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Abstract Background Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. Methods We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. Discussion This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety Trial registration ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019

Abstract Background Harm reduction for people who use drugs (PWUD) is an established evidence-based practice that encompasses a wide variety of services, delivery formats, and settings and has been named a priority in US drug policy. Harm reduction is focused on planning with communities and meeting PWUD where they are and encompasses a wide variety of interventions. We describe and report the feasibility, acceptability, and process implementation outcomes for an innovative pilot drug overdose harm reduction intervention, Block-by-Block (BXB), focused on training for and distribution of naloxone and test strips in areas identified as high risk for fatal overdoses. Case presentation Beginning operations in 2022, BXB operates in five pilot sites in four Illinois counties. Through partnerships with local organizations, BXB delivers harm reduction services in a private setting (home) or in a setting not specifically focused on serving PWUD (businesses, libraries, faith-based organizations, etc.) to reach PWUD and their friends, family and neighbors living in areas disproportionately affected by opioid overdose death. The intervention theory is based on acknowledgement that harm reduction services that require PWUD to visit a mobile unit, van or community organization, may not reach those in need or their friends, neighbors, and family for a variety of reasons including stigma associated with drug use, lack of awareness about these services, or where to locate them. Services delivered include education and training in the use of naloxone and fentanyl, xylazine and benzodiazepine test strips. Leave behind materials include naloxone, test strips and handouts with information on the intervention and local resources. Conclusions Results to date indicate that this intervention is feasible –over half (55%) of the doors approached were answered. Acceptability of the intervention as delivered is high --people at 75% of doors that were answered were interested in and received training and/or supplies. BXB is flexible in that it has been quickly adapted to changes in community conditions, the drug supply, and shifting high risk areas as they developed. This is a promising intervention that leverages available data and resources and is readily implementable in communities with support from a central program administrator and access to geo-coded data.

There is increasing interest in the measurement of methane (CH4) emissions from tree stems in a wide range of ecosystems so as to determine how they contribute to the total ecosystem flux. To date, tree CH4 fluxes are commonly measured using rigid closed chambers (static or dynamic), which often pose challenges as these are bulky and limit measurement of CH4 fluxes to only a very narrow range of tree stem sizes and shapes. To overcome these challenges we aimed to design and test new semi-rigid stem-flux chambers (or sleeves). We compared the CH4 permeability of the new semi-rigid chambers with that of the traditional rigid chamber approach, in the laboratory and in the field, with continuous flow or syringe injections. We found that the semi-rigid chambers had reduced gas permeability and optimal stem gas exchange surface to total chamber volume ratio (Sc / Vtot) better headspace mixing, especially when connected in a dynamic mode to a continuous flow gas analyser. Semi-rigid sleeves can easily be constructed and transported in multiple sizes, are extremely light, cheap to build and fast to deploy. This makes them ideal for use in remote ecosystems where access logistics is complicated.

BackgroundThis study provides an update on the status of the COVID-19 pandemic in Canada, building upon our initial analysis conducted in 2020 by incorporating an additional 2 years of data. ObjectiveThis study aims to (1) summarize the status of the pandemic in Canada when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023; (2) use dynamic and genomic surveillance methods to describe the history of the pandemic in Canada and situate the window of the WHO declaration within the broader history; and (3) provide historical context for the course of the pandemic in Canada. MethodsThis longitudinal study analyzed trends in traditional surveillance data and dynamic panel estimates for COVID-19 transmissions and deaths in Canada from June 2020 to May 2023. We also used sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. For these sequences, we used Nextclade nomenclature to collect clade designations and Pangolin nomenclature for lineage designations of SARS-CoV-2. We used 1-sided t tests of dynamic panel regression coefficients to measure the persistence of COVID-19 transmissions around the WHO declaration. Finally, we conducted a 1-sided t test for whether provincial and territorial weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. ResultsCanada’s speed remained below the outbreak threshold for 8 months by the time of the WHO declaration ending the COVID-19 emergency of international concern. Acceleration and jerk were also low and stable. While the 1-day persistence coefficient remained statistically significant and positive (1.074; P

