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Many authors in recent years note threats to humanistic studies within higher education. They express concern about the overproduction of PhD graduates, the increasing costs of higher education, and other topics. Ethnomusicologists are undoubtedly aware of such issues, yet as a society SEM has not engaged with related publications, nor has it collected much data on specific challenges to our own field. This essay synthesizes literature on trends within the humanities and considers its potential relevance for ethnomusicology. Then, based on interviews with faculty, as well as a 2018 survey circulated to current and former students on the SEM LISTSERV, it briefly considers the state of our discipline in terms of core training, student support, student placement, and other topics. The data suggest that many issues confronting ethnomusicologists resonate with those in other disciplines and that we would benefit from engagement with nationwide dialogues involving the future of graduate studies. Suggestions proposed are many and include an orientation of research toward issues impacting communities near one’s university, greater focus on team-based inquiry rather than individual scholarship, more active collaborations across disciplines, diverse professional training, more attention to shaping the content of K–12 education, communication with diverse audiences, and a research focus on areas of broad public concern whenever possible.

Background To date, very few studies have compared the effects of different types of feeding practices on canine physiology, such as feeding exclusively dry, raw, or homemade foods. Objectives We aimed to report the changes in hematologic, serum biochemical, plasma folate, B-12, and whole blood iron levels in dogs fed two different diets. Methods A pilot study was developed to compare the effects of a heat-processed high carbohydrate (HPHC) and nonprocessed high-fat (NPHF) diet. A total of 33 client-owned Staffordshire Bull Terriers were used; 18 had canine atopic dermatitis, seven were healthy, and eight were grouped as "borderline" dogs since they did not fulfill at least six of Favrot's criteria. The comparisons were made between the diet groups at the end visit of the diet intervention, as well as within the diet groups during the study. Results Significant differences between and within the diet groups were observed, although the majority of outcomes remained within the RIs. The median time of diet intervention was 140 days. Red blood cell counts, mean cell hemoglobin concentrations, and platelet counts were significantly higher, and mean cell hemoglobin, mean cell volume, alkaline phosphatase, inorganic phosphorus, and cholesterol were significantly lower in the dogs fed the NPHF diet compared with those fed the HPHC diet after the diet trial was completed. In addition, folate, B-12, and iron decreased significantly in the NPHF diet group. Conclusions This pilot study indicated that diet had an impact on blood values, although most remained within RIs, pointing out the need for further studies.

Obtaining correct amounts of essential elements, and avoiding toxic metals are key factors in dog health. Through analyzing major and trace elements in hair and blood of 50 healthy companion dogs using ICP-MS, we study their associations with dog characteristics and diet, hypothesizing that eating the same diet long-term results in strong correlations between hair and blood element concentrations, and that dog characteristics and diet affect element status. The correlation between hair and blood was significant for Hg (R = 0.601, p = 0.000) and Pb (R = 0.384, p = 0.010). The following associations were significant (p < 0.05): Dark hair had higher Ca and Mg compared to light hair. Females had higher hair Zn, blood Mn, and blood As compared to males. Blood Mn and Se increased, while blood Pb decreased with age. Raw diet fed dogs had higher hair Zn and Se compared to dry or mixed diet fed dogs, and lower blood Mn compared to dry diet fed dogs. Dry and mixed diet fed dogs had higher blood Cd compared to raw diet fed dogs. Mixed diet fed dogs had higher hair Ca and Mg compared to raw or dry diet fed dogs, and higher hair Pb compared to dry diet fed dogs. Wild game consumption was associated with higher blood Pb, and rice consumption with higher blood As. In conclusion, hair provides an alternative for assessing Hg and Pb exposure, and major and trace elements status is affected by hair color, sex, age, and diet. Supplementary Information The online version contains supplementary material available at 10.1007/s11259-021-09854-8.

