Search

Introduction: Benzodiazepines are frequently prescribed and misused therefore urine drug screening (UDS) is performed in many patient populations. Most current benzodiazepine immunoassays have poor sensitivity, particularly for detecting the metabolites of newer benzodiazepines such as lorazepam in urine. Objectives: We aimed to verify the clinical performance of the new qualitative Roche Benzodiazepines II (BNZ2) immunoassay, as well as compare its performance to the Roche Benzodiazepines Plus (BENZ) assay in two patient populations: UDS in the emergency department (ED) and compliance monitoring. Methods: An initial verification study was performed, selecting for samples containing clonazepam and lorazepam metabolites. Performance of the BNZ2 and BENZ assays was compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the reference method. Sensitivity, specificity, false positive rate (FPR) and false negative rate (FNR) were determined. Results: We verified the performance claims in the initial verification and demonstrated similar precision, with coefficient of variations (CVs) of 12.8% and 7.7% for negative and positive controls, respectively. Furthermore, we observed higher clinical sensitivity and lower FNR with the BNZ2 assay in both the ED and compliance monitoring populations due to improved cross-reactivity for lorazepam and clonazepam metabolites. Despite these improvements, the BNZ2 assay was unable to detect 27% of specimens positive by LC-MS/MS, including specimens from patients using benzodiazepines without prescription. Discussion: Due to its improved performance and rapid turnaround time, the BNZ2 assay should be implemented for UDS in the ED. However, the assay should not replace LC-MS/MS testing for compliance monitoring, as unsuspected benzodiazepine use may go undetected.

We assessed the efficacy of ozonation as an indoor remediation strategy by evaluating how a carpet serves as a sink and long-term source of thirdhand tobacco smoke (THS) while protecting contaminants absorbed in deep reservoirs by scavenging ozone. Specimens from unused carpet that was exposed to smoke in the lab ("fresh THS") and contaminated carpets retrieved from smokers' homes ("aged THS") were treated with 1000 ppb ozone in bench-scale tests. Nicotine was partially removed from fresh THS specimens by volatilization and oxidation, but it was not significantly eliminated from aged THS samples. By contrast, most of the 24 polycyclic aromatic hydrocarbons detected in both samples were partially removed by ozone. One of the home-aged carpets was installed in an 18 m3 room-sized chamber, where its nicotine emission rate was 950 ng day-1 m-2. In a typical home, such daily emissions could amount to a non-negligible fraction of the nicotine released by smoking one cigarette. The operation of a commercial ozone generator for a total duration of 156 min, reaching concentrations up to 10,000 ppb, did not significantly reduce the carpet nicotine loading (26-122 mg m-2). Ozone reacted primarily with carpet fibers, rather than with THS, leading to short-term emissions of aldehydes and aerosol particles. Hence, by being absorbed deeply into carpet fibers, THS constituents can be partially shielded from ozonation.

Intestinal epithelial cells possess the requisite molecular machinery to initiate cell-intrinsic defensive responses against intracellular pathogens, including intracellular parasites. Interferons(IFNs) have been identified as cornerstones of epithelial cell-intrinsic defense against such pathogens in the gastrointestinal tract. Long non-coding RNAs (lncRNAs) are RNA transcripts (>200 nt) not translated into protein and represent a critical regulatory component of mucosal defense. We report here that lncRNA Nostrill facilitates IFN-γ-stimulated intestinal epithelial cell-intrinsic defense against infection by Cryptosporidium, an important opportunistic pathogen in AIDS patients and a common cause of diarrhea in young children. Nostrill promotes transcription of a panel of genes controlled by IFN-γ through facilitating Stat1 chromatin recruitment and thus, enhances expression of several genes associated with cell-intrinsic defense in intestinal epithelial cells in response to IFN-γ stimulation, including Igtp, iNos, and Gadd45g. Induction of Nostrill enhances IFN-γ-stimulated intestinal epithelial defense against Cryptosporidium infection, which is associated with an enhanced autophagy in intestinal epithelial cells. Our findings reveal that Nostrill enhances the transcription of a set of genes regulated by IFN-γ in intestinal epithelial cells. Moreover, induction of Nostrill facilitates the IFN-γ-mediated epithelial cell-intrinsic defense against cryptosporidial infections.