BackgroundThis study updates the initial COVID-19 pandemic surveillance in sub-Saharan Africa (SSA) from 2020 by providing 2 additional years of data for the region. ObjectiveFirst, we aimed to measure whether there was an expansion or contraction in the pandemic in SSA when the World Health Organization (WHO) declared an end to the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we used dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aimed to provide historical context for the course of the pandemic in SSA. MethodsIn addition to updates of traditional surveillance data and dynamic panel estimates from the original study by Post et al (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and used Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t-test to assess whether regional weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with a rolling 6-month window of data across the sample period. ResultsSpeed for the region remained well below the outbreak threshold before and after the WHO declaration. Acceleration and jerk were also low and stable. The 7-day persistence coefficient remained somewhat large (1.11) and statistically significant. However, both shift parameters for the weeks around the WHO declaration were negative, meaning the clustering effect of new COVID-19 cases had become recently smaller. From November 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to 10 was insignificant for the entire sample period. ConclusionsWhile COVID-19 continues to circulate in SSA, the region never reached outbreak status, and the weekly transmission rate remained below 1 case per 100,000 population for well over 1 year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold for its classification as a pandemic. Both standard and enhanced surveillance metrics confirm that the pandemic ended in SSA by the time the WHO made its declaration.

BackgroundHuman mobility data have been used as a potential novel data source to guide policies and response planning during the COVID-19 global pandemic. The COVID-19 Mobility Data Network (CMDN) facilitated the use of human mobility data around the world. Both researchers and policy makers assumed that mobility data would provide insights to help policy makers and response planners. However, evidence that human mobility data were operationally useful and provided added value for public health response planners remains largely unknown. ObjectiveThis exploratory study focuses on advancing the understanding of the use of human mobility data during the early phase of the COVID-19 pandemic. The study explored how researchers and practitioners around the world used these data in response planning and policy making, focusing on processing data and human factors enabling or hindering use of the data. MethodsOur project was based on phenomenology and used an inductive approach to thematic analysis. Transcripts were open-coded to create the codebook that was then applied by 2 team members who blind-coded all transcripts. Consensus coding was used for coding discrepancies. ResultsInterviews were conducted with 45 individuals during the early period of the COVID-19 pandemic. Although some teams used mobility data for response planning, few were able to describe their uses in policy making, and there were no standardized ways that teams used mobility data. Mobility data played a larger role in providing situational awareness for government partners, helping to understand where people were moving in relation to the spread of COVID-19 variants and reactions to stay-at-home orders. Interviewees who felt they were more successful using mobility data often cited an individual who was able to answer general questions about mobility data; provide interactive feedback on results; and enable a 2-way communication exchange about data, meaning, value, and potential use. ConclusionsHuman mobility data were used as a novel data source in the COVID-19 pandemic by a network of academic researchers and practitioners using privacy-preserving and anonymized mobility data. This study reflects the processes in analyzing and communicating human mobility data, as well as how these data were used in response planning and how the data were intended for use in policy making. The study reveals several valuable use cases. Ultimately, the role of a data translator was crucial in understanding the complexities of this novel data source. With this role, teams were able to adapt workflows, visualizations, and reports to align with end users and decision makers while communicating this information meaningfully to address the goals of responders and policy makers.

BackgroundThis study updates our findings from the COVID-19 pandemic surveillance we first conducted in South Asia in 2020 with 2 additional years of data for the region. We assess whether COVID-19 had transitioned from pandemic to endemic at the point the World Health Organization (WHO) ended the public health emergency status for COVID-19 on May 5, 2023. ObjectiveFirst, we aim to measure whether there was an expansion or contraction in the pandemic in South Asia around the WHO declaration. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in South Asia. MethodsIn addition to updating the traditional surveillance data and dynamic panel estimates from our original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional weekly speed or transmission rate per 100,000 population was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. ResultsSpeed for the region had remained below the outbreak threshold for over a year by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day persistence coefficients remained statistically significant and positive (1.168), the 7-day persistence coefficient was negative (–0.185), suggesting limited cluster effects in which cases on a given day predict cases 7 days forward. Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any overall change in the persistence measure around the time of the WHO declaration. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 was statistically insignificant across the entire pandemic. ConclusionsWhile COVID-19 continued to circulate in South Asia, the rate of transmission had remained below the outbreak threshold for well over a year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had ended by the time of the WHO declaration. Prevention policies should be a focus ahead of future pandemics. On that point, policy should emphasize an epidemiological task force with widespread testing and a contact-tracing system.

