Search

Abstract Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was eliminated from New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of SARS-CoV-2. However, in 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five-times higher than typical seasonal patterns. We generated 1470 viral genomes of both RSV-A and RSV-B sampled between 2015–2022 from across New Zealand. Using a phylodynamics approach, we used these data to better understand RSV transmission patterns in New Zealand prior to 2020, and how RSV became re-established in the community following the relaxation of COVID-19 restrictions. We found that in 2021, there was a large epidemic of RSV due to an increase in importations, leading to several large genomic clusters of both RSV-A ON1 and RSV-B BA9 genotypes. However, while a number of viral importations were detected, there was also a major reduction in RSV genetic diversity compared to pre-pandemic years. These data reveal the impact of NPI used during the COVID-19 pandemic on other respiratory infections and highlight the important insights that can be gained from viral genomes.

Abstract Background To summarize clinical presentations, baseline characteristics, diagnosis, treatment, and treatment outcomes through a systematic review of cases of crystal-induced arthritis in prosthetic joints in the literature. Methods A systematic review of case reports and case series was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed through PubMed/MEDLINE, Google Scholar, Embase, Cumulative Index to Nursing & Allied Health, and Web of Science. We identified case reports/case series in English of adult patients presenting with crystal-induced arthritis (gout, calcium pyrophosphate deposition disease) in prosthetic joints. Articles that met the inclusion criteria were utilized for qualitative data synthesis. Results We found 44 cases of crystal-induced arthritis in prosthetic joints from 1984 to 2021. Crystal-induced arthritis in periprosthetic joints most frequently affects patients who had knee arthroplasty and most often presents as monoarticular arthritis that is usually acute in onset. However, several cases in the literature involved patients who had bilateral knee replacements and presented with a concurrent flare of gout or calcium pyrophosphate deposition disease in bilateral knees. Patients with crystal-induced arthritis in prosthetic joints show elevated white blood cell counts with neutrophil predominance and respond favorably to anti-inflammatory treatments, usually within one week. In many cases, crystal-induced arthritis was challenging to differentiate from prosthetic joint infection, with approximately one-third of patients undergoing surgical intervention and 35% receiving antibiotic treatment. Conclusion Crystal-induced arthritis in prosthetic joints can mimic prosthetic joint infections and should always be considered in the differential diagnoses of joint pain in prosthetic joints. We present the first systematic review of crystal-induced arthritis in prosthetic joints to increase awareness of the diagnosis and proper management.

Many consumers suffer from inadequate information and behavioral biases, which can produce internalities, understood as costs that people impose on their future selves. In these circumstances, “Choice Engines,” powered by Artificial Intelligence (AI), might produce significant savings in terms of money, health, safety, or time. Different consumers care about different things, of course, which is a reason to insist on a high degree of freedom of choice, and a high degree of personalization. Nonetheless, it is important to emphasize that Choice Engines and AI might be enlisted by self-interested actors, who might exploit inadequate information or behavioral biases, and thus reduce consumer welfare. It is also important to emphasize that Choice Engines and AI might show behavioral biases, perhaps the same ones that human beings are known to show, perhaps others that have not been named yet, or perhaps new ones, not shown by human beings, that cannot be anticipated.

Metabolic stress in skeletal muscle cells causes sustained metabolic changes, but the mechanisms of the prolonged effects are not fully known. In this study, we tested C2C12 cells with the AMP-activated protein kinase (AMPK) stimulator AICAR and measured the changes in the metabolic pathways and signaling kinases. AICAR caused an acute increase in the phosphorylation of the AMPK target ULK1, the mTORC1 substrate S6K, and the mTORC2 target Akt. Intriguingly, prior exposure to AICAR only decreased glucose-6 phosphate dehydrogenase activity when it underwent three-hour recovery after exposure to AICAR in a bicarbonate buffer containing glucose (KHB) instead of Dulbecco’s Minimum Essential Medium (DMEM). The phosphorylation of the mTORC1 target S6K was increased after recovery in DMEM but not KHB, although this appeared to be specific to S6K, as the phosphorylation of the mTORC1 target site on ULK1 was not altered when the cells recovered in DMEM. The phosphorylation of mTORC2 target sites was also heterogenous under these conditions, with Akt increasing at serine 473 while other targets (SGK1 and PKCα) were unaffected. The exposure of cells to rapamycin (an mTORC1 inhibitor) and PP242 (an inhibitor of both mTOR complexes) revealed the differential phosphorylation of mTORC2 substrates. Taken together, the data suggest that prior exposure to AICAR causes the selective phosphorylation of mTOR substrates, even after prolonged recovery in a nutrient-replete medium.

