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Jean V Rubanick, Medora B Pashmakova, Micah A Bishop, James W Barr Department of Veterinary Small Animal Clinical Sciences, Texas A&M University, College Station, TX, USA Abstract: A hospital-based, prospective cross-sectional study was used to compare kaolin-activated thromboelastography (TEG) parameters with traditional coagulation tests in 29 hospitalized dogs. Cases were included if the attending clinician requested coagulation testing. Blood was obtained from each dog and coagulation (prothrombin time, partial thromboplastin time, antithrombin activity, d-dimer concentration, and fibrinogen concentration) and TEG analyses were performed. Hematocrit (Hct) was also measured. Traditional coagulation results were evaluated for correlation with those from kaolin-activated TEG. Spearman’s correlation was used to calculate correlation coefficients. Fibrinogen was positively correlated with maximum amplitude (Pearson r=0.72, P

Introduction: Salmonella and Campylobacter spp. are commonly reported bacterial foodborne pathogens causing morbidity and mortality worldwide. In rural areas, where there is a high occurrence rate of human–animal interactions and poor hygiene practices, shedding animals present a high risk to humans in acquiring animal-associated infections. Materials and methods: Seasonal prevalence of Campylobacter jejuni, Campylobacter coli, and Salmonella spp. in scavenging indigenous chicken faeces was determined by polymerase chain reaction (PCR). Antimicrobial resistance was studied in Salmonella isolates by disc diffusion method, and whole-genome sequenced isolates were used to determine Salmonella serovars, antimicrobial resistance genes, virulence genes, and plasmid profile. Results: The overall prevalence of Campylobacter in chickens was 7.2% in the dry season and 8.0% in the rainy season (p = 0.39), and that of Salmonella was 11.1% in the dry season and 16.2% in the rainy season (p = 0.29). Salmonella serovars detected were II 35:g,m,s,t:-, Ball, Typhimurium, Haardt/Blockley, Braenderup, and Enteritidis/Gallinarum. One S. II 35:g,m,s,t:- isolate was resistant to ampicillin and the rest were either intermediate resistant or pansusceptible to the tested antimicrobials. The resistance genes observed were CatA, tetJ, and fosA7, most common in Ball than in other serovars. Seven plasmids were identified, more common in serovar Ball and less common in II 35:g,m,s,t:-. Serovar II 35:g,m,s,t:- isolates were missing some of the virulence genes important for Salmonella pathogenicity found in other serovars isolated. Conclusion: PCR detection of Campylobacter spp. and Salmonella spp. in chickens necessitate the improvement of hygiene at the household level and reducing human–chicken interaction as a strategy of preventing humans from acquiring chicken-associated bacteria, which would enter the human food chain. Infrequent use of antimicrobials in this type of poultry is most likely the reason for the low rates of antimicrobial resistance observed in this study.

U.S. history is rooted in the rationalization of family separation to benefit white supremacy, capitalism and mainstream U.S. values. Because of this dark history, the U.S. history has become the world’s leader of legal destruction of families through termination of parental rights. It is the only country in the world that routinely pays people to adopt children whose parents, often women, very much want to be their parent. The Adoption and Safe Families Act, enacted in 1997, wildly changed the legal landscape of the family regulation system. At that time 47% of the children in the system were Black, and the drug war had been targeting Black men for low level offenses, and labeling Black mothers as “crack moms”. The result was an extreme attack on Black families, for which we have yet to recover. Abolition teaches us to unroot oppressive structures, disrupt and dismantle them while simultaneously supporting a praxis of imagination, healing, and building. In this paper, we encourage people not only to work to repeal ASFA, but to interrogate the imagination which entrenched the legitimacy of ASFA. Part I centers the discussion in our imaginations—the world we want to build, and the demands we are making. Part II moves into a discussion about the counter imagination, the ideas and mythology that created ASFA—the legal framework. In this section, we isolate ASFA as a target for abolition and organizing. Part III moves into a practical discussion about ethical ways to mobilize around ASFA. This section is intended to invite the reader to learn, and question, together. It invites questions, thinking, and problem solving in lieu of providing a recommendation.

C’est dans une perspective pluridisciplinaire qui allie didacticiens, linguistes, théoriciens de la littérature et psycholinguistes que nous abordons la question : comment aider les élèves à identifier et à interpréter les implicites dans le texte littéraire pour mieux lire ? Pour ce faire, nous commençons par présenter notre corpus constitué de films réalisés en classe lors de séances de lecture d’un album mettant en jeu deux types d’implicite, les présuppositions et les implicatures, pour lesquels les psycholinguistes ont montré que les enfants dès l’âge de cinq ans avaient une certaine maîtrise dans des contextes favorables. L’intérêt de travailler avec les élèves ces deux sortes d’implicite est qu’il permet de les sensibiliser au fait que toutes les informations d’un texte ne se situent pas sur le même plan et qu’il faut être particulièrement attentif aux choix des mots utilisés dans une histoire pour effectuer un calcul interprétatif correctement fondé. Nous exposons ensuite les pistes – tant linguistiques que littéraires – que nous avons explorées pour outiller les enseignants et cette partie de l’article est l’occasion d’indiquer les prolongements à donner à ce type d’études. Enfin, nous proposons une analyse d’une situation de classe afin de mettre en évidence les stratégies interprétatives des élèves (que celles-ci soient justes ou erronées) lorsqu’ils coconstruisent oralement le sens global d’un texte à partir des indices implicites que sont les présuppositions et les implicatures. Cet examen, qui souligne l’importance du rôle de l’enseignant, conduit dans un effet retour à préciser et à étoffer les pistes théoriques susceptibles d’améliorer l’enseignement de la compréhension de la trame implicite d’un texte.

