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ABSTRACTIntroduction Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received.Methods Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria.Results Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization.Conclusions COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.

Objectives: The accuracy of malaria rapid diagnostic tests is threatened by Plasmodium falciparum with pfhrp2/3 deletions. This study compares gene deletion prevalence determined by multiplex real time polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR) using existing samples with clonality previously determined by microsatellite genotyping. Methods: Multiplex qPCR was used to estimate prevalence of pfhrp2/3 deletions in three sets of previously collected patient samples from Eritrea and Peru. The qPCR was validated by multiplex digital polymerase chain reaction. Sample classification was compared with cPCR, and receiver operating characteristic curve analysis was used to determine the optimal ΔCq threshold that aligned the results of the two assays. Results: qPCR classified 75% (637 of 849) of samples as single, and 212 as mixed-pfhrp2/3 genotypes, with a positive association between clonality and proportion of mixed-pfhrp2/3 genotype samples. The sample classification agreement between cPCR and qPCR was 75.1% (95% confidence interval [CI] 68.6-80.7%) and 47.8% (95% CI 38.9-56.9%) for monoclonal and polyclonal infections. The qPCR prevalence estimates of pfhrp2/3 deletions showed almost perfect (κ = 0.804, 95% CI 0.714-0.895) and substantial agreement (κ = 0.717, 95% CI 0.562-0.872) with cPCR for Peru and 2016 Eritrean samples, respectively. For 2019 Eritrean samples, the prevalence of double pfhrp2/3 deletions was approximately two-fold higher using qPCR. The optimal threshold for matching the assay results was ΔCq = 3. Conclusions: Multiplex qPCR and cPCR produce comparable estimates of gene deletion prevalence when monoclonal infections dominate; however, qPCR provides higher estimates where multi-clonal infections are common.

Abstract Background Rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein-2 (PfHRP2) are exclusively deployed in Uganda, but deletion of the pfhrp2/3 target gene threatens their usefulness as malaria diagnosis and surveillance tools. Methods A cross-sectional survey was conducted at 40 sites across four regions of Uganda in Acholi, Lango, W. Nile and Karamoja from March 2021 to June 2023. Symptomatic malaria suspected patients were recruited and screened with both HRP2 and pan lactate dehydrogenase (pLDH) detecting RDTs. Dried blood spots (DBS) were collected from all patients and a random subset were used for genomic analysis to confirm parasite species and pfhrp2 and pfhrp3 gene status. Plasmodium species was determined using a conventional multiplex PCR while pfhrp2 and pfhrp3 gene deletions were determined using a real-time multiplex qPCR. Expression of the HRP2 protein antigen in a subset of samples was further assessed using a ELISA. Results Out of 2435 symptomatic patients tested for malaria, 1504 (61.8%) were positive on pLDH RDT. Overall, qPCR confirmed single pfhrp2 gene deletion in 1 out of 416 (0.2%) randomly selected samples that were confirmed of P. falciparum mono-infections. Conclusion These findings show limited threat of pfhrp2/3 gene deletions in the survey areas suggesting that HRP2 RDTs are still useful diagnostic tools for surveillance and diagnosis of P. falciparum malaria infections in symptomatic patients in this setting. Periodic genomic surveillance is warranted to monitor the frequency and trend of gene deletions and its effect on RDTs.

ABSTRACTThe COVID-19 pandemic disproportionately affected racial and ethnic minority communities across the United States (U.S.). Despite the disproportionate burden of COVID-19 faced by communities of color, Black and Hispanic communities are less likely to be fully vaccinated than White non-Hispanic Persons. Health inequity and vaccine hesitancy are complex phenomena that require multilevel responses tailored to the unique needs of each community, a process that inherently necessitates a high level of community engagement in order to develop the most effective health interventions. Building on the principles of community based participatory research (CBPR) and with the support of the National Institutes of Health (NIH), Project 2VIDA! was born. A multidisciplinary collaborative of academic researchers, community members, and clinicians whose aim is to foster sustainable partnerships to reduce the burden of COVID-19 in Hispanic and Black communities across Southern California. Our model was designed to meet our community members where they were – whether on their lunch break or picking their children from school. This CBPR model has been well received by community members. Future health interventions focused on reducing health disparities should prioritize the role of the community, leverage the voices of key community partners, and be grounded in equitable power sharing.

Prostate cancer (PCa) appears among the most frequently diagnosed types of malignancies in males. Because of the high demand and increasing detection rate of early PCa, alongside the specificity limitations of the gold standard clinical tools available for the diagnosis and prognosis of prostate cancer, there is an urgent need for more reliable PCa markers and highly sensitive diagnostic tools to avoid under-treatment and over-diagnosis. PCA3, or prostate cancer antigen 3, is a potential prostate cancer biomarker that is more specific and useful for preventing unnecessary repeat biopsies, particularly in men with persistently high prostate-specific antigen indices after a negative biopsy. Additionally, an electrochemically based biosensor would prove to be a powerful diagnostic tool for PCA3 detection in urine because of its simplicity, sensitivity, and cost-effectiveness, in contrast to the more traditional PCa diagnostics that depend on blood testing. This paper aimed to design a novel and simple electrochemical impedimetric biosensor based on a label-free RNA-aptamer (CG3-PCA3) as the molecular recognition element for detecting PCA3. The proposed aptasensor for the detection of PCA3 has been developed using a screen-printed carbon electrode (SPCE) modified by gold nanoparticles (AuNPs), further improving sensitivity and allowing the immobilisation of thiolate aptamers on its surface. The findings presented here demonstrated a high sensitivity to PCA3, with a detection limit of 20 fM in artificial urine and 1 fM in buffer. These results indicate that the PCA3 aptasensor could be a promising tool for routine PCa diagnosis due to its high sensitivity and cost-effectiveness.

The popularization of intelligent healthcare devices and big data analytics significantly boosts the development of Smart Healthcare Networks (SHNs). To enhance the precision of diagnosis, different participants in SHNs share health data that contain sensitive information. Therefore, the data exchange process raises privacy concerns, especially when the integration of health data from multiple sources (linkage attack) results in further leakage. Linkage attack is a type of dominant attack in the privacy domain, which can leverage various data sources for private data mining. Furthermore, adversaries launch poisoning attacks to falsify the health data, which leads to misdiagnosing or even physical damage. To protect private health data, we propose a personalized differential privacy model based on the trust levels among users. The trust is evaluated by a defined community density, while the corresponding privacy protection level is mapped to controllable randomized noise constrained by differential privacy. To avoid linkage attacks in personalized differential privacy, we design a noise correlation decoupling mechanism using a Markov stochastic process. In addition, we build the community model on a blockchain, which can mitigate the risk of poisoning attacks during differentially private data transmission over SHNs. Extensive experiments and analysis on real-world datasets have testified the proposed model, and achieved better performance compared with existing research from perspectives of privacy protection and effectiveness.

