Neurofilament light chain: A novel blood biomarker in patients with ataxia telangiectasia.
Neurofilament light chain (NfL) is recognized as a blood biomarker in several neurodegenerative disorders, but its possible relevance in Ataxia Telangiectasia (A-T) has not been examined. The aim of this study was to investigate the biomarker potential of blood NfL concentrations in patients with A-T. Blood (serum/plasma) NfL concentrations were measured in a Dutch and an American cohort of patients with A-T and compared to control values. Additionally, correlations between NfL concentrations and disease phenotype (classic versus variant A-T) were studied. In total 40 (23 Dutch and 17 American) patients with A-T (32 patients with classic A-T and 7 patients with variant A-T) and 17 age- and gender-matched (to the American cohort) healthy controls were included in this study. Blood (serum/plasma) NfL concentrations in patients with classic A-T and age ≤ 12 years were elevated compared to age matched controls. Patients with classic A-T > 12 years also had higher blood (serum/plasma) NfL concentrations (here: compared to age-dependent reference values found in the literature). Patients with classic A-T had higher blood (serum/plasma) NfL concentrations than patients with the variant phenotype. Blood (serum/plasma) NfL concentrations are elevated in patients with classic A-T and appear to correlate with the disease phenotype (classic versus variant). Therefore, blood (serum/plasma) NfL may be a promising biomarker in A-T.


Femoral tunnel malposition in ACL revision reconstruction.
The Multicenter Anterior Cruciate Ligament (ACL) Revision Study (MARS) group was formed to study a large cohort of revision ACL reconstruction patients. The purpose of this subset analysis study of the MARS database is to describe specific details of femoral tunnel malposition and subsequent management strategies that surgeons chose in the revision setting. The design of this study is a case series. The multicenter MARS database is compiled from a questionnaire regarding 460 ACL reconstruction revision cases returned by 87 surgeons. This subset analysis described technical aspects and operative findings in specifically those cases in which femoral tunnel malposition was cited as the cause of primary ACL reconstruction failure. Of the 460 revisions included for study, 276 (60%) cases cited a specific "technical cause of failure." Femoral tunnel malposition was cited in 219 (47.6%) of 460 cases. Femoral tunnel malposition was cited as the only cause of failure in 117 cases (25.4%). Surgeons judged the femoral tunnel too vertical in 42 cases (35.9%), too anterior in 35 cases (29.9%), and too vertical and anterior in 31 cases (26.5%). Revision reconstruction involved the drilling of an entirely new femoral tunnel in 91 cases (82.1%). For primary reconstruction, autograft tissue was used in 82 cases (70.1%). For revision reconstruction, autograft tissue was used in 61 cases (52.1%) and allograft tissue in 56 cases (47.9%). Femoral tunnel malposition in primary ACL reconstruction was the most commonly cited reason for graft failure in this cohort. Graft selection is widely variable among surgeons.


Perceived compliance in a pinch.
Handling a compliant object using a pinch grasp provides sensory information about deformation and resistive force from both index finger and thumb. In this paper, an object with rigid surfaces and composed of two compliant materials fixed on a central position is used to address how information from the two fingers is integrated into a holistic percept of compliance. Results indicate that with small differences in material compliance there is a small tendency to rely more on the information at the index finger. With larger differences in material compliance participants adopt different movement patterns with the two fingers to explore the objects. Compliance judgments depend on the relative amount of motion and force exerted-the finger that presses more contributes more to the final estimate. This tendency is consistent with the utilization of a unique force signal for the two fingers. The uneven contribution of the sensory information in the pinch leads to predictable compliance discrimination performance from the performance obtained using the fingers independently.


Thickness as prognostic aid in upper aerodigestive tract cancer.
A retrospective review of records and microscopic slides was carried out on 151 patients, encompassing nine specific upper aerodigestive tract cancer sites, correlating depth of invasion with node metastases and outcome. In this preliminary descriptive study, thickness was found to be more closely related to node metastasis and to survival than was surface diameter in middle-stage tumors, particularly in tongue, floor of the mouth, buccal mucosa, gum, and soft palate sites. Thickness, depth of penetration, and bone involvement appear to represent the degree of general tumor aggressiveness better than does surface extent. A substitution of thickness measurement for surface diameter (T) in the present TNM staging system is suggested.


