Language production in Parkinson’s disease : an investigation into the characteristics and underlying cognitive and linguistic mechanisms

Research into language alteration in Parkinson’s Disease (PD) remains relatively limited. Findings to date indicate that both a specific verb processing deficit and altered sentence construction can present as part of the symptom profile. However, questions regarding the underlying nature of the verb processing deficit observed remain and, as far as can be established, no studies have explicitly explored whether the altered verb processing evidenced may be underpinning the observed alteration in measures of sentence construction. This thesis reports on the findings from four component studies, each addressing an identified gap within the current literature relating to verb and sentence processing. Of interest within the first two experimental research questions was the influence of the verbs semantic and grammatical characteristics on retrieval within both a single word and sentence context, and on various measures of sentence construction. In the main, the pattern of performance did not vary between individuals with PD and controls. Average pause length was found to be longer in sentences produced by individuals with PD, however, was not influenced by the verb’s characteristics. The third experimental question was concerned with investigating sentence production within tasks which varied in their nature and linguistic demands. Again, performance was largely comparable between groups, with the exception of average pause length. Whilst pauses were found to be longer in PD, this was not influenced by the demands of the task. Finally, exploratory correlational analyses were conducted to explore the relationship between the linguistic measures taken, and measures of various cognitive abilities. Patterns of association varied between the groups, indicating a complex relationship between language and cognitive measures. The majority of findings went against the predictions made. Collectively, findings indicate that, when verb processing is unimpaired in PD and cognitive functioning of a comparative level to controls, sentence construction is largely unimpaired.Research into language alteration in Parkinson’s Disease (PD) remains relatively limited. Findings to date indicate that both a specific verb processing deficit and altered sentence construction can present as part of the symptom profile. However, questions regarding the underlying nature of the verb processing deficit observed remain and, as far as can be established, no studies have explicitly explored whether the altered verb processing evidenced may be underpinning the observed alteration in measures of sentence construction. This thesis reports on the findings from four component studies, each addressing an identified gap within the current literature relating to verb and sentence processing. Of interest within the first two experimental research questions was the influence of the verbs semantic and grammatical characteristics on retrieval within both a single word and sentence context, and on various measures of sentence construction. In the main, the pattern of performance did not vary between individuals with PD and controls. Average pause length was found to be longer in sentences produced by individuals with PD, however, was not influenced by the verb’s characteristics. The third experimental question was concerned with investigating sentence production within tasks which varied in their nature and linguistic demands. Again, performance was largely comparable between groups, with the exception of average pause length. Whilst pauses were found to be longer in PD, this was not influenced by the demands of the task. Finally, exploratory correlational analyses were conducted to explore the relationship between the linguistic measures taken, and measures of various cognitive abilities. Patterns of association varied between the groups, indicating a complex relationship between language and cognitive measures. The majority of findings went against the predictions made. Collectively, findings indicate that, when verb processing is unimpaired in PD and cognitive functioning of a comparative level to controls, sentence construction is largely unimpaired

Tracking the Martian CO2 Polar Ice Caps in Infrared Images

Researchers at NASA s Jet Propulsion Laboratory have developed a method for automatically tracking the polar caps on Mars as they advance and recede each year (see figure). The seasonal Mars polar caps are composed mainly of CO2 ice and are therefore cold enough to stand out clearly in infrared data collected by the Thermal Emission Imaging System (THEMIS) onboard the Mars Odyssey spacecraft. The Bimodal Image Temperature (BIT) histogram analysis algorithm analyzes raw, uncalibrated data to identify images that contain both "cold" ("polar cap") and "warm" ("not polar cap") pixels. The algorithm dynamically identifies the temperature that separates these two regions. This flexibility is critical, because in the absence of any calibration, the threshold temperature can vary significantly from image to image. Using the identified threshold, the algorithm classifies each pixel in the image as "polar cap" or "not polar cap," then identifies the image row that contains the spatial transition from "polar cap" to "not polar cap." While this method is useful for analyzing data that has already been returned by THEMIS, it has even more significance with respect to data that has not yet been collected. Instead of seeking the polar cap only in specific, targeted images, the simplicity and efficiency of this method makes it feasible for direct, onboard use. That is, THEMIS could continuously monitor its observations for any detections of the polar-cap edge, producing detections over a wide range of spatial and temporal conditions. This effort can greatly contribute to our understanding of long-term climatic change on Mars

Towards Onboard Orbital Tracking of Seasonal Polar Volatiles on Mars

Current conditions on Mars support both a residual polar cap, composed mainly of water ice, and a seasonal cap, composed of CO2, which appears and disappears each winter. Kieffer and Titus characterized the recession of the seasonal south polar cap using an arctangent curve fit based on data from the Thermal Emission Spectrometer on Mars Global Surveyor [1]. They also found significant interannual deviations, at the regional scale, in the recession rate [2]. Further observations will enable the refinement of our models of polar cap evolution in both hemispheres. We have developed the Bimodal Image Temperature (BIT) Histogram Analysis method for the automated detection and tracking of the seasonal polar ice caps on Mars. It is specifically tailored for possible use onboard a spacecraft. We have evaluated BIT on uncalibrated data collected by the Thermal Emission Imaging System (THEMIS) instrument [3] on the Mars Odyssey spacecraft. In this paper, we focus on the northern seasonal cap, but our approach is directly applicable to the future analysis of the southern seasonal ice cap as well

The CATFISH study protocol: an evaluation of a water fluoridation scheme

Abstract Background Tooth decay is the commonest disease of childhood. We have known for over 90 years that fluoride can prevent tooth decay; it is present in nearly all toothpastes and can be provided in mouthwashes, gels and varnishes. The oldest method of applying fluoride is via the water supply at a concentration of 1 part per million. The two most important reviews of water fluoridation in the United Kingdom (the York Review and MRC Report on water fluoridation and health) concluded that whilst there was evidence to suggest water fluoridation provided a benefit in caries reduction, there was a need to improve the evidence base in several areas. Methods/Design This study will use a natural experiment to assess the incidence of caries in two geographical areas, one in which the water supply is returned to being fluoridated following a discontinuation of fluoridation and one that continues to have a non-fluoridated water supply. The oral health of two discrete study populations will be evaluated - those born 9 months after the water fluoridation was introduced, and those who were in their 1st year of school after the introduction of fluoridated water. Both populations will be followed prospectively for 5 years using a census approach in the exposed group along with matched numbers recruitment in a non-exposed control. Parents of the younger cohort will complete questionnaires every 6 months with child clinical examination at ages 3 and 5, whilst the older cohort will have clinical examinations only, at approximately 5, 7 and 11 years old. Discussion This project provides a unique opportunity to conduct a high quality evaluation of the reintroduction of a water fluoridation scheme, which satisfies the inclusion criteria stipulated by the York systematic review and can address the design issues identified in the MRC report. The research will make a major contribution to the understanding of the costs and effects of water fluoridation in the UK in the 21st Century. Its findings will help inform UK policy on this important public health intervention and may have a significant impact on public health policy in other developed countries. There is currently true equipoise in relation to the effectiveness of water fluoridation in contemporary populations and while the biological plausibility is well established, there is a need to examine impact on the changing epidemiological status of dental decay

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose