The PfRCR complex bridges malaria parasite and erythrocyte during invasion.

The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex1, containing PfRH5 (refs. 2,3), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies3-6 or nanobodies1 against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex7,8, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane9, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies5 neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies6, binds to the PfCSS-PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design.

Realtime Diagnosis from Electrocardiogram Artificial Intelligence-Guided Screening for Atrial Fibrillation with Long Follow-Up (REGAL): Rationale and design of a pragmatic, decentralized, randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is associated with increased risks of stroke and dementia. Early diagnosis and treatment could reduce the disease burden, but AF is often undiagnosed. An artificial intelligence (AI) algorithm has been shown to identify patients with previously unrecognized AF; however, monitoring these high-risk patients has been challenging. Consumer wearable devices could be an alternative to enable long-term follow-up. OBJECTIVES: To test whether Apple Watch, used as a long-term monitoring device, can enable early diagnosis of AF in patients who were identified as having high risk based on AI-ECG. DESIGN: The Realtime diagnosis from Electrocardiogram (ECG) Artificial Intelligence (AI)-Guided Screening for Atrial Fibrillation (AF) with Long Follow-up (REGAL) study is a pragmatic trial that will accrue up to 2,000 older adults with a high likelihood of unrecognized AF determined by AI-ECG to reach our target of 1,420 completed participants. Participants will be 1:1 randomized to intervention or control and will be followed up for 2 years. Patients in the intervention arm will receive or use their existing Apple Watch and iPhone and record a 30-second ECG using the watch routinely or if an abnormal heart rate notification is prompted. The primary outcome is newly diagnosed AF. Secondary outcomes include changes in cognitive function, stroke, major bleeding, and all-cause mortality. The trial will utilize a pragmatic, digitally-enabled, decentralized design to allow patients to consent and receive follow-up remotely without traveling to the study sites. SUMMARY: The REGAL trial will examine whether a consumer wearable device can serve as a long-term monitoring approach in older adults to detect AF and prevent cognitive function decline. If successful, the approach could have significant implications on how future clinical practice can leverage consumer devices for early diagnosis and disease prevention. CLINICALTRIALS: GOV: : NCT05923359.

Gliding motility of Plasmodium merozoites.

Plasmodium malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate dependent and powered by an actomyosin motor that drives the posterior translocation of extracellular adhesins which, in turn, propel the parasite forward. Gliding motility is essential for tissue translocation in the sporozoite and ookinete stages; however, the short-lived erythrocyte-invading merozoite stage has never been observed to undergo gliding movement. Here we show Plasmodium merozoites possess the ability to undergo gliding motility in vitro and that this mechanism is likely an important precursor step for successful parasite invasion. We demonstrate that two human infective species, Plasmodium falciparum and Plasmodium knowlesi, have distinct merozoite motility profiles which may reflect distinct invasion strategies. Additionally, we develop and validate a higher throughput assay to evaluate the effects of genetic and pharmacological perturbations on both the molecular motor and the complex signaling cascade that regulates motility in merozoites. The discovery of merozoite motility provides a model to study the glideosome and adds a dimension for work aiming to develop treatments targeting the blood stage invasion pathways.

Brief cognitive behavioural therapy for eating disorders symptomatology among a mixed sample of adolescents and young adults in primary care: A non-randomised feasibility and pilot study.

OBJECTIVE: Brief and accessible therapies for people with an eating disorder is an important health target. Ten-session cognitive behavioural therapy (CBT-T) is a brief treatment evaluated in people with a non-underweight eating disorder. This study aimed to evaluate the feasibility and preliminary effectiveness of CBT-T for young people in primary care. METHOD: This cohort pilot study used group (adolescents vs. young adults) by time (over four time points) Generalised Linear Mixed Model analysis. Participants included 13-25-year-olds attending an early intervention mental health service, receiving 10 sessions of CBT-T. Feasibility was assessed using recruitment, retention and satisfaction. Eating and other pathology measures were administered at baseline, weeks four and 10, and 12-week follow-up. RESULTS: Of the 63 commencing treatment, 38 completed 10 CBT-T sessions (60%). Most (94%) reported high treatment satisfaction. Significant reductions in eating pathology, depression and stress were found. Age group did not yield differences in CBT-T outcome, with large to very large effect sizes across outcome variables. Anxiety was associated with attrition. CONCLUSION: This study provides preliminary support for the use of CBT-T in primary care, across adolescence and early adulthood. Findings require replication in other clinical settings and comparison to other clinical approaches and control populations.

