Cellular and humoral immunogenicity of the COVID-19 vaccine and COVID-19 disease severity in individuals with immunodeficiency.

Background: A well-coordinated adaptive immune response is crucial for limiting COVID-19 disease. Some individuals with immunodeficiency are at a high risk of developing severe COVID-19. Therefore, the development of standardized methods for measuring different arms of the vaccine response in the setting of immunodeficiency is of particular interest. In this study, we compared the vaccine response of individuals living with immunodeficiency with healthy controls in terms of interferon gamma (IFN-γ) production and spike protein-specific antibody level post primary COVID-19 vaccination and booster vaccines. Additionally, the disease severity of those individuals who contracted COVID-19 was assessed. Methods: Whole blood was stimulated overnight from 71 participants and 99 healthy controls. Commercially available PepTivator® peptide pool and trimeric spike protein stimulation were used. ELISA was used to analyze IFN-γ levels. The total SARS-CoV-2 spike protein antibody titre was measured using a Roche Elecsys® S total antibody assay. Patient characteristics, COVID-19 infection status and IDDA 2.1 'Kaleidoscope' scores were recorded. Vaccine responses were scored from zero to three. Results: 99% of healthy controls, 89% of individuals with IEI and 76% with secondary immunodeficiency (SID) had an IFN-γ level above the validated reference range after peptide mix stimulation following primary vaccination. There was an increase in IFN-γ levels in patients with inborn errors of immunity (IEI) following the booster vaccine (p = 0.0156). 100% of healthy controls, 70% of individuals living with IEI and 64% of individuals living with SID had detectable spike protein-specific antibody levels following the primary vaccination. 55% of immunodeficiency patients who had mild COVID-19 and 10% with moderate/severe COVID-19 had detectable antibody and IFN-γ levels post vaccine. The mean pre-infection IDDA 2.1 scores were higher in individuals who developed moderate/severe COVID-19 (25.2 compared to 9.41). Conclusions: Covid whole-blood IGRA is a highly accurate, straightforward and robust assay and can be easily adapted to measure cellular response to COVID-19. A complete evaluation of the vaccine response may be particularly important for individuals living with immunodeficiency. A clinical immunodeficiency score and a validated vaccine response score may be valuable tools in estimating COVID-19 disease risk and identifying individuals living with immunodeficiency who may benefit from enhanced vaccination schedules.

Exploring attentional biases towards facial expressions of pain in men and women.

BACKGROUND: Interpersonal factors may help explain why men and women differ in their perception and expression of pain. Whilst the focus is often on the person in pain, how observers respond to those in pain is important. This study explored whether male-female differences exist in the way observers attend to expressions of pain in others. METHODS: Fifty-three adults (26 females) completed a visual dot-probe task, to measure selective attentional biases to facial expressions of pain and fear. Expression pairs (e.g. pain/neutral) were displayed by either the same male or female actor, and in two different viewing duration conditions: 150 and 1250 ms. Dot-probes appeared in either a congruent or incongruent location to the target expression. RESULTS: No evidence was found for sex-related attentional biases towards pain or fear. However, when examining congruency and incongruency indexes separately, differences emerged. The congruency index analysis indicated that in the 150-ms presentation condition, both men and women were slower during congruent female pain/neutral trials when compared to neutral/neutral trials, and relatively faster at responding during congruent male pain/neutral trials. CONCLUSIONS: There is utility in exploring the attentional processes involved in the decoding of pain-related expressions to understand the influence of sex and gender differences in pain. Although male-female differences were found, this was most clearly related to the actor. Our results point to an early attentional mechanism that orients attention away from female expressions of pain. Future consideration of sex- and gender-related contextual factors in attentional processing is warranted. SIGNIFICANCE: Sex-related factors seem to affect how observers view the pain of others. Our results point to an early attentional mechanism that orients the attention of observers away from female expressions of pain.

Reasons for Treatment Non-Response: A Controlled Study of Patients' Views in Pain Rehabilitation.

BACKGROUND: Understanding successful and unsuccessful behavioural treatment for pain is essential. AIMS: We carried out a retrospective survey of 130 people who had undergone pain rehabilitation based on acceptance and commitment therapy, aiming to identify factors associated with non-response. METHOD: The sample was selected using the reliable change index to define 'responders' and 'non-responders' to key outcome measures. We surveyed a range of treatment-related, systemic, practical and personal factors that may have affected their treatment, and then compared 'non-responders' with 'responders', controlling for factors that might not be causal or specific to non-response. RESULTS: Logistic regression analysis showed two themes that distinguished the groups, 'people outside programme' and 'emotional state'. CONCLUSIONS: These data have clinical implications, as such factors can be addressed directly or incorporated into an assessment of treatment 'readiness'. This study introduced a novel methodology for the investigation of pain treatment response, which allowed a broad study of clinically relevant variables, but with greater rigour than conventional self-reports of 'helpful factors' in treatment.