BackgroundThis study updates the COVID-19 pandemic surveillance in Central Asia we conducted during the first year of the pandemic by providing 2 additional years of data for the region. The historical context provided through additional data can inform regional preparedness and early responses to infectious outbreaks of either the SARS-CoV-2 virus or future pathogens in Central Asia. ObjectiveFirst, we aim to measure whether there was an expansion or contraction in the pandemic in Central Asia when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in Central Asia. MethodsTraditional surveillance metrics, including counts and rates of COVID-19 transmissions and deaths, and enhanced surveillance indicators, including speed, acceleration, jerk, and persistence, were used to measure shifts in the pandemic. To identify the appearance and duration of variants of concern, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. ResultsSpeed for the region had remained below the outbreak threshold for 7 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant, the coefficients were relatively small in magnitude (0.125 and 0.347, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, were both significant and negative, meaning the clustering effect of new COVID-19 cases became even smaller in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 became entirely insignificant for the first time in March 2023. ConclusionsAlthough COVID-19 continues to circulate in Central Asia, the rate of transmission remained well below the threshold of an outbreak for 7 months ahead of the WHO declaration. COVID-19 appeared to be endemic in the region and no longer reached the threshold of a pandemic. Both standard and enhanced surveillance metrics suggest the pandemic had ended by the time of the WHO declaration.

BackgroundThis study updates the COVID-19 pandemic surveillance in the Middle East and North Africa (MENA) we first conducted in 2020 with 2 additional years of data for the region. ObjectiveThe objective of this study is to determine whether the MENA region meets the criteria for moving from a pandemic to endemic. In doing so, this study considers pandemic trends, dynamic and genomic surveillance methods, and region-specific historical context for the pandemic. These considerations continue through the World Health Organization (WHO) declaration of the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. MethodsIn addition to updates to traditional surveillance data and dynamic panel estimates from the original study by Post et al, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional weekly speed of COVID-19 spread was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data from September 4, 2020, to May 12, 2023. ResultsThe speed of COVID-19 spread for the region had remained below the outbreak threshold for 7 continuous months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant and positive, the weekly shift parameters suggested the coefficients had most recently turned negative, meaning the clustering effect of new COVID-19 cases became even smaller in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of the speed of spread equal to 10 became entirely insignificant from October 2022 onward. ConclusionsThe COVID-19 pandemic had far-reaching effects on MENA, impacting health care systems, economies, and social well-being. Although COVID-19 continues to circulate in the MENA region, the rate of transmission remained well below the threshold of an outbreak for over 1 year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had transitioned to endemic by the time of the WHO declaration.

BackgroundIn this study, we built upon our initial research published in 2020 by incorporating an additional 2 years of data for Europe. We assessed whether COVID-19 had shifted from the pandemic to endemic phase in the region when the World Health Organization (WHO) declared the end of the public health emergency of international concern on May 5, 2023. ObjectiveWe first aimed to measure whether there was an expansion or contraction in the pandemic in Europe at the time of the WHO declaration. Second, we used dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we provided the historical context for the course of the pandemic in Europe in terms of policy and disease burden at the country and region levels. MethodsIn addition to the updates of traditional surveillance data and dynamic panel estimates from the original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-tailed t test for whether regional weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. ResultsSpeed for the region had remained below the outbreak threshold for 4 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day and 7-day persistence coefficients remained statistically significant, the coefficients were moderate in magnitude (0.404 and 0.547, respectively; P

BackgroundIn May 2020, the World Health Organization (WHO) declared Latin America and the Caribbean (LAC) the epicenter of the COVID-19 pandemic, with over 40% of worldwide COVID-19–related deaths at the time. This high disease burden was a result of the unique circumstances in LAC. ObjectiveThis study aimed to (1) measure whether the pandemic was expanding or contracting in LAC when the WHO declared the end of COVID-19 as a public health emergency of international concern on May 5, 2023; (2) use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history; and (3) provide, with a focus on prevention policies, a historical context for the course of the pandemic in the region. MethodsIn addition to updates of traditional surveillance data and dynamic panel estimates from the original study, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern (VOCs). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Additionally, we conducted a 1-sided t test for whether the regional weekly speed (rate of novel COVID-19 transmission) was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the period from August 2020 to May 2023. ResultsThe speed of pandemic spread for the region had remained below the outbreak threshold for 6 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant for the 120-day period ending on the week of May 5, 2023, the coefficients were relatively modest in magnitude (0.457 and 0.491, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any change in this clustering effect of cases on future cases. From December 2021 onward, Omicron was the predominant VOC in sequenced viral samples. The rolling t test of speed=10 became entirely insignificant from January 2023 onward. ConclusionsAlthough COVID-19 continues to circulate in LAC, surveillance data suggest COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. However, the region experienced a high COVID-19 burden in the early stages of the pandemic, and prevention policies should be an immediate focus in future pandemics. Ahead of vaccination development, these policies can include widespread testing of individuals and an epidemiological task force with a contact-tracing system.