Coral carbonate production is fundamental to reef accretion and, consequently, the preservation of essential reef ecosystem services, such as wave attenuation and sustained reef biodiversity. However, the unprecedented loss of coral reefs from anthropogenic impacts has put these valuable ecosystem services at risk. To counteract this loss, active rehabilitation of degraded reef sites has accelerated globally. A variety of restoration practices exist, tailored to local site needs and reef types. For sites where there is a significant unconsolidated substrate, Mars Assisted Reef Restoration System (MARRS, or “Reef Stars”) has been utilised to contribute toward rubble stabilisation and reef accretion. However, the effect of the Reef Stars on the local carbonate budgets and structural complexity has not been assessed. For that purpose, we assess coral cover and reef complexity through a census-based approach to identify the contribution of carbonate producers and eroders alongside studying coral skeletal properties to estimate current carbonate budgets on a rehabilitated site compared to natural unrehabilitated reef and rubble patches on the mid-Great Barrier Reef. Our research identified positive ecological processes and ecological functions such as increased carbonate budget, coral cover and structural complexity at the restored site compared to the non-intervened reef and rubble patches. In general, no impacts on skeletal rigour relative to this active reef restoration were found for two key coral species and the Acropora rubble for most of the skeletal traits. However, Pocillopora damicornis hardness seemed to decrease on the restored site compared to the other sites, demonstrating different performances of coral species during restoration activities that should be considered to maximise return-on-effort of restoration activities. Overall, our data demonstrate that consideration of carbonate budgets is important for measuring success of coral restoration initiatives and that coral restoration can be a relevant tool to recover lost local carbonate budgets.

Abstract Background Globally, COVID-19 vaccines have proven to be instrumental for promoting population health by reducing illness from SARS-CoV-2. Vaccine certificates emerged as a potentially promising solution for encouraging vaccination and facilitating the safe reopening of society, however, they were controversial due to criticisms of infringing upon individual rights. While there is extensive literature describing the ethical, legal, and public health implications of vaccine certificates, there is currently a gap in knowledge about the association of vaccine certificates on vaccine uptake during the COVID-19 pandemic and barriers and facilitators to their use. Objectives The objectives of this scoping review are to (i) describe the existing literature on the association of vaccine certificates on the rates of COVID-19 vaccine uptake across several countries and (ii) describe the intrinsic and extrinsic barriers or facilitators that moderate this relationship. Methods We conducted a scoping review based on PRISMA Extension for Scoping Reviews (PRSIMA-ScR) guidelines. We searched three bibliographic databases (APA PsychInfo, Embase Classic + Embase, OVID-Medline) and preprint severs during the first week of July 2023. Three reviewers independently screened the studies based on pre-specified eligibility criteria and performed quality assessments of the primary literature and data extraction. Results Sixteen studies met the inclusion criteria. 14 or these were surveys and 2 were modelling studies. The majority documented that vaccine certificates were significantly associated with increased rates of COVID-19 vaccine uptake (n = 12), motivated by factors such as travel/employer requirements, influence from the government/peers, and trust in the safety, efficacy, and science behind COVID-19 vaccines. Three studies had non-significant or mixed findings. Only one study found a significant decrease in COVID-19 vaccine uptake, motivated by pervasive distrust in the QR code-based system of digital vaccine certificates in Russia. Quality of survey studies was generally high. Conclusion Our findings provide insights into the existing literature on vaccine certificates association with vaccine uptake in several different jurisdictions and barriers and facilitators to their uptake. This information can be used to guide future examinations of the implementation of vaccine certificates and more effective implementations.

Like the majority of non-communicable diseases that have recently gained attention, functional gastrointestinal (GI) disorders (FGID) in both children and adults are caused by a variety of medical conditions. In general, while it is often thought that common conditions such as obesity may cause other problems, for example, asthma or mental health issues, more consideration needs to be given to the possibility that they could both be brought on by a single underlying problem. Based on the variations in non-communicable disease, in recent years, our group has been revisiting the exact role of the intestinal microbiome within the Vertebrata. While the metabolic products of the microbiome have a role to play in the adult, our tentative conclusion is that the fully functioning, mutualistic microbiome has a primary role: to transfer antigen information from the mother to the neonate in order to calibrate its immune system, allowing it to survive within the microbial environment into which it will emerge. Granted that the microbiome possesses such a function, logic suggests the need for a robust, flexible, mechanism allowing for the partition of nutrition in the mature animal, thus ensuring the continued existence of both the vertebrate host and microbial guest, even under potentially unfavourable conditions. It is feasible that this partition process acts by altering the rate of peristalsis following communication through the gut–brain axis. The final step of this animal–microbiota symbiosis would then be when key microbes are transferred from the female to her progeny, either live offspring or eggs. According to this scheme, each animal inherits twice, once from its parents’ genetic material and once from the mother’s microbiome with the aid of the father’s seminal microbiome, which helps determine the expression of the parental genes. The key point is that the failure of this latter inheritance in humans leads to the distinctive manifestations of functional FGID disorders including inflammation and gut motility disturbances. Furthermore, it seems likely that the critical microbiome–gut association occurs in the first few hours of independent life, in a process that we term handshaking. Note that even if obvious disease in childhood is avoided, the underlying disorders may intrude later in youth or adulthood with immune system disruption coexisting with gut–brain axis issues such as excessive weight gain and poor mental health. In principle, investigating and perhaps supplementing the maternal microbiota provide clinicians with an unprecedented opportunity to intervene in long-term disease processes, even before the child is born.

The goal of this project is to survey attorney perceptions of social workers. This will lead to suggestions on how social workers can be more effectively integrated into the courtroom and legal system as well as to suggestions for further study. This goal reflects Person-In-Environment theory by highlighting the importance of attorneys needing to understand the contextual variables social workers can explain to the court, thereby explaining what social, political, and economic issues may have caused a client to be involved in crime in the first place. This goal also reflects Holistic Defense Theory by ensuring that clients legal and social needs are met by highlighting the need for both attorneys and social workers as part of the defense team. Lastly, this project may contribute to making justice in the courtroom reachable for traditionally disaffected people who can be made whole again by legal and social intervention.

Introduction Severe aortic stenosis is a major cause of morbidity and mortality. The existing treatment pathway for transcatheter aortic valve implantation (TAVI) traditionally relies on tertiary Heart Valve Centre workup. However, this has been associated with delays to treatment, in breach of British Cardiovascular Intervention Society targets. A novel pathway with emphasis on comprehensive patient workup at a local centre, alongside close collaboration with a Heart Valve Centre, may help reduce the time to TAVI.Methods The centre performing local workup implemented a novel TAVI referral pathway. Data were collected retrospectively for all outpatients referred for consideration of TAVI to a Heart Valve Centre from November 2020 to November 2021. The main outcome of time to TAVI was calculated as the time from Heart Valve Centre referral to TAVI, or alternative intervention, expressed in days. For the centre performing local workup, referral was defined as the date of multidisciplinary team discussion. For this centre, a total pathway time from echocardiographic diagnosis to TAVI was also evaluated. A secondary outcome of the proportion of referrals proceeding to TAVI at the Heart Valve Centre was analysed.Results Mean±SD time from referral to TAVI was significantly lower at the centre performing local workup, when compared with centres with traditional referral pathways (32.4±64 to 126±257 days, p

This paper explores new methods for disambiguating the identity of individuals in classical Arabic citations (isnāds) using a network-based approach. After training a model to extract name mentions from classical Arabic, we embed these mentions in vector space using fine-tuned BERT representations and use community detection to infer clusters of coreferent mentions. The best-performing clustering approach reduces error on the CoNLL metric by 30%. Then, as a case study, we examine the problem of determining the number of direct transmitters to Ibn ʿAsākir (d. 1176) in a set of isnāds taken from the 12th century historical text Taʾrīkh Madīnat Dimashq (TMD, History of Damascus), using our method to replicate human judgement.

