Search

Abstract The presence of a weekly cycle in the abundance of an atmospheric constituent is a typical fingerprint for the anthropogenic nature of its emission sources. However, while ammonia is mainly emitted as a consequence of human activities, a weekly cycle has never been detected in its abundances at large scale. We expose here for the first time the presence of a weekend effect in the NH3 total columns measured by the IASI satellite sounder over the main agricultural source regions in Europe: northwestern Europe (Belgium-the Netherlands-northwest Germany), the Po Valley, Brittany, and, to a lesser extent, the Ebro Valley. A decrease of 15% relative to the weekly mean is seen on Sunday–Monday observations in northwestern Europe, as a result of reduced NH3 emissions over the weekend. This is confirmed by in situ NH3 concentration data from the National Air Quality Monitoring Network in the Netherlands, where an average reduction of 10% is found around midnight on Sunday. The identified weekend effect presents a strong seasonal variability, with two peaks, one in spring and one in summer, coinciding with the two main (manure) fertilization periods. In spring, a reduction on Sunday–Monday up to 53 and 26% is found in the NH3 satellite columns and in situ concentrations, respectively, as fertilization largely drives atmospheric NH3 abundances at this time of the year.

Abstract Ascaridoids are one of the main parasitic hazards in commercial fish. Candling is the current industrial screening method whereby visible ascaridoid larvae are detected on a light table and manually removed. The aim of this study was to assess the sensitivity (Se) and negative predictive value (NPV) of this method. To make targeted recommendations to the fish industry, the Se was calculated per fish part, larval genus, and fish species. All fish parts (n = 615) were first candled, and larvae were collected, followed by enzymatic digestion to recover the remaining larvae. A fish part was considered positive if at least one larva was detected using candling and/or enzymatic digestion, with both methods combined as reference standard. The overall Se of candling was 31% (95% CI 23–41%) and NPV was 87% (95% CI 85–90%). The Se increased with higher numbers of larvae/100 g infected muscle. A low NPV was found for the belly flaps, therefore we either advise the removal or proper freezing of this part. Lastly, the Se and larval recovery was the highest for the darker and larger Pseudoterranova spp. larvae. Due to the low overall efficacy of candling, further assessment of its cost–benefit and impact on consumers’ health risk should be conducted.

Abstract There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.

Abstract Background Charcot–Marie–Tooth disease type 1A (CMT1A) is a rare, orphan, hereditary neuromuscular disorder with no cure and for which only symptomatic treatment is currently available. A previous phase 2 trial has shown preliminary evidence of efficacy for PXT3003 in treating CMT1A. This phase 3, international, randomized, double-blind, placebo-controlled study further investigated the efficacy and safety of high- or low-dose PXT3003 (baclofen/naltrexone/D-sorbitol [mg]: 6/0.70/210 or 3/0.35/105) in treating subjects with mild to moderate CMT1A. Methods In this study, 323 subjects with mild-to-moderate CMT1A were randomly assigned in a 1:1:1 ratio to receive 5 mL of high- or low-dose PXT3003, or placebo, orally twice daily for up to 15 months. Efficacy was assessed using the change in Overall Neuropathy Limitations Scale total score from baseline to months 12 and 15 (primary endpoint). Secondary endpoints included the 10-m walk test and other assessments. The high-dose group was discontinued early due to unexpected crystal formation in the high-dose formulation, which resulted in an unanticipated high discontinuation rate, overall and especially in the high-dose group. The statistical analysis plan was adapted to account for the large amount of missing data before database lock, and a modified full analysis set was used in the main analyses. Two sensitivity analyses were performed to check the interpretation based on the use of the modified full analysis set. Results High-dose PXT3003 demonstrated significant improvement in the Overall Neuropathy Limitations Scale total score vs placebo (mean difference: − 0.37 points; 97.5% CI [− 0.68 to − 0.06]; p = 0.008), and consistent treatment effects were shown in the sensitivity analyses. Both PXT3003 doses were safe and well-tolerated. Conclusion The high-dose group demonstrated a statistically significant improvement in the primary endpoint and a good safety profile. Overall, high-dose PXT3003 is a promising treatment option for patients with Charcot–Marie–Tooth disease type 1A.