Abstract In mammalian societies, dominance hierarchies translate into inequalities in health, reproductive performance and survival. DNA methylation is thought to mediate the effects of social status on gene expression and phenotypic outcomes, yet a study of social status-specific DNA methylation profiles in different age classes in a wild social mammal is missing. We tested for social status signatures in DNA methylation profiles in wild female spotted hyenas (Crocuta crocuta), cubs and adults, using non-invasively collected gut epithelium samples. In spotted hyena clans, female social status influences access to resources, foraging behavior, health, reproductive performance and survival. We identified 149 differentially methylated regions between 42 high- and low-ranking female spotted hyenas (cubs and adults). Differentially methylated genes were associated with energy conversion, immune function, glutamate receptor signalling and ion transport. Our results provide evidence that socio-environmental inequalities are reflected at the molecular level in cubs and adults in a wild social mammal.

Tobacco-specific nitrosamines (TSNAs) are emitted during smoking and form indoors by nitrosation of nicotine. Two of them, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are human carcinogens with No Significant Risk Levels (NSRLs) of 500 and 14 ng day-1, respectively. Another TSNA, 4-(methylnitrosamino)-4-(3-pyridyl) butanal (NNA), shows genotoxic and mutagenic activity in vitro. Here, we present additional evidence of genotoxicity of NNA, an assessment of TSNA dermal uptake, and predicted exposure risks through different pathways. Dermal uptake was investigated by evaluating the penetration of NNK and nicotine through mice skin. Comparable mouse urine metabolite profiles suggested that both compounds were absorbed and metabolized via similar mechanisms. We then investigated the effects of skin constituents on the reaction of adsorbed nicotine with nitrous acid (epidermal chemistry). Higher TSNA concentrations were formed on cellulose and cotton substrates that were precoated with human skin oils and sweat compared to clean substrates. These results were combined with reported air, dust, and surface concentrations to assess NNK intake. Five different exposure pathways exceeded the NSRL under realistic scenarios, including inhalation, dust ingestion, direct dermal contact, gas-to-skin deposition, and epidermal nitrosation of nicotine. These results illustrate potential long-term health risks for nonsmokers in homes contaminated with thirdhand tobacco smoke.

Natural and artificial approaches are the mainly management strategy used in degraded lands restoration, while few studies examine the effect of the two strategies on soil nutrient properties in an earthquake-triggered degraded ecosystem. We compared soil chemical traits and major nutrient stoichiometry from areas following landslides that had undergone natural restoration (D. NR.) and artificial restoration (D. AR.), as well as neighboring undisturbed areas (Und.), following the 2017 magnitude 7.0 earthquake in Jiuzhaigou, eastern Qinghai-Tibet Plateau. The results showed that soil organic carbon (C), total nitrogen (N), available nitrogen (AN), available phosphorus (AP), exchangeable calcium (eCa), exchangeable magnesium (eMg), C/P, C/K, N/P, N/K, P/K, cation exchange capacity, and vegetation cover in landslides of D. NR. and D. AR. were lower than those in Und. land, while their pH and total potassium (K) concentration were higher. Compared to D. NR., most of these traits were higher in D. AR., except for the C/N, which was reduced in D. AR. Soil C was positively related to AN, C/K, N/P, N/K, P/K in each land type, while in D. NR., it was not related to N, AP, AK, eCa, eMg, C/N, although it was negatively related to P and K concentration. The findings demonstrated that vegetation restoration strategies could affect not only soil nutrient content but also the macronutrient stoichiometry (N, P, K). Furthermore, artificial restoration projects can enhance soil nutrient concentration and facilitate vegetation recovery more quickly than natural restoration, which is primarily driven by soil N rather than P or K.

