Validity and reliability of eye healthcare professionals in the assessment of glaucoma - a systematic review.

OBJECTIVE(S): To explore the validity and reliability of eye healthcare professionals with different levels of training in diagnosing and/or identifying glaucomatous progression. CLINICAL RELEVANCE: Substantial pressure is being placed on our current eye healthcare workforce by chronic diseases such as glaucoma. Shared care schemes and role expansion of professionals other than ophthalmologists are being proposed to alleviate this pressure. A sound evidence base is imperative to determine whether other allied health professionals are skilled and clinically competent, when it comes to taking on these new roles in glaucoma management. METHODS: A systematic review of research articles identified in MEDLINE, CINAHL, Embase, Scopus and Cochrane Library was performed. Studies which investigated rater reliability of various health professionals in diagnosing and/or identifying glaucoma progression against a reference standard were included. RESULTS: Of the 4088 publications identified by the initial database search, 32 met the inclusion criteria. The majority of studies demonstrated positive results, with most finding moderate to substantial agreement for inter- and intra-rater reliability across all testing modalities. The eye health professionals with ophthalmology training consistently attained the greatest agreement. When allied health professionals with different levels of training were compared, those who had completed residency training were significantly better than those who had not. CONCLUSION: The studies included in this review show promising results, including those raters without ophthalmology training. A lack of power calculations, unequal sample sizes in some studies and the diversity of the testing procedures used make it difficult to make sound inferences.

Carer-supported home-based exercises designed to target physical activity levels and functional mobility after stroke: a scoping review.

PURPOSE: To explore the literature on carer-supported home-based exercise programs for people after stroke, as a form of physical activity. The review focus was to examine the training carers receive, the content of programs, and investigate the physical activity levels and functional mobility of people after stroke. MATERIALS AND METHODS: A scoping review was undertaken, guided by Joanna Briggs Institute methodology. The concept of home-based carer-supported exercise, in people after stroke, was searched across five databases. Outcomes of interest were physical activity levels and functional mobility. RESULTS: We screened 2285 references and included 10 studies: one systematic review, five randomised controlled trials, one trial with non-equivalent control, and four uncontrolled studies. Carer training ranged from one to twelve sessions. Exercise interventions commonly including walking, other whole body functional exercises and balance activities. In eight studies interventions were in addition to standard care. Five studies reported significant between-group differences for functional mobility, favouring the intervention. One study reported physical activity levels. CONCLUSION: There was large variation in the volume and content of training provided to carers. Physical activity levels were infrequently objectively reported. Future studies should include greater details on their protocols to allow for replication and implementation into clinical practice.

Carer-supported home-based exercises may improve functional mobility once home after a stroke.The optimal length, content, and model of delivery of carer training, so carers can provide better targeted home-based exercise support to people after stroke, is not known.Better monitoring of participation in home-based exercise and reporting of short and long-term physical activity is needed.

Pushing through the Barriers: Peer Advice to Increase Physical Activity and Reduce Dementia Risk from Participants in a Massive Open Online Alzheimer's Focused Course.

BACKGROUND: Engagement in physical activity is associated with reduced dementia risk but insufficient physical activity is a global trend. OBJECTIVES: We aimed to explore what advice might be offered to others to increase physical activity and to identify enablers and barriers to physical activity for adults interested in dementia prevention and participating in a massive open online course. PARTICIPANTS: Two thousand, one hundred and thirty-two participants contributed to an online discussion forum. DESIGN: Analysis was conducted using Topic modelling analysis followed by thematic analysis. RESULTS: The themes generated from the discussion posts included time constraints, poor health and lack of motivation as barriers to physical activity, and social interaction, incidental activities, and dog ownership as enablers. Peer advice was frequently suggested around scheduling physical activity into the day and joining a friend or organised activity. CONCLUSION: This online discussion forum uniquely captured ideas from a large, diverse group of participants. Future research may benefit from further examining the role of discussion forums and peer advice in dementia risk reduction initiatives.

Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

Unraveling the mystery of "tech red" - a volatile technetium oxide.

