; Bernardi, Giorgio; Mercuri, Nicola B

2011-09-01

There is consensus that amelioration of the motor symptoms of Parkinson's disease is most effective with L-DOPA (levodopa). However, this necessary therapeutic step is biased by an enduring belief that L-DOPA is toxic to the remaining substantia nigra dopaminergic neurons by itself, or by specific metabolites such as dopamine. The concept of L-DOPA toxicity originated from pre-clinical studies conducted mainly in cell culture, demonstrating that L-DOPA or its derivatives damage dopaminergic neurons due to oxidative stress and other mechanisms. However, the in vitro data remain controversial as some studies showed neuroprotective, rather than toxic action of the drug. The relevance of this debate needs to be considered in the context of the studies conducted on animals and in clinical trials that do not provide convincing evidence for L-DOPA toxicity in vivo. This review presents the current views on the pathophysiology of Parkinson's disease, focusing on mitochondrial dysfunction and oxidative/proteolytic stress, the factors that can be affected by L-DOPA or its metabolites. We then critically discuss the evidence supporting the two opposing views on the effects of L-DOPA in vitro, as well as the animal and human data. We also address the problem of inadequate experimental models used in these studies. L-DOPA remains the symptomatic 'hero' of Parkinson's disease. Whether it contributes to degeneration of nigral dopaminergic neurons, or is a 'scapegoat' for explaining undesirable or unexpected effects of the treatment, remains a hotly debated topic. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinicians with dyslexia: a systematic review of effects and strategies.

PubMed

Locke, Rachel; Scallan, Samantha; Mann, Richard; Alexander, Gail

2015-12-01

For educators, an awareness of the impact of dyslexia on learners in the clinical workplace is vital: first, to be able to identify whether dyslexia may underlie certain traits and behaviours; and second, to be able to provide appropriate advice and support when dyslexia is identified. We reviewed the primary research evidence concerning the effects of dyslexia on clinicians (in or after training) in the workplace, and adaptive strategies ('workarounds') that are presently in use. A systematic search of literature was undertaken, followed by a narrative review of studies selected as meeting the inclusion criteria. The review used a priori research questions and focused on studies based on primary research evidence. The review identified five key studies on qualified doctors or nurses with dyslexia. The impact of dyslexia on doctors can include: writing and calculating prescriptions, writing patient notes, and prioritising and making referrals. Strategies to minimise the effects of dyslexia include the use of adaptive technologies, the need for more time for mentors and supervisors, and an awareness of 'enabling' and 'disabling' environments. An awareness of the impact of dyslexia on learners in the clinical workplace is vital The difficulties associated with dyslexia are varied and may be unexpected. Medical educators must therefore be aware of dyslexia and its impact. When supporting a trainee with dyslexia, there is guidance available but educators may struggle to identify strategies and resources that are evidence based, so further research is required. © 2015 John Wiley & Sons Ltd.

Sudden Unexpected Death in Epilepsy Among Patients With Benign Childhood Epilepsy With Centrotemporal Spikes.

PubMed

Doumlele, Kyra; Friedman, Daniel; Buchhalter, Jeffrey; Donner, Elizabeth J; Louik, Jay; Devinsky, Orrin

2017-06-01

Children with benign epilepsy with centrotemporal spikes (BECTS) have traditionally been considered to have a uniformly good prognosis. However, benign may be a misnomer because BECTS is linked to cognitive deficits, a more severe phenotype with intractable seizures, and the potential for sudden unexpected death in epilepsy (SUDEP). To determine if cases of BECTS are present in the North American SUDEP Registry (NASR). The NASR is a clinical and biospecimen repository established in 2011 to promote SUDEP research. The NASR database, which includes medical records, results of electroencephalographic tests, and interviews with family members of patients with epilepsy who died suddenly without other identifiable causes of death, was queried from June 3, 2011, to June 3, 2016, for cases of BECTS. The patients with epilepsy had died suddenly without other identifiable causes of death (eg, drowning, trauma, exposure to toxic substances, or suicide); SUDEP classification was determined by the consensus of 2 epileptologists. Cases of SUDEP among children who received a diagnosis of BECTS among patients reported in the NASR. Three boys (median age at death, 12 years; range, 9-13 years) who received a diagnosis of BECTS by their pediatric epileptologist or neurologists were identified among 189 cases reported in the NASR. The median age of epilepsy onset was 5 years (range, 3-11 years), and the median duration of epilepsy was 4 years (range, 1-10 years). Two deaths were definite SUDEP, and 1 was probable SUDEP. Independent review of clinical and electroencephalographic data supported the diagnosis of BECTS in all 3 patients. None of the patients was prescribed antiseizure drugs, either owing to physician recommendation or mutual decision by the physician and parents. All 3 patients were found dead in circumstances typical of SUDEP. The 3 patients spanned the spectrum of BECTS severity: 1 had only a few seizures, 1 had more than 30 focal motor seizures, and 1 had 4 witnessed generalized tonic-clonic seizures and approximately 30 suspected generalized tonic-clonic seizures. Sudden unexpected death in epilepsy is a very rare outcome in BECTS that clinicians should consider discussing in appropriate circumstances and possibly factoring into treatment decisions.

Field studies on pesticides and birds: Unexpected and unique relations

USGS Publications Warehouse

Blus, L.J.; Henny, Charles J.

1997-01-01

We review the advantages and disadvantages of experimental and field studies for determining effects of pesticides on birds. Important problems or principles initially discovered in the field include effects of DDT (through its metabolite DDE) on eggshell thickness, reproductive success, and population stability; trophic-level bioaccumulation of the lipid-soluble organochlorine pesticides; indirect effects on productivity and survival through reductions in the food supply and cover by herbicides and insecticides; unexpected toxic effects and routes of exposure of organophosphorus compounds such as famphur and dimethoate; effects related to simultaneous application at full strength of several pesticides of different classes; and others. Also, potentially serious bird problems with dicofol, based on laboratory studies, later proved negligible in the field. In refining field tests of pesticides, the selection of a species or group of species to study is important, because exposure routes may vary greatly, and 10-fold interspecific differences in sensitivity to pesticides are relatively common. Although there are limitations with field investigations, particularly uncontrollable variables that must be addressed, the value of a well-designed field study far outweighs its shortcomings.

Field studies on pesticides and birds: unexpected and unique relations

USGS Publications Warehouse

Blus, L.J.; Henny, C.J.

1997-01-01

We review the advantages and disadvantages of experimental and field studies for determining effects of pesticides on birds. Important problems or principles initially discovered in the field include effects of DDT (through its metabolite DDE) on eggshell thickness, reproductive success, and population stability; trophic-level bioaccumulation of the lipid-soluble organochlorine pesticides; indirect effects on productivity and survival through reductions in the food supply and cover by herbicides and insecticides; unexpected toxic effects and routes of exposure of organophosphorus compounds such as famphur and dimethoate; effects related to simultaneous application at full strength of several pesticides of different classes; and others. Also, potentially serious bird problems with dicofol, based on laboratory studies, later proved negligible in the field. In refining field tests of pesticides, the selection of a species or group of species to study is important, because exposure routes may vary greatly, and 10-fold interspecific differences in sensitivity to pesticides are relatively common. Although there are limitations with field investigations, particularly uncontrollable variables that must be addressed, the value of a well-designed field study far outweighs its shortcomings

Influence of Nose Shape and L/D Ratio on Projectile Penetration in Frozen Soil

DTIC Science & Technology

1980-04-01

unexpected when soil properties are considered. Decreasing temperature below -10%C by 100 or 150 has little effect on the constitutive properties of... Effect ....... ............ ............. 10 L/D Influence .......................... .10 Target Temperature Effects ...10. Effect of L/D ratio and mass on flat nose pro- jectile penetration (the solid lines are least square curve fits to the data

Effects of color vision deficiency on detection of color-highlighted targets in a simulated air traffic control display.

DOT National Transportation Integrated Search

1992-01-01

The present study sought to evaluate the effects of color vision deficiency on the gain in conspicuity that is realized when color-highlighting is added as a redundant cue to indicate the presence of unexpected, nontracked aircraft intruding in contr...

When Feedback Harms and Collaboration Helps in Computer Simulation Environments: An Expertise Reversal Effect

ERIC Educational Resources Information Center

Nihalani, Priya K.; Mayrath, Michael; Robinson, Daniel H.

2011-01-01

We investigated the effects of feedback and collaboration on undergraduates' transfer performance when using a computer networking training simulation. In Experiment 1, 65 computer science "novices" worked through an instructional protocol individually (control), individually with feedback, or collaboratively with feedback. Unexpectedly,…

Investigation of major genetic alterations in neuroblastoma.

PubMed

Costa, Régis Afonso; Seuánez, Héctor N

2018-06-01

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. This malignancy shows a wide spectrum of clinical outcome and its prognosis is conditioned by manifold biological and genetic factors. We investigated the tumor genetic profile and clinical data of 29 patients with NB by multiplex ligation-dependent probe amplification (MLPA) to assess therapeutic risk. In 18 of these tumors, MYCN status was assessed by fluorescence in situ hybridization (FISH). Copy number variation was also determined for confirming MLPA findings in two 6p loci. We found 2p, 7q and 17q gains, and 1p and 11q losses as the most frequent chromosome alterations in this cohort. FISH confirmed all cases of MYCN amplification detected by MLPA. In view of unexpected 6p imbalance, copy number variation of two 6p loci was assessed for validating MLPA findings. Based on clinical data and genetic profiles, patients were stratified in pretreatment risk groups according to international consensus. MLPA proved to be effective for detecting multiple genetic alterations in all chromosome regions as requested by the International Neuroblastoma Risk Group (INRG) for therapeutic stratification. Moreover, this technique proved to be cost effective, reliable, only requiring standard PCR equipment, and attractive for routine analysis. However, the observed 6p imbalances made PKHD1 and DCDC2 inadequate for control loci. This must be considered when designing commercial MLPA kits for NB. Finally, four patients showed a normal MLPA profile, suggesting that NB might have a more complex genetic pattern than the one assessed by presently available MLPA kits.

Long-term safety and efficacy of adalimumab for intestinal Behçet's disease in the open label study following a phase 3 clinical trial.

PubMed

Inoue, Nagamu; Kobayashi, Kiyonori; Naganuma, Makoto; Hirai, Fumihito; Ozawa, Morio; Arikan, Dilek; Huang, Bidan; Robinson, Anne M; Thakkar, Roopal B; Hibi, Toshifumi

2017-07-01

Intestinal Behçet's disease (BD) is an immune-mediated inflammatory disorder. We followed up the patients and evaluated safety profile and effectiveness of adalimumab for the treatment of intestinal BD through 100 weeks rolled over from the 52 week clinical trial (NCT01243671). Patients initiated adalimumab therapy at 160 mg at week 0, followed by 80 mg at week 2, followed by 40 mg every other week until the end of the study. Long-term safety and all adverse events (AEs) were examined. The efficacy was assessed on the basis of marked improvement (MI) and complete remission (CR) using a composite efficacy index, which combined global gastrointestinal symptoms and endoscopic assessments. Twenty patients were enrolled in this study; 15 patients received adalimumab treatment until study completion. The incidence of AEs through week 100 was 544.4 events/100 person-years, which was comparable to the incidence through week 52 (560.4 events/100 person-years). No unexpected trend was observed and adalimumab was well tolerated. At weeks 52 and 100, 60.0% and 40.0% of patients showed MI, respectively, and 20.0% and 15.0% of patients showed CR, respectively. This report demonstrates 2 years safety and effectiveness of adalimumab in intestinal BD patients. Patients with intestinal BD refractory to conventional treatment receiving up to 2 years of adalimumab treatment demonstrated safety outcomes consistent with the known profile of adalimumab, and the treatment led to sustained reduction of clinical and endoscopic disease activity.

Indirect vs direct bonding of mandibular fixed retainers in orthodontic patients: Comparison of retainer failures and posttreatment stability. A 2-year follow-up of a single-center randomized controlled trial.

PubMed

Egli, Fabienne; Bovali, Efstathia; Kiliaridis, Stavros; Cornelis, Marie A

2017-01-01

The objectives of this 2-arm parallel trial were to compare the numbers of failures of mandibular fixed retainers bonded with indirect and direct methods and to investigate the posttreatment changes 2 years after placement. Sixty-four consecutive patients from the postgraduate orthodontic clinic of the University of Geneva in Switzerland were randomly allocated to either an indirect or a traditional direct bonding procedure of a mandibular fixed retainer at the end of their orthodontic treatment (T0). Eligibility criteria were the presence of the 4 mandibular incisors and the 2 mandibular canines, and no active caries, restorations, fractures, or periodontal disease of these teeth. The patients were randomized in blocks of 4 (using an online randomization service) with allocation concealment secured by contacting the sequence generator for assignment. The patients were recalled 12 months and 24 months (T3) after retainer bonding. The main outcome was any first-time failure of retainers (ie, at least 1 composite pad debonded or fractured); unexpected posttreatment changes of the mandibular incisors and canines were a secondary outcome. Impressions and lateral cephalograms were taken at T0 and T3: changes in mandibular intercanine and interpremolar distances and mandibular incisor inclination were assessed. Blinding was applicable for outcome assessment only. The chi-square test and Cox regression were used to compare the survival rates of the retainers bonded with direct and indirect methods. Paired t tests were used to assess differences in intercanine and interpremolar distances and mandibular incisor inclination at T0 and T3. Significance was set at P <0.05. Sixty-four patients were randomized in a 1:1 ratio. One patient dropped out at baseline, and 3 patients did not reach the T3 recall. In 24 of 60 (40%) patients, the fixed retainer failed within 2 years: 13 of 30 (43%) in the indirect bonding group and 11 of 30 (37%) in the direct bonding group (log-rank test, P = 0.64). The hazard ratio was 1.26 (95% confidence interval, 0.56-2.81; P = 0.58). Bond failures occurred mainly during the first year. There were no clinically significant changes in mandibular intercanine distance, interpremolar distance, and incisor inclination between T0 and T3, or between groups. In 5 patients (17%), all in the direct bonding group, unexpected posttreatment changes, systematically consisting in a lingual inclination of the mandibular left canine, were observed. In 1 patient (3%), the change was considered clinically severe. No other serious harm was observed. There was no difference in the risks of failure between mandibular retainers bonded with direct and indirect methods. Bonded retainers are effective in maintaining intercanine and interpremolar distances. There seem to be fewer unexpected posttreatment changes with retainers bonded with the indirect compared with the direct method. The trial was not registered. The protocol was not published before trial commencement. No funding or conflict of interest to be declared. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Exploring learning content and knowledge transfer in baccalaureate nursing students using a hybrid mental health practice experience.

PubMed

Booth, Richard G; Scerbo, Christina Ko; Sinclair, Barbara; Hancock, Michele; Reid, David; Denomy, Eileen

2017-04-01

Little research has been completed exploring knowledge development and transfer from and between simulated and clinical practice settings in nurse education. This study sought to explore the content learned, and the knowledge transferred, in a hybrid mental health clinical course consisting of simulated and clinical setting experiences. A qualitative, interpretive descriptive study design. Clinical practice consisted of six 10-hour shifts in a clinical setting combined with six two-hour simulations. 12 baccalaureate nursing students enrolled in a compressed time frame program at a large, urban, Canadian university participated. Document analysis and a focus group were used to draw thematic representations of content and knowledge transfer between clinical environments (i.e., simulated and clinical settings) using the constant comparative data analysis technique. Four major themes arose: (a) professional nursing behaviors; (b) understanding of the mental health nursing role; (c) confidence gained in interview skills; and, (d) unexpected learning. Nurse educators should further explore the intermingling of simulation and clinical practice in terms of knowledge development and transfer with the goal of preparing students to function within the mental health nursing specialty. Copyright © 2017 Elsevier Ltd. All rights reserved.

A standard-driven approach for electronic submission to pharmaceutical regulatory authorities.

PubMed

Lin, Ching-Heng; Chou, Hsin-I; Yang, Ueng-Cheng

2018-03-01

Using standards is not only useful for data interchange during the process of a clinical trial, but also useful for analyzing data in a review process. Any step, which speeds up approval of new drugs, may benefit patients. As a result, adopting standards for regulatory submission becomes mandatory in some countries. However, preparing standard-compliant documents, such as annotated case report form (aCRF), needs a great deal of knowledge and experience. The process is complex and labor-intensive. Therefore, there is a need to use information technology to facilitate this process. Instead of standardizing data after the completion of a clinical trial, this study proposed a standard-driven approach. This approach was achieved by implementing a computer-assisted "standard-driven pipeline (SDP)" in an existing clinical data management system. SDP used CDISC standards to drive all processes of a clinical trial, such as the design, data acquisition, tabulation, etc. RESULTS: A completed phase I/II trial was used to prove the concept and to evaluate the effects of this approach. By using the CDISC-compliant question library, aCRFs were generated automatically when the eCRFs were completed. For comparison purpose, the data collection process was simulated and the collected data was transformed by the SDP. This new approach reduced the missing data fields from sixty-two to eight and the controlled term mismatch field reduced from eight to zero during data tabulation. This standard-driven approach accelerated CRF annotation and assured data tabulation integrity. The benefits of this approach include an improvement in the use of standards during the clinical trial and a reduction in missing and unexpected data during tabulation. The standard-driven approach is an advanced design idea that can be used for future clinical information system development. Copyright © 2018 Elsevier Inc. All rights reserved.

Medicines and Children

MedlinePlus

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Clinical Evaluation of Hair Removal Using an 810 nm Diode Laser With a Novel Scanning Device.

PubMed

Courtney, Erin; Goldberg, David J

2016-11-01

Diode lasers are often considered as the gold standard preference for hair removal due to the deep penetration and ef- fective targeting of the hair follicle. A wide variety of diode lasers are available, which can differ in terms of their parameters (such as fluence, pulse duration, repetition rate, scanner, and cooling). The objective of the study was to evaluate the safety and ef cacy of hair removal with an 810 nm novel scanning diode laser, up to six months after last treatment. A scanning 810 nm diode laser was used for axillary hair removal of 14 female patients who received 3 treatments, 4-6 weeks apart. Follow-up on hair count was conducted 3 and 6 months after last treatment and compared to baseline hair count. No unexpected or signi cant adverse events were recorded. An average hair count reduction of 72.8% after 3 months and 67.6% 6 months after the last treatment is demonstrated. The examined 810 nm diode laser was proven to be safe and effective for hair removal. Results were sustained for 6 months after last treatment. Longer follow-up data are followed for further substantiation of the clinical effect. Scanning technology can provide for potentially faster and safer treatments. J Drugs Dermatol. 2016;15(11):1330-1333..

Modulation of Intestinal Inflammation by Yeasts and Cell Wall Extracts: Strain Dependence and Unexpected Anti-Inflammatory Role of Glucan Fractions

PubMed Central

Jawhara, Samir; Habib, Khalid; Maggiotto, François; Pignede, Georges; Vandekerckove, Pascal; Maes, Emmanuel; Dubuquoy, Laurent; Fontaine, Thierry; Guerardel, Yann; Poulain, Daniel

2012-01-01

Yeasts and their glycan components can have a beneficial or adverse effect on intestinal inflammation. Previous research has shown that the presence of Saccharomyces cerevisiae var. boulardii (Sb) reduces intestinal inflammation and colonization by Candida albicans. The aim of this study was to identify dietary yeasts, which have comparable effects to the anti-C. albicans and anti-inflammatory properties of Sb and to assess the capabilities of yeast cell wall components to modulate intestinal inflammation. Mice received a single oral challenge of C. albicans and were then given 1.5% dextran-sulphate-sodium (DSS) for 2 weeks followed by a 3-day restitution period. S. cerevisiae strains (Sb, Sc1 to Sc4), as well as mannoprotein (MP) and β-glucan crude fractions prepared from Sc2 and highly purified β-glucans prepared from C. albicans were used in this curative model, starting 3 days after C. albicans challenge. Mice were assessed for the clinical, histological and inflammatory responses related to DSS administration. Strain Sc1-1 gave the same level of protection against C. albicans as Sb when assessed by mortality, clinical scores, colonization levels, reduction of TNFα and increase in IL-10 transcription. When Sc1-1 was compared with the other S. cerevisiae strains, the preparation process had a strong influence on biological activity. Interestingly, some S. cerevisiae strains dramatically increased mortality and clinical scores. Strain Sc4 and MP fraction favoured C. albicans colonization and inflammation, whereas β-glucan fraction was protective against both. Surprisingly, purified β-glucans from C. albicans had the same protective effect. Thus, some yeasts appear to be strong modulators of intestinal inflammation. These effects are dependent on the strain, species, preparation process and cell wall fraction. It was striking that β-glucan fractions or pure β-glucans from C. albicans displayed the most potent anti-inflammatory effect in the DSS model. PMID:22848391

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype.

PubMed

Kölker, Stefan; Valayannopoulos, Vassili; Burlina, Alberto B; Sykut-Cegielska, Jolanta; Wijburg, Frits A; Teles, Elisa Leão; Zeman, Jiri; Dionisi-Vici, Carlo; Barić, Ivo; Karall, Daniela; Arnoux, Jean-Baptiste; Avram, Paula; Baumgartner, Matthias R; Blasco-Alonso, Javier; Boy, S P Nikolas; Rasmussen, Marlene Bøgehus; Burgard, Peter; Chabrol, Brigitte; Chakrapani, Anupam; Chapman, Kimberly; Cortès I Saladelafont, Elisenda; Couce, Maria L; de Meirleir, Linda; Dobbelaere, Dries; Furlan, Francesca; Gleich, Florian; González, Maria Julieta; Gradowska, Wanda; Grünewald, Stephanie; Honzik, Tomas; Hörster, Friederike; Ioannou, Hariklea; Jalan, Anil; Häberle, Johannes; Haege, Gisela; Langereis, Eveline; de Lonlay, Pascale; Martinelli, Diego; Matsumoto, Shirou; Mühlhausen, Chris; Murphy, Elaine; de Baulny, Hélène Ogier; Ortez, Carlos; Pedrón, Consuelo C; Pintos-Morell, Guillem; Pena-Quintana, Luis; Ramadža, Danijela Petković; Rodrigues, Esmeralda; Scholl-Bürgi, Sabine; Sokal, Etienne; Summar, Marshall L; Thompson, Nicholas; Vara, Roshni; Pinera, Inmaculada Vives; Walter, John H; Williams, Monique; Lund, Allan M; Garcia-Cazorla, Angeles; Garcia Cazorla, Angeles

2015-11-01

The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QTc interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population. Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases.

Low absolute neutrophil counts in African infants.

PubMed

Kourtis, Athena P; Bramson, Brian; van der Horst, Charles; Kazembe, Peter; Ahmed, Yusuf; Chasela, Charles; Hosseinipour, Mina; Knight, Rodney; Lugalia, Lebah; Tegha, Gerald; Joaki, George; Jafali, Robert; Jamieson, Denise J

2005-07-01

Infants of African origin have a lower normal range of absolute neutrophil counts than white infants; this fact, however, remains under appreciated by clinical researchers in the United States. During the initial stages of a clinical trial in Malawi, the authors noted an unexpectedly high number of infants with absolute neutrophil counts that would be classifiable as neutropenic using the National Institutes of Health's Division of AIDS toxicity tables. The authors argue that the relevant Division of AIDS table does not take into account the available evidence of low absolute neutrophil counts in African infants and that a systematic collection of data from many African settings might help establish the absolute neutrophil count cutpoints to be used for defining neutropenia in African populations.

Creating safety by strengthening clinicians' capacity for reflexivity

PubMed Central

2011-01-01

This commentary explores the nature of creating safety in the here-and-now. Creating safety encompasses two dimensions: revisiting specific behaviours by focusing on substandard performance (reflection), and a more broad-ranging attention to everyday behaviours that are taken as given (reflexivity). The piece pays particular attention to this second dimension of creating safety. Two techniques that promote reflexivity are discussed: video-filming real-time, everyday clinical practice and inviting clinicians' feedback about their own footage, and reflecting on the knowledge and questions that patients and families have about their care, and about unexpected outcomes and clinical incidents. The piece concludes that feedback about everyday practice using these methods is critical to enhancing the safety of everyday activity. PMID:21450780

Health-care management of an unexpected case of Ebola virus disease at the Alcorcón Foundation University Teaching Hospital.