Ozonation is a common remediation approach to eliminate odors from mold, tobacco and fire damage in buildings. Little information exists to: 1) assess its effectiveness; 2) provide guidance on operation conditions; and 3) identify potential risks associated with the presence of indoor ozone and ozonation byproducts. The goal of this study is to evaluate chemical changes in thirdhand smoke (THS) aerosols induced by high levels of ozone, in comparison with THS aerosols aged under similar conditions in the absence of ozone. Samples representing different stages of smoke aging in the absence of ozone, including freshly emitted secondhand smoke (SHS) and THS, were collected inside an 18-m3 room-sized chamber over a period of 42 h after six cigarettes were consumed. The experiments involved collection and analysis of gas phase species including volatile organic compounds (VOCs), volatile carbonyls, semivolatile organic compounds (SVOCs), and particulate matter. VOC analysis was carried out by gas chromatography/mass spectrometry with a thermal desorption inlet (TD-GC/MS), and volatile carbonyls were analyzed by on-line derivatization with dinitrophenylhydrazine (DNPH), followed by liquid chromatography with UV/VIS detection. SVOCs were extracted from XAD-coated denuders and Teflon-coated fiberglass filters in the absence of ozone. In those extracts, tobacco-specific nitrosamines (TSNAs) and other SVOCs were analyzed by gas chromatography with positive chemical ionization-triple quadrupole mass spectrometric detection (GC/PCI-QQQ-MS), and polycyclic aromatic hydrocarbons (PAHs) were quantified by gas chromatography with ion trap mass spectrometric detection (GC/IT-MS) in selected ion monitoring mode. Particulate matter concentration was determined gravimetrically. In a second experiment, a 300 mg h-1 commercial ozone generator was operated during 1 h, one day after smoke was generated, to evaluate the remediation of THS by ozonation. VOCs and volatile carbonyls were analyzed before and after ozonation. Extracts from fabrics that were exposed in the chamber before and after ozonation as surrogates for indoor furnishings were analyzed by GC/IT-MS, and aerosol size distribution was studied with a scanning mobility particle sizer. Ozone concentration was measured with a photometric detector. An estimated 175 mg ozone reacted with THS after 1 h of treatment, corresponding to 58% of the total O3 released during that period. Fabric-bound nicotine was depleted after ozonation, and the surface concentration of PAHs adsorbed to fabric specimens decreased by an order of magnitude due to reaction with ozone, reaching pre-smoking levels. These results suggest that ozonation has the potential to remove harmful THS chemicals from indoor surfaces. However, gas phase concentrations of volatile carbonyls, including formaldehyde, acetaldehyde and acetone were higher immediately after ozonation. Ultrafine particles (UFP, in most cases with size

"Sub-ohm" atomizers with reduced resistance can deliver more power than conventional electronic cigarettes. Typical battery outputs are 100 W or more. These devices are particularly popular among young users, and can be a significant source of volatile carbonyls in the indoor environment. Emissions from next-generation sub-ohm vaping products were characterized by determining e-liquid consumption and volatile aldehydes emissions for several combinations of popular high-power configurations. Tests explored the effect of dilution air flow (air vent opening), puffing volume, and coil assembly configuration. The mass of liquid consumed per puff increased as the puff volume increased from 50 to 100 mL, then remained relatively constant for larger puff volumes up to 500 mL. This is likely due to mass transfer limitations at the wick and coil assembly, which reduced the vaporization rate at higher puff volumes. Carbonyl emission rates were systematically evaluated using a 0.15 Ω dual coil atomizer as a function of the puffing volume and dilution air flow, adjusted by setting the air vents to either 100% (fully open), 50%, 25%, or 0% (closed). The highest formaldehyde emissions were observed for the lowest puff volume (50 mL) when the vents were closed (48 ng mg-1), opened at 25% (39 ng mg-1) and at 50% (32 ng mg-1). By contrast, 50-mL puffs with 100% open vents, and puff volumes >100 mL for any vent aperture, generated formaldehyde yields of 20 ng mg-1 or lower, suggesting that a significant cooling effect resulted in limited carbonyl formation. Considering the effect of the coil resistance when operated at a voltage of 3.8 V, the amount of liquid evaporated per puff decreased as the resistance increased, in the order of 0.15 Ω > 0.25 Ω > 0.6 Ω, consistent with decreasing aerosol temperatures measured at the mouthpiece. Three different configurations of 0.15 Ω coils (dual, quadruple and octuple) were evaluated, observing significant variability. No clear trend was found between carbonyl emission rates and coil resistance or configuration, with highest emissions corresponding to a 0.25 Ω dual coil atomizer. Carbonyl emission rates were compared with those determined using the same methodology for conventional e-cigarettes (lower power tank systems), observing overall lower yields for the sub-ohm devices.

