bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychiatric and neurologic risk factors for incident cases of new‐onset epilepsy in older adults: Data from U.S. Medicare beneficiaries
Authors: Martin Roy C. , Faught Edward , Richman Joshua , Funkhouser Ellen , Kim Yongin , Clements Kay , Pisu Maria
Published: June 2014

Objective

Neurologic diseases such as stroke are risk factors for new‐onset epilepsy in older adults. Recent evidence suggests that psychiatric disorders independently predict epilepsy in older male veterans. Our aim was to examine the relationship between these disorders in a population‐based study of older adults that also included women and minorities.

Methods

We used a national 5% random sample of 2005 Medicare beneficiaries including all 50 US states and Washington, DC. Beneficiaries were 65 years of age or older, with continuous Medicare Part A and Part B coverage and not in managed care plans. Epilepsy cases were identified from claims for physician visits, hospitalizations, and outpatient procedures. We used logistic regressions for the overall sample and stratified by gender to determine whether risk of new‐onset epilepsy was associated with prior history of psychiatric (i.e., depression, psychosis, bipolar disorder, schizophrenia, posttraumatic stress disorder (PTSD), adjustment disorder, and substance abuse/dependence) and neurologic conditions (i.e., cerebrovascular disease, dementia, traumatic brain injury, brain tumor, metastatic cancer).

Results

Preexisting psychiatric disorders were significantly associated with new‐onset epilepsy in the study population as were the neurologic conditions evaluated. Five of the seven psychiatric disorders examined were independently associated with new‐onset epilepsy; substance abuse, psychosis, bipolar disorder, schizophrenia, and depression. Gender interaction effects were found for substance abuse/dependence and brain tumors.

Significance

Both neurologic and psychiatric factors significantly predicted new‐onset epilepsy in a population‐based sample of male and female older adults. These results support earlier findings and extend the understanding of risk models for new‐onset epilepsy in broader older adult populations.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
The pivotal role of the supplementary motor area in startle epilepsy as demonstrated by SEEG epileptogenicity maps
Authors: Job Anne‐Sophie , De Palma Luca , Principe Alessandro , Hoffmann Dominique , Minotti Lorella , Chabardès Stephan , David Olivier , Kahane Philippe
Published: June 2014

Startle seizures belong to reflex epilepsy syndromes. They usually occur in patients with mental deficiency and showing widely extended cortical lesions, often involving the sensorimotor area. Here we report three cases who did not fulfill these criteria, and in whom stereotactic electroencephalography (SEEG) recordings demonstrated the prominent involvement of the supplementary motor area (SMA). Visual analysis was complemented by time‐frequency analysis of SEEG signals using a neuroimaging approach (Epileptogenicity Maps), which showed at seizure onset a significant increase of high frequency oscillations (HFOs, 60–100 Hz) over the premotor and prefrontal areas. Critically, in all cases, the SMA showed ictal HFOs at seizure onset and was included in the surgical resection. All patients became seizure‐free after surgery, and histopathological examinations showed no specific lesion. These cases suggest the prominent but not exclusive role of SMA in startle seizures, and highlight the fact that surgery can be considered even in the absence of any magnetic resonance imaging (MRI) lesion.
Once‐daily USL255 as adjunctive treatment of partial‐onset seizures: Randomized phase III study
Authors: Chung Steve S. , Fakhoury Toufic A. , Hogan R. Edward , Nagaraddi Venkatesh N. , Blatt Ilan , Lawson Balduin , Arnold Stephan , Anders Bob , Clark Annie M. , Laine Dawn , Meadows R. Shawn , Halvorsen Mark B. ,   the PREVAIL Study Group
Published: June 2014

Objective

To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended‐release capsules, as an adjunctive treatment for refractory partial‐onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs.

Methods

In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once‐daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE‐31‐P) and clinical global impression of change (CGI‐C), were evaluated.

Results

Across the entire 11‐week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life.

Significance

The PREVAIL phase III clinical study demonstrated that once‐daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects.
Whole‐exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation
Authors: Venkateswaran Sunita , Myers Ken A. , Smith Amanda C. , Beaulieu Chandree L. , Schwartzentruber Jeremy A. ,   FORGE Canada Consortium, Majewski Jacek , Bulman Dennis , Boycott Kym M. , Dyment David A.
Published: June 2014

We present a 4‐year‐old girl with profound global developmental delay and refractory epilepsy characterized by multiple seizure types (partial complex with secondary generalization, tonic, myoclonic, and atypical absence). Her seizure semiology did not fit within a specific epileptic syndrome. Despite a broad metabolic and genetic workup, a diagnosis was not forthcoming. Whole‐exome sequencing with a trio analysis (affected child compared to unaffected parents) was performed and identified a novel de novo missense mutation in GRIN2A, c.2449A>G, p.Met817Val, as the likely cause of the refractory epilepsy and global developmental delay. GRIN2A encodes a subunit of N‐methyl‐d‐aspartate (NMDA) receptor that mediates excitatory transmission in the central nervous system. A significant reduction in the frequency and the duration of her seizures was observed after the addition of topiramate over a 10‐month period. Further prospective studies in additional patients with mutations in GRIN2A will be required to optimize seizure management for this rare disorder. This report expands the current phenotype associated with GRIN2A mutations.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Seizure frequency and patient‐centered outcome assessment in epilepsy
Authors: Choi Hyunmi , Hamberger Marla J. , Munger Clary Heidi , Loeb Rebecca , Onchiri Frankline M. , Baker Gus , Hauser W. Allen , Wong John B.
Published: June 2014

Objective

Seizure frequency represents a commonly assessed epilepsy status, but in the context of the growing trend toward patient‐centered care, we examined the adequacy of seizure frequency as a measure of epilepsy status as perceived by the patient.

