Search

Management decisions often focus on the habitat selection of marked individuals without considering the contribution to demographic performance in selected habitats. Because habitat selection is not always adaptive, understanding the spatial relationship between habitat selection and demographic performance is critical to management decisions. Mapping both habitat selection and demographic performance for species of conservation concern can help guide population-scale conservation efforts. We demonstrate a quantitative approach to differentiate areas supporting selection and survival at large spatial extents. As a case study, we applied this approach to greater sage-grouse ( Centrocercus urophasianus ; hereafter, sage-grouse), an indicator species for sagebrush ecosystems. We evaluated both habitat selection and survival across multiple reproductive life stages (nesting, brood-rearing) in the Bi-State Distinct Population Segment, a genetically distinct and geographically isolated population of sage-grouse on the southwestern edge of the species' range. Our approach allowed us to identify both mismatches between selection and survival and trade-offs between reproductive life stages. These findings suggest resource demands vary across time, with predation risk being a dominant driver of habitat selection during nesting and early brood-rearing periods when chicks are smaller and flightless, whereas access to forage resources becomes more important during late brood rearing when resources become increasingly limited. Moving beyond identifying and managing habitat solely based on species occupancy or use by incorporating demographic measures allows managers to tailor actions to their specific goals; for example, protections of areas that support high selection and high survival and restoration actions focused on increasing survival in areas of high selection and low survival., (© 2024 Nevada Department of Wildlife, Great Basin Bird Observatory and The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Lumpy skin disease (LSD) poses a significant threat to animal welfare and leads to economic losses in affected countries. LSD outbreaks may also impact trade and regional relationships. South and Southeast Asia, with its dense livestock population and intricate trade networks, are susceptible to LSD outbreaks. Indonesia confirmed its first LSD cases in March 2022, leading to substantial livestock losses by August 2023. Australia, an important player in the global beef industry, faced trade disruptions due to LSD concerns raised by Indonesia and Malaysia, claims that were refuted by Australian authorities. The dispute highlights the need for good surveillance. EPIWATCH®, employing artificial intelligence, provides real-time outbreak signals, and spatial analysis can identify LSD hotspots, leading to timely interventions. This study uses data collected by the EPIWATCH® open-source disease surveillance system at the University of New South Wales in 2022 and 2023 and compares it for timeliness and completeness with data available on the World Animal Health Information System (WAHIS). We found more timely reports of LSD outbreaks in EPIWATCH® compared to WAHIS. In conclusion, open-source surveillance tools like EPIWATCH® can provide timely alerts of disease emergence, such as LSD outbreaks in South and Southeast Asia, which can supplement formal reporting systems., (© 2024 The Author(s). Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

Malaria is initiated as Plasmodium sporozoites are injected into the dermis when an infected mosquito probes on a vertebrate host for a blood meal. Factors in the mosquito saliva, such as AgTRIO, can alter the ability of Anopheles gambiae to transmit Plasmodium. We therefore used CRISPR-Cas9-mediated genome editing to generate AgTRIO knockout (KO) A. gambiae and examined the ability of these mosquitoes to probe on a vertebrate host. AgTRIO KO mosquitoes showed a diminished host probing capacity and required repetitive probing to locate a blood resource to complete a blood meal. This increased probing resulted in enhanced Plasmodium transmission to the vertebrate host. Our data demonstrate the importance of the A. gambiae saliva protein AgTRIO in probing and its influence on the ability of mosquitoes to transmit malaria., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Previous research suggests that curiosity is sometimes induced by novel information one has no relevant knowledge about, but it is sometimes induced by new information about something that one is familiar with and has prior knowledge about. However, the conditions under which novelty or familiarity triggers curiosity remain unclear. Using metacognitive confidence judgments as a proxy to quantify the amount of knowledge, this study evaluates the relationship between the amount of relevant knowledge and curiosity. We reviewed previous studies on the relationship between subjective curiosity and confidence and reanalyzed existing large-sample data. The findings indicate that the relationship between curiosity and confidence differs depending on the nature of the stimuli: epistemic versus perceptual. Regarding perceptual stimuli, curiosity is stronger when individuals have lower confidence levels. By contrast, for epistemic stimuli, curiosity is stronger when individuals have higher confidence levels. These results suggest that curiosity triggered by perceptual stimuli is based on perceived novelty, whereas that triggered by epistemic stimuli is based on familiarity with prior knowledge., (© 2024 The Author(s). Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society (CSS).)

Introduction: Pharmacists are often not recognised as a core part of palliative care teams, despite their ideal placement to assist with the burden of medication management., Objective: This study explored the role of pharmacists working in the rural palliative care team, in the home-based setting., Design: Health care professionals working with palliative care patients in rural South Australia participated in semi-structured interviews. Data were analysed using thematic analysis., Findings: Data from 20 participants identified 10 themes. Theme 1: This model of care gives patients a choice. Theme 2: The pharmacist is a trusted source of support and information. Theme 3: Patient, carer and family distress is reduced. Theme 4: Enables patients to stay at home by improving medication knowledge and decreasing burden; 4.1-Patient, carer and family's understanding about medication management is improved, 4.2-Patient, carer and family travel is decreased, 4.3-Burden associated with getting to the doctor is decreased. Theme 5: Communication between all parties is enhanced; 5.1-Enhanced communication between the patient and health care team, 5.2-Enhanced communication within the health care team. Theme 6: Patient, carer and family burden of coordinating prescriptions and medications is reduced. Theme 7: Benefits health care professionals by improving medication knowledge, reducing workload and stress; 7.1-Understanding about medications and their management is improved, 7.2-Workload is reduced, 7.3-Work-related stress is reduced. Theme 8: The disparity of care between rural and urban patients is reduced. Theme 9: Helps to address rural workforce shortages. Theme 10: Challenges of this model of care; 10.1-A need for greater pharmacist capacity to meet demand, 10.2-A need for increased and sustained funding for the pharmacist role, 10.3-Large amount of travel to get to patients., Conclusion: Rural health care professionals are supportive of pharmacists working as part of the palliative care team in home-based settings and identified many benefits of this model of care., (© 2024 The Authors. Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

The stereoselective synthesis of both enantiomers of N -protected 1,2-diazetidine-3-carboxylic acid (aAze) from homochiral glycidol is described. Orthogonal protection of this novel cyclic α-hydrazino acid allows for selective functionalisation at either N γ or N δ . This novel peptidomimetic building block was incorporated into the pseudotripeptides Gly-γaAze-Ala and Gly-δaAze-Ala.