BMS-986205 (Linrodostat) is a small molecule inhibitor of Indoleamine 2, 3 dioxygenase (IDO) that is currently being evaluated in clinical trials for the oral treatment of advanced cancer. Initially, there were concerns regarding possible toxicity following administration, since BMS-986205 undergoes metabolism to form 4-chloroaniline. However, it was later determined that the downstream metabolites of 4-chloroaniline might be a greater concern. To evaluate the potential toxicity of these metabolites, a sensitive LC-MS/MS analytical method was needed to quantify both the parent compound and multiple metabolites. This presented a challenge since the method required the analysis of multiple analytes while still retaining the analytical sensitivity required to support studies. By utilizing a multi-function analytical method, we were able to quantify the necessary analytes using a complex LC-MS/MS-based method including the application of both negative and positive electrospray ionization.

Background The increased prevalence of atopic dermatitis (AD) in dogs necessitates research in its disease etiology. Objectives To explore the association between puppyhood dietary exposures and prevalence of owner‐reported allergy/atopy skin signs (AASS) after the age of 1 year. Animals Four thousand and twenty‐two dogs were eligible, 1158 cases, and 2864 controls. Methods This cross‐sectional hypothesis‐driven observational study was extracted from the DogRisk food frequency questionnaire. Forty‐six food items and the ratio of 4 major diet types were tested for their association with AASS incidence later in life. Potential puppyhood dietary risk factors for AASS incidence were specified using binary multivariable logistic regression. The model was adjusted for age and sex. Results Eating raw tripe (odds ratio, 95% confidence intervals OR, 95% CI = 0.36, 0.16‐0.79; P = .01), raw organ meats (OR, 95% CI = 0.23, 0.08‐0.67; P = .007), human meal leftovers, and fish oil supplements as well as eating more that 20% of the diet as raw and/or

The capacity to derive, analyse and communicate urban knowledge is increasingly essential for decision-makers managing the complex pressures of rapidly expanding cities. This paper examines the imp...

Author summaryRelapsing fever and Lyme Disease are infectious diseases caused by borrelia bacteria. Relapsing fever occurs sporadically worldwide, whereas distribution of Lyme Disease is restricted to the Northern Hemisphere. Both infections are transmitted to humans by blood eating ticks or lice. These infections are often difficult to diagnose due to nonspecific symptoms. To be able to cause infection, borrelia must circumvent the human immune responses. Here we describe a mechanism, how borrelia bacteria protect themselves in the human host by utilizing host proteins. By using X-ray crystallography, we solved the structure of an outer membrane protein FhbA from a relapsing fever causing borreliae, Borrelia hermsii, in complex with human complement regulator factor H. FhbA has a unique alpha-helical fold that has not been reported earlier. The structure of the complex revealed how FhbA binds factor H in a very specific manner. Factor H bound to FhbA on the surface of borrelia protects bacteria from the complement system and lysis. Based on the structure, we performed structure-guided sequence database analysis, which suggests that similar proteins are present in all relapsing fever causing borrelia and possibly in some Lyme disease agents. Immune evasion facilitates survival of Borrelia, leading to infections like relapsing fever and Lyme disease. Important mechanism for complement evasion is acquisition of the main host complement inhibitor, factor H (FH). By determining the 2.2 angstrom crystal structure of Factor H binding protein A (FhbA) from Borrelia hermsii in complex with FH domains 19-20, combined with extensive mutagenesis, we identified the structural mechanism by which B. hermsii utilizes FhbA in immune evasion. Moreover, structure-guided sequence database analysis identified a new family of FhbA-related immune evasion molecules from Lyme disease and relapsing fever Borrelia. Conserved FH-binding mechanism within the FhbA-family was verified by analysis of a novel FH-binding protein from B. duttonii. By sequence analysis, we were able to group FH-binding proteins of Borrelia into four distinct phyletic types and identified novel putative FH-binding proteins. The conserved FH-binding mechanism of the FhbA-related proteins could aid in developing new approaches to inhibit virulence and complement resistance in Borrelia.