African swine fever remains an important pig disease globally in view of its rapid spread, economic impacts and food implications, with no option of vaccination or treatment. The Southern Highlands zone of Tanzania, an important pig-producing hub in East Africa, is endemic with African swine fever (ASF). From approximately the year 2010, the recurrence of outbreaks has been observed and it has now become a predictable pattern. We conducted exploratory participatory epidemiology and participatory disease surveillance in the Southern Highlands to understand the pig sector and the drivers and facilitators of infections, risk factors and dynamics of ASF in this important pig-producing area. Pigs continue to play a major role in rural livelihoods in the Southern Highlands and pork is a major animal protein source. Outbreaks of diseases, particularly ASF, have continued to militate against the scaling up of pig operations in the Southern Highlands. Intra- and inter-district and trans-border transnational outbreaks of ASF, the most common disease in the Southern Highlands, continue to occur. Trade and marketing systems, management systems, and lack of biosecurity, as well as anthropogenic (human) issues, animals and fomites, were identified as risk factors and facilitators of ASF infection. Changes in human behavior and communication in trade and marketing systems in the value chain, biosecurity and pig management practices are warranted. Relevant training must be implemented alongside the launch of the national ASF control strategy for Tanzania, which already established a roadmap for combating ASF in Tanzania. The high-risk points (slaughter slabs, border areas, and farms with poor biosecurity) and high-risk period (November−March) along the pig value chain must be targeted as critical control points for interventions in order to reduce the burden of infection.

This work investigates the deposition of hybrid layers, for next generation in energy conversion, via spray coating. Understanding the effect that this deposition procedure has on these layers could lead to the rapid development of these technologies, for both laboratory applications and commercialisation. Synthesised zinc ethyl xanthate and poly(3-hexylthiophene-2,5-diyl) was spray-coated on substrates and heated to a temperature of 160 °C, to the hybrid film. Optical, morphological and conductive properties of these films were investigated and linked to the spray coating duration. It was revealed that shorter-duration spray times led to relatively low conductivity and smoother films, moreover, an increase in spraying duration also led to an increase in conductivity, but with increased roughness, from 6.178 nm to 8.317 nm. As the spray time was further increased factors, including film layering effects, led to a gradual decrease in conductivity accompanied by a decrease in the roughness. Smoother films were shown to result in higher light absorption, characterised by wider band gaps, which could be due to the crystal structure of the inorganic phase. The controllability of this rapid, facile, and inexpensive spray deposition process was then demonstrated in fabrication of prototype photovoltaic devices.

Neutron capture and transmission measurements have been performed, and resonance parameter analysis has been completed for dysprosium, Dy, and rhenium, Re. The 60 MeV electron accelerator at RPI Gaerttner LINAC Center produced neutrons in the thermal and epithermal energy regions for these measurements. Transmission measurements were made using 6Li glass scintillation detectors. The neutron capture measurements were made with a 16-segment NaI multiplicity detector. The detectors for all experiments were located at ≈25 m except for thermal transmission, which was done at ≈15 m. The dysprosium samples included one highly enriched 164Dy metal, 6 liquid solutions of enriched 164Dy, two natural Dy metals. The Re samples were natural metals. Their capture yield normalizations were corrected for their high gamma attenuation. The multi-level R-matrix Bayesian computer code SAMMY was used to extract the resonance parameters from the data. 164Dy resonance data were analyzed up to 550 eV, other Dy isotopes up to 17 eV, and Re resonance data up to 1 keV. Uncertainties due to resolution function, flight path, burst width, sample thickness, normalization, background, and zero time were estimated and propagated using SAMMY. An additional check of sample-to-sample consistency is presented as an estimate of uncertainty. The thermal total cross sections and neutron capture resonance integrals of 164Dy and Re were determined from the resonance parameters. The NJOY and INTER codes were used to process and integrate the cross sections. Plots of the data, fits, and calculations using ENDF/B-VII.1 resonance parameters are presented.