BackgroundWith the rapid growth of Nigeria's older population, it has become important to establish age-friendly healthcare systems that support care for older people. This study aimed to explore the barriers and facilitators to the delivery of age-friendly health services from the perspectives of primary healthcare managers in Lagos State, Nigeria.MethodWe conducted 13 key informant interviews including medical officers of health, principal officers of the (Primary Health Care) PHC Board and board members at the state level. Using a grounded theory approach, qualitative data analysis was initially done by rapid thematic analysis followed by constant comparative analysis using Dedoose software to create a codebook. Three teams of two coders each blind-coded the interviews, resolved coding discrepancies, and reviewed excerpts by code to extract themes.ResultsThe main barriers to the delivery of age-friendly services included the lack of recognition of older adults as a priority population group; absence of PHC policies targeted to serve older adults specifically; limited training in care of older adults; lack of dedicated funding for care services for older adults and data disaggregated by age to drive decision-making. Key facilitators included an acknowledged mission of the PHCs to provide services for all ages; opportunities for the enhancement of older adult care; availability of a new building template that supports facility design which is more age-friendly; access to basic health care funds; and a positive attitude towards capacity building for existing workforce.ConclusionWhile we identified a number of challenges, these offer opportunities to strengthen and prioritize services for older adults in PHCs and build on existing facilitators. Work is needed to identify and test interventions to overcome these challenges and improve the responsiveness of the PHC system to older adults through the delivery of age-friendly health services in PHCs in Lagos, Nigeria.

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the ISG15 gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/β signalling. Due to this dual role, ISG15 deficiency can present with various clinical phenotypes, ranging from susceptibility to mycobacterial infection to autoinflammation characterised by necrotising skin lesions, intracerebral calcification, and pulmonary involvement. In this report, we describe novel variants found in two different families that result in complete ISG15 deficiency and severe skin ulceration. Whole exome sequencing identified a heterozygous missense p.Q16X ISG15 variant and a heterozygous multigene 1p36.33 deletion in the proband from the first family. In the second family, a homozygous total ISG15 gene deletion was detected in two siblings. We also conducted further analysis, including characterisation of cytokine dysregulation, interferon-stimulated gene expression, and p-STAT1 activation in lymphocytes and lesional tissue. Finally, we demonstrate the complete and rapid resolution of clinical symptoms associated with ISG15 deficiency in one sibling from the second family following treatment with the Janus kinase (JAK) inhibitor baricitinib.

Pediatric traumatic brain injury (TBI) often induces significant disability in patients, including long-term motor deficits. Early detection of injury severity is key in determining a prognosis and creating appropriate intervention and rehabilitation plans. However, conventional magnetic resonance imaging (MRI) scans, such as T2 Weighted (T2W) sequences, do not reliably assess the extent of microstructural white matter injury. Diffusion tensor imaging (DTI) tractography enables three-dimensional reconstruction of specific white matter tracts throughout the brain in order to detect white matter injury based on anisotropic diffusion. The objective of this study was to employ DTI tractography to detect acute changes to white matter integrity within the intersecting fibers of key motor-related brain regions following TBI. Piglets were assigned to either the sham craniectomy group (sham; n = 6) or the controlled cortical impact TBI group (TBI; n = 6). Gait and MRI were collected at seven days post-surgery (DPS). T2W sequences confirmed a localized injury predominately in the ipsilateral hemisphere in TBI animals. TBI animals, relative to sham animals, showed an increased apparent diffusion coefficient (ADC) and decreased fractional anisotropy (FA) in fiber bundles associated with key brain regions involved in motor function. TBI animals exhibited gait deficits, including stride and step length, compared to sham animals. Together these data demonstrate acute reductions in the white matter integrity, measured by DTI tractography, of fibers intersecting key brain regions that strongly corresponded with acute motor deficits in a pediatric piglet TBI model. These results provide the foundation for the further development of DTI-based biomarkers to evaluate motor outcomes following TBI.

