The mismatch negativity (MMN) component of the auditory event-related potential has been used in the past to study between group differences in the accuracy and retention of information in auditory ...sensory memory (ASM). The MMN is elicited by infrequent ‘deviant’ tones that differ from a repeating ‘standard’ tone. In the present study, the type of deviant and the time interval between tones (stimulus-onset asynchrony: SOA) were manipulated in a study of normal aging. MMN responses of an elderly (mean age
=
69) and a young group (mean age
=
21) to both a duration and a frequency deviant tone were measured at a short (450
ms) and long (3
s) SOA. A smaller and later MMN (recorded at Fz) was observed in the elderly relative to the young group across SOA and Deviant conditions. The results are consistent with an age-related deficit in the encoding of sound properties in ASM. However, analysis of the MMN reversal at the mastoids provides some support for the proposal that the elderly have an additional deficit related to the retention of information in ASM.
Chronic obstructive pulmonary disease (COPD) is a common, costly, and incurable respiratory disease affecting 1.2 million people in the United Kingdom alone. Acute COPD exacerbations requiring ...hospitalization place significant demands on health services, and the incidence of COPD in poor, remote, and rural populations is up to twice that of cities.
myCOPD is a commercial, digital health, self-management technology designed to improve COPD outcomes and mitigate demands on health services. In this pragmatic real-world feasibility study, we aimed to evaluate myCOPD use and its clinical effectiveness at reducing hospitalizations, inpatient bed days, and other National Health Service (NHS) resource use.
myCOPD engagement and NHS resource use was monitored for up to 1 year after myCOPD activation and was compared against health service use in the year prior to activation. A total of 113 participants from predominantly remote and rural communities were recruited via community-based care settings, including scheduled home visits, outpatient appointments, pulmonary rehabilitation, and phone or group appointments. There were no predetermined age, disease severity, geographical, or socioeconomic inclusion or exclusion criteria.
Out of 113 participants, 89 activated myCOPD (78.8%), with 56% (50/89) of those participants doing so on the day of enrollment and 90% (80/89) doing so within 1 month. There was no correlation between participant enrollment, activation, or myCOPD engagement and either age, socioeconomics, rurality, or COPD severity. Most active participants used at least one myCOPD module and entered their symptom scores at least once (79/89, 89%). A subgroup (15/89, 17%) recorded their symptom scores very frequently (>1 time every 5 days), 14 of whom (93%) also used four or five myCOPD modules. Overall, there were no differences in hospital admissions, inpatient bed days, or other health service use before or after myCOPD activation, apart from a modest increase in home visits. Subgroup analysis did, however, identify a trend toward reduced inpatient bed days and hospital admissions for those participants with very high myCOPD usage.
Our results suggest that neither age, wealth, nor geographical location represent significant barriers to using myCOPD. This finding may help mitigate perceived risks of increased health inequalities associated with the use of digital health technologies as part of routine care provision. Despite high levels of activation, myCOPD did not reduce overall demands on health services, such as hospital admissions or inpatient bed days. Subgroup analysis did, however, suggest that very high myCOPD usage was associated with a moderate reduction in NHS resource use. Thus, although our study does not support implementation of myCOPD to reduce health service demands on a population-wide basis, our results do indicate that highly engaged patients may derive benefits.
Aim
The aim of this study was to translate the Dutch patient‐reported outcome measure‐haemorrhoidal impact and satisfaction score (PROM‐HISS) to English and perform a cross‐cultural validation.
...Method
The ISPOR good practice guidelines for the cross‐cultural validation of PROMs were followed and included two steps: (1) Two forward and two backward translations. The forward translation concerned the translation from the source language (Dutch) to the target language (English), performed by two independent English speakers, one medical doctor and one nonmedical. Subsequently, a discussion about discrepancies in the reconciled version was performed by a stakeholder group. (2) Cognitive interviews were held with patients with haemorrhoidal disease (HD), probing the comprehensibility and comprehensiveness of the PROM‐HISS.
Results
Discrepancies in the reconciled forward translation concerned the terminology of HD symptoms. Furthermore, special attention was paid to the response options, ranging from “not at all”, indicating minor symptoms, to “a lot”, implying many symptoms. Consensus among the stakeholder group about the final version of the translated PROM‐HISS was reached. Interviews were conducted with 10 native English‐speaking HD patients (30% female), with a mean age of 44 years (24–83) and primarily diagnosed with grade II HD (80%). The mean time to complete the PROM‐HISS was 1 min 43 s. Patients showed a good understanding of the questions and response options, found all items relevant and did not miss important symptoms or topics.