In the quest for the development of accurate, reliable, and cost-effective biosensing technology for early diagnostics of prostate cancer, we describe here an electrochemical biosensor combining a simple transducing method of differential pulse voltammetry (DPV) with an RNA-based aptamer labelled with a methylene blue redox group acting as a highly specific bioreceptor to the prostate cancer biomarker PCA3. A series of DPV measurements on screen-printed gold electrodes is functionalised with a redox-labelled aptamer in solutions (either buffer or synthetic urine) containing PCA3 in a wide range of concentrations from 0.1 picomolar (pM) to 10 nanomolar (nM). In these measurements, the current peak values correlate with the concentration of PCA3 and yield a low detection limit (LDL) of 0.1 pM. Furthermore, the binding kinetics study revealed the high affinity of the aptamer to the target PCA3 with the affinity constants KD of about 3.0 × 10−8 molar. In addition, the AFM study showed the increase in the molecular layer roughness caused by the binding of PCA3, which is a large RNA molecular fragment.

Mosquitoes harbor a wide diversity of microorganisms, including viruses that are human pathogens, or that are insect specific. We used metatranscriptomics, an unbiased high-throughput molecular approach, to describe the composition of viral and other microbial communities in six medically important mosquito species from across Western Australia: Aedes vigilax, Culex annulirostris, Cx. australicus, Cx. globocoxitus, Cx. pipiens biotype molestus, and Cx. quinquefasciatus. We identified 42 viral species, including 13 novel viruses, from 19 families. Culex mosquitoes exhibited a significantly higher diversity of viruses than Aedes mosquitoes, and no virus was shared between the two genera. Comparison of mosquito populations revealed a heterogenous distribution of viruses between geographical regions and between closely related species, suggesting that geography and host species may play a role in shaping virome composition. We also detected bacterial and parasitic microorganisms, among which Wolbachia bacteria were detected in three members of the Cx. pipiens complex, Cx. australicus, Cx. pipiens biotype molestus, and Cx. quinquefasciatus. In summary, our unbiased metatranscriptomics approach provides important insights into viral and other microbial diversity in Western Australian mosquitoes that vector medically important viruses.

Vaccine certificates have been implemented worldwide, aiming to promote vaccination rates and to reduce the spread of COVID-19. However, their use during the COVID-19 pandemic was controversial and has been criticized for infringing upon medical autonomy and individual rights. We administered a national online survey exploring social and demographic factors predicting the degree of public approval of vaccine certificates in Canada. We conducted a multivariate linear regression which revealed which factors were predictive of vaccine certificate acceptance in Canada. Self-reported minority status (p

The literatures on global commodity chains and global value chains rest on an unquestioned assumption: the continual expansion of globalization. The Trump Administration's trade wars challenged this foundational assumption and even today the new Biden regime also hints at the shift away from global supply chains. We find that the prior administration’s efforts caused continued disruption of long-established commodity chains in steel, aluminum, automobiles, and other manufactured products. Flows of raw materials, intermediate products and components, and finished goods now confront higher costs. Firms continue efforts to restructure commodity chains in ways that will require the disarticulation of some nodes and the creation of new nodes. We claim that these trade wars and breakdown of global commodity chains (GCCs) may in fact mark the start of the breakdown of the U.S.-led world order. This shift harkens the onset of a new era of economic and geopolitical conflict. A key question: has this disruption of old patterns and rise of new ones continued in the post-Trump era? Does the familiar pattern of globalization continue – or is competition, contestation and disarticulation leading to sectoral economic changes that drive larger patterns of economic ascent, dominance, and decline in the world economy?

Humans and other vertebrates define body axis left-right asymmetry in the early stages of embryo development. The mechanism behind left-right establishment is not fully understood. Symmetry breaking occurs in a dedicated organ called the left-right organizer (LRO) and involves motile cilia generating fluid-flow therein. However, it has been a matter of debate whether the process of symmetry breaking relies on a chemosensory or a mechanosensory mechanism (Shinohara et al., 2012). Novel tailored manipulations for LRO fluid extraction in living zebrafish embryos allowed us to pinpoint a physiological developmental period for breaking left-right symmetry during development. The shortest critical time-window was narrowed to one hour and characterized by a mild counterclockwise flow. The experimental challenge consisted in emptying the LRO of its fluid, abrogating simultaneously flow force and chemical determinants. Our findings revealed an unprecedented recovery capacity of the embryo to re-fil and re-circulate new LRO fluid. The embryos that later developed laterality problems were found to be those that had lower anterior angular velocity and thus less anterior-posterior heterogeneity. Next, aiming to test the presence of any secreted determinant, we replaced the extracted LRO fluid by a physiological buffer. Despite some transitory flow homogenization, laterality defects were absent unless viscosity was altered, demonstrating that symmetry breaking does not depend on the nature of the fluid content but is rather sensitive to fluid mechanics. Altogether, we conclude that the zebrafish LRO is more sensitive to fluid dynamics for symmetry breaking.

Objectives: Characterizing the psychometric attributes of the Persian variant of partners in health (PIH) in multiple sclerosis (MS), Diabetes, and Low Back Pain (LBP) patients. Methods: In this cross-sectional study, 183 MS, diabetes, and LBP patients (70 male, 113 female) were treated with PIH post-forward-backward translation. Confirmatory factor analysis was used for studying the factor structure. Cronbach’s α and McDonald’s Ω coefficients were used to analyze PIH internal consistency. We used an interclass correlation coefficient to evaluate test-retest reliability. Criterion validity was determined by studying the correlation of PIH and Short Form (36) Health Survey (SF-36), Diabetes Self-Management Scale (DSMS), and Self-Efficacy in Chronic Disease Self-Management (SES6G). Results: The median age of the participants was 49.73±15.16 years, 113 (61.75%) of them were female, 64 (35.0%) had MS, 66 (36.1%) had diabetes, and 53 (29.0%) had LBP. Content validity was determined across all areas (clarity, relevancy, simplicity) by a content validity index ≥0.82. Additionally, all items were confirmed via a content validity ratio ≥0.78. The outcome of CFA depicts that the statistics presented as model fit were as follows: CFI= 0.938, NFI= 0.899, and RMSEA= 0.085. All PIH items exhibited valid internal consistency (0.886-0.893). The PIH showed sufficient test-retest reliability regarding its corresponding subscales (0.554-0.679). The construct validity was confirmed by the total scores of PIH correlated with the total score of SF-36, SES6G, and DSMS. Discussion: The Persian variant of the PIH showed sufficient validity and reliability as a measure to assess self-management in patients suffering from chronic disease (MS, diabetes, and LBP).

While the importance of the intestinal microbiome has been realised for a number of years, the significance of the phrase microbiota–gut–brain axis is only just beginning to be fully appreciated. Our recent work has focused on the microbiome as if it were a single entity, modifying the expression of the genetic inheritance of the individual by the generation of interkingdom signalling molecules, semiochemicals, such as dopamine. In our view, the purpose of the microbiome is to convey information about the microbial environment of the mother so as to calibrate the immune system of the new-born, giving it the ability to distinguish harmful pathogens from the harmless antigens of pollen, for example, or to help distinguish self from non-self. In turn, this requires the partition of nutrition between the adult and its microbiome to ensure that both entities remain viable until the process of reproduction. Accordingly, the failure of a degraded microbiome to interact with the developing gut of the neonate leads to failure of this partition in the adult: to low faecal energy excretion, excessive fat storage, and concomitant problems with the immune system. Similarly, a weakened gut–brain axis distorts interoceptive input to the brain, increasing the risk of psychiatric diseases such as autism. These effects account for David Barker’s 1990 suggestion of “the fetal and infant origins of adult disease”, including schizophrenia, and David Strachan’s 1989 observation of childhood immune system diseases, such as hay fever and asthma. The industrialisation of modern life is increasing the intensity and scale of these physical and psychiatric diseases and it seems likely that subclinical heavy metal poisoning of the microbiome contributes to these problems. Finally, the recent observation of Harald Brüssow, that reported intestinal bacterial composition does not adequately reflect the patterns of disease, would be accounted for if microbial eukaryotes were the key determinant of microbiome effectiveness. In this view, the relative success of “probiotic” bacteria is due to their temporary immune system activation of the gut–brain axis, in turn suggesting a potential mechanism for the placebo effect.