Abstract The vast majority of adult cancer cells achieve cellular immortality by activating a telomere maintenance mechanism (TMM). While this is mostly achieved by the de-silencing of hTERT telomerase gene expression, an alternative homologous recombination-based and telomerase-independent mechanism, known as ALT (Alternative Lengthening of Telomeres), is frequently activated in a subset of tumors, including paediatric cancers. Being absent from normal cells, the ALT mechanism offers interesting perspectives for new targeted cancer therapies. To date, however, the development of better translationally applicable tools for ALT detection in tumor sections is still needed. Here, using a newly derived ALT-positive cancer cell mouse xenograft model, we extensively examined how the previously known ALT markers could be used as reliable tools for ALT diagnosis in tumor sections. We found that, together with the detection of ultra-bright telomeric signals (UBS), an ALT hallmark, native telomeric FISH, that detects single-stranded C-rich telomeric DNA, provides a very sensitive and robust tool for ALT diagnosis in tissues. We applied these assays to paediatric tumor samples and readily identified three ALT-positive tumors for which the TMM was confirmed by the gold-standard C-circle amplification assay. Although the latter offers a robust assay for ALT detection in the context of research laboratories, it is more difficult to set up in histopathological laboratories and could therefore be conveniently replaced by the combination of UBS detection and native telomeric FISH.

Abstract Several plant lectins, or carbohydrate-binding proteins, interact with glycan moieties on the surface of immune cells, thereby influencing the immune response of these cells. Orysata, a mannose-binding lectin from rice, has been reported to exert immunomodulatory activities on insect cells. While the natural lectin is non-glycosylated, recombinant Orysata produced in the yeast Pichia pastoris (YOry) is modified with a hyper-mannosylated N-glycan. Since it is unclear whether this glycosylation can affect the YOry activity, non-glycosylated rOrysata was produced in Escherichia coli (BOry). In a comparative analysis, both recombinant Orysata proteins were tested for their carbohydrate specificity on a glycan array, followed by the investigation of the carbohydrate-dependent agglutination of red blood cells (RBCs) and the carbohydrate-independent immune responses in Drosophila melanogaster S2 cells. Although YOry and BOry showed a similar carbohydrate-binding profiles, lower concentration of BOry were sufficient for the agglutination of RBCs and BOry induced stronger immune responses in S2 cells. The data are discussed in relation to different hypotheses explaining the weaker responses of glycosylated YOry. In conclusion, these observations contribute to the understanding how post-translational modification can affect protein function, and provide guidance in the selection of the proper expression system for the recombinant production of lectins.

Objectives To estimate the prevalence, incidence and longevity of antibodies against SARS-CoV-2 among primary healthcare providers (PHCPs).Design Prospective cohort study with 12 months of follow-up.Setting Primary care in Belgium.Participants Any general practitioner (GP) working in primary care in Belgium and any other PHCP from the same GP practice who physically manages (examines, tests, treats) patients were eligible. A convenience sample of 3648 eligible PHCPs from 2001 GP practices registered for this study (3044 and 604 to start in December 2020 and January 2021, respectively). 3390 PHCPs (92,9%) participated in their first testing time point (2820 and 565, respectively) and 2557 PHCPs (70,1%) in the last testing time point (December 2021).Interventions Participants were asked to perform a rapid serological test targeting IgM and IgG against the receptor binding domain of SARS-CoV-2 and to complete an online questionnaire at each of maximum eight testing time points.Primary and secondary outcome measures The prevalence, incidence and longevity of antibodies against SARS-CoV-2 both after natural infection and after vaccination.Results Among all participants, 67% were women and 77% GPs. Median age was 43 years. The seroprevalence in December 2020 (before vaccination availability) was 15.1% (95% CI 13.5% to 16.6%), increased to 84.2% (95% CI 82.9% to 85.5%) in March 2021 (after vaccination availability) and reached 93.9% (95% CI 92.9% to 94.9%) in December 2021 (during booster vaccination availability and fourth (delta variant dominant) COVID-19 wave). Among not (yet) vaccinated participants the first monthly incidence of antibodies against SARS-CoV-2 was estimated to be 2.91% (95% CI 1.80% to 4.01%). The longevity of antibodies is higher in PHCPs with self-reported COVID-19 infection.Conclusions This study confirms that occupational health measures provided sufficient protection when managing patients. High uptake of vaccination resulted in high seroprevalence of SARS-CoV-2 antibodies in PHCPs in Belgium. Longevity of antibodies was supported by booster vaccination and virus circulation.Trial registration number NCT04779424.

Abstract For more than a decade human papillomavirus (HPV) vaccine have been implemented in most high-income countries, and more recently also in several low- and middle-income countries. The vaccines are safe and their impact and effectiveness in preventing HPV vaccine type infection and associated diseases has been thoroughly established. Currently, the primary recommended cohorts for immunisation are adolescents, 9–15 years of age but HPV is an ubiquitous infection that is mainly (but not exclusively) sexually transmitted. Sexually active adults remain susceptible to infection and continued transmission of the virus, representing a reservoir of infection in the population. A recent meeting, conducted by the HPV Prevention and Control Board (HPV-PCB), reviewed the current status of HPV vaccination of adults, discussed limitations, challenges and benefits of HPV vaccination of adults, evaluated the effectiveness of HPV vaccination after treatment of post cervical cancer and precancerous lesions, and discussed the potential impact of adult vaccination on cervical cancer elimination strategies in light of the current and future HPV vaccine shortage. HPV-PCB is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV prevention and control programs. The HPV-PCB concluded that, given the current data available on adult HPV vaccination and the ongoing vaccine supply constraints, it is too early to implement routine vaccination of adults. Many research gaps need to be filled before we have a better understanding of the efficacy and broader public health impact of HPV vaccination in adult women.