We present a genome assembly from an individual male Nematopogon swammerdamella (the Large Longhorn; Arthropoda; Insecta; Lepidoptera; Adelidae). The genome sequence is 699.5 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.46 kilobases in length.

Background: Psychological First Aid (PFA) is practiced worldwide. This practice in English is guided through a small collection of training manuals. Despite ubiquitous practice and formal training materials, little is known about what topics are covered and in what depth in these influential manuals. As such, we analyzed the topic structure of these training manuals. Objective: To model the PFA manuals’ topics with the goal of identifying a set of topics with recurrent themes and evaluating the extent to which each manual demonstrated those themes. Method: This machine learning study employed an unsupervised topic modelling design using Latent Dirichlet Allocation. The variables are (1) the distribution of a word across documents and (2) the distribution of a word across topics. The level of measurement for all variables is continuous. The unit of analysis is words. Preprocessing and data analysis were carried out using the Orange Data Mining Toolbox (Demšar et al., ). This programme is a Python GUI. Results: Results indicated a ten-topic structure to the universe of the English PFA training manuals. These topics were: (1) Refugees, (2) Orientation Activities, (3) Community-Based Applications, (4) PTSD & Other Psychological Issues, (5) Training Materials, (6) Specific Helper Instructions, (7) PFA Scholarship, (8) MHPSS, (9) General Curriculum, and (10) Australian Specific Delivery. The depth of discourse on each topic varied widely between manuals. Conclusions: The Academics of the PFA topic shows a strong representation of the corpus and suggests current training manuals have stayed true to its evidence-supported practice. The topic of Community-Based Applications strongly represents the corpus and suggests that training models incorporate community-based applications. The scientific foundation and practical implementation of the training guides are essential elements. Limitations and implications were also discussed.

IntroductionTraditional studies of the population called “heritage speakers” (HS) have treated this group as distinct from other bilingual populations, e.g., simultaneous or late bilinguals (LB), focusing on group differences in the competencies of the first-acquired language or “heritage language”. While several explanations have been proposed for such differences (e.g., incomplete acquisition, attrition, differential processing mechanisms), few have taken into consideration the individual variation that must occur, due to the fluctuation of factors such as exposure and use that characterize all bilinguals. In addition, few studies have used implicit measures, e.g., psychophysiological methods (ERPs; Eye-tracking), that can circumvent confounding variables such as resorting to conscious metalinguistic knowledge.MethodologyThis study uses pupillometry, a method that has only recently been used in psycholinguistic studies of bilingualism, to investigate pupillary responses to three syntactic island constructions in two groups of Spanish/English bilinguals: heritage speakers and late bilinguals. Data were analyzed using generalized additive mixed effects models (GAMMs) and two models were created and compared to one another: one with group (LB/HS) and the other with groups collapsed and current and historical use of Spanish as continuous variables.ResultsResults show that group-based models generally yield conflicting results while models collapsing groups and having usage as a predictor yield consistent ones. In particular, current use predicts sensitivity to L1 ungrammaticality across both HS and LB populations. We conclude that individual variation, as measured by use, is a critical factor tha must be taken into account in the description of the language competencies and processing of heritage and late bilinguals alike.