Sex differences in the decoding of pain-related body postures.

BACKGROUND: Pain can be detected through nonverbal cues, including facial expressions, vocalisations, and body posture. While there are sex differences in how emotional expressions are recognized, these differences have not always been found for pain. One reason for this inconsistency may be methodological, as pain studies tend not to be designed to investigate individual differences in expression recognition. Also, few studies consider sex differences outside facial expression. METHODS: This study applied an image degradation method used to examine individual differences in emotion recognition, to investigate sex differences in the decoding of pain body postures. Forty participants (20 male) were presented with a series of body posture images depicting pain at differing levels of image degradation. Happiness, anger and sadness expressions were also included for comparison. RESULTS: Results showed significant effects of image degradation, affect type, and actor sex. Females were rated as presenting more intense pain than males; this pattern was also found for fear, but not anger or happiness. The accuracy of pain intensity judgements was reduced as image clarity decreased. Male actors depicting pain were recognized with greater accuracy than female actors. Interestingly, similar patterns were found for anger and fear expressions. CONCLUSIONS: We conclude that sex has a significant influence on pain decoding under certain conditions, and while there are similarities with the way pain and core emotions are decoded, this may depend on the type of emotion presented. This also suggests that sex-related effects in the recognition of pain expressions may include body postural cues. SIGNIFICANCE: Observer's judgements of pain displayed through body postures are driven by the sex of the person in pain.

Rapid annotation of interictal epileptiform discharges via template matching under Dynamic Time Warping.

BACKGROUND: EEG interpretation relies on experts who are in short supply. There is a great need for automated pattern recognition systems to assist with interpretation. However, attempts to develop such systems have been limited by insufficient expert-annotated data. To address these issues, we developed a system named NeuroBrowser for EEG review and rapid waveform annotation. NEW METHODS: At the core of NeuroBrowser lies on ultrafast template matching under Dynamic Time Warping, which substantially accelerates the task of annotation. RESULTS: Our results demonstrate that NeuroBrowser can reduce the time required for annotation of interictal epileptiform discharges by EEG experts by 20-90%, with an average of approximately 70%. COMPARISON WITH EXISTING METHOD(S): In comparison with conventional manual EEG annotation, NeuroBrowser is able to save EEG experts approximately 70% on average of the time spent in annotating interictal epileptiform discharges. We have already extracted 19,000+ interictal epileptiform discharges from 100 patient EEG recordings. To our knowledge this represents the largest annotated database of interictal epileptiform discharges in existence. CONCLUSION: NeuroBrowser is an integrated system for rapid waveform annotation. While the algorithm is currently tailored to annotation of interictal epileptiform discharges in scalp EEG recordings, the concepts can be easily generalized to other waveforms and signal types.

Why go online when you have pain? A qualitative analysis of teenagers' use of the Internet for pain management advice.

BACKGROUND: Adolescents are routinely recognized as native to online technologies. However, we know from previous research that this familiarity does not often translate into its use for help-seeking around health. We designed this study to examine the experience of adolescents in using the Internet to access pain management information, specifically why some adolescents may be reluctant to use these resources. METHODS: Twenty-six healthy, school attending, adolescents aged between 14 and 17 years old were recruited to a qualitative study of focus groups. Seventeen participants were female and nine were male. Participation was limited to those who self-selected as frequent users of the Internet, but who were loath to use it as a resource for health information as we wished to explore reasons for non-use. All data were thematically analysed. RESULTS: Most participants reported using the Internet to seek health information at least once. Experiences with online content were typically negative and drawn on only when all other sources of information and pain coping were exhausted. Three themes emerged, Drivers of Internet use, Barriers, and Anxiety around use. Adolescent health websites were reported to be confusing, anxiety provoking and hard to negotiate. The Internet was judged to be less accessible than other forms of pain and health coping information. Secondary themes related to topic embarrassment, the strive for independence and reassurance, preferred information source failure, curiosity, website design, availability of OTC analgesics, effort, fear-provoking narratives, mistrust of quality of online content and pain-related anxiety. CONCLUSIONS: Counter to many positive reports of the health benefits of Internet use during information seeking, its value is questionable to some adolescents. Typical experience was anxiety provoking, unlikely to yield helpful results, and wasteful comparative to off-line resources for pain.

Return to work with chronic pain: employers' and employees' views.