Landowners' incentives for constructing wetlands in an agricultural area in south Sweden.
Eutrophication of the Baltic Sea has in Sweden led to the initiation of government schemes aiming to increase wetland areas in agricultural regions and thereby reduce nutrient transport to the sea. Landowners play a significant role as providers of this ecosystem service and are currently offered subsidies to cover their costs for constructing and maintaining wetlands. We undertook a grounded theory study, in which landowners were interviewed, aiming at identifying landowners' incentives for constructing wetlands on their land. The study showed that adequate subsidies, additional services that the wetland could provide to the landowner, local environmental benefits, sufficient knowledge, and peers' good experiences could encourage landowners to construct wetlands. Perceived hindrances were burdensome management, deficient knowledge, time-consuming application procedures and unclear effectiveness of nutrient reduction. The main reason for not creating a wetland, however, was that the land was classified as productive by the landowner, i.e., suitable for food production. Current schemes are directed toward landowners as individuals and based on subsidies to cover costs. We propose that landowners instead are approached as ecosystem service entrepreneurs and contracted after a tendering process based on nutrient reduction effects. This would lead to new definitions of production and may stimulate improved design and placement of wetlands.


Normal and aberrant splicing of LMNA.
The LMNA gene gives rise to at least three isoforms (lamin A, C, lamin AΔ10) as a result of normal alternative splicing, regulated by cis- and trans-acting regulatory factors, as well as the 5' and 3' untranslated regions of the gene. The two main isoforms, lamin A and C, are constitutive components of the fibrous nuclear lamina and have diverse physiological roles, ranging from mechanical nuclear membrane maintenance to gene regulation. The clinical spectrum of diseases (called 'laminopathies') caused by LMNA mutations is broad, including at least eight well-characterised phenotypes, some of which are confined to the skeletal muscles or skin, while others are multisystemic. This review discusses the different alternatively spliced isoforms of LMNA and the regulation of LMNA splicing, as well as the subgroup of mutations that affect splicing of LMNA pre-mRNA, and also seeks to bridge the mis-splicing of LMNA at transcript level and the resulting clinical phenotypes. Finally, we discuss the manipulation of LMNA splicing by splice-switching antisense oligonucleotides and its therapeutic potential for the treatment of some laminopathies.


Balancing and pointing tasks in dyslexic and control adults.
Developmental dyslexia may affect as much as 15% of the population, but the aetiology of the disorder is still being debated. The cerebellar theory of dyslexia proposes that cerebellar dysfunction could lead to the myriad of symptoms seen in dyslexic individuals, both in literacy and non-literacy domains. The cerebellum is crucial to the fluent performance of motor skills. Previous studies have found that dyslexic children are worse than control children on certain motor and balancing tasks. Here the performance of 28 dyslexic compared to 26 control adults on rapid pointing and balancing measures, tasks which are thought to reflect cerebellar function, was investigated. There were no significant differences between the dyslexic and control participants on the balancing tasks or when the speed and accuracy of pointing were analysed separately. However, when the speed and accuracy of pointing were combined, the dyslexic participants showed poorer performance than the controls (p = 0.045). Furthermore, there were significant relationships between performance on the pointing task and literacy skills, and regression analysis showed that the error and speed of pointing contributed significantly to the variance in literacy skill. The implications for the role of the cerebellum and processing speed in dyslexia are discussed.


Making oneself predictable: reduced temporal variability facilitates joint action coordination.
Performing joint actions often requires precise temporal coordination of individual actions. The present study investigated how people coordinate their actions at discrete points in time when continuous or rhythmic information about others' actions is not available. In particular, we tested the hypothesis that making oneself predictable is used as a coordination strategy. Pairs of participants were instructed to coordinate key presses in a two-choice reaction time task, either responding in synchrony (Experiments 1 and 2) or in close temporal succession (Experiment 3). Across all experiments, we found that coactors reduced the variability of their actions in the joint context compared with the same task performed individually. Correlation analyses indicated that the less variable the actions were, the better was interpersonal coordination. The relation between reduced variability and improved coordination performance was not observed when pairs of participants performed independent tasks next to each other without intending to coordinate. These findings support the claim that reducing variability is used as a coordination strategy to achieve predictability. Identifying coordination strategies contributes to the understanding of the mechanisms involved in real-time coordination.


Diseases of Old Age in Two Paintings by Rembrandt.
Two paintings of older men by Rembrandt (1609-1669) are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person's response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt's own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject's foot and the second involving the subject's hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age.