PubMed

Rodríguez-Caravaca, Gil; Timermans, Rafael; Parra-Ramírez, Juan Manuel; Domínguez-Hernández, Francisco Javier; Algora-Weber, Alejandro; Delgado-Iribarren, Alberto; Hermida-Gutiérrez, Guillermo

2015-04-01

The first Ebola virus infected patient outside Africa was diagnosed and treated at Alcorcón Foundation University Teaching Hospital (AFUTH). We describe the integrated management strategy (medical, occupational health, preventive and public health) applied to the case. Descriptive study of health-care management of an unexpected case of Ebola virus disease (EVD) at AFUTH treated on 6 October 2014. We describe the clinical evolution of the patient while he was attended at the Emergency Department, the drawing-up process of the action protocol, the process of training of hospital staff, the administrative management for transferring the patient to the referral centre, and the measures implemented for cleaning, disinfection and management of waste. Qualitative variables are expressed as percentages. Our centre designed and updated, from May to October, five versions of the acting and care protocol for patients with EVD. The protocol was in force at the AFUTH when a nursing assistant was attended on 6 October 2014. All preventive, diagnostic and therapeutic measures outlined in the protocol were applied and 206 professionals had received training and information about care procedures with a suspect case. Health-care management of an unexpected case of EVD was adequate and there was no secondary cases in our staff as a result. All resources available should be used to fight EVD. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The role of post-mortem investigations in determining the cause of sudden unexpected death in infancy.

PubMed

Weber, M A; Ashworth, M T; Risdon, R A; Hartley, J C; Malone, M; Sebire, N J

2008-12-01

Several autopsy protocols have been suggested for investigating sudden unexpected deaths in infancy (SUDI). The aim of this study is to provide data on the utility of such post-mortem investigations from a large paediatric autopsy series to inform future policy. Retrospective analysis of >1500 consecutive post-mortem examinations carried out by specialist paediatric pathologists at a single centre during a 10-year period according to a common autopsy protocol that included the use of detailed ancillary investigations. SUDI was defined as the sudden unexpected death of an infant aged from 7 to 365 days. All data capture and cause of death classification were carried out according to defined criteria. Of 1516 paediatric post-mortem examinations, 546 presented as SUDI. In 202 infants (37%), death was explained by the autopsy findings. The other 344 cases (63%) remained unexplained. Of the explained deaths, over half (58%) were infective, most commonly due to pneumonia (22%). The component of the post-mortem examination that primarily determined the final cause of death was histological examination in 92 infants (46%), macroscopic examination in 61 (30%), microbiological investigations in 38 (19%) and clinical history in 10 (5%). This constitutes the largest single-institution autopsy study of SUDI. Ten years on from the Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) SUDI studies, the ascertainment of a cause of death at autopsy has improved. However, with almost two thirds of SUDI remaining unexplained, alternative and/or additional diagnostic techniques are required to improve detection rates of identifiable causes of death at autopsy.

Making psycholinguistics musical: self-paced reading time evidence for shared processing of linguistic and musical syntax.

PubMed

Slevc, L Robert; Rosenberg, Jason C; Patel, Aniruddh D

2009-04-01

Linguistic processing, especially syntactic processing, is often considered a hallmark of human cognition; thus, the domain specificity or domain generality of syntactic processing has attracted considerable debate. The present experiments address this issue by simultaneously manipulating syntactic processing demands in language and music. Participants performed self-paced reading of garden path sentences, in which structurally unexpected words cause temporary syntactic processing difficulty. A musical chord accompanied each sentence segment, with the resulting sequence forming a coherent chord progression. When structurally unexpected words were paired with harmonically unexpected chords, participants showed substantially enhanced garden path effects. No such interaction was observed when the critical words violated semantic expectancy or when the critical chords violated timbral expectancy. These results support a prediction of the shared syntactic integration resource hypothesis (Patel, 2003), which suggests that music and language draw on a common pool of limited processing resources for integrating incoming elements into syntactic structures. Notations of the stimuli from this study may be downloaded from pbr.psychonomic-journals.org/content/supplemental.

Driving performance changes of middle-aged experienced taxi drivers due to distraction tasks during unexpected situations.

PubMed

Kim, Hyung-Sik; Choi, Mi-Hyun; Choi, Jin-Seung; Kim, Hyun-Joo; Hong, Sang-Pyo; Jun, Jae-Hoon; Tack, Gye-Rae; Kim, Boseong; Min, Ung-Chan; Lim, Dae-Woon; Chung, Soon-Cheol

2013-10-01

This study investigated the effects of distraction taskssuch as sending a text message with a cellphone and searching navigation with car navigation system-on the driving performance of 29 highly experienced taxi drivers in their 50s. All participants were instructed to drive using a driving simulator for 2 min. while maintaining a constant distance from the vehicle in front and a constant speed. Participants drove without any distractions for the first minute. For an additional minute, they performed Driving Only or performed a task while driving (Driving + Sending Text Message or Driving + Searching Navigation). An unexpected situation, in which the participant had to stop abruptly due to a sudden stop of the preceding vehicle, occurred during this period. Driving performance during the unexpected situation was evaluated by car control variables, medial-lateral coefficient of variation and brake time, and by motion variables such as the jerk-cost function. Compared to Driving Only, jerk-cost function, medial-lateral coefficient of variation, and brake time increased during Driving + Sending Text Message or Driving + Searching Navigation.

Unexpected inhibition of CO 2 gas hydrate formation in dilute TBAB solutions and the critical role of interfacial water structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Ngoc N.; Nguyen, Anh V.; Nguyen, Khoi T.

Gas hydrates formed under moderated conditions open up novel approaches to tackling issues related to energy supply, gas separation, and CO 2 sequestration. Several additives like tetra-n-butylammonium bromide (TBAB) have been empirically developed and used to promote gas hydrate formation. Here we report unexpected experimental results which show that TBAB inhibits CO 2 gas hydrate formation when used at minuscule concentration. We also used spectroscopic techniques and molecular dynamics simulation to gain further insights and explain the experimental results. They have revealed the critical role of water alignment at the gas-water interface induced by surface adsorption of tetra-n-butylammonium cation (TBAmore » +) which gives rise to the unexpected inhibition of dilute TBAB solution. The water perturbation by TBA + in the bulk is attributed to the promotion effect of high TBAB concentration on gas hydrate formation. We explain our finding using the concept of activation energy of gas hydrate formation. Our results provide a step toward to mastering the control of gas hydrate formation.« less

Integration of a computerized two-finger gripper for robot workstation safety

NASA Technical Reports Server (NTRS)

Sneckenberger, John E.; Yoshikata, Kazuki

1988-01-01

A microprocessor-based controller has been developed that continuously monitors and adjusts the gripping force applied by a special two-finger gripper. This computerized force sensing gripper system enables the endeffector gripping action to be independently detected and corrected. The gripping force applied to a manipulated object is real-time monitored for problem situations, situations which can occur during both planned and errant robot arm manipulation. When unspecified force conditions occur at the gripper, the gripping force controller initiates specific reactions to cause dynamic corrections to the continuously variable gripping action. The force controller for this intelligent gripper has been interfaced to the controller of an industrial robot. The gripper and robot controllers communicate to accomplish the successful completion of normal gripper operations as well as unexpected hazardous situations. An example of an unexpected gripping condition would be the sudden deformation of the object being manipulated by the robot. The capabilities of the interfaced gripper-robot system to apply workstation safety measures (e.g., stop the robot) when these unexpected gripping effects occur have been assessed.

Assessing the influence of a passive, upper extremity exoskeletal vest for tasks requiring arm elevation: Part II - "Unexpected" effects on shoulder motion, balance, and spine loading.

PubMed

Kim, Sunwook; Nussbaum, Maury A; Mokhlespour Esfahani, Mohammad Iman; Alemi, Mohammad Mehdi; Jia, Bochen; Rashedi, Ehsan

2018-03-07

Adopting a new technology (exoskeletal vest designed to support overhead work) in the workplace can be challenging since the technology may pose unexpected safety and health consequences. A prototype exoskeletal vest was evaluated for potential unexpected consequences with a set of evaluation tests for: usability (especially, donning & doffing), shoulder range of motion (ROM), postural control, slip & trip risks, and spine loading during overhead work simulations. Donning/doffing the vest was easily done by a wearer alone. The vest reduced the max. shoulder abduction ROM by ∼10%, and increased the mean center of pressure velocity in the anteroposterior direction by ∼12%. However, vest use had minimal influences on trip-/slip-related fall risks during level walking, and significantly reduced spine loadings (up to ∼30%) especially during the drilling task. Use of an exoskeletal vest can be beneficial, yet the current evaluation tests should be expanded for more comprehensiveness, to enable the safe adoption of the technology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sensorimotor dysfunction of grasping in schizophrenia: a side effect of antipsychotic treatment?

PubMed Central

Nowak, D A; Connemann, B J; Alan, M; Spitzer, M

2006-01-01

Background Antipsychotic treatment in schizophrenia is frequently associated with extrapyramidal side effects. Objective behavioural measures to evaluate the severity of extrapyramidal side effects in the clinical setting do not exist. Objectives This study was designed to investigate grasping movements in five drug naive and 13 medicated subjects with schizophrenia and to compare their performance with that of 18 healthy control subjects. Deficits of grip force performance were correlated with clinical scores of both parkinson‐like motor disability and psychiatric symptom severity Methods Participants performed vertical arm movements with a handheld instrumented object and caught a weight that was dropped into a handheld cup either expectedly from the opposite hand or unexpectedly from the experimenter's hand. The scaling of grip force and the temporospatial coupling between grip and load force profiles was analysed. The psychiatric symptom severity was assessed by the positive and negative symptom score of schizophrenia and the brief psychiatric rating scale. Extrapyramidal symptoms were assessed by the unified Parkinson's disease rating scale. Results Drug naive subjects with schizophrenia performed similar to healthy controls. In contrast, medicated subjects with schizophrenia exhibited excessive grip force scaling and impaired coupling between grip and load force profiles. These performance deficits were strongly correlated with the severity of both extrapyramidal side effects related to antipsychotic therapy and negative symptoms related to the underlying pathology. Conclusions These data provide preliminary evidence that deficits of sensorimotor performance in schizophrenia are, at least in part, related to the side effects of antipsychotic treatment. The investigation of grasping movements may provide a sensitive measure to objectively evaluate extrapyramidal side effects related to antipsychotic therapy. PMID:16614027

Further characterization of the GlyT-1 inhibitor Org25935: anti-alcohol, neurobehavioral, and gene expression effects.

PubMed

Lidö, Helga Höifödt; Jonsson, Susanne; Hyytiä, Petri; Ericson, Mia; Söderpalm, Bo

2017-05-01

The glycine transporter-1 inhibitor Org25935 is a promising candidate in a treatment concept for alcohol use disorder targeting the glycine system. Org25935 inhibits ethanol-induced dopamine elevation in brain reward regions and reduces ethanol intake in Wistar rats. This study aimed to further characterise the compound and used ethanol consumption, behavioral measures, and gene expression as parameters to investigate the effects in Wistar rats and, as pharmacogenetic comparison, Alko-Alcohol (AA) rats. Animals were provided limited access to ethanol in a two-bottle free-choice paradigm with daily drug administration. Acute effects of Org25935 were estimated using locomotor activity and neurobehavioral status. Effects on gene expression in Wistar rats were measured with qPCR. The higher but not the lower dose of Org25935 reduced alcohol intake in Wistar rats. Unexpectedly, Org25935 reduced both ethanol and water intake and induced strong CNS-depressive effects in AA-rats (withdrawn from further studies). Neurobehavioral effects by Org25935 differed between the strains (AA-rats towards sedation). Org25935 did not affect gene expression at the mRNA level in the glycine system of Wistar rats. The data indicate a small therapeutic range for the anti-alcohol properties of Org25935, a finding that may guide further evaluations of the clinical utility of GlyT-1 inhibitors. The results point to the importance of pharmacogenetic considerations when developing drugs for alcohol-related medical concerns. Despite the lack of successful clinical outcomes, to date, the heterogeneity of drug action of Org25935 and similar agents and the unmet medical need justify further studies of glycinergic compounds in alcohol use disorder.

The Impact of Disulfiram Treatment on the Reinforcing Effects of Cocaine: A Randomized Clinical Trial

PubMed Central

Haile, Colin N.; De La Garza, Richard; Mahoney, James J.; Nielsen, David A.; Kosten, Thomas R.; Newton, Thomas F.

2012-01-01

Background Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users. Methods Seventeen non-treatment seeking, cocaine-dependent volunteers participated in this double-blind, placebo-controlled, laboratory-based study. A cross-over design was utilized in which participants received placebo in one phase and disulfiram (250 mg/d) in the other. Following three days of study medication participants completed two choice sessions. In one they made 10 choices between receiving an intravenous infusion of saline or money that increased in value (US$ 0.05–16) and in the other cocaine (20 mg) or money. Results Participants chose cocaine more than saline under both disulfiram and placebo conditions (p<0.05). Unexpectedly, disulfiram increased both the number of cocaine and saline infusion choices (p<0.05). We next examined the relationship between disulfiram dose and cocaine choices. Disulfiram dose (mg/kg bodyweight) was negatively correlated with number of choices for cocaine (p<0.05). Disulfiram also enhanced cocaine-induced increases in cardiovascular measures (p's<0.05–0.01). Conclusions Disulfiram's impact on the reinforcing effects of cocaine depends on dose relative to body weight. Our results suggest that the use of weight-based medication doses would produce more reliable effects, consistent with weight-based dosing used in pediatrics and in preclinical research. Trial Registration Clinicaltrials.gov NCT00729300 PMID:23144826

Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials.

PubMed

Will, Elke; Bailey, Jeff; Schuesler, Todd; Modlich, Ute; Balcik, Brenden; Burzynski, Ben; Witte, David; Layh-Schmitt, Gerlinde; Rudolph, Cornelia; Schlegelberger, Brigitte; von Kalle, Christof; Baum, Christopher; Sorrentino, Brian P; Wagner, Lars M; Kelly, Patrick; Reeves, Lilith; Williams, David A

2007-04-01

Although retroviral vectors are one of the most widely used vehicles for gene transfer, there is no uniformly accepted pre-clinical model defined to assess their safety, in particular their risk related to insertional mutagenesis. In the murine pre-clinical study presented here, 40 test and 10 control mice were transplanted with ex vivo manipulated bone marrow cells to assess the long-term effects of the transduction of hematopoietic cells with the retroviral vector MSCV-MGMT(P140K)wc. Test mice had significant gene marking 8-12 months post-transplantation with an average of 0.93 vector copies per cell and 41.5% of peripheral blood cells expressing the transgene MGMT(P140K), thus confirming persistent vector expression. Unexpectedly, six test mice developed malignant lymphoma. No vector was detected in the tumor cells of five animals with malignancies, indicating that the malignancies were not caused by insertional mutagenesis or MGMT(P140K) expression. Mice from a concurrent study with a different transgene also revealed additional cases of vector-negative lymphomas of host origin. We conclude that the background tumor formation in this mouse model complicates safety determination of retroviral vectors and propose an improved study design that we predict will increase the relevance and accuracy of interpretation of pre-clinical mouse studies.

Update in cardiology: vascular risk and cardiac rehabilitation.

PubMed

Galve, Enrique; Alegría, Eduardo; Cordero, Alberto; Fácila, Lorenzo; Fernández de Bobadilla, Jaime; Lluís-Ganella, Carla; Mazón, Pilar; de Pablo Zarzosa, Carmen; González-Juanatey, José Ramón

2014-03-01

Cardiovascular disease develops in a slow and subclinical manner over decades, only to manifest suddenly and unexpectedly. The role of prevention is crucial, both before and after clinical appearance, and there is ample evidence of the effectiveness and usefulness of the early detection of at-risk individuals and lifestyle modifications or pharmacological approaches. However, these approaches require time, perseverance, and continuous development. The present article reviews the developments in 2013 in epidemiological aspects related to prevention, includes relevant contributions in areas such as diet, weight control methods (obesity is now considered a disease), and physical activity recommendations (with warnings about the risk of strenuous exercise), deals with habit-related psychosocial factors such as smoking, provides an update on emerging issues such as genetics, addresses the links between cardiovascular disease and other pathologies such as kidney disease, summarizes the contributions of new, updated guidelines (3 of which have recently been released on topics of considerable clinical importance: hypertension, diabetes mellitus, and chronic kidney disease), analyzes the pharmacological advances (largely mediocre except for promising lipid-related results), and finishes by outlining developments in the oft-neglected field of cardiac rehabilitation. This article provides a briefing on controversial issues, presents interesting and somewhat surprising developments, updates established knowledge with undoubted application in clinical practice, and sheds light on potential future contributions. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

[Manufacture of autologous serum eye drops for out-patient therapy : cooperation between ophthalmic clinic and transfusion medicine department].

PubMed

Dietrich, T; Weisbach, V; Seitz, B; Jacobi, C; Kruse, F E; Eckstein, R; Cursiefen, C

2008-11-01

Autologous serum eye drops are an important therapy option in severe ocular surface disorders and the therapeutic effectiveness has been demonstrated in many clinical studies. The production and use of autologous serum eye drops is strictly controlled by legal regulations in Germany: Both the German Medicines Act (AMG) and the Blood Transfusion Act regulate production, distribution and application, unless it is carried out by one person under controlled conditions in a hospital setting. In cooperation with the ophthalmic clinic and the department of transfusion medicine, a standard operating procedure (SOP) was developed and a license for production and delivery of autologous serum eye drops was obtained from the appropriate local authorities. The experiences of the first two years of practice were analyzed. By an interfaculty cooperation, the possibility of legal and feasible out-patient treatment with autologous eye drops has been established at the University Hospital Erlangen. From 07/2005 to 07/2007, there ware 240 prescriptions for autologous serum eye drops. Unexpectedly, a relatively high rate (3.3%) of patients with primarily unknown viral or bacterial infectious diseases were found, which were diagnosed during the screening. These patients had to be excluded from autologous serum eye drop therapy. The treatment with autologous serum eye drops in an out-patient setting is possible, when the infrastructure for manufacture and delivery is provided in accordance with existing regulations.

Integrating Social Media and Mobile Sensor Data for Clinical Decision Support: Concept and Requirements.

PubMed

Denecke, Kerstin

2016-01-01

Social media are increasingly used by individuals for the purpose of collecting data and reporting on the personal health status, on health issues, symptoms and experiences with treatments. Beyond, fitness trackers are more used by individuals to monitor their fitness and health. The health data that is becoming available due to these developments could provide a valuable source for continuous health monitoring, prevention of unexpected health events and clinical decision making since it gives insights into behavior and life habits. However, an integration of the data is challenging. This paper aims triggering the discussion about this current topic. We present a concept for integrating social media data with mobile sensor data and clinical data using digital patient modelling. Further, we collect requirements and challenges for a possible realization of the concept. Challenges include the data volume, reliability and semantic interoperability.

[Assessment of SUSARs. Clinical evaluation of single cases in terms of regulatory requirements].

PubMed

Wroblewski, H; Schmickler, M

2005-04-01

In the course of implementing the European directives on pharmaceutical law, focus is set on suspected unexpected serious adverse reactions (SUSARs). SUSARs are essential for expedited reporting to authorities and ethics committees. During on-line monitoring of the study, the investigator documents all adverse events. Serious adverse events are forwarded to the sponsor in due time. The sponsor identifies SUSARs for expedited reporting. Clinical causality assessment between the investigational product and the adverse event is substantial in this process. This requires a balanced clinical assessment of all case relevant aspects and information available reflecting the complexity of the specific case, which cannot be covered by algorithms in general. In the setting of on-line monitoring, SUSARs ensure the safety of the patient and the study. In addition, SUSARs are relevant for generation of the safety profile of the substance.

Sudden unexpected death under acute influence of cannabis.

PubMed

Hartung, Benno; Kauferstein, Silke; Ritz-Timme, Stefanie; Daldrup, Thomas

2014-04-01

The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

WE-G-209-03: PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kemp, B.

2016-06-15

Digital radiography, CT, PET, and MR are complicated imaging modalities which are composed of many hardware and software components. These components work together in a highly coordinated chain of events with the intent to produce high quality images. Acquisition, processing and reconstruction of data must occur in a precise way for optimum image quality to be achieved. Any error or unexpected event in the entire process can produce unwanted pixel intensities in the final images which may contribute to visible image artifacts. The diagnostic imaging physicist is uniquely qualified to investigate and contribute to resolution of image artifacts. This coursemore » will teach the participant to identify common artifacts found clinically in digital radiography, CT, PET, and MR, to determine the causes of artifacts, and to make recommendations for how to resolve artifacts. Learning Objectives: Identify common artifacts found clinically in digital radiography, CT, PET and MR. Determine causes of various clinical artifacts from digital radiography, CT, PET and MR. Describe how to resolve various clinical artifacts from digital radiography, CT, PET and MR.« less

WE-G-209-02: CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kofler, J.

2016-06-15

Digital radiography, CT, PET, and MR are complicated imaging modalities which are composed of many hardware and software components. These components work together in a highly coordinated chain of events with the intent to produce high quality images. Acquisition, processing and reconstruction of data must occur in a precise way for optimum image quality to be achieved. Any error or unexpected event in the entire process can produce unwanted pixel intensities in the final images which may contribute to visible image artifacts. The diagnostic imaging physicist is uniquely qualified to investigate and contribute to resolution of image artifacts. This coursemore » will teach the participant to identify common artifacts found clinically in digital radiography, CT, PET, and MR, to determine the causes of artifacts, and to make recommendations for how to resolve artifacts. Learning Objectives: Identify common artifacts found clinically in digital radiography, CT, PET and MR. Determine causes of various clinical artifacts from digital radiography, CT, PET and MR. Describe how to resolve various clinical artifacts from digital radiography, CT, PET and MR.« less

WE-G-209-04: MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pooley, R.

2016-06-15

Digital radiography, CT, PET, and MR are complicated imaging modalities which are composed of many hardware and software components. These components work together in a highly coordinated chain of events with the intent to produce high quality images. Acquisition, processing and reconstruction of data must occur in a precise way for optimum image quality to be achieved. Any error or unexpected event in the entire process can produce unwanted pixel intensities in the final images which may contribute to visible image artifacts. The diagnostic imaging physicist is uniquely qualified to investigate and contribute to resolution of image artifacts. This coursemore » will teach the participant to identify common artifacts found clinically in digital radiography, CT, PET, and MR, to determine the causes of artifacts, and to make recommendations for how to resolve artifacts. Learning Objectives: Identify common artifacts found clinically in digital radiography, CT, PET and MR. Determine causes of various clinical artifacts from digital radiography, CT, PET and MR. Describe how to resolve various clinical artifacts from digital radiography, CT, PET and MR.« less

Designing a critical care nurse-led rapid response team using only available resources: 6 years later.

PubMed

Mitchell, Anne; Schatz, Marilyn; Francis, Heather

2014-06-01

Rapid response teams have been introduced to intervene in the care of patients whose condition deteriorates unexpectedly by bringing clinical experts quickly to the patient's bedside. Evidence supporting the need to overcome failure to deliver optimal care in hospitals is robust; whether rapid response teams demonstrate benefit by improving patient safety and reducing the occurrence of adverse events remains controversial. Despite inconsistent evidence regarding the effectiveness of rapid response teams, concerns regarding care and costly consequences of unaddressed deterioration in patients' condition have prompted many hospitals to implement rapid response teams as a patient safety strategy. A cost-neutral structure for a rapid response team led by a nurse from the intensive care unit was implemented with the goal of reducing cardiopulmonary arrests occurring outside the intensive care unit. The results of 6 years' experience indicate that a sustainable and effective rapid response team response can be put into practice without increasing costs or adding positions and can decrease the percentage of cardiopulmonary arrests occurring outside the intensive care unit. ©2014 American Association of Critical-Care Nurses.

Zolpidem-induced sleepwalking, sleep related eating disorder, and sleep-driving: fluorine-18-flourodeoxyglucose positron emission tomography analysis, and a literature review of other unexpected clinical effects of zolpidem.

PubMed

Hoque, Romy; Chesson, Andrew L

2009-10-15

Zolpidem is a hypnotic which acts at the GABAA receptor and is indicated for short-term insomnia. Sleep related disorders including somnambulism, sleep related eating and sleep-driving have been reported with zolpidem. A 51-year-old insomniac who used zolpidem 10 mg nightly starting at 44 years of age is described. A few weeks after starting zolpidem she began walking, eating, and had one episode of driving while asleep. Episodes of sleep related eating, sleepwalking, and sleeptalking occurred 3 nights per week, 1 to 2 h after sleep onset. After her evaluation, the patient's zolpidem was gradually discontinued, and all sleep related activities immediately ceased. An 18F-FDG-PET was obtained 2 months after discontinuation of zolpidem. The following day, FDG was administered 1 h after oral administration of 10 mg zolpidem, and then a second PET was performed. We report the results and a review of the literature regarding other unintended effects seen with zolpidem use.

3 CFR - Unexpected Urgent Refugee and Migration Needs

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Unexpected Urgent Refugee and Migration Needs... Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the authority vested...) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended, (22 U.S.C. 2601(c)(1...

3 CFR - Unexpected Urgent Refugee and Migration Needs

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Unexpected Urgent Refugee and Migration Needs Presidential Documents Other Presidential Documents Presidential Determination No. 2012-6 of April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the authority vested in me as President by the Constitution...

77 FR 21389 - Unexpected Urgent Refugee and Migration Needs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the... 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the ``Act''), as amended, (22 U.S.C... United States Emergency Refugee and Migration Assistance Fund, for the purpose of meeting unexpected and...