Background: While anecdotal evidence has long claimed that a raw meat-based diet (RMBD) improves the metabolic health of canines, no rigorous scientific study has clarified this issue. Canine atopic dermatitis (CAD) has also been linked to metabolic health, but its relation to diet remains poorly understood. This study investigates whether dietary choice is linked to metabolic health in healthy and CAD-diagnosed canines via targeted serum and urine metabolomic analysis of polar, non-ionic metabolites, as well as whether the underlying CAD condition modulates the response to nutritional intake. Materials and Methods: Serum metabolites of client-owned Staffordshire bull terriers, divided into CAD-diagnosed (n = 14) and healthy (n = 6) cohorts, were studied. Urine metabolites of a subset of the CAD-diagnosed canines (n = 8) were also studied. The canines were split into two cohorts based on diet. The first cohort were fed a commercially available high-fat, moderate-protein, low-carbohydrate RMBD (n = 11, CAD diagnosed n = 8, healthy n = 3). Those in the second cohort were fed a commercially available moderate-fat, moderate-protein, high-carbohydrate kibble diet (KD) (n = 9: CAD diagnosed n = 6, healthy n = 3). The diet intervention period lasted approximately 4.5 months (median 135 days). Statistical analyses of the serum profiles across all dogs (n = 20) and the urine profiles of the CAD-diagnosed subset (n = 8) were performed. Results and Discussion: The KD cohort was found to have higher concentrations of methionine than the RMBD cohort, both in serum (all dogs, p < 0.0001) and in urine (CAD-only cohort, p < 0.0002), as well as cystathionine and 4-pyridoxic acid. Methionine plays important roles in homocysteine metabolism, and elevated levels have been implicated in various pathologies. The CAD (n = 14) cohort dogs showed starker metabolic changes in response to diet regarding these pathways compared to the healthy (n = 6) cohort. However, there was no significant change in CAD severity as a result of either diet. Likely due to the higher meat content of the RMBD, higher concentrations of several carnitines and creatine were found in the RMBD cohort. Citrulline was found in higher concentrations in the KD cohort. Our findings provide insight into the relationship between diet and the serum and urine metabolite profiles of canines. They also suggest that neither diet significantly affected CAD severity.

Background: Inflammatory bowel disease (IBD) is an idiopathic multifactorial disease in humans and dogs, usually assigned to the interactions between genes, gut microbiota, diet, environment, and the immune system. We aimed to investigate the modifiable early life exposures associated with IBD in dogs. Materials and Methods: The study data was extracted from the validated owner-reported DogRisk food frequency questionnaire. This was a cross-sectional questionnaire-based study that tested 21 different early life dietary and environmental, demographic and genetic variables for their association with IBD or not, in adult dogs. A total of 7,015 dogs participated in this study. The study covered early life periods; prenatal, neonatal, early, and late postnatal periods. Two feeding patterns, a non-processed meat-based diet (NPMD) and an ultra-processed carbohydrate-based diet (UPCD) were studied. Data was analyzed using logistic regression analysis with a backward stepwise deletion. Results: From the final models we found that the NPMD during early and late postnatal periods were significantly associated with lower IBD risk later in life. The UPCD during the same periods was associated with a higher risk of IBD incidence. Also, the maternal diet during the neonatal period showed a non-significant trend of lower IBD risk in the offspring with the NPMD and a higher IBD risk with the UPCD. Additionally, the normal body weight of puppies during the first 6 months of age was associated with a lower risk of IBD in adulthood while, slim puppies associated significantly with IBD in adulthood. From the non-modifiable background variables, we identified the maternal history of IBD as the strongest risk factor for later incidence of IBD. Furthermore, male dogs were twice as likely to develop IBD as female dogs were. Conclusions: It is reassuring for owners to know that they themselves can have an impact on their dog's health. A high-fat, low-carbohydrate NPMD exposure during early life, and a normal body condition in puppyhood were significantly associated with less IBD in adult dogs. The opposite was true for UPCD exposure and abnormal body condition score in 6 month old puppies.

