The impact of positron emission tomography on primary tumour delineation and dosimetric outcome in intensity modulated radiotherapy of early T-stage nasopharyngeal carcinoma

Background: In intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC), accurate delineation of the gross tumour volume (GTV) is important. Image registration of CT and MRI has been routinely used in treatment planning. With recent development of positron emission tomography (PET), the aims of this study were to evaluate the impact of PET on GTV delineation and dosimetric outcome in IMRT of early stage NPC patients.Methods: Twenty NPC patients with T1 or T2 disease treated by IMRT were recruited. For each patient, 2 sets of NP GTVs were delineated separately, in which one set was performed using CT and MRI registration only (GTVCM), while the other set was carried out using PET, CT and MRI information (GTVCMP). A 9-field IMRT plan was computed based on the target volumes generated from CT and MRI (PTVCM). To assess the geometric difference between the GTVCM and GTVCMP, GTV volumes and DICE similarity coefficient (DSC), which measured the geometrical similarity between the two GTVs, were recorded. To evaluate the dosimetric impact, the Dmax, Dmin, Dmean and D95 of PTVs were obtained from their dose volume histograms generated by the treatment planning system.Results: The overall mean volume of GTVCMP was greater than GTVCM by 4.4 %, in which GTVCMP was slightly greater in the T1 group but lower in the T2 group. The mean DSC of the whole group was 0.79 ± 0.05. Similar mean DSC values were also obtained from the T1 and T2 groups separately. The dosimetric parameters of PTVCM fulfilled the planning requirements. When applying this plan to the PTVCMP, the average Dmin (56.9 Gy) and D95 (68.6 Gy) of PTVCMP failed to meet the dose requirements and demonstrated significant differences from the PTVCM (p = 0.001 and 0.016 respectively), whereas the doses to GTVCMP did not show significant difference with the GTVCM.Conclusion: In IMRT of early stage NPC, PET was an important imaging modality in radiotherapy planning so as to avoid underdosing the PTV, although its effect on GTV delineation was not significant. It was recommended that PET images should be included in the treatment planning of NPC patients.Department of Health Technology and Informatic

Optimum Small Optical Beam Displacement Measurement

We derive the quantum noise limit for the optical beam displacement of a TEM00 mode. Using a multimodal analysis, we show that the conventional split detection scheme for measuring beam displacement is non-optimal with 80% efficiency. We propose a new displacement measurement scheme that is optimal for small beam displacement. This scheme utilises a homodyne detection setup that has a TEM10 mode local oscillator. We show that although the quantum noise limit to displacement measurement can be surpassed using squeezed light in appropriate spatial modes for both schemes, the TEM10 homodyning scheme out-performs split detection for all values of squeezing.Comment: 13 pages, 7 figure

Between-occupation differences in work-related COVID-19 mitigation strategies over time: Analysis of the Virus Watch Cohort in England and Wales

OBJECTIVES: COVID-19 mitigations have had a profound impact on workplaces, however, multisectoral comparisons of how work-related mitigations were applied are limited. This study aimed to investigate (i) occupational differences in the usage of key work-related mitigations over time and (ii) workers' perceptions of these mitigations. METHODS: Employed/self-employed Virus Watch study participants (N=6279) responded to a mitigation-related online survey covering the periods of December 2020-February 2022. Logistic regression was used to investigate occupation- and time-related differences in the usage of work-related mitigation methods. Participants' perceptions of mitigation methods were investigated descriptively using proportions. RESULTS: Usage of work-related mitigation methods differed between occupations and over time, likely reflecting variation in job roles, workplace environments, legislation and guidance. Healthcare workers had the highest predicted probabilities for several mitigations, including reporting frequent hand hygiene [predicted probability across all survey periods 0.61 (95% CI 0.56-0.66)] and always wearing face coverings [predicted probability range 0.71 (95% CI 0.66-0.75) - 0.80 (95% CI 0.76-0.84) across survey periods]. There were significant cross-occupational trends towards reduced mitigations during periods of less stringent national restrictions. The majority of participants across occupations (55-88%) agreed that most mitigations were reasonable and worthwhile even after the relaxation of national restrictions; agreement was lower for physical distancing (39-44%). CONCLUSIONS: While usage of work-related mitigations appeared to vary alongside stringency of national restrictions, agreement that most mitigations were reasonable and worthwhile remained substantial. Further investigation into the factors underlying between-occupational differences could assist pandemic planning and prevention of workplace COVID-19 transmission

The changing contributory role to infections of work, public transport, shopping, hospitality and leisure activities throughout the SARS-CoV-2 pandemic in England and Wales