A comprehensive analysis of the HEP (High Energy Physics) experiment traffic across LHCONE (Large Hadron Collider Open Network Environment) and other networks, is essential for immediate network optimisation (for example by the NOTED project) and highly desirable for long-term network planning. Such an analysis requires two steps: tagging of network packets to indicate the type and owner of the traffic being carried and then processing of the tagged packets. The RNTWG (Research Network Technical Working Group) has defined a specification to identify the experiment and the application that originates a given network flow, named scitags (Scientific Network Tags) that is applied to the flow label field of the IPv6 header. We report here on the second step: processing of packets tagged according to this specification. We developed P4flow as a software-defined networking approach by using P4 (Programming Protocol-Independent Packet Processors), a language for programming the data plane of network devices to accounting and process IPv6 packets with a scitags-based stamp in the flow label field, to understand the network utilisation and the applications used by the WLCG (Worldwide Large Hadron Collider Computing Grid) sites. With P4flow, and exploiting the control plane capabilities provided by RARE/FreeRtr (an Open Source Network Operating System developed by the GÉANT community), we cannot only generate statistics concerning the traffic per experiment and application but can also, using an Intel Tofino P4-programmable ASIC Ethernet Switch, decide how to forward traffic matching defined flow labels. This latter capability is particularly interesting as we prepare for a future where LHC experiments will be sharing network links with other major science collaborations such as SKA and ITER.

The NOTED (Network Optimised Transfer of Experimental Data) project has successfully demonstrated the ability to dynamically provision network links to increase the effective bandwidth available for FTS-driven transfers between endpoints, such as WLCG sites, by inspecting on-going data transfers and so identifying those that are bandwidth-limited for a long period of time. Recently, the architecture of NOTED has been improved and the software has been packaged for easy distribution. These improved capabilities and features of NOTED have been tested and demonstrated at various international conferences. For example, during demonstrations at Supercomputing 2022, independent instances of NOTED at CHCERN (Switzerland) and DE-KIT (Germany) monitored large data transfers generated by the ATLAS experiment between these sites and CA-TRIUMF (Canada). We report here on this and other events, highlighting how NOTED can predict link congestion or a notable increase in the network utilisation over an extended period of time and, where appropriate, automatically reconfigure network topology to introduce an additional or an alternative and betterperforming path by using dynamic circuit provisioning systems such as SENSE and AutoGOLE.

Abstract Background Inflammatory myofibroblastic tumor (IMT) is an ultra‐rare soft tissue neoplasm associated with fusion proteins encompassing the anaplastic lymphoma kinase (ALK) protein fused to a variety of partner proteins. Data regarding response to ALK‐targeting agents based on fusion partner is limited. Case A 30‐year‐old female sought emergency care after onset of abdominal and lower back pain in 2019. Computed tomography (CT) demonstrated a cystic, mesenteric mass within the pelvis measuring up to 8.9 cm. Complete laparoscopic excision of the mass from the mesentery of the right colon and terminal ileum was performed. Pathologic assessment revealed IMT with a fusion between sequestosome 1 and ALK (SQSTM1::ALK), described in only two other cases of IMT. Four months after surgery, CT revealed multi‐focal, unresectable disease recurrence. She was referred to the University of Washington/Fred Hutchinson Cancer Center and placed on therapy with alectinib, after which she experienced a partial response. Three years after IMT recurrence, disease remains under control. Conclusion This is the third reported case of IMT associated with the novel SQSTM1::ALK fusion protein, and the second treated with alectinib. Treatment with the ALK inhibitor alectinib appears to be active in this setting.

Summary: Background: COVID-19 booster vaccine uptake rates are behind the rate of primary vaccination in many countries. Governments and non-governmental institutions rely on a range of interventions aiming to increase booster uptake. Yet, little is known how experts and the general public evaluate these interventions. Methods: We applied a novel crowdsourcing approach to provide rapid insights on the most promising interventions to promote uptake of COVID-19 booster vaccines. In the first phase (December 2021), international experts (n = 78 from 17 countries) proposed 46 unique interventions. To reduce noise and potential bias, in the second phase (January 2022), experts (n = 307 from 34 countries) and representative general population samples from the UK (n = 299) and the US (n = 300) rated the proposed interventions on several evaluation criteria, including effectiveness and acceptability, on a 5-point Likert-type scale. Findings: Sanctions were evaluated as potentially most effective but least accepted. Evaluations by expert and general population samples were considerably aligned. Interventions that received the most positive evaluations regarding both effectiveness and acceptability across evaluation groups were: a day off work after getting vaccinated, financial incentives, tax benefits, promotional campaigns, and mobile vaccination teams. Interpretation: The results provide useful insights to help governmental and non-governmental institutions in their decisions about which interventions to implement. Additionally, the applied crowdsourcing method may be used in future studies to retrieve rapid insights on the comparative evaluation of (health) policies. Funding: This study received funding from the Austrian Science Fund (SFB F63) and the University of Vienna.