Inattentional blindness in older adults: Effects of attentional set and to-be-ignored distractors.

PubMed

Horwood, Sally; Beanland, Vanessa

2016-04-01

Inattentional blindness (IB) involves failing to detect an unexpected visual stimulus while undertaking another task. Previous research has predominantly investigated IB using young adult samples, with few studies exploring whether or how an observer's age affects their detection of unexpected events. To help address this gap, we compared younger adults (18-25 years of age) and older adults (60-80 years of age) on two IB tasks: one dynamic, one static. In the static task, older age was associated with substantially increased IB rates: 89 % for older adults versus 5 % for younger adults. In the dynamic task, we systematically manipulated the presence of to-be-ignored distractors and whether the unexpected stimulus color matched the observers' attentional set. We found a main effect of age on IB: As in the static task, older age was associated with increased IB rates (38 % for older adults vs. 8 % for younger adults). The presence of to-be-ignored distractors and attentional set mismatch interacted to substantially increase IB rates, but age did not interact with either factor. Overall, the results indicate that older age is associated with large increases in IB rates across a range of tasks. The pattern of results is consistent with attentional capacity models of cognitive aging, suggesting that older adults' reduced cognitive resources result in failure to consciously process stimuli that are inconsistent with their attentional set.

Light-controlled inhibition of malignant glioma by opsin gene transfer

PubMed Central

Yang, F; Tu, J; Pan, J-Q; Luo, H-L; Liu, Y-H; Wan, J; Zhang, J; Wei, P-F; Jiang, T; Chen, Y-H; Wang, L-P

2013-01-01

Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach. PMID:24176851

Light-controlled inhibition of malignant glioma by opsin gene transfer.

PubMed

Yang, F; Tu, J; Pan, J-Q; Luo, H-L; Liu, Y-H; Wan, J; Zhang, J; Wei, P-F; Jiang, T; Chen, Y-H; Wang, L-P

2013-10-31

Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach.

Unexpected lower testosterone in faster growing farmed saltwater crocodile (Crocodylus porosus) hatchlings.

PubMed

Finger, John W; Thomson, Peter C; Isberg, Sally R

2016-01-15

Agricultural production of the saltwater crocodile (Crocodylus porosus) is an emergent industry in northern Australia with many of the factors affecting production remaining unknown. In this study, we sought to expand upon our previous findings of reference corticosterone and immune function by reporting baseline sex hormone levels [testosterone (TEST) and estradiol (ESTR)] and their association with growth. This was achieved by sampling 253 hatchling crocodiles repeatedly at 3, 6, and 9months of age. Sampling age had a significant effect on both TEST (p<0.001) and ESTR (p<0.001) suggesting climatic/abiotic factors have an influence even in prepubescent crocodiles. Stress, as measured by plasma corticosterone, had no detectable effect on plasma ESTR or TEST levels. Unexpectedly however, TEST was higher in slower-growing crocodiles, which is contrary to what has been reported for the American alligator. ESTR was not associated with growth. Copyright © 2015 Elsevier Inc. All rights reserved.

Causes of death after fluid bolus resuscitation: new insights from FEAST.

PubMed

Myburgh, John; Finfer, Simon

2013-03-14

The Fluid Expansion as Supportive Therapy (FEAST study) was an extremely well conducted study that gave unexpected results. The investigators had reported that febrile children with impaired perfusion treated in low-income countries without access to intensive care are more likely to die if they receive bolus resuscitation with albumin or saline compared with no bolus resuscitation at all. In a secondary analysis of the trial, published in BMC Medicine, the authors found that increased mortality was evident in patients who presented with clinical features of severe shock in isolation or in conjunction with features of respiratory or neurological failure. The cause of excess deaths was primarily refractory shock and not fluid overload. These features are consistent with a potential cardiotoxic or ischemia-reperfusion injury following resuscitation with boluses of intravenous fluid. Although these effects may have been amplified by the absence of invasive monitoring, mechanical ventilation or vasopressors, the results provide compelling insights into the effects of intravenous fluid resuscitation and potential adverse effects that extend beyond the initial resuscitation period. These data add to the increasing body of literature about the safety and efficacy of intravenous resuscitation fluids, which may be applicable to management of other populations of critically ill patients.

Diabetes and the Motivated Patient: Understanding Perlocutionary Effect in Health Communication.

PubMed

Roth, Erin G; Girling, Laura M; Chard, Sarah; Wallace, Brandy Harris; Eckert, J Kevin

2017-04-01

Health care providers (HCP) understand the importance of keeping patients motivated but may be unaware how their words may have unintended negative effects upon their patient's lives. People with diabetes report being told by their HCP that they are "cured" or that they are praised for strides made in weight loss and/or lowered blood glucose, and interpret these messages in unexpected ways. For this paper, we focus upon one case to illustrate the depth and nuance of the patient-provider communication as it emerged within a larger interview-based ethnographic study. Audio-recorded interviews and transcriptions were analyzed discursively. Discourse analysis reveals the ways ideology affects how the patient responds to HCP's utterances and how this affects diabetes self-care. Findings indicate significant perlocutionary effects upon health outcomes, varying both positively and/or negatively. This study points to the importance of carefully considering the power of words and whenever possible knowing the patient's ideological orientation to their world. HCPs should be explicit and deliberate with their communication. Sensitization to the various ways patients hear and react to messages in a clinical setting may lead to improved health outcomes, especially for those with chronic health conditions such as diabetes mellitus.

Distraction and Facilitation--Two Faces of the Same Coin?

ERIC Educational Resources Information Center

Wetzel, Nicole; Widmann, Andreas; Schroger, Erich

2012-01-01

Unexpected and task-irrelevant sounds can capture our attention and may cause distraction effects reflected by impaired performance in a primary task unrelated to the perturbing sound. The present auditory-visual oddball study examines the effect of the informational content of a sound on the performance in a visual discrimination task. The…

An Unexpected Effect: Restitution Maintains Object Throwing.

ERIC Educational Resources Information Center

Jensen, Mary

1988-01-01

This study examined effects of restitution on object throwing behavior of an adolescent male with severe mental retardation. Restitution was shown to maintain throwing behavior. When the subject was not forced to pick up what he threw (no restitution), throwing dropped to zero and was maintained at a very low rate. (Author/PB)

An Unexpected Heat Engine

ERIC Educational Resources Information Center

Trout, K. P.; Gaston, Charles A.

2012-01-01

It's common knowledge that light can produce chemical and electronic changes (photography is based on those effects); however, many people consider light to have no mechanical effect. Some are familiar with the novelty of a radiometer that spins when placed in the light. Fewer are aware that a cymbal will vibrate audibly if hit by the light from a…

Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators

PubMed Central

Flierl, Ulrike; Nero, Tracy L.; Lim, Bock; Arthur, Jane F.; Yao, Yu; Jung, Stephanie M.; Gitz, Eelo; Pollitt, Alice Y.; Zaldivia, Maria T.K.; Jandrot-Perrus, Martine; Schäfer, Andreas; Nieswandt, Bernhard; Andrews, Robert K.; Parker, Michael W.; Gardiner, Elizabeth E.

2015-01-01

Nucleotide-based drug candidates such as antisense oligonucleotides, aptamers, immunoreceptor-activating nucleotides, or (anti)microRNAs hold great therapeutic promise for many human diseases. Phosphorothioate (PS) backbone modification of nucleotide-based drugs is common practice to protect these promising drug candidates from rapid degradation by plasma and intracellular nucleases. Effects of the changes in physicochemical properties associated with PS modification on platelets have not been elucidated so far. Here we report the unexpected binding of PS-modified oligonucleotides to platelets eliciting strong platelet activation, signaling, reactive oxygen species generation, adhesion, spreading, aggregation, and thrombus formation in vitro and in vivo. Mechanistically, the platelet-specific receptor glycoprotein VI (GPVI) mediates these platelet-activating effects. Notably, platelets from GPVI function–deficient patients do not exhibit binding of PS-modified oligonucleotides, and platelet activation is fully abolished. Our data demonstrate a novel, unexpected, PS backbone–dependent, platelet-activating effect of nucleotide-based drug candidates mediated by GPVI. This unforeseen effect should be considered in the ongoing development programs for the broad range of upcoming and promising DNA/RNA therapeutics. PMID:25646267

Recent advances in and limitations of cardiac output monitoring by means of electrical impedance tomography.

PubMed

Pikkemaat, Robert; Lundin, Stefan; Stenqvist, Ola; Hilgers, Ralf-Dieter; Leonhardt, Steffen

2014-07-01

Currently, the monitoring of cardiac output (CO) and stroke volume (SV) is mainly performed using invasive techniques. Therefore, performing CO monitoring noninvasively by means of electrical impedance tomography (EIT) would be advantageous for intensive care. Our hypothesis was that, by means of EIT, it is possible to assess heart rate (HR) and to quantify changes in SV due to changes in ventilator settings. CO (HR and SV) of 14 pigs (32-40 kg body weight) was changed by incremental increases in positive end-expiratory pressure levels (0, 5, 10, 15, and 20 cm·H2O; ramp maneuver). This ramp maneuver was applied 4 times in each animal, yielding 43 evaluable single experiments. At each positive end-expiratory pressure level, SV was assessed by transpulmonary thermodilution using a PiCCO device. EIT data were acquired using a Dräger EIT Evaluation Kit 2. The EIT-based SV-related signal, Z(SV) (in [AU]), showed only a weak correlation (after excluding 2 measurements) with SV(TTD) of r = 0.58 (95% confidence interval, 0.43-0.71). If Z(SV) is calibrated by the reference 1 time for each experiment (defined as SVEIT), the correlation is approximately 0.85 (95% confidence interval, 0.78-0.90). A possible reason for the moderate correlation is the unexpected scaling pattern, leading to amplification of the cardiac impedance signal, found in some animals. The scaling is probably due to the imperfect reconstruction (i.e., a change of sensitivity) of the EIT images or to a change in the position of the heart. The hypothesis that EIT can be used to monitor CO and SV was confirmed, but further studies are required before this technique can be applied in clinical practice. HR was determined robustly and accurately. For SV monitoring, promising results were obtained in 80% of the experiments. However, unexpected scaling of the cardiac EIT signal causing inaccurate estimation of SV remains an issue. Before robust assessment of SV by EIT is suitable for clinical practice, the cause of and compensation for undesired scaling effects need to be investigated.

3 CFR - Unexpected Urgent Refugee and Migration Needs Relating to Syria

Code of Federal Regulations, 2014 CFR

2014-01-01

... 3 The President 1 2014-01-01 2014-01-01 false Unexpected Urgent Refugee and Migration Needs Relating to Syria Presidential Documents Other Presidential Documents Presidential Determination No. 2013-4 of January 29, 2013 Unexpected Urgent Refugee and Migration Needs Relating to Syria Memorandum for the Secretary of State By the authority vested i...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Libya

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Libya Presidential Documents Other Presidential Documents Presidential Determination No. 2011-8 of March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya Memorandum for the Secretary of State By the authority vested in me...

3 CFR - Unexpected Urgent Refugee and Migration Needs Resulting from Flooding in Pakistan

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... Determination No. 2010-14 of September 3, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from... the Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

3 CFR - Unexpected Urgent Refugee and Migration Needs Resulting from Violence in Kyrgyzstan

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... Determination No. 2010-12 of August 26, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from... the Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

Effects of anxiety sensitivity and expectations on the modulation of the startle eyeblink response during a caffeine challenge.

PubMed

Benke, Christoph; Blumenthal, Terry D; Modeß, Christiane; Hamm, Alfons O; Pané-Farré, Christiane A

2015-09-01

The way in which the tendency to fear somatic arousal sensations (anxiety sensitivity), in interaction with the created expectations regarding arousal induction, might affect defensive responding to a symptom provocation challenge is not yet understood. The present study investigated the effect of anxiety sensitivity on autonomic arousal, startle eyeblink responses, and reported arousal and alertness to expected vs. unexpected caffeine consumption. To create a match/mismatch of expected and experienced arousal, high and low anxiety sensitive participants received caffeine vs. no drug either mixed in coffee (expectation of arousal induction) or in bitter lemon soda (no expectation of arousal induction) on four separate occasions. Autonomic arousal (heart rate, skin conductance level), respiration (end-tidal CO2, minute ventilation), defensive reflex responses (startle eyeblink), and reported arousal and alertness were recorded prior to, immediately and 30 min after beverage ingestion. Caffeine increased ventilation, autonomic arousal, and startle response magnitudes. Both groups showed comparable levels of autonomic and respiratory responses. The startle eyeblink responses were decreased when caffeine-induced arousal occurred unexpectedly, e.g., after administering caffeine in bitter lemon. This effect was more accentuated in high anxiety sensitive persons. Moreover, in high anxiety sensitive persons, the expectation of arousal (coffee consumption) led to higher subjective alertness when administering caffeine and increased arousal even if no drug was consumed. Unexpected symptom provocation leads to increased attention allocation toward feared arousal sensations in high anxiety sensitive persons. This finding broadens our understanding of modulatory mechanisms in defensive responding to bodily symptoms.

Adaptation of muscles of the lumbar spine to sudden imbalance in patients with lower back pain caused by military training.

PubMed

Gao, Ying; Shi, Jian-guo; Ye, Hong; Liu, Zhi-rong; Zheng, Long-bao; Ni, Zhi-ming; Fan, Liang-quan; Wang, Jian; Hou, Zhen-hai

2014-11-01

This study aims to investigate the effects of sudden load changes (expected and unexpected imbalance) on the activity of muscles of the lumbar spine and their central motor control strategy in military personnel with or without chronic low back pain (LBP). Bilateral sudden imbalance was examined (2 × 2 factorial design). The 117th PLA Hospital, Hangzhou, China Twenty-one male subjects with lower back pain and 21 male healthy control subjects were active members of the Nanjing Military Region land forces. Independent variables: LBP vs. healthy controls and imbalance anticipation (expected and unexpected imbalance). rapid reaction time (RRT) and intensity of rapid reaction (IRR) of bilateral lumbar (L3-L4) erector spinae (ES), lumbar (L5-S1) multifidus (MF), and abdominal external oblique muscles. Results Under expected or unexpected sudden imbalance conditions, subjects with LBP demonstrated significantly greater IRR than healthy controls in ipsilateral and contralateral ES and MF, respectively (P < 0.05 for all). IRR of contralateral ES was significantly larger than that of the ipsilateral ES. A significant group effect of RRT of both ipsilateral and contralateral ES muscles and a significant time expectation effect on RRT of contralateral MF muscles were also observed. RRT of the contralateral ES muscles was significantly lower than that of the ipsilateral ES muscles (P < 0.001). Sudden imbalance prolonged RRT of selected trunk muscles in patients with chronic LBP. The activation amplitude increased. The results may provide a theoretical basis for a study on the pathogenesis of chronic LBP.

Anxiety sensitivity and expectation of arousal differentially affect the respiratory response to caffeine.

PubMed

Pané-Farré, Christiane A; Alius, Manuela G; Modeß, Christiane; Methling, Karen; Blumenthal, Terry; Hamm, Alfons O

2015-06-01

This study aimed to test how expectations and anxiety sensitivity influence respiratory and autonomic responses to caffeine. The current study investigated the effects of expected vs. unexpected caffeine ingestion in a group of persons prone to the anxiety-provoking effect of caffeine (high anxiety sensitive persons, that is, persons scoring at least one SD above the mean on the Anxiety Sensitivity Index (Peterson and Reiss 1992)) as compared to low-anxious controls. Autonomic arousal (heart rate, skin conductance level), respiratory responding (expired CO2, minute ventilation), and subjective report were assessed in high and low anxiety sensitive participants immediately after beverage consumption and at absorption peak (30 min post-consumption) in four separate sessions during which either coffee (expectation of caffeine) or bitter lemon soda (no expectation of caffeine) was crossed with 4 mg/kg caffeine vs. no drug. High and low anxiety sensitive persons showed comparable autonomic arousal and symptom reports to caffeine which was modulated by expectation, i.e., greater for coffee. Respiratory responding (CO2 decrease, minute ventilation increase) was more accentuated when caffeine was both expected and administered in the low anxiety sensitive group but more accentuated when caffeine was unexpectedly administered in the high anxiety sensitive group. Autonomic arousal and respiratory effects were observable within a few minutes after caffeine administration and were most pronounced at maximum absorption. The results highlight the modulating role of expectancies in respiratory responding to caffeine in low vs. high anxiety sensitive persons and might have important implications for the better understanding of unexpected panic attacks.

Should I stay or should I go? Attentional disengagement from visually unique and unexpected items at fixation.

PubMed

Brockmole, James R; Boot, Walter R

2009-06-01

Distinctive aspects of a scene can capture attention even when they are irrelevant to one's goals. The authors address whether visually unique, unexpected, but task-irrelevant features also tend to hold attention. Observers searched through displays in which the color of each item was irrelevant. At the start of search, all objects changed color. Critically, the foveated item changed to an unexpected color (it was novel), became a color singleton (it was unique), or both. Saccade latency revealed the time required to disengage overt attention from this object. Singletons resulted in longer latencies, but only if they were unexpected. Conversely, unexpected items only delayed disengagement if they were singletons. Thus, the time spent overtly attending to an object is determined, at least in part, by task-irrelevant stimulus properties, but this depends on the confluence of expectation and visual salience. (c) 2009 APA, all rights reserved.

Reflections on a Time-Limited Mother-Baby Yoga Program at the Wee Ones Nursery

ERIC Educational Resources Information Center

Pickholtz, Naomi

2012-01-01

This brief article discusses a yoga program offered to mothers and babies who were participating in a prison nursery. The author describes the goals and the sometimes unexpected effects of the program.

[Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)].

PubMed

Eckhardt, K; Cremer-Schaeffer, P; König, J; Paeschke, N

2005-02-01

With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member states.

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire Presidential Documents Other Presidential Documents Presidential Determination No. 2011-7 of March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire Memorandum for the Secretary of State By the...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa Presidential Documents Other Presidential Documents Presidential Determination No. 2011-12 of August 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa Memorandum for the Secretary of State By...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks for...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... 8, 2010 Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks... section 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended, (22 U.S.C...

Investigating Teachers' Appraisal of Unexpected Moments and Underlying Values: An Exploratory Case in the Context of Changing Mathematics Classroom Discourse

ERIC Educational Resources Information Center

Cavanna, Jillian M.; Herbel-Eisenmann, Beth; Seah, Wee Tiong

2015-01-01

This article provides an exploratory case study that examines what one teacher indicated as unexpected as she worked to become more purposeful about her classroom discourse practices. We found that she highlighted three areas as being unexpected: (1) aspects of lesson enactment; (2) characteristics of student learning and (3) her own…

The detection of faked identity using unexpected questions and mouse dynamics.

PubMed

Monaro, Merylin; Gamberini, Luciano; Sartori, Giuseppe

2017-01-01

The detection of faked identities is a major problem in security. Current memory-detection techniques cannot be used as they require prior knowledge of the respondent's true identity. Here, we report a novel technique for detecting faked identities based on the use of unexpected questions that may be used to check the respondent identity without any prior autobiographical information. While truth-tellers respond automatically to unexpected questions, liars have to "build" and verify their responses. This lack of automaticity is reflected in the mouse movements used to record the responses as well as in the number of errors. Responses to unexpected questions are compared to responses to expected and control questions (i.e., questions to which a liar also must respond truthfully). Parameters that encode mouse movement were analyzed using machine learning classifiers and the results indicate that the mouse trajectories and errors on unexpected questions efficiently distinguish liars from truth-tellers. Furthermore, we showed that liars may be identified also when they are responding truthfully. Unexpected questions combined with the analysis of mouse movement may efficiently spot participants with faked identities without the need for any prior information on the examinee.

Looking good or doing better? Patterns of decoupling in the implementation of clinical directorates.

PubMed

Mascia, Daniele; Morandi, Federica; Cicchetti, Americo

2014-01-01

The interest toward hospital restructuring has risen significantly in recent years. In spite of its potential benefits, often organizational restructuring in health care produces unexpected consequences. Extant research suggests that institutional theory provides a powerful theoretical lens through which hospital restructuring can be described and explained. According to this perspective, the effectiveness of change is strongly related to the extent to which innovative arrangements, tools, or practices are adopted and implemented within hospitals. Whenever these new arrangements require a substantial modification of internal processes and practices, resistance to implementation emerges and organizational change is likely to become neutralized. This study analyzes how hospital organizations engage in decoupling by adopting but not implementing a new organizational model named clinical directorate. We collected primary data on the diffusion of the clinical directorate model, which was mandated by law in the Italian National Health Service to improve hospital services. We surveyed the adoption and implementation of the clinical directorate model by monitoring the presence of clinical governance tools (measures for the quality improvement of hospital services) within single directorates. In particular, we compared hospitals that adopted the model before (early adopters) or after (later adopters) the mandate was introduced. Hospitals were engaged in decoupling by adopting the new arrangement but not implementing internal practices and tools for quality improvement. The introduction of the law significantly affected the decoupling, with late-adopter hospitals being less likely to implement the adopted model. The present research shows that changes in quality improvement processes may vary in relation to policy makers' interventions aimed at boosting the adoption of new hospital arrangements. Hospital administrators need to be aware and identify the institutional changes that might be driven by law to be able to react consistently with expectations of policymakers.

Compound Heterozygosity of Dominant and Recessive COL7A Alleles in a Severely Affected Patient with a Family History of Dystrophic Epidermolysis Bullosa: Clinical Findings, Genetic Testing, and Treatment Implications.

PubMed

Watson, Kendra D; Schoch, Jennifer J; Beek, Geoffrey J; Hand, Jennifer L

2017-03-01

An 8-year-old girl born to a family with more than three generations of dominant dystrophic epidermolysis bullosa (DDEB) presented with life-threatening confluent skin erosions, mitten hand deformity, and failure to thrive. Reassessment of her family history and genetic testing showed compound heterozygous COL7A mutations, one inherited from her DDEB-affected mother and one from her unaffected, healthy father. This family illustrates the risk of unexpected, severe, autosomal recessive epidermolysis bullosa (EB) in a family with milder, multigenerational autosomal dominant EB. Clinicians should recognize the clinical spectrum of dystrophic EB and recommend genetic consultation when the phenotype conflicts with family history. © 2017 Wiley Periodicals, Inc.

Korotkoff Sounds - The Improbable also Occurs

PubMed Central

Estañol, Bruno; Delgado, Guillermo; Borgstein, Johannes

2013-01-01

Very few discoveries have had such a large impact on and relevance to clinical medicine as the noninvasive measurement of the diastolic blood pressure. A number of gifted physiologists and clinicians were ineffectively in search of a noninvasive method to determine the diastolic pressure. Nonetheless, the quantification of the diastolic BP was not achieved by any of these clinical or physiological researchers, but by an unlikely and unexpected figure: Nikolai Sergeevich Korotkoff (1874-1920), a young Russian army surgeon, working under precarious conditions in the hardship of diverse wars. It is easy to dismiss the achievement of Korotkoff as a serendipitous discovery, similar to that of Alexander Fleming in the discovery of penicillin. However, Nassim N. Taleb's recent black swan theory may serve to illustrate his discovery in a new and, perhaps, surprising way. PMID:24343557

Benign infantile seizures followed by autistic regression in a boy with 16p11.2 deletion.

PubMed

Milone, Roberta; Valetto, Angelo; Bertini, Veronica; Sicca, Federico

2017-06-01

Benign infantile seizures (BIS) are usually a self-limiting condition, which may be associated with heterozygous mutations in the PRRT2 gene at chromosome 16p11.2. Here, we report a boy with a deletion in 16p11.2, presenting with BIS and typical neurodevelopment in the first year of life, unexpectedly followed by severe autistic regression. 16p11.2 deletions are typically associated with intellectual disability, autism, and language disorders, and only rarely with BIS. This clinical report shows that the neurodevelopmental prognosis in BIS patients may not always be benign, and suggests that array CGH screening should be considered for affected infants in order to rule out deletions at 16p11.2 and long-term clinical follow-up.

[Post-mortem microbiology analysis].

PubMed

Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

2013-12-01

Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. Crown Copyright © 2012. Published by Elsevier Espana. All rights reserved.

Driver response to unexpected situations when using and in-vehicle information system

DOT National Transportation Integrated Search

1999-12-01

This investigation is one of a series of studies aimed at investigating Advanced Traveler Information Systems (ATIS) and Commercial Vehicle Operations (CVO) applications and their effect on driver behavior and performance. A field experiment was cond...

The Next Step: Managing Your District's Technology Operations.

ERIC Educational Resources Information Center

Pereus, Stephen C.

