bluuebunny/crossref_metadata_2025_split huggingface dataset:
What factors influence recruitment to a birth cohort of infants with Down’s syndrome?
Authors: Williams Georgina M , Neville Patricia , Gillespie Kathleen M , Leary Sam D , Hamilton-Shield Julian P , Searle Aidan J 
Published: March 2018

ObjectiveTo understand how to maximise recruitment of young infants with Down’s syndrome (DS) into research through qualitative interviews with parents and care providers. In complex neonatal and genetic conditions such as DS, frequently diagnosed after birth, parents may go through a period of adaptation. These factors need consideration when overcoming barriers to recruitment.Participants and designParticipants, who were drawn from health professionals and volunteers working with families experiencing DS, were recruited using a purposive sampling strategy. Semistructured telephone interviews were completed with nine paediatricians, three research nurses and six family support workers. Five of those interviewed had a child with DS. The interviews were transcribed and analysed thematically.ResultsA positive decision to take part in a ‘from-birth’ cohort study depends on factors such as the child’s overall health, parent demographics (educational background and ethnicity), medical interactions that take place with the families (communication) and study logistics. The data suggest that recruitment methods need to take all these factors into consideration. Multiple recruitment methods should be considered including face to face, through parent and support groups, websites and social media. There also needs to be flexibility in the research timings to fit around the needs of the child and parents.ConclusionResearchers need to be aware of the variable responses elicited by families to a diagnosis of DS for their baby and be sensitive to the child’s current medical status. This does not preclude recruitment into studies, but to maximise uptake good communication and flexibility is essential.
Can child restraint product information developed using consumer testing sustain correct use 6 months after child restraint purchase? Study protocol for a cluster randomised controlled trial
Authors: Brown Julie , Elkington Jane , Hall Alexandra , Keay Lisa , Charlton Judith L , Hunter Kate , Koppel Sjaan , Hayen Andrew , Bilston Lynne E 
Published: March 2018

BackgroundWith long-standing and widespread high rates of errors in child restraint use, there is a need to identify effective methods to address this problem. Information supplied with products at the point of sale may be a potentially efficient delivery point for such a countermeasure. The aim of this study is to establish whether product materials developed using a consumer-driven approach reduce errors in restraint use among purchasers of new child restraint systems.MethodsA cluster randomised controlled trial (cRCT) will be conducted. Retail stores (n=22) in the greater Sydney area will be randomised into intervention sites (n=11) and control sites (n=11), stratified by geographical and socioeconomic indicators. Participants (n=836) will enter the study on purchase of a restraint. Outcome measures are errors in installation of the restraint as observed by a trained researcher during a 6-month follow-up home assessment, and adjustment checks made by the parent when the child is placed into the restraint (observed using naturalistic methods). Process evaluation measures will also be collected during the home visit. An intention-to-treat approach will be used for all analyses. Correct use and adjustment checks made by the parent will be compared between control and intervention groups using a logistic regression model. The number of installation errors between groups will be compared using Poisson regression.DiscussionThis cRCT will determine the effectiveness of targeted, consumer-driven information on actual error rates in use of restraints. More broadly, it may provide a best practice model for developing safety product information.Trial registration numberACTRN12617001252303p; Pre-results.
Heritability of proprioceptive senses
Authors: Missitzi Julia , Geladas Nickos , Misitzi Angelica , Misitzis Leonidas , Classen Joseph , Klissouras Vassilis 
Published: March 2018