Overlap between common genetic polymorphisms underpinning kidney traits and cardiovascular disease phenotypes: the CKDGen consortium.
Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits. We conducted 2 targeted analyses. First, we examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5×10(-4) (0.05/325 tests). Vascular outcomes were analyzed in participants from the AortaGen (20,634), CARDIoGRAM (86,995), CHARGE Eye (15,358), CHARGE IMT (31,181), ICBP (69,395), and NeuroCHARGE (12,385) consortia. Tests for kidney outcomes were conducted in up to 67,093 participants from the CKDGen consortium. We used 19 kidney SNPs and 64 vascular SNPs. Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria. In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic (P = 9.3 ×10(-10)) and diastolic (P = 1.6 ×10(-14)) blood pressure and coronary artery disease (P = 2.2 ×10(-6)), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus (P = 1.06 ×10(-07) and P = 7.05 ×10(-08)). The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations. Overall, although we confirmed one locus (SH2B3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself.


Alterations in human trabecular meshwork cell homeostasis by selenium.
Epidemiological evidence indicates that selenium supplementation may increase risk for glaucoma and ocular hypertension. The purpose of this study was to determine the effects of selenium on trabecular meshwork cells, a likely site of pathology for glaucoma. Human trabecular meshwork (HTM) cells and human umbilical vein endothelial cells (HUVECs) were treated with selenium (MSeA) at or near physiologically relevant concentrations. Selenium uptake by cells was monitored using mass spectrometry. Alterations in protein secretion, intracellular signaling, and cell morphology were monitored; and the role of integrin signaling in MSeA-induced morphological alterations was investigated using divalent cation treatments. Radiolabeling was used to assess protein synthesis and secretion, while luciferase and MTT assays monitored total cellular ATP and cell viability, respectively. Whereas detectible changes in intracellular selenium were observed after exposure to 1-10 microM MSeA for 24hr, the majority remained in the conditioned medium. Selenium-induced morphological changes (< or =3 hr) occurred before alterations in protein secretion and intracellular signaling (3-6 hr). Zinc treatment prevented selenium-mediated alterations in protein secretion and changes in cell-matrix adhesion. MSeA treatment (5 microM) led to a 60% decrease in protein synthesis after 3 hr and a 30% reduction in secretion, although significant alterations in cell viability and total ATP were not observed after MSeA treatment. Selenium altered several indicators of HTM cell homeostasis, but did not affect viability at physiologically relevant doses. Similar results with HUVECs have implications for understanding selenium's mechanisms of action as an anti-angiogenic agent.


Phenotypic characteristics associated with virulence of clinical isolates from the Sporothrix complex.
The Sporothrix complex members cause sporotrichosis, a subcutaneous mycosis with a wide spectrum of clinical manifestations. Several specific phenotypic characteristics are associated with virulence in many fungi, but studies in this field involving the Sporothrix complex species are scarce. Melanization, thermotolerance, and production of proteases, catalase, and urease were investigated in 61 S. brasiliensis, one S. globosa, and 10 S. schenckii strains. The S. brasiliensis strains showed a higher expression of melanin and urease compared with S. schenckii. These two species, however, presented similar thermotolerances. Our S. globosa strain had low expression of all studied virulence factors. The relationship between these phenotypes and clinical aspects of sporotrichosis was also evaluated. Strains isolated from patients with spontaneous regression of infection were heavily melanized and produced high urease levels. Melanin was also related to dissemination of internal organs and protease production was associated with HIV-coinfection. A murine sporotrichosis model showed that a S. brasiliensis strain with high expression of virulence factors was able to disseminate and yield a high fungal burden in comparison with a control S. schenckii strain. Our results show that virulence-related phenotypes are variably expressed within the Sporothrix complex species and might be involved in clinical aspects of sporotrichosis.


β-Caryophyllene as a Potential Protective Agent Against Myocardial Injury: The Role of Toll-Like Receptors.
Myocardial infarction (MI) remains one of the major causes of mortality around the world. A possible mechanism involved in myocardial infarction is the engagement of Toll-like receptors (TLRs). This study was intended to discover the prospective cardioprotective actions of β-caryophyllene, a natural sesquiterpene, to ameliorate isoproterenol (ISO)-induced myocardial infarction through HSP-60/TLR/MyD88/NFκB pathway. β-Caryophyllene (100 or 200 mg/kg/day orally) was administered for 21 days then MI was induced via ISO (85 mg/kg, subcutaneous) on 20th and 21st days. The results indicated that ISO induced a significant infarcted area associated with several alterations in the electrocardiogram (ECG) and blood pressure (BP) indices and caused an increase in numerous cardiac indicators such as creatine phosphokinase (CPK), creatine kinase-myocardial bound (CK-MB), lactate dehydrogenase (LDH), and cardiac tropinine T (cTnT). In addition, ISO significantly amplified heat shock protein 60 (HSP-60) and other inflammatory markers, such as TNF-α, IL-Iβ, and NFκB, and affected TLR2 and TLR4 expression and their adaptor proteins; Myeloid differentiation primary response 88 (MYD88), and TIR-domain-containing adapter-inducing interferon-β (TRIF). On the other hand, consumption of β-caryophyllene significantly reversed the infarcted size, ECG and BP alterations, ameliorated the ISO elevation in cardiac indicators; it also notably diminished HSP-60, and subsequently TLR2, TLR4, MYD88, and TRIF expression, with a substantial reduction in inflammatory mediator levels. This study revealed the cardioprotective effect of β-caryophyllene against MI through inhibiting HSP-60/TLR/MyD88/NFκB signaling pathways.