Conclusion
The translated English language PROM‐HISS is a valid tool to assess symptoms of HD, its impact on daily activities and patient satisfaction with HD treatment.
Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with ...inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy‐seven long covid patients and 50 frequency‐matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty‐one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.
Two auditory event-related potential (ERP) waveforms, mismatch negativity (MMN) and repetition positivity (RP), are sensitive to repetition of auditory stimuli. Increasing repetition of standards ...produces larger MMN amplitudes to deviant stimuli in an oddball paradigm, known as the memory trace effect, and attributed to increasing strength of the memory trace for standards. RP to standards also increases as a function of repetition in a ‘roving’ oddball paradigm where the standard changes in pitch following presentation of a deviant tone. As the sensory memory trace representing standard stimuli must be continually updated in the roving paradigm, RP has been proposed to reflect memory trace formation. Given that RP to date has only been observed in roving oddball paradigms, we examined whether RP and the MMN memory trace effect are present in both roving and standard oddball paradigms in 24 young adults (mean age: 22.4±5years). Four, 8, or 16 standards preceded a deviant. We observed RP at Fz in standard ERPs in the roving but not constant paradigm. At mastoid sites, RP was observed in both paradigms. A memory trace effect was not observed at Fz in either paradigm. Our findings suggest that different generator sites in the brain model local and global auditory information with generators of mastoid activity primarily sensitive to local or short term stimulus history of auditory regularities while generators of frontal site activity retain more global information regarding stimulus history over a longer time period.
► RP wave seen during roving oddball paradigm at Fz ► Inverted RP wave seen at mastoids in both constant and roving oddball paradigms ► RP at frontal and mastoid sites is differentially sensitive to paradigm. ► Modelling of auditory environment consistent with a predictive coding framework
Research Doctorate - Doctor of Philosophy
It is well established that there are changes in cognition and in peripheral sensory mechanisms that occur with age. However, there is much less known about ...the cause of either change or indeed the relationship between age-related change in sensory processing and age-associated cognitive decline. Understanding these mechanisms could improve our capacity to devise strategies which could assist older adults in aging successfully. In this thesis, I aim to bridge a gap in our knowledge concerning the relationship between age-related change in sensory processing and age-associated cognitive decline by studying the effect of age on what can be considered an intermediary process, sensory memory (in the auditory modality). I continue this line of research by examining the relationship between auditory sensory memory and other types of memory for auditory information in young and older adults. To address these goals, I adopted a cognitive neuroscience approach, relating electrophysiological data to data derived from behavioural memory assessments. In the following thesis, I present a literature review, four studies, and a general discussion of results. Several waveforms of the auditory event-related potential (ERP), including N1, P2, repetition positivity (RP), and mismatch negativity (MMN) were studied. More specifically, in study 1, we looked at the effect of age on N1 and P2 amplitude. In study 2, we examined the conditions eliciting two repetition effects, RP and the MMN memory trace effect, in the auditory ERP of young adults. Studies 3 and 4 concerned the effect of age on RP and the relationship between RP and implicit memory for contextual information as well as explicit memory for auditory information. We concluded that i) age affects auditory sensory memory, ii) the potential relationship between auditory sensory memory and implicit memory for auditory information requires re-investigation, and iii) there is a relationship between auditory sensory memory and explicit memory for auditory information that is altered with age. That is, we concluded that RP occurring in the N1/P2 and MMN latency period indicates memory trace formation and that age affects RP amplitude (restricted to an anterior RP generator). In addition, we showed that RP may be related to implicit memory (priming) in both young and older adults. Across two studies, we found a positive correlation between the response to repetition in the ERP (due to RP activity) and explicit auditory verbal memory in young adults but a negative correlation in older adults. Therefore, although age-related change in RP could reflect the capacity of older adults to encode the context of auditory stimulation, this is potentially due to compensatory activity. We argue it is possible that implicit memory changes with age as a result of age-related change in explicit episodic memory. As a result of well established changes that occur in episodic memory with age, older adults may begin to rely on implicit memory as a source of memory more so than young adults. Our data shows that the implicit memory system may, as a result, favour content over contextual information. An important theme outlined in the discussion of results involves the idea that age-related changes in cognition that are commonly interpreted as cognitive deficits may in fact be beneficial in certain circumstances. We review our results in relation to cognitive theories of aging and find that several theories are applicable to the data, including the frontal hypothesis (incorporating the inhibitory deficit hypothesis), the information degradation hypothesis, and the speed of processing hypothesis. Future research in this area could focus on exploring whether top-down or bottom-up or influences primarily contribute to the age effect on auditory sensory memory and RP, as well as evaluating our hypothesis that the age-related change in RP may be beneficial for explicit item memory but detrimental for implicit contextual memory in older adults (i.e. compensatory mechanisms). While the studies presented in this thesis have provided the foundations guiding our understanding of these issues, researchers in the field of cognitive neuroscience are well equipped to resolve such questions in the future.