A cross-sectional hypothesis generating study was performed to investigate modifiable exposures such as whether feeding pattern (a non-processed meat based diet, NPMD, or an ultra-processed carbohydrate based diet, UPCD), certain environmental factors and their timing of exposure might be associated with the development of canine atopic dermatitis (CAD). Also, genetic and demographic factors were tested for associations with CAD. The data was collected from the validated internet-based DogRisk food frequency questionnaire in Finland. A total of 2236 dogs were eligible for the study (the owners reported 406 cases and 1830 controls). Our main interest was to analyze modifiable early risk factors of CAD, focusing on nutritional and environmental factors. We tested four early life periods; prenatal, neonatal, early postnatal and late postnatal periods. Twenty-two variables were tested for associations with CAD using logistic regression analysis. From the final models we identified novel dietary associations with CAD: the NPMD during the prenatal and early postnatal periods had a significant negative association with the incidence of CAD in adult dogs (age above 1 year). Oppositely, UPCD was associated with a significantly higher risk for CAD incidence. Other variables that were associated with a significantly lower risk for CAD were maternal deworming during pregnancy, sunlight exposure during early postnatal period, normal body condition score during the early postnatal period, the puppy being born within the same family that it would stay in, and spending time on a dirt or grass surface from 2 to 6 months. Also, the genetic factors regarding maternal history of CAD, allergy-prone breeds and more than 50% white-colored coat all showed a significant positive association with CAD incidence in agreement with previous findings. Although no causality can be established, feeding NPMD early in life seemed to be protective against CAD, while UPCD could be considered a risk factor. Prospective intervention studies are needed to establish the causal effects of the protective role of NPMD on prevalence of CAD during the fetal and early postnatal life.

Bruton’s tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fce receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.

Background To date, very few studies have compared the effects of different types of feeding practices on canine physiology, such as feeding exclusively dry, raw, or homemade foods. Objectives We aimed to report the changes in hematologic, serum biochemical, plasma folate, B12, and whole blood iron levels in dogs fed two different diets. Methods A pilot study was developed to compare the effects of a heat‐processed high carbohydrate (HPHC) and nonprocessed high‐fat (NPHF) diet. A total of 33 client‐owned Staffordshire Bull Terriers were used; 18 had canine atopic dermatitis, seven were healthy, and eight were grouped as “borderline” dogs since they did not fulfill at least six of Favrot's criteria. The comparisons were made between the diet groups at the end visit of the diet intervention, as well as within the diet groups during the study. Results Significant differences between and within the diet groups were observed, although the majority of outcomes remained within the RIs. The median time of diet intervention was 140 days. Red blood cell counts, mean cell hemoglobin concentrations, and platelet counts were significantly higher, and mean cell hemoglobin, mean cell volume, alkaline phosphatase, inorganic phosphorus, and cholesterol were significantly lower in the dogs fed the NPHF diet compared with those fed the HPHC diet after the diet trial was completed. In addition, folate, B12, and iron decreased significantly in the NPHF diet group. Conclusions This pilot study indicated that diet had an impact on blood values, although most remained within RIs, pointing out the need for further studies.

Physiologic changes in the cardiac, respiratory, and renal systems in pregnancy likely impact ventilatory control. Though obstructive sleep apnea and snoring are common in the pregnant population, the predisposition to central respiratory events during sleep and the prevalence of such events is less well studied. The aim of this study was to assess the presence of central apneas during sleep in pregnant women and non-pregnant controls suspected of sleep disordered breathing. Twenty-five pregnant women referred for polysomnography for sleep disordered breathing were compared with non-pregnant controls matched for age, body mass index, gender, and apnea hypopnea index (AHI). Central apnea index was defined as the number of central apneas per hour of sleep, and mixed apnea index was defined as the number of mixed apneas per hour of sleep. Sixty-four percent of pregnant women had a respiratory disturbance index >5 events per hour of sleep. Mean body mass index was 44.1 ± 6.9 kg/m2 pregnant compared to 44.0 ± 7.3 kg/m2 in controls. The total number of central apneas observed during sleep in the pregnant group consisted of two central apneas in one patient, and of 98 central apneas in 11 patients in the control group (p = 0.05). Median central apnea index was low in both groups (pregnant 0, interquartile range (IQR) 0, 0 vs. non-pregnant 0, IQR 0, 0.2, p = 0.04). Mixed apnea index was similarly low in both groups. Despite some physiologic changes of pregnancy that impact ventilatory control, the prevalence of central sleep apnea was low in our sample of overweight pregnant women with sleep-disordered breathing.