Background: Following increases in deaths due to alcohol during the COVID-19 pandemic, there have been renewed calls to increase resources in alcohol screening and brief intervention (SBI). Research has shown that community pharmacy could be a promising setting for SBI. This review aimed to investigate the barriers and facilitators to SBI delivery in community pharmacy to inform its further development., Methods: A systematic search of four databases (MEDLINE, EMBASE, CINAHL, and PsycINFO) was conducted in October 2021 to identify relevant published qualitative or mixed-method studies. Relevant qualitative data were extracted from the included studies and a framework synthesis was performed using the Capability-Opportunity-Motivation-Behaviour (COM-B) model., Results: Two thousand two hundred and ten articles were screened and nine studies were included in the review (seven in the United Kingdom and two in Australia). Identified barriers and facilitators to delivering SBI corresponded to all components of the COM-B model. Facilitators included non-confrontational communication skills, aligning SBI with existing pharmacy services and pharmacist role legitimacy. Barriers included multiple demands on staff time, a lack of staff experience with screening tools, and staff concerns of causing offence. Using the Behaviour Change Wheel (BCW), we propose five elements of a pharmacy SBI to address identified barriers., Conclusions: Research into SBI in community pharmacy is limited in comparison to other healthcare settings and this review provides an understanding of the barriers and facilitators to the delivery of SBI in community pharmacy from a behavioural perspective. Through the use of COM-B and BCW, our findings could inform the development of future pharmacy-based SBI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Introduction: This feasibility study aims to develop and test a new model of practice in Australia using digital technologies to enable pharmacists to monitor early signs and symptoms of medicine-induced harms in residential aged care., Methods and Analysis: Thirty residents will be recruited from an aged care facility in South Australia. The study will be conducted in two phases. In phase I, the study team will work with aged care software providers and developers of digital technologies (a wearable activity tracker and a sleep tracking sensor) to gather physical activity and sleep data, as well as medication and clinical data from the electronic medication management system and aged care clinical software. Data will be centralised into a cloud-based monitoring platform (TeleClinical Care (TCC)). The TCC will be used to create dashboards that will include longitudinal visualisations of changes in residents' health, function and medicine use over time. In phase II, the on-site pharmacist will use the centralised TCC platform to monitor each resident's medicine, clinical, physical activity and sleep data to identify signs of medicine-induced harms over a 12-week period.A mixed methods process evaluation applying the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) evaluation framework will be used to assess the feasibility of the service. Outcome measures include service reach, changes in resident symptom scores (measured using the Edmonton Symptom Assessment System), number of medication adverse events detected, changes in physical activity and sleep, number of pharmacist recommendations provided, cost analysis and proportion of all pharmacists' recommendations implemented at 4-week, 8-week and 12-week postbaseline period., Ethics and Dissemination: Ethical approval has been obtained from the University of South Australia's Human Research Ethics Committee (205098). Findings will be disseminated through published manuscripts, conference presentations and reporting to the study funder., Trial Registration Number: ACTRN12623000506695., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The paper examines the health system's response to COVID-19 in Sierra Leone. It aims to explore how the pandemic affected service delivery, health workers, patient access to services, leadership, and governance. It also examines to what extent the legacy of the 2013-16 Ebola outbreak influenced the COVID-19 response and public perception. Using the WHO Health System Building Blocks Framework, we conducted a qualitative study in Sierra Leone where semi-structured interviews were conducted with health workers, policymakers, and patients between Oct-Dec 2020. We applied thematic analysis using both deductive and inductive approaches. Twelve themes emerged from the analysis: nine on the WHO building blocks, two on patients' experiences, and one on Ebola. We found that routine services were impacted by enhanced infection prevention control measures. Health workers faced additional responsibilities and training needs. Communication and decision-making within facilities were reported to be coordinated and effective, although updates cascading from the national level to facilities were lacking. In contrast with previous health emergencies which were heavily influenced by international organisations, we found that the COVID-19 response was led by the national leadership. Experiences of Ebola resulted in less fear of COVID-19 and a greater understanding of public health measures. However, these measures also negatively affected patients' livelihoods and their willingness to visit facilities. We conclude, it is important to address existing challenges in the health system such as resources that affect the capacity of health systems to respond to emergencies. Prioritising the well-being of health workers and the continued provision of essential routine health services is important. The socio-economic impact of public health measures on the population needs to be considered before measures are implemented., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Repurposing is one of the key opportunities to address the unmet rare diseases therapeutic need. Based on cases of drug repurposing in small population conditions, and previous work in drug repurposing, we analyzed the most important lessons learned, such as the sharing of clinical observations, reaching out to regulatory scientific advice at an early stage, and public-private collaboration. In addition, current upcoming trends in the field of drug repurposing in rare diseases were analyzed, including the role these trends could play in the rare diseases' ecosystem. Specifically, we cover the opportunities of innovation platforms, the use of real-world data, the use of artificial intelligence, regulatory initiatives in repurposing, and patient engagement throughout the repurposing project. The outcomes from these emerging activities will help progress the field of drug repurposing for the benefit of patients, public health and medicines development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Jonker, O’Connor, Cavaller-Bellaubi, Fetro, Gogou, ’T Hoen, de Kort, Stone, Valentine and Pasmooij.)

Importance: When a female mosquito takes a blood meal from a mammalian host, components of the blood meal can affect mosquito fitness and indirectly influence pathogen infectivity. We identified a pathway involving an Anopheles gambiae adiponectin receptor, which, triggered by adiponectin from an incoming blood meal, decreases Plasmodium infection in the mosquito. Activation of this pathway negatively regulates lipophorin expression, an important lipid transporter that both enhances egg development and Plasmodium infection. This is an unrecognized cross-phyla interaction between a mosquito and its vertebrate host. These processes are critical to understanding the complex life cycle of mosquitoes and Plasmodium following a blood meal and may be applicable to other hematophagous arthropods and vector-borne infectious agents., Competing Interests: The authors declare no conflict of interest.

Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting., Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey., Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD., Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting., Competing Interests: Conflict of interest: A.J. Simpson has received funding to his institution from Boehringer Ingelheim (BI) to undertake an educational meeting. A. West has received support from BI for speaking at or chairing educational events, and attendance and travel to educational meetings; and is part of an advisory board for BI and Avalyn Pharmaceuticals. A. John has received funding from BI to attend an educational event. A.M. Wilson has received grants from Aseptika, Brainomix and BASF, has received speakers’ fees from BI, has received support for attending meetings by Chiesi, and has institutional interests with Celgene Corporation, GSK and Insmed Inc. A. Crawshaw has received speakers’ fees from BI and AstraZeneca (AZ). A.U. Wells has undertaken advisory board activity and consultant work for BI, Roche and Veracyte. C.C. Huntley has received an honorarium for educational content from BI and sponsorship for conference attendance. D. Dosanjh has received a speaker's fee from BI, meeting attendance costs from AZ and is part of the advisory board for AZ, Gilead, BI and Synairgen. E. Renzoni has received institutional funding, honoraria for educational events and funding for conference attendance from BI, and is member of the advisory board for BI and Roche. F. Chua has received consulting fees, honoraria, support for conference attendance and is an advisory board member for BI. G. Saini has received institutional payment for educational presentation from BI. G. Dixon, H. Stone, L.M. Nicol and I.A. Forrest have received support for educational event attendance from BI. J.C.L. Rodrigues has received grant funding from NIHR, consulting fees from NHSx and HeartFlow, honoraria from Sanofi, Aidence and 4-C Research market research, meeting attendance support from Aidence and HeartFlow, leadership role in Heart and Lung Imaging LTD (HLH), stock in Radnet and shares in HLH. K. Tsaneva-Atanasova has financial support from EPSRC grant. M. Naqvi has received a grant from NHS Digital, honoraria from BI, AZ and Roche, support for meeting attendance from BI and advisory board membership for BI, and is ILD Pharmacist Network Chair and ILD-IN Co-chair. M.G. Jones has received grants from Royal Society, BI, NC3Rs, MRC, AAIR Charity and the British Lung Foundation. P.M. George has received an institutional grant from BI, honoraria from BI, Roche, Teva, Cipla and Brainomix, meeting attendance support from BI and Roche and has stock in Brainomix. P. Molyneaux has grant funding from AZ, consulting fees from Roche, BI, AZ, Trevi and Qureight, and honoraria from BI and Roche; and is an associate editor of this journal. P. Rivera-Ortega has received grant funding from MRC, institutional grant funding from BI, Roche, CSL Behring, Fibrogen, Vicore Pharma AB, Gilead Sciences and Galecto, consulting fees from BI and Roche, honoraria from BI, Roche and Respiratory Effectiveness Group (REG), support for meeting attendance from BI and REG, is a chair of the REG and member of the Global Writing Group Committee for REMAP-ILD. R.K. Coker has received honoraria from BI. S. Agnew has received honoraria from BI, support for meeting attendance from BI and is member of the BTS ILD registry advisory board. S.L. Barratt has received consulting fees and honoraria from BI. S. Hart has received research grant from BI, consulting fees from Trevi Therapeutics, honoraria and support for meeting attendance from BI and Chiesi, was Chair of the BTS Standard of Care Committee 2019–2022, and is a Trustee of Action for Pulmonary Fibrosis and an associate editor of this journal. S. Barth received honoraria from BI for educational meeting facilitating. T. Garfoot received support to attend the ILD IN annual conference. T. Gatheral has received speakers’ fees from BI. Conflict of interest: The remaining authors have no competing interests., (Copyright ©The authors 2024.)

Antibiotics used systemically to treat infections may have off-target effects on the gut microbiome, potentially resulting in the emergence of drug-resistant bacteria or selection of pathogenic species. These organisms may present a risk to the host and spread to the environment with a risk of transmission in the community. To investigate the risk of emergent antibiotic resistance in the gut microbiome following systemic treatment with antibiotics, this metagenomic analysis project used next-generation sequencing, a custom-built metagenomics pipeline, and differential abundance analysis to study the effect of antibiotics (ampicillin, ciprofloxacin, and fosfomycin) in monotherapy and different combinations at high and low doses, to determine the effect on resistome and taxonomic composition in the gut of Balb/c mice. The results showed that low-dose monotherapy treatments showed little change in microbiome composition but did show an increase in expression of many antibiotic-resistant genes (ARGs) posttreatment. Dual combination treatments allowed the emergence of some conditionally pathogenic bacteria and some increase in the abundance of ARGs despite a general decrease in microbiota diversity. Triple combination treatment was the most successful in inhibiting emergence of relevant opportunistic pathogens and completely suppressed all ARGs after 72 h of treatment. The relative abundances of mobile genetic elements that can enhance transmission of antibiotic resistance either decreased or remained the same for combination therapy while increasing for low-dose monotherapy. Combination therapy prevented the emergence of ARGs and decreased bacterial diversity, while low-dose monotherapy treatment increased ARGs and did not greatly change bacterial diversity.