Outcomes for infants whose mothers had an eating disorder in the perinatal period: A systematic review of the evidence.

OBJECTIVE: To establish any health outcomes for infants to age one, associated with their mother having a diagnosis of an active eating disorder during pregnancy or the 12-month postnatal period. METHOD: A qualitative systematic literature review of numerous databases (Medline, PsycINFO, CINAHL, Scopus, Cochrane Library, MedNar, PsycExtra, National Institute for Health and Care Excellence and Open Grey) was performed examining any infant health outcomes. RESULTS: This resulted in 22 included studies (17 cohort, 3 cross-sectional, 1 case controlled and 1 mixed methods study). A range of adverse infant outcomes including poor birth, growth and interactional feeding outcomes were identified. DISCUSSION: Antenatal identification and treatment for women with an eating disorder during the perinatal period and their infants are vital. Optimizing pregnancy nutrition, maternal eating disorder symptoms and feeding interactions appear particularly important.

OBJETIVO: Establecer cualquier resultado de salud para los lactantes hasta la edad de un año, asociado con que su madre tenga un diagnóstico de un trastorno de la conducta alimentaria activo durante el embarazo o en el período postnatal de 12 meses. MÉTODO: Se realizó una revisión cualitativa sistemática de la literatura de numerosas bases de datos (Medline, PsycINFO,CINAHL,Scopus, Cochrane Library, MedNar, PsycExtra, National Institute for Health and Care Excellence y Open Grey) que examinó cualquier resultado de salud infantil. RESULTADOS: Esto dio lugar a 22 estudios incluidos (17 de cohorte, 3 transversales, 1 estudio de caso controlado y 1 estudio de métodos mixtos). Se identificaron una variedad de resultados adversos para los lactantes, incluidos los resultados deficientes al nacimiento, el crecimiento y en la interacción con la alimentación. DISCUSIÓN: La identificación prenatal y el tratamiento para las mujeres con un trastorno de la conducta alimentaria durante el período perinatal y sus infantes son vitales. La optimización de la nutrición del embarazo, los síntomas del trastorno alimentario materno y las interacciones alimentarias parecen particularmente importantes. PALABRAS CLAVE: Trastornos de la Conducta Alimentaria y de la Ingestión de Alimentos; Anorexia nerviosa; Bulimia Nerviosa; Trastorno por Atracón; Embarazo; Parto; Período posparto; Infante, Recién Nacido; Bienestar Infantil; Desarrollo Infantil; Pronóstico; Madre.

Disordered eating, body image concerns, and weight control behaviors in primary school aged children: A systematic review and meta-analysis of universal-selective prevention interventions.

OBJECTIVE: Body image concerns and extreme weight control behaviors frequently develop in childhood indicating an important age group for the implementation of universal-selective prevention approaches. This systematic review aimed to evaluate the effect of universal-selective prevention interventions addressing disordered eating, body image concerns, and/or extreme weight control behaviors in children aged 6-12 years. METHOD: Nine databases were searched up to April 2021. Studies were included if they delivered a universal-selective prevention intervention to children aged 6-12 years and reported outcomes relating to body image, disordered eating, or weight control behaviors. The review was conducted in line with the PRISMA Guidelines. RESULTS: A total of 42 articles describing 39 studies included in the review, with most (n = 24; 57%) classified as neutral quality. Thirty studies implemented an eating disorder specific universal-selective program and nine implemented lifestyle interventions plus content to address disordered eating risk factors. Meta-analysis (n = 16 studies) revealed an improvement in body image-related outcomes across all studies (standardized mean difference [SMD] 0.26 [95%CI 0.01, 0.51]); with a high level of heterogeneity (Î2 = 89.9%; p < .01). Meta-analysis according to gender revealed a general improvement in body image-related outcomes for girls (SMD 0.40 [95%CI 0.07, 0.73]), but not boys (SMD 0.23 [95%CI -0.24, 0.70]). DISCUSSION: By investigating child, parental and teaching interventions and including outcomes such as weight control and disordered eating behaviors, a trend toward a reduction in eating disorder risk factors was observed, particularly body image-related outomes in girls. Future directions include embedded disordered eating prevention materials within existing lifestyle interventions and inclusion of more diverse samples.