Heritability studies using the twin model have provided the basis to disentangle genetic and environmental factors that contribute to several complex human traits. However, the relative importance of these factors to individual differences in proprioception is largely unknown despite the fact that proprioceptive senses are of great importance, allowing us to respond to stimuli stemming from the space around us and react to altering circumstances. Hence, a total of 44 healthy male twins (11 MZ and 11 DZ pairs), 19–28 yr old, were examined for movement, position, and force sense at the elbow joint, and their heritability estimates were computed. Results showed that genetic factors explained 1) 72 and 76% of the total variance of movement sense at the start and the end of the movement, respectively, 2) 60 to 77% of the total variance of position sense, depending on the angle of elbow flexion and whether forearm positioning was active or passive, and 3) 73 and 70% of the total variance of the force sense at 90 and 60° of elbow flexion, respectively. It is concluded that proprioception assessed by these conscious sensations is to a substantial degree genetically dependent, with heritability indexes ranging from 0.60 to 0.77, depending on the task.NEW & NOTEWORTHY Proprioceptive acuity varies among people, but it is not known how much of this variability is due to differences in their genes. This study is the first to report that proprioception, expressed as movement sense, position sense, and force sense, is substantially heritable, and it is conceivable that this may have implications for motor learning and control, neural development, and neurorehabilitation.
Identification and quantification of human microcirculatory leukocytes using handheld video microscopes at the bedside
Authors: Uz Zühre , van Gulik Thomas M. , Aydemirli Mehtap D. , Guerci Philippe , Ince Yasin , Cuppen Diede , Ergin Bulent , Aksu Ugur , de Mol Bas A. , Ince Can 
Published: March 2018

Leukocyte recruitment and adhesion to the endothelium are hallmarks of systemic inflammation that manifest in a wide range of diseases. At present, no method is available to directly measure leukocyte kinetics at the bedside. In this study, we validate a new method to identify and quantify microcirculatory leukocytes observed by handheld vital microscopy (HVM) using space-time diagram (STD) analysis. Video clips ( n = 59) containing one capillary-postcapillary venule unit where leukocytes could be observed emanating from a capillary into a venule in cardiac surgery patients ( n = 20) were included. STD analysis and manual counting were used to quantify the number of leukocytes (total, rolling, and nonrolling). Pearson’s correlation and Bland-Altman analysis were used to determine agreement between the STDs and manual counting. For reproducibility, intra- and interobserver coefficients of variation (CVs) were assessed. Leukocyte (rolling and nonrolling) and red blood cell velocities were assessed. The STDs and manual counting procedures for the quantification of rolling leukocytes showed good agreement ( r = 0.8197, P < 0.0001), with a Bland-Altman analysis mean difference of −0.0 (−6.56; 6.56). The overall intraobserver CV for the STD method was 1.5%. The overall interobserver CVs for the STD and the manual method were 5.6% and 9.4%, respectively. The nonrolling velocity was significantly higher than the rolling velocity (812 ± 519 µm/s vs. 201 ± 149 µm/s, P = 0.001). STD results agreed with the manual counting procedure results, had a better reproducibility, and could assess the leukocyte velocity. STD analysis using bedside HVM imaging presented a new methodology for quantifying leukocyte kinetics and functions in the microcirculation. NEW & NOTEWORTHY In this study, we introduce space-time diagram analysis of sublingual microcirculation imaging using handheld vital microscopy to identify and quantify the presence and kinetics of human microcirculatory leukocytes. We validated the methodology by choosing anatomical units consisting of a capillary connected to a venule, which allowed precise identification of leukocytes.
CD16A Activation of NK Cells Promotes NK Cell Proliferation and Memory-Like Cytotoxicity against Cancer Cells
Authors: Pahl Jens H.W. , Koch Joachim , Götz Jana-Julia , Arnold Annette , Reusch Uwe , Gantke Thorsten , Rajkovic Erich , Treder Martin , Cerwenka Adelheid 
Published: March 2018