We show that a Tc2O5 molecular species is the likely identity of an unknown volatile oxide which has remained uncharacterized for 50+ years. Exploration of this molecule's absorption spectra and intermolecular self-interactions provides a close match to experimental data and an explanation for volatility and resistance to crystallization.

Identification, purification, and subcellular localization of prostate-specific membrane antigen PSM' protein in the LNCaP prostatic carcinoma cell line.

An alternatively spliced variant of prostate-specific membrane antigen (PSMA) designated PSM' was originally described following identification of its mRNA in normal prostate. We have purified the PSM' protein from LNCaP cells using two immunoaffinity columns in tandem. The first column contained a monoclonal antibody (7E11) that was reactive with the NH2 terminus of PSMA, which specifically depleted the LNCaP lysate of full-length PSMA. The nonbinding fraction was then passed over a second column composed of a monoclonal antibody (PEQ226.5), the epitope of which was located within the 134-437 domain of PSMA and shared with PSM'. The protein eluted from the second immunoaffinity column produced a Mr 95,000 band on SDS-PAGE, which was slightly lower than the full-length PSMA at Mr 100,000. The band was NH2-terminally sequenced through 15 residues, and the assigned sequence coincided with the predicted sequence for PSM' protein minus the first two NH2 terminus amino acids. The PSM' protein, therefore, began with residue 60 of PSMA (alanine). LNCaP cells were fractionated, and PSM' was localized to the cytoplasm.

Cortical and subcortical afferent connections of a posterior division of feline area 7 (area 7p).

Area 7 of the cat, as identified cytoarchitecturally, includes cortex both on the middle suprasylvian gyrus and on the anterior lateral gyrus. The aim of the experiments reported here was to determine whether within this zone there are subdivisions with qualitatively different patterns of afferent connectivity. Deposits of distinguishable retrograde tracers were placed at 29 sites in and around area 7 of 15 cats; cortical and subcortical telencephalic structures were then scanned for retrograde labeling. Our results indicate that cortex on the anterior lateral gyrus, although often included in area 7, is indistinguishable on connectional grounds from adjacent somesthetic cortex (area 5b). Cortex with strong links to visual, oculomotor, and association areas is confined to the middle suprasylvian gyrus and the adjacent lateral bank of the lateral sulcus. We refer to this discrete, connectionally defined zone as posterior area 7 (area 7p). Area 7p receives input from visual areas 19, 20a, 20b, 21a, 21b, AMLS, ALLS, and PLLS; from frontal oculomotor cortex (areas 6m and 6l); and from cortical association areas (posterior cingulate cortex, the granular insula, the posterior ectosylvian gyrus, and posterior area 35). Thalamic projections to area 7p arise from three specific nuclei (pulvinar; nucleus lateralis intermedius, pars caudalis; nucleus ventralis anterior) and from the intralaminar complex (nuclei centralis lateralis, paracentralis and centralis medialis). Neurons in a division of the claustrum immediately beneath the somatosensory and visual zones project to area 7p. Within area 7p, anterior-posterior regional differentiation is present, as indicated by the spatial ordering of projections from cingulate and frontal cortex, the thalamus, and the claustrum. Area 7p, as delineated by connectional analysis in this study, resembles cortex of the primate inferior parietal lobule both in its location relative to other cortical districts and in its pattern of neural connectivity.

Aerobic power and cardiovascular response to stress.