The catabolic activity of the ruminal microbial community of cattle enables the conversion of low-quality feedstuffs into meat and milk. The rate at which this conversion occurs is termed feed efficiency, which is of crucial importance given that feed expenses account for up to 70% of the cost of animal production. The present study assessed the relationship between cattle feed efficiency and the composition of their ruminal microbial communities during the feedlot finishing period. Angus steers (n = 65) were fed a feedlot finishing diet for 82 days and their growth performance metrics were evaluated. These included the dry matter intake (DMI), average daily gain (ADG), and residual feed intake (RFI). Steers were rank-ordered based upon their RFI, and the five lowest RFI (most efficient) and five highest RFI (least efficient) steers were selected for evaluations. Ruminal fluid samples were collected on days 0 and 82 of the finishing period. Volatile fatty acids (VFA) were quantified, and microbial DNA was extracted and the 16S rRNA gene was sequenced. The results showed that the ADG was not different (p = 0.82) between efficiency groups during the 82-day feedlot period; however, the efficient steers had lower (p = 0.03) DMI and RFI (p = 0.003). Less-efficient (high RFI) steers developed higher (p = 0.01) ruminal Methanobrevibacter relative abundances (p = 0.01) and tended (p = 0.09) to have more Methanosphaera. In high-efficiency steers (low RFI), the relative abundances of Ruminococcaceae increased (p = 0.04) over the 82-day period. The molar proportions of VFA were not different between the two efficiency groups, but some changes in the concentration of specific VFA were observed over time. The results indicated that the ruminal microbial populations of the less-efficient steers contained a greater relative abundance of methanogens compared to the high-efficiency steers during the feedlot phase, likely resulting in more energetic waste in the form or methane and less dietary energy being harvested by the less-efficient animals.

The objective of this study was to determine the impact of varying dietary manganese and selenium concentrations, antioxidant cofactors, on the growth performance and fecal microbial populations of nursery pigs. The piglets (N = 120) were blocked by weight (5.22 ± 0.7 kg) and sex. The pens (n = 5/treatment) within a block were randomly assigned to diets in a 2 × 3 factorial design to examine the effects of Se (0.1 and 0.3 mg/kg added Se) and Mn (0, 12, and 24 mg/kg added Mn) and were fed in three phases (P1 = d 1–7, P2 = d 8–21, P3 = d 22–35). The pigs and orts were weighed weekly. Fecal samples were collected d 0 and 35 for 16S rRNA bacterial gene sequencing and VFA analysis. The data were analyzed as factorial via GLM in SAS. There was a linear response (p < 0.05) in overall ADG across dietary Mn. Supplementing 24 mg/kg Mn tended to decrease (p < 0.10) the relative abundance of many bacteria possessing pathogenic traits relative to Mn controls. Meanwhile, increasing Mn concentration tended to foster the growth of bacteria correlated with gut health and improved growth (p < 0.10). The data from this study provide preliminary evidence on the positive effects of manganese on growth and gut health of nursery pigs.

Abstract Background Clinical trial investigators may need to evaluate treatment effects in a specific subgroup (or subgroups) of participants in addition to reporting results of the entire study population. Such subgroups lack power to detect a treatment effect, but there may be strong justification for borrowing information from a larger patient group within the same trial, while allowing for differences between populations. Our aim was to develop methods for eliciting expert opinions about differences in treatment effect between patient populations, and to incorporate these opinions into a Bayesian analysis. Methods We used an interaction parameter to model the relationship between underlying treatment effects in two subgroups. Elicitation was used to obtain clinical opinions on the likely values of the interaction parameter, since this parameter is poorly informed by the data. Feedback was provided to experts to communicate how uncertainty about the interaction parameter corresponds with relative weights allocated to subgroups in the Bayesian analysis. The impact on the planned analysis was then determined. Results The methods were applied to an ongoing non-inferiority trial designed to compare antiretroviral therapy regimens in 707 children living with HIV and weighing ≥ 14 kg, with an additional group of 85 younger children weighing