Abstract Peru was the first country where pfhrp2 and pfhrp3 gene deletions were detected despite the fact that rapid diagnostics tests are not commonly used for confirmatory malaria diagnosis. This context provides a unique scenario to study the dynamics of pfhrp2 and pfhrp3 gene deletions without apparent RDTs selection pressure. In this study we characterized the presence of pfhrp2 and pfhrp3 genes on 325 P. falciparum samples collected in Iquitos and surrounding communities between 2011 and 2018 in order to understand the dynamics of gene deletion prevalence, potential associations with clinical symptomatology and parasite genetic background. P. falciparum presence was confirmed by microscopy and PCR of 18 s rRNA, pfmsp1 and pfmsp2. Gene deletions were assessed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCRs. Confirmation of absence of HRP2 expression was assessed by ELISA of HRP2 and pLDH. Genotyping of 254 samples were performed using a panel of seven neutral microsatellite markers. Overall, pfhrp2 and pfhrp3 dual gene deletions were detected in 67% (217/324) parasite samples. Concordance between pfhrp2 deletion and negligible HRP2 protein levels was observed (Cohen's Kappa = 0.842). Prevalence of gene deletions was heterogeneous across study sites (adjusted p

Background and purpose: Metallic implants cause artefacts in computed tomography (CT) images and can introduce significant errors to structure visualisation and dosimetric calculation within the radiotherapy planning process. This study evaluated an orthopaedic metal artefact reduction algorithm and its effect on the CT number, image noise, structure delineation, and treatment dose. Methods: Raw CT data were reconstructed using standard filtered back projection and an artefact reduction algorithm to create ‘standard’ and ‘corrected’ images. A phantom containing tissue-mimicking inserts and two titanium plugs was imaged. The average CT number was compared to baseline data acquired without metal inserts. Data from 11 pelvic external beam radiotherapy (EBRT) patients with bi- or uni-lateral hip implants were retrospectively analysed. The clinically used treatment plans were re-computed on the corrected images. A prostate-mimicking phantom containing metal ‘implants’ was imaged, and 11 observers contoured both reconstructions. Results: The artefact reduction algorithm improved the CT number in those areas most affected by metal artefacts and decreased noise by 19 % (P =.04) Changes in dose distributions on corrected images compared to those calculated using the current clinical protocol were clinically insignificant. Volumes contoured on the corrected phantom images had larger Dice coefficients than those contoured on the standard images (P =.001), as well as a 36 % lower standard deviation in volumes. Conclusion: This study demonstrates that the metal artefact reduction software reduces the error in CT numbers, can improve delineation accuracy, and can reduce inter-observer variability. It has the potential to streamline the planning pathway and improve treatment planning accuracy.

Transcatheter aortic valve implantation (TAVI) is an effective and established treatment for symptomatic aortic stenosis. However, there is a lack of consensus concerning the need for peri- and post-procedural anti-thrombotic medication. Contemporary guidelines recommend that anti-thrombotic therapy is balanced against a patient’s bleeding risk following TAVI, but do not fully consider the evolving evidence base. The purpose of the Delphi panel recommendations presented here is to provide a consensus elicited from a panel of experts who regularly prescribe anti-thrombotic therapy post-TAVI. The goal was to address evidence gaps across four key topics: anti-thrombotic therapy (anti-platelet and/or anti-coagulant) in TAVI patients in sinus rhythm; anti-thrombotic therapy in TAVI patients with AF; direct oral anti-coagulants versus vitamin K antagonists; and the need for UK/Ireland specific guidance. This consensus statement aims to inform clinical decision-making by providing a concise, evidence-based summary of best practice for prescribing anti-thrombotic therapies following TAVI and highlights areas where further research is needed.

Models of particle acceleration in solar eruptive events suggest that roughly equal energy may go into accelerating electrons and ions. However, while previous solar X-ray spectroscopic imagers have transformed our understanding of electron acceleration, only one resolved image of γ-ray emission from solar accelerated ions has ever been produced. This paper outlines a new satellite instrument concept—the large imaging spectrometer for solar accelerated nuclei (LISSAN)—with the capability not only to observe hundreds of events over its lifetime, but also to capture multiple images per event, thereby imaging the dynamics of solar accelerated ions for the first time. LISSAN provides spectroscopic imaging at photon energies of 40 keV–100 MeV on timescales of ≲10 s with greater sensitivity and imaging capability than its predecessors. This is achieved by deploying high-resolution scintillator detectors and indirect Fourier imaging techniques. LISSAN is suitable for inclusion in a multi-instrument platform such as an ESA M-class mission or as a smaller standalone mission. Without the observations that LISSAN can provide, our understanding of solar particle acceleration, and hence the space weather events with which it is often associated, cannot be complete.

The purpose of this article is to provide a direction for translational research based on an analysis of the nature of complex, immune-related conditions such as obesity and coeliac disease. In essence, it seems that the prevalence of these non-communicable diseases is related to the degradation of the microbiome during the industrialisation of society, and that their nature can be used to infer the functions of the “pre-industrial” microbiome. Based on this analysis, the key point is the necessity for the fully functioning microbiome, acting alongside the parental genetic inheritance of the child, to be in place immediately after birth. In our view, this is achieved by the seemingly accidental process of maternal microbial inheritance during normal birth. Note, however, that this is not possible if the microbiome of the mother is itself degraded following previous problems. Under these conditions the health of a child may be affected from the moment of birth, although, with the exception of atopic diseases, such as eczema and food allergy, the consequences may not become apparent until late childhood or as an adult. In this way, this microbiome function deficiency hypothesis incorporates the epidemiological observations of David Strachan and David Barker in that their onset can be traced to early childhood. Coeliac disease has been chosen as an illustrative example of a multifactorial disorder due to the fact that, in addition to a series of immune system manifestations and a potential problem with food absorption, there is also a significant psychological component. Finally, it is worth noting that an ingestible sensor calibrated to the detection of interkingdom communication molecules (semiochemicals) within the intestine may offer a practical way of assessment and, perhaps, amelioration of at least some of the consequences of non-communicable disease.

