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The World Bank will publish the nine volumes of Disease Control Priorities, 3rd edition, in 2015-16. Volume 1 - Essential Surgery-identifies 44 surgical procedures as essential on the basis that they address substantial needs, are cost eff ective, and are feasible to implement. This report summarises and critically assesses the volume's five key findings. First, provision of essential surgical procedures would avert about 1.5 million deaths a year, or 6-7% of all avertable deaths in low-income and middle-income countries. Second, essential surgical procedures rank among the most cost eff ective of all health interventions. The surgical platform of the first-level hospital delivers 28 of the 44 essential procedures, making investment in this platform also highly cost eff ective. Third, measures to expand access to surgery, such as task sharing, have been shown to be safe and effective while countries make long-term investments in building surgical and anaesthesia workforces. Because emergency procedures constitute 23 of the 28 procedures provided at first-level hospitals, expansion of access requires that such facilities be widely geographically diffused. Fourth, substantial disparities remain in the safety of surgical care, driven by high perioperative mortality rates including anaesthesia-related deaths in low-income and middle-income countries. Feasible measures, such as WHO's Surgical Safety Checklist, have led to improvements in safety and quality. Fifth, the large burden of surgical disorders, cost-eff ectiveness of essential surgery, and strong public demand for surgical services suggest that universal coverage of essential surgery should be financed early on the path to universal health coverage. We point to estimates that full coverage of the component of universal coverage of essential surgery applicable to first-level hospitals would require just over US$3 billion annually of additional spending and yield a benefit-cost ratio of more than 10:1. It would efficiently and equitably provide health benefits, financial protection, and contributions to stronger health systems.

Abstract Objectives To assess racial and ethnic minority parents’ perceptions about barriers to well-child visit attendance. Methods For this cross-sectional qualitative study, we recruited parents of pediatric primary care patients who were overdue for a well-child visit from the largest safety net healthcare organization in central Massachusetts to participate in semi-structured interviews. The interviews focused on understanding potential knowledge, structural, and experiential barriers for well-child visit attendance. Interview content was inductively coded and directed content analysis was performed to identify themes. Results Twenty-five racial and ethnic minority parents participated; 17 (68%) of whom identified Spanish as a primary language spoken at home. Nearly all participants identified the purpose, significance, and value of well-child visits. Structural barriers were most cited as challenges to attending well-child visits, including parking, transportation, language, appointment availability, and work/other competing priorities. While language emerged as a distinct barrier, it also exacerbated some of the structural barriers identified. Experiential barriers were cited less commonly than structural barriers and included interactions with office staff, racial/ethnic discrimination, appointment reminders, methods of communication, wait time, and interactions with providers. Conclusions Racial and ethnic minority parents recognize the value of well-child visits; however, they commonly encounter structural barriers that limit access to care. Furthermore, a non-English primary language compounds the impact of these structural barriers. Understanding these barriers is important to inform health system policies to enhance access and delivery of pediatric care with a lens toward reducing racial and ethnic-based inequities.

Abstract Background The combination of radiotherapy and immunotherapy (immunoradiotherapy) has been increasingly used for treating a wide range of cancers. However, some tumors are resistant to immunoradiotherapy. We have previously shown that MER proto-oncogene tyrosine kinase (MerTK) expressed on macrophages mediates resistance to immunoradiotherapy. We therefore sought to develop therapeutics that can mitigate the negative impact of MerTK. We designed and developed a MerTK specific antisense oligonucleotide (ASO) and characterized its effects on eliciting an anti-tumor immune response in mice. Methods 344SQR cells were injected into the right legs on day 0 and the left legs on day 4 of 8-12 weeks old female 129sv/ev mice to establish primary and secondary tumors, respectively. Radiation at a dose of 12 Gy was given to the primary tumors on days 8, 9, and 10. Mice received either anti-PD-1, anti-CTLA-4 or/and MerTK ASO starting from day 1 post tumor implantation. The composition of the tumor microenvironment and the level of MerTK on macrophages in the tumor were evaluted by flow cytometry. The expression of immune-related genes was investigated with NanoString. Lastly, the impact of MerTK ASO on the structure of the eye was histologically evaluated. Results Remarkably, the addition of MerTK ASO to XRT+anti-PD1 and XRT+anti-CTLA4 profoundly slowed the growth of both primary and secondary tumors and significantly extended survival. The ASO significantly reduced the expression of MerTK in tumor-associated macrophages (TAMs), reprograming their phenotype from M2 to M1. In addition, MerTK ASO increased the percentage of Granzyme B+ CD8+ T cells in the secondary tumors when combined with XRT+anti-CTLA4. NanoString results demonstrated that the MerTK ASO favorably modulated immune-related genes for promoting antitumor immune response in secondary tumors. Importantly, histological analysis of eye tissues demonstrated that unlike small molecules, the MerTK ASO did not produce any detectable pathology in the eyes. Conclusions The MerTK ASO can significantly downregulate the expression of MerTK on TAMs, thereby promoting antitumor immune response. The combination of MerTK ASO with immunoradiotherapy can safely and significantly slow tumor growth and improve survival. Graphical Abstract

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a poor prognosis. Doxorubicin is part of standard curative therapy for TNBC, but chemotherapy resistance remains an important clinical challenge. Bocodepsin (OKI-179) is a small molecule class I histone deacetylase (HDAC) inhibitor that promotes apoptosis in TNBC preclinical models. The purpose of this study was to investigate the combination of bocodepsin and doxorubicin in preclinical TNBC models and evaluate the impact on terminal cell fate, including apoptosis and senescence. Methods TNBC cell lines were treated with doxorubicin and CellTiter-Glo was used to assess proliferation and determine doxorubicin sensitivity. Select cell lines were treated with OKI-005 (in vitro version of bocodepsin) and doxorubicin and assessed for proliferation, apoptosis as measured by Annexin V/PI, and cell cycle by flow cytometry. Immunoblotting was used to assess changes in mediators of apoptosis, cell cycle arrest, and senescence. Senescence was measured by the senescence-associated β-galactosidase assay. An MDA-MB-231 xenograft in vivo model was treated with bocodepsin, doxorubicin, or the combination and assessed for inhibition of tumor growth. shRNA knockdown of p53 was performed in the CAL-51 cell line and proliferation, apoptosis and senescence were assessed in response to combination treatment. Results OKI-005 and doxorubicin resulted in synergistic antiproliferative activity in TNBC cells lines regardless of p53 mutation status. The combination led to increased apoptosis and decreased senescence. In vivo, the combination resulted in increased tumor growth inhibition compared to either single agent. shRNA knock-down of p53 led to increased doxorubicin-induced senescence that was decreased with the addition of OKI-005 in vitro. Conclusion The addition of bocodepsin to doxorubicin resulted in synergistic antiproliferative activity in vitro, improved tumor growth inhibition in vivo, and promotion of apoptosis which makes this a promising combination to overcome doxorubicin resistance in TNBC. Bocodepsin is currently in clinical development and has a favorable toxicity profile compared to other HDAC inhibitors supporting the feasibility of evaluating this combination in patients with TNBC.