Abstract Background Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. An important determinant for CJD risk and phenotype is the M129V polymorphism of the human prion protein gene (PRNP), but there are also other coding and non-coding polymorphisms inside this gene. Methods We tested whether three non-coding polymorphism located inside the PRNP regulatory region (C-101G, G310C and T385C) were associated with risk of CJD and with age at onset in a United Kingdom population-based sample of 131 sporadic CJD (sCJD) patients and 194 controls. Results We found no disease association for either PRNP C-101G or PRNP T385C. Although the crude analysis did not show a significant association between PRNP G310C and sCJD (OR: 1.5; 95%CI = 0.7 to 2.9), after adjusting by PRNP M129V genotype, it resulted that being a C allele carrier at PRNP G310C was significantly (p = 0.03) associated with a 2.4 fold increased risk of developing sCJD (95%CI = 1.1 to 5.4). Additionally, haplotypes carrying PRNP 310C coupled with PRNP 129M were significantly overrepresented in patients (p = 0.02) compared to controls. Cases of sCJD carrying a PRNP 310C allele presented at a younger age (on average 8.9 years younger than those without this allele), which was of statistical significance (p = 0.05). As expected, methionine and valine homozygosity at PRNP M129V increased significantly the risk of sCJD, alone and adjusted by PRNP G310C (OR MM/MV = 7.3; 95%CI 3.9 to 13.5 and OR VV/MV = 4.0; 95%CI 1.7 to 9.3). Conclusions Our findings support the hypothesis that genetic variations in the PRNP promoter may have a role in the pathogenesis of sCJD.

Abstract Background Our purpose was to develop an induced musculoskeletal pain model of acute low back pain and examine the relationship among pain, disability and fear in this model. Methods Delayed onset muscle soreness was induced in 52 healthy volunteers (23 women, 17 men; average age 22.4 years; average BMI 24.3) using fatiguing trunk extension exercise. Measures of pain intensity, unpleasantness, and location, and disability, were tracked for one week after exercise. Results Pain intensity ranged from 0 to 68 with 57.5% of participants reporting peak pain at 24 hours and 32.5% reporting this at 48 hours. The majority of participants reported pain in the low back with 33% also reporting pain in the legs. The ratio of unpleasantness to intensity indicated that the sensation was considered more unpleasant than intense. Statistical differences were noted in levels of reported disability between participants with and without leg pain. Pain intensity at 24 hours was correlated with pain unpleasantness, pain area and disability. Also, fear of pain was associated with pain intensity and unpleasantness. Disability was predicted by sex, presence of leg pain, and pain intensity; however, the largest amount of variance was explained by pain intensity (27% of a total 40%). The second model, predicting pain intensity only included fear of pain and explained less than 10% of the variance in pain intensity. Conclusions Our results demonstrate a significant association between pain and disability in this model in young adults. However, the model is most applicable to patients with lower levels of pain and disability. Future work should include older adults to improve the external validity of this model.

Abstract Background Genetic analysis of the human prion protein gene (PRNP) in suspect cases of Creutzfeldt-Jakob disease (CJD) is necessary for accurate diagnosis and case classification. Previous publications on the genetic variation at the PRNP locus have highlighted the presence of numerous polymorphisms, in addition to the well recognised one at codon 129, with significant variability between geographically distinct populations. It is therefore of interest to consider their influence on susceptibility or the clinico-pathological disease phenotype. This study aimed to characterise the frequency and effect of PRNP open reading frame polymorphisms other than codon 129 in both disease and control samples sourced from the United Kingdom population. Methods DNA was extracted from blood samples and genetic data obtained by full sequence analysis of the prion protein gene or by restriction fragment length polymorphism analysis using restriction enzymes specific to the gene polymorphism under investigation. Results 147 of 166 confirmed cases of variant CJD (vCJD) in the UK have had PRNP codon 129 genotyping and all are methionine homozygous at codon 129; 118 have had full PRNP gene sequencing. Of the latter, 5 cases have shown other polymorphic loci: at codon 219 (2, 1.69%), at codon 202 (2, 1.69%), and a 24 bp deletion in the octapeptide repeat region (1, 0.85%). E219K and D202D were not found in sporadic CJD (sCJD) cases and therefore may represent genetic risk factors for vCJD. Genetic analysis of 309 confirmed UK sCJD patients showed codon 129 genotype frequencies of MM: 59.5% (n = 184), MV: 21.4% (n = 66), and VV: 19.1% (n = 59). Thirteen (4.2%) had the A117A polymorphism, one of which also had the P68P polymorphism, four (1.3%) had a 24 bp deletion, and a single patient had a novel missense variation at codon 167. As the phenotype of this latter case is similar to sCJD and in the absence of a family history of CJD, it is unknown whether this is a form of genetic CJD, or simply a neutral polymorphism. Conclusions This analysis of PRNP genetic variation in UK CJD patients is the first to show a comprehensive comparison with healthy individuals (n = 970) from the same population, who were genotyped for the three most common variations (codon 129, codon 117, and 24 bp deletion). These latter two genetic variations were equally frequent in UK sCJD or vCJD cases and a normal (healthy blood donor) UK population.