Abstract Background Quality human resources constitute an essential pillar of an effective health system. This paper analyzes the outcomes of blended learning for post-Ebola capacity strengthening of health professionals in Guinea. Methods Two courses lasting 3 months each (7–8 modules) were developed and implemented: one in Primary Health Care (eSSP) and the other in Sexual and Reproductive Health Services Management (eSSR). Both eSSP and eSSR courses were offered online on the Moodle platform, followed by a face-to-face capacity-building workshop. A cross-sectional study using a mixed-methods approach was conducted in 2018–19. As outcomes, we described learners’ sociodemographic characteristics, course completion and success, and perceptions of the courses and support from the instructors, analyzed the factors associated with learners’ successful completion and reported on learners’ feedback on their blended learning experience. Quantitative data were analyzed using the STATA 15 software, and qualitative data were analyzed through content analysis. Results Overall, 282 health professionals were enrolled for both eSSP and eSSR courses. The completion rate was 69.5% (196/282). The success rate for learners who completed the courses was 80% (156/196), and the overall success rate for enrollees was 55% (156/282). The dropout and abstention rates were 22 and 9%, respectively. On both eSSP and eSSR courses, the success rate of women enrolled was higher than or equal to men’s. The success rate of medical doctors enrolled (53% for eSSP and 67% for eSSR) was higher than for other health professionals, in particular nurses (9% for eSSP) and midwives (40% for eSSR). Course type was associated with success (AOR = 1.93; 95% CI = 1.15–3.24). Most learners strongly agreed that the courses are relevant for targeted health professionals (81 to 150/150), pdf course materials are well-structured and useful (105/150), the content of the modules is relevant, comprehensible, and clear (90/150), self-assessment quizzes are helpful (105/150), summative assessment assignments are relevant (90/150), the course administrators and IT manager were responsive to learners’ concerns (90/150), they will recommend the courses to colleagues and friends (120/150). Conclusion Two blended courses for capacity strengthening of health professionals were successfully developed and implemented in Guinea.

BackgroundThree blended courses on Primary Health Care (eSSP), Management of Sexual and Reproductive Health Services (eSSR), and Research Methods (eMR) were developed and implemented between 2017 and 2021 by the Maferinyah National Training and Research Center in Rural Health, a training and research institution of the Ministry of Health in Guinea. The study objectives were to evaluate the reasons for dropout and abstention, the learners' work behavior following the training, and the impact of the behavior change on the achievements of learners' organizations or services.MethodsWe evaluated the three implemented courses in 2021, focusing on levels 3 and 4 of the Kirkpatrick training evaluation model. Quantitative and qualitative data were collected through an open learning platform (Moodle), via an electronic questionnaire, during the face-to-face component of the courses (workshops), and at learners' workplaces. Descriptive statistics and thematic analysis were performed for quantitative and qualitative data, respectively.ResultsOut of 1,016 applicants, 543 including 137 (25%) women were enrolled in the three courses. Over the three courses, the completion rates were similar (67–69%) along with 20–29% dropout rates. Successful completion rates were 72% for eSSP, 83% for eMR and 85% for eSSR. Overall success rate (among all enrollees) ranged from 50% (eSSP) to 58% (eSSR). The majority (87%) of the learners reported applying the knowledge and skills they acquired during the courses through activities such as supervision (22%), service delivery (20%), and training workshops (14%). A positive impact of the training on utilization/coverage of services and increased revenues for their health facilities were also reported by some trainees.ConclusionThese findings showed fair success rates and a positive impact of the training on learners' work behavior and the achievements of their organizations.