Introduction IgG4 related disease (IgG4-RTD) is an infrequent disease with possible multiple organ involvement. It is characteristic to find inflammatory nodules with IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis. We present a patient with an inflammatory pseudotumor in the right upper lobe, mimicking a primary lung tumor. Case report Our patient, a 48-year old heavy smoker (25 pack/year) with no relevant medical background, referred chest pain, non-productive cough and sporadic nightly fever. Image findings revealed a mass in the right upper lobe, with increased SUV in PET-scan, and mediastinal lymphadenopathies. Primary lung tumor was suspected and right upper lobectomy was performed. Due to absence of cellular atypia and the intense plasmacytic activity in the lesion, immunohistochemical analysis was performed: abundant IgG4 plasma cells were identified, with a IgG4/IgG relation of 74%. Diagnosis of IgG4- inflammatory pseudotumor was made. Discussion After an extensive bibliographic review, we found just one similar case reported with an IgG4-lung pseudotumor without systemic disease. Due to the broad spectrum of clinical features of IgG4-RTD, and the potential multiple organ involvement, it is hard to find a classification and diagnostic criteria with high sensitivity and specificity, nevertheless they can be useful in clinical practice. Conclusion There are several benign inflammatory diseases which can mimic a primary lung tumor. Although incidence is low, IgG4 pseudotumor should be considered as a differential diagnosis in the absence of malignancy.

Background Unfavourable clot microstructure is associated with adverse outcomes in ST elevation myocardial infarction (STEMI). We investigated the effect of comorbidities and anti-platelet treatment on clot microstructure in STEMI patients using fractal dimension (d f ), a novel biomarker of clot microstructure derived from the visco-elastic properties of whole blood. Methods Patients with STEMI (n = 187) were recruited sequentially receiving aspirin with Clopidogrel (n = 157) then Ticagrelor (n = 30). Patient characteristics and blood for rheological analysis obtained. We quantified d f using sequential frequency sweep tests to obtain the phase angle of the Gel Point which is synonymous with the clot microstructure. Results Higher d f was observed in males (1.755 ± 0.068) versus females (1.719 ± 0.061, p = .001), in patients with diabetes (1.786 ± 0.067 vs 1.743 ± 0.046, p

Post-border surveillance for forestry’s high priority pests and pathogens is conducted routinely through established programs focused on the main points-of-entry and across the major plantation growing regions. Currently, most diagnostic protocols used to identify fungal phytopathogens sampled during these surveys rely on traditional methods, such as morphological examination and DNA barcoding techniques. This stepwise process from isolation to species identification is often regarded as slow, expensive, and limited due to the need for disease manifestation and/or comprehensive expertise for rapid and accurate detection. In this study, we applied a recently validated high-throughput, dual-marker amplicon sequencing approach on insect surveillance traps from across Australia to assess its performance for the targeted surveillance of the Ophiostomatales, an order of fungi comprising notable phytopathogens which are vectored by bark beetles. By using a recently validated assay we were able to confidently characterize a range of Ophiostomatalean taxa known to be present in Australia, while reporting eight first detections from environmental DNA. Our study demonstrates the value of targeted multi-barcode amplicon sequencing for high-throughput screening of fungi caught in post-border surveillance traps, in addition to emphasizing research priorities that require further investigation before such methods can be implemented routinely for biosecurity.

Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1+, GPR56+, and CD57+/- T cells (termed CGC+) with comorbid conditions in a cohort of 134 PWH co-infected with CMV on long-term ART. We found that PWH with cardiometabolic diseases (non-alcoholic fatty liver disease, calcified coronary arteries, or diabetes) had higher circulating CGC+CD4+ T cells compared to metabolically healthy PWH. The traditional risk factor most correlated with CGC+CD4+ T cell frequency was fasting blood glucose, as well as starch/sucrose metabolites. While unstimulated CGC+CD4+ T cells, like other memory T cells, depend on oxidative phosphorylation for energy, they exhibited higher expression of carnitine palmitoyl transferase 1A compared to other CD4+ T cell subsets, suggesting a potentially greater capacity for fatty acid β-oxidation. Lastly, we show that CMV-specific T cells against multiple viral epitopes are predominantly CGC+. Together, this study suggests that among PWH, CGC+ CD4+ T cells are frequently CMV-specific and are associated with diabetes, coronary arterial calcium, and non-alcoholic fatty liver disease. Future studies should assess whether anti-CMV therapies could reduce cardiometabolic disease risk in some individuals.

Reptiles are an important part of the vertebrate fauna in the temperate woodlands of south-eastern Australia. However, compared to birds and mammals, the long-term occurrence of reptiles across woodland growth types-old growth, regrowth, and replantings-remains poorly understood. Here, using 18-years of data gathered at 218 sites across 1.5 million hectares in New South Wales South West Slopes bioregion, we sought to quantify patterns of temporal change in reptile occurrence and determine if such changes varied between woodland growth types. Despite extensive sampling, almost 75% of our 6341 surveys produced no detections of reptiles. Significant survey effort exceeding 2000 surveys was needed over a prolonged period of time to record detections of 26 reptile species in our study area. Our analyses showed a temporal increase in estimated reptile species richness and abundance over 18 years. Such increases characterized all three vegetation structural types we surveyed. At the individual species level, we had sufficient data to construct models for five of the 26 species recorded. Three of these species were least commonly detected in replantings, whereas the remaining two were most often detected in replantings relative to old growth and regrowth woodland. We found evidence of a temporal increase in two skink species, a decline in one gecko species, and no change in the remaining two skink species. Although detections were consistently low, active searches were the best survey method, and we suggest using this method in habitats known to be hotspots for reptiles, such as rocky outcrops, if the aim is to maximize the number of individuals and species detected. Our findings highlight the value of all three broad vegetation structure types in contributing to woodland reptile biodiversity.

Background: World Health Organization has called for research into predictive factors for selecting persons who could be successfully treated with shorter durations of direct-acting antiviral (DAA) therapy for hepatitis C. We evaluated early virological response as a means of shortening treatment and explored host, viral and pharmacokinetic contributors to treatment outcome. Methods: Duration of sofosbuvir and daclatasvir (SOF/DCV) was determined according to day 2 (D2) virologic response for HCV genotype (gt) 1- or 6-infected adults in Vietnam with mild liver disease. Participants received 4- or 8-week treatment according to whether D2 HCV RNA was above or below 500 IU/ml (standard duration is 12 weeks). Primary endpoint was sustained virological response (SVR12). Those failing therapy were retreated with 12 weeks SOF/DCV. Host IFNL4 genotype and viral sequencing was performed at baseline, with repeat viral sequencing if virological rebound was observed. Levels of SOF, its inactive metabolite GS-331007 and DCV were measured on days 0 and 28. Results: Of 52 adults enrolled, 34 received 4 weeks SOF/DCV, 17 got 8 weeks and 1 withdrew. SVR12 was achieved in 21/34 (62%) treated for 4 weeks, and 17/17 (100%) treated for 8 weeks. Overall, 38/51 (75%) were cured with first-line treatment (mean duration 37 days). Despite a high prevalence of putative NS5A-inhibitor resistance-associated substitutions (RASs), all first-line treatment failures cured after retreatment (13/13). We found no evidence treatment failure was associated with host IFNL4 genotype, viral subtype, baseline RAS, SOF or DCV levels. Conclusions: Shortened SOF/DCV therapy, with retreatment if needed, reduces DAA use in patients with mild liver disease, while maintaining high cure rates. D2 virologic response alone does not adequately predict SVR12 with 4-week treatment. Funding: Funded by the Medical Research Council (Grant MR/P025064/1) and The Global Challenges Research 70 Fund (Wellcome Trust Grant 206/296/Z/17/Z).