ABSTRACT There are no licensed vaccines for human cytomegalovirus (HCMV), and current antiviral drugs that target viral proteins are toxic and prone to resistance. Targeting host pathways essential for virus replication provides an alternate strategy that may reduce opportunities for drug resistance to occur. Oxidative stress is triggered by numerous viruses including HCMV. Peroxynitrite is a reactive nitrogen species that is formed during oxidative stress. Herein, we identified that HCMV rapidly induces the generation of intracellular peroxynitrite upon infection in a manner partially dependent upon xanthine oxidase generation. Peroxynitrite promoted HCMV infection in both cell-free and cell-associated infection systems in multiple cell types. Inhibiting peroxynitrite within the first 24 hours of infection prevented HCMV replication and peroxynitrite promoted cell entry and pp65 translocation into the host cell nuclei. Furthermore, using the murine cytomegalovirus model, we demonstrated that antagonizing peroxynitrite significantly reduces cytomegalovirus replication and pathogenesis in vivo. Overall, our study highlights a proviral role for peroxynitrite in CMV infection and implies that RNS and/or the mechanisms that induce their production could be targeted as a novel strategy to inhibit HCMV infection.IMPORTANCEHuman cytomegalovirus (HCMV) causes significant disease in individuals with impaired or immature immune systems, such as transplant patients and after congenital infection. Antiviral drugs that target the virus directly are toxic and are susceptible to antiviral drug resistance due to virus mutations. An alternate strategy is to target processes within host cells that are required by the virus for replication. Herein, we show that HCMV infection triggers a highly reactive molecule, peroxynitrite, during the initial stages of infection. Peroxynitrite was required for the initial entry of the virus into the cell and promotes virus replication in multiple cell types, suggesting a broad pro-viral function. Importantly, targeting peroxynitrite dramatically inhibited cytomegalovirus replication in cells in the laboratory and in mice, suggesting that therapeutic targeting of this molecule and/or the cellular functions it regulates could represent a novel strategy to inhibit HCMV infection.

Undergraduate nursing programs are increasingly using non-traditional community health placements within their curricula, though their impact on the organizations and clients they serve has not been widely explored. Therefore, this article aims to examine the use of non-traditional community health placements in undergraduate nursing programs using the political economy of health inequities as an analytical framework. We discuss the limits of non-traditional placements in addressing health inequities, suggesting our work contributes to the perception that something is being done to address the dual unregulated drug poisoning and housing crises while failing to tackle their root causes. We theorize that non-traditional health placements allow nursing programs to continue to graduate enough nurses to meet increasing workforce demands under prolonged austerity measures that have reduced funding to both post-secondary institutions and public health. Finally, we discuss strategies to mitigate harm and commit to more equitable partnerships. Keywords: political economy of health inequities, health equity, non-traditional placements, community health nursing, nursing education

AimTo co-create parental presence practice recommendations across Canadian NICUs during pandemics caused by respiratory pathogens such as COVID-19.MethodsRecommendations were developed through evidence, context, Delphi and Values and Preferences methods. For Delphi 1 and 2, participants rated 50 items and 20 items respectively on a scale from 1 (very low importance) to 5 (very high). To determine consensus, evidence and context of benefits and harms were presented and discussed within the Values and Preference framework for the top-ranked items. An agreement of 80% or more was deemed consensus.ResultsAfter two Delphi rounds (n = 59 participants), 13 recommendations with the highest rated importance were identified. Consensus recommendations included 6 strong recommendations (parents as essential caregivers, providing skin-to-skin contact, direct or mothers' own expressed milk feeding, attending medical rounds, mental health and psychosocial services access, and inclusion of parent partners in pandemic response planning) and 7 conditional recommendations (providing hands-on care tasks, providing touch, two parents present at the same time, food and drink access, use of communication devices, and in-person access to medical rounds and mental health and psychosocial services).ConclusionThese recommendations can guide institutions in developing strategies for parental presence during pandemics caused by respiratory pathogens like COVID-19

BackgroundLeptospirosis is a neglected zoonosis which remains poorly known despite its epidemic potential, especially in tropical islands where outdoor lifestyle, vulnerability to invasive reservoir species and hot and rainy climate constitute higher risks for infections. Burden remains poorly documented while outbreaks can easily overflow health systems of these isolated and poorly populated areas. Identification of generic patterns driving leptospirosis dynamics across tropical islands would help understand its epidemiology for better preparedness of communities. In this study, we aim to model leptospirosis seasonality and outbreaks in tropical islands based on precipitation and temperature indicators.Methodology/principal findingsWe adjusted machine learning models on leptospirosis surveillance data from seven tropical islands (Guadeloupe, Reunion Island, Fiji, Futuna, New Caledonia, and Tahiti) to investigate 1) the effect of climate on the disease's seasonal dynamic, i.e., the centered seasonal profile and 2) inter-annual anomalies, i.e., the incidence deviations from the seasonal profile. The model was then used to estimate seasonal dynamics of leptospirosis in Vanuatu and Puerto Rico where disease incidence data were not available. A robust model, validated across different islands with leave-island-out cross-validation and based on current and 2-month lagged precipitation and current and 1-month lagged temperature, can be constructed to estimate the seasonal dynamic of leptospirosis. In opposition, climate determinants and their importance in estimating inter-annual anomalies highly differed across islands.Conclusions/significanceClimate appears as a strong determinant of leptospirosis seasonality in tropical islands regardless of the diversity of the considered environments and the different lifestyles across the islands. However, predictive and expandable abilities from climate indicators weaken when estimating inter-annual outbreaks and emphasize the importance of these local characteristics in the occurrence of outbreaks.

Anthropogenic climate change is undeniably altering planet Earth, and agricultural emissions are a significant contributor to this crisis. Agriculture, specifically cattle farming, is a key emitter of GHG emissions, accounting for 14.5% of global GHG emissions. This paper thus asks, given that cattle farming contributes a significant amount of total global GHG emissions, if the elimination of cattle farming in the EU is a sustainable way to reduce total GHG emissions. This paper explores the sustainability of cattle farming in the EU and highlights the vital role that EU cattle farming plays in the EU economy and in meeting the global food supply. It also explores the role that beef consumption plays in human diets. By researching the available literature, this paper finds that the complete elimination of cattle farming in the EU would have devastating effects on the EU economy and would leave the global food demand largely unmet. Not to mention that the environmental benefits of eliminating cattle farming become less significant when accounting for the emissions of new economic activity on ex-cattle grazing lands. Thus, this paper highlights the importance of improving cattle management and changing dietary patterns to mitigate GHG emissions in the context of a worsening climate and an increasing global food demand that must be met.

Abstract Iron is a key nutrient for bacterial growth. The source can be either heme or siderophore-Fe complexes. Siderophores are small molecules synthesized by bacteria to scavenge iron from the bacterial environment. The pathogen Pseudomonas aeruginosa can express at least 15 different iron uptake pathways and all but one involve a TonB-dependent transporter (TBDT) for the uptake of iron across the outer membrane. Little is known about how bacteria modulate and adapt the expression of their different iron import pathways according to their environment. Here, we have developed fluorescent reporters between the promoter region of genes encoding a TBDT and the fluorescent reporter mCherry. With these constructs, we can follow the expression of TBDTs under different growth conditions. Mathematical modelling of the data obtained showed the transcription and expression of the gene encoding the TBDT PfeA to have a sigmoidal shape, whereas it was logarithmic for the TBDT gene foxA. Maximum transcription for pfeA was reached in the presence of 3 µM enterobactin, the siderophore recognized by PfeA, whereas the maximum was not reached for foxA with 100 µM nocardamine, the siderophore of FoxA.

Chronic wounds present a significant socioeconomic burden forecasted to increase in prevalence and cost. Minimally manipulated human placental tissues have been increasingly employed and proven to be advantageous in the treatment of chronic wounds, showing improved clinical outcomes and cost-effectiveness. However, technological advances have been constrained by minimal manipulation and homologous use criteria. This study focuses on the characterization of a novel dehydrated human umbilical cord particulate (dHUCP) medical device, which offers a unique allogeneic technological advancement and the first human birth tissue device for wound management. Characterization analyses illustrated a complex extracellular matrix composition conserved in the dHUCP device compared to native umbilical cord, with abundant collagens and glycosaminoglycans imbibing an intricate porous scaffold. Dermal fibroblasts readily attached to the intact scaffold of the dHUCP device. Furthermore, the dHUCP device elicited a significant paracrine proliferative response in dermal fibroblasts, in contrast to fibrillar collagen, a prevalent wound device. Biocompatibility testing in a porcine full-thickness wound model showed resorption of the dHUCP device and normal granulation tissue maturation during healing. The dHUCP device is a promising advancement in wound management biomaterials, offering a unique combination of structural complexity adept for challenging wound topographies and a microenvironment supportive of tissue regeneration.