Vaporizable cannabis concentrates (VCCs) consumed as a liquid (vaping) or a waxy solid (dabbing) are becoming increasingly popular. However, their associated emissions and impacts have not been fully described. Mixtures containing different proportions of 12 VCC terpenoids and high MW compounds were heated at 100-500 °C inside a room-sized chamber to simulate emissions. Terpenoids, thermal degradation byproducts, and ultrafine particles (UFPs) were quantified in the chamber air. Air samples contained over 50% of emitted monoterpenes and less than 40% of released sesquiterpenes and terpene alcohols. Eleven degradation byproducts were quantified, including acrolein (1.3-3.9 μg m-3) and methacrolein (2.0 μg m-3). A large amount of UFPs were released upon heating and remained airborne for at least 3 h. The mode diameter increased from 80 nm at 100 °C to 140 nm at 500 °C, and particles smaller than 250 nm contributed to 90% of PM1.0. The presence of 0.5% of lignin, flavonoid, and triterpene additives in the heated mixtures resulted in a threefold increase in the particle formation rate and PM1.0 concentration, suggesting that these high-molecular-weight compounds enhanced aerosol inception and growth. Predicted UFP emission rates in typical consumption scenarios (6 × 1011-2 × 1013 # min-1) were higher than, or comparable with, other common indoor sources such as smoking and cooking.

Abstract Historical datasets can establish a critical baseline of plant–animal interactions for understanding contemporary interactions in the context of global change. Pollen is often incidentally preserved on animals in natural history collections. Techniques for removing pollen from insects have largely been developed for fresh insect specimens or historical specimens with large amounts of pollen on specialized structures. However, many key pollinating insects do not have these specialized structures and thus, there is a need for a method to extract pollen from these small and fragile insects. Here, we propose a precision glycerine jelly swab tool to allow for the precise removal of pollen from old, small and fragile insect specimens. We use this tool to remove pollen from five families of insects collected in the late 1970s. Additionally, we compare our method with four previously published techniques for removing pollen from pinned contemporary specimens. We show the functionality of the precision glycerine jelly swab for removing small quantities of pollen across insect families. We found that across the five methods, all removed pollen; yet, it was clear that some are better suited for fragile specimens. In particular, the traditional glycerine jelly swab and the precision glycerine jelly swabs both performed well for removing pollen from bee faces. The shaking wash resulted in specimen fracture and residue left behind, the ethanol rinses left setae matted, and the glycerol swabbing left residue on the specimen. Additionally, we present photographs documenting the effects of these methods on pinned honey bee specimens. The precision glycerine jelly swab opens up opportunities to sample pollen from a variety of insects in natural history collections. These pollen samples can be incorporated into downstream analyses for pollen identification either via microscopy or DNA sequencing, and the resulting plant–insect interaction data can establish historical baselines for contemporary comparison. Beyond our application of this method to pollen on insects, this precision glycerine jelly swab tool could be used to explore pollen placement specialization or to sample bryophyte, fungal and tree fern spores dispersing on animals.

Abstract Understanding sexual reproduction and recruitment in seagrasses is crucial to their conservation and restoration. Flowering, seed production, seed recruitment, and seedling establishment data for the seagrass Posidonia australis was collected annually between 2013 and 2018 in meadows at six locations around Rottnest Island, Western Australia. Variable annual rates of flowering and seed production were observed among meadows between northern and southern sides of the island and among years. Meadows on the northern shore consistently flowered more intensely and produced more seeds across the years of the survey. Inter‐site variation in clonal diversity and size of clones, seed production, wind and surface currents during pollen and seed release, and the large, but variable, impact of seed predation are likely the principal drivers of successful recruitment into established meadows and in colonizing unvegetated sands. The prolific but variable annual reproductive investment increases the probability of low levels of continuous recruitment from seed in this seagrass, despite high rates of abiotic and biotic disturbance at seedling, shoot, and patch scales. This strategy also imparts a level of ecological resilience to this long‐lived and persistent species.

Abstract Background This trial explores SM‐88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) Methods Forty‐nine patients were randomized to daily 460 or 920 mg oral SM‐88 with MPS (SM‐88 Regimen). The primary endpoint was objective response rate (RECIST 1.1). Results Thirty‐seven patients completed ≥ one cycle of SM‐88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality‐of‐life (QOL) was maintained and trended in favor of 920 mg. SM‐88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention‐to‐treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7–4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01). Conclusions SM‐88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second‐line treatment of patients with mPDAC. ClinicalTrials.gov Identifier: NCT03512756.