CABI has been involved in identifying and combatting emerging fungal disease of plants for over 100 years and in doing so has built a wealth of resources to support farmers and practitioners in reducing crop loss. CABI does not achieve this alone – being an international, inter-governmental, not-for-profit organisation, its 49 Member Countries guide and influence its work, which a network of global partners helps deliver. This work is becoming more relevant in light of increasing threats from climate change, invasive species and pathogens becoming resistant to biocides. Here, we focus on how climate change is influencing disease occurrence and how CABI’s work and resources can help in the battle to manage emerging and spreading diseases. CABI’s culture collection maintains living and active strains of pathogens and biocontrol agents for use as reference materials, its diagnostic advisory service and network of partners helps identify problems and provide solutions and CABI’s information resources underpin it all.

Abstract Mitochondrial dysfunction is a feature of type I and type II diabetes, but there is a lack of consistency between reports and links to disease development. We aimed to investigate if mitochondrial structure–function remodelling occurs in the early stages of diabetes by employing a mouse model (GENA348) of Maturity Onset Diabetes in the Young, exhibiting hyperglycemia, but not hyperinsulinemia, with mild left ventricular dysfunction. Employing 3-D electron microscopy (SBF-SEM) we determined that compared to wild-type, WT, the GENA348 subsarcolemma mitochondria (SSM) are ~ 2-fold larger, consistent with up-regulation of fusion proteins Mfn1, Mfn2 and Opa1. Further, in comparison, GENA348 mitochondria are more irregular in shape, have more tubular projections with SSM projections being longer and wider. Mitochondrial density is also increased in the GENA348 myocardium consistent with up-regulation of PGC1-α and stalled mitophagy (down-regulation of PINK1, Parkin and Miro1). GENA348 mitochondria have more irregular cristae arrangements but cristae dimensions and density are similar to WT. GENA348 Complex activity (I, II, IV, V) activity is decreased but the OCR is increased, potentially linked to a shift towards fatty acid oxidation due to impaired glycolysis. These novel data reveal that dysregulated mitochondrial morphology, dynamics and function develop in the early stages of diabetes.

Abstract Background Intensive malaria control may have additional benefits beyond reducing the incidence of symptomatic malaria. We compared antibiotic treatment of children before and after the implementation of highly effective malaria control interventions in Tororo, a historically high transmission area of Uganda. Methods Two successive cohorts of children, aged 0.5 to 10 years, were followed from September 2011 to October 2019 in a dedicated study clinic. Universal distribution of long-lasting insecticidal nets was conducted in 2013 and 2017. Sustained indoor residual spraying of insecticide (IRS) was initiated in December 2014. Generalized linear mixed-effects models were used to compare the incidence of antimalarial and antibiotic treatments before and after vector control measures were implemented. Results Comparing the period prior to the implementation of IRS to the period after IRS had been sustained for 4–5 years, the adjusted incidence of malaria treatments decreased from 2.68 to 0.05 per person-year (incidence rate ratio [IRR] = 0.02, 95% CI 0.01–0.03, p < 0.001), and the adjusted incidence of antibiotic treatments decreased from 4.14 to 1.26 per person-year (IRR = 0.30, 95% CI 0.27–0.34, p < 0.001). The reduction in antibiotic usage was primarily associated with fewer episodes of symptomatic malaria and fewer episodes of fever with sub-microscopic parasitemia, both of which were frequently treated with antibiotics. Conclusions In a historically high transmission setting, the implementation of highly effective vector control interventions was followed by a marked reduction in antibiotic treatment of children. This added benefit of malaria control could have important implications for antibiotic prescribing practices, efforts to curtail antimicrobial resistance, and health system costs.

Abstract Eritrea was the first African country to complete a nationwide switch in 2016 away from HRP2-based RDTs due to high rates of false-negative RDT results caused by Plasmodium falciparum parasites lacking hrp2/hrp3 genes. A cross-sectional survey was conducted during 2019 enrolling symptomatic malaria patients from nine health facilities across three zones consecutively to investigate the epidemiology of P. falciparum lacking hrp2/3 after the RDT switch. Molecular analyses of 715 samples revealed the overall prevalence of hrp2-, hrp3-, and dual hrp2/3-deleted parasites as 9.4% (95%CI 7.4–11.7%), 41.7% (95% CI 38.1–45.3%) and 7.6% (95% CI 5.8–9.7%), respectively. The prevalence of hrp2- and hrp3-deletion is heterogeneous within and between zones: highest in Anseba (27.1% and 57.9%), followed by Gash Barka (6.4% and 37.9%) and Debub zone (5.2% and 43.8%). hrp2/3-deleted parasites have multiple diverse haplotypes, with many shared or connected among parasites of different hrp2/3 status, indicating mutant parasites have likely evolved from multiple and local parasite genetic backgrounds. The findings show although prevalence of hrp2/3-deleted parasites is lower 2 years after RDT switching, HRP2-based RDTs remain unsuitable for malaria diagnosis in Eritrea. Continued surveillance of hrp2/3-deleted parasites in Eritrea and neighbouring countries is required to monitor the trend.

Background Increased levels of wellbeing contribute to people being more productive, resilient, physically healthy and showing lower levels of mental illness. Using mobile apps to increase wellbeing in young people is becoming the method of choice. This study sought to critically appraise the current evidence base with regards to young people's (16–24 years of age) engagement with wellbeing apps . Methods A systematic review of the literature and narrative synthesis was conducted to investigate users’ characteristics and other potential engagement elements. A total of 11,245 titles, 160 abstracts and 68 full-text articles published between 2002 and 2021 were screened, of which 22 studies were included. Results Main themes/findings indicated that a user's engagement with wellbeing apps was dependant on the presence of strong identity elements, including motivation, mood and values; design elements such as meaningful rewards, short duration of studies and seamless automatic delivery with low contact with researchers; and being innovative and contextualised. The majority of the studies did not report outcomes by social determinants such as ethnicity, education and others. Conclusion This research reflects on the need to consider participants’ individuality when designing app mediated wellbeing interventions.

Summary: Background: Niemann-Pick disease type C (NPC) is a rare prematurely fatal lysosomal lipid storage disease with limited therapeutic options. The prominent neuropathological hallmarks include hypomyelination and cerebellar atrophy. We previously demonstrated the efficacy of recombinant human heat shock protein 70 (rhHSP70) in preclinical models of the disease. It reduced glycosphingolipid levels in the central nervous system (CNS), improving cerebellar myelination and improved behavioural phenotypes in Npc1nih (Npc1−/−) mice. Furthermore, treatment with arimoclomol, a well-characterised HSP amplifier, attenuated lysosomal storage in NPC patient fibroblasts and improved neurological symptoms in Npc1−/− mice. Taken together, these findings prompted the investigation of the effects of HSP amplification on CNS myelination. Methods: We administered bimoclomol daily or rhHSP70 6 times per week to Npc1−/− (BALB/cNctr-Npc1m1N/J, also named Npc1nih) mice by intraperitoneal injection from P7 through P34 to investigate the impact on CNS myelination. The Src-kinase inhibitor saracatinib was administered with/without bimoclomol twice daily to explore the contribution of Fyn kinase to bimoclomol's effects. Findings: Treatment with either bimoclomol or rhHSP70 improved myelination and increased the numbers of mature oligodendrocytes (OLs) as well as the ratio of active-to-inactive forms of phosphorylated Fyn kinase in the cerebellum of Npc1−/− mice. Additionally, treatment with bimoclomol preserved cerebellar weight, an effect that was abrogated when co-administered with saracatinib, an inhibitor of Fyn kinase. Bimoclomol-treated mice also exhibited increased numbers of immature OLs within the cortex. Interpretation: These data increase our understanding of the mechanisms by which HSP70 regulates myelination and provide further support for the clinical development of HSP-amplifying therapies in the treatment of NPC. Funding: Funding for this study was provided by Orphazyme A/S (Copenhagen, Denmark) and a Pathfinder Award from The Wellcome Trust.