AbstractCD16A is a potent cytotoxicity receptor on human natural killer (NK) cells, which can be exploited by therapeutic bispecific antibodies. So far, the effects of CD16A-mediated activation on NK cell effector functions beyond classical antibody-dependent cytotoxicity have remained poorly elucidated. Here, we investigated NK cell responses after exposure to therapeutic antibodies such as the tetravalent bispecific antibody AFM13 (CD30/CD16A), designed for the treatment of Hodgkin lymphoma and other CD30+ lymphomas. Our results reveal that CD16A engagement enhanced subsequent IL2- and IL15-driven NK cell proliferation and expansion. This effect involved the upregulation of CD25 (IL2Rα) and CD132 (γc) on NK cells, resulting in increased sensitivity to low-dose IL2 or to IL15. CD16A engagement initially induced NK cell cytotoxicity. The lower NK cell reactivity observed 1 day after CD16A engagement could be recovered by reculture in IL2 or IL15. After reculture in IL2 or IL15, these CD16A-experienced NK cells exerted more vigorous IFNγ production upon restimulation with tumor cells or cytokines. Importantly, after reculture, CD16A-experienced NK cells also exerted increased cytotoxicity toward different tumor targets, mainly through the activating NK cell receptor NKG2D. Our findings uncover a role for CD16A engagement in priming NK cell responses to restimulation by cytokines and tumor cells, indicative of a memory-like functionality. Our study suggests that combination of AFM13 with IL2 or IL15 may boost NK cell antitumor activity in patients by expanding tumor-reactive NK cells and enhancing NK cell reactivity, even upon repeated tumor encounters. Cancer Immunol Res; 6(5); 517–27. ©2018 AACR.
Elevated Plasma Haptoglobin Level as a Potential Marker for Poor Prognosis in Acute Cerebral Infarction
Authors: Zhang Tao , Xiang Lei 
Published: March 2018

Background: Relationship between peripheral circulation concentration of haptoglobin (Hp) and risk of cerebrovascular disease has not been well investigated so far. The aim of the study was to reveal the prognostic significance of Hp on acute cerebral infarction. Methods: A total of 200 patients with acute cerebral infarction and 200 controls were included. Research data were collected from their medical records. Blood samples were obtained on admission. Hp phenotyping was performed using a native polyacrylamide gel electrophoresis. Plasma Hp levels were determined using enzyme-linked immunosorbent assays. The patients were followed up yearly, and endpoint was overall death. Results: Plasma levels of Hp were significantly elevated in the patients than in the controls (p < 0.001). Three-year overall death in the follow-up period was associated with the high plasma level of Hp (Hazard ratio [HR] 2.33, 95% CI 1.74–3.12). But, 3-year overall death was not related to Hp phenotyping (Hp 2–1 vs. 1–1: HR 1.07, 95% CI 0.66–1.73; Hp 2–2 vs. 1–1: HR 1.08, 95% CI 0.67–1.74). Conclusion: Peripheral circulation concentration of Hp might be an independent prognostic factor for acute cerebral infarction. But there was no relationship between Hp phenotyping and prognosis in this disease.
The Nature of Schizophrenia: Signposts to Prevention
Authors: McGorry Patrick D. 
Published: March 2018

Objective To describe the characteristics of schizophrenia relevant to conducting indicated preventive interventions. Method A systematic review of the literature informed by experiences at the Personal Assistance and Crisis Evaluation (PACE) clinic. Results Primary prevention requires a sophisticated knowledge of key causal risk factors relevant to the expression of a disorder. The causal risk factors most useful from an intervention standpoint may turn out to be somewhat removed from the neurobiology of the disorder and may even be relatively non-specific, so that tackling them could reduce the risks for a range of mental disorders. The frontier for more specific prevention in schizophrenia and related psychosis is currently represented by indicated preventive interventions for subthreshold symptoms. Again, these may be relatively broad spectrum early in the prepsychotic phase but more proximal to onset, greater treatment specificity can be explored. However, this can be viewed more as preventively orientated treatment rather than primary prevention per se. Early detection of first episode psychosis and optimal intensive treatment of first episodes and the critical early years after diagnosis also represent increasingly attractive preventive foci in psychotic disorders. Conclusion As evidence accumulates, implementation of evidence-based practice in real work settings is a major challenge as it is throughout the mental health service system. The momentum of preventively orientated treatment must be maintained through the 2nd National Mental Health Strategy and in the face of recent misleading polemic regarding the treatability of psychotic disorders, especially schizophrenia. The evidence demonstrates that schizophrenia and related disorders have never been more treatable.
Should we Ignore Dimensional Risk Factors in Prevention of Schizophrenia? Signposts to Prevention
Authors: McConaghy Nathaniel 
Published: March 2018