T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria.
Endemic Burkitt's lymphoma, a tumour of children in which B lymphocytes are infected with Epstein-Barr virus (EBV), is common in areas of Africa where malaria is holoendemic. The tumour is characterized by chromosome translocations; usually the terminal portion of chromosome 8 containing the c-myc gene is translocated to chromosome 14, near the enhancer of the immunoglobulin heavy-chain locus. Less frequent are translocations of chromosome 8 to the kappa light-chain locus of chromosome 2 or to the lambda light-chain locus of chromosome 22. In vitro, EBV induces B cells to proliferate and secrete immunoglobulin and antibody. However, in vivo the infected B lymphocytes are under immunological control, so that abnormal proliferation is found only in immunosuppressed patients. Such patients are subsequently liable to develop lymphomas. Burkitt believed that the tumour he had described resulted from interaction between a virus(es) and a "reticuloendothelial system altered by chronic and heavy infection by malarial or other parasites". We report here that during an attack of Plasmodium falciparum malaria, T-cell subpopulations are radically altered so that, in vitro, B lymphocytes infected with EBV proliferate abnormally to secrete large amounts of immunoglobulin and antibody. This phenomenon offers some explanation for the increased incidence of Burkitt's tumour and the high levels of immunoglobulin found in people living in areas where P. falciparum malaria is common.


Challenges in relating concentrations of aromas and tastes with flavor features of foods.
Flavor sensations in food are highly influenced by the aroma and taste compounds. Reviewing the extensive literature of recent years in this field has shown that the reconstitution of flavor based on aroma and taste compounds poses numerous problems. These are of different nature and include among others (a) chemical transformations among these compounds, (b) changes in the concentrations of the compounds responsible for the perceived flavor, (c) interactions among the chemical compounds that enhance or reduce a specific flavor sensation, and finally, (d) the complexity of the different food matrices and its influence in the flavor perception. Another difficulty that flavor scientists must face is how to properly model and visualize the complex relationships existing between the chemical composition of foods and the flavor perception. These problems have repercussions on the reconstitution of the flavor signature of food based on the natural concentrations of its key aroma and taste compounds. Therefore, the main aim of this review is to deal with all these issues to propose potential solutions for a robust transformation in a science-based quality approach.


Feasibility and effectiveness of a brief meditation-based stress management intervention for patients diagnosed with or at risk for coronary heart disease: a pilot study.
Extensive research has led to the development of a psychobiological model of cardiovascular disease. This model suggests that psychological factors such as depression, anxiety, hostility, and stress may affect the development and progression of coronary heart disease (CHD). Recent studies have also demonstrated that meditation-based stress reduction programs are useful interventions for patients with various medical and psychological symptoms. The objective of this pilot study was to gather preliminary information regarding the feasibility of implementing a brief meditation-based stress management (MBSM) program for patients with CHD, and those at high risk for CHD, at a major metropolitan hospital that serves a predominately non-local patient population. The secondary aim of this study was to investigate the possibility that such an intervention might reduce depression, as well as perceived stress, anxiety, and hostility, while improving general health scores. The overall feasibility results indicate that this MBSM intervention was highly feasible with regard to both recruitment and retention of participants. In fact, 40% of patients requested further training. In addition, after completion of the 4-week intervention, participants reported significant reductions in depression and perceived stress. In conclusion, the present study demonstrated that the brief meditation-based stress management program was well-received by patients and can successfully be used as a supportive program for patients at risk or diagnosed with CHD.