Abstract Host cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59–0.92) and 0.76 (95% CI 0.58–0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

Abstract Anisakidae, marine nematodes, are underrecognized fish-borne zoonotic parasites. Studies on factors that could trigger parasites to actively migrate out of the fish are very limited. The objective of this study was to assess the impact of different environmental conditions (temperature, CO2 and O2) on larval motility (in situ movement) and mobility (migration) in vitro. Larvae were collected by candling or enzymatic digestion from infected fish, identified morphologically and confirmed molecularly. Individual larvae were transferred to a semi-solid Phosphate Buffered Saline agar, and subjected to different temperatures (6 ℃, 12 ℃, 22 ℃, 37 ℃) at air conditions. Moreover, different combinations of CO2 and O2 with N2 as filler were tested, at both 6 °C and 12 °C. Video recordings of larvae were translated into scores for larval motility and mobility. Results showed that temperature had significant influence on larval movements, with the highest motility and mobility observed at 22 ℃ for Anisakis spp. larvae and 37 ℃ for Pseudoterranova spp. larvae. During the first 10 min, the median migration of Anisakis spp. larvae was 10 cm at 22 ℃, and the median migration of Pseudoterranova spp. larvae was 3 cm at 37 ℃. Larval mobility was not significantly different under the different CO2 or O2 conditions at 6 °C and 12 ℃. It was concluded that temperature significantly facilitated larval movement with the optimum temperature being different for Anisakis spp. and Pseudoterranova spp., while CO2 and O2 did not on the short term. This should be further validated in parasite-infected/spiked fish fillets.

Objective The tendency to flexibly adjust goals that are hindered by chronic illness is related to indicators of wellbeing. However, cognitive flexibility is often impaired in persons with an acquired brain injury (ABI), possibly affecting the ability to flexibly adjust goals. In this study we examined whether cognitive flexibility is positively related with the ability to disengage from goals to reengage with goals in persons with ABI. Second, we explored whether goal adjustment abilities are predictive of a unique proportion of the variance inabilities are predictive of quality of life and life satisfaction after controlling for personality traits. Method Seventy-eight persons with an ABI completed a set of questionnaires. Goal disengagement and goal reengagement were assessed using the Wrosch Goal Adjustment Scale (GAS). Indicators of wellbeing were measured with the European Brain Injury Questionnaire (EBIQ) and the Satisfaction with Life Scale (SWLS). The percentage of perseverative errors on the Wisconsin Card Sorting Test (WCST) was used as an indicator of cognitive inflexibility. Big Five personality traits were assessed via the NEO Five Factor Inventory (NEO-FFI). Four hierarchical multiple regression analyses were then conducted. The first two analyses tested the effect of cognitive flexibility on goal adjustment tendencies. The second two analyses tested whether goal adjustment has a predictive value for life satisfaction and QOL beyond personality. Results Cognitive flexibility was positively related to goal reengagement, but not to goal disengagement. Goal reengagement was positively associated with both quality of life and life satisfaction after controlling for demographic, illness characteristics and personality factors. Goal disengagement was negatively related to life satisfaction. Conclusion Flexible goal adjustment abilities have a unique explanatory value for indicators of wellbeing, beyond personality traits. The findings indicate that in persons with lower cognitive flexibility, goal reengagement ability might be negatively affected, and should be taking into account during rehabilitation.

Abstract Objective We conducted a descriptive cross-sectional study using survey and programme data to assess district-level performance along the HIV care cascade (HIV testing target achievement, linkage to ART and ART coverage) in order to formulate district-specific recommendations, taking into consideration prevalence and yield of testing. Results Data from 60 districts were analysed. Forty-eight districts (80.0%) surpassed 90% of their 2018 HIV testing targets. Linkage to ART was less than 90% in 40 districts (83.3%). Thirty districts (50.0%) had ART coverage above 90%. Of the 30 districts with suboptimal (

Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B epitope-specific annotation model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T cell clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.

Rapidly attending towards potentially harmful stimuli to prevent possible damage to the body is a critical component of adaptive behavior. Research suggests that individuals display an attentional bias, i.e., preferential allocation of attention, for consciously perceived bodily sensations that signal potential threat, like itch or pain. Evidence is not yet clear whether an attentional bias also exists for stimuli that have been presented for such a short duration that they do not enter the stream of consciousness. This study investigated whether a preconscious attentional bias towards itch-related pictures exists in 127 healthy participants and whether this can be influenced by priming with mild itch-related stimuli compared to control stimuli. Mild itch was induced with von Frey monofilaments and scratching sounds, while control stimuli where of matched modalities but neutral. Attentional bias was measured with a subliminal pictorial dot-probe task. Moreover, we investigated how attentional inhibition of irrelevant information and the ability to switch between different tasks, i.e., cognitive flexibility, contribute to the emergence of an attentional bias. Attentional inhibition was measured with a Flanker paradigm and cognitive flexibility was measured with a cued-switching paradigm. Contrary to our expectations, results showed that participants attention was not biased towards the itch-related pictures, in facts, attention was significantly drawn towards the neutral pictures. In addition, no effect of the itch-related priming was observed. Finally, this effect was not influenced by participants' attentional inhibition and cognitive flexibility. Therefore, we have no evidence for a preconscious attentional bias towards itch stimuli. The role of preconscious attentional bias in patients with chronic itch should be investigated in future studies.