Objective: We explored individual Muslim women’s reproductive healthcare experiences, preferences, beliefs, and behaviors in the emergency department (ED) and in general. Methods: This was a qualitative study conducted at a community ED using semi-structured interviews with a piloted interview guide. We interviewed participants awaiting care in the ED with the following criteria: female gender; English or Arabic speaking; aged ≥18 years; and self-identified as Muslim. We conducted interviews in both English and Arabic until thematic saturation was reached. Transcripts were coded using an iteratively developed codebook, maintaining intercoder agreement greater than 80%. We used an inductive thematic analysis to identify themes, and results were interpreted in the context of interview language and patient’s age. Results: We interviewed 26 Muslim-identified female ED patients. We found that cultural representation and sensitivity among ED staff mitigated discrimination and promoted inclusion for Muslim ED patients. However, assumptions about Muslim identity also impacted the participants’ healthcare. Most participants endorsed a preference for a female clinician for their reproductive healthcare in general, but not necessarily for other areas of medicine. Clinician cultural concordance was not always preferred for participants in the ED due to fears about the loss of confidentiality. Marital status impacted beliefs about reproductive and sexual health in the context of Muslim identity. Overall, family planning was acceptable and encouraged in this patient population. Conclusion: The themes elucidated in this study may guide clinicians in developing culturally sensitive practices when providing reproductive healthcare to the Muslim population.

Colorectal cancer (CRC) is one of the leading causes of death in the United States and worldwide. Recent evidence has corroborated a strong correlation between poor diet and the development of CRC, and further research is being conducted to investigate the association between intestinal microbiome and the development of cancer. New studies have established links with certain foods and synthetic food compounds that may be effective in reducing the risk for carcinogenesis by providing protection against cancer cell proliferation and antagonizing oncogenic pathways. Prebiotics are gaining popularity as studies have demonstrated chemo-preventive as well as anticancer potential of prebiotics. This paper aims to discuss the wide definition and scope of prebiotics by reviewing the studies that provide insights into their effects on human health in the context of colorectal cancer.

Abstract Lysophosphatidic acid (LPA) is a bioactive lipid which increases in concentration locally and systemically across different cancer types. Yet, the exact mechanism(s) of how LPA affects CD8 T cell immunosurveillance during tumor progression remain unknown. We show LPA receptor (LPAR) signaling by CD8 T cells promotes tolerogenic states via metabolic reprogramming and potentiating exhaustive-like differentiation to modulate anti-tumor immunity. We found LPA levels predict response to immunotherapy and Lpar5 signaling promotes cellular states associated with exhausted phenotypes on CD8 T cells. Importantly, we show that Lpar5 regulates CD8 T cell respiration, proton leak, and reactive oxygen species. Together, our findings reveal that LPA serves as a lipid-regulated immune checkpoint by modulating metabolic efficiency through LPAR5 signaling on CD8 T cells. Our study offers key insights into the mechanisms governing adaptive anti-tumor immunity and demonstrates LPA could be exploited as a T cell directed therapy to improve dysfunctional anti-tumor immunity.

Clinical illness (CI) scoring using visual observation is the most widely applied method of detecting respiratory disease in cattle but has limited effectiveness in practice. In contrast, body-mounted sensor technology effectively facilitates disease detection. To evaluate whether a combination of movement behavior and CI scoring is effective for disease detection, cattle were vaccinated to induce a temporary inflammatory immune response. Cattle were evaluated before and after vaccination to identify the CI variables that are most indicative of sick cattle. Respiratory rate (H2 = 43.08, P < 0.0001), nasal discharge (H2 = 8.35, P = 0.015), and ocular discharge (H2 = 16.38, P = 0.0003) increased after vaccination, and rumen fill decreased (H2 = 20.10, P < 0.0001). Locomotor activity was measured via leg-mounted sensors for the four days preceding and seven days following vaccination. A statistical model that included temperature, steps, lying time, respiratory rate, rumen fill, head position, and excess saliva was developed to distinguish between scores from before and after vaccination with a sensitivity of 0.898 and specificity of 0.915. Several clinical illness signs were difficult to measure in practice. Binoculars were required for scoring respiratory rate and eye-related metrics, and cattle had to be fitted with colored collars for individual identification. Scoring each animal took up to three minutes in a small research pen; therefore, technologies that can automate both behavior monitoring and identification of clinical illness signs are key to improving capacity for BRD detection and treatment.

Pancreatic ductal adenocarcinoma (PDAC) presents at advanced stages and is refractory to most treatment modalities. Wnt signaling activation plays a critical role in proliferation and chemotherapeutic resistance. Minimal media conditions, growth factor dependency, and Wnt dependency were determined via Wnt inhibition for seven patient derived organoids (PDOs) derived from pancreatic tumor organoid libraries (PTOL). Organoids demonstrating response in vitro were assessed in vivo using patient-derived xenografts. Wnt (in)dependent gene signatures were identified for each organoid. Panc269 demonstrated a trend of reduced organoid growth when treated with ETC-159 in combination with paclitaxel or gemcitabine as compared with chemotherapy or ETC-159 alone. Panc320 demonstrated a more pronounced anti-proliferative effect in the combination of ETC-159 and paclitaxel but not with gemcitabine. Panc269 and Panc320 were implanted into nude mice and treated with ETC-159, paclitaxel, and gemcitabine as single agents and in combination. The combination of ETC-159 and paclitaxel demonstrated an anti-tumor effect greater than ETC-159 alone. Extent of combinatory treatment effect were observed to a lesser extent in the Panc320 xenograft. Wnt (in)dependent gene signatures of Panc269 and 320 were consistent with the phenotypes displayed. Gene expression of several key Wnt genes assessed via RT-PCR demonstrated notable fold change following treatment in vivo. Each pancreatic organoid demonstrated varied niche factor dependencies, providing an avenue for targeted therapy, supported through growth analysis following combinatory treatment of Wnt inhibitor and standard chemotherapy in vitro. The clinical utilization of this combinatory treatment modality in pancreatic cancer PDOs has thus far been supported in our patient-derived xenograft models treated with Wnt inhibitor plus paclitaxel or gemcitabine. Gene expression analysis suggests there are key Wnt genes that contribute to the Wnt (in)dependent phenotypes of pancreatic tumors, providing plausible mechanistic explanation for Wnt (in)dependency and susceptibility or resistance to treatment on the genotypic level.

A supermassive black hole surrounded by a dense, nuclear star cluster resides at the center of many galaxies. In this dense environment, high-velocity collisions frequently occur between stars. About 10% of the stars within the Milky Way’s nuclear star cluster collide with other stars before evolving off the main sequence. Collisions preferentially affect tightly bound stars, which orbit most quickly and pass through regions of the highest stellar density. Over time, collisions therefore shape the bulk properties of the nuclear star cluster. We examine the effect of collisions on the cluster’s stellar density profile. We show that collisions produce a turning point in the density profile, which can be determined analytically. Varying the initial density profile and collision model, we characterize the evolution of the stellar density profile over 10 Gyr. We find that old, initially cuspy populations exhibit a break around 0.1 pc in their density profile, while shallow density profiles retain their initial shape outside of 0.01 pc. The initial density profile is always preserved outside of a few tenths of a parsec irrespective of initial conditions. We generalize this model to an arbitrary galactic nucleus and show that the location of the collisional break can be simply estimated from the nuclear properties. Lastly, we comment on the implications of collisions for the luminosity and color of stars in the collisionally shaped inner cluster.