Objectives: This study aims to create an enhanced EPIRISK tool in order to correctly predict COVID-19 severity in various countries. The original EPIRISK tool was developed in 2018 to predict the epidemic risk and prioritise response. The tool was validated against nine historical outbreaks prior to 2020. However, it rated many high-income countries that had poor performance during the COVID-19 pandemic as having lower epidemic risk., Study Design: This study was designed to modify EPIRISK by reparameterizing risk factors and validate the enhanced tool against different outbreaks, including COVID-19., Methods: We identified three factors that could be indicators of poor performance witnessed in some high-income countries: leadership, culture and universal health coverage. By adding these parameters to EPIRISK, we created a series of models for the calibration and validation. These were tested against non-COVID outbreaks in nine countries and COVID-19 outbreaks in seven countries to identify the best-fit model. The COVID-19 severity was determined by the global incidence and mortality, which were equally divided into four levels., Results: The enhanced EPIRISK tool has 17 parameters, including seven disease-related and 10 country-related factors, with an algorithm developed for risk level classification. It correctly predicted the risk levels of COVID-19 for all seven countries and all nine historical outbreaks., Conclusions: The enhanced EPIRSIK is a multifactorial tool that can be widely used in global infectious disease outbreaks for rapid epidemic risk analysis, assisting first responders, government and public health professionals with early epidemic preparedness and prioritising response to infectious disease outbreaks., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite the benefits of eating insects (entomophagy), Western society is often inclined to reject this practice based on initial reactions of disgust. It is suggested there is potential to overcome this attitude through increasing interest and gaining knowledge of the benefits. One way to accomplish this is through an adapted utility-value intervention, traditionally applied in education research, to increase interest and perceived value in a topic. Across two studies (each with a one-month follow-up) participants researched and wrote an essay designed to increase interest and value in entomophagy or a control essay. Participants then completed a rating task assessing their willingness to try insect and familiar foods, along with other key attributes (e.g., sustainability). The utility-value intervention increased willingness to try insect foods as well as other key attributes compared to a non-insect control essay (Study 1). Unexpectedly, we also found a potentially similar (but smaller) effect of researching an insect-based recipe (Study 2) on willingness to try. The effects found in both studies were consistent at follow-up. These findings indicate the usefulness of utility-value interventions in encouraging entomophagy but also suggest that exposure to information about insect food, although less effective than a utility-value intervention, may also be sufficient., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Healthcare workers (HCWs) are at risk of SARS-CoV-2 infections due to occupational exposure. The use of airborne personal protective equipment (PPE) significantly reduces this risk. In June 2021, an epidemic of the Delta variant began in New South Wales (NSW), Australia. Concurrent PPE guidelines, set by the Clinical Excellence Commission (CEC), restricted the use of respirators., Objective: To understand the relationship of PPE guidelines with workplace-acquired HCW SARS-CoV-2 infections in different clinical settings and to examine the relationship between rates of community transmission and workplace-acquired HCW infections during the Delta outbreak in NSW., Methods: Total SARS-CoV-2 HCW infections between 13 June and 30 October 2021 (first four months of the Delta wave) were estimated from the government COVID-19 surveillance reports and compared with the surveillance reports of community transmission. In the absence of a detailed reporting of HCW infections, open-source data including news articles, media releases, and epidemiological surveillance reports were also collected. Data were extracted on HCW cases of SARS-CoV-2 from four hospitals, including the number of HCW cases (per NSW Health definition), clinical setting, PPE guidelines, and evidence of increasing local transmission., Results: SARS-CoV-2 infections in HCW identified as workplace-acquired infections ( n  = 177) and those without a known transmission source ( n  = 532) increased during the period of increasing community transmission ( n  = 75,014) in NSW. Four hospital COVID-19 clusters affecting 20 HCWs were identified between June and October 2021. HCW clusters occurred in general wards where staff were recommended to wear surgical masks. No workplace-acquired HCW infections were reported in these hospitals from critical care wards, where respirators were recommended during the same outbreak weeks., Conclusions: Differences in PPE policy across different wards may leave healthcare staff at risk of SARS-CoV-2 infection. During periods of high community transmission, respirators should be provided to protect hospital staff. Formal reporting of HCW infections should occur., Competing Interests: All authors are employed by the Kirby Institute of the University of New South Wales. The authors declare that they have no conflicts of interest., (Copyright © 2023 Danielle Hutchinson et al.)

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons. A subset of enhancer traps was expressed in CNS neurons known to produce and secrete insulin, an essential regulator of growth, development, and metabolism. Fly lines described here were generated and characterized through studies by students and teachers in an international network of genetics classes at public, independent high schools, and universities serving a diversity of students, including those underrepresented in science. Thus, a unique partnership between secondary schools and university-based programs has produced and characterized novel resources in Drosophila, establishing instructional paradigms devoted to unscripted experimental science., Competing Interests: Conflicts of interest statement The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Background: On February 25, 2022, Russian forces took control of the Chernobyl power plant after continuous fighting within the Chernobyl exclusion zone. Continual events occurred in the month of March, which raised the risk of potential contamination of previously uncontaminated areas and the potential for impacts on human and environmental health. The disruption of war has caused interruptions to normal preventive activities, and radiation monitoring sensors have been nonfunctional. Open-source intelligence can be informative when formal reporting and data are unavailable., Objective: This paper aimed to demonstrate the value of open-source intelligence in Ukraine to identify signals of potential radiological events of health significance during the Ukrainian conflict., Methods: Data were collected from search terminology for radiobiological events and acute radiation syndrome detection between February 1 and March 20, 2022, using 2 open-source intelligence (OSINT) systems, EPIWATCH and Epitweetr., Results: Both EPIWATCH and Epitweetr identified signals of potential radiobiological events throughout Ukraine, particularly on March 4 in Kyiv, Bucha, and Chernobyl., Conclusions: Open-source data can provide valuable intelligence and early warning about potential radiation hazards in conditions of war, where formal reporting and mitigation may be lacking, to enable timely emergency and public health responses., (©Haley Stone, David Heslop, Samsung Lim, Ines Sarmiento, Mohana Kunasekaran, C Raina MacIntyre. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 28.06.2023.)

Background: There is an increased risk of SARS-CoV-2 transmission during mass gatherings and a risk of asymptomatic infection. We aimed to estimate the use of masks during Black Lives Matter (BLM) protests and whether these protests increased the risk of COVID-19. Two reviewers screened 496 protest images for mask use, with high inter-rater reliability. Protest intensity, use of tear gas, government control measures, and testing rates were estimated in 12 cities. A correlation analysis was conducted to assess the potential effect of mask use and other measures, adjusting for testing rates, on COVID-19 epidemiology 4 weeks (two incubation periods) post-protests. Mask use ranged from 69 to 96% across protests. There was no increase in the incidence of COVID-19 post-protest in 11 cities. After adjusting for testing rates, only Miami, which involved use of tear gas and had high protest intensity, showed a clear increase in COVID-19 after one incubation period post-protest. No significant correlation was found between incidence and protest factors. Our study showed that protests in most cities studied did not increase COVID-19 incidence in 2020, and a high level of mask use was seen. The absence of an epidemic surge within two incubation periods of a protest is indicative that the protests did not have a major influence on epidemic activity, except in Miami. With the globally circulating highly transmissible Alpha, Delta, and Omicron variants, layered interventions such as mandated mask use, physical distancing, testing, and vaccination should be applied for mass gatherings in the future., (© 2022. The Author(s).)