Type II diabetes affects over 530 million individuals worldwide and contributes to a host of neurological pathologies. Uncontrolled high blood glucose (hyperglycemia) is a major factor in diabetic pathology, and glucose regulation is a common goal for maintenance in patients. We have found that the neuronal growth factor progranulin protects against hyperglycemic stress in neurons, and although its mechanism of action is uncertain, our findings identified Glycogen Synthase Kinase 3β (GSK3β) as being potentially involved in its effects. In this study, we treated mouse primary cortical neurons exposed to high-glucose conditions with progranulin and a selective pharmacological inhibitor of GSK3β before assessing neuronal health and function. Whole-cell and mitochondrial viability were both improved by progranulin under high-glucose stress in a GSK3β—dependent manner. This extended to autophagy flux, indicated by the expressions of autophagosome marker Light Chain 3B (LC3B) and lysosome marker Lysosome-Associated Membrane Protein 2A (LAMP2A), which were affected by progranulin and showed heterogeneous changes from GSK3β inhibition. Lastly, GSK3β inhibition attenuated downstream calcium signaling and neuronal firing effects due to acute progranulin treatment. These data indicate that GSK3β plays an important role in progranulin’s neuroprotective effects under hyperglycemic stress and serves as a jumping-off point to explore progranulin’s protective capabilities in other neurodegenerative models.

Objectives: To investigate trends of osteoporosis treatment rates, and factors affecting osteoporosis treatment after hip fracture admission within a single health care system in Hawaii. Methods: A retrospective chart review was conducted of patients aged 50 years or older and hospitalized for hip fractures between January 1, 2011 and December 31, 2019 at Hawaii Pacific Health, a large health care system in Hawaii. We collected data on basic demographics and osteoporosis medication prescription from electronic medical records. We evaluated trends of osteoporosis treatment rates and performed logistic regression to determine factors associated with osteoporosis treatment. Results: The mean for treatment rates for osteoporosis from 2011 to 2019 was 17.2% (range 8.8%–26.0%). From 2011 to 2019 there was a small increase in treatment rates from 16.3% in 2011 to 24.1% in 2019. Men were less likely to receive osteoporosis treatment after admission for hip fracture. Patients discharged to a facility were more likely to receive osteoporosis treatment. As compared to women, men who had a hip fracture were less likely to receive dual-energy X-ray absorptiometry scan, and osteoporosis medication before hip fracture admission. Conclusions: The use of osteoporosis medication for secondary prevention after admission for hip fracture in Hawaii from 2011 to 2019 was low. However, there was a small increase in treatment rates from 2011 to 2019. Disparities in treatment of osteoporosis after hip fracture were noted in men. Significant work is needed to increase treatment rates further, and to address the disparity in osteoporosis treatment between men and women.

Chronic hyperglycemia in type II diabetes results in impaired autophagy function, accumulation of protein aggregates, and neurodegeneration. However, little is known about how to preserve autophagy function under hyperglycemic conditions. In this study, we tested whether progranulin (PGRN), a neurotrophic factor required for proper lysosome function, can restore autophagy function in neurons under high-glucose stress. We cultured primary cortical neurons derived from E18 Sprague-Dawley rat pups to maturity at 10 days in vitro (DIV) before incubation in high glucose medium and PGRN for 24-72 h before testing for autophagy flux, protein turnover, and mitochondrial function. We found that although PGRN by itself did not upregulate autophagy, it attenuated impairments in autophagy seen under high-glucose conditions. Additionally, buildup of the autophagosome marker light chain 3B (LC3B) and lysosome marker lysosome-associated membrane protein 2A (LAMP2A) changed in both neurons and astrocytes, indicating a possible role for glia in autophagy flux. Protein turnover, assessed by remaining advanced glycation end-product levels after a 6-h incubation, was preserved with PGRN treatment. Mitochondrial activity differed by complex, although PGRN appeared to increase overall activity in high glucose. We also found that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and glycogen synthase kinase 3β (GSK3β), kinases implicated in autophagy function, increased with PGRN treatment under stress. Together, our data suggest that PGRN prevents hyperglycemia-induced decreases in autophagy by increasing autophagy flux via increased ERK1/2 kinase activity in primary rat cortical neurons.