OBJETIVO: Las preocupaciones sobre la imagen corporal y los comportamientos de control de peso extremo se desarrollan con frecuencia en la infancia, lo que indica un grupo de edad importante para la implementación de enfoques de prevención universal-selectiva. Esta revisión sistemática tuvo como objetivo evaluar el efecto de las intervenciones de prevención universal-selectivas que abordan la alimentación disfuncional, los problemas de imagen corporal y/o los comportamientos extremos de control de peso en niños de 6 a 12 años de edad. MÉTODO: Se realizaron búsquedas en nueve bases de datos hasta abril 2021. Se incluyeron estudios que habían incluido una intervención de prevención universal-selectiva en niños de 6 a 12 años de edad e informaron resultados relacionados con la imagen corporal, la alimentación disfuncional o los comportamientos de control de peso. El examen se llevó a cabo de conformidad con los lineamientos PRISMA. RESULTADOS: Un total de 42 artículos que describieron 39 estudios incluidos en la revisión, con la mayoría (n = 24; 57%) de calidad neutra. Treinta estudios implementaron un programa selectivo universal específico de trastornos de la conducta alimentaria y nueve implementaron intervenciones de estilo de vida más contenido para abordar la alimentación disfuncional. El metanálisis (n = 16 estudios) reveló una mejoría en los resultados relacionados con la imagen corporal en todos los estudios (DME 0,26 [IC95%: 0,00 a 0,53]); con un alto nivel de heterogeneidad (Î2 = 91,1%; p < 0,01). El metanálisis según el sexo reveló una mejora general en los resultados relacionados con la imagen corporal para las niñas (DME 0,40 [IC95%: 0,07 a 0,73]), pero no para los niños (DME 0,23 [IC95%: −0,24 a 0,70]). DISCUSIÓN: Al investigar las intervenciones tanto de los padres como de la enseñanza e incluir resultados como el control de peso y las conductas alimentarias de riesgo, se observó una tendencia hacia una reducción de los factores de riesgo de los trastornos de la conducta alimentaria. En concreto, mejoras en las variables relacionadas con la imagen corporal, especialmente en las niñas. Las direcciones futuras incluyen materiales de prevención de la alimentación disfuncional incorporados dentro de las intervenciones de estilo de vida existentes y la inclusión de muestras más diversas. PALABRAS CLAVE: Niños, trastornos de la conducta alimentaria y de la alimentación, alimentación disfuncional, prevención, imagen corporal, revisión sistemática, metanálisis.

Metastatic Carcinoma of Prostate as a Mimicker of SAPHO Syndrome.

Paraneoplastic arthritides are a group of immune-mediated inflammatory arthropathies associated with occult or manifest malignancy. Musculoskeletal spread of an underlying malignancy may also mimic many rheumatologic conditions. Distinguishing primary rheumatologic condition from paraneoplastic arthritides versus direct musculoskeletal spread of malignancy can be challenging especially in individuals with prior history of cancer and new musculoskeletal complaints. SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is an uncommon, although under recognized autoimmune disorder. Two musculoskeletal manifestations, namely inflammatory osteitis and hyperostosis of anterior chest wall with or without dermatologic manifestations, constitute a unifying feature of SAPHO syndrome. However, diagnosis of SAPHO syndrome is one of exclusion, and a wide variety of disorders including infections, malignancy (chondrosarcoma/osteosarcoma/metastasis), metabolic bone disorders (Paget's disease), osteoarthritis, seronegative spondyloarthropathy (spA) and osteonecrosis form part of a broad differential diagnosis. We present the case of a man, aged 72 years, with signs and symptoms of SAPHO syndrome and skin findings. Detailed history, radiological imaging, dermatology appearance, and role of immunohistochemical markers, especially staining for NKX3.1 protein with a novel antibody, led to a diagnosis of metastatic prostate adenocarcinoma. To our knowledge, this is the first case of metastatic adenocarcinoma of the prostate manifesting as SAPHO syndrome and cutaneous metastasis.

Matrix Metalloproteinase Triple-Helical Peptide Inhibitors: Potential Cross-Reactivity with Caspase-11.

Triple-helical peptide inhibitors (THPIs) of matrix metalloproteinases (MMPs) have recently been demonstrated to be effective in a variety of animal models of disease, coincidental with knockout studies. However, passenger mutations have been described in MMP knockout mice that impact the activity of other proteins, including caspase-11. Thus, it is possible that the results observed with THPIs may be based on inhibition of caspase-11, not MMPs. The present study evaluated whether THPIs were cross-reactive with caspase-11. Two different THPIs were tested, one that is known to inhibit MMP-1 and MMP-8 (GlyΨ{PO2H-CH2}Ile-His-Lys-Gln THPI) and one that is selective for MMP-2 and MMP-9 (α1(V)GlyΨ{PO2H-CH2}Val [mep14,32,Flp15,33] THPI). No inhibition of caspase-11 was observed with GlyΨ{PO2H-CH2}Ile-His-Lys-Gln THPI, even at an inhibitor concentration of 5 µM, while 5 µM α1(V)GlyΨ{PO2H-CH2}Val [mep14,32,Flp15,33] THPI exhibited 40% inhibition of caspase-11. Further testing of GlyΨ{PO2H-CH2}Ile-His-Lys-Gln THPI revealed nM inhibition of MMP-2, MMP-9, and MMP-13. Thus, the effectiveness of GlyΨ{PO2H-CH2}Ile-His-Lys-Gln THPI observed in a sepsis animal model may not be due to caspase-11 inhibition, but may be due to broader MMP inhibition than previously thought.

Discharge from the acute hospital: trauma patients' perceptions of care.

Objective The involvement of orthopaedic trauma patients in the decision-making regarding discharge destination from the acute hospital and their perceptions of the care following discharge are poorly understood. The aim of the present study was to investigate orthopaedic trauma patient experiences of discharge from the acute hospital and transition back into the community. Methods The present qualitative study performed in-depth interviews, between October 2012 and November 2013, with patients aged 18-64 years with lower limb trauma. Thematic analysis was used to derive important themes. Results Ninety-four patients were interviewed, including 35 discharged to in-patient rehabilitation. Key themes that emerged include variable involvement in decision-making regarding discharge, lack of information and follow-up care on discharge and varying opinions regarding in-patient rehabilitation. Readiness for discharge from in-patient rehabilitation also differed widely among patients, with patients often reporting being ready for discharge before the planned discharge date and feeling frustration at the need to stay in in-patient care. There was also a difference in patients' perception of the factors leading to recovery, with patients discharged to rehabilitation more commonly reporting external factors, such as rehabilitation providers and physiotherapy. Conclusion The insights provided by the participants in the present study will help us improve our discharge practice, especially the need to address the concerns of inadequate information provision regarding discharge and the role of in-patient rehabilitation. What is known about the topic? There is no current literature describing trauma patient involvement in decision-making regarding discharge from the acute hospital and the perception of how this decision (and destination choice; e.g. home or in-patient rehabilitation) affects their outcome. What does this paper add? The present large qualitative study provides information on patients' opinion of discharge from the acute hospital following trauma and how this could be improved from their perception. Patients are especially concerned with the lack of information provided to them on discharge, their lack of involvement and understanding of the choices made with regard to their discharge and describe concerns regarding their follow-up care. There is also a feeling from the patients that they are ready to leave rehabilitation before their actual planned discharge date, a concept that needs further investigation. What are the implications for practitioners? The patient insights gained by the present study will lead to a change in discharge practice, including increased involvement of the patient in the decision-making in terms of discharge from both the acute and rehabilitation hospitals and a raised awareness of the need to provide written information and follow-up telephone calls to patients following discharge. Further research into many aspects of patient discharge from the acute hospital should be considered, including the use of rehabilitation prediction tools to ensure patient involvement in decision-making and a discharge and/or follow-up coordinator to ensure patients are aware of how to access information after discharge.

Climate change and thermal comfort in Hong Kong.

Thermal comfort is a major issue in cities and it is expected to change in the future due to the changing climate. The objective of this paper is to use the universal thermal comfort index (UTCI) to compare the outdoor thermal comfort in Hong Kong in the past (1971-2000) and the future (2046-2065 and 2081-2100). The future climate of Hong Kong was determined by the general circulation model (GCM) simulations of future climate scenarios (A1B and B1) established by the Intergovernmental Panel on Climate Change (IPCC). Three GCMs were chosen, GISS-ER, GFDL-CM2.1 and MRI-CGCM2.3.2, based on their performance in simulating past climate. Through a statistical downscaling procedure, the future climatic variables were transferred to the local scale. The UTCI is calculated by four predicted climate variables: air temperature, wind speed, relative humidity and solar radiation. After a normalisation procedure, future UTCI profiles for the urban area of Hong Kong were created. Comparing the past UTCI (calculated by observation data) and future UTCI, all three GCMs predicted that the future climate scenarios have a higher mode and a higher maximum value. There is a shift from 'No Thermal Stress' toward 'Moderate Heat Stress' and 'Strong Heat Stress' during the period 2046-2065, becoming more severe for the later period (2081-2100). Comparing the two scenarios, B1 exhibited similar projections in the two time periods whereas for A1B there was a significant difference, with both the mode and maximum increasing by 2°C from 2046-2065 to 2081-2100.