Introduction: Although fosfomycin is currently approved for treating urinary tract infections, it is increasingly being used as salvage therapy for various infectious syndromes outside the urinary tract. This systematic review evaluates clinical and microbiological cure rates in patients with bacterial infections not restricted to the urinary tract where fosfomycin was used off-label., Materials and Methods: Articles from two databases (Pubmed and Scopus) were reviewed. The dosage, route, and duration of fosfomycin therapy along with the details of adjunctive antimicrobial agents were noted. The final outcomes captured were clinical or microbiological cures., Results: A total of 649 articles, not including duplicates, were selected for the title and abstract screening. After title and abstract screening, 102 articles were kept for full-text screening. Of the 102 articles, 23 studies (n=1227 patients) were kept in the final analysis. Of the 1227 patients, 301 (25%) received fosfomycin as monotherapy, and the remaining 926 75%) received fosfomycin in combination with at least one other antimicrobial agent. Most of the patients received intravenous fosfomycin (n=1046, 85%). Staphylococcus spp and Enterobacteriaceae were the most common organisms. The pooled clinical and microbiological cure rates were 75% and 84%, respectively., Conclusion: Fosfomycin has moderate clinical success in patients with non-urinary tract infections, especially when used with other antimicrobials. Due to the paucity of randomized controlled trials, fosfomycin's use should be limited to situations where no alternatives are supported by better clinical evidence., Competing Interests: Conflict of interest Nothing to declare.

The use of artificial intelligence (AI) to generate automated early warnings in epidemic surveillance by harnessing vast open-source data with minimal human intervention has the potential to be both revolutionary and highly sustainable. AI can overcome the challenges faced by weak health systems by detecting epidemic signals much earlier than traditional surveillance. AI-based digital surveillance is an adjunct to-not a replacement of-traditional surveillance and can trigger early investigation, diagnostics and responses at the regional level. This narrative review focuses on the role of AI in epidemic surveillance and summarises several current epidemic intelligence systems including ProMED-mail, HealthMap, Epidemic Intelligence from Open Sources, BlueDot, Metabiota, the Global Biosurveillance Portal, Epitweetr and EPIWATCH. Not all of these systems are AI-based, and some are only accessible to paid users. Most systems have large volumes of unfiltered data; only a few can sort and filter data to provide users with curated intelligence. However, uptake of these systems by public health authorities, who have been slower to embrace AI than their clinical counterparts, is low. The widespread adoption of digital open-source surveillance and AI technology is needed for the prevention of serious epidemics.

Objective: Employ the hollow fiber infection model (HFIM) to study sequential antibiotic administration (ampicillin, ciprofloxacin and fosfomycin) using human pharmacokinetic profiles to measure changes in the rate of antibiotic resistance development and compare this to simultaneous combination therapy with the same antibiotic combinations., Methods: Escherichia coli CFT073, a clinical uropathogenic strain, was exposed individually to clinically relevant pharmacokinetic concentrations of ampicillin on day 1, ciprofloxacin on day 2 and fosfomycin on day 3. This sequence was continued for 10 days in the HFIM. Bacterial samples were collected at different time points to enumerate total and resistant bacterial populations. The results were compared with the simultaneous combination therapy previously studied., Results: Sequential antibiotic treatment (ampicillin-ciprofloxacin-fosfomycin sequence) resulted in the early emergence of single and multi-antibiotic-resistant subpopulations, while the simultaneous treatment regimen significantly delayed or prevented the emergence of resistant subpopulations., Conclusion: Sequential administration of these antibiotic monotherapies did not significantly delay the emergence of resistant subpopulations compared to simultaneous treatment with combinations of the same antibiotics. Further studies are warranted to evaluate different sequences of the same antibiotics in delaying emergent resistance.

Cardiovascular disease has become a growing global and public health concern among non-communicable diseases (NCDs). The purpose of the study was to focus on the increasing prevalence of the risk factors of cardiovascular diseases (CVD), irrespective of age and gender, and its effect on public health worldwide. A literature search was done in the electronic database: Medline, PubMed, Web of Science, Google Scholar, and the World Health Organization (WHO) website, based on recent research and the prevalence of the risk factors of cardiovascular diseases. Moreover, a manual search for published work has also been done. The coronary heart disease studies were not restricted during the search by sample size because of the limited number of studies in selected countries. The study reviews the potential risk factors responsible for coronary heart disease globally. Smoking was highly prevalent among the United States and Pakistani populations, but hypertension and diabetes were more common in Tanzania and the United Kingdom. However, dyslipidaemia and obesity were common in almost all the selected countries. CVD risk factors are highly prevalent in some countries, varying socioeconomic, gender, and educational levels. Furthermore, there has always been a need for awareness in the public and educational programs for a healthy lifestyle, intake of nutritional food, and increased physical activity to improve health conditions and reduce the risk of cardiovascular diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Adhikary et al.)