Primary structure and sequence analysis of RNA2 of a mechanically transmitted barley mild mosaic virus isolate: an evolutionary relationship between bymo- and furoviruses.
The RNA2 nucleotide sequence of a mechanically transmitted isolate of barley mild mosaic virus (BaMMV) has been determined. A combination of Northern blot and sequence analysis indicates that this RNA2 lacks approximately 1000 nucleotides of its C-terminal protein (P2) gene, with respect to Polymyxa graminis transmitted BaMMV. This is confirmed by sequence comparison with RNA2 of a fungus transmitted BaMMV isolate, which reveals the presence of a single deletion located in the 3'-terminal part of the P2 gene. As a consequence, this RNA2 codes for a P2 protein of only 34 K. Sequence homology between the bymovirus P2 protein and the capsid readthrough protein of beet necrotic yellow vein virus and soil-borne wheat mosaic virus suggests an evolutionary relationship between bymo- and furoviruses.


Geographical distribution of fertility rates in 70 low-income, lower-middle-income, and upper-middle-income countries, 2010-16: a subnational analysis of cross-sectional surveys.
Understanding subnational variation in age-specific fertility rates (ASFRs) and total fertility rates (TFRs), and geographical clustering of high fertility and its determinants in low-income and middle-income countries, is increasingly needed for geographical targeting and prioritising of policy. We aimed to identify variation in fertility rates, to describe patterns of key selected fertility determinants in areas of high fertility. We did a subnational analysis of ASFRs and TFRs from the most recent publicly available and nationally representative cross-sectional Demographic and Health Surveys and Multiple Indicator Cluster Surveys collected between 2010 and 2016 for 70 low-income, lower-middle-income, and upper-middle-income countries, across 932 administrative units. We assessed the degree of global spatial autocorrelation by using Moran's I statistic and did a spatial cluster analysis using the Getis-Ord Gi* local statistic to examine the geographical clustering of fertility and key selected fertility determinants. Descriptive analysis was used to investigate the distribution of ASFRs and of selected determinants in each cluster. TFR varied from below replacement (2·1 children per women) in 36 of the 932 subnational regions (mainly located in India, Myanmar, Colombia, and Armenia), to rates of 8 and higher in 14 subnational regions, located in sub-Saharan Africa and Afghanistan. Areas with high-fertility clusters were mostly associated with areas of low prevalence of women with secondary or higher education, low use of contraception, and high unmet needs for family planning, although exceptions existed. Substantial within-country variation in the distribution of fertility rates highlights the need for tailored programmes and strategies in high-fertility cluster areas to increase the use of contraception and access to secondary education, and to reduce unmet need for family planning. Wellcome Trust, the UK Foreign, Commonwealth and Development Office, and the Bill & Melinda Gates Foundation.


Bread wheat gliadin cytotoxicity: a new three-dimensional cell model.
In an attempt to clarify the role of gliadin toxicity in the pathogenesis of gluten intolerance (celiac disease), previous in vitro studies have been based on two-dimensional human cell cultures. However, the specific morphological and biochemical properties of in vivo tissue are better maintained in three-dimensional cell cultures (multicellular spheroids, MCS). The aim of this study was to develop a three-dimensional in vitro model to investigate the effects of gliadin on epithelial cells and broaden our understanding of the early tissue damage occurring in celiac disease. The three-dimensionally growing Lovo cell line was exposed to increasing concentrations of peptic-tryptic-digested bread wheat gliadin (from 125 to 1000 microg/mL) for 7 days in order to evaluate cell viability (colony-forming assay), and at the standard concentration of 500 microg/mL for 7 days in order to evaluate MCS diameters, volumes and cell morphology using light and electron microscopy. In comparison with the controls, the cell viability of the gliadin-treated MCS was significantly reduced (20-80%), but there was no difference in size. Various degrees of cell damage (autophagic vacuoles and intra-cytoplasmic lipid-like droplets) were detected by both light and electron microscopy. This is the first study investigating the effects of gliadin on MCS. Lovo MCS seem to be responsive to gliadin exposure, thus confirming previous results obtained using two-dimensional cell cultures. The data suggest that three-dimensional cell cultures may be useful in broadening our understanding of some of the early effects of gliadin peptides on epithelial cells.