Background: Understanding how non-household activities contributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections under different levels of national health restrictions is vital. // Methods: Among adult Virus Watch participants in England and Wales, we used multivariable logistic regressions and adjusted-weighted population attributable fractions (aPAF) assessing the contribution of work, public transport, shopping, and hospitality and leisure activities to infections. // Results: Under restrictions, among 17,256 participants (502 infections), work [adjusted odds ratio (aOR) 2.01 (1.65–2.44), (aPAF) 30% (22–38%)] and transport [(aOR 1.15 (0.94–1.40), aPAF 5% (-3–12%)], were risk factors for SARS-CoV-2 but shopping, hospitality and leisure were not. Following the lifting of restrictions, among 11,413 participants (493 infections), work [(aOR 1.35 (1.11–1.64), aPAF 17% (6–26%)] and transport [(aOR 1.27 (1.04–1.57), aPAF 12% (2–22%)] contributed most, with indoor hospitality [(aOR 1.21 (0.98–1.48), aPAF 7% (-1–15%)] and leisure [(aOR 1.24 (1.02–1.51), aPAF 10% (1–18%)] increasing. During the Omicron variant, with individuals more socially engaged, among 11,964 participants (2335 infections), work [(aOR 1.28 (1.16–1.41), aPAF (11% (7–15%)] and transport [(aOR 1.16 (1.04–1.28), aPAF 6% (2–9%)] remained important but indoor hospitality [(aOR 1.43 (1.26–1.62), aPAF 20% (13–26%)] and leisure [(aOR 1.35 (1.22–1.48), aPAF 10% (7–14%)] dominated. // Conclusions: Work and public transport were important to transmissions throughout the pandemic with hospitality and leisure’s contribution increasing as restrictions were lifted, highlighting the importance of restricting leisure and hospitality alongside advising working from home, when facing a highly infectious and virulent respiratory infection

Assessing the Predictive Validity of Simple Dementia Risk Models in Harmonized Stroke Cohorts

BACKGROUND AND PURPOSE: Stroke is associated with an increased risk of dementia. To assist in the early identification of individuals at high risk of future dementia, numerous prediction models have been developed for use in the general population. However, it is not known whether such models also provide accurate predictions among stroke patients. Therefore, the aim of this study was to determine whether existing dementia risk prediction models that were developed for use in the general population can also be applied to individuals with a history of stroke to predict poststroke dementia with equivalent predictive validity. METHODS: Data were harmonized from 4 stroke studies (follow-up range, ≈12–18 months poststroke) from Hong Kong, the United States, the Netherlands, and France. Regression analysis was used to test 3 risk prediction models: the Cardiovascular Risk Factors, Aging and Dementia score, the Australian National University Alzheimer Disease Risk Index, and the Brief Dementia Screening Indicator. Model performance or discrimination accuracy was assessed using the C statistic or area under the curve. Calibration was tested using the Grønnesby and Borgan and the goodness-of-fit tests. RESULTS: The predictive accuracy of the models varied but was generally low compared with the original development cohorts, with the Australian National University Alzheimer Disease Risk Index (C-statistic, 0.66) and the Brief Dementia Screening Indicator (C-statistic, 0.61) both performing better than the Cardiovascular Risk Factors, Aging and Dementia score (area under the curve, 0.53). CONCLUSIONS: Dementia risk prediction models developed for the general population do not perform well in individuals with stroke. Their poor performance could have been due to the need for additional or different predictors related to stroke and vascular risk factors or methodological differences across studies (eg, length of follow-up, age distribution)

Macrophage coordination of the interferon lambda immune response

Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14+ monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes

Symptom profiles of community cases infected by influenza, RSV, rhinovirus, seasonal coronavirus, and SARS-CoV-2 variants of concern

Respiratory viruses that were suppressed through previous lockdowns during the COVID-19 pandemic have recently started to co-circulate with SARS-CoV-2. Understanding the clinical characteristics and symptomatology of different respiratory viral infections can help address the challenges related to the identification of cases and the understanding of SARS-CoV-2 variants' evolutionary patterns. Flu Watch (2006-2011) and Virus Watch (2020-2022) are household community cohort studies monitoring the epidemiology of influenza, respiratory syncytial virus, rhinovirus, seasonal coronavirus, and SARS-CoV-2, in England and Wales. This study describes and compares the proportion of symptoms reported during illnesses infected by common respiratory viruses. The SARS-CoV-2 symptom profile increasingly resembles that of other respiratory viruses as new strains emerge. Increased cough, sore throat, runny nose, and sneezing are associated with the emergence of the Omicron strains. As SARS-CoV-2 becomes endemic, monitoring the evolution of its symptomatology associated with new variants will be critical for clinical surveillance

Surveillance of emerging drugs of abuse in Hong Kong: Validation of an analytical tool

© 2015, Hong Kong Academy of Medicine Press. All rights reserved. Objective: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Design: Cross-sectional study. Setting: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. Participants: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Main outcome measures: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. Results: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. Conclusions: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.Link_to_subscribed_fulltex