Patient perspectives of care in a regionalised trauma system: lessons from the Victorian State Trauma System.

OBJECTIVES: To explore injured patients' experiences of trauma care to identify areas for improvement in service delivery. DESIGN, SETTING AND PARTICIPANTS: Qualitative study using in-depth, semi-structured interviews, conducted from 1 April 2011 to 31 January 2012, with 120 trauma patients registered by the Victorian State Trauma Registry and the Victorian Orthopaedic Trauma Outcomes Registry and managed at the major adult trauma services (MTS) in Victoria. MAIN OUTCOME MEASURES: Emergent themes from patients' experiences of acute, rehabilitation and post-discharge care in the Victorian State Trauma System (VSTS). RESULTS: Patients perceived their acute hospital care as high quality, although 3s with communication and surgical management delays were common. Discharge from hospital was perceived as stressful, and many felt ill prepared for discharge. A consistent emerging theme was the sense of a lack of coordination of post-discharge care, and the absence of a consistent point of contact for ongoing management. Most patients' primary point of contact after discharge was outpatient clinics at the MTS, which were widely criticised because of substantial delays in receiving an appointment, prolonged waiting times, limited time with clinicians, lack of continuity of care and inability to see senior clinicians. CONCLUSIONS: This study highlights perceived 3s in the patient care pathway in the VSTS, especially those relating to communication, information provision and post-discharge care. Trauma patients perceived the need for a single point of contact for coordination of post-discharge care.

Does recall of preinjury disability change over time?

BACKGROUND: Pre-injury disability must be determined when assessing whether treatment programs return people to pre-injury status, however there is little empirical evidence to support recommendations that this be done as soon as possible after injury to prevent recall bias. OBJECTIVES: To determine disagreement between recall of pre-injury disability at different time points post-injury and bias towards under- or overestimating pre-injury disability. METHODS: Self-reported pre-injury global disability was assessed within days, 6 months and 12 months post-injury in patients admitted to two level 1 adult trauma centres. Kappa statistics and multiple logistic regression models identified predictors of disagreement between time-points. RESULTS: Pre-injury disability was measured at all time-points in 801 patients. Pre-injury disability at baseline was rated as none, mild, moderate, marked and severe in 80%, 12%, 5.1%, 1.9% and 1.0% respectively. Absolute agreement between baseline and 6 and 12 months respectively, was 79% and 80%. Corresponding kappa values (95% confidence intervals) were 0.33 (0.26-0.40) and 0.32 (0-25-0.38). Patients over 65 years or not completing high school were more likely to report less pre-injury disability at 6 and 12 months than at baseline with adjusted odds ratios (95% confidence intervals) for these groups being 8.24 (4.32-15.72) and 1.93 (1.03-3.64) respectively. CONCLUSIONS: There was little evidence of recall bias in an adult trauma population if self-reported global pre-injury disability was assessed 6 months post-injury. The recall of pre-injury disability up to 6 months post-injury can be used to determine return to pre-injury status, if assessment is not feasible shortly after injury.

Quantifying urban heat island intensity in Hong Kong SAR, China.

This paper addresses the methodological concerns in quantifying urban heat island (UHI) intensity in Hong Kong SAR, China. Although the urban heat island in Hong Kong has been widely investigated, there is no consensus on the most appropriate fixed point meteorological sites to be used to calculate heat island intensity. This study utilized the Local Climate Zones landscape classification system to classify 17 weather stations from the Hong Kong Observatory's extensive fixed point meteorological observation network. According to the classification results, the meteorological site located at the Hong Kong Observatory Headquarters is the representative urban weather station in Hong Kong, whereas sites located at Tsak Yue Wu and Ta Kwu Ling are appropriate rural or nonurbanized counterparts. These choices were validated and supported quantitatively through comparison of long-term annual and diurnal UHI intensities with rural stations used in previous studies. Results indicate that the rural stations used in previous studies are not representative, and thus, the past UHI intensities calculated for Hong Kong may have been underestimated.

Land surface and air temperature dynamics: The role of urban form and seasonality.