BACKGROUND: The sickness certification and return to work (RTW) of people with chronic pain are important health and economic issues for employees, employers, taxpayers and the UK government. The 'fit note' and a national educational programme promoting RTW were introduced in 2010 to curb rising rates of sickness absence. AIMS: To investigate employers' and employees' experiences of managing RTW when someone has taken sick leave for chronic pain and to explore the perceived efficacy of the fit note. METHODS: A qualitative study, comprising semi-structured interviews with employers who had managed sick leave cases and employees who had experienced sick leave for chronic pain. Interviews were recorded, transcribed and the data analysed using constructivist grounded theory principles. RESULTS: Five themes were elicited. Firstly, frequent enquiry after health status was seen as intrusive by some employees but part of good practice by employers and acknowledging this difference was useful. Secondly, being able to trust employees due to their performance track record was helpful for employers when dealing with complex chronic pain conditions. Thirdly, feeling valued increased employees' motivation to RTW. Fourthly, guidelines about maintaining contact with absent employees were useful if used flexibly. Finally, both parties valued the fit note for its positive language, interrogative format and biomedical authority. CONCLUSIONS: The fit note was perceived to be helpful if used in combination with other strategies for managing sick leave and RTW for people with chronic pain. These strategies may be applicable to other fluctuating, long-term conditions with medically unexplained elements.

Emotion-focused coping and distraction: sex differences in the influence of anxiety sensitivity during noxious heat stimulation.

While previous research has indicated that the relative efficacy of attentional strategies on pain may be influenced by anxiety sensitivity (AS) and sex, no study appears to have examined this within the context of an emotion-focus versus distraction paradigm. The present study compared the effect of attentional emotion-focus and distraction instructions on pain response with noxious heat stimulation in 114 healthy adults (62 women and 52 men) varying in levels of AS. Results indicated that men reported a significantly higher mean tolerance time than women. Moderated regression analysis also revealed a significant strategy × anxiety sensitivity × sex interaction on pain tolerance. For those low in AS, relative efficacy was dependent upon sex, with distraction superior to emotion-focusing in women, but with strategies equivalent in men. For those high in AS, however, distraction resulted in uniformly greater pain tolerance than attentional emotion-focusing. These results indicate that AS and sex may be influential in determining the relative effectiveness of distraction and emotion-based attentional strategies for pain management.

Supporting anthropological research with efficient rotation invariant shape similarity measurement.

The matching of two-dimensional shapes is an important problem with many applications in anthropology. Examples of objects that anthropologists are interested in classifying, clustering and indexing based on shape include bone fragments, projectile points (arrowheads/spearpoints), petroglyphs and ceramics. Interest in matching such objects originates from the fundamental question for many biological anthropologists and archaeologists: how can we best quantify differences and similarities? This interest is fuelled in part by a movement that notes: 'an increasing number of archaeologists are showing interest in employing Darwinian evolutionary theory to explain variation in the material record'. Aiding such research efforts with computers requires a shape similarity measure that is invariant to many distortions, including scale, offset, noise, partial occlusion, etc. Most of these distortions are relatively easy to handle, either in the representation of the data or in the similarity measure used. However, rotation invariance seems to be uniquely difficult. Current approaches typically try to achieve rotation invariance in the representation of the data, at the expense of poor discrimination ability, or in the distance measure, at the expense of efficiency. In this work, we show that we can take the slow but accurate approaches and dramatically speed them up. On real world problems, our technique can take current approaches and make them four orders of magnitude faster, without false dismissals. Moreover, our technique can be used with any of the dozens of existing shape representations and with all the most popular distance measures, including Euclidean distance, dynamic time warping and longest common subsequence. We show the applications of our work to several important problems in anthropology, including clustering and indexing of skulls, projectile points and petroglyphs.

Selective attentional biases for physical threat in physical anxiety sensitivity.

Anxiety sensitivity is a trait susceptibility associated with the fear of anxiety-related sensations. One reason why such fears exist may be because those high in anxiety sensitivity selectively attend towards such sensations. However, few studies have actually investigated these cognitive biases in high anxiety sensitive individuals. The current study, therefore, sought to investigate selective attentional biases using the visual dot-probe paradigm. Since recent research suggests that at least one component of anxiety sensitivity is linked to the fear of physical sensations, individual were selected on the basis as to whether they were high or low in their anxious concern for physical sensations. In order to determine whether a general or specific attentional bias exists, the emotionality of material presented to participants was varied in terms of whether it was physically threat-related, socially threat-related, or positive. Consistent with predictions, those high in physical anxiety sensitivity were found to exhibit a selective attentional bias in favour of the location of physically threatening material. Furthermore, those low in anxiety sensitivity were found to avoid such material. Interestingly, a similar attentional bias was not found for either socially threatening or positive material. If anything, those high in physical anxiety sensitivity avoided positive material. These findings are discussed in light of current theories of anxiety sensitivity and future research.