Abstract Background Variant Creutzfeldt-Jakob disease (vCJD) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE) material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571) previously examined in Alzheimer's disease (AD). Methods Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression. Results There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype. Conclusion This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease.

Abstract Background The mechanisms thorough which spinal manipulative therapy (SMT) exerts clinical effects are not established. A prior study has suggested a dorsal horn modulated effect; however, the role of subject expectation was not considered. The purpose of the current study was to determine the effect of subject expectation on hypoalgesia associated with SMT. Methods Sixty healthy subjects agreed to participate and underwent quantitative sensory testing (QST) to their leg and low back. Next, participants were randomly assigned to receive a positive, negative, or neutral expectation instructional set regarding the effects of a specific SMT technique on pain perception. Following the instructional set, all subjects received SMT and underwent repeat QST. Results No interaction (p = 0.38) between group assignment and pain response was present in the lower extremity following SMT; however, a main effect (p < 0.01) for hypoalgesia was present. A significant interaction was present between change in pain perception and group assignment in the low back (p = 0.01) with participants receiving a negative expectation instructional set demonstrating significant hyperalgesia (p < 0.01). Conclusion The current study replicates prior findings of c- fiber mediated hypoalgesia in the lower extremity following SMT and this occurred regardless of expectation. A significant increase in pain perception occurred following SMT in the low back of participants receiving negative expectation suggesting a potential influence of expectation on SMT induced hypoalgesia in the body area to which the expectation is directed.

Abstract Background A polymorphism at codon 129 of the prion protein gene (PRNP) is the only well-known genetic risk factor for Creutzfeldt-Jakob disease (CJD). However, there is increasing evidence that other loci outside the PRNP open reading frame might play a role in CJD aetiology as well. Methods We studied tau protein gene (MAPT) haplotypic variations in a population of sporadic and variant CJD patients. We tested 6 MAPT haplotype tagging SNPs (htSNPs) in a Dutch population-based sample of sporadic CJD (sCJD) patients and a cognitively normal control group of similar age distribution. We genotyped the same polymorphisms in two other sample groups of sCJD cases from Italy and the UK. In addition, we compared MAPT haplotypes between sCJD and variant CJD (vCJD) patients. Results Single locus and haplotype analyses did not detect any significant difference between sCJD cases and controls. When we compared MAPT haplotypes between sCJD and variant CJD (vCJD) patients, we found that two of them were represented differently (H1f: 8% in sCJD versus 2% in vCJD; H1j:1% in sCJD versus 7% in vCJD). However, these two haplotypes were rare in both groups of patients, and taking the small sample sizes into account, we cannot exclude that the differences are due to chance. None of the p-values remained statistically significant after applying a multiple testing correction. Conclusion Our study shows no evidence for an association between MAPT gene variations and sCJD, and some weak evidence for an association to vCJD.

Abstract Background The underlying causes of spinal manipulation hypoalgesia are largely unknown. The beneficial clinical effects were originally theorized to be due to biomechanical changes, but recent research has suggested spinal manipulation may have a direct neurophysiological effect on pain perception through dorsal horn inhibition. This study added to this literature by investigating whether spinal manipulation hypoalgesia was: a) local to anatomical areas innervated by the lumbar spine; b) correlated with psychological variables; c) greater than hypoalgesia from physical activity; and d) different for A-delta and C-fiber mediated pain perception. Methods Asymptomatic subjects (n = 60) completed baseline psychological questionnaires and underwent thermal quantitative sensory testing for A-delta and C-fiber mediated pain perception. Subjects were then randomized to ride a stationary bicycle, perform lumbar extension exercise, or receive spinal manipulation. Quantitative sensory testing was repeated 5 minutes after the intervention period. Data were analyzed with repeated measures ANOVA and post-hoc testing was performed with Bonferroni correction, as appropriate. Results Subjects in the three intervention groups did not differ on baseline characteristics. Hypoalgesia from spinal manipulation was observed in lumbar innervated areas, but not control (cervical innervated) areas. Hypoalgesic response was not strongly correlated with psychological variables. Spinal manipulation hypoalgesia for A-delta fiber mediated pain perception did not differ from stationary bicycle and lumbar extension (p > 0.05). Spinal manipulation hypoalgesia for C-fiber mediated pain perception was greater than stationary bicycle riding (p = 0.040), but not for lumbar extension (p = 0.105). Conclusion Local dorsal horn mediated inhibition of C-fiber input is a potential hypoalgesic mechanism of spinal manipulation for asymptomatic subjects, but further study is required to replicate this finding in subjects with low back pain.

Psoriasis is a debilitating inflammatory condition that affects physiological and psychological states of millions around the world. Conventional biologic and nonbiologic therapies are fraught with profound adverse side effect profiles, frequent injection requirements, suboptimal outcomes, and other detriments. An enhanced understanding of the role of cytokines in psoriasis, particularly interleukins 12, 17, and 23, has afforded improved therapeutic strategies. Herein, we described the role of cytokines in psoriasis as well as current and prospective therapeutic approaches to treat this debilitating disease.