Abstract Collaborative conservation brings diverse stakeholders together to sustain healthy landscapes and strengthen communities. Organizations fostering collaborative conservation depend on philanthropy to advance collaborative conservation, while philanthropic organizations depend on these organizations to advance their missions. Both face challenges engaging with each other as they work toward shared goals, yet open dialogue about how funders and practitioners work together is rare. The authors of this paper represent equal numbers of funders and practitioners who, together, identified eight best practices that are practical, effective actions funders and practitioners can take to better achieve shared conservation goals. These eight best practices are: (1) collaborate, (2) nurture relationships, (3) invest in capacity, (4) plan well, implement well, (5) engage diversity, (6) support entrepreneurial spirit, (7) reduce burdens, and (8) tell our story. By centering around collaboration, relationships, and diversity, these best practices exemplify several growing and valuable trends in philanthropy that support collaborative conservation.

Human respiratory syncytial virus (RSV) is the primary cause of acute lower respiratory tract infections in children and the elderly worldwide, for which neither a vaccine nor an effective therapy is approved. The entry of RSV into the host cell is mediated by stepwise structural changes in the surface RSV fusion (RSV-F) glycoprotein. Recent progress in structural and functional studies of RSV-F glycoprotein revealed conformation-dependent neutralizing epitopes which have become attractive targets for vaccine and therapeutic development. As RSV-F is present on viral surface in a trimeric form, a trivalent binding interaction between a candidate fusion inhibitor and the respective epitopes on each of the three monomers is expected to prevent viral infection at higher potency than a monovalent or bivalent inhibitor. Here we demonstrate a novel RSV entry inhibitory approach by implementing a trimeric DNA nanostructure as a template to display up to three linear peptide moieties that simultaneously target an epitope on the surface of the prefusion RSV-F protein. In order to design synthetic binding peptides that can be coupled to the DNA nanostructure, the prefusion RSV-F-specific monoclonal antibody (D25) was selected. Complementarity-determining region 3 (CDR3) derived peptides underwent truncation and alanine-scanning mutagenesis analysis, followed by systematic sequence modifications using non-canonical amino acids. The most effective peptide candidate was used as a binding moiety to functionalize the DNA nanostructure. The designed DNA-peptide construct was able to block RSV infection on cells more efficiently than the monomeric peptides, however a more moderate reduction of viral load was observed in the lungs of infected mice upon intranasal application, likely due to dissociation or absorption of the underlying DNA structure by cells in the lungs. Taken together, our results point towards the inhibitory potential of a novel trimeric DNA-peptide based approach against RSV and open the possibility to apply this platform to target other viral infections.

Abstract The ophiostomatoid fungi are an assemblage of ascomycetes which are arguably best-known for their associations with bark and ambrosia beetles (Curculonidae) and blue stain (sap stain) of many economically important tree species. These fungi are considered a significant threat to coniferous forests, which has resulted in numerous studies characterising the diversity of bark beetles and their ophiostomatoid associates globally. The diversity of ophiostomatoid fungi present in Australian pine plantations, however, remains largely undetermined. The aims of this study were therefore to reconsider the diversity of ophiostomatoid fungi associated with Pinus in Australia, and to establish the baseline of expected taxa found within these plantation ecosystems. To achieve this, we reviewed Australian plant pathogen reference collections, and analysed samples collected during forest health surveillance programs from the major pine growing regions in south-eastern Australia. In total, 135 ophiostomatoid isolates (15 from reference collections and 120 collected during the current study) were assessed using morphological identification and ITS screening which putatively distinguished 15 taxonomic groups. Whole genome sequencing (WGS) of representative isolates from each taxon was performed to obtain high-quality sequence data for multi-locus phylogenetic analysis. Our results revealed a greater than expected diversity, expanding the status of ophiostomatoid fungi associated with Pinus in Australia to include 14 species from six genera in the Ophiostomatales and a single species residing in the Microascales. While most of these were already known to science, our study includes seven first records for Australia and the description of one new species, Graphilbum ipis-grandicollis sp. nov.. This study also provides an early example of whole genome sequencing (WGS) approaches replacing traditional PCR-based methods for taxonomic surveys. This not only allowed for robust multi-locus sequence extraction during taxonomic assessment, but also permitted the rapid establishment of a curated genomic database for ophiostomatoid fungi which will continue to aid in the development of improved diagnostic resources and capabilities for Australian biosecurity.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

The reduction of excessive weight remains a major public health challenge, with control currently limited to a calorie reduction strategy. Currently, attempts are being made at revisiting the fibre hypothesis based on the African studies of Denis Burkitt, that the lack of dietary fibre in the modern diet was responsible for the occurrence of obesity and many of the other non-communicable diseases of what he called “Western civilization”. However, the dilemma is that Burkitt himself stressed that other peoples of his day, such as the Maasai, remained healthy without consuming such high fibre diets. Equally, the present obesity epidemic is accompanied by diseases of a malfunctioning immune system and of poor mental health that do not seem to be adequately explained simply by a deficiency of dietary fibre. Though unknown in Burkitt’s day, an increasing degradation of a mutualistic intestinal microbiome would offer a better fit to the observed epidemiology, especially if the microbiome is not effectively passed on from mother to child at birth. Taking the broader view, in this article we posit a view of the microbiome as a cofactor of mammalian evolution, in which a maternal microbial inheritance complements the parental genetic inheritance of the animal, both engaging epigenetic processes. As this would require the microbiome to be fully integrated with the animal as it develops into an adult, so we have a meaningful evolutionary role for the microbiome–gut–brain axis. By a failure to correctly establish a microbiome–gut interface, the inhibition of maternal microbial inheritance sets the scene for the future development of non-communicable disease: compromised immune system function on the one hand and dysfunctional gut–brain communication on the other. The basic principle is that the fully functioning, diverse, microbiome achieves interkingdom communication by the generation of messenger chemicals, semiochemicals. It is envisaged that the in situ detection of these as yet ill-defined chemical entities by means of an ingestible sensor would indicate the severity of disease and provide a guide as to its amelioration.

Introducción: Entre el 5-10% de los pacientes que se someten a cirugía curativa por cáncer colorrectal (CCR) presentarán en algún momento recurrencia de su enfermedad a nivel pulmonar. El tratamiento quirúrgico de las metástasis pulmonares (MP) fue ganando popularidad a través de los años, diferentes publicaciones informan una tasa de supervivencia global a los 5 años de entre 30% a 60%. Presentamos una revisión de pacientes con resecciones por MP de CCR tratados en un único centro en Argentina. Materiales y métodos: Se realizó un estudio descriptivo, observacional, retrospectivo entre 2008 y 2018. Se incluyeron todos los pacientes con resecciones de MP de CCR. El objetivo primario fue evaluar la supervivencia global y supervivencia libre de enfermedad. Como objetivo secundario se evaluaron posibles factores pronósticos. Resultados: Se realizaron un total de 99 cirugías en los 68 pacientes, la resección fue múltiple en un 48,5%, siendo más de 3 nódulos en un 13%. La supervivencia global y libre de progresión a los 5 años fue del 55% y del 27% respectivamente. En el análisis estadístico encontramos que las lesiones en más de un lóbulo (p=0.015) y la resección de más de 3 nódulos (p=0.011) presentaron una menor supervivencia global. Conclusiones: En este análisis retrospectivo evidenciamos valores comparables a la literatura mundial con respecto a morbilidad, mortalidad, supervivencia global y libre de progresión. En nuestra serie los pacientes con enfermedad en más de un lóbulo o más de tres lesiones resecadas presentan significativamente menor supervivencia global.