Methods

Between 2006 and 2008, we assessed seizure frequency, mood, and preference‐based health‐related quality of life (HRQOL) measured with the visual analog scale metric in 182 adult patients sampled consecutively. Using nonparametric tests and Monte Carlo computer simulations, we analyzed the relationship between preference‐based HRQOL and seizure frequency, and using regression analyses, we tested for significant predictors of preference‐based HRQOL.

Results

Only patients who had been seizure‐free for >1 year had significantly higher preference‐based HRQOL (p < 0.0001) than those who experienced any recurrent seizure, regardless of their seizure frequency. Among patients with recurrent seizures, preference‐based HRQOL and seizure frequency were not monotonically, linearly related. For patients with similar seizure frequency, preference‐based HRQOL varied substantially with large overlaps in preference‐based HRQOL across different seizure frequency categories. The Monte Carlo simulation found that seizure frequency was a poor predictor of preference‐based HRQOL about one third of the time. The presence of depressive symptoms was an independent predictor of preference‐based HRQOL measure, accounting for 33.5% of the variation in scores between patients.

Significance

Our findings highlight the importance of attaining complete seizure freedom and the substantial variation in preference‐based HRQOL among patients with similar seizure frequencies. To improve assessment of patient‐centered outcomes in epilepsy, we encourage adding direct measurement of preference‐based HRQOL into clinical care..

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Responses by Central‐Place Foragers to Manipulations of Brood Size: Parent Flickers Respond to Proximate Cues but do not Increase Work Rate
Authors: Gow Elizabeth A. , Wiebe Karen L.
Published: June 2014

Manipulations of brood size measure the willingness or ability of parents to invest in offspring and different reproductive roles may lead to differences in feeding effort between the sexes. Parental investment in birds is usually assessed by quantifying feeding rates, but this provides an incomplete picture of parental effort because it fails to account for how parents collect food on the landscape. We studied northern flickers (Colaptes auratus), a woodpecker in which males provide the majority of parental care and used a repeated measures design and short‐term (24 h) brood enlargements (N = 35) and reductions (N = 27) to assess effects of treatment on feeding rates to nestlings and parental foraging behaviour. Parents of enlarged broods did not significantly increase feeding rate, resulting in a decline in nestling mass. Parents of reduced broods decreased their feeding rates by 84%, but increased per capita feeding rates, resulting in nestling mass gain. The variation in feeding rates to enlarged broods was not influenced by feather corticosterone, body condition, feather re‐growth rate or mass change between the incubation and nestling periods. Foraging pattern on the landscape remained the same during the enlarged treatment for both sexes. We conclude that flickers respond to proximate cues in brood demands, but do not increase feeding rates to enlarged broods, at least in the short term. A literature review suggested that this lack of response is atypical for short‐lived species. We hypothesize that parents in species with large home ranges and long nestling periods face energetic limitations that constrain their ability to respond to enlarged broods. We encourage future studies to assess foraging behaviour on the landscape to document important trade‐offs for parents such as predation risk and energy expenditure while feeding offspring.
Catechol‐O‐methyltransferase gene methylation and substance use in adolescents: the TRAILS study
Authors: van der Knaap L. J. , Schaefer J. M. , Franken I. H. A. , Verhulst F. C. , van Oort F. V. A. , Riese H.
Published: June 2014

Substance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol‐O‐methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val108/158Met polymorphism modulates COMT activity and thus dopamine levels, and has been linked to substance use. COMT gene methylation, on the other hand, may affect expression and thus indirectly COMT activity. We investigated whether methylation of the COMT gene was associated with adolescents' substance use. Furthermore, we explored whether the COMT Val108/158Met polymorphism interacts with COMT gene methylation in association with substance use. In 463 adolescents (mean age = 16, 50.8% girls), substance use (cigarette smoking, alcohol and cannabis use) was assessed with self‐report questionnaires. From blood samples, COMT Val108/158Met genotype and methylation rates of membrane bound (MB) and soluble (S) COMT promoters were assessed. MB‐COMT promoter methylation was associated with non‐daily smoking [odds ratio (OR) = 1.82, P = 0.03], but not with daily smoking (OR = 1.20, P = 0.34), MB‐COMT promoter methylation was not associated with alcohol use. Adolescents with the Met/Met genotype and high rates of MB‐COMT promoter methylation were less likely to be high‐frequent cannabis users than adolescents with the Val/Val or Val/Met genotype. S‐COMT promoter methylation was not associated with substance use. These results indicate that there is an association between substance use and COMT gene methylation. Although this association is complex, combining genetic and epigenetic variation of the COMT gene may be helpful in further elucidating the influence of the dopamine system on substance use in adolescence.
Microbial Groundwater Sampling Protocol for Fecal‐Rich Environments
Authors: Harter Thomas , Watanabe Naoko , Li Xunde , Atwill Edward R. , Samuels William
Published: June 2014