Abstract Background COVID-19 shut down trial courts across the country, prolonging case resolution of charged, detained, and incarcerated people. We report on the implementation of rapid COVID-19 testing at Trial Courts in Massachusetts (MA), focusing on the outcomes of adoption and acceptability. Methods Guided by the Expert Recommendations in Implementing Change (ERIC) framework, we chose six strategies to guide implementation. After assembling a group of stakeholders, including representatives of the Trial Court, Department of Public Health (DPH) and vendors providing COVID-19 testing, we implemented rapid COVID-19 testing at Trial Court locations in December 2021. We collected data on (1) adoption of COVID-19 testing, (2) number of stakeholders who attended meetings, (3) number of tests performed at Trial Court sites, and (4) acceptability of COVID-19 testing using a QR-code anonymous survey. Results There was a high percentage of attendance at stakeholder meetings (> 70% at each meeting). 243 COVID-19 tests were conducted on eight occasions at four Trial Court sites between December 2021 and February 2022. Participants who responded to the QR-code survey reflected favorably on COVID-19 testing at MA Trial Court sites. Conclusion COVID-19 testing at Massachusetts Trial Court sites was possible through stakeholder engagement. Several cases of COVID-19 were identified prior to entry into the Trial Court. Funding for rapid COVID-19 testing should be provided to help keep trial courts open as the pandemic continues to evolve.

Temperate insectivorous bats value high prey abundance and appropriate vegetative structure when selecting foraging habitats. Forests, particularly in the eastern United States, provide prime foraging habitats for bats but can be heavily impacted by non-native plants, which may alter arthropod diversity and abundance, as well as vegetative structure. To investigate the associations between non-native plants and insect abundance, vegetative structure, and, consequently, bat activity, we performed vegetation surveys, insect trapping, and acoustic monitoring at 23 forested plots in northern New Jersey, USA. We predicted that non-native vegetation would either positively influence bat activity by increasing structural openness (thus, facilitating flight) or negatively influence bat activity by lowering the abundance of putative prey. We also hypothesized that vegetative characteristics, and therefore non-native vegetation, impact bats differently depending on their foraging habitat preferences. The percent of non-native cover of the ground and midstory vegetative layers of our study plots ranged from 0 to 92.92% (x¯ = 46.94 ± 5.77 SE) and was significantly correlated with structural vegetative characteristics, such as midstory clutter (β = 0.01 ± 0.006 SE), but not putative prey abundance (β = −0.81 ± 2.57 SE). Generalized linear models with only vegetative characteristics best predicted overall bat activity and foraging, which were greatest in areas with a high percent non-native vegetation and low midstory clutter. Although percent non-native vegetation and midstory clutter were also significant effects for bats that prefer to forage in open areas, neither vegetative characteristics nor prey abundance were significant effects for clutter-loving bats. Such findings suggest that vegetative structure is more important than prey availability for predicting overall insectivorous bat activity, but other factors, such as foraging strategy and life history traits, can impact how bat guilds respond to non-native vegetation. Therefore, more research is required to reveal additional mechanisms by which non-native plants impact bats.

The natural assemblage of a symbiotic bacterial microbiome (bacteriome) with microalgae in marine ecosystems is now being investigated as a means to increase algal productivity for industry. When algae are grown in open pond settings, biological contamination causes an estimated 30% loss of the algal crop. Therefore, new crop protection strategies that do not disrupt the native algal bacteriome are needed to produce reliable, high-yield algal biomass. Bacteriophages offer an unexplored solution to treat bacterial pathogenicity in algal cultures because they can eliminate a single species without affecting the bacteriome. To address this, we identified a highly virulent pathogen of the microalga Nannochloropsis gaditana, the bacterium Bacillus safensis, and demonstrated rescue of the microalgae from the pathogen using phage. 16S rRNA amplicon sequencing showed that phage treatment did not alter the composition of the bacteriome. It is widely suspected that the algal bacteriome could play a protective role against bacterial pathogens. To test this, we compared the susceptibility of a bacteriome-attenuated N. gaditana culture challenged with B. safensis to a N. gaditana culture carrying a growth-promoting bacteriome. We showed that the loss of the bacteriome increased the susceptibility of N. gaditana to the pathogen. Transplanting the microalgal bacteriome to the bacteriome-attenuated culture reconstituted the protective effect of the bacteriome. Finally, the success of phage treatment was dependent on the presence of beneficial bacteriome. This study introduces two synergistic countermeasures against bacterial pathogenicity in algal cultures and a tractable model for studying interactions between microalgae, phages, pathogens, and the algae microbiome.

Abstract Background High-throughput phenotyping is crucial for the genetic and molecular understanding of adaptive root system development. In recent years, imaging automata have been developed to acquire the root system architecture of many genotypes grown in Petri dishes to explore the Genetic x Environment (GxE) interaction. There is now an increasing interest in understanding the dynamics of the adaptive responses, such as the organ apparition or the growth rate. However, due to the increasing complexity of root architectures in development, the accurate description of the topology, geometry, and dynamics of a growing root system remains a challenge. Results We designed a high-throughput phenotyping method, combining an imaging device and an automatic analysis pipeline based on registration and topological tracking, capable of accurately describing the topology and geometry of observed root systems in 2D + t. The method was tested on a challenging Arabidopsis seedling dataset, including numerous root occlusions and crossovers. Static phenes are estimated with high accuracy ( $$R^2=0.996$$ R 2 = 0.996 and $$0.923$$ 0.923 for primary and second-order roots length, respectively). These performances are similar to state-of-the-art results obtained on root systems of equal or lower complexity. In addition, our pipeline estimates dynamic phenes accurately between two successive observations ( $$R^2=0.938$$ R 2 = 0.938 for lateral root growth). Conclusions We designed a novel method of root tracking that accurately and automatically measures both static and dynamic parameters of the root system architecture from a novel high-throughput root phenotyping platform. It has been used to characterise developing patterns of root systems grown under various environmental conditions. It provides a solid basis to explore the GxE interaction controlling the dynamics of root system architecture adaptive responses. In future work, our approach will be adapted to a wider range of imaging configurations and species.

Introduction: Intercellular adhesion molecule 1 (ICAM-1) is a critical molecule responsible for interactions between cells. Previous studies have suggested that ICAM-1 triggers cell-to-cell transmission of HIV-1 or HTLV-1, that SARS-CoV-2 shares several features with these viruses via interactions between cells, and that SARS-CoV-2 cell-to-cell transmission is associated with COVID-19 severity. From these previous arguments, it is assumed that ICAM-1 can be related to SARS-CoV-2 cell-to-cell transmission in COVID-19 patients. Indeed, the time-dependent change of the ICAM-1 expression level has been detected in COVID-19 patients. However, signaling pathways that consist of ICAM-1 and other molecules interacting with ICAM-1 are not identified in COVID-19. For example, the current COVID-19 Disease Map has no entry for those pathways. Therefore, discovering unknown ICAM1-associated pathways will be indispensable for clarifying the mechanism of COVID-19.Materials and methods: This study builds ICAM1-associated pathways by gene network inference from single-cell omics data and multiple knowledge bases. First, single-cell omics data analysis extracts coexpressed genes with significant differences in expression levels with spurious correlations removed. Second, knowledge bases validate the models. Finally, mapping the models onto existing pathways identifies new ICAM1-associated pathways.Results: Comparison of the obtained pathways between different cell types and time points reproduces the known pathways and indicates the following two unknown pathways: (1) upstream pathway that includes proteins in the non-canonical NF-κB pathway and (2) downstream pathway that contains integrins and cytoskeleton or motor proteins for cell transformation.Discussion: In this way, data-driven and knowledge-based approaches are integrated into gene network inference for ICAM1-associated pathway construction. The results can contribute to repairing and completing the COVID-19 Disease Map, thereby improving our understanding of the mechanism of COVID-19.