Pancreatic adenocarcinoma remains one of the most lethal cancers globally, with a significant need for improved therapeutic options. While the recent breakthroughs of immunotherapy through checkpoint inhibitors have dramatically changed treatment paradigms in other malignancies based on considerable survival benefits, this is not so for pancreatic cancer. Chemotherapies with modest benefits are still the cornerstone of advanced pancreatic cancer treatment. Pancreatic cancers are inherently immune-cold tumors and have been largely refractory to immunotherapies in clinical trials. Understanding and overcoming the current failures of immunotherapy through elucidating resistance mechanisms and developing novel therapeutic approaches are essential to harnessing the potential durable benefits of immune-modulating therapy in pancreatic cancer patients.

Cryptosporidium is a zoonotic apicomplexan parasite that infects the gastrointestinal epithelium and other mucosal surfaces in humans. It is an important opportunistic pathogen in AIDS patients and a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. The intestinal epithelial cells provide the first line of defense against Cryptosporidium infection and play a central role in activating and regulating the host’s antiparasitic response. Increasing evidence suggests that long noncoding RNAs (lncRNAs) participate in host-pathogen interactions and play a regulatory role in the pathogenesis of diseases but the underlying molecular mechanisms are not fully understood. We previously identified a panel of host lncRNAs that are upregulated in murine intestinal epithelial cells following Cryptosporidium infection, including U90926. We demonstrate here that U90926 is acting in a pro-parasitic manner in regulating intestinal epithelial cell-autonomous antiparasitic defense. Inhibition of U90926 resulted in a decreased infection burden of the parasite while overexpression of U90926 showed an increase in infection burden in cultured murine intestinal epithelial cells. Induction of U90926 suppressed transcription of epithelial defense genes involved in controlling Cryptosporidium infection through epigenetic mechanisms. Specifically, transcription of Aebp1, which encodes the Aebp1 protein, a potent modulator of inflammation and NF-κB signaling, was suppressed by U90926. Gain- or loss-of-function of Aebp1 in the host’s epithelial cells caused reciprocal alterations in the infection burden of the parasite. Interestingly, Cryptosporidium carries the Cryptosporidium virus 1 (CSpV1), a double-stranded (ds) RNA virus coding two dsRNA fragments, CSpV1-dsRdRp and CSpV1-dsCA. Both CSpV1-dsRdRp and CSpV1-dsCA can be delivered into infected cells as previously reported. We found that cells transfected with in vitro transcribed CSpV1-dsCA or CSpV1-dsRdRp displayed an increased level of U90926, suggesting that CSpV1 is involved in the upregulation of U90926 during Cryptosporidium infection. Our study highlights a new strategy by Cryptosporidium to hijack a host lncRNA to suppress epithelial cell-autonomous antiparasitic defense and allow for a robust infection.

Photocatalytic building surfaces can harness sunlight to reduce urban air pollution. The NOx abatement capacity of TiO2-coated granules used in roofing products was evaluated for commercial product development. A laboratory test chamber and ancillary setup were built following conditions prescribed by ISO Standard 22197-1. It was validated by exposing reference P25-coated aluminum plates to a 3 L min−1 air flow enriched in 1 ppm NO under UVA irradiation (360 nm, 11.5 W m−2). We characterized prototype granule-surfaced asphalt shingles and loose granules prepared with different TiO2 loadings and post-treatment formulations. Tests performed at surface temperatures of 25 and 60 °C showed that NOx abatement was more effective at the higher temperature. Preliminary tests explored the use of 1 ppm NO2 and of 1 ppm and 0.3 ppm NO/NO2 mixtures. Specimens were aged in a laboratory accelerated weathering apparatus, and by exposure to the outdoor environment over periods that included dry and rainy seasons. Laboratory aging led to higher NO removal and NO2 formation rates, and the same catalyst activation was observed after field exposure with frequent precipitation. However, exposure during the dry season reduced the performance. This inactivation was mitigated by cleaning the surface of field-exposed specimens. Doubling the TiO2 loading led to a 50–150% increase in NO removal and NOx deposition rates. Application of different post-treatment coatings decreased NO removal rates (21–35%) and NOx deposition rates (26–74%) with respect to untreated granules. The mass balance of nitrogenated species was assessed by extracting granules after UV exposure in a 1 ppm NO-enriched atmosphere.