Attitudes and characteristics of health professionals working in Aboriginal health.
There is an unacceptable gap in health status between Aboriginal and non-Aboriginal people in Australia. Linked to social inequalities in health and political and historical marginalisation, this health gap must be urgently addressed. It is important that health professionals, the majority of whom in Australia are non-Aboriginal, are confident and equipped to work in Aboriginal health in order to contribute towards closing the health gap. The purpose of this study was to explore the attitudes and characteristics of non-Aboriginal health professionals working in Aboriginal health. The research was guided and informed by a social constructionist epistemology and a critical theoretical approach. It was set within a larger healthy eating and physical activity program delivered in one rural and one metropolitan community in South Australia from 2005 to 2010. Non-Aboriginal staff working in the health services where the program was delivered and who had some experience or an interest working in Aboriginal health were invited to participate in a semi-structured interview. Dietitians working across South Australia (rural and metropolitan locations) were also invited to participate in an interview. Data were coded into themes that recurred throughout the interview and this process was guided by critical social research. Thirty-five non-Aboriginal health professionals participated in a semi-structured interview about their experiences working in Aboriginal health. The general attitudes and characteristics of non-Aboriginal health professionals were classified using four main groupings, ranging from a lack of practical knowledge ('don't know how'), a fear of practice ('too scared'), the area of Aboriginal health perceived as too difficult ('too hard') and learning to practice regardless ('barrier breaker'). Workers in each group had different characteristics including various levels of willingness to work in the area; various understandings of Australia's historical relationship with Aboriginal peoples; varying awareness of their own cultural identity and influence on working with Aboriginal people; and different levels of (dis)comfort expressed in discussions about social, political and intercultural issues that impact on the healthcare encounter. These groupings can be used to assist non-Aboriginal health professionals to reflect on their own levels of confidence, attitudes, characteristics, experiences, approaches and assumptions to Aboriginal health, as an important precursor to further practice and development in Aboriginal health. By encouraging self-reflection of non-Aboriginal health professionals about where their experiences, characteristics and confidence lie, the groupings presented in this paper can be used to encourage non-Aboriginal health professionals, rather than Aboriginal clients or workers, to be the focus for change and deliver health care that is more acceptable to patients and clients, hence influencing health service delivery. The groupings presented can also begin to enable discussions between all health professionals about working together in Aboriginal health.


Getting help for others: An examination of indirect helping in young children.
When young children recruit others to help a person in need, media reports often treat it as a remarkable event. Yet it is unclear how commonly children perform this type of pro-social behavior and what forms of social understanding, cognitive abilities, and motivational factors promote or discourage it. In this study, 48 three- to four-year-old children could choose between two actors to retrieve an out-of-reach object for a third person; during this event, one actor was physically unable to provide help. Nearly all of children's responses appropriately incorporated the actors' action capacities, indicating that rational prosocial reasoning-the cognitive basis for effective indirect helping-is common at this young age. However, only half of children actually directed an actor to help, suggesting that additional motivational factors constrained their prosocial actions. A behavioral measure of social inhibition and within-task scaffolding that increased children's personal involvement were both strongly associated with children's initiation of indirect helping behavior. These results highlight social inhibition and recognizing one's own potential agency as key motivational challenges that children must overcome to recruit help for others. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Determinants of annual change in physical activity in COPD.
Daily physical activity (PA) is reduced in patients with COPD. Previous cross-sectional analyses indicate various predictors for a low level of PA including airway obstruction, exacerbations and co-morbidities. However, information from longitudinal studies evaluating PA in the context of disease progression, survival and co-morbidities is scant. In a heterogeneous cohort of COPD patients, we annually assessed the number of steps per day over 1 week and potential determinants including lung function, exacerbations and co-morbidities. Univariable and multivariable mixed effect models were used to investigate associations between the change in steps per day (dependent variable) and possible predictors and their annual changes. A total of 177 COPD patients (46% GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 1/2, 38% stage 3 and 16% stage 4) with a mean (min/max) follow-up time of 2.7 (1/5) years were annually assessed. The number of steps per day decreased significantly over time (P < 0.001) with a mean annual change of -508 steps. The decrease in activity was significantly associated with forced expiratory volume in 1 s (FEV1 ) % predicted (P = 0.020) but not with annual changes in FEV1 . Hyperinflation, exacerbations, co-morbidities and their annual changes, and survival did not significantly affect change in PA. COPD patients have a substantial decrease of PA over time. This decrease seems to be determined by the degree of airflow limitation. However, patients with a greater annual decline in lung function did not show a greater decrease in PA. The rate of decline in PA did not differ between survivors and non-survivors in this cohort.


Safety skills training for surgeons: A half-day intervention improves knowledge, attitudes and awareness of patient safety.
Education and training of health care professionals is necessary to achieve sustainable improvements in patient safety. Despite its inherently risky nature, little training specifically in safety has been conducted in the surgical disciplines. In this study we explored the effects of a safety skills training program on surgical residents' knowledge, attitudes, and awareness of patient safety. A half-day training program incorporating safety awareness, analysis, and improvement skills was delivered to surgical residents from 19 hospitals in London, United Kingdom. Participants were assessed in terms of safety knowledge (MCQs) and attitudes to safety (validated questionnaire; scale 1 to 5) before and after training. To determine long-term effects, 6 months after training participants identified and reported on observed safety events in their own workplace by using an observational form for data collection. A total of 27 surgeons participated in the training program. Knowledge of safety significantly improved after the course (mean pre = 45.26% vs mean post = 70.59%, P < .01) as did attitudes to error analysis and improving safety (mean pre 3.50 vs mean post 3.97, P < .001) and ability to influence safety (mean pre 3.22 vs mean post 3.49, P < .01). After the course, participants reported richer, detailed sets of observations demonstrating enhanced understanding, recognition, and analysis of patient safety issues in their workplace. Safety skills training with positive educational outcomes can be delivered in a half day. Such a course may allow patient safety to be integrated into any curriculum, thereby training the next generation of the healthcare workforce to maintain the safety momentum.