Abstract Satellite altimetry, which measures water level with global coverage and high resolution, provides an unprecedented opportunity for a wide and refined understanding of the changing tides in the coastal area. But its sampling frequency is too low to satisfy the Nyquist frequency requirement and too few data points per year are available to recognize a sufficient number of tidal constituents to capture the trend of tidal changes on a yearly basis. To address these issues, a novel regularized least‐square approach is developed to relax the sampling interval limit to the range of 9–11 days, reaching the revisit time of the existing satellites. In this method, the prior information of the regional tidal amplitudes is used to support a least square analysis to obtain the amplitudes of the tidal constituents for water elevation time series of different lengths and time intervals. Synthetic data experiments performed in Delaware Bay and Galveston Bay showed that the proposed method can determine the tidal amplitudes with high accuracy and the sampling interval can be extended to the application level of major altimetry satellites. The proposed algorithm was further validated using the data of the altimetry mission, Jason‐3, to show its applicability to irregular and noisy data. The new method could help identify the changing tides with sea‐level rise and anthropogenic activities in coastal areas, informing coastal flooding risk assessment and ecosystem health analysis.

Abstract The red imported fire ant (RIFA), Solenopsis invicta (Buren), is a notorious, invasive species with broad impacts on ecosystems, economies, and human health. While incidental reports to the Virginia Department of Agriculture and Consumer Services (VDACS) indicate a recent range expansion in Virginia, the full extent of RIFA spread in the area is currently unknown. In this study, we examined the distribution of RIFA in Virginia using multiple data sources: (1) during the summers of 2020 and 2021, we conducted a series of prospective visual surveys along public roadways in southern Virginia, (2) we used data from multiyear VDACS infestation reports covering the period 2016–2021, and (3) we surveyed local naturalists, county extension agents, and land managers. We compared the resulting data with an earlier predictive model quantifying the potential spread of RIFA and constructed a species distribution model to explore the potential range expansion of RIFA in the United States based on new occurrence data and bioclimatic variables. RIFA was found in seven Virginia counties beyond the current federal quarantine zone, and our data show that it has spread much further than predicted 15 years ago. Our species distribution model suggests that the range of RIFA is likely to increase further under the currently projected climate change scenarios, both in Virginia and more generally across the United States, with the lower Midwest expected to be one of the most affected areas. This study provides insights into the range expansion of RIFA at the border of its suitable North American habitat and elucidates some of the environmental factors associated with its current and future spread. In doing so, it provides information to advise sound management practices and prevention efforts.

Inhibitory CD4+ T cells have been linked with suboptimal immune responses against cancer and pathogen chronicity. However, the mechanisms that underpin the development of these regulatory cells, especially in the context of ongoing antigen exposure, have remained obscure. To address this knowledge gap, we undertook a comprehensive functional, phenotypic, and transcriptomic analysis of interleukin (IL)-10-producing CD4+ T cells induced by chronic infection with murine cytomegalovirus (MCMV). We identified these cells as clonally expanded and highly differentiated TH1-like cells that developed in a T-bet-dependent manner and coexpressed arginase-1 (Arg1), which promotes the catalytic breakdown of L-arginine. Mice lacking Arg1-expressing CD4+ T cells exhibited more robust antiviral immunity and were better able to control MCMV. Conditional deletion of T-bet in the CD4+ lineage suppressed the development of these inhibitory cells and also enhanced immune control of MCMV. Collectively, these data elucidated the ontogeny of IL-10-producing CD4+ T cells and revealed a previously unappreciated mechanism of immune regulation, whereby viral persistence was facilitated by the site-specific delivery of Arg1.

Superpuffs are planets with exceptionally low densities ( ρ ≲ 0.1 g cm ^−3 ) and core masses ( M _c ≲ 5 M _⊕ ). Many lower-mass ( M _p ≲ 10 M _⊕ ) superpuffs are expected to be unstable to catastrophic mass loss via photoevaporation and/or boil-off, whereas the larger gravitational potentials of higher-mass ( M _p ≳ 10 M _⊕ ) superpuffs should make them more stable to these processes. We test this expectation by studying atmospheric loss in the warm, higher-mass superpuff TOI-1420b ( M = 25.1 M _⊕ , R = 11.9 R _⊕ , ρ = 0.08 g cm ^−3 , T _eq = 960 K). We observed one full transit and one partial transit of this planet using the metastable helium filter on Palomar/WIRC and found that the helium transits were 0.671% ± 0.079% (8.5 σ ) deeper than the TESS transits, indicating an outflowing atmosphere. We modeled the excess helium absorption using a self-consistent 1D hydrodynamics code to constrain the thermal structure of the outflow given different assumptions for the stellar XUV spectrum. These calculations then informed a 3D simulation, which provided a good match to the observations with a modest planetary mass-loss rate of 10 ^10.82 g s ^−1 ( ${M}_{p}/\dot{M}\approx 70$ Gyr). Superpuffs with M _p ≳ 10 M _⊕ , like TOI-1420b and WASP-107b, appear perfectly capable of retaining atmospheres over long timescales; therefore, these planets may have formed with the unusually large envelope mass fractions they appear to possess today. Alternatively, tidal circularization could have plausibly heated and inflated these planets, which would bring their envelope mass fractions into better agreement with expectations from core-nucleated accretion.

Atmospheric escape shapes the fate of exoplanets, with statistical evidence for transformative mass loss imprinted across the mass–radius–insolation distribution. Here, we present transit spectroscopy of the highly irradiated, low-gravity, inflated hot Saturn HAT-P-67 b. The Habitable Zone Planet Finder spectra show a detection of up to 10% absorption depth of the 10833 Å helium triplet. The 13.8 hr of on-sky integration time over 39 nights sample the entire planet orbit, uncovering excess helium absorption preceding the transit by up to 130 planetary radii in a large leading tail. This configuration can be understood as the escaping material overflowing its small Roche lobe and advecting most of the gas into the stellar—and not planetary—rest frame, consistent with the Doppler velocity structure seen in the helium line profiles. The prominent leading tail serves as direct evidence for dayside mass loss with a strong day-/nightside asymmetry. We see some transit-to-transit variability in the line profile, consistent with the interplay of stellar and planetary winds. We employ one-dimensional Parker wind models to estimate the mass-loss rate, finding values on the order of 2 × 10 ^13 g s ^−1 , with large uncertainties owing to the unknown X-ray and ultraviolet (XUV) flux of the F host star. The large mass loss in HAT-P-67 b represents a valuable example of an inflated hot Saturn, a class of planets recently identified to be rare, as their atmospheres are predicted to evaporate quickly. We contrast two physical mechanisms for runaway evaporation: ohmic dissipation and XUV irradiation, slightly favoring the latter.

BackgroundSelf-reported questions on blindness and vision problems are collected in many national surveys. Recently released surveillance estimates on the prevalence of vision loss used self-reported data to predict variation in the prevalence of objectively measured acuity loss among population groups for whom examination data are not available. However, the validity of self-reported measures to predict prevalence and disparities in visual acuity has not been established. ObjectiveThis study aimed to estimate the diagnostic accuracy of self-reported vision loss measures compared to best-corrected visual acuity (BCVA), inform the design and selection of questions for future data collection, and identify the concordance between self-reported vision and measured acuity at the population level to support ongoing surveillance efforts. MethodsWe calculated accuracy and correlation between self-reported visual function versus BCVA at the individual and population level among patients from the University of Washington ophthalmology or optometry clinics with a prior eye examination, randomly oversampled for visual acuity loss or diagnosed eye diseases. Self-reported visual function was collected via telephone survey. BCVA was determined based on retrospective chart review. Diagnostic accuracy of questions at the person level was measured based on the area under the receiver operator curve (AUC), whereas population-level accuracy was determined based on correlation. ResultsThe survey question, “Are you blind or do you have serious difficulty seeing, even when wearing glasses?” had the highest accuracy for identifying patients with blindness (BCVA ≤20/200; AUC=0.797). The highest accuracy for detecting any vision loss (BCVA