2001-01-01

Discusses benefits and especially risks involved with educational technology: unexpected costs; possible negative effects on student achievement; legal, ethical, and security issues; and resistance to change. Success ensues from providing leadership and vision, updating technology planning, evaluating alternatives, setting standards, involving…

Unexpected Benefits of Reducing Aerosol Cooling Effects

EPA Science Inventory

Impacts of aerosol cooling are not limited to changes in surface temperature since modulation of atmospheric dynamics resulting from the increased stability can deteriorate local air quality and impact human health. Health impacts from two manifestations of the aerosol direct eff...

Monitoring radiation use in cardiac fluoroscopy imaging procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, Nathaniel T.; Steiner, Stefan H.; Smith, Ian R.

2011-01-15

Purpose: Timely identification of systematic changes in radiation delivery of an imaging system can lead to a reduction in risk for the patients involved. However, existing quality assurance programs involving the routine testing of equipment performance using phantoms are limited in their ability to effectively carry out this task. To address this issue, the authors propose the implementation of an ongoing monitoring process that utilizes procedural data to identify unexpected large or small radiation exposures for individual patients, as well as to detect persistent changes in the radiation output of imaging platforms. Methods: Data used in this study were obtainedmore » from records routinely collected during procedures performed in the cardiac catheterization imaging facility at St. Andrew's War Memorial Hospital, Brisbane, Australia, over the period January 2008-March 2010. A two stage monitoring process employing individual and exponentially weighted moving average (EWMA) control charts was developed and used to identify unexpectedly high or low radiation exposure levels for individual patients, as well as detect persistent changes in the radiation output delivered by the imaging systems. To increase sensitivity of the charts, we account for variation in dose area product (DAP) values due to other measured factors (patient weight, fluoroscopy time, and digital acquisition frame count) using multiple linear regression. Control charts are then constructed using the residual values from this linear regression. The proposed monitoring process was evaluated using simulation to model the performance of the process under known conditions. Results: Retrospective application of this technique to actual clinical data identified a number of cases in which the DAP result could be considered unexpected. Most of these, upon review, were attributed to data entry errors. The charts monitoring the overall system radiation output trends demonstrated changes in equipment performance associated with relocation of the equipment to a new department. When tested under simulated conditions, the EWMA chart was capable of detecting a sustained 15% increase in average radiation output within 60 cases (<1 month of operation), while a 33% increase would be signaled within 20 cases. Conclusions: This technique offers a valuable enhancement to existing quality assurance programs in radiology that rely upon the testing of equipment radiation output at discrete time frames to ensure performance security.« less

Test-potentiated learning: three independent replications, a disconfirmed hypothesis, and an unexpected boundary condition.

PubMed

Wissman, Kathryn T; Rawson, Katherine A

2018-04-01

Arnold and McDermott [(2013). Test-potentiated learning: Distinguishing between direct and indirect effects of testing. Journal of Experimental Psychology: Learning, Memory, and Cognition, 39, 940-945] isolated the indirect effects of testing and concluded that encoding is enhanced to a greater extent following more versus fewer practice tests, referred to as test-potentiated learning. The current research provided further evidence for test-potentiated learning and evaluated the covert retrieval hypothesis as an alternative explanation for the observed effect. Learners initially studied foreign language word pairs and then completed either one or five practice tests before restudy occurred. Results of greatest interest concern performance on test trials following restudy for items that were not correctly recalled on the test trials that preceded restudy. Results replicate Arnold and McDermott (2013) by demonstrating that more versus fewer tests potentiate learning when trial time is limited. Results also provide strong evidence against the covert retrieval hypothesis concerning why the effect occurs (i.e., it does not reflect differential covert retrieval during pre-restudy trials). In addition, outcomes indicate that the magnitude of the test-potentiated learning effect decreases as trial length increases, revealing an unexpected boundary condition to test-potentiated learning.

Bromelain has paradoxical effects on blood coagulability: a study using thromboelastography.

PubMed

Kaur, Harmanpreet; Corscadden, Kathryn; Lott, Carlene; Elbatarny, Hisham S; Othman, Maha

2016-10-01

Bromelain is a crude extract from pineapple that is known for a wide array of pharmacological effects including protein digestion, fibrinolytic and anti-immune inflammatory effects and has been popularly used as a phytotherapeutic drug. However, its clinical values and applications remain understudied. The aim of this study was to investigate the effect of bromelain on the coagulability of blood using thromboelastography (TEG). We identified 0.4 U/ml as the minimum concentration of bromelain that results in modification of a normal TEG tracing. We studied the effects of this dose on whole blood samples obtained from normal and hypercoagulable individuals using TEG and evaluated their plasma using conventional tests including prothrombin time (PT) and activated partial thromboplastin time (APTT). We extended this analysis to investigate the effect of bromelain on platelet aggregation in normal blood and on the coagulability of mice blood in vivo in response to a clinically relevant dose injected intraperitoenally. The addition of bromelain ex vivo reduced coagulability of both normal and hypercoagulable blood significantly and resulted in 47 and 22% prolongation of PT and 20 and 10% prolongation of APTT in normal and hypercoagulable samples, respectively and inhibited adenosine di-phosphate (ADP)-induced platelet aggregation by 19%. In vivo, there was a considerable variation in TEG parameters in blood obtained from mice and unexpectedly a paradoxical effect toward hypercoagulability was shown in response to 1.5 mg/kg bromelain injected intraperitoneally into seven different animals. However, these results were not statistically significant when compared with the saline-injected animals. Although the in-vitro findings in this small study indicate a potential anticoagulant effect for bromelain, this needs to be interpreted with caution as neither an oral nor intravenous routes were evaluated. The paradoxical in-vivo data following intraperitoneal administration show the complexity of the effects of bromelain beyond platelets and indicate possible effects on other cells or proteins that require further investigations.

[H1N1 influenza vaccines in Tunisia: efficiency and safety].

PubMed

Chaabane, Amel; Aouam, Karim; Ben Fredj, Nadia; Toumi, Adnen; Braham, Dorra; A Boughattas, Naceur; Chakroun, Mohamed

2011-01-01

We carried out this study in order to evaluate the effectiveness and the safety of the two H1N1 vaccines available in Tunisia: Focetria(®) and Panenza(®). It's a prospective epidemiological study including 601 vaccinated subjects. The vaccine effectiveness was based on the occurrence of flu clinical symptoms after vaccination. The safety was based on the occurrence of unexpected events after vaccines administration. The vaccines imputability was established according to Begaud et al. method. The number of subjects vaccinated by Focetria(®) is more important than Panenza(®). The efficiency of vaccines would be 93.6%. Neither the medical statue nor the type of the vaccine used influence the occurrence of a flu episode after vaccination. We recorded 406 adverse effects (32.4%) with a high score of imputability (I3). Focetria(®) adverse effects were more frequent than Panenza(®) ones (p = 0.009). Almost all adverse events disappeared within few days. The two vaccines used in Tunisia remain enough efficient to face the influenza (H1N1) pandemia and are well tolerated independently of the demographic and pathological statue of the vaccinated person as well as nature of the vaccine used. © 2011 Société Française de Pharmacologie et de Thérapeutique.

[Not Available].

PubMed

Chaabane, Amel; Aouam, Karim; Fredj, Nadia Ben; Toumi, Adnen; Braham, Dorra; Boughattas, Naceur A; Chakroun, Mohamed

2011-01-01

We carried out this study in order to evaluate the effectiveness and the safety of the two H1N1 vaccines available in Tunisia: Focetria® and Panenza®. It's a prospective epidemiological study including 601 vaccinated subjects. The vaccine effectiveness was based on the occurrence of flu clinical symptoms after vaccination. The safety was based on the occurrence of unexpected events after vaccines administration. The vaccines imputability was established according to Begaud et al. The number of subjects vaccinated by Focetria® is more important than Panenza®. The efficiency of vaccines would be 93.6%. Neither the medical statue nor the type of the vaccine used influence the occurrence of a flu episode after vaccination. We recorded 406 adverse effects (32.4%) with a high score of imputability (I3). Focetria® adverse effects were more frequent than Panenza® ones (p=0.009). Almost all adverse events disappeared within few days. The two vaccines used in Tunisia remain enough efficient to face the influenza (H1N1) pandemia and are well tolerated independently of the demographic and pathological statue of the vaccinated person as well as nature of the vaccine used. Copyright © 2011 Société Française de Pharmacologie et de Thérapeutique. Publié par Elsevier Masson SAS.

The semisynthetic flavonoid monoHER sensitises human soft tissue sarcoma cells to doxorubicin-induced apoptosis via inhibition of nuclear factor-κB

PubMed Central

Jacobs, H; Bast, A; Peters, G J; van der Vijgh, W J F; Haenen, G R M M

2011-01-01

Background: Despite therapeutic advances, the prognosis of patients with metastatic soft tissue sarcoma (STS) remains extremely poor. The results of a recent clinical phase II study, evaluating the protective effects of the semisynthetic flavonoid 7-mono-O-(β-hydroxyethyl)-rutoside (monoHER) on doxorubicin-induced cardiotoxicity, suggest that monoHER enhances the antitumour activity of doxorubicin in STSs. Methods: To molecularly explain this unexpected finding, we investigated the effect of monoHER on the cytotoxicity of doxorubicin, and the potential involvement of glutathione (GSH) depletion and nuclear factor-κB (NF-κB) inactivation in the chemosensitising effect of monoHER. Results: MonoHER potentiated the antitumour activity of doxorubicin in the human liposarcoma cell line WLS-160. Moreover, the combination of monoHER with doxorubicin induced more apoptosis in WLS-160 cells compared with doxorubicin alone. MonoHER did not reduce intracellular GSH levels. On the other hand, monoHER pretreatment significantly reduced doxorubicin-induced NF-κB activation. Conclusion: These results suggest that reduction of doxorubicin-induced NF-κB activation by monoHER, which sensitises cancer cells to apoptosis, is involved in the chemosensitising effect of monoHER in human liposarcoma cells. PMID:21245867

A Healthy Balance of Plasma Cholesterol by a Novel Annurca Apple-Based Nutraceutical Formulation: Results of a Randomized Trial.

PubMed

Tenore, Gian Carlo; Caruso, Domenico; Buonomo, Giuseppe; D'Avino, Maria; Campiglia, Pietro; Marinelli, Luciana; Novellino, Ettore

2017-03-01

Cardiovascular diseases are nowadays preferential targets of preventive medicine through a straightforward therapy on lipid profile. However, statins, the first-line lipid-lowering drug therapy, specifically act on low-density lipoprotein cholesterol (LDL-C), having a modest effect on plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Today, a number of novel HDL-targeted therapies are emerging, along with unexpected side effects. Thus, novel and possibly safe substances, able to correct impaired lipid profile in humans, are still in great demand. Herein, based on encouraging clinical data, we formulated a nutraceutical product (AppleMetS ® , AMS), based on a polyphenolic extract from Annurca apple, and demonstrated that two capsules a day of AMS, after one month, have a LDL-C lowering outcome equivalent to 40 mg of simvastatin or 10 mg of atorvastatin. Nevertheless, different from statin-based therapy, AMS exerted a notable effect on HDL (+49.2%). Based on the trial results, we can assert that AMS formulation could effectively integrate the current therapeutic arsenal to correct impaired lipid profile in humans. Specifically, AMS may be considered a complementary and/or alternative safe substance suitable for the treatment of mildly hypercholesterolemic subjects who do not present occurrence of atheromatous plaques yet.

Image-guided percutaneous microwave ablation of small renal tumours: short- and mid-term outcomes.

PubMed

Genson, Pierre-Yves; Mourey, Eric; Moulin, Morgan; Favelier, Sylvain; Di Marco, Lucy; Chevallier, Olivier; Cercueil, Jean-Pierre; Krausé, Denis; Cormier, Luc; Loffroy, Romaric

2015-10-01

The purpose is to assess the short- and mid-term outcomes of microwave ablation (MWA) of small renal tumours in selected patients. From August 2012 to February 2015, 29 renal tumours in 23 patients (17 male, 6 female, mean age 75 years) were treated by percutaneous MWA under imaging guidance. The tumours were 1-4.7 cm in diameter (mean size, 2.7 cm). Therapeutic effects were assessed at follow-up with magnetic resonance imaging (MRI). All patients were followed up for 2-25 months (mean, 12.2 months) to observe the therapeutic effects and complications. Changes in renal function at day 1 after treatment were statistically analyzed using the Student paired t-test or the paired Wilcoxon test. Technical success was achieved in all cases. One severe bleeding complication post-procedure occurred leading to death. No other unexpected side effects were observed after the MWA procedures. Clinical effectiveness was 100%. None of the patients showed recurrence on MRI imaging follow-up. No significant changes in renal function were noted after treatment (P=0.57). Our preliminary study demonstrates that the use of MWA for the treatment of small renal tumours can be applied as safely and efficiently as other ablative techniques in selected patients not eligible for surgery.

A Healthy Balance of Plasma Cholesterol by a Novel Annurca Apple-Based Nutraceutical Formulation: Results of a Randomized Trial

PubMed Central

Tenore, Gian Carlo; Caruso, Domenico; Buonomo, Giuseppe; D'Avino, Maria; Campiglia, Pietro; Marinelli, Luciana

2017-01-01

Abstract Cardiovascular diseases are nowadays preferential targets of preventive medicine through a straightforward therapy on lipid profile. However, statins, the first-line lipid-lowering drug therapy, specifically act on low-density lipoprotein cholesterol (LDL-C), having a modest effect on plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Today, a number of novel HDL-targeted therapies are emerging, along with unexpected side effects. Thus, novel and possibly safe substances, able to correct impaired lipid profile in humans, are still in great demand. Herein, based on encouraging clinical data, we formulated a nutraceutical product (AppleMetS®, AMS), based on a polyphenolic extract from Annurca apple, and demonstrated that two capsules a day of AMS, after one month, have a LDL-C lowering outcome equivalent to 40 mg of simvastatin or 10 mg of atorvastatin. Nevertheless, different from statin-based therapy, AMS exerted a notable effect on HDL (+49.2%). Based on the trial results, we can assert that AMS formulation could effectively integrate the current therapeutic arsenal to correct impaired lipid profile in humans. Specifically, AMS may be considered a complementary and/or alternative safe substance suitable for the treatment of mildly hypercholesterolemic subjects who do not present occurrence of atheromatous plaques yet. PMID:28296588

Vitamin E supplementation during the dry period in dairy cattle. Part II: oxidative stress following vitamin E supplementation may increase clinical mastitis incidence postpartum.

PubMed

Bouwstra, R J; Nielen, M; Newbold, J R; Jansen, E H J M; Jelinek, H F; van Werven, T

2010-12-01

The aim of this study was to evaluate, retrospectively, which physiological states influenced the effect of vitamin E supplements during the dry period on the level of oxidative stress at 2 wk antepartum. Furthermore the effect of oxidative stress at 2 wk antepartum on the risk of clinical mastitis in early lactation was investigated. Cows experience oxidative stress around calving. Vitamin E is able to decrease oxidative stress by scavenging free radicals. Normally, vitamin E radicals formed when vitamin E reacts with free radicals are regenerated by a network of other antioxidants, termed the "vitamin E regeneration system" (VERS). In case of vitamin E supplementation, VERS should be sufficient to regenerate formed vitamin E radicals; if not, oxidative stress might increase instead of decrease. Additionally, the level of oxidative stress and vitamin E might be important physiological states to evaluate before supplementation. In a clinical trial, 296 cows on 5 farms were randomly divided into 2 groups, supplemented with a mineral mix between dry off and calving that supplied 3,000 or 135 IU/d, respectively. Blood samples collected at dry off and 2 wk antepartum were analyzed for vitamin E, reactive oxygen metabolites, ferric-reducing ability of plasma, glutathione peroxidase, and malondialdehyde. Cows were allocated retrospectively into 8 subgroups based on the level of oxidative stress, vitamin E, and VERS status at dry off. To evaluate whether differences in physiological states at dry off influenced the effect of vitamin E supplementation on the level of oxidative stress, group effects (supplemented vs. control) were studied with Student's t-test for all 8 subgroup at 2 wk antepartum. Differences in physiological states at dry off influenced the effect of vitamin E supplements. In 2 insufficient VERS subgroups, the supplemented group had higher levels of free radicals at 2 wk antepartum compared with the control group. Relative risk calculation was used to study the effect of oxidative stress at 2 wk antepartum on the incidence of mastitis in the first 100 d of lactation. Higher levels of oxidative stress at 2 wk antepartum were related to higher risk of clinical mastitis. In conclusion, not every dry cow responded well to high vitamin E supplementation. This subgroup analysis provides a possible explanation for the unexpected adverse effects observed in the clinical trial. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Positive Effects of Converting a Food and Bioprocessing Analysis Course to an Inquiry-Guided Approach

ERIC Educational Resources Information Center

Harris, Gabriel K.; Cvitkusic, Sanja; Draut, Amanda S.; Hathorn, Chelani S.; Stephens, Amanda M.; Constanza, Karen E.; Leonardelli, Michael J.; Watkins, Ruth H.; Dean, Lisa O.; Hentz, Nathaniel G.

2012-01-01

Food science laboratory courses are traditionally taught as a series of preplanned laboratories with known endpoints. In contrast, inquiry-guided (IG) laboratories allow students to ask questions, think through problems, design experiments, then adapt and learn in response to unexpected results. This study examined the effects of converting the…

Chapter 1: A conservation assessment framework for forest carnivores.

Treesearch

Leonard F. Ruggiero; William J. Zielinski; Keith B. Aubry; Steven W. Buskirk; L. Jack Lyon

1994-01-01

Controversy over managing public lands is neither an unexpected nor recent development. In the 1970's, debate over land management began to focus on the effects of timber management practices on wildlife. This was most evident in the Pacific Northwest where the public was beginning to express strong concerns about the effects of timber harvest in late-successional...

Post-marketing safety surveillance conducted in Korea (2008-2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™).

PubMed

Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

2016-10-02

According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice.

An intriguing high performance liquid chromatogram of a double heterozygosity for Hb Q-India/Hb D-Punjab.

PubMed

Badyal, Rama Kumari; Chhabra, Sanjeev; Sharma, Prashant; Das, Reena

2014-01-01

Cation exchange high performance liquid chromatography (HPLC) is commonly utilized as the first method of screening for thalassemias and hemoglobinopathies worldwide. This method of diagnosis requires knowledge of the clinical background and complete blood counts as well as skill and experience in interpreting the sometimes complex results produced. An asymptomatic 27-year-old pregnant North Indian woman was found to have a highly unusual chromatographic pattern with multiple unexpected peaks during routine antenatal screening. Most concerning was a C-window peak as Hb C (HBB: c.19G>A) is rare in ethnic Asian Indian populations. Cellulose acetate electrophoresis at alkaline pH (8.6) and parental screening were performed. These revealed the correct diagnosis to be a double heterozygosity for Hb Q-India (HBA1: c.193G>C) (an uncommon asymptomatic α-globin chain variant) plus Hb D-Punjab (HBB: c.364G>C) (a β-globin chain variant that is common in this region and is asymptomatic in the heterozygous state). The unexpected C-window peak was the hybrid of the abnormal α-Q-India and β-D-Punjab globin chains. Another small peak was explained as a variant Hb A2 formed by the combination of α-Q-India and δ-globin chains. Hematopathologists should be cognizant of the complex pattern resulting from coinheritance of both α- and β-globin structural variants. Second-line testing and parental testing are invaluable in resolving unknown peaks, especially if rare or unexpected variants are being considered. Although both Hb Q-India and Hb D-Punjab are relatively common in northwestern India, to the best of our knowledge, only two recent reports describe a total of three cases of such diagnostically puzzling coinheritance.

[Analysis of how elderly internet users react to unexpected situations].

PubMed

Haesner, Marten; Steinert, Anika; O'Sullivan, Julie Lorraine; Steinhagen-Thiessen, Elisabeth

2015-12-01

Although internet usage among older adults is steadily increasing, there is still a digital divide between generations. Younger internet users seem to be more open towards new media. Recent studies showed the negative influence of computer anxiety on internet usage. It is not known how older adults deal with computer and internet issues in their home environment and which problem-solving strategies they apply. The behavior of elderly people in unexpected situations when using an internet portal was analyzed to establish whether older users can solve the problems without assistance and what individual reactions (e.g. facial expressions and gesticulations) they show during the interaction. In a clinical trial with 50 older adults aged 60 years and older various typical problems which may occur while using web platforms were simulated and user behavior was analyzed using logging data, videography and with questionnaires to measure the subjective opinion of the study participants. The study participants had severe problems in solving the tasks on their own and many of them could not find a suitable solution at all. Overall, the videography data indicated an increased concentration of the participants during the whole session, which is in contrast to the low levels of perceived mental workload reported by the participants. Regarding task completion, no differences were found between seniors with and without cognitive impairment. The results showed the serious difficulties of older adults when dealing with unexpected events while using a web platform. For developers of internet platforms for inexperienced seniors, it seems to be crucial to incorporate a simple integration of all available features within the platform, without including features requiring high multi-tasking skills.

Post-marketing safety surveillance conducted in Korea (2008–2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™)

PubMed Central

Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

2016-01-01

ABSTRACT Purpose: According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). Methods: During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. Results: A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. Conclusions: We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice. PMID:27494163

Learning from the unexpected in life and DNA self-assembly

PubMed Central

2015-01-01

Summary The greatest lessons in life and science often arise from the unexpected. Thus, rather than viewing these experiences as hindering our progress, they should be embraced and appreciated for their ability to lead to new discoveries. In this perspective, I will discuss the unexpected events that have shaped my career path and the early stages of my independent research program. PMID:26877793

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire Presidential Documents Other Presidential Documents Presidential Determination No. 2011-11 of June 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya and Côte d'Ivoire Memorandum for the Secretary of...

Identifying black swans in NextGen: predicting human performance in off-nominal conditions.

PubMed

Wickens, Christopher D; Hooey, Becky L; Gore, Brian F; Sebok, Angelia; Koenicke, Corey S

2009-10-01

The objective is to validate a computational model of visual attention against empirical data--derived from a meta-analysis--of pilots' failure to notice safety-critical unexpected events. Many aircraft accidents have resulted, in part, because of failure to notice nonsalient unexpected events outside of foveal vision, illustrating the phenomenon of change blindness. A model of visual noticing, N-SEEV (noticing-salience, expectancy, effort, and value), was developed to predict these failures. First, 25 studies that reported objective data on miss rate for unexpected events in high-fidelity cockpit simulations were identified, and their miss rate data pooled across five variables (phase of flight, event expectancy, event location, presence of a head-up display, and presence of a highway-in-the-sky display). Second, the parameters of the N-SEEV model were tailored to mimic these dichotomies. The N-SEEV model output predicted variance in the obtained miss rate (r = .73). The individual miss rates of all six dichotomous conditions were predicted within 14%, and four of these were predicted within 7%. The N-SEEV model, developed on the basis of an independent data set, was able to successfully predict variance in this safety-critical measure of pilot response to abnormal circumstances, as collected from the literature. As new technology and procedures are envisioned for the future airspace, it is important to predict if these may compromise safety in terms of pilots' failing to notice unexpected events. Computational models such as N-SEEV support cost-effective means of making such predictions.

Attentional gain and processing capacity limits predict the propensity to neglect unexpected visual stimuli.

PubMed

Papera, Massimiliano; Richards, Anne

2016-05-01

Exogenous allocation of attentional resources allows the visual system to encode and maintain representations of stimuli in visual working memory (VWM). However, limits in the processing capacity to allocate resources can prevent unexpected visual stimuli from gaining access to VWM and thereby to consciousness. Using a novel approach to create unbiased stimuli of increasing saliency, we investigated visual processing during a visual search task in individuals who show a high or low propensity to neglect unexpected stimuli. When propensity to inattention is high, ERP recordings show a diminished amplification concomitantly with a decrease in theta band power during the N1 latency, followed by a poor target enhancement during the N2 latency. Furthermore, a later modulation in the P3 latency was also found in individuals showing propensity to visual neglect, suggesting that more effort is required for conscious maintenance of visual information in VWM. Effects during early stages of processing (N80 and P1) were also observed suggesting that sensitivity to contrasts and medium-to-high spatial frequencies may be modulated by low-level saliency (albeit no statistical group differences were found). In accordance with the Global Workplace Model, our data indicate that a lack of resources in low-level processors and visual attention may be responsible for the failure to "ignite" a state of high-level activity spread across several brain areas that is necessary for stimuli to access awareness. These findings may aid in the development of diagnostic tests and intervention to detect/reduce inattention propensity to visual neglect of unexpected stimuli. © 2016 Society for Psychophysiological Research.

Sudden unexpected nocturnal death in Chiari type 1 malformation and potential role of opioid analgesics

PubMed Central

Roohi, Fereydoon; Gropen, Toby; Kula, Roger W.