Inherently, confined animal farming operations (CAFOs) and other intense fecal‐rich environments are potential sources of groundwater contamination by enteric pathogens. The ubiquity of microbial matter poses unique technical challenges in addition to economic constraints when sampling wells in such environments. In this paper, we evaluate a groundwater sampling protocol that relies on extended purging with a portable submersible stainless steel pump and Teflon® tubing as an alternative to equipment sterilization. The protocol allows for collecting a large number of samples quickly, relatively inexpensively, and under field conditions with limited access to capacity for sterilizing equipment. The protocol is tested on CAFO monitoring wells and considers three cross‐contamination sources: equipment, wellbore, and ambient air. For the assessment, we use Enterococcus, a ubiquitous fecal indicator bacterium (FIB), in laboratory and field tests with spiked and blank samples, and in an extensive, multi‐year field sampling campaign on 17 wells within 2 CAFOs. The assessment shows that extended purging can successfully control for equipment cross‐contamination, but also controls for significant contamination of the well‐head, within the well casing and within the immediate aquifer vicinity of the well‐screen. Importantly, our tests further indicate that Enterococcus is frequently entrained in water samples when exposed to ambient air at a CAFO during sample collection. Wellbore and air contamination pose separate challenges in the design of groundwater monitoring strategies on CAFOs that are not addressed by equipment sterilization, but require adequate QA/QC procedures and can be addressed by the proposed sampling strategy.
Historians of the Late Medieval English Parliament
Authors: Dodd Gwilym
Published: June 2014

What accounts for the emergence of the medieval parliament? What were its main functions? Whose interests did parliament serve and how powerful were the Commons? These are straightforward questions, but historians have been debating the answers for well over a hundred years, since Archbishop William Stubbs published hisConstitutional Historyin 1875. This discussion surveys the main contributions to this discussion, tracing the rise and fall, and rise again, of the historiography of medieval parliaments. More recent work has demonstrated that the antecedents of parliamentary assemblies can be traced back to before the Conquest, but the focus of this discussion lies in the later medieval period and, particularly, the late 13th and 14th centuries, the period which has attracted most attention and discussion in modern scholarship.
Liberalism and Constitutionalism in Latin America in the 19th Century
Authors: Adelman Jeremy
Published: June 2014

For generations, 19th century Latin American history has been portrayed as a period of anarchic turmoil, wasted energy, and pointless division. It was the age of caudillos and of political breakup. But recent evidence paints a very different picture. More and more historians see the period from 1821 (when the wars of independence ended) to 1860s as an era of experimentation and innovation, of building new institutions to replace the old. This essay reprises some of the primary lines of investigation. It explores the ways in which Latin Americans built a hybrid model of constitutionalism, adapted from elements circulating around the Atlantic world. It explores how people charted new meanings of citizenship by applying new legal tools and practices of public organization in the civic sphere. It examines the experiments in political organizing and vertical alliances. Finally, it suggests that older intellectual and ideological coordinates of secular vs religious, liberal vs conservative, fail to capture the very strong emphasis on pragmatic republican strains in 19th century statebuilders.
Shifting Between Biomedical and Social Medicine: International Health Organizations in the 20th Century
Authors: Borowy Iris
Published: June 2014

International health organizations emerged in the 19th century as a means to reconcile the needs of a world of increasing trade and mobility with the increasing threat of the spread of diseases. Inexorably, they have assumed a growing list of responsibilities. Throughout the 20th century, their work has been torn between two approaches to health: one biomedical, which saw health as a function of pathogens and diseases and called for vertical campaigns against specific diseases, another social, which considered diseases mere symptoms of underlying problems of poverty and inequality and which favored horizontal programs of social change. Inevitably, the activities of international health organizations like the Rockefeller Foundation, the League of Nations Health Organisation, the World Health Organization, the World Bank, and others have maneuvered between those positions. The international eradication campaigns against malaria (unsuccessful) and smallpox (successful) and the principles adopted at the Conference of Alma‐Ata stand out as pivotal examples of biomedical and social approaches to health in the post‐WWII period. Implicitly, international health organizations have provided a mirror image of how those in power, the community of nations and – eventually – all citizens and voters, have decided to organize their interaction with their biological environments, their material and immaterial resources, their political priorities, and with each other.
Squamous cell carcinomas in situ arising in seborrheic keratoses: an association with concomitant immunosuppression?
Authors: Boyd Alan S. , Su Pei F. , Shyr Yu , Tang Yi W.
Published: June 2014

Background

Seborrheic keratoses (SK) are the most common cutaneous neoplasm in humans. Given their numbers, a squamous cell carcinoma in situ (SCCIS) arising from an SK would not be unexpected, although this occurrence has not been widely reported.