Abstract Objective To examine prevalence, demographic, and incident factors associated with opioid-positivity in Illinois suicide decedents who died by causes other than poisoning. Method Cross-sectional study of Illinois’ suicide decedents occurring between January 2015 and December 2017. Data come from the National Violent Death Reporting System. We used Chi-square tests to compare decedent and incident circumstance characteristics by opioid toxicology screen status. Incident narratives were analyzed to obtain physical and mental health histories and circumstances related to fatal injury events. Results Of 1007 non-poisoning suicide decedents screened for opioids, 16.4% were opioid-positive. White race, age 75 and over, and widowed or unknown marital status were associated with opioid-positivity. Among opioid-positive decedents, 25% had a history of substance use disorder (SUD), 61% depression, and 19% anxiety. The majority (52%) of opioid-positive decedents died by firearm, a higher percentage than opioid-negative decedents. Conclusion The opioid overdose crisis largely has not overlapped with non-poisoning suicide in this study. Overall, our analyses have not identified additional risk factors for suicide among opioid-positive suicide decedents. However, the overlap between opioid-positivity, SUD, and physical and mental health problems found among decedents in our data suggest several suicide prevention opportunities. These include medication assisted treatment for SUD which has been shown to reduce suicide, screening for opioid/benzodiazepine overlap, and limiting access to lethal means during opioid use. Improved death scene investigations for substances and use of the Prescription Drug Monitoring Program to document prescriptions are needed to further understanding of the role of substances in non-poisoning suicide.

Early childhood is an important development period for establishing healthy physical activity (PA) habits. The objective of this study was to evaluate PA levels in a representative sample of U.S. preschool-aged children. The study sample included 301 participants (149 girls, 3–5 years of age) in the 2012 U.S. National Health and Examination Survey National Youth Fitness Survey. Participants were asked to wear an ActiGraph accelerometer on their wrist for 7 days. A machine learning random forest classification algorithm was applied to accelerometer data to estimate daily time spent in moderate- and vigorous-intensity PA (MVPA; the sum of minutes spent in running, walking, and other moderate- and vigorous-intensity PA) and total PA (the sum of MVPA and light-intensity PA). We estimated that U.S. preschool-aged children engaged in 28 min/day of MVPA and 361 min/day of total PA, on average. MVPA and total PA levels were not significantly different between males and females. This study revealed that U.S. preschool-aged children engage in lower levels of MVPA and higher levels of total PA than the minimum recommended by the World Health Organization.

Dynamic changes in the oral microbiome have gained attention due to their potential diagnostic role in neurological diseases such as Alzheimer’s disease and Parkinson’s disease. Traumatic brain injury (TBI) is a leading cause of death and disability in the United States, but no studies have examined the changes in oral microbiome during the acute stage of TBI using a clinically translational pig model. Crossbred piglets (4–5 weeks old, male) underwent either a controlled cortical impact (TBI, n = 6) or sham surgery (sham, n = 6). The oral microbiome parameters were quantified from the upper and lower gingiva, both buccal mucosa, and floor of the mouth pre-surgery and 1, 3, and 7 days post-surgery (PS) using the 16S rRNA gene. Faith’s phylogenetic diversity was significantly lower in the TBI piglets at 7 days PS compared to those of sham, and beta diversity at 1, 3, and 7 days PS was significantly different between TBI and sham piglets. However, no significant changes in the taxonomic composition of the oral microbiome were observed following TBI compared to sham. Further studies are needed to investigate the potential diagnostic role of the oral microbiome during the chronic stage of TBI with a larger number of subjects.

Numerous studies have examined the link between the presence of specific gastrointestinal bacteria and the feed efficiency of cattle. However, cattle undergo dietary changes during their productive life which can cause fluctuations in their microbial consortium. The objective of the present study was to assess changes in the fecal microbiome of beef steers genetically selected to be divergent in feedlot feed efficiency, to determine whether differences in their fecal microbiomes could be detected as early as weaning, and continued throughout the rearing process regardless of dietary changes. Fecal samples were collected at weaning, yearling age, and slaughter for a group of 63 steers. Based on their feedlot-finishing performance, the steers were selected and divided into two groups according to their residual feed intake (RFI): efficient steers (low-RFI; n = 7) and inefficient steers (high-RFI; n = 8). To ascertain the fecal microbial consortium and volatile fatty acid (VFA) content, 16S rRNA gene sequencing and VFA analysis were performed. Overall, bacterial evenness and diversity were greater at weaning compared to yearling and slaughter for both efficiency groups (P < 0.001). Feedlot RFI linearly decreased as both Shannon diversity and Ruminococcaceae abundance increased (R2 = 65.6 and 60.7%, respectively). Abundances of Ruminococcaceae, Rikenellaceae, and Christensenellaceae were higher at weaning vs. yearling age and slaughter (P < 0.001); moreover, these families were consistently more abundant in the feces of the low-RFI steers (for most of the timepoints evaluated; P ≤ 0.05), compared to the high-RFI steers. Conversely, abundances of Bifidobacteriaceae were numerically higher in the feces of the high-RFI steers throughout their lifespan. Total VFA concentrations increased at slaughter compared to weaning and yearling for both efficiency groups (P < 0.001). The acetate:propionate ratio decreased linearly (P < 0.001) throughout the life of the steers regardless of their efficiency, reflective of dietary changes. Our results indicate that despite fluctuations due to animal age and dietary changes, specific bacterial families may be correlated with feed efficiency of steers. Furthermore, such differences may be identifiable at earlier stages of the production cycle, potentially as early as weaning.