2014-01-01

Background: Chiari malformation type 1 (CM1) is a common congenital anomaly of the craniocervical junction. CM1 is reported to run a usually benign course and patients typically experience no symptoms or chronic, slowly progressive symptoms. However, recent reports indicate that a subset of patients with CM1 may present with acute deterioration and sudden unexpected death (SUD). We report a case of SUD during sleep in a young man with CM1, which we believe was related to the administration of common and therapeutic doses of narcotic analgesics for the management of pain. We will clarify the pathophysiology of acute deterioration and SUD in CM1 and the possibility that the adverse effects of opiate analgesics likely were the leading cause of death in our patient. Case Description: In this review, we present a 29-year-old male with worsening headache secondary to previously diagnosed CM1. The patient died suddenly and unexpectedly after administration of common and therapeutic doses of narcotic analgesics for the management of pain. Conclusion: The mechanism(s) of acute neurological deterioration and sudden death in patients with CM1 remains poorly understood. We believe the rapid fatal deterioration in our patient following administration of opioids suggests that this category of medication may cause sudden unexpected “neurogenic” cardiac death in CM1 patients by inducing sleep-related breathing difficulties and associated hypercapnia. Hypercapnia by further increasing intracranial pressure can result in a sudden pressure-induced decompensation of the cardiopulmonary control centers in the brain stem and cause instantaneous cardiorespiratory arrest. PMID:24778905

Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm.

PubMed

Jeter, Joanne M; Curiel-Lewandrowski, Clara; Stratton, Steven P; Myrdal, Paul B; Warneke, James A; Einspahr, Janine G; Bartels, Hubert G; Yozwiak, Michael; Bermudez, Yira; Hu, Chengcheng; Bartels, Peter; Alberts, David S

2016-02-01

Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage. ©2015 American Association for Cancer Research.

That note sounds wrong! Age-related effects in processing of musical expectation.

PubMed

Halpern, Andrea R; Zioga, Ioanna; Shankleman, Martin; Lindsen, Job; Pearce, Marcus T; Bhattacharya, Joydeep

2017-04-01

Part of musical understanding and enjoyment stems from the ability to accurately predict what note (or one of a small set of notes) is likely to follow after hearing the first part of a melody. Selective violation of expectations can add to aesthetic response but radical or frequent violations are likely to be disliked or not comprehended. In this study we investigated whether a lifetime of exposure to music among untrained older adults would enhance their reaction to unexpected endings of unfamiliar melodies. Older and younger adults listened to melodies that had expected or unexpected ending notes, according to Western music theory. Ratings of goodness-of-fit were similar in the groups, as was ERP response to the note onset (N1). However, in later time windows (P200 and Late Positive Component), the amplitude of a response to unexpected and expected endings was both larger in older adults, corresponding to greater sensitivity, and more widespread in locus, consistent with a dedifferentiation pattern. Lateralization patterns also differed. We conclude that older adults refine their understanding of this important aspect of music throughout life, with the ability supported by changing patterns of neural activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Intraarticular glucocorticoid treatment reduces inflammation in synovial cell infiltrations more efficiently than in synovial blood vessels.

PubMed

af Klint, Erik; Grundtman, Cecilia; Engström, Marianne; Catrina, Anca Irinel; Makrygiannakis, Dimitrios; Klareskog, Lars; Andersson, Ulf; Ulfgren, Ann-Kristin

2005-12-01

To investigate whether intraarticular (IA) glucocorticoid (GC) therapy diminishes synovial cell infiltration, vascularity, expression of proinflammatory cytokines, and adhesion molecule levels in patients with chronic arthritides. Thirty-one patients with chronic arthritides received a single IA injection of triamcinolone hexacetonide to treat active large-joint inflammation. Synovial biopsy specimens were obtained with arthroscopic guidance before and 9-15 days after injection. The presence of T lymphocytes, macrophages, intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), the pan-endothelial marker CD31, and the proinflammatory cytokines interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor (TNF), and high mobility group box chromosomal protein 1 (HMGB-1) was studied by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction. IA GC treatment resulted in good clinical response in 29 of 31 joints. After therapeutic intervention, the number of synovial T lymphocytes declined, whereas the number of macrophages remained unchanged. Overall synovial protein expression of TNF, IL-1beta, extranuclear HMGB-1, VEGF, and ICAM-1 was reduced at followup tissue sampling, while no significant effects were observed regarding vascularity. In contrast, expression of IL-1alpha, VEGF, and cytoplasmic HMGB-1 protein in vascular endothelial cells was not affected. GC therapy down-regulated levels of messenger RNA encoding IL-1alpha and IL-1beta, but not TNF or HMGB-1. Synovial cell infiltration and proinflammatory cytokine expression were affected in a multifaceted manner by IA GC treatment. Marked reduction of synovial T lymphocytes, TNF, IL-1beta, extranuclear HMGB-1, ICAM-1, and VEGF occurred in association with beneficial clinical effects. Unexpectedly, macrophage infiltration and proinflammatory endothelial cytokine expression remained unchanged. These findings may reflect mechanisms controlling the transiency of clinical improvement frequently observed after IA GC injection.

Potentiator Ivacaftor Abrogates Pharmacological Correction of ΔF508 CFTR in Cystic Fibrosis

PubMed Central

Cholon, Deborah M.; Quinney, Nancy L.; Fulcher, M. Leslie; Esther, Charles R.; Das, Jhuma; Dokholyan, Nikolay V.; Randell, Scott H.; Boucher, Richard C.; Gentzsch, Martina

2014-01-01

Cystic Fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR). Newly developed “correctors” such as lumacaftor (VX-809) that improve CFTR maturation and trafficking and “potentiators” such as ivacaftor (VX-770) that enhance channel activity may provide important advances in CF therapy. Although VX-770 has demonstrated substantial clinical efficacy in the small subset of patients with a mutation (G551D) that affects only channel activity, a single compound is not sufficient to treat patients with the more common CFTR mutation, ΔF508. Thus, patients with ΔF508 will likely require treatment with both correctors and potentiators to achieve clinical benefit. However, whereas the effectiveness of acute treatment with this drug combination has been demonstrated in vitro, the impact of chronic therapy has not been established. In studies of human primary airway epithelial cells, we found that both acute and chronic treatment with VX-770 improved CFTR function in cells with the G551D mutation, consistent with clinical studies. In contrast, chronic VX-770 administration caused a dose-dependent reversal of VX-809-mediated CFTR correction in ΔF508 homozygous cultures. This result reflected the destabilization of corrected ΔF508 CFTR by VX-770, dramatically increasing its turnover rate. Chronic VX-770 treatment also reduced mature wild-type CFTR levels and function. These findings demonstrate that chronic treatment with CFTR potentiators and correctors may have unexpected effects that cannot be predicted from short-term studies. Combining of these drugs to maximize rescue of ΔF508 CFTR may require changes in dosing and/or development of new potentiator compounds that do not interfere with CFTR stability. PMID:25101886

The impact of DSM-5 on the diagnosis and severity indicator of eating disorders in a treatment-seeking sample.

PubMed

Nakai, Yoshikatsu; Nin, Kazuko; Noma, Shun'ichi; Teramukai, Satoshi; Fujikawa, Kei; Wonderlich, Stephen A

2017-11-01

To examine the impact of the DSM-5 on the diagnoses and severity indicators of eating disorders, we conducted a comparative study on the classification of eating disorders including subtypes of anorexia nervosa (AN) between the DSM-IV and DSM-5 criteria. In addition, we studied the association of the DSM-5 severity criteria and clinical variables. Participants were 304 outpatients, aged 16-45 years, with eating disorders, diagnosed using semi-structured clinical interviews and the eating disorder examination questionnaire (EDE-Q). The severity of AN, bulimia nervosa (BN), and binge-eating disorder (BED) was rated from mild to extreme using the DSM-5 severity criteria. The DSM-5 remarkably reduced the number of diagnoses in the residual category from 37.5% to 9.2% and effectively differentiated the diagnostic groups in eating disorder psychopathology. Unexpectedly, however, the scores of all the EDE-Q subscales significantly decreased as severity ratings increased in the DSM-5 AN. Furthermore, while the AN binge-eating/purging group reported significantly lower severity ratings than the AN restricting group, the former displayed more severe eating disorder psychopathology than the latter. In the BN and BED groups, the level of eating concern increased as severity ratings increased, but the severity groups did not differ on other eating pathology variables. The DSM-5 effectively reduced the reliance on residual categories and differentiated the diagnostic groups in eating disorder psychopathology. However, our findings show limited support for the DSM-5 severity specifiers for eating disorders. It is necessary to test additional clinical or functional variables for severity specifiers across eating disorders. © 2017 Wiley Periodicals, Inc.

Preclinical Evaluation of a Replication-Deficient Recombinant Adenovirus Serotype 5 Vaccine Expressing Guanylate Cyclase C and the PADRE T-helper Epitope

PubMed Central

Snook, Adam E.; Baybutt, Trevor R.; Hyslop, Terry; Waldman, Scott A.

2016-01-01

There is an unmet need for improved therapeutics for colorectal cancer, the second leading cause of cancer mortality worldwide. Adjuvant chemotherapy only marginally improves survival in some patients and has no benefit in others, underscoring the clinical opportunity for novel immunotherapeutic approaches to improve survival in colorectal cancer. In that context, guanylate cyclase C (GUCY2C) is an established biomarker and therapeutic target for metastatic colorectal cancer with immunological characteristics that promote durable antitumor efficacy without autoimmunity. Preliminary studies established non-replicating human type 5 adenovirus (Ad5) expressing GUCY2C as safe and effective to induce GUCY2C-specific immune responses and antitumor immunity in mice. This study characterized the biodistribution, immunogenicity, and safety of a vector expressing GUCY2C fused with the human CD4+ T helper cell epitope PADRE (Ad5-GUCY2C-PADRE) to advance this vaccine into clinical trials in colorectal cancer patients. Ad5-GUCY2C-PADRE levels were highest in the injection site and distributed in vivo primarily to draining lymph nodes, the liver, spleen and, unexpectedly, to the bone marrow. Immune responses following Ad5-GUCY2C-PADRE administration were characterized by PADRE-specific CD4+ T-cell and GUCY2C-specific B-cell and CD8+ T-cell responses, producing antitumor immunity targeting GUCY2C-expressing colorectal cancer metastases in the lungs, without acute or chronic autoimmune or other toxicities. Collectively, these data support Ad5-GUCY2C-PADRE as a safe and effective vaccination strategy in preclinical models and position Ad5-GUCY2C-PADRE for Phase I clinical testing in colorectal cancer patients. PMID:27903079

Antibody screening & identification in the general patient population at a tertiary care hospital in New Delhi, India.

PubMed

Makroo, Raj Nath; Bhatia, Aakanksha; Hegde, Vikas; Chowdhry, Mohit; Thakur, Uday Kumar; Rosamma, N L

2014-09-01

The development of alloantibodies can significantly complicate transfusion therapy and results in difficulties in cross-matching of blood. Most literature on alloimmunization is limited to multitransfused individuals, with very few studies on the general hospital patients. This study was aimed at assessing the frequency and type of unexpected red cell antibodies in the general patient population at a multispecialty tertiary care centre in New Delhi, India. The results of 49,077 antibody screening tests carried out on patients, from January 2009 to December 2012 were analyzed. The clinical and transfusion records were reviewed. The data were compiled and statistically analysed. A total of 49,077 (29,917; 60.96% males and 19,160; 39.04% females) patient samples were screened for the presence of unexpected antibodies. Antibody screening was positive in 403 patients (0.82%). In the serum samples of 164 patients only autoantibodies were identified, 27 revealed autoantibodies with one or more underlying alloantibodies, while 212 patients had only alloantibody/ies in their serum. The overall alloimmunization rate was 0.49 per cent. Antibodies against the Rh system were the most frequent (64.1%), the most common alloantibody identified being anti E (37.2%), followed by anti D (19.2%). Since clinically significant antibodies are frequently detected in our patient population, antibody screening and if required, identification is the need of the hour. Since antibodies against the common Rh and Kell blood group antigens are the most frequent, provision of Rh and Kell matched red cells may be of protective value.

Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone.

PubMed

Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng

2018-02-14

The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

Image-based compound profiling reveals a dual inhibitor of tyrosine kinase and microtubule polymerization.

PubMed

Tanabe, Kenji

2016-04-27

Small-molecule compounds are widely used as biological research tools and therapeutic drugs. Therefore, uncovering novel targets of these compounds should provide insights that are valuable in both basic and clinical studies. I developed a method for image-based compound profiling by quantitating the effects of compounds on signal transduction and vesicle trafficking of epidermal growth factor receptor (EGFR). Using six signal transduction molecules and two markers of vesicle trafficking, 570 image features were obtained and subjected to multivariate analysis. Fourteen compounds that affected EGFR or its pathways were classified into four clusters, based on their phenotypic features. Surprisingly, one EGFR inhibitor (CAS 879127-07-8) was classified into the same cluster as nocodazole, a microtubule depolymerizer. In fact, this compound directly depolymerized microtubules. These results indicate that CAS 879127-07-8 could be used as a chemical probe to investigate both the EGFR pathway and microtubule dynamics. The image-based multivariate analysis developed herein has potential as a powerful tool for discovering unexpected drug properties.

A case of malignant pheochromocytoma with Holt-Oram syndrome.

PubMed

Yoshihara, Ai; Tanabe, Akiyo; Saito, Hiroshi; Hizuka, Naomi; Ishizawa, Akira; Horikawa, Reiko; Takano, Kazue

2008-03-01

A 23-year-old female patient with malignant pheochromocytoma was admitted to the Tokyo Women's Medical University. The patient had been clinically diagnosed with Holt-Oram syndrome at birth. Since she had complex congenital heart disease, chronic heart failure, and severe hypoxia, the risk surrounding surgery to remove the primary tumor was predicted to be very high, and subsequently, chemotherapy was performed. The patient was not able to continue chemotherapy due to adverse effects. However, for one year, both her hypertension and catecholamine-dependent symptoms were well controlled by an alpha-adrenergic and beta-adrenergic receptor blockade, although the patient did experience high plasma norepinephrine levels. To our knowledge, this is the first report of a patient with the combination of malignant pheochromocytoma and Holt-Oram syndrome. A correlation between chronic hypoxia and pheochromocytoma has been reported. This instructive case reminds us to consider the possibility of pheochromocytoma with congenital heart disease when these types of unexpected or unusual symptoms are encountered.

What is the reward? Medical students’ learning and personal development during a research project course

PubMed Central

Möller, Riitta; Shoshan, Maria; Heikkilä, Kristiina

2015-01-01

Background Until recently, the outcome of medical students’ research projects has mainly been assessed in terms of scientific publications, whereas other results important for students’ development have been less studied. The aim of this study was to investigate medical students’ experiences of learning as an outcome of the research project course. Method Written reflections of 50 students were analyzed by manifest inductive content analysis. Results Three categories emerged: ‘thinking as a scientist’, ‘working as a scientist’, and ‘personal development’. Students became more aware about the nature of knowledge, how to generate new knowledge, and developed skills in scientific thinking and critical appraisal. Unexpectedly, effects on personal characteristics, such as self-confidence, self-discipline, independence, and time management skills were also acknowledged. Conclusions We conclude that individual research projects enhance research-specific skills and competencies needed in evidence-based clinical work and are beneficial for personal and professional development. PMID:26344390

A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome

PubMed Central

Doyle, Jefferson J; Doyle, Alexander J; Wilson, Nicole K; Habashi, Jennifer P; Bedja, Djahida; Whitworth, Ryan E; Lindsay, Mark E; Schoenhoff, Florian; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Ehsan, Hamid; Huso, David; Thomas, Craig J; Caulfield, Mark J; Van Eyk, Jennifer E; Judge, Daniel P; Dietz, Harry C

2015-01-01

Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents. DOI: http://dx.doi.org/10.7554/eLife.08648.001 PMID:26506064

Poster — Thur Eve — 49: Unexpected Output Drops: Pitted Blackholes in Tungsten

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hudson, A; Pierce, G; University of Calgary, Department of Oncology, Calgary AB

2014-08-15

During the daily measurement of radiation output of a 6 MV beam on a Varian Trilogy Linear Accelerator the output dropped below 2% and initiated a call to action by physics to determine the cause. Over the course of weeks the cause of the issue was diagnosed to be a defect in the target, resulting in a drop in output and an asymmetry of the beam. Steps were taken to return the machine to clinical service while parts were on order while ensuring the safety of patient treatment. The machine target was replaced and the machine continues to operate asmore » expected. A drop in output is usually a rarity and a defect in the target is possibly more rare. This experience demonstrated the importance of routine QC measurement, recording and analyzing daily output and symmetry values. In addition, this event showcased the importance of a multi-disciplinary approach in a high-pressure situation to effectively troubleshoot unique events to ensure consistence, safety patient treatment.« less

Hypervitaminosis D in Guinea Pigs with α-Mannosidosis

PubMed Central

Jensen, JanLee A; Brice, Angela K; Bagel, Jessica H; Mexas, Angela M; Yoon, Sea Young; Wolfe, John H

2013-01-01

A colony of guinea pigs (n = 9) with α-mannosidosis was fed a pelleted commercial laboratory guinea pig diet. Over 2 mo, all 9 guinea pigs unexpectedly showed anorexia and weight loss (11.7% to 30.0% of baseline weight), and 3 animals demonstrated transient polyuria and polydipsia. Blood chemistry panels in these 3 guinea pigs revealed high-normal total calcium, high-normal phosphate, and high ALP. Urine specific gravity was dilute (1.003, 1.009, 1.013) in the 3 animals tested. Postmortem examination of 7 animals that were euthanized after failing to respond to supportive care revealed renal interstitial fibrosis with tubular mineralization, soft tissue mineralization in multiple organs, hepatic lipidosis, and pneumonia. Analysis of the pelleted diet revealed that it had been formulated with a vitamin D3 content of more than 150 times the normal concentration. Ionized calcium and 25-hydroxyvitamin D values were both high in serum saved from 2 euthanized animals, confirming the diagnosis of hypervitaminosis D. This report discusses the clinical signs, blood chemistry results, and gross and histologic findings of hypervitaminosis D in a colony of guinea pigs. When unexpected signs occur colony-wide, dietary differentials should be investigated at an early time point. PMID:23582422

Identifying and Investigating Unexpected Response to Treatment: A Diabetes Case Study.

PubMed

Ozery-Flato, Michal; Ein-Dor, Liat; Parush-Shear-Yashuv, Naama; Aharonov, Ranit; Neuvirth, Hani; Kohn, Martin S; Hu, Jianying

2016-09-01

The availability of electronic health records creates fertile ground for developing computational models of various medical conditions. We present a new approach for detecting and analyzing patients with unexpected responses to treatment, building on machine learning and statistical methodology. Given a specific patient, we compute a statistical score for the deviation of the patient's response from responses observed in other patients having similar characteristics and medication regimens. These scores are used to define cohorts of patients showing deviant responses. Statistical tests are then applied to identify clinical features that correlate with these cohorts. We implement this methodology in a tool that is designed to assist researchers in the pharmaceutical field to uncover new features associated with reduced response to a treatment. It can also aid physicians by flagging patients who are not responding to treatment as expected and hence deserve more attention. The tool provides comprehensive visualizations of the analysis results and the supporting data, both at the cohort level and at the level of individual patients. We demonstrate the utility of our methodology and tool in a population of type II diabetic patients, treated with antidiabetic drugs, and monitored by the HbA1C test.

Hypervitaminosis D in guinea pigs with α-mannosidosis.

PubMed

Jensen, Janlee A; Brice, Angela K; Bagel, Jessica H; Mexas, Angela M; Yoon, Sea Young; Wolfe, John H

2013-04-01

A colony of guinea pigs (n = 9) with α-mannosidosis was fed a pelleted commercial laboratory guinea pig diet. Over 2 mo, all 9 guinea pigs unexpectedly showed anorexia and weight loss (11.7% to 30.0% of baseline weight), and 3 animals demonstrated transient polyuria and polydipsia. Blood chemistry panels in these 3 guinea pigs revealed high-normal total calcium, high-normal phosphate, and high ALP. Urine specific gravity was dilute (1.003, 1.009, 1.013) in the 3 animals tested. Postmortem examination of 7 animals that were euthanized after failing to respond to supportive care revealed renal interstitial fibrosis with tubular mineralization, soft tissue mineralization in multiple organs, hepatic lipidosis, and pneumonia. Analysis of the pelleted diet revealed that it had been formulated with a vitamin D3 content of more than 150 times the normal concentration. Ionized calcium and 25-hydroxyvitamin D values were both high in serum saved from 2 euthanized animals, confirming the diagnosis of hypervitaminosis D. This report discusses the clinical signs, blood chemistry results, and gross and histologic findings of hypervitaminosis D in a colony of guinea pigs. When unexpected signs occur colony-wide, dietary differentials should be investigated at an early time point.

Transcranial magnetic stimulation: language function.

PubMed

Epstein, C M

1998-07-01

Studies of language using transcranial magnetic stimulation (TMS) have focused both on identification of language areas and on elucidation of function. TMS may result in either inhibition or facilitation of language processes and may operate directly at a presumptive site of language cortex or indirectly through intracortical networks. TMS has been used to create reversible "temporary lesions," similar to those produced by Wada tests and direct cortical electrical stimulation, in cerebral cortical areas subserving language function. Rapid-rate TMS over the left inferior frontal region blocks speech output in most subjects. However, the results are not those predicted from classic models of language organization. Speech arrest is obtained most easily over facial motor cortex, and true aphasia is rare, whereas right hemisphere or bilateral lateralization is unexpectedly prominent. A clinical role for these techniques is not yet fully established. Interfering with language comprehension and verbal memory is currently more difficult than blocking speech output, but numerous TMS studies have demonstrated facilitation of language-related tasks, including oral word association, story recall, digit span, and picture naming. Conversely, speech output also facilitates motor responses to TMS in the dominant hemisphere. Such new and often-unexpected findings may provide important insights into the organization of language.

ETIOLOGY, TRIGGERS AND NEUROCHEMICAL CIRCUITS ASSOCIATED WITH UNEXPECTED, EXPECTED, AND LABORATORY-INDUCED PANIC ATTACKS

PubMed Central

Johnson, Philip L.; Federici, Lauren M.; Shekhar, Anantha

2014-01-01

Panic disorder (PD) is a severe anxiety disorder that is characterized by recurrent panic attacks (PA), which can be unexpected (uPA, i.e., no clear identifiable trigger) or expected (ePA). Panic typically involves an abrupt feeling of catastrophic fear or distress accompanied by physiological symptoms such as palpitations, racing heart, thermal sensations, and sweating. Recurrent uPA and ePA can also lead to agoraphobia, where subjects with PD avoid situations that were associated with PA. Here we will review recent developments in our understanding of PD, which includes discussions on: symptoms and signs associated with uPA and ePAs; Diagnosis of PD and the new DSM-V; biological etiology such as heritability and gene x environment and gene x hormonal development interactions; comparisons between laboratory and naturally occurring uPAs and ePAs; neurochemical systems that are associated with clinical PAs (e.g. gene associations; targets for triggering or treating PAs), adaptive fear and panic response concepts in the context of new NIH RDoc approach; and finally strengths and weaknesses of translational animal models of adaptive and pathological panic states. PMID:25130976

The costs (or benefits) associated with attended objects do little to influence inattentional blindness.

PubMed

Stothart, Cary R; Wright, Timothy J; Simons, Daniel J; Boot, Walter R

2017-02-01

We sometimes fail to notice unexpected objects or events when our attention is directed elsewhere, a phenomenon called inattentional blindness. We explored whether unexpected objects that shared the color of consequential objects would be noticed more often. In three pre-registered experiments, participants played a custom video game in which they avoided both low- and high-cost missiles (Experiment 1 and 2) or tried to hit rewarding missiles while avoiding costly ones (Experiment 3). After participants had played the game for about 8min, an unexpected object moved across the screen. Although participants selectively avoided more costly missiles when playing, they were no more likely to notice an unexpected object when its color was associated with greater costs. Apparently, people are no more likely to notice unexpected objects that are associated with negative consequences. Future research should examine whether objects that are themselves consequential are noticed more frequently. Copyright © 2016 Elsevier B.V. All rights reserved.

IMPLICATIONS OF NEW ARSENIC STANDARDS ON OKLAHOMA WATER RESOURCES

EPA Science Inventory

The new national standard for arsenic in drinking water supplies, slated to take effect in 2006, is having an unexpected impact on a number of Oklahoma communities. Currently, several municipalities in north central Oklahoma are in compliance with existing arsenic standards (50 ...

Identifying effects and applications of fixed and variable speed limits.

DOT National Transportation Integrated Search

2016-08-01

In Indiana, distracted driving and unexpected queues have led to an increase in the amount of back-of-queue crashes, particularly on approach to : work zones. This report presents new strategies for the assessment of both transportation safety and tr...

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1984-01-01

Two demonstrations are described. The first shows the effect of polarity on solubility. The second is based on the unexpected formation of a precipitate of barium nitrate when barium carbonate or barium phosphate is treated with dilute nitric acid. List of materials needed and procedures used are included. (JN)

40 CFR 440.148 - Best Management Practices (BMP).

Code of Federal Regulations, 2010 CFR

2010-07-01

... incursion into the plant site. (b) Berm construction: Berms, including any pond walls, dikes, low dams and... that pollutant materials removed from the process water and wastewater streams will be retained in... continue their effectiveness and to protect from unexpected and catastrophic failure. ...