Objective

This study compares the immune status of patients with a SCCIS arising contiguously from SK (SK/SCCIS) and the number of daily medications taken by these patients. The biopsy tissue was evaluated for the presence of human papillomavirus DNA.

Methods

Over a 5‐year period at our institution, 13 cases of SK/SCCIS were diagnosed. For each case, age‐ and sex‐matched control patients with a histologically diagnosed unremarkable SK were randomly selected. The number of patients taking immunosuppressing medications was determined from each group and compared statistically. In addition, polymerase chain reaction analysis of the 13 SK/SCCIS biopsies was performed.

Results

Five of the 13 study patients took immunosuppressive medications compared to none of the 39 control patients (P = 0.0005). None of the biopsies demonstrated the presence of human papillomavirus DNA by polymerase chain reaction.

Conclusions

Immunocompromised patients with SKs appear to carry a greater risk of these otherwise innocuous lesions developing an SCCIS, although given the small number of patients evaluated, further research into this possible association is warranted.
Demodex folliculorum: its association with oily skin surface rather than rosacea lesions
Authors: Porta Guardia Carlos A.
Published: June 2014

Background

Despite the predilection of Demodex folliculorum (DF) for human sebum, observational studies addressing a relationship between this agent and rosacea paid no attention to the effect of a potentially acting confounder, the oily nature of the skin.

Objectives

To analyze whether a relationship exists between the presence of the mite in rosacea and oily cutis.

Materials and methods

An observational study on 63 rosacea cases and 61 healthy controls, both discriminated according to their predominance of oily or dry cutis, was carried out to investigate demodectic density by the skin surface biopsy.

Results

While comparisons on the density of DF revealed no differences between patients and controls (Mann–Whitney U‐test, P = 0.35), persons with an oily cutis had increased amounts of this mite on the skin surface (Mann–Whitney U‐test, P < 0.05), irrespective of whether they had rosacea or not.

Conclusions

The association between DF and oily skin rather than rosacea lesions gives no support for this agent being implied in disease pathogenesis.
An investigation into the MMP1 gene promoter region polymorphism – 1607 2G with recessive dystrophic epidermolysis bullosa disease severity in northeastern Mexican patients
Authors: Garza‐Gómez Jorge , Cerda‐Flores Ricardo M. , Gómez‐Flores Minerva , Salas‐Alanís Julio C. , Ocampo‐Candiani Jorge , Martínez‐Garza Laura E. , South Andrew P. , Gallardo‐Blanco Hugo L.
Published: June 2014

Background

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic skin blistering disorder caused by mutations in the gene COL7A1 encoding type VII collagen. Most of the patients' clinical severity depends in part on the nature and location of the mutations, ranging from the mild form described as RDEBother‐generalized (RDEB‐O) to the more aggressive phenotype described as RDEBsevere‐generalized (RDEB‐sev gen). However, interfamilial and interindividual differences in subjects with identical COL7A1 mutations suggest the presence of modifier elements, which may influence severity. There is a single nucleotide polymorphism (SNP) at the promoter of the MMP1 gene‐encoding matrix metalloproteinase type 1, which has been studied as a genetic disease modifier in different patient cohorts with different findings.

Methods

We tested the SNP in 30 patients with RDEB and 130 controls whose four grandparents were born in northeastern Mexico. Patients were clinically classified as RDEB‐sev gen and RDEB‐O by three dermatologists. The SNPStats, RXC, and SPSS software were used to perform statistical testing.

Results

The allele frequencies for 2G were 0.607, 0.562, and 0.642 for RDEB‐O, RDEB‐sev gen, and the control group, respectively. When the genotype frequencies were compared, there was no significant difference between RDEB‐sev gen (OR = 0.38, CI 95% 0.12–1.21), RDEB‐O (OR = 1.03, CI 95% 0.21–4.96), and the control group.

Conclusion

We found no significant association in relation to the severity of the study subjects and the SNP at the promoter of the MMP1 gene.
Lived‐experience participation in nurse education: Reducing stigma and enhancing popularity
Authors: Happell Brenda , Byrne Louise , Platania‐Phung Chris , Harris Scott , Bradshaw Julie , Davies Jonathan
Published: June 2014

Mental health nursing consistently emerges as less popular than other specialties, and both service users and mental health practitioners are affected by negative attitudes. Education is fundamental to attracting students to the field of mental health nursing. The aim of this study was to determine the impact of undergraduate mental health curricula on student attitudes to people with mental illness, and career interest in mental health nursing. A traditional mental health course was compared to a course delivered by a person with lived experience of mental illness (and mental health service use) for its impact on student attitudes and career intentions in mental health nursing (cohort 1: n = 70, cohort 2: n = 131, respectively). In both cohorts, attitudes were measured via self‐report, before and after the course, and changes were investigated through within‐subjects t‐tests. The lived experience‐led course demonstrated statistically‐significant positive changes in intentions to pursue mental health nursing and a decrease in negative stereotypes, which were not observed in the traditional course. The valuable contribution of mental health nursing emerged in the traditional, but not lived‐experience‐led, programmes. These findings support the value of an academic with lived experience of mental health challenges in promoting attraction to mental health nursing as a career option.
Tumour necrosis factor‐α promotes liver ischaemia‐reperfusion injury through the PGC‐1α/Mfn2 pathway
Authors: Li Jun , Ke Wenbo , Zhou Qi , Wu Yongzhong , Luo Hong , Zhou Hong , Yang Bin , Guo Yu , Zheng Qichang , Zhang Yong
Published: June 2014