The rise and fall of long-latency Plasmodium vivax.
Until World War II the only clinical phenotype of Plasmodium vivax generally recognised in medicine was one associated with either a long (8-9 months) incubation period or a similarly long interval between initial illness and the first relapse. Long-latency P. vivax 'strains' were the first in which relapse, drug resistance and pre-erythrocytic development were described. They were the infections in which primaquine radical cure dosing was developed. A long-latency 'strain' was the first to be fully sequenced. Although long-latency P. vivax is still present in some parts of Asia, North Africa and the Americas, in recent years it has been largely forgotten.


Susceptibility of greater sage-grouse to experimental infection with West Nile virus.
Populations of greater sage-grouse (Centrocercus urophasianus) have declined 45-80% in North America since 1950. Although much of this decline has been attributed to habitat loss, recent field studies have indicated that West Nile virus (WNV) has had a significant negative impact on local populations of grouse. We confirm the susceptibility of greater sage-grouse to WNV infection in laboratory experimental studies. Grouse were challenged by subcutaneous injection of WNV (10(3.2) plaque-forming units [PFUs]). All grouse died within 6 days of infection. The Kaplan-Meier estimate for 50% survival was 4.5 days. Mean peak viremia for nonvaccinated birds was 10(6.4) PFUs/ml (+/-10(0.2) PFUs/ml, standard error of the mean [SEM]). Virus was shed cloacally and orally. Four of the five vaccinated grouse died, but survival time was increased (50% survival=9.5 days), with 1 grouse surviving to the end-point of the experiment (14 days) with no signs of illness. Mean peak viremia for the vaccinated birds was 10(2.3) PFUs/ml (+/-10(0.6) PFUs/ml, SEM). Two birds cleared the virus from their blood before death or euthanasia. These data emphasize the high susceptibility of greater sage-grouse to infection with WNV.


Effects of methanol in blood pressure and heart rate in the rat.
Methanol ingestion is an uncommon form of poisoning that can cause severe metabolic disturbances, blindness, permanent neurologic dysfunction and death. While methanol itself may be harmless, it converts, in vivo, to highly toxic formic acid. Methanol intoxication clinically manifests as ocular toxicity. The present study investigated the cardiovascular effects of methanol. On the day of the experiment, Wistar rats were anesthetized with urethane. The femoral artery on one side was exposed, and a polyethylene catheter was inserted into the artery for recording arterial blood pressure (ABP). The catheter was attached to a pressure transducer (Statham - P23D). Systolic blood pressure (BP), mean ABP, and heart rate were recorded on a power-lab data acquisition system with a computerized analysis program. Rats were administered with different dilutions (9.5%, 19.0%, 28.5%, 38.0%, 47.5%, 57.0%, 66.5%, 76%) of methanol (95% v/v, i.v.). Of all dilutions of methanol, 66.5% dilution showed maximum decrease of diastolic BP from 124.64 ± 5.39 to 62.30 ± 11.90 mmHg; 76.0% dilution showed maximum decrease of systolic BP from 165.70 ± 5.57 to 112.11 ± 12.0 mmHg, and mean ABP from 160.61 ± 12.45 to 86.14 ± 4.11 mmHg. The heart rate increased (from 250 beats/s to near about 275 beats/s) following administration of methanol dilution from 19.0% till 76.0%. The present study is consistent with previous studies suggesting that methanol ingestion leads to severe hypotension as observed from decrease in diastolic BP, systolic BP, and mean ABP. However, severe increase of heart rate suggests activation of a compensatory mechanism to offset hypotension that eventually leads to death in methanol poisoning. Hence, this study emphasizes the need to monitor all the hemodynamic parameters in accidental methanol poisoning.