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

PubMed

Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

2015-01-01

Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials. ClinicalTrials.gov NCT01050621.

High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial

PubMed Central

Hoffer, L. John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H.

2015-01-01

Background Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. Methods and Findings We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Conclusions Despite IVC’s biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC’s value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials. Trial Registration ClinicalTrials.gov NCT01050621 PMID:25848948

Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus.

PubMed

Temel, Yasin; Boothman, Laura J; Blokland, Arjan; Magill, Peter J; Steinbusch, Harry W M; Visser-Vandewalle, Veerle; Sharp, Trevor

2007-10-23

Bilateral, high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the surgical therapy of choice for movement disability in advanced Parkinson's disease (PD), but this procedure evokes debilitating psychiatric effects, including depressed mood, of unknown neural origin. Here, we report the unexpected finding that HFS of the STN inhibits midbrain 5-hydroxytryptamine (5-HT) neurons to evoke depression-related behavioral changes. We found that bilateral HFS of the STN consistently inhibited (40-50%) the firing rate of 5-HT neurons in the dorsal raphe nucleus of the rat, but not neighboring non-5-HT neurons. This effect was apparent at clinically relevant stimulation parameters (> or =100 Hz, > or =30 microA), was not elicited by HFS of either neighboring or remote structures to the STN, and was still present in rat models of PD. We also found that bilateral HFS of the STN evoked clear-cut, depressive-like behavior in a widely used experimental paradigm of depression (forced swim test), and this effect was also observed in a PD model. Importantly, the depressive-like behavior elicited by HFS of the STN was reversed by a selective 5-HT-enhancing antidepressant, thereby linking the behavioral change to decreased 5-HT neuronal activity. Overall, these findings link reduced 5-HT function to the psychiatric effects of HFS of the STN observed in PD patients and provide a rational basis for their clinical management. More generally, the powerful interaction between the STN and 5-HT system uncovered here offers insights into the high level of comorbidity of basal ganglia disease and mood disorder.

Basal Cell Carcinoma of the Dorsal Foot: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany Y; Rubin, Ashley G; Jiang, Shang I Brian

2017-01-01

Ultraviolet radiation is a well-known risk factor for basal cell carcinoma (BCC). Therefore, the high incidence of BCCs in sun-exposed areas such as the head and neck is unsurprising. However, unexpectedly, BCCs on the sun-protected dorsal foot have also been reported, and tumor occurrence here suggests that other factors besides ultraviolet radiation may play a role in BCC pathogenesis. Because only few dorsal foot BCCs have been reported, data on their clinical features and management are limited. To perform an updated review of the literature on clinical characteristics and treatment of dorsal foot BCCs. We conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal foot," "basal cell carcinoma foot," and "basal cell carcinoma toe." We identified 20 cases of dorsal foot BCCs in the literature, 17 of which had sufficient data for analysis. Only 1 case was treated with Mohs micrographic surgery. We present 8 additional cases of dorsal foot BCCs treated with Mohs micrographic surgery. Basal cell carcinomas on the dorsal foot are rare, and potential risk factors include Caucasian descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment option.

A Rhesus Monkey Model of Self Injury: Effects of Relocation Stress on Behavior and Neuroendocrine Function

PubMed Central

Davenport, Matthew D.; Lutz, Corrine K.; Tiefenbacher, Stefan; Novak, Melinda A.; Meyer, Jerrold S.

2008-01-01

Background Self-injurious behavior (SIB), a disorder that afflicts many individuals within both clinical and non-clinical populations, has been linked to states of heightened stress and arousal. However, there are no published longitudinal data on the relationship between increases in stress and changes in the incidence of SIB. The present study investigated the short- and long-term behavioral and neuroendocrine responses of SIB and control monkeys to the stress of relocation. Methods Twenty adult male rhesus macaques were exposed to the stress of relocation to a new housing arrangement in a newly constructed facility. Daytime behavior, sleep, and multiple measures of hypothalamic-pituitary-adrenocortical (HPA) axis function were investigated before and after the move. Results Relocation induced a complex pattern of short- and long-term effects in the animals. The SIB animals showed a long-lasting increase in self-biting behavior as well as evidence of sleep disturbance. Both groups exhibited elevated cortisol levels in saliva, serum, and hair, and also an unexpected delayed increase in circulating concentrations of corticosteroid binding globulin (CBG). Conclusions Our results indicate that relocation is a significant stressor for rhesus macaques, and that this stressor triggers an increase in self-biting behavior as well as sleep disturbance in monkeys previously identified as suffering from SIB. These findings suggest that life stresses may similarly exacerbate SIB in humans with this disorder. The HPA axis results underscore the potential role of CBG in regulating long-term neuroendocrine responses to major stressors. PMID:18164279

Experimental analysis of the relationship between depressed mood and compulsive buying.

PubMed

Kyrios, Michael; McQueen, Paul; Moulding, Richard

2013-06-01

Compulsive buying is a serious but understudied problem, where individuals are unable to resist or control their buying behaviour, leading to substantial social and financial problems. To date there has been a lack of experimental research into the disorder. The relationship between mood and compulsive buying was examined in compulsive buyers (N = 18) and non-clinical controls (N = 17), using experimental information-processing paradigms. In study 1, it was expected that, if buying behaviours function as a coping strategy for depressed mood, then an induction of depressed mood would lead to an enhanced memory for appealing consumer-objects in compulsive buyers, but not controls. In study 2, we examined the association between emotional and functional constructs and consumer items. It was expected that compulsive buyers would show stronger semantic relationships and thus better episodic memory for object-emotion pairs, relative to object-function pairs, for appealing items. Unexpectedly, in study 1 the memory-facilitating effect of depressed mood was evident among control participants and absent among compulsive buyers. In study 2, compulsive buyers showed a lesser association of undesirable objects with positive emotional concepts than did non-clinical controls, and compulsive buyers were found to more strongly associate all consumer items with emotional concepts than with concepts of function. Key limitations were low power and possible floor effects due to error frequency data. These findings provide insights into the processes underlying CB phenomena, in particular supporting the role of mood in compulsive buying. Copyright © 2012 Elsevier Ltd. All rights reserved.

Restriction of foot supination by ankle braces in sudden fall situations.

PubMed

Podzielny, S; Hennig, E M

1997-06-01

OBJECTIVE: To investigate the restriction of foot supination in different shoe orthotic combinations for unexpected ankle turns. DESIGN: A supination platform was used to experimentally induce sudden ankle turns. BACKGROUND: This study expanded on previous investigations of the effectiveness of different ankle braces and the influence of shoe material on foot supination. METHODS: For 21 male subjects pressure distribution data, achilles tendon angle, and supination velocity were collected. A comparison between a shoe with cut upper material and an intact shoe was done to show the influence of upper material on supination. The effectiveness of four different orthotics inside of an intact shoe were tested in comparison to the same shoe without ankle brace. Additionally, subjects rated their perceived supination movement of the foot. RESULTS: Between experimental conditions no large differences for the pressure distribution patterns were found. Three of the ankle braces reduced foot supination as well as supination velocities. More than two times lower supination values were measured for a footwear condition in which the upper material was cut away. Already during the free-fall most ankle braces caused a substantial reduction of foot inversion. CONCLUSION: The experiments demonstrated the influence of the upper material of a shoe and different orthotics on foot supination. Biomechanical measurements are necessary because of limited capabilities of subjects in detecting subtalar angular motions. RELEVANCE: This study investigated the effectiveness of different shoe conditions and ankle braces under experimental conditions that simulated unexpected ankle turns, the most frequent causes of sport injuries. The results of the study provide insights into which factors influence the amount of foot supination during unexpected ankle turns.

Adaptation of muscles of the lumbar spine to sudden imbalance in patients with lower back pain caused by military training

PubMed Central

Gao, Ying; Shi, Jian-guo; Ye, Hong; Liu, Zhi-rong; Zheng, Long-bao; Ni, Zhi-ming; Fan, Liang-quan; Wang, Jian; Hou, Zhen-hai

2014-01-01

Objective This study aims to investigate the effects of sudden load changes (expected and unexpected imbalance) on the activity of muscles of the lumbar spine and their central motor control strategy in military personnel with or without chronic low back pain (LBP). Design Bilateral sudden imbalance was examined (2 × 2 factorial design). Setting The 117th PLA Hospital, Hangzhou, China Participants Twenty-one male subjects with lower back pain and 21 male healthy control subjects were active members of the Nanjing Military Region land forces. Outcome measures Independent variables: LBP vs. healthy controls and imbalance anticipation (expected and unexpected imbalance). Dependent variables: rapid reaction time (RRT) and intensity of rapid reaction (IRR) of bilateral lumbar (L3–L4) erector spinae (ES), lumbar (L5–S1) multifidus (MF), and abdominal external oblique muscles. Results Under expected or unexpected sudden imbalance conditions, subjects with LBP demonstrated significantly greater IRR than healthy controls in ipsilateral and contralateral ES and MF, respectively (P < 0.05 for all). IRR of contralateral ES was significantly larger than that of the ipsilateral ES. A significant group effect of RRT of both ipsilateral and contralateral ES muscles and a significant time expectation effect on RRT of contralateral MF muscles were also observed. RRT of the contralateral ES muscles was significantly lower than that of the ipsilateral ES muscles (P < 0.001). Conclusions Sudden imbalance prolonged RRT of selected trunk muscles in patients with chronic LBP. The activation amplitude increased. The results may provide a theoretical basis for a study on the pathogenesis of chronic LBP. PMID:24621023

Unexpected persistence of extended-spectrum β-lactamase-producing Enterobacteriaceae in the faecal microbiota of hospitalised patients treated with imipenem.

PubMed

Grall, N; Lazarevic, V; Gaïa, N; Couffignal, C; Laouénan, C; Ilic-Habensus, E; Wieder, I; Plesiat, P; Angebault, C; Bougnoux, M E; Armand-Lefevre, L; Andremont, A; Duval, X; Schrenzel, J

2017-07-01

Imipenem is active against extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) but favours the intestinal emergence of resistance. The effects of imipenem on intestinal microbiota have been studied using culture-based techniques. In this study, the effects were investigated in patients using culture and metagenomic techniques. Seventeen hospitalised adults receiving imipenem were included in a multicentre study (NCT01703299, http://www.clinicaltrials.gov). Most patients had a history of antibiotic use and/or hospitalisation. Stools were collected before, during and after imipenem treatment. Bacterial and fungal colonisation was assessed by culture, and microbiota changes were assessed using metagenomics. Unexpectedly, high colonisation rates by imipenem-susceptible ESBL-E before treatment (70.6%) remained stable over time, suggesting that imipenem intestinal concentrations were very low. Carriage rates of carbapenem-resistant Gram-negative bacilli (0-25.0%) were also stable over time, whereas those of yeasts (64.7% before treatment) peaked at 76.5% during treatment and decreased thereafter. However, these trends were not statistically significant. Yeasts included highly diverse colonising Candida spp. Metagenomics showed no global effect of imipenem on the bacterial taxonomic profiles at the sequencing depth used but demonstrated specific changes in the microbiota not detected with culture, attributed to factors other than imipenem, including sampling site or treatment with other antibiotics. In conclusion, culture and metagenomics were highly complementary in characterising the faecal microbiota of patients. The changes observed during imipenem treatment were unexpectedly limited, possibly because the microbiota was already disturbed by previous antibiotic exposure or hospitalisation. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Spatial Analysis of Case-Mix and Dialysis Modality Associations.

PubMed

Phirtskhalaishvili, Tamar; Bayer, Florian; Edet, Stephane; Bongiovanni, Isabelle; Hogan, Julien; Couchoud, Cécile

2016-01-01

♦ Health-care systems must attempt to provide appropriate, high-quality, and economically sustainable care that meets the needs and choices of patients with end-stage renal disease (ESRD). France offers 9 different modalities of dialysis, each characterized by dialysis technique, the extent of professional assistance, and the treatment site. The aim of this study was 1) to describe the various dialysis modalities in France and the patient characteristics associated with each of them, and 2) to analyze their regional patterns to identify possible unexpected associations between case-mixes and dialysis modalities. ♦ The clinical characteristics of the 37,421 adult patients treated by dialysis were described according to their treatment modality. Agglomerative hierarchical cluster analysis was used to aggregate the regions into clusters according to their use of these modalities and the characteristics of their patients. ♦ The gradient of patient characteristics was similar from home hemodialyis (HD) to in-center HD and from non-assisted automated peritoneal dialysis (APD) to assisted continuous ambulatory peritoneal dialysis (CAPD). Analyzing their spatial distribution, we found differences in the patient case-mix on dialysis across regions but also differences in the health-care provided for them. The classification of the regions into 6 different clusters allowed us to detect some unexpected associations between case-mixes and treatment modalities. ♦ The 9 modalities of treatment available make it theoretically possible to adapt treatment to patients' clinical characteristics and abilities. However, although we found an overall appropriate association of dialysis modalities to the case-mix, major inter-region heterogeneity and the low rate of peritoneal dialysis (PD) and home HD suggest that factors besides patients' clinical conditions impact the choice of dialysis modality. The French organization should now be evaluated in terms of patients' quality of life, satisfaction, survival, and global efficiency. Copyright © 2016 International Society for Peritoneal Dialysis.

Spatial Analysis of Case-Mix and Dialysis Modality Associations

PubMed Central

Phirtskhalaishvili, Tamar; Bayer, Florian; Edet, Stephane; Bongiovanni, Isabelle; Hogan, Julien; Couchoud, Cécile

2016-01-01

♦ Background: Health-care systems must attempt to provide appropriate, high-quality, and economically sustainable care that meets the needs and choices of patients with end-stage renal disease (ESRD). France offers 9 different modalities of dialysis, each characterized by dialysis technique, the extent of professional assistance, and the treatment site. The aim of this study was 1) to describe the various dialysis modalities in France and the patient characteristics associated with each of them, and 2) to analyze their regional patterns to identify possible unexpected associations between case-mixes and dialysis modalities. ♦ Methods: The clinical characteristics of the 37,421 adult patients treated by dialysis were described according to their treatment modality. Agglomerative hierarchical cluster analysis was used to aggregate the regions into clusters according to their use of these modalities and the characteristics of their patients. ♦ Result: The gradient of patient characteristics was similar from home hemodialyis (HD) to in-center HD and from non-assisted automated peritoneal dialysis (APD) to assisted continuous ambulatory peritoneal dialysis (CAPD). Analyzing their spatial distribution, we found differences in the patient case-mix on dialysis across regions but also differences in the health-care provided for them. The classification of the regions into 6 different clusters allowed us to detect some unexpected associations between case-mixes and treatment modalities. ♦ Conclusions: The 9 modalities of treatment available make it theoretically possible to adapt treatment to patients' clinical characteristics and abilities. However, although we found an overall appropriate association of dialysis modalities to the case-mix, major inter-region heterogeneity and the low rate of peritoneal dialysis (PD) and home HD suggest that factors besides patients' clinical conditions impact the choice of dialysis modality. The French organization should now be evaluated in terms of patients' quality of life, satisfaction, survival, and global efficiency. PMID:26475843

Which is the main molecular target responsible for the cardiovascular benefits in the EMPA-REG OUTCOME trial? A journey through the kidney, the heart and other interesting places.

PubMed

Luconi, M; Raimondi, L; Di Franco, A; Mannucci, E

2016-12-01

The results of the EMPA-REG-OUTCOME trial on type 2 diabetic patients at high risk for prior cardiovascular events showed that empagliflozin produces a remarkable reduction in the rates of hospitalization for heart failure (35%), cardiovascular death (38%), and all-cause death (32%). This unexpected cardio-protective action cannot be accounted for by the improvement of "classical" cardiovascular risk factors. This review aims at summarizing current knowledge on the cardiovascular action of SGLT2 inhibitors and discuss the different hypotheses formulated to explain the results of the EMPA-REG-OUTCOME-study. We discuss in detail the major cardiovascular outcomes of the study in the light of the potential systemic and myocardial mechanisms of action of the drug. In addition, we propose and speculate on a direct effect of empagliflozin on cardiomyocytes. The available evidence is insufficient to establish any of the proposed mechanisms of cardiovascular action of empagliflozin. While awaiting for the results of ongoing clinical studies with other SGLT2 inhibitors, the most promising putative mechanisms still deserve to be confirmed with specifically designed, yet unavailable, pre-clinical studies. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

How Magnus Bends the Flying Ball--Experimenting and Modeling

ERIC Educational Resources Information Center

Timková, V.; Ješková, Z.

2017-01-01

Students are well aware of the effect of the deflection of sports balls when they have been given a spin. A volleyball, tennis, or table tennis ball served with topspin results in an additional downward force that makes the ball difficult to catch and return. In soccer, the effect of sidespin causes the ball to curve unexpectedly sideways,…

[Effects of Drugs Given During Pregnancy and Lactation on the Unborn Child and Neonate.

ERIC Educational Resources Information Center

Kelsey, Frances O.

This symposium presentation outlines the activity of the Food and Drug Administration (FDA) in regulating the use during pregnancy and lactation of drugs which affect the fetus and neonate. When presented with an unexpected adverse effect of a drug or of a class of drugs, the FDA can take several steps. These steps include ordering total removal…

Managing the Unexpected: Complexity as Distributed Sensemaking

NASA Astrophysics Data System (ADS)

Weick, Karl E.

In 1998 the Centers for Disease Control (CDC) published a statement of their strategy entitled "Preventing Emerging Infectious Diseases: A Strategy for the 21st Century." They described their central challenge this way: "because we do not know what new diseases will arise, we must always be prepared for the unexpected" (p. vii). Soon after they published that statement CDC was confronted with an unexpected emerging disease, the West Nile Virus, which they misdiagnosed initially.

Effects of autonomy-supportive and controlling styles on situational self-determined motivation: some unexpected results of the commitment procedure.

PubMed

Amoura, Camille; Berjot, Sophie; Gillet, Nicolas; Caruana, Sylvain; Finez, Lucie

2015-02-01

Distinct and simultaneous effects of autonomy-supportive and controlling styles, usually considered as mutually exclusive, on situational self-determined motivation are tested. In Study 1, economics students (N = 100; 57 men, 43 women; M age = 21.5 yr.) were randomly assigned to one of the four experimental conditions (high vs. low) of autonomy supportive and/or controlling behaviors during a task. Results supported the independence of those constructs. An unexpected effect in regards to Self-determination Theory was found in the Low autonomy - High control condition in which self-determined motivation was observed. The interpretation for this specific condition, an effect due to the attempt to reduce cognitive dissonance triggered by the commitment procedure, was tested. In Study 2, sport students (N = 80, 44 men, 36 women; M age = 19.2 yr.) were randomly assigned to one of the three experimental conditions: No commitment, Commitment plus self-affirmation, and Commitment without self-affirmation. Results supported Study 1's interpretation: motivation was lower when participants were recruited without a commitment procedure or when they were invited to self-affirm than when participants recruited with a commitment procedure.

The Classical Vacuum.

ERIC Educational Resources Information Center

Boyer, Timothy H.

1985-01-01

The classical vacuum of physics is not empty, but contains a distinctive pattern of electromagnetic fields. Discovery of the vacuum, thermal spectrum, classical electron theory, zero-point spectrum, and effects of acceleration are discussed. Connection between thermal radiation and the classical vacuum reveals unexpected unity in the laws of…

Development of electrophysiological indices of neurological toxicity for organophosphate pesticides and depressant drugs.

DOT National Transportation Integrated Search

1979-05-01

Accurate control of eye movements and rapid detection of unexpected events in the periphery of the visual field are critically important in the aviation environment. We have studied the effects of certain drugs and environmental pollutants on brain m...

Participant Modelling Training Programme: Tutoring the Paraprofessional.

ERIC Educational Resources Information Center

Romi, Shlomo; Teichman, Meir

1998-01-01

A participant-modeling training program designed to improve self-efficacy and the ability to cope effectively with stressful situations was implemented with young paraprofessional counselors who work in conjunction with youth-advancement counselors. Results are presented for self-efficacy and motivation variables. Unexpected findings are…

WE-G-209-00: Identifying Image Artifacts, Their Causes, and How to Fix Them

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Digital radiography, CT, PET, and MR are complicated imaging modalities which are composed of many hardware and software components. These components work together in a highly coordinated chain of events with the intent to produce high quality images. Acquisition, processing and reconstruction of data must occur in a precise way for optimum image quality to be achieved. Any error or unexpected event in the entire process can produce unwanted pixel intensities in the final images which may contribute to visible image artifacts. The diagnostic imaging physicist is uniquely qualified to investigate and contribute to resolution of image artifacts. This coursemore » will teach the participant to identify common artifacts found clinically in digital radiography, CT, PET, and MR, to determine the causes of artifacts, and to make recommendations for how to resolve artifacts. Learning Objectives: Identify common artifacts found clinically in digital radiography, CT, PET and MR. Determine causes of various clinical artifacts from digital radiography, CT, PET and MR. Describe how to resolve various clinical artifacts from digital radiography, CT, PET and MR.« less

The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia.

PubMed

de Rooij, Martin F M; Kuil, Annemieke; Geest, Christian R; Eldering, Eric; Chang, Betty Y; Buggy, Joseph J; Pals, Steven T; Spaargaren, Marcel

2012-03-15

Small-molecule drugs that target the B-cell antigen receptor (BCR) signalosome show clinical efficacy in the treatment of B-cell non-Hodgkin lymphoma. These agents, including the Bruton tyrosine kinase (BTK) inhibitor PCI-32765, display an unexpected response in patients with chronic lymphocytic leukemia (CLL): a rapid and sustained reduction of lymphadenopathy accompanied by transient lymphocytosis, which is reversible upon temporary drug deprivation. We hypothesized that this clinical response reflects impaired integrin-mediated adhesion and/or migration. Here, we show that PCI-32765 strongly inhibits BCR-controlled signaling and integrin α(4)β(1)-mediated adhesion to fibronectin and VCAM-1 of lymphoma cell lines and primary CLL cells. Furthermore, PCI-32765 also inhibits CXCL12-, CXCL13-, and CCL19-induced signaling, adhesion, and migration of primary CLL cells. Our data indicate that inhibition of BTK by PCI-32765 overcomes BCR- and chemokine-controlled integrin-mediated retention and homing of malignant B cells in their growth- and survival-supporting lymph node and bone marrow microenvironment, which results in clinically evident CLL regression.

Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry in Clinical Microbiology: What Are the Current Issues?

PubMed Central

Welker, Martin; Pincus, David; Charrier, Jean-Philippe; Girard, Victoria

2017-01-01

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized the identification of microbial species in clinical microbiology laboratories. MALDI-TOF-MS has swiftly become the new gold-standard method owing to its key advantages of simplicity and robustness. However, as with all new methods, adoption of the MALDI-TOF MS approach is still not widespread. Optimal sample preparation has not yet been achieved for several applications, and there are continuing discussions on the need for improved database quality and the inclusion of additional microbial species. New applications such as in the field of antimicrobial susceptibility testing have been proposed but not yet translated to the level of ease and reproducibility that one should expect in routine diagnostic systems. Finally, during routine identification testing, unexpected results are regularly obtained, and the best methods for transmitting these results into clinical care are still evolving. We here discuss the success of MALDI-TOF MS in clinical microbiology and highlight fields of application that are still amenable to improvement. PMID:28840984

Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry in Clinical Microbiology: What Are the Current Issues?

PubMed

van Belkum, Alex; Welker, Martin; Pincus, David; Charrier, Jean Philippe; Girard, Victoria

2017-11-01

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized the identification of microbial species in clinical microbiology laboratories. MALDI-TOF-MS has swiftly become the new gold-standard method owing to its key advantages of simplicity and robustness. However, as with all new methods, adoption of the MALDI-TOF MS approach is still not widespread. Optimal sample preparation has not yet been achieved for several applications, and there are continuing discussions on the need for improved database quality and the inclusion of additional microbial species. New applications such as in the field of antimicrobial susceptibility testing have been proposed but not yet translated to the level of ease and reproducibility that one should expect in routine diagnostic systems. Finally, during routine identification testing, unexpected results are regularly obtained, and the best methods for transmitting these results into clinical care are still evolving. We here discuss the success of MALDI-TOF MS in clinical microbiology and highlight fields of application that are still amenable to improvement. © The Korean Society for Laboratory Medicine.

WE-G-209-01: Digital Radiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schueler, B.