Background: Comprehensive medication management (CMM) programs optimize the effectiveness and safety of patients' medication regimens, but CMM may be underutilized. Whether healthcare claims data can identify patients appropriate for CMM is not well-studied., Aim: Determine the face validity of a claims-based algorithm to prioritize patients who likely need CMM., Method: We used claims data to construct patient-level markers of "regimen complexity" and "high-risk for adverse effects," which were combined to define four categories of claims-based CMM-need (very likely, likely, unlikely, very unlikely) among 180 patient records. Three clinicians independently reviewed each record to assess CMM need. We assessed concordance between the claims-based and clinician-review CMM need by calculating percent agreement as well as kappa statistic., Results: Most records identified as 'very likely' (90%) by claims-based markers were identified by clinician-reviewers as needing CMM. Few records within the 'very unlikely' group (5%) were identified by clinician-reviewers as needing CMM. Interrater agreement between CMM-based algorithm and clinician review was moderate in strength (kappa = 0.6, p < 0.001)., Conclusion: Claims-based pharmacy measures may offer a valid approach to prioritize patients into CMM-need groups. Further testing of this algorithm is needed prior to implementation in clinic settings., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The use of real-time benefit tool (RTBT) may help increase transparency of patients' out-of-pocket (OOP) costs, thereby reducing patients' OOP spend and increasing prescription obtainment., Objective: We have previously reported on the potential benefit of RTBT in electronic health records at a large health system. We explore the benefit of RTBT by subgroups of prescriptions (i.e., order types)., Methods: In a retrospective cohort, we reviewed orders generated with and without RTBT use. We compared the 2 groups on key metrics related to prescription obtainment (fill rate, modification rate, cancellation rate, time to ready, time to sold, abandonment rate, and cancellation and transfer rate). Subgroup analysis included orders without over-the-counter (OTC) medications, orders without specialty medications, and orders without OTC and specialty medications., Results: Fill rate, cancellation rate, time to ready, time to sold, abandonment rate, and cancellation and transfer rate were statistically significantly different between the RTBT and non-RTBT groups, favoring the RTBT group (all, P < 0.01). Differences in modification rates were not statistically significant between the 2 groups., Conclusion: RTBTs have the potential to increase prescription obtainment. A consistent difference in key outcome measures between the RTBT and the non-RTBT groups was apparent among prescription orders regardless of whether OTC and specialty medications were included in the analysis., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Three claims-based pharmacy markers (complex, costly and risky medications) were developed to help automatically identify patients for comprehensive medication management., Objective: To evaluate the association between newly-developed markers and healthcare outcomes., Methods: This was a two-year retrospective cohort study using PharMetrics Plus patient-level administrative claims in 2014 and 2015. We included all claims from 1,541,873 individuals with: (1) 24-month medical and pharmacy enrollment in 2014 and 2015, (2) aged between 18 and 63 in 2014, and (3) known gender. Independent/control variables came from 2014 while outcomes came from 2014 (concurrent analysis) and 2015 (prospective analysis). Three pharmacy markers, separately or together, were added to four base models to predict concurrent and prospective healthcare costs (total, medical, and pharmacy) and utilization (having any hospitalization, having any emergency department visit, and having any readmission). We applied linear regression for costs while logistic regression for utilization. Measures of model performances and coefficients were derived from a 5-fold cross-validation repeated 20 times., Results: Individuals with 1+ complex, risky or costly medication markers had higher comorbidity, healthcare costs and utilization than their counterparts. Nine binary risky category markers performed the best among the three types of risky medication markers; the Medication Complexity Score and three-level complex category both outperformed a simpler complex medication indicator. Adding three novel pharmacy markers separately or together into the base models provided the greatest improvement in explaining pharmacy costs, compared with medical (non-medication) costs. These pharmacy markers also added value in explaining healthcare utilization among the simple base models., Conclusions: Three claims-based pharmacy indicators had positive associations with healthcare outcomes and added value in predicting them. This initial study suggested that these novel markers can be used by pharmacy case management programs to help identify potential high-risk patients most likely to benefit from clinical pharmacist review and other interventions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The diversity of influenza A viruses (IAV) is primarily hosted by two highly divergent avian orders: Anseriformes (ducks, swans and geese) and Charadriiformes (gulls, terns and shorebirds). Studies of IAV have historically focused on Anseriformes, specifically dabbling ducks, overlooking the diversity of hosts in nature, including gull and goose species that have successfully adapted to human habitats. This study sought to address this imbalance by characterizing spillover dynamics and global transmission patterns of IAV over 10 years at greater taxonomic resolution than previously considered. Furthermore, the circulation of viral subtypes in birds that are either host-adapted (low pathogenic H13, H16) or host-generalist (highly pathogenic avian influenza-HPAI H5) provided a unique opportunity to test and extend models of viral evolution. Using Bayesian phylodynamic modelling we uncovered a complex transmission network that relied on ecologically divergent bird hosts. The generalist subtype, HPAI H5 was driven largely by wild geese and swans that acted as a source for wild ducks, gulls, land birds, and domestic geese. Gulls were responsible for moving HPAI H5 more rapidly than any other host, a finding that may reflect their long-distance, pelagic movements and their immuno-naïve status against this subtype. Wild ducks, long viewed as primary hosts for spillover, occupied an optimal space for viral transmission, contributing to geographic expansion and rapid dispersal of HPAI H5. Evidence of inter-hemispheric dispersal via both the Pacific and Atlantic Rims was detected, supporting surveillance at high latitudes along continental margins to achieve early detection. Both neutral (geographic expansion) and non-neutral (antigenic selection) evolutionary processes were found to shape subtype evolution which manifested as unique geographic hotspots for each subtype at the global scale. This study reveals how a diversity of avian hosts contribute to viral spread and spillover with the potential to improve surveillance in an era of rapid global change., Competing Interests: The authors have declared that no competing interests exist.