Identification of new epitopes from four different tumor-associated antigens: recognition of naturally processed epitopes correlates with HLA-A*0201-binding affinity.

Forty-two wild-type and analogue peptides derived from p53, carcinoembryonic Ag, Her2/neu, and MAGE2/3 were screened for their capacity to induce CTLs, in vitro, capable of recognizing tumor target lines. All the peptides bound HLA-A*0201 and two or more additional A2 supertype alleles with an IC(50) of 500 nM or less. A total of 20 of 22 wild-type and 9 of 12 single amino acid substitution analogues were found to be immunogenic in primary in vitro CTL induction assays, using normal PBMCs and GM-CSF/IL-4-induced dendritic cells. These results suggest that peripheral T cell tolerance does not prevent, in this system, induction of CTL responses against tumor-associated Ag peptides, and confirm that an HLA class I affinity of 500 nM or less is associated with CTL epitope immunogenicity. CTLs generated by 13 of 20 of the wild-type epitopes, 6 of 9 of the single, and 2 of 5 of the double substitution analogues tested recognized epitopes generated by endogenous processing of tumor-associated Ags and expressed by HLA-matched cancer cell lines. Further analysis revealed that recognition of naturally processed Ag was correlated with high HLA-A2.1-binding affinity (IC(50) = 200 nM or less; p = 0.008), suggesting that high binding affinity epitopes are frequently generated and can be recognized as a result of natural Ag processing. These results have implications for the development of cancer vaccines, in particular, and for the process of epitope selection in general.

Investigating the effects of anxiety sensitivity and coping on the perception of cold pressor pain in healthy women.

Research indicates that anxiety sensitivity may be related to the negative experience of pain, especially amongst women. Further evidence with chronic pain patients indicates that anxiety sensitivity may result in avoidance pain-coping strategies. However, this effect has not yet been experimentally investigated in healthy groups. Therefore, the current study sought to investigate the effect of anxiety sensitivity and coping on women's responses to pain. Thirty women who were classified as high in anxiety sensitivity and 30 women classified as low in anxiety sensitivity participated. Within each anxiety sensitivity group, half the participants (n = 15) were randomly instructed to either focus on or avoid cold pressor pain sensations. As expected, women high in anxiety sensitivity were found to report higher levels of sensory and affective pain. Also, and consistent with previous research into anxiety sensitivity, no differences were found between anxiety sensitivity groups for measures of pain threshold or pain tolerance. The pain coping instruction manipulation was found to moderate pain experience, in that the avoidance strategy resulted in higher pain ratings compared to when instructed to focus. Finally, high anxiety sensitive women reported greater pain when instructed to avoid rather than focus on cold pressor pain. These results are discussed in light of previous research and future directions for pain management.

Selective attentional bias for pain-related stimuli amongst pain fearful individuals.

Recent research indicates that people who are fearful of pain tend to report more negative pain experiences. It also seems that attentional mechanisms may be particularly important in the perception of painful stimuli, especially amongst pain fearful individuals. Drawing on a paradigm used to examine biased cognitive processes in the emotional disorders, the current study investigated whether the fear of pain would be related to a greater selective attentional bias in favour of pain-related stimuli. In order to determine the nature of this bias, stimuli material were varied in terms of whether they were related to pain sensations, were related to socially threatening situations or were relatively positive. Those with a high fear of pain exhibited a selective attentional bias towards pain-related information, compared to those classified as low in the fear of pain. No group differences were found for either social threat or positive stimuli. These results indicate that one reason why those with a high fear of pain are particularly susceptible to negative pain experiences could be due to biased attentional processes. Suggestions for cognitive interventions designed to reduce such biases are discussed, as are directions for future research.

Hypoalgesic effect of caffeine in normotensive men and women.

Evidence from both hypertensive and normotensive individuals indicate that elevated blood pressure is associated with decreased pain sensitivity. The current study sought to experimentally raise blood pressure using 250 mg caffeine, and investigate its effects on the cold pressor pain experiences of 25 men and 25 women. In a placebo-controlled repeated-measures experiment, caffeine increased systolic and diastolic blood pressure, as well as producing more clearheaded and energetic feelings. Caffeine produced higher pain threshold and pain tolerance levels compared to placebo, and women had a lower tolerance to pain than men. Finally, a significant association was found between caffeine-related increase in systolic blood pressure and caffeine-related increase in pain tolerance. Furthermore, this association was the strongest in women. These results are discussed in light of future directions for pain and hypertension research.