Introduction This article describes the protocol of an Ebola vaccine clinical trial which investigates the safety and immunogenicity of a two-dose prophylactic Ebola vaccine regimen comprised of two Ebola vaccines (Ad26.ZEBOV and MVA-BN-Filo) administered 56 days apart, followed by a booster vaccination with Ad26.ZEBOV offered at either 1 year or 2 years (randomisation 1:1) after the first dose. This clinical trial is part of the EBOVAC3 project (an Innovative Medicines Initiative 2 Joint Undertaking), and is the first to evaluate the safety and immunogenicity of two different booster vaccination arms in a large cohort of adults.Methods and analysis This study is an open-label, monocentric, phase 2, randomised vaccine trial. A total of 700 healthcare providers and frontliners are planned to be recruited from the Tshuapa province in the Democratic Republic of the Congo (DRC). The primary and secondary objectives of the study assess the immunogenicity of the first (Ad26.ZEBOV), second (MVA-BN-Filo) and booster (Ad26.ZEBOV) dose. Immunogenicity is assessed through the evaluation of EBOV glycoprotein binding antibody responses after vaccination. Safety is assessed through the collection of serious adverse events from the first dose until 6 months post booster vaccination and the collection of solicited and unsolicited adverse events for 1 week after the booster dose.Ethics and dissemination The protocol was approved by the National Ethics Committee of the Ministry of Health of the DRC (n°121/CNES/BN/PMMF/2019). The clinical trial was registered on 4 December 2019 on ClinicalTrials.gov. Trial activities are planned to finish in October 2022. All participants are required to provide written informed consent and no study-related procedures will be performed until consent is obtained. The results of the trial will be added on ClinicalTrials.gov, published in peer-reviewed journals and presented at international conferences.Trial registration number NCT04186000; Pre-results.

As part of its core business of gathering population-based information on new cancer diagnoses, the Belgian Cancer Registry receives free-text pathology reports, describing results of (pre-)malignant specimens. These reports are provided by 82 laboratories and written in 2 national languages, Dutch or French. For breast cancer, the reports characterize the status of estrogen receptor, progesterone receptor, and Erb-b2 receptor tyrosine kinase 2. These biomarkers are related with tumor growth and prognosis and are essential to define therapeutic management. The availability of population-scale information about their status in breast cancer patients can therefore be considered crucial to enrich real-world scientific studies and to guide public health policies regarding personalized medicine. The main objective of this study is to expand the data available at the Belgian Cancer Registry by automatically extracting the status of these biomarkers from the pathology reports. Various types of numeric features are computed from over 1,300 manually annotated reports linked to breast tumors diagnosed in 2014. A range of popular machine learning classifiers, such as support vector machines, random forests and logistic regressions, are trained on this data and compared using their F1 scores on a separate validation set. On a held-out test set, the best performing classifiers achieve F1 scores ranging from 0.89 to 0.92 for the four classification tasks. The extraction is thus reliable and allows to significantly increase the availability of this valuable information on breast cancer receptor status at a population level.

In Italy, the paper package leaflet (PPL) is the official document that is approved by the Italian Medicines Agency (AIFA) for each medicine. PPLs of all medicines, including vaccines, are freely available online by accessing the AIFA website. To investigate people’s attitudes toward possible access to the PPLs of vaccines and the acceptability of switching to an electronic package leaflet (e-leaflet) in the future, we surveyed three target groups (pregnant women, young parents, and older people) in Italy, via an online survey. We collected 321 questionnaires from the cohorts, which comprised 104 pregnant women, 105 young parents, and 112 older people. The results indicate in all target groups that health care professionals (HCPs) do not usually offer the vaccine PPL during the vaccination session: only about 10.7% of respondents receive the PPL without asking for it, with pregnant women receiving it the most frequently. The acceptance rate for switching from a PPL to an e-leaflet is fairly high in all target groups (76.9% in pregnant women, 81.9% in young parents, and 66.1% in the elderly), especially if the option exists to request a paper print, to make sure that people with a low level of digital skills can access the PPL information as well. HCPs have an important role in ensuring access to the PPLs of vaccines. HCPs should be trained to inform their patients about the different options for accessing the PPLs (as well as online access) to increase their patients’ knowledge and satisfaction.