Digital radiography, CT, PET, and MR are complicated imaging modalities which are composed of many hardware and software components. These components work together in a highly coordinated chain of events with the intent to produce high quality images. Acquisition, processing and reconstruction of data must occur in a precise way for optimum image quality to be achieved. Any error or unexpected event in the entire process can produce unwanted pixel intensities in the final images which may contribute to visible image artifacts. The diagnostic imaging physicist is uniquely qualified to investigate and contribute to resolution of image artifacts. This coursemore » will teach the participant to identify common artifacts found clinically in digital radiography, CT, PET, and MR, to determine the causes of artifacts, and to make recommendations for how to resolve artifacts. Learning Objectives: Identify common artifacts found clinically in digital radiography, CT, PET and MR. Determine causes of various clinical artifacts from digital radiography, CT, PET and MR. Describe how to resolve various clinical artifacts from digital radiography, CT, PET and MR.« less

The effects of learning on event-related potential correlates of musical expectancy.

PubMed

Carrión, Ricardo E; Bly, Benjamin Martin

2008-09-01

Musical processing studies have shown that unexpected endings in familiar musical sequences produce extended latencies of the P300 component. The present study sought to identify event-related potential (ERP) correlates of musical expectancy by entraining participants with rule-governed chord sequences and testing whether unexpected endings created similar responses. Two experiments were conducted in which participants performed grammaticality classifications without training (Experiment 1) and with training (Experiment 2). In both experiments, deviant chords differing in instrumental timbre elicited a MMN/P3a waveform complex. Violations related to learned patterns elicited an early right anterior negativity and P3b. Latency and amplitude of peak components were modulated by the physical characteristics of the chords, expectations due to prior knowledge of musical harmony, and contextually defined expectations developed through entrainment.

Evidence for goal-independent attentional capture from validity effects with unexpected novel color cues--a response to Burnham (2007).

PubMed

Horstmann, Gernot; Becker, Stefanie I

2011-06-01

Can a stimulus capture attention independent of the observer's goals and intentions? In a recent review, (Burnham, Psychonomic Bulletin & Review, 14, 392-422, 2007) argued that there is no convincing evidence that attention capture is ever completely independent of the goals and intentions of the observer. By contrast, surprise capture studies have shown that a color singleton can capture attention on its unannounced first occurrence, if it is new and unexpected, and hence is not part of the intentional set. However, the evidence from surprise capture studies has been criticized on methodological grounds. Here, we tested surprise capture in a new paradigm that avoids previous methodological complications. The results refute the prior criticisms and reinstate surprise capture as prime evidence for goal-independent capture.

An Unexpected Complication of Bone Marrow Aspiration and Trephine Biopsy: Arteriovenous Fistula

PubMed Central

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Kutlu, Ramazan; Koroglu, Mustafa; Yigit, Ali; Unlu, Serkan

2014-01-01

Objective To report a case of arteriovenous fistula (AVF) following bone marrow aspiration and trephine biopsy. Clinical Presentation and Intervention A 76-year-old man was diagnosed with acute myeloblastic leukemia. Pain and hematoma were detected in his left leg and hip 4 days after bone marrow aspiration and trephine biopsy. A pelvic arteriography was performed, and a diagnosis of AVF was made. Conclusion This case shows that clinicians should be aware of AVF, especially in cases with refractory bleeding after bone marrow aspiration and trephine biopsy despite normal blood coagulation parameters. PMID:24481007

Epidemiology, molecular virology and diagnostics of Schmallenberg virus, an emerging orthobunyavirus in Europe

PubMed Central

2013-01-01

After the unexpected emergence of Bluetongue virus serotype 8 (BTV-8) in northern Europe in 2006, another arbovirus, Schmallenberg virus (SBV), emerged in Europe in 2011 causing a new economically important disease in ruminants. The virus, belonging to the Orthobunyavirus genus in the Bunyaviridae family, was first detected in Germany, in The Netherlands and in Belgium in 2011 and soon after in the United Kingdom, France, Italy, Luxembourg, Spain, Denmark and Switzerland. This review describes the current knowledge on the emergence, epidemiology, clinical signs, molecular virology and diagnosis of SBV infection. PMID:23675914

Bilateral acute angle closure glaucoma after hyperopic LASIK correction

PubMed Central

Osman, Essam A.; Alsaleh, Ahmed A.; Al Turki, Turki; AL Obeidan, Saleh A.

2009-01-01

Acute angle closure glaucoma is unexpected complication following laser in situ keratomileusis (LASIK). We are reporting a 49-years-old lady that was presented to the emergency department with acute glaucoma in both eyes soon after LASIK correction. Diagnosis was made on detailed clinical history and examination, slit lamp examination, intraocular pressure measurement and gonioscopy. Laser iridotomy in both eyes succeeded in controlling the attack and normalizing the intraocular pressure (IOP) more than 6 months of follow-up. Prophylactic laser iridotomy is essential for narrow angle patients before LASIK surgery if refractive laser surgery is indicated. PMID:23960863

Syncope cluster in a patient with vasovagal history.

PubMed

Zyśko, Dorota; Sokalski, Leszek; Gajek, Jacek; Loboz-Grudzień, Krystyna

2010-10-01

We report a case of a 55 year-old man with a history of vasovagal syncope who experienced six unexpected syncopal events over the course of two hours. Two of these occurred in the supine position during ECG monitoring, which showed a long-lasting sinus pause. Before the last syncopal episode, the ECG recording was started at the moment when the patient had the recurrence of presyncopal symptoms. Recordings showed sinus rhythm slowing for 12 s and then sinus arrest lasting for 29 s. A thorough clinical examination revealed no relevant abnormalities. The patient was treated with a permanent pacemaker implantation.

Pre-eruptive intracoronal resorption in a third upper molar: clinical, tomographic and histological analysis.

PubMed

Lenzi, R; Marceliano-Alves, M F; Alves, Frf; Pires, F R; Fidel, S

2017-06-01

Radiolucent or hypodense lesions in the crown of unerupted teeth may be due to pre-eruptive intracoronal resorption. Clinicians must be aware of this risk so that they can diagnose and appropriately treat this condition. The purpose of this study is to present a well-documented clinical case of pre-eruptive intracoronal resorption in an impacted third upper left molar of a 63 year old female patient. This was an unexpected finding, which occurred after cone-beam computed tomography was used to investigate the first upper left molar, which had an acute periradicular abscess. A multidisciplinary team followed up the case to describe clinical, radiographic and histological findings. The available treatment options were discussed, and the tooth extraction was the option chosen. Previous case studies describing such resorption in third upper molars have not been reported. This case shows that all permanent teeth in a pre-eruptive stage must be analysed radiographically to detect early pre-eruptive intracoronal resorption. © 2016 Australian Dental Association.

[Benefit-risk assessment of vaccination strategies].

PubMed

Hanslik, Thomas; Boëlle, Pierre Yves

2007-04-01

This article summarises the various stages of the risk/benefit assessment of vaccination strategies. Establishing the awaited effectiveness of a vaccination strategy supposes to have an epidemiologic description of the disease to be prevented. The effectiveness of the vaccine strategy will be thus expressed in numbers of cases, hospitalizations or deaths avoided. The effectiveness can be direct, expressed as the reduction of the incidence of the infectious disease in the vaccinated subjects compared to unvaccinated subjects. It can also be indirect, the unvaccinated persons being protected by the suspension in circulation of the pathogenic agent, consecutive to the implementation of the vaccination campaign. The risks of vaccination related to the adverse effects detected during the clinical trials preceding marketing are well quantified, but other risks can occur after marketing: e.g., serious and unexpected adverse effects detected by vaccinovigilance systems, or risk of increase in the age of cases if the vaccination coverage is insufficient. The medico-economic evaluation forms a part of the risks/benefit assessment, by positioning the vaccine strategy comparatively with other interventions for health. Epidemiologic and vaccinovigilance informations must be updated very regularly, which underlines the need for having an operational and reliable real time monitoring system to accompany the vaccination strategies. Lastly, in the context of uncertainty which often accompanies the risks/benefit assessments, it is important that an adapted communication towards the public and the doctors is planned.

[Hypertrophic cardiomyopathy: an intraoperative death case analysis and substantiation of the standards of perioperative anesthetic management in a non-cardiosurgery clinic].

PubMed

Fedosiuk, Roman N; Shchupachynska, Liliia O

2018-01-01

The article is based on the case analysis of a sudden and unexpected intraoperative death of a 51-year-old female patient with hypertrophic cardiomyopathy, who was undergoing a non-cardiac operation in a non-cardiosurgery clinic, from acute precipitation of left ventricular outflow tract obstruction provoked by surgery and anesthesia. It emphasizes the importance of raising non-cardiac anesthesiologists' awareness of the issue and having clear standards of pre-operative evaluation and perioperative management of patients with hypertrophic cardiomyopathy in order to avoid fatal medical errors. A literature review on the disease with an accent on anesthesia-related issues is also given, and four standards of perioperative anesthetic management of patients with hypertrophic cardiomyopathy presenting for non-cardiac surgery in general hospital settings are developed and offered.

[Ethical guidelines on genetic testing and gene therapy].

PubMed

Fukushima, Yoshimitsu

2005-03-01

According to the recent and rapid advances in molecular genetics research, genetic testing and gene therapy have a potential of giving unexpected influence to the human beings. To prevent and to solve various ethical, legal and social implementations (ELSI) of genetic testing and gene therapy, several guidelines have been established. In Japan, all researchers and all clinicians have to know and keep the following three guidelines on genetic testing and a guideline on gene therapy: 1) "Guidelines for Researches on Human Genome and Gene (2001)" by the three Ministries (Education, Health and Economy), 2) "Guidelines for Genetic Testing (2001)" by the Genetic--medicine--related 10 societies, 3) "Ethical Principles on Entrusted Genetic Testing (2001)" by the Japan Registered Clinical Laboratories Association, and 4) "Guidelines for Clinical Research on Gene Therapy (2002)" by the two Ministries (Health and Education).

Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates

PubMed Central

Dostalek, Miroslav; Prueksaritanont, Thomayant; Kelley, Robert F.

2017-01-01

ABSTRACT Pharmacokinetic studies play an important role in all stages of drug discovery and development. Recent advancements in the tools for discovery and optimization of therapeutic proteins have created an abundance of candidates that may fulfill target product profile criteria. Implementing a set of in silico, small scale in vitro and in vivo tools can help to identify a clinical lead molecule with promising properties at the early stages of drug discovery, thus reducing the labor and cost in advancing multiple candidates toward clinical development. In this review, we describe tools that should be considered during drug discovery, and discuss approaches that could be included in the pharmacokinetic screening part of the lead candidate generation process to de-risk unexpected pharmacokinetic behaviors of Fc-based therapeutic proteins, with an emphasis on monoclonal antibodies. PMID:28463063

Infections of the head and ocular structures in the horse.

PubMed

Gerard, Mathew P; Wotman, Kathryn L; Komáromy, András M

2006-08-01

Infectious conditions of the equine head are commonly encountered in clinical practice. Pathogenic bacterial, viral, and fungal organisms may localize in the extensive nasal passages, paranasal sinuses, and guttural pouches, creating a range of clinical signs and conditions that can be severe enough to lead to unexpected fatality. Renewed interest in equine dentistry has led to a greater recognition of dental disease that is associated with infection. This article focuses on bacterial and fungal infections of the main anatomic regions of the equine head, where advances in diagnosis and management have been made or consolidated in recent years. It also addresses recent advances made in the area of infectious equine corneal disease, including bacterial, viral, and fungal etiologies. Recent developments in equine recurrent uveitis as it relates to infectious diseases and ocular manifestations of systemic disease are also discussed.

Five critical elements to ensure the precision medicine.

PubMed

Chen, Chengshui; He, Mingyan; Zhu, Yichun; Shi, Lin; Wang, Xiangdong

2015-06-01

The precision medicine as a new emerging area and therapeutic strategy has occurred and was practiced in the individual and brought unexpected successes, and gained high attentions from professional and social aspects as a new path to improve the treatment and prognosis of patients. There will be a number of new components to appear or be discovered, of which clinical bioinformatics integrates clinical phenotypes and informatics with bioinformatics, computational science, mathematics, and systems biology. In addition to those tools, precision medicine calls more accurate and repeatable methodologies for the identification and validation of gene discovery. Precision medicine will bring more new therapeutic strategies, drug discovery and development, and gene-oriented treatment. There is an urgent need to identify and validate disease-specific, mechanism-based, or epigenetics-dependent biomarkers to monitor precision medicine, and develop "precision" regulations to guard the application of precision medicine.

The Effect of Nursing Quality Improvement and Mobile Health Interventions on Infant Sleep Practices: A Randomized Clinical Trial.

PubMed

Moon, Rachel Y; Hauck, Fern R; Colson, Eve R; Kellams, Ann L; Geller, Nicole L; Heeren, Timothy; Kerr, Stephen M; Drake, Emily E; Tanabe, Kawai; McClain, Mary; Corwin, Michael J

2017-07-25

Inadequate adherence to recommendations known to reduce the risk of sudden unexpected infant death has contributed to a slowing in the decline of these deaths. To assess the effectiveness of 2 interventions separately and combined to promote infant safe sleep practices compared with control interventions. Four-group cluster randomized clinical trial of mothers of healthy term newborns who were recruited between March 2015 and May 2016 at 16 US hospitals with more than 100 births annually. Data collection ended in October 2016. All participants were beneficiaries of a nursing quality improvement campaign in infant safe sleep practices (intervention) or breastfeeding (control), and then received a 60-day mobile health program, in which mothers received frequent emails or text messages containing short videos with educational content about infant safe sleep practices (intervention) or breastfeeding (control) and queries about infant care practices. The primary outcome was maternal self-reported adherence to 4 infant safe sleep practices of sleep position (supine), sleep location (room sharing without bed sharing), soft bedding use (none), and pacifier use (any); data were collected by maternal survey when the infant was aged 60 to 240 days. Of the 1600 mothers who were randomized to 1 of 4 groups (400 per group), 1263 completed the survey (78.9%). The mean (SD) maternal age was 28.1 years (5.8 years) and 32.8% of respondents were non-Hispanic white, 32.3% Hispanic, 27.2% non-Hispanic black, and 7.7% other race/ethnicity. The mean (SD) infant age was 11.2 weeks (4.4 weeks) and 51.2% were female. In the adjusted analyses, mothers receiving the safe sleep mobile health intervention had higher prevalence of placing their infants supine compared with mothers receiving the control mobile health intervention (89.1% vs 80.2%, respectively; adjusted risk difference, 8.9% [95% CI, 5.3%-11.7%]), room sharing without bed sharing (82.8% vs 70.4%; adjusted risk difference, 12.4% [95% CI, 9.3%-15.1%]), no soft bedding use (79.4% vs 67.6%; adjusted risk difference, 11.8% [95% CI, 8.1%-15.2%]), and any pacifier use (68.5% vs 59.8%; adjusted risk difference, 8.7% [95% CI, 3.9%-13.1%]). The independent effect of the nursing quality improvement intervention was not significant for all outcomes. Interactions between the 2 interventions were only significant for the supine sleep position. Among mothers of healthy term newborns, a mobile health intervention, but not a nursing quality improvement intervention, improved adherence to infant safe sleep practices compared with control interventions. Whether widespread implementation is feasible or if it reduces sudden and unexpected infant death rates remains to be studied. clinicaltrials.gov Identifier: NCT01713868.

Sudden unexpected death related to enterovirus myocarditis: histopathology, immunohistochemistry and molecular pathology diagnosis at post-mortem

PubMed Central

2012-01-01

Background Viral myocarditis is a major cause of sudden unexpected death in children and young adults. Until recently, coxsackievirus B3 (CVB3) has been the most commonly implicated virus in myocarditis. At present, no standard diagnosis is generally accepted due to the insensitivity of traditional diagnostic tests. This has prompted health professionals to seek new diagnostic approaches, which resulted in the emergence of new molecular pathological tests and a more detailed immunohistochemical and histopathological analysis. When supplemented with immunohistochemistry and molecular pathology, conventional histopathology may provide important clues regarding myocarditis underlying etiology. Methods This study is based on post-mortem samples from sudden unexpected death victims and controls who were investigated prospectively. Immunohistochemical investigations for the detection of the enteroviral capsid protein VP1 and the characterization and quantification of myocardial inflammatory reactions as well as molecular pathological methods for enteroviral genome detection were performed. Results Overall, 48 sudden unexpected death victims were enrolled. As for controls, 37 cases of unnatural traffic accident victims were studied. Enterovirus was detected in 6 sudden unexpected death cases (12.5 %). The control samples were completely enterovirus negative. Furthermore, the enteroviral capsid protein VP1 in the myocardium was detected in enterovirus-positive cases revealed by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Unlike control samples, immunohistochemical investigations showed a significant presence of T and B lymphocytes in sudden unexpected death victims. Conclusions Our findings demonstrate clearly a higher prevalence of viral myocarditis in cases of sudden unexpected death compared to control subjects, suggesting that coxsackie B enterovirus may contribute to myocarditis pathogenesis significantly. PMID:22966951

Evaluation of the DAVROS (Development And Validation of Risk-adjusted Outcomes for Systems of emergency care) risk-adjustment model as a quality indicator for healthcare

PubMed Central

Wilson, Richard; Goodacre, Steve W; Klingbajl, Marcin; Kelly, Anne-Maree; Rainer, Tim; Coats, Tim; Holloway, Vikki; Townend, Will; Crane, Steve

2014-01-01

Background and objective Risk-adjusted mortality rates can be used as a quality indicator if it is assumed that the discrepancy between predicted and actual mortality can be attributed to the quality of healthcare (ie, the model has attributional validity). The Development And Validation of Risk-adjusted Outcomes for Systems of emergency care (DAVROS) model predicts 7-day mortality in emergency medical admissions. We aimed to test this assumption by evaluating the attributional validity of the DAVROS risk-adjustment model. Methods We selected cases that had the greatest discrepancy between observed mortality and predicted probability of mortality from seven hospitals involved in validation of the DAVROS risk-adjustment model. Reviewers at each hospital assessed hospital records to determine whether the discrepancy between predicted and actual mortality could be explained by the healthcare provided. Results We received 232/280 (83%) completed review forms relating to 179 unexpected deaths and 53 unexpected survivors. The healthcare system was judged to have potentially contributed to 10/179 (8%) of the unexpected deaths and 26/53 (49%) of the unexpected survivors. Failure of the model to appropriately predict risk was judged to be responsible for 135/179 (75%) of the unexpected deaths and 2/53 (4%) of the unexpected survivors. Some 10/53 (19%) of the unexpected survivors died within a few months of the 7-day period of model prediction. Conclusions We found little evidence that deaths occurring in patients with a low predicted mortality from risk-adjustment could be attributed to the quality of healthcare provided. PMID:23605036

Structural imaging biomarkers of sudden unexpected death in epilepsy

PubMed Central

Wandschneider, Britta; Koepp, Matthias; Scott, Catherine; Micallef, Caroline; Balestrini, Simona; Sisodiya, Sanjay M.; Thom, Maria; Harper, Ronald M.; Sander, Josemir W.; Vos, Sjoerd B.; Duncan, John S.; Lhatoo, Samden

2015-01-01

Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies. PMID:26264515

Bacillus Calmette-Guérin vaccination at birth: Effects on early childhood infections, growth, and development.

PubMed

Kjærgaard, Jesper

2016-11-01

The Bacillus Calmette-Guérin vaccine (BCG), which is used to protect against tuberculosis, has been associated with a variety of other effects since it was developed almost 100 years ago. Most notably, observational studies and randomized clinical trials from low-income countries indicate that it protects against unrelated infections, i.e. a so-called non-specific effect. The Danish Calmette Study was conducted to study these effects in a high-income population. The immune response to BCG is not fully understood but involves a pro-inflammatory profiling of the immune system, also when exposed to unrelated pathogens. Immune changes have been implicated in changes in both child growth and child development and for that reason we also studied these outcomes. We randomized 4262 children at birth to receive BCG vaccination at birth or to a no-intervention control group. We had pre-specified subgroup analyses of child sex, prematurity, and maternal BCG vaccination. The statistical analysis plan was finalized prior to unblinding of the data. Follow-up for the outcomes reported in this thesis consisted of telephone interviews and clinical examination at age 3 and 13 months, as well as online developmental questionnaires distributed to the parents at 12 months and additionally to the parents of premature children at age 6 and 22 months. The outcomes of this thesis were number of parent reported infections, child growth and body composition, and child psychomotor development. Overall, there was no effect of BCG on either incidence of infections, growth, body composition or psychomotor development. A subgroup analysis of children of mothers who were BCG vaccinated showed a reduced incidence of infections from 0 to 3 months among BCG vaccinated children (incidence rate ratio = 0.62, CI: 0.39 to 0.98), but there was no effect from 3 to 13 months. Previous research has shown that maternal exposure to BCG or mycobacteria can alter the effect of BCG in the offspring, and thus the unexpected lack of effect on overall infections can possibly be explained by the lack of maternal exposure to BCG in our study, as only 17% of the mothers were BCG vaccinated. In the studies where non-specific protective effects of BCG have previously been found, most of the mothers were BCG vaccinated or exposed to mycobacteria. Premature children had a non-significant increased risk of infection, which was corroborated by an analysis of hospitalizations for infections (not reported in this thesis). This was also unexpected as previous research indicated a more beneficial effect among low birth weight children. The study did not have power enough to exclude a negative effect of BCG on the development of premature children, and thus a cautious approach to vaccinating premature children may be prudent in a high-income setting. We succeeded in recruiting the planned number of participants and had high follow-up rates for most outcomes. A limitation is that it was not feasible to blind the parents to the randomization group. In conclusion, BCG did not have any public health benefit on incidence of infections and did not affect child growth or child development in the present study.

Language and music: differential hemispheric dominance in detecting unexpected errors in the lyrics and melody of memorized songs.

PubMed

Yasui, Takuya; Kaga, Kimitaka; Sakai, Kuniyoshi L

2009-02-01

Using magnetoencephalography (MEG), we report here the hemispheric dominance of the auditory cortex that is selectively modulated by unexpected errors in the lyrics and melody of songs (lyrics and melody deviants), thereby elucidating under which conditions the lateralization of auditory processing changes. In experiment 1 using familiar songs, we found that the dipole strength of responses to the lyrics deviants was left-dominant at 140 ms (M140), whereas that of responses to the melody deviants was right-dominant at 130 ms (M130). In experiment 2 using familiar songs with a constant syllable or pitch, the dipole strength of frequency mismatch negativity elicited by oddballs was left-dominant. There were significant main effects of experiment (1 and 2) for the peak latencies and for the coordinates of the dipoles, indicating that the M140 and M130 were not the frequency mismatch negativity. In experiment 3 using newly memorized songs, the right-dominant M130 was observed only when the presented note was unexpected one, independent of perceiving unnatural pitch transitions (i.e., perceptual saliency) and of selective attention to the melody of songs. The consistent right-dominance of the M130 between experiments 1 and 3 suggests that the M130 in experiment 1 is due to unexpected notes deviating from well-memorized songs. On the other hand, the left-dominant M140 was elicited by lyrics deviants, suggesting the influence of top-down linguistic information and the memory of the familiar songs. We thus conclude that the left- lateralized M140 and right-lateralized M130 reflect the expectation based on top-down information of language and music, respectively.

77 FR 42947 - Unexpected Urgent Refugee and Migration Needs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

... unexpected and urgent refugee and migration needs, including by contributions to international, governmental, and nongovernmental organizations and payment of administrative expenses of the Bureau of Population...

School Crisis Response: Expecting the Unexpected.

ERIC Educational Resources Information Center

Lichtenstein, Robert; And Others

1994-01-01

The typical administrator certification program does not devote specific attention to shootings, suicide, terminal illness, and natural disasters. A crisis of major proportion calls for enlightened leadership: a take-charge manner, combined with effective teamwork and delegation of vital operations. Crisis teams should exist at regional, district,…

The Kalamazoo Promise Scholarship

ERIC Educational Resources Information Center

Bartik, Timothy J.; Lachowska, Marta

2014-01-01

This study takes advantage of the unexpected announcement of the Kalamazoo Promise to study its effects on student achievement and behavior in high school. The Kalamazoo Promise provides college scholarships to graduates of Kalamazoo Public Schools (KPS), a midsized urban school district in Michigan that is racially and economically diverse.…

Moment measurements in dynamic and quasi-static spine segment testing using eccentric compression are susceptible to artifacts based on loading configuration.