BACKGROUND: Patient effort to comply with complex medication instructions is known to be related to nonadherence and subsequent medical complications or health care costs. A widely used Medication Regimen Complexity Index (MRCI) has been used with electronic health records (EHRs) to identify patients who could benefit from pharmacist intervention. A similar claims-derived measure may be better suited for clinical decision support, since claims offer a more complete view of patient care and health utilization. OBJECTIVE: To define and validate a novel insurance claims-based medication complexity score (MCS) patterned after the widely used MRCI, derived from EHRs. METHODS: Insurance claims and EHR data were provided by HealthPartners (N = 54,988) (Bloomington, Minnesota) and The Johns Hopkins Health System (N = 28,589) (Baltimore, Maryland) for years 2013 and 2017, respectively. Yearly measures of medication complexity were developed for each patient and evaluated with one another using rank correlation within different clinical subgroupings. Indicators for the presence of individually complex prescriptions were also developed and assessed using exact agreement. Complexity measures were then correlated with select covariates to further validate the concordance between MCS and MRCI with respect to clinical metrics. These included demographic, comorbidity, and health care utilization markers. Prescribed medications in each system's EHR were coded using the previously validated MRCI weighting rules. Insurance claims for retail pharmacy medications were coded using our novel MCS, which closely followed MRCI scoring rules. RESULTS: EHR-based MRCI and claims-based MCS were significantly correlated with one another for most clinical subgroupings. Likewise, both measures were correlated with several covariates, including count of active medications and chronic conditions. The MCS was, in most cases, more associated with key health covariates than was MRCI, although both were consistently significant. We found that the highest correlation between MCS and MRCI is obtained with patients who have similar counts of pharmacy records between EHRs and claims (HealthPartners: P = 0.796; Johns Hopkins Health System: P = 0.779). CONCLUSIONS: The findings suggest good correspondence between MCS and MRCI and that claims data represent a useful resource for assessing medication complexity. Claims data also have major practical advantages, such as interoperability across health care systems, although they lack the detailed clinical context of EHRs. DISCLOSURES: The Johns Hopkins University holds the copyright to the Adjusted Clinical Groups (ACG) system and receives royalties from the global distribution of the ACG system. This revenue supports a portion of the authors' salary. No additional or external funding supported this work. The authors have no conflict of interest to disclose.

BACKGROUND: Pharmacists optimize medication use and ensure the safe and effective delivery of pharmacotherapy to patients using comprehensive medication management (CMM). Identifying and prioritizing individual patients who will most likely benefit from CMM can be challenging. Health systems have far more candidates for CMM than there are clinical pharmacists to provide this service. Furthermore, current evidence lacks widely accepted standards or automated mechanisms for identifying patients who would likely benefit from a pharmacist consultation. Existing tools to prioritize patients for pharmacist review often require manual chart review by a pharmacist or other clinicians or data collection by patient survey. OBJECTIVES: To (1) create new medication risk markers for identifying and prioritizing patients within a population and (2) identify patients who met these new markers, assess their clinical characteristics, and compare them with criteria that are widely used for medication therapy management (MTM). METHODS: Along with published literature, a panel of subject matter experts informed the development of 3 medication risk markers. To assess the prevalence of markers developed, we used Multum, a medication database, for medication-level characteristics, and for patient-level characteristics, we used QuintilesIMS, an administrative claims database derived from health plans across the United States, with data for 1,541,873 eligible individuals from 2014-2015. We compared the health care costs, utilization, and medication gap among patients identified through MTM criteria (both broad and narrow, as these are provided as ranges) and our new medication management score markers. RESULTS: We developed 3 claims-derivable markers: (1) instances when a patient filled a medication with high complexity that could affect adherence, (2) instances where a patient filled a medication defined as costly within a therapeutic category that could affect access, and (3) instances when a patient filled a medication defined as risky that could increase incidence of adverse drug events. In the QuintilesIMS database, individuals with 2 new medication risk markers plus at least 3 conditions and more than $3,017 in medication costs when compared with individuals meeting narrow MTM eligibility criteria (≥ 8 medications, ≥ 3 conditions, and > $3,017 medication costs) had increased costs ($36,000 vs $26,100 total; $24,800 vs 21,400 medical; $11,300 vs $4,800 pharmacy); acute care utilization (0.328 vs 0.256 inpatient admissions and 0.627 vs 0.579 emergency department visits); and 1 or more gaps in medication adherence(41.5% vs 34.7%). CONCLUSIONS: We identified novel markers of medication use risk that can be determined using insurance claims and can be useful to identify patients for CMM programs and prioritize patients who would benefit from clinical pharmacist intervention. These markers were associated with higher costs, acute care utilization, and gaps in medication use compared with the overall population and within certain subgroups. Providing CMM to these patients may improve health system performance in relevant quality measures. Evaluation of CMM services delivered by a pharmacist using these markers requires further investigation. DISCLOSURES: No outside funding supported this study. All authors are Johns Hopkins employees. The Johns Hopkins University receives royalties for nonacademic use of software based on the Johns Hopkins Adjusted Clinical Group (ACG) methodology. Chang, Kitchen, Weiner, and Kharrazi receive a portion of their salary support from this revenue. The authors have no conflicts of interests relevant to this study.