Tumour necrosis factor (TNF)‐α has been considered to induce ischaemia‐reperfusion injury (IRI) of liver which is characterized by energy dysmetabolism. Peroxisome proliferator–activated receptor‐γ co‐activator (PGC)‐1α and mitofusion2 (Mfn2) are reported to be involved in the regulation of mitochondrial function. However, whether PGC‐1α and Mfn2 form a pathway that mediates liver IRI, and if so, what the underlying involvement is in that pathway remain unclear. In this study, L02 cells administered recombinant human TNF‐α had increased TNF‐α levels and resulted in down‐regulation of PGC‐1α and Mfn2 in a rat liver IRI model. This was associated with hepatic mitochondrial swelling, decreased adenosine triphosphate (ATP) production, and increased levels of reactive oxygen species (ROS) and alanine aminotransferase (ALT) activity as well as cell apoptosis. Inhibition of TNF‐α by neutralizing antibody reversed PGC‐1α and Mfn2 expression, and decreased hepatic injury and cell apoptosis both in cell culture and in animals. Treatment by rosiglitazone sustained PGC‐1α and Mfn2 expression both in IR livers, and L02 cells treated with TNF‐α as indicated by increased hepatic mitochondrial integrity and ATP production, reduced ROS and ALT activity as well as decreased cell apoptosis. Overexpression of Mfn2 by lentiviral‐Mfn2 transfection decreased hepatic injury in IR livers and L02 cells treated with TNF‐α. However, there was no up‐regulation of PGC‐1α. These findings suggest that PGC‐1α and Mfn2 constitute a regulatory pathway, and play a critical role in TNF‐α‐induced hepatic IRI. Inhibition of the TNF‐α or PGC‐1α/Mfn2 pathways may represent novel therapeutic interventions for hepatic IRI.
Validation of a non‐linear model of health
Authors: Topolski Stefan , Sturmberg Joachim
Published: June 2014

Purpose

The purpose of this study was to evaluate the veracity of a theoretically derived model of health that describes a non‐linear trajectory of health from birth to death with available population data sets.

Methods

The distribution of mortality by age is directly related to health at that age, thus health approximates 1/mortality. The inverse of available all‐cause mortality data from various time periods and populations was used as proxy data to compare with the theoretically derived non‐linear health model predictions, using both qualitative approaches and quantitative one‐sampleKolmogorov–Smirnov analysis withMonteCarlo simulation.

Results

The mortality data's inverse resembles a log–normal distribution as predicted by the proposed health model. The curves have identical slopes from birth and follow a logarithmic decline from peak health in young adulthood. A majority of the sampled populations had a good to excellent quantitative fit to a log–normal distribution, supporting the underlying model assumptions. Post hoc manipulation showed the model predictions to be stable.

Conclusions

This is a first theory of health to be validated by proxy data, namely the inverse of all‐cause mortality. This non‐linear model, derived from the notion of the interaction of physical, environmental, mental, emotional, social and sense‐making domains of health, gives physicians a more rigorous basis to direct health care services and resources away from disease‐focused elder care towards broad‐based biopsychosocial interventions earlier in life.
Requirements of a new communication technology for handover and the escalation of patient care: a multi‐stakeholder analysis
Authors: Johnston Maximilian J. , King Dominic , Arora Sonal , Cooper Kerri , Panda Neha Aparajita , Gosling Rebecca , Singh Kaushiki , Sanders Bradley , Cox Benita , Darzi Ara
Published: June 2014

Rationale, aims and objectives

In order to enable safe and efficient information transfer between health care professionals during clinical handover and escalation of care, existing communication technologies must be updated. This study aimed to provide a user‐informed guide for the development of an application‐based communication system (ABCS), tailored for use in patient handover and escalation of care.

Methods

Current methods of inter‐professional communication in health care along with information system needs for communication technology were identified through literature review. A focus group study was then conducted according to a topic guide developed by health innovation and safety researchers. Fifteen doctors and 11 nurses from three London hospitals participated in a mixture of homogeneous and heterogeneous sessions. The sessions were recorded and transcribed verbatim before being subjected to thematic analysis.

Results

Seventeen information system needs were identified from the literature review. Participants identified six themes detailing user perceptions of current communication technology, attitudes to smartphone technology and anticipated requirements of an application produced for handover and escalation of care. Participants were in favour of an ABCS over current methods and expressed enthusiasm for a system with integrated patient information and group‐messaging functions.