Background: Brain-computer interface (BCI) systems are controlled by users through neurophysiological input for a variety of applications, including communication, environmental control, and motor rehabilitation. Although individuals with severe speech and physical impairment are the primary users of this technology, BCIs have emerged as a potential tool for broader populations, including delivering cognitive training/interventions with neurofeedback (NFB). Methods: This paper describes the development and preliminary testing of a protocol for use of a BCI system with NFB as an intervention for people with mild Alzheimer's disease (AD). The intervention focused on training visual attention and language skills, as AD is often associated with functional impairments in both. This funded pilot study called for enrolling five participants with mild AD in a six-week BCI EEG-based NFB intervention that followed a four-to-seven-week baseline phase. While two participants completed the study, the remaining three participants could not complete the intervention phase because of COVID-19 restrictions. Results: Preliminary pilot results suggested: (1) participants with mild AD were able to participate in a study with multiple assessments per week and complete all outcome measures, (2) most outcome measures were reliable during the baseline phase, and (3) all participants with mild AD learned to operate a BCI spelling system with training. Conclusions: Although preliminary results demonstrate practical feasibility to deliver NFB intervention using a BCI to adults with AD, completion of the protocol in its entirety with more participants is needed to further assess whether implementing NFB-based cognitive intervention is justified by functional treatment outcomes. Trial registration: This study was registered with ClinicalTrials.gov (NCT03790774).

This paper describes a newly established community-based participatory research partnership that brings together professionals from several disciplines to gain greater insight into the needs of children and the families of children seeking mental health services in a community setting. This paper, written from the perspective of graduate students, outlines the successes and challenges that have accompanied the establishment of our university-community partnership. Informed by the interactive and contextual model of collaboration (Suarez-Balcazar et al., 2005), this paper outlines key elements of developing and sustaining a community-based partnership and offers reflections on our personal experiences and lessons learned as graduate students within the partnership. Our examination reveals that adequate and consistent communication and the early establishment of trust and mutual respect among partners have been integral components of the emergence and success of this partnership.

Abstract Background Genetic diversity and parasite relatedness are essential parameters for assessing impact of interventions and understanding transmission dynamics of malaria parasites, however data on its status in Plasmodium falciparum populations in Uganda is limited. Microsatellite markers and DNA sequencing were used to determine diversity and molecular characterization of P. falciparum parasite populations in Uganda. Methods A total of 147 P. falciparum genomic DNA samples collected from cross-sectional surveys in symptomatic individuals of 2–10 years were characterized by genotyping of seven highly polymorphic neutral microsatellite markers (n = 85) and genetic sequencing of the Histidine Rich Protein 2 (pfhrp2) gene (n = 62). ArcGIS was used to map the geographical distribution of isolates while statistical testing was done using Student's t-test or Wilcoxon's rank-sum test and Fisher’s exact test as appropriate at P ≤ 0.05. Results Overall, 75.5% (95% CI 61.1–85.8) and 24.5% (95% CI14.2–38.9) of parasites examined were of multiclonal (mixed genotype) and single clone infections, respectively. Multiclonal infections occurred more frequently in the Eastern region 73.7% (95% CI 48.8–89.1), P

Analysis of a unique data set of U.S. veterinary firms and veterinarians provides evidence of significant differences in earnings between self-employed males and females. After controlling for important concomitant variables, including training and experience, self-employed female veterinarians generally own smaller clinics and have lower earnings than their male counterparts. This study considers which demographic/economic factors may be associated with observed gender differences in earnings. The gender gap for average earnings is about 44 percent; however, when controlling for certain characteristics, the gap narrows to as little as 23 percent, depending on the model specification. Firm size was found to be the strongest contributing factor in explaining the gender gap in earnings, and so, possible explanations for differences in firm size have also been discussed. Whilst the analysis is not conclusive, there is evidence that self-employed females may face customer discrimination, which may constrain the growth and size of female-owned firms. (JEL D21)

Gastro-intestinal nematode (GIN) parasites are a major cause of production losses in grazing cattle, primarily through reduced growth rates in young animals. Control of these parasites relies heavily on anthelmintic drugs; however, with growing reports of resistance to currently available anthelmintics, alternative methods of control are required. A major hurdle in this work has been the lack of physiologically relevant in vitro infection models that has made studying precise interactions between the host and the GINs difficult. Such mechanistic insights into the infection process will be valuable for the development of novel targets for drugs, vaccines, or other interventions. Here we created bovine gastric epithelial organoids from abomasal gastric tissue and studied their application as in vitro models for understanding host invasion by GIN parasites. Transcriptomic analysis of gastric organoids across multiple passages and the corresponding abomasal tissue showed conserved expression of tissue-specific genes across samples, demonstrating that the organoids are representative of bovine gastric tissue from which they were derived. We also show that self-renewing and self-organising three-dimensional organoids can also be serially passaged, cryopreserved, and resuscitated. Using Ostertagia ostertagi, the most pathogenic gastric parasite in cattle in temperate regions, we show that cattle gastric organoids are biologically relevant models for studying GIN invasion in the bovine abomasum. Within 24 h of exposure, exsheathed larvae rapidly and repeatedly infiltrated the lumen of the organoids. Prior to invasion by the parasites, the abomasal organoids rapidly expanded, developing a ‘ballooning’ phenotype. Ballooning of the organoids could also be induced in response to exposure to parasite excretory/secretory products. In summary, we demonstrate the power of using abomasal organoids as a physiologically relevant in vitro model system to study interactions of O. ostertagi and other GIN with bovine gastrointestinal epithelium.

Abstract Background Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. This study examined the changing pattern of Anopheles species in three areas of Uganda with markedly different transmission intensities and different levels of vector control. Methods From October 2011 to June 2016 mosquitoes were collected monthly using CDC light traps from 100 randomly selected households in three areas: Walukuba (low transmission), Kihihi (moderate transmission) and Nagongera (high transmission). LLINs were distributed in November 2013 in Walukuba and Nagongera and in June 2014 in Kihihi. IRS was implemented only in Nagongera, with three rounds of bendiocarb delivered between December 2014 and June 2015. Mosquito species were identified morphologically and by PCR (Polymerase Chain Reaction). Results In Walukuba, LLIN distribution was associated with a decline in Anopheles funestus vector density (0.07 vs 0.02 mosquitoes per house per night, density ratio [DR] 0.34, 95% CI: 0.18–0.65, p = 0.001), but not Anopheles gambiae sensu stricto (s.s.) nor Anopheles arabiensis. In Kihihi, over 98% of mosquitoes were An. gambiae s.s. and LLIN distribution was associated with a decline in An. gambiae s.s. vector density (4.00 vs 2.46, DR 0.68, 95% CI: 0.49–0.94, p = 0.02). In Nagongera, the combination of LLINs and multiple rounds of IRS was associated with almost complete elimination of An. gambiae s.s. (28.0 vs 0.17, DR 0.004, 95% CI: 0.002–0.009, p