The relationship between aerobic fitness as measured by maximal O2 uptake (VO2max) and the cardiovascular response to laboratory stressors was examined in two experiments. First, 34 male college students were screened on the basis of their heart rate (HR) response to a reaction time-shock avoidance (RT-AV) task. The six individuals showing an average HR increase of 45 beats/min (reactives) and the six subjects showing an average increase of 8 beats/min (nonreactives) did not differ in VO2max (47.7 +/- 2 vs. 48.7 +/- 1 ml.kg-1.min-1, respectively). However, a statistically significant association between a reported family history of hypertension and peak HR response to RT-AV was seen. In the second series of experiments, the plasma catecholamine and cardiovascular responses of eight elite endurance-trained athletes (VO2max 70.6 +/- 1 ml.kg-1.min-1) and eight untrained volunteers (VO2max 45.5 +/- 1 ml.kg-1.min-1) were compared on the following: RT-AV, reaction time for monetary reward (RT-AP), cold pressor, isometric handgrip, and orthostatic challenge (standing). The trained group exhibited a significantly lower mean HR at rest (P less than 0.05), otherwise there were no significant differences between the two groups. The results indicate that although individual differences (e.g., family history of hypertension and high resting HR) can be related to the potential for cardiovascular responses to novel laboratory challenges, the contribution of fitness to this characteristic is much less clear. Further exploration of questions pertaining to fitness and stress should focus on individuals with a predisposition to stress reactivity.

Relationship of racial stressors to blood pressure responses and anger expression in black college students.

The physiological effects of racism, as a stressor, were examined as they related to blood pressure (BP) and anger experiences in Black college students. Current research has failed to consider the stressful effects of racism as a factor contributing to the higher incidence of essential hypertension among Blacks. Twenty-seven Black college students viewed three excerpts showing racist situations involving Blacks; anger-provoking, nonracist situations; and neutral situations. After each scene, BP was taken, and a mood checklist was administered. The Framingham Anger Scale and the Anger Expression Scale were administered. Analyses revealed that BP significantly increased during the presentation of racist stimuli but not of anger-provoking or neutral stimuli. Self-reports of state anger, as measured by the mood checklist, were significant for both the anger-provoking and racist stimuli. BP scores were significantly correlated to the two trait anger measures. Exposure to racist stimuli was associated with BP increases among Blacks. Such cumulative exposure to racism may have important implications for the etiology of essential hypertension.

Type A behavior pattern, parental history of hypertension, and cardiovascular reactivity in college males.

Two risk factors for cardiovascular disorders, parental history of hypertension and the Type A behavior pattern, were investigated concurrently with respect to cardiovascular reactivity to challenging situations. Sixty-four college males were given both the Structured Interview (SI) and Jenkins Activity Survey (JAS) for the Type A behavior pattern and a family health questionnaire to determine parental history of hypertension. The students were monitored for blood pressure (BP), heart rate (HR), and pulse transit time (PTT) response to four tasks: cold pressor, isometric handgrip exercise, a reading comprehension task, and backwards digit span. Type As based on SI classification had significantly higher HR levels across all tasks than did Type Bs, as well as higher diastolic BP levels in the cold pressor task. No main effects for Type A-B using JAS classification were found. Positive parental history students had higher HR and shorter PTT levels across all the tasks. Type A and parental history did interact in a limited way on some tasks, but the interactions were also dependent on the Type A classification used.

Physiological correlates of the coronary-prone behavior pattern in women during examination stress.

This research is an assessment of the physiological correlates of Type A behavior in college-aged women. Subjects were monitored while they took a midterm statistics examination; the dependent variables were systolic and diastolic blood pressure, heart rate, and heart rate variability. Type A or B behavior was assessed with the student form of the Jenkins Activity Survey. The results indicated that Type A women had higher levels of systolic blood pressure and heart rate, and lower levels of heart rate variability. Thus, when the stressor was a genuine examination, Type A behavior in young women was associated with increased physiological response levels compared to Type B's, a finding consistent with the hypothesis that Type A behavior is associated with sympathetic nervous system activity.

Hardiness, type A behavior, and the stress-illness relation in working women.

Hardiness has been proposed as a stress-resistance resource in maintaining health. This construct has been shown to act in conjunction with the Type A behavior pattern in affecting illness. In this study, we examined this relation in women (N = 82) with the use of the Structured Interview and the Jenkins Activity Survey to assess Type A behavior. As expected, there was a strong stress-illness association. However, there were no hardiness main effects nor interactions between stress, Type A behavior, and hardiness. Hardiness was significantly associated with age, education level, and marital status. No differences in hardiness composition were found between high stress/high illness and high stress/low illness groups. Only the Powerlessness scale of hardiness was related to illness. These results are discussed in comparison with other hardiness studies. Particular attention is focused on possible sex differences, and implications for future research are suggested.