Background: The trematode Heterobilharzia americana (HA) causes granulomatous gastrointestinal and hepatic disease in dogs. Before 2008, diagnosis relied on saline fecal sedimentation or histopathology, and earlier reports primarily described dogs with advanced disease or cases diagnosed incidentally at necropsy. The advent of a fecal PCR test has facilitated the diagnosis of HA and provided insights into manifestations and response to treatment., Objectives: Describe the clinical findings, response to treatment, and outcome for dogs infected with HA., Animals: Sixty dogs diagnosed with HA between 2010 and 2019., Methods: Retrospective study. Medical records were searched for dogs diagnosed with HA by fecal PCR testing, identification of ova in feces, or histopathology., Results: Mean age was 7.5 (±4.1) years and weight was 23.2 (±10.18) kg. Clinical signs included diarrhea (55.8%), vomiting (46.2%), and weight loss with or without anorexia (15.4%). Laboratory abnormalities included hyperglobulinemia (42.6%) and increased liver enzyme activities (30%). More than 40% of dogs had an eosinophil count >500/μL. Hypercalcemia attributable to HA was identified in only 4 dogs. Pinpoint hyperechoic foci were noted in intestines, liver, or mesenteric lymph nodes during transabdominal ultrasonography in 64.4% of dogs. Survival data was available for 34 dogs, of which 73.5% (25) were alive 6 months after diagnosis., Conclusions and Clinical Importance: Hyperglobulinemia, high eosinophil count, and ultrasonographic evidence of visceral mineralization were suggestive of infection. Hypercalcemia was uncommon. Combination treatment with praziquantel and fenbendazole was variably effective, and 17.6% of treated dogs with known outcome died as a result of HA infection., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

During the Pacific marine heatwave of 2014-2016, abundance and quality of several key forage fish species in the Gulf of Alaska were simultaneously reduced throughout the system. Capelin (Mallotus catervarius), sand lance (Ammodytes personatus), and herring (Clupea pallasii) populations were at historically low levels, and within this community abrupt declines in portfolio effects identify trophic instability at the onset of the heatwave. Although compensatory changes in age structure, size, growth or energy content of forage fish were observed to varying degrees among all these forage fish, none were able to fully mitigate adverse impacts of the heatwave, which likely included both top-down and bottom-up forcing. Notably, changes to the demographic structure of forage fish suggested size-selective removals typical of top-down regulation. At the same time, changes in zooplankton communities may have driven bottom-up regulation as copepod community structure shifted toward smaller, warm water species, and euphausiid biomass was reduced owing to the loss of cold-water species. Mediated by these impacts on the forage fish community, an unprecedented disruption of the normal pelagic food web was signaled by higher trophic level disruptions during 2015-2016, when seabirds, marine mammals, and groundfish experienced shifts in distribution, mass mortalities, and reproductive failures. Unlike decadal-scale variability underlying ecosystem regime shifts, the heatwave appeared to temporarily overwhelm the ability of the forage fish community to buffer against changes imposed by warm water anomalies, thereby eliminating any ecological advantages that may have accrued from having a suite of coexisting forage species with differing life-history compensations., (© 2021 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Some of the longest and most comprehensive marine ecosystem monitoring programs were established in the Gulf of Alaska following the environmental disaster of the Exxon Valdez oil spill over 30 years ago. These monitoring programs have been successful in assessing recovery from oil spill impacts, and their continuation decades later has now provided an unparalleled assessment of ecosystem responses to another newly emerging global threat, marine heatwaves. The 2014-2016 northeast Pacific marine heatwave (PMH) in the Gulf of Alaska was the longest lasting heatwave globally over the past decade, with some cooling, but also continued warm conditions through 2019. Our analysis of 187 time series from primary production to commercial fisheries and nearshore intertidal to offshore oceanic domains demonstrate abrupt changes across trophic levels, with many responses persisting up to at least 5 years after the onset of the heatwave. Furthermore, our suite of metrics showed novel community-level groupings relative to at least a decade prior to the heatwave. Given anticipated increases in marine heatwaves under current climate projections, it remains uncertain when or if the Gulf of Alaska ecosystem will return to a pre-PMH state.