Due to the scarcity of air temperature (Ta) observations, urban heat studies often rely on satellite-derived Land Surface Temperature (LST) to characterise the near-surface thermal environment. However, there remains a lack of a quantitative understanding on how LST differs from Ta within urban areas and what are the controlling factors of their interaction. We use crowdsourced air temperature measurements in Sydney, Australia, combined with urban landscape data, Local Climate Zones (LCZ), high-resolution satellite imagery, and machine learning to explore the influence of urban form and fabric on the interaction between Ta and LST. Results show that LST and Ta have distinct spatiotemporal characteristics, and their relationship differs by season, ecological infrastructure, and building morphology. We found greater seasonal variability in LST compared to Ta, along with more pronounced intra-urban spatial variability in LST, particularly in warmer seasons. We also observed a greater temperature difference between LST and Ta in the built environment compared to the natural LCZs, especially during warm days. Natural LCZs (areas with mostly dense and scattered trees) showed stronger LST-Ta relationships compared to built areas. In particular, we observe that built areas with higher building density (where the heat vulnerability is likely more pronounced) show insignificant or negative relationships between LST- Ta in summer. Our results also indicate that surface cover, distance from the ocean, and seasonality significantly influence the distribution of hot and cold spots for LST and Ta. The spatial distribution for Ta hot spots does not always overlap with LST. We find that relying solely on LST as a direct proxy for the urban thermal environment is inappropriate, particularly in densely built-up areas and during warm seasons. These findings provide new perspectives on the relationship between surface and canopy temperatures and how these relate to urban form and fabric.

Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites.

Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have been studied extensively in P. falciparum and are hypothesized to have overlapping, but critical roles just prior to host cell entry. The zoonotic malaria parasite, P. knowlesi, has larger invasive merozoites and contains a smaller, less redundant, DBP and RBL repertoire than P. falciparum. One DBP (DBPα) and one RBL, normocyte binding protein Xa (NBPXa) are essential for invasion of human RBCs. Taking advantage of the unique biological features of P. knowlesi and iterative CRISPR-Cas9 genome editing, we determine the precise order of key invasion milestones and demonstrate distinct roles for each family. These distinct roles support a mechanism for phased commitment to invasion and can be targeted synergistically with invasion inhibitory antibodies.

UBA1 and DNMT3A mutations in VEXAS syndrome. A case report and literature review.

Vacuoles, E1 enzyme, X linked, autoinflammatory, somatic (VEXAS) syndrome is a recently described X-linked autoinflammatory condition associated with somatic mutation of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. It often coexists with myelodysplastic syndrome, which can occur due to DNA (cytosine-5)-methyltransferase 3A (DNMT3A) mutation. These patients, predominantly males, present after the fifth decade of life with unique systemic inflammatory clinical features and have haematological abnormalities and vacuolated precursor cells on bone marrow pathology. Here we describe a unique case of VEXAS syndrome in a patient harbouring DNMT3A gene mutation with coexisting UBA1 mutation with a review of literature.

Background climate modulates the impact of land cover on urban surface temperature.

Cities with different background climates experience different thermal environments. Many studies have investigated land cover effects on surface urban heat in individual cities. However, a quantitative understanding of how background climates modify the thermal impact of urban land covers remains elusive. Here, we characterise land cover and their impacts on land surface temperature (LST) for 54 highly populated cities using Landsat-8 imagery. Results show that urban surface characteristics and their thermal response are distinctly different across various climate regimes, with the largest difference for cities in arid climates. Cold cities show the largest seasonal variability, with the least seasonality in tropical and arid cities. In tropical, temperate, and cold climates, normalised difference built-up index (NDBI) is the strongest contributor to LST variability during warm months followed by normalised difference vegetation index (NDVI), while normalised difference bareness index (NDBaI) is the most important factor in arid climates. These findings provide a climate-sensitive basis for future land cover planning oriented at mitigating local surface warming.

A citizen centred urban network for weather and air quality in Australian schools.

High-quality, standardized urban canopy layer observations are a worldwide necessity for urban climate and air quality research and monitoring. The Schools Weather and Air Quality (SWAQ) network was developed and distributed across the Greater Sydney region with a view to establish a citizen-centred network for investigation of the intra-urban heterogeneity and inter-parameter dependency of all major urban climate and air quality metrics. The network comprises a matrix of eleven automatic weather stations, nested with a web of six automatic air quality stations, stretched across 2779 km2, with average spacing of 10.2 km. Six meteorological parameters and six air pollutants are recorded. The network has a focus on Sydney's western suburbs of rapid urbanization, but also extends to many eastern coastal sites where there are gaps in existing regulatory networks. Observations and metadata are available from September 2019 and undergo routine quality control, quality assurance and publication. Metadata, original datasets and quality-controlled datasets are open-source and available for extended academic and non-academic use.