Limited evidence is available regarding the association between acute exposure to ambient air pollutants and the risk of urticaria, even though the skin is an organ with direct contact with the external environment. This study utilized generalized additive models to investigate the association between particulate matter with an aerodynamic diameter smaller than 10 μm (PM10) and 2.5 μm (PM2.5), nitrogen dioxide (NO2) and sulfur dioxide (SO2), and daily outpatient visits for urticaria in Guangzhou, China from 2013 to 2017. We also estimated the attributable fraction of urticaria outpatient visits due to air pollution. A total of 216,648 outpatient visits due to urticaria occurred during the study period. All air pollutants were significantly associated with an increased excess risk of urticaria. Each 10 μg/m3 increase in PM2.5, PM10, NO2, and SO2 was associated with an increase of 1.23% (95% CI: 0.42%, 2.06%), 0.88% (95% CI: 0.28%, 1.49%), 3.09% (95% CI: 2.16%, 4.03%), and 2.82% (95% CI: 0.93%, 4.74%) in hospital visits for urticaria at lag05, respectively. It was estimated that 3.77% (95% CI: 1.26%, 6.38%), 1.91% (95% CI: 0.60%, 3.26%), 6.36% (95% CI: 4.38%, 8.41%), and 0.08% (95% CI: 0.03%, 0.14%) of urticaria outpatient visits were attributable to PM2.5, PM10, NO2, and SO2 using the World Health Organization’s air quality guideline as the reference. Relatively stronger associations were observed during the cold season. This study indicates that short-term air pollution may play a significant role in outpatient visits for urticaria, and that such relationships could be modified by season.

This paper deals with a new analytical model for microfluidic passive mixers. Two common approaches already exist for such a purpose. On the one hand, the resolution of the advection-diffusion-reaction equation (ADRE) is the first one and the closest to physics. However, ADRE is a partial differential equation that requires finite element simulations. On the other hand, analytical models based on the analogy between microfluidics and electronics have already been established. However, they rely on the assumption of homogeneous fluids, which means that the mixer is supposed to be long enough to obtain a perfect mixture at the output. In this paper, we derive an analytical model from the ADRE under several assumptions. Then we integrate these equations within the electronic-equivalent models. The resulting models computed the relationship between pressure and flow rate in the microfluidic circuit but also takes the concentration gradients that can appear in the direction perpendicular to the channel into account. The model is compared with the finite element simulation performed with COMSOL Multiphysics in several study cases. We estimate that the global error introduced by our model compared to the finite element simulation is less than 5% in every use case. In counterparts, the cost in terms of computational resources is drastically reduced. The analytical model can be implemented in a large range of modelling and simulation languages, including SPICE and hardware description language such as Verilog-AMS. This feature is very interesting in the context of the in silico prototyping of large-scale microfluidic devices or multi-physics devices involving microfluidic circuits, e.g. lab-on-chips.

Abstract Background Dengue dynamics result from the complex interactions between the virus, the host and the vector, all being under the influence of the environment. Several studies explored the link between weather and dengue dynamics and some investigated the impact of climate change on these dynamics. Most attempted to predict incidence rate at a country scale or assess the environmental suitability at a global or regional scale. Here, we propose a new approach which consists in modeling the risk of dengue outbreak at a local scale according to climate conditions and study the evolution of this risk taking climate change into account. We apply this approach in New Caledonia, where high quality data are available. Methods We used a statistical estimation of the effective reproduction number (R t ) based on case counts to create a categorical target variable : epidemic week/non-epidemic week. A machine learning classifier has been trained using relevant climate indicators in order to estimate the probability for a week to be epidemic under current climate data and this probability was then estimated under climate change scenarios. Results Weekly probability of dengue outbreak was best predicted with the number of days when maximal temperature exceeded 30.8°C and the mean of daily precipitation over 80 and 60 days prior to the predicted week respectively. According to scenario RCP8.5, climate will allow dengue outbreak every year in New Caledonia if the epidemiological and entomological contexts remain the same. Conclusion We identified locally relevant climatic factor driving dengue outbreaks in New Caledonia and assessed the inter-annual and seasonal risk of dengue outbreak under different climate change scenarios up to the year 2100. We introduced a new modeling approach to estimate the risk of dengue outbreak depending on climate conditions. This approach is easily reproducible in other countries provided that reliable epidemiological and climate data are available.

Gastrointestinal stromal tumors (GISTs) are tumors of the digestive tract. To date, there have been no neurological paraneoplastic syndromes or symptoms associated with metastatic GISTs. Tyrosine kinase inhibitors (TKIs) are the typical class of agents used in management of this malignancy. Avapritinib, a new TKI, has been associated with myriad neurological adverse events with fairly rapid resolution in clinical trials. Herein, we present the case of a patient with metastatic GIST who, after starting treatment with avapritinib, developed rapidly progressive and persisting severe neuropsychiatric symptoms, including profound parkinsonism and encephalopathy, while concurrently receiving therapy with the antipsychotic olanzapine. We posit that the patient could be conceptualized as having a relative vulnerability to medication effects in the setting of metastatic GIST - possibly driven by an immune-mediated process - and that the addition of avapritinib triggered an overtly evident, clinically significant cascade of neurological deterioration.

Cancer treatment has come a long way in increasing overall survival; however, evasion of the immune system continues to be a challenge in treating individuals with established disease burdens. Due to the difficulty in stimulating an immune response against cancer, approaches utilizing combination adjuvants with different mechanisms may be beneficial. A combination of these adjuvants with other adjuvants or other treatments has demonstrated synergistic effects in the form of a robust and sustained immune response, demonstrating the importance of further development. This review discusses the intricacies of immune evasion, applications of adjuvants with different mechanisms of action, and adjuvants used for cancer immunotherapy in clinical trials.

Edible insects have gained attention due to their impressive nutritional composition, as well as their efficient use of natural resources. However, a research gap remains on the applications of insect chitosan, especially as it relates to their potential use as food packaging material. Chitosan from two reared cricket species (Acheta domesticus and Gryllodes sigillatus) was evaluated for use as food packaging material. Cricket chitosan films (CCF) were structurally similar to commercial shrimp chitosan films (SCF) at controlled glycerol levels, as seen by shared spectral peaks in FT-IR analyses. Mechanical properties of CCF showed they had equal or greater tensile strength when compared to commercial SCF, although flexibility was lower. Scanning electron microscopy showed increased roughness of microstructure, likely increasing the tortuosity. As a result, CCF had improved water vapor permeability compared to commercial SCF. Melanin complexes present in cricket chitin and chitosan increased hydrophobicity and decreased light transmittance. This study also revealed that intrinsic species differences, which occur during insect and crustacean exoskeleton development, could have effects on the functionality of chitosan packaging materials. Overall, CCF were found to be as effective as commercial SCF, while providing additional advantages. CCF derived from reared crickets have good mechanical and barrier properties, and improved water resistance and light barrier characteristics. Edible cricket chitosan has the potential to be used as bio-based packaging material for food and pharmaceutical applications.