Conclusion

Despite concerns regarding confidentiality and information governance a robust guide for development and implementation of an ABCS was produced, taking input from multiple stakeholders into account. Handover and escalation of care are vital processes for patient safety and communication within these must be optimized. An ABCS for health care professionals would be a welcome innovation and may lead to improvements in patient safety.
Explaining the unexplainable – the impact of physicians’ attitude towards litigation on their incident disclosure behaviour
Authors: Renkema Erik , Broekhuis Manda H. , Ahaus Kees
Published: June 2014

Rationale, aims and objectives

This study aims to provide in‐depth insight into the emotions and thoughts of physicians towards malpractice litigation, and how these relate to their incident disclosure behaviour.

Methods

Thirty‐one Dutch physicians were interviewed and completed short questionnaires regarding malpractice litigation. We used hierarchical cluster analysis to identify physician clusters. Additional qualitative data were analysed.

Results

Physicians vary largely in their attitude towards malpractice litigation, and their attitude is not straightforward related to their disclosure behaviour. Based on their responses physicians could be divided into two clusters: one with a positive and one with a negative attitude. Physicians with a negative attitude showed often, but also 6 out of 15 not, a reluctance to disclose, whereas the majority in the positive attitude cluster (12 out of 16) showed no reluctance. If, what and how physicians disclose incidents depends on a complex interplay of their emotions and thoughts regarding litigation, and not only on their fear of litigation as many studies assume.

Conclusions

Due to the variation among physicians in their litigation attitude and behaviour in terms of incident disclosure the oft‐heard call for ‘openness’ about medical incidents will not be easy to achieve. A coaching system in which physicians can share and discuss their differing attitudes and disclosure principles, teaching medical students and junior physicians about disclosure, and explaining how to organize emotional and legal support for oneself in case of litigation could decrease stress feelings and support open disclosure behaviour.
Dietitians’ perceptions of communicating with preadolescent, overweight children in the consultation setting: the potential for e‐resources
Authors: Raaff C. , Glazebrook C. , Wharrad H.
Published: June 2014

Background

There are calls to enhance existing child weight management interventions and to develop new treatment approaches. The potential for interactive electronic resources (e‐resources) to support child–dietitian communication has yet to be explored. Towards developing such a tool, the present study aimed to understand dietetic attitudes and approaches to communicating with preadolescent overweight children in individual consultations to support behaviour change.

Methods

A purposive sample of 18 dietitians, providing weight management advice to overweight 7–11‐year‐old children, took part in the study. Individual semi‐structured telephone interviews were conducted. Data were transcribed and then analysed using inductive thematic analysis. Content analysis was used to interpret dietetic attitude towards e‐resources.

Results

Six overarching themes were identified describing dietitians’ views: the complexity of treating childhood obesity, the strategic balance of dietetic communication focus between child and parent, the child's capacity to communicate affecting their contribution, dietetic approaches to verbal child communication and the features of resources that can support them, as well as dietetic expectations for resources. Independent inter‐rater agreement for the themes was 76.9% and 73.1%, respectively. The majority of dietitians (n = 13) supported the concept of introducing an interactive multimedia e‐resource into child weight management consultations.

Conclusions

Most dietitians sought to engage the preadolescent child in the consultation, using dietetic visual aids to complement verbal strategies and to serve as scaffolding for the conversation. There is scope for interactive e‐resources to enhance communication, provided that they are flexibly tailored to meet the needs of the dietitian and the overweight child.
The design and delivery of a PKA inhibitory polypeptide to treat SCA1
Authors: Hearst Scoty M. , Shao Qingmei , Lopez Mariper , Raucher Drazen , Vig Parminder J. S.
Published: June 2014

Spinocerebellar ataxia‐1 (SCA1) is a neurodegenerative disease that primarily targets Purkinje cells (PCs) of the cerebellum. The exact mechanism of PC degeneration is unknown, however, it is widely believed that mutant ataxin‐1 becomes toxic because of the phosphorylation of its serine 776 (S776) residue by cAMP‐dependent protein kinase A (PKA). Therefore, to directly modulate mutant ATXN1 S776 phosphorylation and aggregation, we designed a therapeutic polypeptide to inhibit PKA. This polypeptide comprised of a thermally responsive elastin‐like peptide (ELP) carrier, which increases peptide half‐life, a PKA inhibitory peptide (PKI), and a cell‐penetrating peptide (Synb1). We observed that our therapeutic polypeptide, Synb1‐ELP‐PKI, inhibited PKA activity at concentrations similar to the PKI peptide. Additionally, Synb1‐ELP‐PKI significantly suppressed mutant ATXN1 S776 phosphorylation and intranuclear inclusion formation in cell culture. Further, Synb1‐ELP‐PKI treatment improved SCA1 PC morphology in cerebellar slice cultures. Furthermore, the Synb1‐ELP peptide carrier crossed the blood–brain barrier and localized to the cerebellum via the i.p. or intranasal route. Here, we show the intranasal delivery of ELP‐based peptides to the brain as a novel delivery strategy. We also demonstrate that our therapeutic polypeptide has a great potential to target the neurotoxic S776 phosphorylation pathway in the SCA1 disease.