PubMed

Van Toen, Carolyn; Carter, Jarrod W; Oxland, Thomas R; Cripton, Peter A

2014-12-01

The tolerance of the spine to bending moments, used for evaluation of injury prevention devices, is often determined through eccentric axial compression experiments using segments of the cadaver spine. Preliminary experiments in our laboratory demonstrated that eccentric axial compression resulted in "unexpected" (artifact) moments. The aim of this study was to evaluate the static and dynamic effects of test configuration on bending moments during eccentric axial compression typical in cadaver spine segment testing. Specific objectives were to create dynamic equilibrium equations for the loads measured inferior to the specimen, experimentally verify these equations, and compare moment responses from various test configurations using synthetic (rubber) and human cadaver specimens. The equilibrium equations were verified by performing quasi-static (5 mm/s) and dynamic experiments (0.4 m/s) on a rubber specimen and comparing calculated shear forces and bending moments to those measured using a six-axis load cell. Moment responses were compared for hinge joint, linear slider and hinge joint, and roller joint configurations tested at quasi-static and dynamic rates. Calculated shear force and bending moment curves had similar shapes to those measured. Calculated values in the first local minima differed from those measured by 3% and 15%, respectively, in the dynamic test, and these occurred within 1.5 ms of those measured. In the rubber specimen experiments, for the hinge joint (translation constrained), quasi-static and dynamic posterior eccentric compression resulted in flexion (unexpected) moments. For the slider and hinge joints and the roller joints (translation unconstrained), extension ("expected") moments were measured quasi-statically and initial flexion (unexpected) moments were measured dynamically. In the cadaver experiments with roller joints, anterior and posterior eccentricities resulted in extension moments, which were unexpected and expected, for those configurations, respectively. The unexpected moments were due to the inertia of the superior mounting structures. This study has shown that eccentric axial compression produces unexpected moments due to translation constraints at all loading rates and due to the inertia of the superior mounting structures in dynamic experiments. It may be incorrect to assume that bending moments are equal to the product of compression force and eccentricity, particularly where the test configuration involves translational constraints and where the experiments are dynamic. In order to reduce inertial moment artifacts, the mass, and moment of inertia of any loading jig structures that rotate with the specimen should be minimized. Also, the distance between these structures and the load cell should be reduced.

Does semantic preactivation reduce inattentional blindness?

PubMed

Kreitz, Carina; Schnuerch, Robert; Furley, Philip A; Gibbons, Henning; Memmert, Daniel

2015-04-01

We are susceptible to failures of awareness if a stimulus occurs unexpectedly and our attention is focused elsewhere. Such inattentional blindness is modulated by various parameters, including stimulus attributes, the observer's cognitive resources, and the observer's attentional set regarding the primary task. In three behavioral experiments with a total of 360 participants, we investigated whether mere semantic preactivation of the color of an unexpected object can reduce inattentional blindness. Neither explicitly mentioning the color several times before the occurrence of the unexpected stimulus nor priming the color more implicitly via color-related concepts could significantly reduce the susceptibility to inattentional blindness. Even putting the specific color concept in the main focus of the primary task did not lead to reduced inattentional blindness. Thus, we have shown that the failure to consciously perceive unexpected objects was not moderated by semantic preactivation of the objects' most prominent feature: its color. We suggest that this finding reflects the rather general principle that preactivations that are not motivationally relevant for one's current selection goals do not suffice to make an unexpected object overcome the threshold of awareness.

Pharmacokinetic Herb-Drug Interactions: Insight into Mechanisms and Consequences.

PubMed

Oga, Enoche F; Sekine, Shuichi; Shitara, Yoshihisa; Horie, Toshiharu

2016-04-01

Herbal medicines are currently in high demand, and their popularity is steadily increasing. Because of their perceived effectiveness, fewer side effects and relatively low cost, they are being used for the management of numerous medical conditions. However, they are capable of affecting the pharmacokinetics and pharmacodynamics of coadministered conventional drugs. These interactions are particularly of clinically relevance when metabolizing enzymes and xenobiotic transporters, which are responsible for the fate of many drugs, are induced or inhibited, sometimes resulting in unexpected outcomes. This article discusses the general use of herbal medicines in the management of several ailments, their concurrent use with conventional therapy, mechanisms underlying herb-drug interactions (HDIs) as well as the drawbacks of herbal remedy use. The authors also suggest means of surveillance and safety monitoring of herbal medicines. Contrary to popular belief that "herbal medicines are totally safe," we are of the view that they are capable of causing significant toxic effects and altered pharmaceutical outcomes when coadministered with conventional medicines. Due to the paucity of information as well as sometimes conflicting reports on HDIs, much more research in this field is needed. The authors further suggest the need to standardize and better regulate herbal medicines in order to ensure their safety and efficacy when used alone or in combination with conventional drugs.

Apolipoprotein E genotypes do not influence the age of onset in Huntington's disease

PubMed Central

Saft, C; Andrich, J; Brune, N; Gencik, M; Kraus, P; Przuntek, H; Epplen, J

2004-01-01

Objective: The ε4 allele of the apolipoprotein E (ApoE) gene has been defined as a critical factor for early onset neurodegeneration in Pick's, Parkinson's, and Alzheimer's disease. Unexpectedly, the ε4 allele appeared to delay the age of onset in Huntington's disease (HD) patients. Furthermore, sex specific effects were reported on earlier age of onset due to the ApoE ε2ε3 genotype in males with HD. The age of onset of HD is known to be negatively correlated with increasing lengths of pathogenetic CAG expansions in the huntingtin gene. Methods: In order to examine the effects of CAG block lengths, we have correlated ApoE genotypes with the age of onset in 145 patients symptomatic for HD with psychiatric and somatic symptoms (depression, psychosis, dementia, choreic, and other movement disorders) harbouring only modestly expanded huntingtin alleles (41–45 CAGs). Results: The negative correlation between age of onset and CAG block length was established in our HD cohort. Statistically significant effects of the ε4 allele were not obvious regarding clinical characteristics including age of onset, nor were any sex differences for the ε2ε3 genotype observed. Conclusion: The ApoE genotype does not affect the course of HD significantly. PMID:15548484

Possible Oxcarbazepine Inductive Effects on Aripiprazole Metabolism: A Case Report.

PubMed

McGrane, Ian R; Loveland, Joshua G; de Leon, Jose

2017-01-01

Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness. A limited number of reports are available which discuss reduced atypical antipsychotic concentrations secondary to oxcarbazepine CYP3A4 induction. We report a young boy taking oxcarbazepine (1200 mg/d) who presented with an unexpectedly low serum aripiprazole concentration. Utilizing therapeutic drug monitoring, pharmacogenetic testing, and a tool to evaluate drug-drug interactions, we estimate that oxcarbazepine possibly reduced his serum aripiprazole concentration by 68%. Our report is important, as it is the first to describe a drug-drug interaction between oxcarbazepine and aripiprazole. This report should encourage the completion of in vitro and clinical studies and the publication of case reports describing the possible inductive effects of oxcarbazepine on atypical antipsychotics (including cariprazine, lurasidone, quetiapine, aripiprazole, brexpiprazole, iloperidone, and risperidone) mediated by induction of the CYP3A4 metabolic pathway.

Causes of death after fluid bolus resuscitation: new insights from FEAST

PubMed Central

2013-01-01

The Fluid Expansion as Supportive Therapy (FEAST study) was an extremely well conducted study that gave unexpected results. The investigators had reported that febrile children with impaired perfusion treated in low-income countries without access to intensive care are more likely to die if they receive bolus resuscitation with albumin or saline compared with no bolus resuscitation at all. In a secondary analysis of the trial, published in BMC Medicine, the authors found that increased mortality was evident in patients who presented with clinical features of severe shock in isolation or in conjunction with features of respiratory or neurological failure. The cause of excess deaths was primarily refractory shock and not fluid overload. These features are consistent with a potential cardiotoxic or ischemia-reperfusion injury following resuscitation with boluses of intravenous fluid. Although these effects may have been amplified by the absence of invasive monitoring, mechanical ventilation or vasopressors, the results provide compelling insights into the effects of intravenous fluid resuscitation and potential adverse effects that extend beyond the initial resuscitation period. These data add to the increasing body of literature about the safety and efficacy of intravenous resuscitation fluids, which may be applicable to management of other populations of critically ill patients. PMID:23497460

Failure to replicate the deleterious effects of safety behaviors in exposure therapy.

PubMed

Sy, Jennifer T; Dixon, Laura J; Lickel, James J; Nelson, Elizabeth A; Deacon, Brett J

2011-05-01

The current study attempted to replicate the finding obtained by Powers, Smits, and Telch (2004; Journal of Consulting and Clinical Psychology, 72, 448-545) that both the availability and utilization of safety behaviors interfere with the efficacy of exposure therapy. An additional goal of the study was to evaluate which explanatory theories about the detrimental effects of safety behaviors best account for this phenomenon. Undergraduate students (N=58) with high claustrophobic fear were assigned to one of three treatment conditions: (a) exposure only, (b) exposure with safety behavior availability, and (c) exposure with safety behavior utilization. Participants in each condition improved substantially, and there were no significant between-group differences in fear reduction. Unexpectedly, exposure with safety behavior utilization led to significantly greater improvement in self-efficacy and claustrophobic cognitions than exposure only. The extent to which participants inferred danger from the presence of safety aids during treatment was associated with significantly less improvement on all outcome measures. The findings call into question the hypothesized deleterious effects of safety behaviors on the outcome of exposure therapy and highlight a possible mechanism through which the mere presence of safety cues during exposure trials might affect treatment outcomes depending on participants' perceptions of the dangerousness of exposure stimuli. Published by Elsevier Ltd.

Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

PubMed

Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer

2015-01-01

We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination.

PubMed

Warner, Daniel A; Addis, Elizabeth; Du, Wei-guo; Wibbels, Thane; Janzen, Fredric J

2014-09-15

Steroid hormones affect sex determination in a variety of vertebrates. The feminizing effects of exposure to estradiol and the masculinizing effects of aromatase inhibition during development are well established in a broad range of vertebrate taxa, but paradoxical findings are occasionally reported. Four independent experiments were conducted on two turtle species with temperature-dependent sex determination (Chrysemys picta and Chelydra serpentina) to quantify the effects of egg incubation temperature, estradiol, and an aromatase inhibitor on offspring sex ratios. As expected, the warmer incubation temperatures induced female development and the cooler temperatures produced primarily males. However, application of an aromatase inhibitor had no effect on offspring sex ratios, and exogenous applications of estradiol to eggs produced male offspring across all incubation temperatures. These unexpected results were remarkably consistent across all four experiments and both study species. Elevated concentrations of estradiol could interact with androgen receptors or inhibit aromatase expression, which might result in relatively high testosterone concentrations that lead to testis development. These findings add to a short list of studies that report paradoxical effects of steroid hormones, which addresses the need for a more comprehensive understanding of the role of sex steroids in sexual development. Copyright © 2014 Elsevier Inc. All rights reserved.

Do whole-food animal feeding studies have any value in the safety assessment of GM crops?

PubMed

Herman, Rod A; Ekmay, Ricardo

2014-02-01

The use of whole-food (grain meal contained in feed) animal-feeding studies to support the safety assessment of genetically modified crops has been contentious. This may be, in part, a consequence of poorly agreed upon study objectives. Whole-food animal-feeding studies have been postulated to be useful in detecting both expected and unexpected effects on the composition of genetically modified crops. While the justification of animal feeding studies to detect unexpected effects may be inadequately supported, there may be better justification to conduct such studies in specific cases to investigate the consequences of expected compositional effects including expression of transgenic proteins. Such studies may be justified when (1) safety cannot reasonably be predicted from other evidence, (2) reasonable hypothesis for adverse effects are postulated, (3) the compositional component in question cannot be isolated or enriched in an active form for inclusion in animal feeding studies, and (4) reasonable multiples of exposure can be accomplished relative to human diets. The study design for whole-food animal-feeding studies should be hypotheses-driven, and the types of data collected should be consistent with adverse effects that are known to occur from dietary components of biological origin. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Relativistic Magnetron Priming Experiments and Theory

DTIC Science & Technology

2010-03-29

rest mass and charge of an electron, respectively, c is the speed of light, and V is the voltage drop across the anode-cathode gap. D is the effective ...and Verboncoeur1 as an effect generated by a multipactor model that also requires a seed electron to initiate the process. The existence of a seed...Discovery of unexpected effects of ions in magnetically insulated crossed-field gap. 2) Buneman-Hartree condition was critically re-examined in a

Improving the Clinical Skills Performance of Graduating Medical Students Using “WISE OnCall,” a Multimedia Educational Module

PubMed Central

Szyld, Demian; Uquillas, Kristen; Green, Brad R.; Yavner, Steven D.; Song, Hyuksoon; Nick, Michael W.; Ng, Grace M.; Pusic, Martin V.; Riles, Thomas S.; Kalet, Adina

2017-01-01

Introduction “Transitions to residency” programs are designed to maximize quality and safety of patient care, as medical students become residents. However, best instructional or readiness assessment practices are not yet established. We sought to study the impact of a screen-based interactive curriculum designed to prepare interns to address common clinical coverage issues (WISE OnCall) on the clinical skills demonstrated in simulation and hypothesize that performance would improve after completing the module. Methods Senior medical students were recruited to participate in this single group prestudy/poststudy. Students responded to a call from a standardized nurse (SN) and assessed a standardized patient (SP) with low urine output, interacted with a 45-minute WISE OnCall module on the assessment and management of oliguria, and then evaluated a different SP with low urine output of a different underlying cause. Standardized patients assessed clinical skills with a 37-item, behaviorally anchored checklist measuring clinical skills (intraclass correlation coefficient [ICC], 0.55–0.81). Standardized nurses rated care quality and safety and collaboration and interprofessional communication using a 33-item literature-based, anchored checklist (ICC, 0.47–0.52). Standardized patient and SN ratings of the same student performance were correlated (r, 0.37–0.62; P < 0.01). Physicians assessed clinical reasoning quality based on the students’ patient encounter note (ICC, 0.55–0.68), ratings that did not correlate with SP and SN ratings. We compared pre-post clinical skills performance and clinical reasoning. Fifty-two medical students (31%) completed this institutional review board –approved study. Results Performance as measured by the SPs, SNs, and the postencounter note all showed improvement with mostly moderate to large effect sizes (range of Cohen’s d, 0.30–1.88; P < 0.05) after completion of the online module. Unexpectedly, professionalism as rated by the SP was poorer after the module (Cohen’s d, −0.93; P = 0.000). Discussion A brief computer-based educational intervention significantly improved graduating medical students' clinical skills needed to be ready for residency. PMID:29076970

The rural hospital doctors workforce in New Zealand.

PubMed

Lawrenson, Ross A; Nixon, Garry; Steed, Robin H

2011-01-01

The sustainability of New Zealand's rural hospitals has been in question for some years. Increasingly, clinical services have been centralised and specialist staff have moved to bigger centres. As well as clinical services, the governance of these hospitals has shifted, often due to a shortage of vocationally registered medical practitioners available to lead the clinical services. In 2009 the Medical Council of New Zealand (MCNZ) approved a new vocational scope of practice in Rural Hospital Medicine (RHM). The present study was designed to establish the current composition of the rural hospital medical workforce at the introduction of this new scope of practice. This study was a 2009 cross-sectional survey of rural hospitals approved for RHM training by the MCNZ. Hospital managers were surveyed using a mailed questionnaire. All medical practitioners providing medical care in these hospitals in 2009 were identified, and each was mailed an additional questionnaire. In all, 28 rural hospitals and 107 medical practitioners who provided clinical services were identified; 28 responses (100%) were received to the hospital managers' survey and 69 responses (64%) to the doctors' survey. The managers' survey revealed a shortage of medical practitioners and significant use of locum staff. The workforce had a median age of 47 years, was predominantly male (75%) and principally trained overseas (68%), and 54% was vocationally registered. A proportion of the hospitals (35%) did not have a recognised clinical leader or an active process for credentialing new medical staff. The findings were not unexpected but do quantify the shortage of medical practitioners and the governance issues facing small rural hospitals in New Zealand. The scope of RHM has the potential to attract new doctors into practice, providing greater stability and clinical leadership for these important facilities. The study provides a baseline for a future evaluation of the effectiveness of the introduction of the new scope of practice.

An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq

DTIC Science & Technology

2010-05-01

Christopher E. Curtis, MC USAt 188143 ABSTRACT Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Cases have been...MILITARY MEDICINE, 175,5:367,2010 An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq CPT Jeremy B. Fisher, SP USA *; CPT...Turkey.3-S We report an unexpected case of Lyme disease from Iraq. CASE REPORT A 28-year-old active duty Army male, on a deployment to northern Iraq

Effects of pushing height on trunk posture and trunk muscle activity when a cart suddenly starts or stops moving.

PubMed

Lee, Yun-Ju; Hoozemans, Marco J M; van Dieën, Jaap H

2012-01-01

Unexpected sudden (un)loading of the trunk may induce inadequate responses of trunk muscles and uncontrolled trunk motion. These unexpected perturbations may occur in pushing tasks, when the cart suddenly starts moving (unloading) or is blocked by an obstacle (loading). In pushing, handle height affects the user's working posture, which may influence trunk muscle activity and trunk movement in response to the perturbation. Eleven healthy male subjects pushed a 200 kg cart with handles at shoulder and hip height in a start condition (sudden release of brakes) and a stop condition (bumping into an obstacle). Before the perturbation, the baseline of the trunk inclination, internal moment and trunk extensor muscle activity were significantly higher when pushing at hip height than at shoulder height. After the perturbation, the changes in trunk inclination and internal moment were significantly larger when pushing at shoulder height than at hip height in both conditions. The opposite directions of changes in trunk inclination and internal moment suggest that the unexpected perturbations caused uncontrolled trunk motion. Pushing at shoulder height may impose a high risk of low-back injury due to the low trunk stiffness and large involuntary trunk motion occurring after carts suddenly move or stop.

Inattentional blindness for a gun during a simulated police vehicle stop.

PubMed

Simons, Daniel J; Schlosser, Michael D

2017-01-01

People often fail to notice unexpected objects and events when they are focusing attention on something else. Most studies of this "inattentional blindness" use unexpected objects that are irrelevant to the primary task and to the participant (e.g., gorillas in basketball games or colored shapes in computerized tracking tasks). Although a few studies have examined noticing rates for personally relevant or task-relevant unexpected objects, few have done so in a real-world context with objects that represent a direct threat to the participant. In this study, police academy trainees (n = 100) and experienced police officers (n = 75) engaged in a simulated vehicle traffic stop in which they approached a vehicle to issue a warning or citation for running a stop sign. The driver was either passive and cooperative or agitated and hostile when complying with the officer's instructions. Overall, 58% of the trainees and 33% of the officers failed to notice a gun positioned in full view on the passenger dashboard. The driver's style of interaction had little effect on noticing rates for either group. People can experience inattentional blindness for a potentially dangerous object in a naturalistic real-world context, even when noticing that object would change how they perform their primary task and even when their training focuses on awareness of potential threats.

Controlled English for Effective Communication during Coalition Operations

DTIC Science & Technology

2013-06-01

Linguistic variations and cultural differences often create unexpected challenges for effective communication and thus for Command and Control (C2...CE), and CE-based tools to improve cross- linguistic /cross-cultural communication. We will discuss various types of linguistic variations and cultural...human-computer interaction, reasoning, and explanation CE and CE-based tools can play an important role in facilitating cross- linguistic and cross

Applying metabolomics to cardiometabolic intervention studies and trials: past experiences and a roadmap for the future.

PubMed

Rankin, Naomi J; Preiss, David; Welsh, Paul; Sattar, Naveed

2016-10-01

Metabolomics and lipidomics are emerging methods for detailed phenotyping of small molecules in samples. It is hoped that such data will: (i) enhance baseline prediction of patient response to pharmacotherapies (beneficial or adverse); (ii) reveal changes in metabolites shortly after initiation of therapy that may predict patient response, including adverse effects, before routine biomarkers are altered; and( iii) give new insights into mechanisms of drug action, particularly where the results of a trial of a new agent were unexpected, and thus help future drug development. In these ways, metabolomics could enhance research findings from intervention studies. This narrative review provides an overview of metabolomics and lipidomics in early clinical intervention studies for investigation of mechanisms of drug action and prediction of drug response (both desired and undesired). We highlight early examples from drug intervention studies associated with cardiometabolic disease. Despite the strengths of such studies, particularly the use of state-of-the-art technologies and advanced statistical methods, currently published studies in the metabolomics arena are largely underpowered and should be considered as hypothesis-generating. In order for metabolomics to meaningfully improve stratified medicine approaches to patient treatment, there is a need for higher quality studies, with better exploitation of biobanks from randomized clinical trials i.e. with large sample size, adjudicated outcomes, standardized procedures, validation cohorts, comparison witth routine biochemistry and both active and control/placebo arms. On the basis of this review, and based on our research experience using clinically established biomarkers, we propose steps to more speedily advance this area of research towards potential clinical impact. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles.

PubMed

Yu, Kyung-Rok; Natanson, Hannah; Dunbar, Cynthia E

2016-10-01

Hematopoietic stem and progenitor cells (HSPCs) have great therapeutic potential because of their ability to both self-renew and differentiate. It has been proposed that, given their unique properties, a small number of genetically modified HSPCs could accomplish lifelong, corrective reconstitution of the entire hematopoietic system in patients with various hematologic disorders. Scientists have demonstrated that gene addition therapies-targeted to HSPCs and using integrating retroviral vectors-possess clear clinical benefits in multiple diseases, among them immunodeficiencies, storage disorders, and hemoglobinopathies. Scientists attempting to develop clinically relevant gene therapy protocols have, however, encountered a number of unexpected hurdles because of their incomplete knowledge of target cells, genomic control, and gene transfer technologies. Targeted gene-editing technologies using engineered nucleases such as ZFN, TALEN, and/or CRISPR/Cas9 RGEN show great clinical promise, allowing for the site-specific correction of disease-causing mutations-a process with important applications in autosomal dominant or dominant-negative genetic disorders. The relative simplicity of the CRISPR/Cas9 system, in particular, has sparked an exponential increase in the scientific community's interest in and use of these gene-editing technologies. In this minireview, we discuss the specific applications of gene-editing technologies in human HSPCs, as informed by prior experience with gene addition strategies. HSPCs are desirable but challenging targets; the specific mechanisms these cells evolved to protect themselves from DNA damage render them potentially more susceptible to oncogenesis, especially given their ability to self-renew and their long-term proliferative potential. We further review scientists' experience with gene-editing technologies to date, focusing on strategies to move these techniques toward implementation in safe and effective clinical trials.

A phase III, randomized, double-blind, matched-pairs, active-controlled clinical trial and preclinical animal study to compare the durability, efficacy and safety between polynucleotide filler and hyaluronic acid filler in the correction of crow's feet: a new concept of regenerative filler.

PubMed

Pak, Chang Sik; Lee, Jongho; Lee, Hobin; Jeong, Jaehoon; Kim, Eun-Hee; Jeong, Jinwook; Choi, Hyeyeon; Kim, Byunghwi; Oh, Sujin; Kim, Iksoo; Heo, Chan Yeong

2014-11-01

The Rejuran® is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran® on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire®; and Group 3 were treated with Rejuran®. The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran® treatment for crow's feet on one side and Yvoire-Hydro® on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran® group showed similar durability and inflammatory response to the Yvoire® group. Upon efficacy assessment, the Rejuran® group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran®, as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.

Effectiveness of 'rehabilitation in the home' service.

PubMed

Bharadwaj, Sneha; Bruce, David

2014-11-01

Rehabilitation in the home (RITH) services increasingly provide hospital substitution services. This study examines clinical outcomes in a large metropolitan RITH service in Western Australia. The 2010 database of Fremantle Hospital RITH service was interrogated to identify the clinical profile of cases, length of stay (LOS) and clinical outcomes. Negative outcomes included death or unexpected hospital readmission. Multiple logistic regression modelling was used to explore associations with negative outcomes. This study was reviewed by the Institutional Review Board which deemed it not to require ethics approval. There were 1348 cases managed by RITH: 70.6% were aged≥65 years; elective joint replacement (29.7%), medical conditions (20%), stroke (13%), hip fractures (10%) were major contributors. The majority (93.3%) were discharged after a median of 9 days. Negative outcomes occurred in 90 cases (6.7%), including five deaths (0.4%) and 85 readmissions (6.3%). Independent associations with negative outcomes included older age (odds ratio (OR) (95% CI); 1.02, P=0.006), orthopaedic conditions (OR 1.91, P=0.004) and longer inpatient LOS (OR 1.96, P=0.003). Age above 80 years was independently associated with risk of negative outcome (OR 2.99, P=0.004). RITH had a low rate of negative outcomes. The database proved useful for monitoring quality of service provision. WHAT IS KNOWN ABOUT THE TOPIC?: Rehabilitation in the home environment has proven cost effective for multiple conditions, particularly stroke and elective joint surgery, among others, facilitating better quality of life, with reduced rates of delirium and mortality. Overall there are few negative outcomes and death is rare. WHAT DOES THIS PAPER ADD?: Although RITH services are widely utilised as bed substitution services, there is scant literature on clinical outcomes while within the service. This study focuses on frequency of good and poor clinical outcomes in a well-established RITH service in Western Australia, suggesting pattern recognition of an at-risk cohort by identifying potentially useful predictors of poor outcome. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?: RITH services are a safe alternative for many, including older people. Health administration databases are useful tools to monitor clinical outcomes. Clinical indicators such as older age, long hospital stay and orthopaedic diagnoses may be useful predictors of poor outcomes in such services.