Immune checkpoint inhibitors have been found to be effective in metastatic MSI-high colorectal cancers (CRC), however, have no efficacy in microsatellite stable (MSS) cancers, which comprise the majority of mCRC cases. Cabozantinib is a small molecule multi-tyrosine kinase inhibitor that is FDA approved in advanced renal cell, medullary thyroid, and hepatocellular carcinoma. Using Human Immune System (HIS) mice, we tested the ability of cabozantinib to prime MSS-CRC tumors to enhance the potency of immune checkpoint inhibitor nivolumab. In four independent experiments, we implanted distinct MSS-CRC patient-derived xenografts (PDXs) into the flanks of humanized BALB/c-Rag2nullIl2rγnullSirpαNOD (BRGS) mice that had been engrafted with human hematopoietic stem cells at birth. For each PDX, HIS-mice cohorts were treated with vehicle, nivolumab, cabozantinib, or the combination. In three out of the four models, the combination had a lower tumor growth rate compared to vehicle or nivolumab-treated groups. Furthermore, interrogation of the HIS in immune organs and tumors by flow cytometry revealed increased Granzyme B+, TNFα+ and IFNγ+ CD4+ T cells among the human tumor infiltrating leukocytes (TIL) that correlated with reduced tumor growth in the combination-treated HIS-mice. Notably, slower growth correlated with increased expression of the CD4+ T cell ligand, HLA-DR, on the tumor cells themselves. Finally, the cabozantinib/nivolumab combination was tested in comparison to cobimetinib/atezolizumab. Although both combinations showed tumor growth inhibition, cabozantinib/nivolumab had enhanced cytotoxic IFNγ and TNFα+ T cells. This pre-clinical in vivo data warrants testing the combination in clinical trials for patients with MSS-CRC.

ABSTRACT: Objectives: Dalbavancin is a long-lasting lipoglycopeptide active against Gram-positive bacteria, especially methicillin-resistant staphylococci. Few data are available on dalbavancin use for treatment of prosthetic joint infections (PJIs). We describe a cohort of patients treated for PJI with dalbavancin and review the literature regarding this condition. Methods: All adult patients with PJI from the French dalbavancin national cohort from 1 June 2017 to 1 January 2019 were included. We collected clinical and microbiological characteristics and outcome through a standardised questionnaire. Clinical cure was defined as absence of clinical signs of infection at last visit. Failure was a composite criterion defined by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. The literature review was performed using PubMed. Results: Seventeen patients were included. Bacteria were identified in 16 cases: Staphylococcus aureus (n = 10), including methicillin-resistant S. aureus (n = 1); and coagulase-negative staphylococci (n = 10), including methicillin-resistant Staphylococcus epidermidis (n = 4). Sixteen patients (94.1%) had received antibiotic therapy prior to dalbavancin use (mean of 2.2 ± 1.3 lines). Clinical cure was achieved in 8/17 patients after a median follow-up of 299.0 (IQR 97.0–476.0) days. We reviewed all cases of PJI treated with dalbavancin available in the literature and the overall clinical cure was estimated at 73.1%. Conclusion: Our study and literature data suggest that use of dalbavancin in PJI could be considered, even as salvage therapy. Dalbavancin appears to be a safe and easy treatment for patients with staphylococcal PJIs.

ABSTRACT: Objectives: Ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) are two novel antibacterials with known efficacy against Gram-negative bacteria (GNB). We aimed to describe the efficacy and safety of surgical management combined with C/A or C/T treatment for bone and joint infections (BJIs). Methods: We conducted an observational, bicentric study of patients treated with C/A or C/T for a BJI between May 2016 and June 2019. Failure was defined as the need for unplanned additional antibiotic treatment or orthopaedic surgery, or death due to the BJI up to the patient's latest visit. Results: Overall, 15 patients were included. Nine patients were treated with C/A, mainly for polymicrobial BJI due to multidrug-resistant (MDR) bacteria (Enterobacteriaceae, n = 7). Six patients were male, the median age was 66 years and the median Charlson comorbidity index (CCI) was 5. It was the first septic episode at the site in 3/9 patients. The cure rate was 7/9 (median follow-up, 272 days). Two patients showed C/A-related confusion. Five patients were treated with C/T for BJI involving MDR Pseudomonas aeruginosa. Four patients were male, the median age was 53 years and the median CCI was 2. All patients had previous septic episodes at the infection site. The cure rate was 3/5 (median follow-up, 350 days). One patient was successfully treated by C/T then C/A for multistage spondylodiscitis. Conclusion: In our experience, C/A and C/T are two effective and safe options, even as salvage treatment for BJI due to MDR-GNB despite the absence of label, however more data are warranted.

Abstract Background Improving the knowledge and understanding of the environmental determinants of malaria vector abundance at fine spatiotemporal scales is essential to design locally tailored vector control intervention. This work is aimed at exploring the environmental tenets of human-biting activity in the main malaria vectors (Anopheles gambiae s.s., Anopheles coluzzii and Anopheles funestus) in the health district of Diébougou, rural Burkina Faso. Methods Anopheles human-biting activity was monitored in 27 villages during 15 months (in 2017–2018), and environmental variables (meteorological and landscape) were extracted from high-resolution satellite imagery. A two-step data-driven modeling study was then carried out. Correlation coefficients between the biting rates of each vector species and the environmental variables taken at various temporal lags and spatial distances from the biting events were first calculated. Then, multivariate machine-learning models were generated and interpreted to (i) pinpoint primary and secondary environmental drivers of variation in the biting rates of each species and (ii) identify complex associations between the environmental conditions and the biting rates. Results Meteorological and landscape variables were often significantly correlated with the vectors’ biting rates. Many nonlinear associations and thresholds were unveiled by the multivariate models, for both meteorological and landscape variables. From these results, several aspects of the bio-ecology of the main malaria vectors were identified or hypothesized for the Diébougou area, including breeding site typologies, development and survival rates in relation to weather, flight ranges from breeding sites and dispersal related to landscape openness. Conclusions Using high-resolution data in an interpretable machine-learning modeling framework proved to be an efficient way to enhance the knowledge of the complex links between the environment and the malaria vectors at a local scale. More broadly, the emerging field of interpretable machine learning has significant potential to help improve our understanding of the complex processes leading to malaria transmission, and to aid in developing operational tools to support the fight against the disease (e.g. vector control intervention plans, seasonal maps of predicted biting rates, early warning systems). Graphical abstract

Insect-derived chitin and chitosan have gained interest as alternative sources to that derived from crustaceans; however, little information is available on chitin from the house cricket (Acheta domesticus) and tropical banded cricket (Gryllodes sigillatus), two cricket species commonly reared in the United States for human consumption. In this study, chitin was successfully isolated and purified from these two cricket species; using FTIR, chitins were found to be in alpha-crystalline form. Cricket chitosan was produced from both species with varying degrees of deacetylation (DDA) by varying alkaline conversion duration. G. sigillatus chitosan was larger (524 kDa) than A. domesticus chitosan (344 kDa). Both cricket chitosans showed similar (p > 0.05) lipid-binding capacity to that of shrimp chitosan. Both chitosans were as effective at inhibiting microbial growth of surrogate foodborne pathogens as the commercial shrimp chitosan. At a concentration of 0.50 mg/mL cricket chitosan, approximately 100% of Listeria innocua growth was inhibited, due to a contribution of both chitosan and the solvent-acetic acid. At the same concentration, growth of Escherichia coli was inhibited 90% by both cricket chitosan samples with ~80% DDA, where a decrease in the DDA led to decreased antimicrobial activity. However, varying the DDA had no effect on chitosan’s lipid-binding capacity. As more edible insects become a normalized protein source in our diet, the use of by-products, such as chitin and chitosan, derived from insect protein processing, show promising applications for the pharmaceutical and food industries.

The super enhancement of silicon band edge luminescence when co-implanted with boron and carbon is reported. The role of boron in the band edge emissions in silicon was investigated by deliberately introducing defects into the lattice structures. We aimed to increase the light emission intensity from silicon by boron implantation, leading to the formation of dislocation loops between the lattice structures. The silicon samples were doped with a high concentration of carbon before boron implantation and then annealed at a high temperature to activate the dopants into substitutional lattice sites. Photoluminescence (PL) measurements were performed to observe the emissions at the near-infrared region. The temperatures were varied from 10 K to 100 K to study the effect of temperature on the peak luminescence intensity. Two main peaks could be seen at ~1112 and 1170 nm by observing the PL spectra. The intensities shown by both peaks in the samples incorporated with boron are significantly higher than those in pristine silicon samples, and the highest intensity in the former was 600 times greater than that in the latter. Transmission electron microscopy (TEM) was used to study the structure of post-implant and post-anneal silicon sample. The dislocation loops were observed in the sample. Through a technique compatible with mature silicon processing technology, the results of this study will greatly contribute to the development of all Si-based photonic systems and quantum technologies.