Background: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD)., Aim: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab., Results: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure., Conclusion: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Originating as a cluster of unexplained cases of pneumonia in Wuhan, China, a novel coronavirus disease, officially named as COVID-19 by WHO, has now reached a pandemic level. In the wake of this global health crisis, stringent public health measures were implemented to curtail the spread of COVID-19. At a local level, the University Hospitals of North Midlands National Health Service Trust suspended all elective and outpatient activity, primarily to address the current potential implications of the COVID-19 outbreak. Within respiratory physiology, all but urgent and emergency work was suspended., Methods: In June 2020, the service commenced its restoration/recovery plan, which was based on national and international guidelines to ensure safe practice for patients and staff alike. The plan was a roadmap developed to upscale the respiratory physiology service to deliver urgent and routine care and to assist the service to undertake the essential task of managing the patient backlog as a consequence of the interruption of service. Patient concerns and anxieties due to the pandemic was a key aspect of the restoration/recovery plan. The service developed numerous initiatives along with a questionnaire to assess patient experience following attendance for investigations or assessment., Results: The questionnaire confirmed that the initiatives put in place as part of the restoration/recovery plan achieve high levels of satisfaction in terms of communication, interaction within the service, professionalism and importantly patient safety., Conclusion: COVID-19 had a significant impact on routine clinical care and out-patient activity. This brought about significant change in service delivery that required a strict regimen to ensure COVID-19 free status and minimise cross-contamination of service users. The systems and processes introduced demonstrated positive responses and confirmed the objective of patient safety, which translated to the service users., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Aged-care facilities (ACF's) provide unique challenges when implementing infection control methods for respiratory outbreaks such as COVID-19. Research on this highly vulnerable setting is lacking and there was no national reporting data of COVID-19 cases in ACFs in Australia early in the pandemic. We aimed to estimate the burden of aged-care worker (ACW) infections and outbreaks of COVID-19 in Australian aged-care., Methods: A line list of publicly available aged-care related COVID-19 reported cases from January 25 to June 10, 2020 was created and was enhanced by matching data extracted from media reports of aged-care related COVID-19 relevant outbreaks and reports. Rate ratios (RR) were used to predict risk of infection in ACW and aged-care residents, and were calculated independently, by comparing overall cases to ACW and aged-care residents' cases., Results: A total of 14 ACFs with COVID-19 cases were recorded by June 2020 nationwide, with a high case fatality rate (CFR) of 50% (n = 34) and 100% (n = 3) seen in two ACFs. Analysis on the resident risk found that the COVID-19 risk is 1.27 times higher (unadjusted RR 1.27 95% confidence interval [CI] 1.00 to1.61; P = 0.047) as compared with the risk of infection in the general population. In over 60% of cases identified in ACFs, the source of infection in the index case was unknown. A total of 28 deaths associated within ACFs were reported, accounting for 54.9% of total deaths in New South Wales and 26.9% of total deaths in Australia., Conclusions: This high-risk population requires additional prevention and control measures, such as routine testing of all staff and patients regardless of symptoms. Prompt isolation and quarantine as soon as a case is confirmed within a facility is essential., (© 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Entomophagy - the consumption of insects - is often rejected by Western society despite its benefits over traditional animal-based proteins. While several factors have been identified as potential predictors of people's willingness to try insect foods, this study introduced an under-explored factor: curiosity, which is a powerful motivator of behaviour that can overcome negative emotions and motivate us to seek new experiences. In two experiments (Ns = 240 and 248), participants (all UK residents, 99.6% British citizens) rated a number of food dishes, half of which contained insects, on a number of factors including curiosity and willingness to try the dish. Across both studies, curiosity predicted willingness to try both insect and non-insect foods above and beyond other factors. Furthermore, we unexpectedly (but consistently) observed a "curiosity-boosting effect" in which curiosity positively interacted with other predictors, increasing their effect on willingness to try insect foods, but not familiar foods. These findings suggest that curiosity promotes the willingness to try insect food in two different manners: A direct effect (above and beyond other factors) and a boosting effect., (Copyright © 2021. Published by Elsevier Ltd.)

Neutralizing antibodies (NAbs) are effective in treating COVID-19, but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment during prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. Real-time imaging revealed that the virus spread sequentially from the nasal cavity to the lungs in mice and thereafter systemically to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days. In addition to direct neutralization, depletion studies indicated that Fc effector interactions of NAbs with monocytes, neutrophils, and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimal in vivo efficacy against SARS-CoV-2., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We could visualize virus spread sequentially from the nasal cavity to the lungs and thereafter systemically to various organs including the brain, which culminated in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days. In addition to direct Fab-mediated neutralization, Fc effector interactions of NAbs with monocytes, neutrophils and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimal in vivo efficacy against SARS-CoV-2.

Choral singing has become a major risk during the coronavirus disease 2019 (COVID-19) pandemic due to high infection rates. Our visualization and velocimetry results reveal that the majority of droplets expelled during singing follow the ambient airflow pattern. These results point toward the possibility of COVID-19 spread by small airborne droplets during singing., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The assumption that functional magnetic resonance imaging (fMRI) noise has constant volatility has recently been challenged by studies examining heteroscedasticity arising from head motion and physiological noise. The present study builds on this work using latest methods from the field of financial mathematics to model fMRI noise volatility., Methods: Multi-echo phantom and human fMRI scans were used and realised volatility was estimated. The Hurst parameter H ∈ (0,1), which governs the roughness/irregularity of realised volatility time series, was estimated. Calibration of H was performed pathwise, using well-established neural network calibration tools., Results: In all experiments the volatility calibrated to values within the rough case, H < 0.5, and on average fMRI noise was very rough with 0.03 < H < 0.05. Some edge effects were also observed, whereby H was larger near the edges of the phantoms., Discussion: The findings suggest that fMRI volatility is not only non-constant, but also substantially more irregular than a standard Brownian motion. Thus, further research is needed to examine the impact such pronounced oscillations in the volatility of fMRI noise have on data analyses., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: There are no publicly available national data on healthcare worker infections in Australia. It has been documented in many countries that healthcare workers (HCW) are at increased occupational risk of COVID-19. We aimed to estimate the burden of COVID-19 on Australia HCW and the health system by obtaining and organizing data on HCW infections, analyzing national HCW cases in regards to occupational risk and analyzing healthcare outbreak., Methods: We searched government reports and websites and media reports to create a comprehensive line listing of Australian HCW infections and nosocomial outbreaks between January 25 th and July 8 th , 2020. A line list of HCW related COVID-19 reported cases was created and enhanced by matching data extracted from media reports of healthcare related COVID-19 relevant outbreaks and reports, using matching criteria. Rates of infections and odds ratios (ORs) for HCW were calculated per state, by comparing overall cases to HCW cases. To investigate the sources of infection amongst HCW, transmission data were collated and graphed to show distribution of sources., Results: We identified 36 hospital outbreaks or HCW infection reports between January 25 th and July 8 th , 2020. According to our estimates, at least 536 HCW in Australia had been infected with COVID-19, comprising 6.03% of all reported infections. The rate of HCW infection was 90/100000 and of community infection 34/100,000. HCW were 2.69 times more likely to contract COVID-19 (95% CI 2.48 to 2.93; P < 0.001). The timing of hospital outbreaks did not always correspond to community peaks. Where data were available, a total of 131 HCW across 21 outbreaks led to 1656 HCW being furloughed for quarantine. In one outbreak, one hospital was closed and 1200 HCW quarantined., Conclusion: The study shows that HCW were at nearly 3 times the risk of infection. Of concern, this nearly tripling of risk occurred during a period of low community prevalence suggesting failures at multiple hazard levels including PPE policies within the work environment. Even in a country with relatively good control of COVID-19, HCW are at greater risk of infection than the general community and nosocomial outbreaks can have substantial effects on workforce capacity by the quarantine of numerous HCW during an outbreak. The occurrence of hospital outbreaks even when community incidence was low highlights the high risk setting that hospitals present. Australia faced a resurgence of COVID-19 after the study period, with multiple hospital outbreaks. We recommend formal reporting of HCW infections, testing protocols for nosocomial outbreaks, cohorting of workforce to minimize the impact, and improved PPE guidelines to provide precautionary and optimal protection for HCW., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established. Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population. Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death. Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P  = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71). Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.