Background: Over the past two decades, various species of forage fish have been successfully implanted with miniaturized acoustic transmitters and subsequently monitored using stationary acoustic receivers. When acoustic receivers are configured in an array, information related to fish direction can potentially be determined, depending upon the number and relative orientation of the acoustic receivers. However, it can be difficult to incorporate directional information into frequentist mark-recapture methods. Here we show how an empirical Bayesian approach can be used to develop a model that incorporates directional movement information into the Arnason-Schwarz modeling framework to describe survival and migration patterns of a Pacific herring (Clupea pallasii) population in coastal Alaska, USA., Methods: We acoustic-tagged 326 adult Pacific herring during April 2017 and 2018 while on their spawning grounds in Prince William Sound Alaska, USA. To monitor their movements, stationary acoustic receivers were deployed at strategic locations throughout the Sound. Receivers located at the major entrances to the Gulf of Alaska were arranged in parallel arrays to determine the directional movements of the fish. Informative priors were used to incorporate the directional information recorded at the entrance arrays into the model., Results: A seasonal migratory pattern was found at one of Prince William Sound's major entrances to the Gulf of Alaska. At this entrance, fish tended to enter the Gulf of Alaska during spring and summer after spawning and return to Prince William Sound during the fall and winter. Fish mortality was higher during spring and summer than fall and winter in both Prince William Sound and the Gulf of Alaska., Conclusions: An empirical Bayesian modeling approach can be used to extend the Arnason-Schwarz modeling framework to incorporate directional information from acoustic arrays to estimate survival and characterize the timing and direction of migratory movements of forage fish.

It has been hypothesized that idiopathic hypertriglyceridemia in Miniature Schnauzers is hereditary, but the gene responsible has yet to be identified. The objective of this study was to determine if there were coding variants in the apolipoprotein C2 (APOC2) gene in Miniature Schnauzers with idiopathic hypertriglyceridemia. Blood samples from 12 Miniature Schnauzers with idiopathic hypertriglyceridemia were analyzed. Genomic DNA was extracted from whole blood, and the three coding exons of APOC2 were amplified by PCR. The PCR amplicons were sequenced and analyzed for variants relative to the canine reference genome (CanFam3.1 assembly). A second objective was to determine the extent of variation in coding exons of APOC2 in a large and diverse canine population using the Dog Biomedical Variant Database Consortium variant catalog, comprised of whole genome sequencing variant calls from 582 dogs of 126 breeds and eight wolves. There were no variants detected in the coding exons of APOC2 for any of the 12 Miniature Schnauzers with idiopathic hypertriglyceridemia. Variants in the coding exons of APOC2 were also rare in the Dog Biomedical Variant Database Consortium variant catalog; a single synonymous variant was identified in a heterozygous state in a Tibetan Mastiff. Thus, we concluded that coding variants in APOC2 are unlikely to be a major cause of idiopathic hypertriglyceridemia in North American Miniature Schnauzers and furthermore, that such coding variants are rare in the canine population., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The contents of 1056 stomachs were included in a trophic-guild analysis to document separation amongst 16 groundfish species inhabiting Pacific herring Clupea pallasii and walleye pollock Gadus chalcogrammus nursery fjords in Prince William Sound, Alaska and to determine the relative contribution of C. pallasii and G. chalcogrammus to that separation. A total of five multi-species feeding guilds and one outlier species were determined through multivariate analyses. Major gradients of trophic separation spanned from invertebrates (mostly shrimps, crabs and unidentified decapods) to fishes (mostly unidentified fishes, C. pallasii and G. chalcogrammus) a pattern that was influenced by intra and interspecific differences in predator lengths. While C. pallasii and G. chalcogrammus were important to the overall guild structure, within-guild similarities were consistently highest due to unidentified fishes. In general, larger predators consumed the largest C. pallasii and G. chalcogrammus, with the smaller-on-average predators consuming smaller C. pallasii and fewer or smaller G. chalcogrammus. Regardless of guild inclusion, groundfishes primarily consumed pre-recruit C. pallasii and G. chalcogrammus (i.e., younger than age 3 years fishes), which has the potential to negatively influence recruitment of these forage fishes to the adult, spawning population., (© 2019 The Fisheries Society of the British Isles.)