In this paper, two of the most common calibration methods of synchronous TDCs, which are the bin-by-bin calibration and the average-bin-width calibration, are first presented and compared. Then, an innovative new robust calibration method for asynchronous TDCs is proposed and evaluated. Simulation results showed that: (i) For a synchronous TDC, the bin-by-bin calibration, applied to a histogram, does not improve the TDC’s differential non-linearity (DNL); nevertheless, it improves its Integral Non-Linearity (INL), whereas the average-bin-width calibration significantly improves both the DNL and the INL. (ii) For an asynchronous TDC, the DNL can be improved up to 10 times by applying the bin–by-bin calibration, whereas the proposed method is almost independent of the non-linearity of the TDC and can improve the DNL up to 100 times. The simulation results were confirmed by experiments carried out using real TDCs implemented on a Cyclone V SoC-FPGA. For an asynchronous TDC, the proposed calibration method is 10 times better than the bin-by-bin method in terms of the DNL improvement.

Summary: The COVID-19 pandemic and the ongoing epidemic of mass incarceration are closely intertwined, as COVID-19 entered US prisons and jails at astounding rates. Although observers warned of the swiftness with which COVID-19 could devastate people who are held and work in prisons and jails, their warnings were not heeded quickly enough. Incarcerated populations were deprioritised, and COVID-19 infected and killed those in jails and prisons at rates that outpaced the rates among the general population. The COVID-19 pandemic highlighted what has been long-known: mass incarceration is a key component of structural racism that creates and exacerbates health inequities. It is imperative that the public health, particularly epidemiology, public policy, advocacy, and medical communities, are catalysed by the COVID-19 pandemic to drastically rethink the USA's criminal legal system and the public health emergency that it has created and to push for progressive reform.

BackgroundCOVID-19 and mass incarceration are closely intertwined with prisons having COVID-19 case rates much higher than the general population. COVID-19 has highlighted the relationship between incarceration and health, but prior work has not explored how COVID-19 spread in communities have influenced case rates in prisons. Our objective was to understand the relationship between COVID-19 case rates in the general population and prisons located in the same county.MethodsUsing North Carolina's (NC) Department of Health and Human Services data, this analysis examines all COVID-19 tests conducted in NC from June-August 2020. Using interrupted time series analysis, we assessed the relationship between substantial community spread (50/100,000 detected in the last seven days) and active COVID-19 case rates (cases detected in the past 14 days/100,000) within prisons.ResultsFrom June-August 2020, NC ordered 29,605 tests from prisons and detected 1,639 cases. The mean case rates were 215 and 427 per 100,000 in the general and incarcerated population, respectively. Once counties reached substantial COVID-19 spread, the COVID-19 prison case rate increased by 118.55 cases per 100,000 (95% CI: -3.71, 240.81).ConclusionsCommunity COVID-19 spread contributes to COVID-19 case rates in prisons. In counties with prisons, community spread should be closely monitored. Stringent measures within prisons (e.g., vaccination) and decarceration should be prioritized to prevent COVID-19 outbreaks.

Despite adequate infection prophylaxis, variation in self-reported quality of life (QOL) throughout the intravenous immunoglobulin (IVIG) infusion cycle is a widely reported but infrequently studied phenomenon. To better understand this phenomenon, subjects with humoral immunodeficiency receiving replacement doses of IVIG were studied over 3 infusion cycles. Questionnaire data from 6 time points spread over 3 IVIG infusions cycles (infusion day and 7 days after each infusion) were collected in conjunction with monitoring the blood for number of regulatory T-cells (Treg) and levels of 40 secreted analytes: primarily cytokines, chemokines, and growth factors. At day 7, self-reported well-being increased, and self-reported fatigue decreased, reflecting an overall improvement in QOL 7 days after infusion. Over the same period, percentage of Treg cells in the blood increased (p

While infectious diseases (ID) are a well-documented public health issue in carceral settings, research on ID screening and treatment in jails is lacking. A survey was sent to 1,126 jails in the United States to identify the prevalence of health screenings at intake and characteristics of care for ID; 371 surveys were completed correctly and analyzed. Despite conflicting Centers for Disease Control (CDC) guidance, only seven percent of surveyed jails test individuals for HIV at admission. In 46% of jails, non-healthcare personnel perform ID screenings. Jails in less urban areas were more likely to report healthcare screenings performed by correctional officers. Survey findings indicate that HIV, HCV and TB testing during jail admissions and access to PrEP are severely lacking in less urban jails in particular. Recommendations are provided to improve ID surveillance and address the burden of ID in correctional facilities.

There has been significant progress made in the field of nanopore biosensor development and sequencing applications, which address previous limitations that restricted widespread nanopore use. These innovations, paired with the large-scale commercialization of biological nanopore sequencing by Oxford Nanopore Technologies, are making the platforms a mainstay in contemporary research laboratories. Equipped with the ability to provide long- and short read sequencing information, with quick turn-around times and simple sample preparation, nanopore sequencers are rapidly improving our understanding of unsolved genetic, transcriptomic, and epigenetic problems. However, there remain some key obstacles that have yet to be improved. In this review, we provide a general introduction to nanopore sequencing principles, discussing biological and solid-state nanopore developments, obstacles to single-base detection, and library preparation considerations. We present examples of important clinical applications to give perspective on the potential future of nanopore sequencing in the field of molecular diagnostics.

We use the rapid binary population synthesis code COMPAS to investigate commonly used prescriptions for the determination of mass transfer stability in close binaries and the orbital separations after stable mass transfer. The degree of orbital tightening during nonconservative mass transfer episodes is governed by the poorly constrained angular momentum carried away by the ejected material. Increased orbital tightening drives systems toward unstable mass transfer leading to a common envelope. We find that the fraction of interacting binaries that will undergo only stable mass transfer throughout their lives fluctuates between a few and ∼20% due to uncertainty in the angular momentum loss alone. If mass transfer is significantly nonconservative, stability prescriptions that rely on the assumption of conservative mass transfer underpredict the number of systems which experience unstable mass transfer and stellar mergers. This may substantially impact predictions about the rates of various transients, including luminous red novae, stripped-envelope supernovae, X-ray binaries, and the progenitors of coalescing compact binaries.

Betelgeuse, the nearest red supergiant, dimmed to an unprecedented level in early 2020. The star emerged from this “Great Dimming” episode with its typical, roughly 400 days pulsation cycle halved, and a new dominant period of around 200 days. The dimming event has been attributed to a surface mass ejection, in which rising material drove shocks through the stellar atmosphere and expelled some material, partially obscuring the star as it formed molecules and dust. In this paper, we use hydrodynamic simulations to reveal the connections between Betelgeuse's vigorously convective envelope, the surface mass ejection, and the pulsation mode switching that ensued. An anomalously hot convective plume, generated rarely but naturally in the star's turbulent envelope, can rise and break free from the surface, powering an upwelling that becomes the surface mass ejection. The rising plume also breaks the phase coherence of the star's pulsation, causing the surface to keep expanding even as the deeper layers contract. This drives a switch from the 400 days fundamental mode of pulsation, in which the whole star expands and contracts synchronously, to the 200 days first overtone, where a radial node separates the interior and exterior of the envelope moving in opposite phase. We predict that the star's convective motions will damp the overtone oscillation and Betelgeuse will return to its previous, 400 days fundamental-mode pulsation in the next 5–10 yr. With its resolved surface and unprecedentedly detailed characterization, Betelgeuse opens a window to episodic surface mass ejection in the late-stage evolution of massive stars.