The relationship of stress, type A behavior and powerlessness to physiological responses in female clerical workers.

The present study examined the relationship of stress levels, Type A behavior, and feelings of powerlessness to physiological reactivity in a group of adult women employed as secretaries. Reactivity was assessed by monitoring blood pressure, heart rate and frontalis EMG while subjects engaged in a series of tasks: rest, mental arithmetic, vigilance, a structured interview and a work interview. When Type A behavior was assessed by a structured interview, Type A's had higher overall levels of systolic and diastolic blood pressure, a tendency toward greater EMG reactivity, and high stress Type A's had higher heart rates than low stress Type A's. When Type A was assessed by a questionnaire, Type A interacted with stress levels and lack of control such that high stress, high powerlessness Type A's had higher overall levels of systolic and diastolic blood pressure and high powerlessness Type A's had higher levels of heart rate than high powerlessness Type B's. While reactivity was not related to Type A behavior, it was related to stress levels. Women with high levels of background stress responded with larger increases in systolic blood pressure and a tendency toward larger increases in heart rate. This research emphasizes the importance of examining multiple factors, especially when relating individual differences in risk to psychophysiological reactivity.

The relationship of parenting styles and social competency to Type A behavior in children.

This study examined parenting styles, Type A behavior in parents and children, and social competence in children. Fifty 1st-6th grade children, parents, and their teachers participated. Type A behavior in parents was associated with a controlling style of parenting, but not with pressuring the child to achieve. Parenting styles of achievement pressure and high control were related to impatient and aggressive behaviors in children, as measured by the MYTH, a teacher-scored Type A behavior instrument. In addition, impatience and aggressiveness in the children were negatively correlated with the child's social competency and ability to function in school. Parenting practices, Type A behavior, and social competency in children may play important roles in the origins of detrimental components of Type A behavior, such as impatience and aggression.

The anger recall interview and cardiovascular reactivity in women: an examination of context and experience.

Recent research has focused on the role of hostility as a risk factor for coronary heart disease. Hostility has been linked independently to cardiovascular mortality and, as a component of Type A behavior, to atherogenesis and myocardial infarction; however, the mechanisms by which hostility manifests its effects on the cardiovascular system have not been determined. In addition, hostility has been evaluated as a trait measure, with little emphasis on how anger-provoking episodes may be perceived by individuals. The present study seeks to evaluate the affective experience of hostility, through an anger recall interview, and relate qualities of that experience to one potential mechanism of cardiovascular risk, cardiovascular reactivity. Fifty-eight women, classified by structured interview as Type A or B, participated in an anger recall interview while their heart rate and blood pressure were monitored. Type A women manifested greater systolic reactivity when their anger was in response to frustration of autonomy needs, while Type B women exhibited greater heart rate reactivity in response to frustration of affiliation needs. All women who suppressed anger expression experienced higher pressor responses than women who expressed anger assertively. Future investigations may find the content of an interview as useful as the procedure itself in studies of cardiovascular reactivity.

Control, type A behavior and cardiovascular responsivity in adult women employed as clerical workers.

The purpose of the present study was to examine the relationship among control, Type A behavior and cardiovascular responsivity in female clerical workers. Control was examined by assessing locus of control and by employing a learned helplessness paradigm. Helplessness was varied by three treatment conditions on a concept identification task: (1) a helplessness condition where noncontingent feedback was provided, (2) a moderate helplessness condition, and (3) a no helplessness (no feedback) condition. The effects of these treatments on performance were examined by measuring trials to criterion on a subsequent anagram task. Heart rate and blood pressure were monitored during rest periods and tasks. Both Types A and B women exhibited learned helplessness. Type As who experienced the helplessness treatment responded with greater increases in systolic blood pressure and greater decreases in heart rate variability on the anagram task. During the helplessness task itself, Type A women with an external locus of control were the most reactive group as indexed by heart rate and heart rate variability. For those women experiencing moderate helplessness, external locus of control Type As had higher systolic blood pressure levels on both tasks. These results suggest that task-induced lack of control or external locus of control is associated with increased cardiovascular reactivity in Type A women.