Production of value-added compounds from a renewable aromatic polymer, lignin, has proven to be challenging. Chemical procedures, involving harsh reaction conditions, are costly and often result in nonselective degradation of lignin linkages. Therefore, enzymatic catalysis with selective cleavage of lignin bonds provides a sustainable option for lignin valorization. In this study, we describe the first functionally characterized fungal intracellular β-etherase from the wood-degrading white-rot basidiomycete

Background: The disease state can modulate the penetration of large antibody-sized therapeutic molecules into affected tissues. Suitable bioanalytical methods are required for the quantitative analysis of drug tissue levels to enable a better understanding of the parameters influencing drug penetration and target engagement. Results: Described is a sensitive and selective LC–MS/MS assay for the quantification of human mAb molecules in mouse tissues. By homogenizing tissues directly into serum, a common serum calibration curve can be used for multiple tissues. A generic procedure was used for affinity enrichment. An analytical range of 20 – 20,000 ng/ml was achieved in serum. Conclusion: The method described here can be applied for the quantitative analysis of mAb and Fc-fusion therapeutic molecules in a variety of animal tissue matrices.

To assess the validity of using the Apnea Risk Evaluation System (ARES) Unicorder for detecting obstructive sleep apnea (OSA) in pregnant women.Sixteen pregnant women, mean age (SD) = 29.8 (5.4) years, average gestational age (SD) = 28.6 (6.3) weeks, mean body mass index (SD) = 44.7 (6.9) kg/m(2) with signs and symptoms of OSA wore the ARES Unicorder during one night of laboratory polysomnography (PSG). PSG was scored according to AASM 2007 criteria, and PSG AHI and RDI were compared to the ARES 1%, 3%, and 4% AHIs calculated with the ARES propriety software.Median PSG AHI and PSG RDI were 3.1 and 10.3 events/h of sleep, respectively. Six women had a PSG AHI ≥ 5 events/h of sleep and 11 had a PSG RDI ≥ 5 events/h of sleep. PSG AHI and RDI were strongly correlated with the ARES AHI measures. When compared with polysomnographic diagnosis of OSA, the ARES 3% algorithm provided the best balance between sensitivity (1.0 for PSG AHI, 0.91 for PSG RDI) and specificity (0.5 for PSG AHI, 0.8 for PSG RDI) for detecting sleep disordered breathing in our sample.The ARES Unicorder demonstrated reasonable consistency with PSG for diagnosing OSA in this small, heterogeneous sample of obese pregnant women.

Pregnancy physiology may predispose women to the development of airflow limitations during sleep. The goal of this study was to evaluate whether pregnant women suspected of sleep-disordered breathing (SDB) are more likely to have airflow limitations compared to non-pregnant controls.We recruited pregnant women referred for polysomnography for a diagnosis of SDB. Non-pregnant female controls matched for age, body mass index (BMI), and apnoea-hypopnoea index (AHI) were identified from a database. We examined airflow tracings for changes in amplitude and shape. We classified airflow limitation by (a) amplitude criteria defined as decreased airflow ofor =10 s without desaturation or arousal (FL 10), or decreased airflow of any duration combined with either 1-2% desaturation or arousal, (FL 1-2%); and (b) shape criteria defined as the presence of flattening or oscillations of the inspiratory flow curve.We identified 25 case-control pairs. Mean BMI was 44.0±6.9 in cases and 44.1±7.3 in controls. Using shape criteria, pregnant women had significantly more flow-limited breaths throughout total sleep time (32.4±35.8 vs. 9.4±17.9, p0.0001) and in each stage of sleep (p0.0001) than non-pregnant controls. In a subgroup analysis, pregnant women without a diagnosis of obstructive sleep apnoea (OSA) who had an AHI5 had similar findings (p0.0001). There was no difference in airflow limitation by amplitude criteria between pregnant women and controls (p=0.22).Pregnant women suspected of OSA have more frequent shape-defined airflow limitations than non-pregnant controls, even when they do not meet polysomnographic OSA criteria.