Objective The objective was to outline the development of the concept of allusive thinking as a genetic marker of predisposition to schizophrenia and relate this to other cognitive markers of this predisposition. Method Publications were reviewed which were considered relevant to the objective. Results Allusive thinking as detected clinically could be measured objectively from subjects' performance on an Object Sorting Test. Using this test it was shown that parents, both of patients with schizophrenia and of university students with allusive thinking, themselves showed allusive thinking, indicating it was familially transmitted. Subjects with allusive thinking showed reduced cortical evoked brain P300 potentials, suggesting the transmission was genetic. The hypothesis that allusive thinking was associated with weaker cortical inhibitory processes was supported by the finding that subjects with such thinking chose more remote word associations. It was suggested that reasons allusive thinking has not been used as a marker in intervention studies is that as a dimension of abstract thinking, marked allusive thinking is not associated with a high risk of developing schizophrenia, and that administration of the Object Sorting Test is time-consuming. Other dimensional cognitive factors, such as psychoticism and perceptual anhedonia and aberration, are independent of allusive thinking and are also associated with a low risk of developing schizophrenia. Genetic transmission of schizophrenia would appear to involve a number of predisposing factors distributed dimensionally in the population with the contribution of each factor being small. Conclusions As they are associated with only a low risk of predisposition to schizophrenia, cognitive markers may not be of immediate value in the prevention of schizophrenia when compared with the less specific markers used for this purpose. However, it would seem that their study will be necessary if the nature of the genetic transmission of the illness is to be understood. This understanding could be expected to ultimately lead to more effective prevention.
Phenotypic Markers as Risk Factors in Schizophrenia: Neurocognitive Functions
Authors: Michie Patricia T. , Kent Aaron , Stienstra Renee , Castine Rochelle , Johnston Julie , Dedman Kellie , Wichmann Helen , Box Juliette , Rock Daniel , Rutherford Elizabeth , Jablensky Assen 
Published: March 2018

Objective To review the literature on neurocognitive measures as risk markers for schizophrenia and to present data from the Perth family study of schizophrenia. Of all the risk markers that have been identified, the most promising are deficits in sustained attention. Method Inclusion in the review was determined by whether the research addressed a number of key questions: methods of assessing sustained attention; evidence of sustained attention deficits in patients and first-degree relatives including children; the importance of attentional dysfunction in the schizophrenic process and functional outcome; and the biological basis of sustained attention deficits. Results Sustained attention deficits are evident in both patients and a proportion of their first-degree relatives, a finding replicated in preliminary data from the Perth family study. The literature suggests that the attention deficit is a stable enduring trait that is independent of clinical state. The neural basis of the deficit may be a functional disconnection between prefrontal and parietal cortex. Attention impairment is an important predictor of functional outcome in patients and the development of social dysfunction in adulthood in the at-risk offspring of patients. However, sustained attention deficits that are measured in childhood results in an unacceptable high false-positive rate (21%) when predicting which at-risk offspring of parents with schizophrenia will develop a schizophrenia spectrum disorder, although the overall classification accuracy (78%) is impressive. Conclusions The main findings are that sustained attention deficits are important risk markers for schizophrenia but need to be supplemented by other neurocognitive risk markers to improve predictive accuracy.
Neuromotor Markers of Risk for Schizophrenia
Authors: McNeil Thomas F. , Cantor-Graae Elizabeth 
Published: March 2018