Type A behavior and physiological responsivity in young women.

The purpose of this study was to assess the coronary-prone behavior pattern and physiological responses to stress in young women. Thirty-seven women, aged 18-25 yr, were tested; half were studying in nontraditional fields for women, half in traditional. Based on the Jenkins Activity Survey, women in the male-dominated fields of study were more Type A. Subjects were monitored while resting and while solving mental arithmetic problems and visual puzzles; the dependent variables were heart rate, and blood pressure. Comparisons were made based on both the Jenkins Activity Survey and the structured interview, and using both median splits and extreme groups. There were no physiological differences between Types A and B women. Possible methodological issues accounting for the lack of results are considered.

Gender and cardiovascular responses: what is the role of hostility?

Two experiments are reported investigating hostility group by gender effects on heart rate and blood pressure. In experiment 1, 58 males and 59 females were tested with a protocol that included baseline, reaction time with and without harassment, and recovery. In experiment 2, 55 males and 50 females participated in a procedure of baseline, Stroop color--word conflict, anger recall interview, and recovery. Based on Buss-Durkee subscales, genders were divided into high and low neurotic hostility and expressed hostility groups. High expressed hostility was associated with greater diastolic reactivity to all tasks in males, but not in females. Low expressed hostility was associated with greater heart rate and systolic reactivity, specifically during the anger recall interview. High neurotic hostility in males and females was associated with greater diastolic reactivity to the anger task only, while low Neurotic hostility males had higher resting systolic pressures. These results suggest that outward expression of hostility in men may increase their coronary heart disease risk; however, results for both men and women support an association between cardiovascular reactivity and a lack of match between self-reported anger management style and task demands.

An alternative approach for achieving cardiovascular baseline: viewing an aquatic video.

Due to the importance of baseline and recovery levels in the computation of reactivity, two studies were conducted to determine an alternative method to traditional rest for achieving baseline and recovery levels of cardiovascular measurements. Watching a relaxing, aquatic video was compared with a traditional resting baseline to determine the better method for achieving low baseline levels. In addition, watching the video was compared with traditional rest during 5-min post-task recovery periods. Systolic (SBP) and diastolic blood pressure (DBP) decreased more during the baseline period when subjects viewed the video than when subjects rested quietly. Similarly, subjects displayed greater recovery following the mental tasks when they watched a video than when they merely sat quietly. It is recommended that researchers standardize baseline procedures by showing a relaxing video before administering tasks for the assessment of cardiovascular reactivity.

Psychophysiological correlates of individual differences in patterns of hemodynamic reactivity.

The present study delineates a method for the quantification of six hemodynamic reactivity patterns, in response to a laboratory stressor, and examines the psychophysiological correlates of individual differences in these patterns. One hundred and ninety-four young adult men and women participated in rest periods and two laboratory stressors, mental arithmetic and an anger recall interview. Measures were taken of blood pressure, heart rate, and cardiac output, from which total peripheral resistance was derived, as well as state reports of feelings during the tasks. Six hemodynamic reactor patterns were identified: Non-reactors, Mild Myocardials, Mild Vasculars, Myocardials, Vasculars, and Dual Reactors, each associated with a unique profile of cardiac output and total peripheral resistance change. Myocardial reactors to the interview had the highest resting levels of blood pressure and total peripheral resistance. Dual reactors had the largest increases in diastolic reactivity; Dual and Myocardial reactors had the largest increases in systolic reactivity. The extreme reactor groups (Dual, Myocardial, Vascular) all reported greater task invigoration than the Non-reactors, who reported greater efforts to relax. Reactor groups were similar on anger-related trait affect. Based on both resting blood pressure and magnitude of task-induced reactivity, Myocardial and Dual reactors may be at the greatest risk for subsequent hypertension.