Social competition in school: relationships with bullying, Machiavellianism and personality.

BACKGROUND: Bullying is investigated as part of the individual's general framework of attitudes towards interpersonal relationships, social competition and motivation in school. AIMS: It was hypothesised that bullying behaviour and pro-bullying attitudes would be associated with socially competitive attitudes in the classroom, Machiavellianism, and the personality constructs of Psychoticism and Extraversion. SAMPLES: 198 9- to 12-year-old children from two Glasgow primary schools. METHODS: Children completed several measures: a newly developed questionnaire assessing motivations behind social competition and effort in class, the Kiddie-Mach scale, the Pro-Victim scale, items from the Olweus Bullying Questionnaire, and the Junior Eysenck Personality Questionnaire. RESULTS: A 'Desire for social success' factor (incorporating a deliberate lack of effort) was negatively correlated with support for victims of bullying, even after partialling out Machiavellianism, Psychoticism, and social desirability. Pro-victim attitudes were in turn negatively correlated with Machiavellianism and Psychoticism, and positively correlated with Lie score. Finally, children categorised as bullies scored significantly higher than controls on Machiavellianism, and significantly lower in terms of pro-victim attitudes. CONCLUSIONS: Results are discussed in terms of further study and implications for classroom practice and anti-bullying policy.

Erectile dysfunction in general medicine practice: prevalence and clinical correlates.

Erectile dysfunction (ED) is a common problem in general medical practice affecting especially the elderly and those with cardiovascular disease and diabetes mellitus. A study was undertaken by questionnaire distributed to consecutive adult male attendees at 62 general medical practices. 1240 completed questionnaires were available for analysis. The mean age of participants was 56.4y (range 18-91 y). 488 men (39.4%) reported ED: 119 (9.6%) 'occasionally', 110 (8.9%) 'often', and 231 (18.6%) 'all the time' (complete ED). Among 707 men aged 40-69y 240 (33.9%) reported ED and 84 (11.9%) had complete ED. The prevalence of complete ED increased with age, rising from 2.0% in the 40-49 y age group to 44.9% in the 70-79 y age group. Only 11.6% of men with ED had received treatment. Hypertension, ischaemic heart disease, peripheral vascular disease and diabetes mellitus were frequently associated with ED. 40% of diabetic men aged 60 y or older had ED all the time.

Exploring the factor structure of the Mood and Anxiety Symptom Questionnaire (MASQ).

L. A. Clark and Watson (1991) proposed a tripartite model of anxiety and depression defined in terms of common symptoms relating to general distress, anxiety-specific symptoms of hyperarousal, and depression-specific symptoms of low positive affect and loss of interest. To aid the measurement of and discrimination between anxiety and depression they developed the Mood and Anxiety Symptom Questionnaire (MASQ). Although potentially useful, the MASQ is still in an early stage of development, and there is an indication that a discrepancy exists between items and scales. Therefore, the aim of this study was to explore the items and factors of the MASQ and determine whether a pattern similar to that suggested by L. A. Clark and Watson would emerge. Factor analysis of the MASQ revealed 3 factors relating to general distress, positive affect, and anxious arousal. Inspection of the individual items indicated that some refinements are required.

Avoidance versus focused attention and the perception of pain: differential effects for men and women.

The aim of the current investigation was to compare the effects of two different attentional strategies (focused vs. avoidance) on how males and females respond to experimentally induced pain. One hundred healthy adults were instructed to either attend towards or away from cold pressor pain. Measures of pain tolerance, pain threshold and recovery were taken, as were self-report measures of sensory and affective pain experiences. As expected, gender was found to moderate tolerance to pain: males were found to be more tolerant to cold pressor pain than females. With respect to the self-report measures, males reported less sensory pain when they attended toward the pain than when they avoided it. However, a similar effect was not found in women, suggesting that attentional focusing may only be a useful strategy for males. These results are discussed in light of previous research.

Partnerships for comprehensive school health: collaboration among colleges/universities, state-level organizations, and local school districts.

A qualitative survey on the collaborative experiences of colleges and universities, state-level organizations, and school districts related to comprehensive school health programs in 12 states found four primary collaborative outcomes: training, consultation, research, and networking. Five common dimensions of collaboration also were identified: interpersonal and organizational interactions, level of awareness and understanding of comprehensive school health programs, organizational priorities and reward systems, political forces, and availability and sharing of resources. The potential for such linkages to advance comprehensive school health programs remains largely untapped. Recommendations for developing such collaborations are presented.