Objective To evaluate the possibility of using neuromotor deviation (NMD) as an individual-orientated, early life marker for increased risk for schizophrenia. Method Previous findings based on systematic examination of NMD are summarised concerning schizophrenia patients and individuals at heightened genetic risk for schizophrenia. Results Significantly increased rates of NMD are found in patients with schizophrenia, both after and long before disease onset. Neuromotor deviation can be efficiently studied at all ages from infancy to adulthood, and is typically not in itself stigmatising. Neuromotor deviation may represent an unstable characteristic of individuals from infancy to middle-to-late childhood, possibly attaining greater stability thereafter. Neuromotor deviation may also be more stable over time in the high-risk offspring of parents with schizophrenia than in other children. Neuromotor deviation in childhood predicts subsequent serious mental disturbance in genetic high-risk children. The efficiency of NMD for predicting schizophrenia in unselected samples is unknown, as is the optimal age(s) for assessing NMD to predict schizophrenia in high-risk and normal-risk groups. Neuromotor deviation is also found in the well relatives of schizophrenia patients, individuals developing a broad range of mental and physical disorders, and mentally normal individuals in the general population. Conclusions Neuromotor deviation should definitely be included in batteries of methods for identifying individuals with notably heightened risk of schizophrenia. However, NMD is not pathognomonic for schizophrenia, and the investigation of NMD during childhood and adolescence must thus be used judiciously in order to avoid possible stigmatisation. Further research should be done concerning the specific forms and developmental timing of NMD as related to schizophrenia.
Schizotypy: Phenotypic Marker as Risk Factor
Authors: Catts Stanley V. , Fox Allison M. , Ward Philip B. , McConaghy Nathaniel 
Published: March 2018

Objective To evaluate measures of schizotypy as familial risk factors for schizophrenia with the aim of making recommendations for assessing schizotypy as part of screening procedures for identifying people at risk of schizophrenia. Method Published studies using self-report and interview-based measures of schizotypy to assess relatives of patients with schizophrenia are reviewed. A parent study is reported evaluating the diagnostic accuracy of parental schizotypy as assessed by three questionnaire-based measures: the Chapman Perceptual Aberration and Physical Anhedonia Scales, and the Eysenck Psychoticism Scale. Group scores for these self-report ratings of 23 parent-pairs of patients with schizophrenia, 20 parent-pairs of patients with chronic nonpsychotic psychiatric disorder, and 19 parent-pairs of healthy comparison subjects are compared. Results Consistent with published evidence that self-report measures of psychosis-proneness and schizotypy do not consistently reflect familial risk factors that are specific for schizophrenia, scores on questionnaire measures of schizotypy did not distinguish the parents of patients with schizophrenia from the parents in the other two groups. Conclusions Interview-based assessments of schizotypy better assess familial risk factors than self-report measures of schizotypy. Questionnaire measures of schizotypy should be supplemented by interview-based assessments when screening for individuals at risk of schizophrenia.
Biological Markers and Schizophrenia
Authors: Copolov David , Crook Jeremy 
Published: March 2018

ObjectiveThe delivery of biological markers for schizophrenia would greatly assist preventative strategies by identifying at-risk individuals who could then be monitored and treated in a manner with a view to minimising subsequent morbidity. This paper aims to present a selection of biological measures that may indicate risk of schizophrenia.MethodA selective and brief review is provided of intensively studied putative markers, including enlarged cerebral ventricles, dopamine D2receptor density, amphetamine-stimulated central nervous system dopamine release, plasma homovanillic acid and smooth pursuit eye tracking dysfunction.ResultsA number of biological measures have been reported to be correlated with schizophrenia.ConclusionsPresently, none of these measures has satisfactory performance characteristics in terms of predictive validity, noninvasiveness, ease of testing and low cost that would enable their widespread use. However, a few have potential for further investigation and development.
Structural Brain Imaging and the Prevention of Schizophrenia: Can We Identify Neuroanatomical Markers for Young People at Risk for the Development of Schizophrenia?
Authors: Ward Philip B. 
Published: March 2018

ObjectiveTo examine the potential role of measures derived from structural brain imaging as phenotypic markers for the development of schizophrenia.MethodLiterature review of results of MRI-based assessments of brain structure in patients with schizophrenia, their first-degree relatives and factors that affect interpretation of such results.ResultsReliable differences in brain structure can be detected in patients with schizophrenia, including those experiencing a first episode of psychosis. Further research is required to determine whether these differences are progressive, how they relate to potential confounding factors such as comorbid substance abuse and the functional consequences of the relatively subtle changes observed.ConclusionsFurther research is needed before structural brain change can be considered as a phenotypic marker for those at risk of developing schizophrenia. Large-scale collaborative research in clinical and normal volunteer groups using standardised assessment protocols would enable the early identification of those findings with predictive power in at-risk populations.