We present the case of an infant referred to our NICU born at 39 weeks' gestation with persistent hypoglycemia with elevated insulin levels (HI) requiring diazoxide to maintain normoglycemia. Additionally, polycystic kidney disease (PKD) was detected by ultrasound. Molecular genetic testing revealed pathogenic variants in the PMM2 gene, i.e., a variant in the promoter region and a missense variant in the coding region. The precoding variant was recently described in 11 European families with similar phenotypes, either in a homozygous state or as compound heterozygous with a pathogenic coding variant. In neonates with HI associated with PKD, this rare recessive disorder should be considered., Competing Interests: The authors have no conflicts of interest − personal, professional, or financial − to disclose., (Copyright © 2020 by S. Karger AG, Basel.)

Objective: To report our cumulative experience from a dedicated iron deficiency anaemia (IDA) clinic over the last 15 years-with particular emphasis on referral rate, uptake of investigation, impact on endoscopy services, diagnostic yield of gastrointestinal (GI) investigation and the issue of recurrent IDA., Method: A series of analyses of a register of 2808 referrals to the Poole IDA clinic between 2004 and 2018., Results: The study population of 2808 had a sex ratio of 1.9 (female/male ratio) and a median age of 72 years (IQR: 60-79). A rising referral rate over the study period appears to be plateauing at around 2 cases per 1000 population per annum. On the basis of a snapshot audit, investigation of IDA may now account for over 20% of all diagnostic endoscopies.Overall, 86% of cases underwent examination of the upper and lower GI tract. Significant GI pathology was identified in 27% of the investigated cohort. Adenocarcinoma of the upper or lower GI tract was found in 8.3%, the majority in the right colon. The prevalence of recurrent IDA was estimated at 12.4%, and the results of investigation of this subgroup are reported., Conclusion: Unexplained IDA is common, particularly in those over 60 years, and may be the first indication of underlying GI malignancy in over 8% of cases. Unresolved challenges include accommodating the resulting endoscopy workload, establishing a risk/benefit ratio for investigating those with major comorbidities and the management of recurrent IDA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools., Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following., Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico., Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed., Competing Interests: All authors declared or they have no potential conflicts of interest. The following authors, indicated relations with the pharmaceutical industry: Dr. Larenas Linnemann reports personal fees from Allakos, Amstrong, 10.13039/100004325Astrazeneca, 10.13039/100001003Boehringer Ingelheim, 10.13039/100007560Chiesi, DBV Technologies, Grunenthal, 10.13039/100004330GSK, MEDA, Menarini, 10.13039/100007054MSD, 10.13039/100004336Novartis, 10.13039/100004319Pfizer, 10.13039/100004336Novartis, 10.13039/100004339Sanofi, Siegfried, 10.13039/100011110UCB, Gossamer, grants from 10.13039/100004319Sanofi, 10.13039/100004325Astrazeneca, Novartis, 10.13039/100011110UCB, GSK, 10.13039/100006259TEVA, 10.13039/100001003Boehringer Ingelheim, 10.13039/100007560Chiesi, Purina institute., outside the submitted work; Dr. Moncayo Coello reports personal fees from 10.13039/100004325AstraZeneca, personal fees from 10.13039/100004339Sanofi, personal fees from 10.13039/100004330Grünenthal, personal fees from 10.13039/100011218Sandoz, outside the submitted work; Dr. Partida-Gaytan reports personal fees from 10.13039/100012690Nestlé Nutrition Institute, personal fees from 10.13039/100004330GlaxoSmithKline Mexico, personal fees from Instituto Nacional de Pediatria, personal fees from Healthy Kids Polanco S.C., outside the submitted work., (© 2020 The Authors.)

The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times. This study assessed the performance of the BioFire FilmArray Pneumonia Panel (PN panel) and Pneumonia Plus Panel (PNplus panel), an FDA-cleared sample-to-answer assay that enables the detection of viruses, atypical bacteria, bacteria, and antimicrobial resistance marker genes from lower respiratory tract specimens (sputum and bronchoalveolar lavage [BAL] fluid). Semiquantitative results are also provided for the bacterial targets. This paper describes selected analytical and clinical studies that were conducted to evaluate performance of the panel for regulatory clearance. Prospectively collected respiratory specimens (846 BAL and 836 sputum specimens) evaluated with the PN panel were also tested by quantitative reference culture and molecular methods for comparison. The PN panel showed a sensitivity of 100% for 15/22 etiologic targets using BAL specimens and for 10/24 using sputum specimens. All other targets had sensitivities of ≥75% or were unable to be calculated due to low prevalence in the study population. Specificity for all targets was ≥87.2%, with many false-positive results compared to culture that were confirmed by alternative molecular methods. Appropriate adoption of this test could provide actionable diagnostic information that is anticipated to impact patient care and antimicrobial stewardship decisions., (Copyright © 2020 Murphy et al.)

Lower respiratory tract infections, including hospital-acquired and ventilator-associated pneumonia, are common in hospitalized patient populations. Standard methods frequently fail to identify the infectious etiology due to the polymicrobial nature of respiratory specimens and the necessity of ordering specific tests to identify viral agents. The potential severity of these infections combined with a failure to clearly identify the causative pathogen results in administration of empirical antibiotic agents based on clinical presentation and other risk factors. We examined the impact of the multiplexed, semiquantitative BioFire FilmArray Pneumonia panel (PN panel) test on laboratory reporting for 259 adult inpatients submitting bronchoalveolar lavage (BAL) specimens for laboratory analysis. The PN panel demonstrated a combined 96.2% positive percent agreement (PPA) and 98.1% negative percent agreement (NPA) for the qualitative identification of 15 bacterial targets compared to routine bacterial culture. Semiquantitative values reported by the PN panel were frequently higher than values reported by culture, resulting in semiquantitative agreement (within the same log 10 value) of 43.6% between the PN panel and culture; however, all bacterial targets reported as >10 5 CFU/ml in culture were reported as ≥10 5 genomic copies/ml by the PN panel. Viral targets were identified by the PN panel in 17.7% of specimens tested, of which 39.1% were detected in conjunction with a bacterial target. A review of patient medical records, including clinically prescribed antibiotics, revealed the potential for antibiotic adjustment in 70.7% of patients based on the PN panel result, including discontinuation or de-escalation in 48.2% of patients, resulting in an average savings of 6.2 antibiotic days/patient., (Copyright © 2020 Buchan et al.)