Objectives We aimed to assess the level of adherence to COVID-19 preventive measures in the Democratic Republic of the Congo (DRC) and to identify factors associated with non-adherence.Design A cross-sectional population-based online survey.Settings The study was conducted in 22 provinces of the DRC. Five provinces with a satisfactory number of respondents were included in the analysis: Haut Katanga, Kasaï-Central, Kasaï-Oriental, Kinshasa and North Kivu.Participants The participants were people aged ≥18 years, living in the DRC. A total of 3268 participants were included in the study analysis.Interventions Both convenience sampling (surveyors themselves contacted potential participants in different districts) and snowball sampling (the participants were requested to share the link of the questionnaire with their contacts) methods were used.Primary and secondary outcome measures We computed adherence scores using responses to 10 questions concerning COVID-19 preventive measures recommended by the WHO and the DRC Ministry of Health. We used logistic regression analysis with generalised estimating equations to identify factors of poor adherence. We also asked about the presence or absence of flu-like symptoms during the preceding 14 days, whether a COVID-19 test was done and the test result.Results Data from 3268 participants were analysed. Face masks were not used by 1789 (54.7%) participants. Non-adherence to physical distancing was reported by 1364 (41.7%) participants. 501 (15.3%) participants did not observe regular handwashing. Five variables were associated with poor adherence: lower education level, living with other people at home, being jobless/students, living with a partner and not being a healthcare worker.Conclusion Despite compulsory restrictions imposed by the government, only about half of the respondents adhered to COVID-19 preventive measures in the DRC. Disparities across the provinces are remarkable. There is an urgent need to further explore the reasons for these disparities and factors associated with non-adherence.

BACKGROUND:The last evaluation to assess outcomes for patients receiving antiretroviral therapy (ART) through the Zimbabwe public sector was conducted in 2011, covering the 2007-2010 cohorts. The reported retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. We report findings of a follow-up evaluation for the 2012-2015 cohorts to assess the implementation and impact of recommendations from this prior evaluation. METHODS:A nationwide retrospective study was conducted in 2016. Multi-stage proportional sampling was used to select health facilities and study participants records. The data extracted from patient manual records included demographic, baseline clinical characteristics and patient outcomes (active on treatment, died, transferred out, stopped ART and lost to follow-up (LTFU)) at 6, 12, 24 and 36 months. The data were analysed using Stata/IC 14.2. Retention was estimated using survival analysis. The predictors associated with attrition were determined using a multivariate Cox regression model. RESULTS:A total of 3,810 participants were recruited in the study. The median age in years was 35 (IQR: 28-42). Overall, retention increased to 92.4% (p-value = 0.060), 86.5% (p-value

BackgroundSince the scale-up of the HIV "Treat All" recommendation, evidence on its real-world effect on predictors of attrition (either death or lost to follow-up) is lacking. We conducted a retrospective study using Zimbabwe ART program data to assess the association between "Treat All" and, patient-mix, programmatic characteristics, retention and predictors of attrition.MethodsWe used patient-level data from the electronic patient monitoring system (ePMS) from the nine districts, which piloted the "Treat All" recommendation. We compared patient-mix, programme characteristics, retention and predictors of attrition (lost to follow-up, death or stopping ART) in two cohorts; before (April/May 2016) and after (January/February 2017) "Treat All". Retention was estimated using survival analysis. Predictors of attrition were determined using a multivariable Cox regression model. Interactions were used to assess the change in predictors of attrition before and after "Treat All".ResultsWe analysed 3787 patients, 1738 (45.9%) and 2049 (54.1%) started ART before and after "Treat All", respectively. The proportion of men was higher after "Treat All" (39.4.% vs 36.2%, p = 0.044). Same-day ART initiation was more frequent after "Treat All" (43.2% vs 16.4%; pConclusionAttrition was higher after "Treat All"; being male, WHO Stage 4, and pregnancy predicted attrition in both before and after Treat All. However, pregnancy became a less strong risk factor for attrition after "Treat All" implementation.

BackgroundTurkey is an intermediate hepatitis B virus (HBV) endemic country. However, prevalence among Turkish migrants in Belgium is unknown, especially in those born in Belgium with a foreign-born parent, i.e. second-generation migrants (SGM).AimsTo evaluate the prevalence of HBV infection and associated risk factors in Turkish first-generation migrants (FGM), i.e. foreign-born, and SGM.MethodsBetween September 2017 and May 2019, free outreach testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and antibodies against HBsAg was offered to Turkish migrants in Middle-Limburg, Belgium. Face-to-face questionnaire assessed HBV risk factors. HBsAg positive patients were referred and followed up. Turkish SGM were stratified into birth cohort born before and after 1987, since those born after 1987 should be covered by the universal infant vaccination program.ResultsA total of 1,081/1,113 (97.1%) Turkish did go for HBV testing. Twenty-six (2.4%) were HBsAg positive; 11/26 were unaware of their status and 10/11 were successfully referred. HBsAg prevalence was 3.0% in FGM and 1.5% in SGM, p = .070. Only one out of seven HBsAg positive SGM was born after 1987. In the multiple generalized estimating equations model, the most important risk factors for anti-HBc positivity were male gender (p = .021), older age (p < .001), FGM (p < .001), low educational level of the mother (p = .003), HBV infected mother (p = .008), HBV infected siblings (p = .002), HBV infected other family member (p = .004), gynaecological examination in Turkey or unsafe male circumcision (p = .032) and dental treatment in Turkey (p = .049).ConclusionOutreach testing was well-accepted and referral to specialist care was generally successful. National HBV screening should be implemented in the Turkish FGM population and might be considered in SGM not covered by primary prevention strategies.