image

Protein kinase A (PKA) phosphorylates mutant ataxin‐1 and makes it resistant to degradation. We designed a PKA inhibitory polypeptide. Our polypeptide comprised a thermally responsive elastin‐like peptide (ELP) carrier, a PKA inhibitory peptide (PKI) and a cell‐penetrating peptide (Synb1). Synb1‐ELP‐PKI, inhibited PKA activity in various in vitro models. The polypeptide crossed the blood–brain barrier when administered intraperitoneally or intranasally. We demonstrate that our polypeptide is a potential candidate for Spinocerebellar ataxia‐1 (SCA1) therapy.
Hippocampal proteoglycans brevican and versican are linked to spatial memory of Sprague–Dawley rats in the morris water maze
Authors: Saroja Sivaprakasam R. , Sase Ajinkya , Kircher Susanne G. , Wan Jia , Berger Johannes , Höger Harald , Pollak Arnold , Lubec Gert
Published: June 2014

Proteoglycans (PGs) are major constituents of the extracellular matrix and have recently been proposed to contribute to synaptic plasticity. Hippocampal PGs have not yet been studied or linked to memory. The aim of the study, therefore, was to isolate and characterize rat hippocampal PGs and determine their possible role in spatial memory. PGs were extracted from rat hippocampi by anion‐exchange chromatography and analyzed by nano LC‐MS/MS. Twenty male Sprague–Dawley rats were tested in the morris water maze. PGs agrin, amyloid beta A4 protein, brevican, glypican‐1, neurocan, phosphacan, syndecan‐4, and versican were identified in the hippocampi. Brevican and versican levels in the membrane fraction were higher in the trained group, correlating with the time spent in the target quadrant. α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor GluR1 was co‐precipitated with brevican and versican. Levels for a receptor complex containing GluR1 was higher in trained while GluR2 and GluR3‐containing complex levels were higher in yoked rats. The findings provide information about the PGs present in the rat hippocampus, demonstrating that versican and brevican are linked to memory retrieval in the morris water maze and that PGs interact with α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor GluR1, which is linked to memory retrieval.

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Proteoglycans (PGs) are major constituents of the extracellular matrix of the brain and were proposed to contribute to synaptic plasticity. This report addressed PGs in rat hippocampus and suggests that PGs brevican and versican are linked to spatial memory, and form a complex with the GluR1 subunit of the AMPA receptor, a key signaling molecule in memory mechanisms.
The anti‐seizure drugs vinpocetine and carbamazepine, but not valproic acid, reduce inflammatory IL‐1β and TNF‐α expression in rat hippocampus
Authors: Gómez Carlos D. , Buijs Rudolf M. , Sitges María
Published: June 2014

In the present study, the effects of the two classical anti‐epileptic drugs, carbamazepine and valproic acid, and the non‐classical anti‐seizure drug vinpocetine were investigated on the expression of the pro‐inflammatory cytokines IL‐1β and TNF‐α in the hippocampus of rats by PCR or western blot after the administration of one or seven doses. Next, the effects of the anti‐seizure drugs were investigated on the rise in cytokine expression induced by lipopolysaccharides (LPS) inoculation in vivo. To validate our methods, the changes induced by the pro‐convulsive agents 4‐aminopyridine, pentylenetetrazole and pilocarpine were also tested. Finally, the effect of the anti‐seizure drugs on seizures and on the concomitant rise in pro‐inflammatory cytokine expression induced by 4‐aminopyridine was explored. Results show that vinpocetine and carbamazepine reduced the expression of IL‐1β and TNF‐α from basal conditions, and the increase in both pro‐inflammatory cytokines induced by LPS. In contrast, valproic acid failed to reduce both the expression of the cytokines from basal conditions and the rise in IL‐1β and TNF‐α expression induced by LPS. Tonic‐clonic seizures induced either by 4‐aminopyridine, pentylenetetrazole or pilocarpine increased the expression of IL‐1β and TNF‐α markedly. 4‐aminopyridine‐induced changes were reduced by all the tested anti‐seizure drugs, although valproic acid was less effective. We conclude that the anti‐seizure drugs, vinpocetine and carbamazepine, whose mechanisms of action involve a decrease in ion channels permeability, also reduce cerebral inflammation.

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The mechanism of action of anti‐seizure drugs like vinpocetine and carbamazepine involves a decrease in Na+ channels permeability. We here propose that this mechanism of action also involves a decrease in cerebral inflammation.
Neuroprotective effect of exercise in rat hippocampal slices submitted to in vitro ischemia is promoted by decrease of glutamate release and pro‐apoptotic markers
Authors: Mourão Flávio Afonso Gonçalves , Leite Hércules Ribeiro , de Carvalho Luciana Estefani Drumond , Ferreira e Vieira Talita Hélen , Pinto Mauro Cunha Xavier , de Castro Medeiros Daniel , Andrade Ian Lara Lamounier , Gonçalves Daniela Fontes , Pereira Grace Schenatto , Dutra Moraes Márcio Flávio , Massensini André Ricardo
Published: June 2014