The microorganisms inhabiting the gastrointestinal tract (GIT) of ruminants have a mutualistic relationship with the host that influences the efficiency and health of the ruminants. The GIT microbiota interacts with the host immune system to influence not only the GIT, but other organs in the body as well. The objective of this review is to highlight the importance of the role the gastrointestinal microbiota plays in modulating the health of a host through communication with different organs in the body through the microbiome-gut-organ axes. Among other things, the GIT microbiota produces metabolites for the host and prevents the colonization of pathogens. In order to prevent dysbiosis of the GIT microbiota, gut microbial therapies can be utilized to re-introduce beneficial bacteria and regain homeostasis within the rumen environment and promote gastrointestinal health. Additionally, controlling GIT dysbiosis can aid the immune system in preventing disfunction in other organ systems in the body through the microbiome-gut-brain axis, the microbiome-gut-lung axis, the microbiome-gut-mammary axis, and the microbiome-gut-reproductive axis.

The gastrointestinal microbiota of cattle is important for feedstuff degradation and feed efficiency determination. This study evaluated the fecal microbiome of Angus steers with distinct feed efficiencies during the feedlot-finishing phase. Angus steers (n = 65), fed a feedlot-finishing diet for 82 days, had growth performance metrics evaluated. Steers were ranked based upon residual feed intake (RFI), and the 5 lowest RFI (most efficient) and 5 highest RFI (least efficient) steers were selected for evaluation. Fecal samples were collected on 0-d and 82-d of the finishing period and microbial DNA was extracted and evaluated by 16S rRNA gene sequencing. During the feedlot trial, inefficient steers had decreased (p = 0.02) Ruminococcaceae populations and increased (p = 0.01) Clostridiaceae populations. Conversely, efficient steers had increased Peptostreptococcaceae (p = 0.03) and Turicibacteraceae (p = 0.01), and a trend for decreased Proteobacteria abundance (p = 0.096). Efficient steers had increased microbial richness and diversity during the feedlot period, which likely resulted in increased fiber-degrading enzymes in their hindgut, allowing them to extract more energy from the feed. Results suggest that cattle with better feed efficiency have greater diversity of hindgut microorganisms, resulting in more enzymes available for digestion, and improving energy harvest in the gut of efficient cattle.

The ruminal microbiota of Angus cows and steers were characterized using 16s rRNA gene sequencing, and the expression of their metabolic pathways was predicted. Samples were collected on weaning day from the steers and the cows, and subsequently on three other occasions from the steers. Results showed that microbial richness, evenness, and diversity decreased (p < 0.001) in the rumen of the steers as they were weaned and transitioned to a high-concentrate feedlot diet. However, on the day of weaning, microbial evenness was similar to that observed in the rumen of cows (p = 0.12). The abundance of archaea was similar (p = 0.59) between the cows and steers at weaning, but it decreased (p = 0.04) in the rumen of steers after weaning, and remained stable (p ≥ 0.44) for the remainder of their lives. Likewise, no difference (p = 0.51) in the abundance of Bacteroidetes was detected between the cows and the calves on the day they were weaned, but the abundance of this phylum increased (p = 0.001) and remained stable after that. These results suggest that cows may have a strong influence on the composition, and help modulate the ruminal microbiota of young calves; however, following weaning, their ruminal microbiotas tend to differentiate from that state observed at earlier ages.