BackgroundGlobal health security (GHS) and universal health coverage (UHC) are key global health agendas which aspire for a healthier and safer world. However, there are tensions between GHS and UHC strategy and implementation. The objective of this study was to assess the relationship between GHS and UHC using two recent quantitative indices.MethodsWe conducted a macro-analysis to determine the presence of relationship between GHS index (GHSI) and UHC index (UHCI). We calculated Pearson's correlation coefficient and the coefficient of determination. Analyses were performed using IBM SPSS Statistics Version 25 with a 95% level of confidence.FindingsThere is a moderate and significant relationship between GHSI and UHCI (r = 0.662, p0.05). The risk of GHS threats a significant and negative correlation with the capacity for GHS (r = -0.604, pConclusionThe aspiration for GHS will not be realized without UHC; hence, the tension between these two global health agendas should be transformed into a synergistic solution. We argue that strengthening the health systems, in tandem with the principles of primary health care, and implementing a "One Health" approach will progressively enable countries to achieve both UHC and GHS towards a healthier and safer world that everyone aspires to live in.

Abstract Foraging mode plays a pivotal role in traditional reconstructions of squamate evolution. Transitions between modes are said to spark concerted changes in the morphology, physiology, behaviour, and life history of lizards. With respect to their sensory systems, species that adopt a sit-and-wait strategy are thought to rely on visual cues primarily, while actively hunting species would predominantly use chemical information. The morphology of the tongue and the vomeronasal-organs is believed to mirror this dichotomy. Still, support for this idea of concerted evolution of the morphology of the lizard sensory system merely originates from studies comparing only a few, distantly related taxa that differ in many aspects of their biology besides foraging mode. Hence, we compared vomeronasal-lingual morphology among closely related lizard species (Lacertidae). Our findings show considerable interspecific variation indicating that the chemosensory system of lacertids has undergone substantial change over a short evolutionary time. Although our results imply independent evolution of tongue and vomeronasal-organ form, we find evidence for co-variation between sampler and sensor, hinting towards an ‘optimization’ for efficient chemoreception. Furthermore, our findings suggest species’ degree of investment in chemical signalling, and not foraging behaviour, as a leading factor driving the diversity in vomeronasal-lingual morphology among lacertid species.

Abstract The design of efficient and robust pulse sequences is a fundamental requirement in quantum control. Numerical methods can be used for this purpose, but with relatively little insight into the control mechanism. Here, we show that the free rotation of a classical rigid body plays a fundamental role in the control of two-level quantum systems by means of external electromagnetic pulses. For a state to state transfer, we derive a family of control fields depending upon two free parameters, which allow us to adjust the efficiency, the time and the robustness of the control process. As an illustrative example, we consider the quantum analog of the tennis racket effect, which is a geometric property of any classical rigid body. This effect is demonstrated experimentally for the control of a spin 1/2 particle by using techniques of Nuclear Magnetic Resonance. We also show that the dynamics of a rigid body can be used to implement one-qubit quantum gates. In particular, non-adiabatic geometric quantum phase gates can be realized based on the Montgomery phase of a rigid body. The robustness issue of the gates is discussed.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects the motor system and presents with progressive muscle weakness. Most patients survive for only 2-5 years after disease onset, often due to failure of the respiratory muscles. ALS is a familial disease in ∼10% of patients, with the remaining 90% developing sporadic ALS. Over the past decade, major advances have been made in our understanding of the genetics and neuropathology of ALS. To date, around 20 genes are associated with ALS, with the most common causes of typical ALS associated with mutations in SOD1, TARDBP, FUS and C9orf72. Advances in our understanding of the genetic basis of ALS have led to the creation of different models of this disease. The molecular pathways that have emerged from these systems are more heterogeneous than previously anticipated, ranging from protein aggregation and defects in multiple key cellular processes in neurons, to dysfunction of surrounding non-neuronal cells. Here, we review the different model systems used to study ALS and discuss how they have contributed to our current knowledge of ALS disease mechanisms. A better understanding of emerging disease pathways, the detrimental effects of the various gene mutations and the causes underlying motor neuron denegation in sporadic ALS will accelerate progress in the development of novel treatments.