Ventilatory control and supplemental oxygen in premature infants with apparent chronic lung disease.
Our goal was to evaluate changes in respiratory pattern among premature infants born at <29 weeks gestation who underwent a physiological challenge at 36 weeks postmenstrual age with systematic reductions in supplemental oxygen and inspired airflow. Subjects were all infants enrolled in the Prematurity and Respiratory Outcomes Project at St. Louis Children's Hospital and eligible for a physiological challenge protocol because they were receiving supplemental oxygen or augmented airflow alone as part of their routine care. Continuous recording of rib cage and abdominal excursion and haemoglobin oxygen saturation (SpO2%) were made in the newborn intensive care unit. 37 of 49 infants (75.5%) failed the challenge, with severe or sustained falls in SpO2%. Also, 16 of 37 infants (43.2%) who failed had marked increases in the amount of periodic breathing at the time of challenge failure. An unstable respiratory pattern is unmasked with a decrease in inspired oxygen or airflow support in many premature infants. Although infants with significant chronic lung disease may also be predisposed to more periodic breathing, these data suggest that the classification of chronic lung disease of prematurity based solely on clinical requirements for supplemental oxygen or airflow do not account for multiple mechanisms that are likely contributing to the need for respiratory support.


Pleural procedural complications: prevention and management.
Pleural disease is common with a rising case frequency. Many of these patients will be symptomatic and require diagnostic and/or therapeutic procedures. Patients with pleural disease present to a number of different medical specialties, and an equally broad range of clinicians are therefore required to have practical knowledge of these procedures. There is often underestimation of the morbidity and mortality associated with pleural interventions, even those regarded as being relatively straightforward, with potentially significant implications for processes relating to patient safety and informed consent. The advent of thoracic ultrasound (TUS) has had a major influence on patient safety and the number of physicians with the necessary skill set to perform pleural procedures. As the variety and complexity of pleural interventions increases, there is increasing recognition that early specialist input can reduce the risk of complications and number of procedures a patient requires. This review looks at the means by which complications of pleural procedures arise, along with how they can be managed or ideally prevented.


Propofol detection and quantification in human blood: the promise of feedback controlled, closed-loop anesthesia.
The performance of a membrane-coated voltammetric sensor for propofol (2,6-diisopropylphenol) has been characterized in long term monitoring experiments using an automated flow analytical system (AFAS) and by analyzing human serum and whole blood samples by standard addition. It is shown that the signal of the membrane-coated electrochemical sensor for propofol is not influenced by the components of the pharmaceutical formulation of propofol (propofol injectable emulsion). The current values recorded with the electrochemical propofol sensor in buffer solutions and human serum samples spiked with propofol injectable emulsion showed excellent correlation with the peak heights recorded with an UV-Vis detector during the HPLC analysis of these samples (R(2) = 0.997 in PBS and R(2) = 0.975 in human serum). However, the determination of propofol using the electrochemical method is simpler, faster and has a better detection limit (0.08 ± 0.05 μM) than the HPLC method (0.4 ± 0.2 μM). As a first step towards feedback controlled closed-loop anesthesia, the membrane-coated electrochemical sensor has been implemented onto surface of an intravenous catheter. The response characteristics of the membrane-coated carbon fiber electrode on the catheter surface were very similar to those seen using a macroelectrode.


Informal Caregiving Networks for Hospice Patients With Cancer and Their Impact on Outcomes: A Brief Report.
This prospective study investigates informal care networks and their impact on hospice outcomes. Primary caregivers (N = 47) were the main source of data from 2 time points: within a week of enrollment in hospice and bereavement. Data were also collected from 42 secondary caregivers. Intraclass correlation coefficients (ICCs) determined correspondence between primary and secondary caregivers regarding informal care network size. Correlations were used to test associations between variables. Nonparametric paired sample tests were used to analyze change in anger and guilt. The ICC found poor correspondence (-0.13) between primary and secondary caregivers' network descriptions. Correlational analyses found a strong/moderate negative association between quality of dying (QOD) and grief (r = -0.605, P < .05). Study participants reported increased anger (0.4, P < .05, range 1-5) and guilt (0.4, P < .05, range 1-5), particularly among caregivers with high levels of support. Findings suggest that improving QOD may facilitate postdeath coping for caregivers.


Modeling of the wave transmission properties of large arteries using nonlinear elastic tubes.
We propose a new, simple way of constructing elastic tubes which can be used to model the nonlinear elastic properties of large arteries. The tube models are constructed from a silicon elastomer (Sylgard 184, Dow Corning), which exhibits a nonlinear behavior with increased stiffness at high strains. Tests conducted on different tube models showed that, with the proper choice of geometric parameters, the elastic properties, in terms of area-pressure relation and compliance, can be similar to that of real arteries.