The role of physical exercise as a neuroprotective agent against ischemic injury has been extensively discussed. Nevertheless, the mechanisms underlying the effects of physical exercise on cerebral ischemia remain poorly understood. Here, we investigate the hypothesis that physical exercise increases ischemic tolerance by decreasing the induction of cellular apoptosis and glutamate release. Rats (n = 50) were submitted to a swimming exercise protocol for 8 weeks. Hippocampal slices were then submitted to oxygen and glucose deprivation. Cellular viability, pro‐apoptotic markers (Caspase 8, Caspase 9, Caspase 3, and apoptosis‐inducing factor), and glutamate release were analyzed. The percentage of cell death, the amount of glutamate release, and the expression of the apoptotic markers were all decreased in the exercise group when compared to the sedentary group after oxygen and glucose deprivation. Our results suggest that physical exercise protects hippocampal slices from the effects of oxygen and glucose deprivation, probably by a mechanism involving both the decrease of glutamatergic excitotoxicity and apoptosis induction.

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Exercise reduces excitotoxicity and apoptosis. The mechanisms underlying neuroprotective effects of regular exercise are still not fully understood. Here, we showed that swim training promotes neuroprotection decreasing pro‐apoptotic markers as caspases 8, 9, 3, and apoptose‐Inducing Factor (AIF) as well as glutamate release from hippocampal slices. Our data reinforce the idea that exercise affords a neuroprotective effect.
Leadership and teamwork in medical emergencies: performance of nursing students and registered nurses in simulated patient scenarios
Authors: Endacott Ruth , Bogossian Fiona E , Cooper Simon J , Forbes Helen , Kain Victoria J , Young Susan C. , Porter Joanne E ,   the First2Act Team
Published: June 2014

Aims and objectives

To examine nursing students' and registered nurses' teamwork skills whilst managing simulated deteriorating patients.

Background

Studies continue to show the lack of timely recognition of patient deterioration. Management of deteriorating patients can be influenced by education and experience.

Design

Mixed methods study conducted in two universities and a rural hospital in Victoria, and one university in Queensland, Australia.

Methods

Three simulation scenarios (chest pain, hypovolaemic shock and respiratory distress) were completed in teams of three by 97 nursing students and 44 registered nurses, equating to a total of 32 student and 15 registered nurse teams. Data were obtained from (1) Objective Structured Clinical Examination rating to assess performance; (2) Team Emergency Assessment Measure scores to assess teamwork; (3) simulation video footage; (4) reflective interview during participants' review of video footage. Qualitative thematic analysis of video and interview data was undertaken.

Results

Objective structured clinical examination performance was similar across registered nurses and students (mean 54% and 49%); however, Team Emergency Assessment Measure scores differed significantly between the two groups (57% vs 38%,t = 6·841,p < 0·01). In both groups, there was a correlation between technical (Objective Structured Clinical Examination) and nontechnical (Team Emergency Assessment Measure) scores for the respiratory distress scenario (student teams:r = 0·530,p = 0·004, registered nurse teamsr = 0·903,p < 0·01) and hypovolaemia scenario (student teams:r = 0·534,p = 0·02, registered nurse teams:r = 0·535,p = 0·049). Themes generated from the analysis of the combined quantitative and qualitative data were as follows: (1) leadership and followership behaviours; (2) help‐seeking behaviours; (3) reliance on previous experience; (4) fixation on a single detail; and (5) team support.

Conclusions

There is scope to improve leadership, team work and task management skills for registered nurses and nursing students. Simulation appears to be beneficial in enabling less experienced staff to assess their teamwork skills.

Relevance to clinical practice

There is a need to encourage less experienced staff to become leaders and for all staff to develop improved teamwork skills for medical emergencies.
A PRIMER ON GLOBAL GAMES APPLIED TO MACROECONOMICS AND FINANCE
Authors: Jorge José , Rocha Joana
Published: June 2014

This paper shows how to solve global games applied to macroeconomics and finance. We ascertain the roles of public and private information for the determination of a unique equilibrium, and discuss the informative role of market prices. We examine the impact of public information on social welfare, comparing models with and without complementarities at the aggregate level.
Urban canyon effect: storm drains enhance call characteristics of the Mientien tree frog
Authors: Tan W.‐H. , Tsai C.‐G. , Lin C. , Lin Y. K.
Published: June 2014

Anthropogenic structures, such as wall surfaces, may change the acoustic environment for signals transmitted by animals, creating novel environments that animals must either adapt to or abandon. Animals can potentially use those structures to manipulate sound characteristics. In many anuran species, successful reproduction depends on long‐range propagation and perception of advertisement calls. Callers may select natural perches or human‐made objects to assist call propagation. Male Mientien tree frogs Kurixalus idiootocus frequently perch and call in roadside concrete drainages – miniature urban canyons. We used a combination of field and indoor experiments to test two hypotheses: (1) transmission of calls emitted inside drains is enhanced; (2) males selected perches inside drains that facilitated call transmission. A field survey indicated that male Mientien tree frogs preferred calling inside rather than outside drains. A playback showed that calls emitted from inside drains were enhanced in both amplitude and note duration. In an indoor experiment using a replica of a concrete drain, males preferred one particular type of call perch. However, we found no difference in sound properties between random locations inside the drain model and the perch location preferred by calling males.