Abstract Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This secondary immune response is hypothesized to confer protection against herpes zoster. We longitudinally sampled 36 adults over the course of one year after re-exposure to chickenpox. The resulting 183 samples and those of 14 controls were assessed for VZV-specific T-cell immunity and antibody titres. The percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in re-exposed grandparents compared to control participants up to 9 months after re-exposure. Using a longitudinal mixture modelling approach, we found that 25% and 17% of re-exposed grandparents showed a boosting of VZV-specific CD4+ IL-2-producing T-cells and VZV-specific antibodies, respectively. The antibody boosting occurred exclusively in cytomegalovirus (CMV) IgG-positive participants. CMV IgG-positive participants also had higher VZV IE62-specific CD4+ IFN-γ-producing T-cell percentages and VZV-specific antibody titres. The protective effect of re-exposure to chickenpox is likely limited, as boosting only occurred in 17–25% of the VZV re-exposed grandparents and for less than one year.

BackgroundSedentary behavior is a growing public health concern in young adolescents from low- and middle-income countries (LMICs). However, a paucity of multinational studies, particularly in LMICs, have investigated correlates of leisure-time sedentary behavior (LTSB) in young adolescents. In the current study, we assessed socio-demographic, socio-economic, socio-cultural and health behavior related correlates of LTSB among adolescents aged 12-15 years who participated in the Global school-based Student Health Survey (GSHS).MethodsSelf-reported LTSB, which was a composite variable assessing time spent sitting and watching television, playing computer games, talking with friends during a typical day excluding the hours spent sitting at school and doing homework, was analyzed in 181,793 adolescents from 66 LMICs [mean (SD) age 13.8 (1.0) years; 49% girls). Multivariable logistic regression was used to assess the potential LTSB correlates.ResultsThe overall prevalence of ≥3 hours/day of LTSB was 26.4% (95%CI = 25.6%-27.2%). Increasing age (OR = 1.14; 95%CI = 1.11-1.17), past 30-day smoking (OR = 1.85; 95%CI = 1.69-2.03), alcohol consumption (OR = 2.01; 95%CI = 1.85-2.18), and bullying victimization (OR = 1.39; 95%CI = 1.31-1.48) were positively associated with increased LTSB across the entire sample of 181,793 adolescents. Food insecurity (OR = 0.93; 95%CI = 0.89-0.97) and low parental support/monitoring (OR = 0.91; 95%CI = 0.85-0.98) were negatively associated with LTSB. There were some variations in the correlates between countries.ConclusionsOur data indicate that in adolescents aged 12 to 15 years living in LMICs, LTSB is a complex and multi-dimensional behavior determined by socio-demograhic, sociocultural, socio-economic, and health behavior related factors. Future longitudinal data are required to confirm/refute these findings, and to inform interventions which aim to reduce sedentary levels in adolescents living in LMICs.

Caleb Parker,1 Amy Corneli,1 Kawango Agot,2 Jacob Odhiambo,2 Jesse Asewe,2 Khatija Ahmed,3 Joseph Skhosana,3 Malebo Ratlhagana,3 Michele Lanham,1 Christina Wong,1 Jennifer Deese,1 Rachel Manongi,4 Lut Van Damme,1On behalf of the FEM-PrEP recruitment group 1FHI 360, Global Health, Population and Nutrition, Durham, NC, USA; 2Impact Research and Development Organization, Kisumu, Kenya; 3Setshaba Research Centre, Soshanguve, Pretoria, South Africa; 4Kilimanjaro Christian Medical Centre, Moshi, Tanzania Abstract: We implemented an empirically informed, geographically based recruitment approach for FEM-PrEP, a human immunodeficiency virus (HIV) prevention clinical trial of daily oral emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) for HIV prevention. During the formative research phase, we conducted a modification of the Priorities for Local AIDS Control Efforts (PLACE) method and used those data and staff experiences to identify and prioritize for recruitment geographic areas where HIV incidence might be high. During the clinical trial, we implemented a routinely monitored and flexible recruitment plan in the geographical areas identified in the formative research. We describe three lessons learnt from implementing this approach: 1) the PLACE data were critical in identifying places presumed to be high risk; 2) staff experiences, in combination with PLACE data, were needed to inform a practical recruitment strategy; and 3) recruiting in establishments in priority areas identified by the PLACE data led to screening many HIV-positive women at the Bondo site (Kenya), placing additional burden on clinic staff. These lessons learnt highlight the critical importance of having a flexible and monitored recruitment strategy. Although we successfully recruited a study population at higher risk for HIV, FEM-PrEP was unable to determine the effectiveness of FTC/TDF for HIV prevention, due to low adherence to the study product among participants. We must shift the paradigm of recruitment for clinical trials of new products from focusing on identifying populations with high incidence to identifying populations at risk who are motivated and able to adhere to the study product regimen. Keywords: recruitment, PrEP, PLACE, FEM-PrEP, HIV prevention clinical trial, women