Antibiotic resistance is one of the major threats to public health today. To address this problem requires an urgent comprehensive approach. Strategic and multitargeted combination therapy has been increasingly used clinically to treat bacterial infections. The hollow-fibre infection model (HFIM) is a well-controlled in vitro bioreactor system that is increasingly being used in the assessment of resistance emergence with monotherapies and combination antibiotic therapies. In this study, the HFIM was evaluated as a reliable in vitro method to quantitatively and reproducibly analyse the emergence of antibiotic resistance using ampicillin, fosfomycin and ciprofloxacin and their simultaneous combinations against Escherichia coli CFT073, a clinical uropathogenic strain. Bacteria were exposed to clinically relevant pharmacokinetic (PK) concentrations of the drugs for 10 days. Drug and bacterial samples were collected at different time points for PK analysis and to enumerate total and resistant bacterial populations, respectively. The results demonstrated that double or triple combinations significantly delayed the emergence of resistant E. coli CFT073 subpopulations. These findings suggest that strategic combinations of antimicrobials may play a role in controlling the emergence of resistance during treatment. Further animal and human trials will be needed to confirm this and to ensure that there is no adverse impact on the host microbiome or unexpected toxicity. The HFIM system could potentially be used to identify clinically relevant combination dosing regimens for use in a clinical trial evaluating the appearance of resistance to antibacterial drugs., (Published by Elsevier B.V.)

Rasch's logistic model for growth is explained by reviewing his analysis of piglet growth. An early formulation was given in India when Rasch visited with Rao to describe the statistic metameter as the distinguishing characteristic for determining the rate of growth. Next, several examples are given demonstrating growth with plots of growth over time using characteristic time with truncated data. The results of these growth plots and analyses are summarized given their implications and restraints for using this approach in determining rate of growth.

Identification of genes associated with childhood-onset nephrotic syndrome has significantly advanced our understanding of the pathogenesis of this complex disease over the past two decades, however the precise etiology in many cases remains unclear. At this time, we still rely on invasive kidney biopsy to determine the underlying cause of nephrotic syndrome in adults. In children, response to steroid therapy has been shown to be the best indicator of prognosis, and therefore all children are treated initially with corticosteroids. Because this strategy exposes a large number of children to the toxicities of steroids without providing any benefit, many researchers have sought to find a marker that could predict a patient's response to steroids at the time of diagnosis. Additionally, the identification of such a marker could provide prognostic information about a patient's response to medications, progression to end stage renal disease, and risk of disease recurrence following transplantation. Major advances have been made in understanding how genetic biomarkers can be used to predict a patient's response to therapies and disease course, especially after transplantation. Research attempting to identify urine- and serum-based biomarkers which could be used for the diagnosis, differentiation, and prognosis of nephrotic syndrome has become an area of emphasis. In this review, we explore the most exciting biomarkers and their potential clinical applications., (Copyright © 2019 Stone, Magella and Bennett.)

Numerous methods exist for fluorescently labeling proteins either as direct fusion proteins (GFP, RFP, YFP, etc.-attached to the protein of interest) or utilizing accessory proteins to produce fluorescence (SNAP-tag, CLIP-tag), but the significant increase in size that these accompanying proteins add may hinder or impede proper protein folding, cellular localization, or oligomerization. Fluorescently labeling proteins with biarsenical dyes, like FlAsH, circumvents this issue by using a short 6-amino acid tetracysteine motif that binds the membrane-permeable dye and allows visualization of living cells. Here, we report the successful adaptation of FlAsH dye for live-cell imaging of two genera of spirochetes, Leptospira and Borrelia , by labeling inner or outer membrane proteins tagged with tetracysteine motifs. Visualization of labeled spirochetes was possible by fluorescence microscopy and flow cytometry. A subsequent increase in fluorescent signal intensity, including prolonged detection, was achieved by concatenating two copies of the 6-amino acid motif. Overall, we demonstrate several positive attributes of the biarsenical dye system in that the technique is broadly applicable across spirochete genera, the tetracysteine motif is stably retained and does not interfere with protein function throughout the B. burgdorferi infectious cycle, and the membrane-permeable nature of the dyes permits fluorescent detection of proteins in different cellular locations without the need for fixation or permeabilization. Using this method, new avenues of investigation into spirochete morphology and motility, previously inaccessible with large fluorescent proteins, can now be explored.

Background: Renal damage is a progressive complication of sickle cell disease (SCD). Microalbuminuria is common in children with SCD, while a smaller number of children have more severe renal manifestations necessitating kidney biopsy. There is limited information on renal biopsy findings in children with SCD and subsequent management and outcome., Methods: This is a multicenter retrospective analysis of renal biopsy findings and clinical outcomes in children and adolescents with SCD. We included children and adolescents (age ≤ 20 years) with SCD who had a kidney biopsy performed at a pediatric nephrology unit. The clinical indication for biopsy, biopsy findings, subsequent treatments, and outcomes were analyzed., Results: Thirty-six SCD patients (ages 4-19 years) were identified from 14 centers with a median follow-up of 2.6 years (0.4-10.4 years). The indications for biopsy were proteinuria (92%) and elevated creatinine (30%). All biopsies had abnormal findings, including mesangial hypercellularity (75%), focal segmental glomerulosclerosis (30%), membranoproliferative glomerulonephritis (16%), and thrombotic microangiopathy (2%). There was increased use of hydroxyurea, angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers following renal biopsy. At last follow-up, 3 patients were deceased, 2 developed insulin-dependent diabetes mellitus, 6 initiated chronic hemodialysis, 1 received a bone marrow transplant, and 1 received a kidney transplant., Conclusions: Renal biopsies, while not commonly performed in children with SCD, were universally abnormal. Outcomes were poor in this cohort of patients despite a variety of post-biopsy interventions. Effective early intervention to prevent chronic kidney disease (CKD) is needed to reduce morbidity and mortality in children with SCD.