This study comprises two parts, one based at the Wash and one at Teesside, dye-marking of samples of oystercatcher, grey plover, knot, sanderling, dunlin, bar-tailed godwit, curlew, redshank and ...turnstone was undertaken to determine differences in the degree of mobility within the Wash. Most information relates to spring tide roosts. Wash Wader Ringing Group recaptures within the Wash, within a single season, were examined for sanderlings and dunlin. There were few results for grey plover, bar-tailed godwit, curlew or redshank. Results for other species indicate a range of mobility - in order of increasing mobility these are dunlin and turnstone, sanderling, oystercatcher, knot. Under lying reasons for mobility were associated with flights to spring tide roosts, increases in diurnal time spent feeding and, possibly, exploratory flights in search of unpredictable food resources. At Teesside, individually colour-ringed sanderlings were studied for differences in timing of use of Teesside and differences in degree of mobility. Generally, individuals display consistency in returning to Teesside each year and arrival and departure dates are similar from year to year for each individual. A continuum of sanderling mobility is apparent. There appears to be a balance between net advantages and disadvantages accruing from variations in mobility as estimates of survival rates indicate'. Heightened mobility was apparent by some individuals during severe winters and was interpreted as movement in search of better foraging conditions.
Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide ...care.
We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure.
The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P=0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P=0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001).
In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.).
Following the discovery of synergistic action between oxacillin and manuka honey against methicillin-resistant Staphylococcus aureus, this study was undertaken to search for further synergistic ...combinations of antibiotics and honey that might have potential in treating wounds. Fifteen antibiotics were tested with and without sublethal concentrations of manuka honey against each of MRSA and Pseudomonas aeruginosa using disc diffusion, broth dilution, E strip, chequerboard titration and growth curves. Five novel antibiotic and manuka honey combinations were found that improved antibacterial effectiveness in vitro and these offer a new avenue of future topical treatments for wound infections caused by these two important pathogens.
During the early stages of the UK 2021-2022 H5N1 high-pathogenicity avian influenza virus (HPAIV) epizootic in commercial poultry, 12 infected premises (IPs) were confirmed by four real-time ...reverse-transcription-polymerase chain reaction (RRT)-PCRs, which identified the viral subtype and pathotype. An assessment was undertaken to evaluate whether a large sample throughput would challenge laboratory capacity during an exceptionally large epizootic; hence, assay performance across our test portfolio was investigated. Statistical analysis of RRT-PCR swab testing supported it to be focused on a three-test approach, featuring the matrix (M)-gene, H5 HPAIV-specific (H5-HP) and N1 RRT-PCRs, which was successfully assessed at 29 subsequent commercial IPs. The absence of nucleotide mismatches in the primer/probe binding regions for the M-gene and limited mismatches for the H5-HP RRT-PCR underlined their high sensitivity. Although less sensitive, the N1 RRT-PCR remained effective at flock level. The analyses also guided successful surveillance testing of apparently healthy commercial ducks from at-risk premises, with pools of five oropharyngeal swabs tested by the H5-HP RRT-PCR to exclude evidence of infection. Serological testing at anseriform H5N1 HPAIV outbreaks, together with quantitative comparisons of oropharyngeal and cloacal shedding, provided epidemiological information concerning the chronology of initial H5N1 HPAIV incursion and onward spread within an IP.
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