This study characterized emissions from IQOS, a heated tobacco product promoted as a less harmful alternative to cigarettes. Consumable tobacco plugs were analyzed by headspace GC/MS to assess the influence of heating temperature on the emission profile. Yields of major chemical constituents increased from 4.1 mg per unit at 180 °C to 6.2 mg at 200 °C, and 10.5 mg at 220 °C. The Health Canada Intense smoking regime was used to operate IQOS in an environmental chamber, quantifying 33 volatile organic compounds in mainstream and sidestream emissions. Aldehydes, nitrogenated species, and aromatic species were found, along with other harmful and potentially harmful compounds. Compared with combustion cigarettes, IQOS yields were in most cases 1-2 orders of magnitude lower. However, yields were closer to, and sometimes higher than electronic cigarettes. Predicted users' daily average intake of benzene, formaldehyde, acetaldehyde and acrolein were 39 μg, 32 μg, 2.2 mg and 71 μg, respectively. Indoor air concentrations were estimated for commonly encountered scenarios, with acrolein levels of concern (over 0.35 μg m-3) derived from IQOS used in homes and public spaces. Heated tobacco products are a weaker indoor pollution source than conventional cigarettes, but their impacts are neither negligible nor yet fully understood.

Abstract This is a review of the current state of molecular profiling in gastrointestinal (GI) cancers and what to expect from this evolving field in the future. Individualized medicine is moving from broad panel testing of numerous genes or gene products in tumor biopsy samples, identifying biomarkers of prognosis and treatment response, to relatively noninvasive liquid biopsy assays, building on what we have learned in our tumor analysis and growing into its own evolving predictive and prognostic subspecialty. Hence, the field of GI precision oncology is exploding, and this review endeavors to summarize where we are now in preparation for the journey ahead.

With a growing body of literature on the topic of ecosystem service (ES), there is an urgent need to summarize ES research in the context of ecological restoration programs (ERPs) in China and identify knowledge gaps for future directions. We conducted a systematic literature review of articles to examine the use of ES approaches for ERP assessments. Our results showed that previous studies mainly focused on the Shaanxi Province, and more than half of the reviewed studies considered no more than three ES types simultaneously. All ES categories were not covered equally; most of the studies focused on provisioning and regulating services, while cultural services have received little attention. Although regional-scale and short-term assessments dominated the reviewed papers, we suggest that multiple temporal and spatial scales for ERP assessments should be given more attention in future work. Moreover, we highlight that an oversimplified land use/land cover (LULC) categorization scheme may potentially lead to inaccuracies and biases in ESs detection under restoration programs. Based on this review, our findings can guide future ERP assessments by using the ES approach. Meanwhile, given the global LULC change brought by the proliferation of plantations under ERPs, our results are also expected to provide a path forward to assess ESs associated with LULC change globally.

Strategic planning in universities is frequently positioned as vital for clarifying future directions, providing a coherent basis for decision-making, establishing priorities, and improving organizational performance. Models for successful strategic planning abound and often present the process as linear and straightforward. In this essay, we examine our own experiences of strategic planning for a new educational development centre situated in a Faculty of a research intensive university. Drawing from the literature, we provide a brief history of strategic planning in university contexts and consider criticisms and benefits. We investigate complicated issues related to our own process and, throughout, we argue that in spite of established formulas for creating a strategic plan, the process is non-linear and messy. We end this paper with recommendations for educational developer colleagues.

Stretch of myocardium, such as occurs upon increased filling of the cardiac chamber, induces two distinct responses: an immediate increase in twitch force followed by a slower increase in twitch force that develops over the course of several minutes. The immediate response is due, in part, to modulation of myofilament Ca2+ sensitivity by sarcomere length (SL). The slowly developing force response, termed the Slow Force Response (SFR), is caused by a slowly developing increase in intracellular Ca2+ upon sustained stretch. A blunted immediate force response was recently reported for myocardium isolated from homozygous giant titin mutant rats (HM) compared to muscle from wild-type littermates (WT). Here, we examined the impact of titin isoform on the SFR. Right ventricular trabeculae were isolated and mounted in an experimental chamber. SL was measured by laser diffraction. The SFR was recorded in response to a 0.2 μm SL stretch in the presence of [Ca2+]o = 0.4 mM, a bathing concentration reflecting ∼50% of maximum twitch force development at 25 °C. Presence of the giant titin isoform (HM) was associated with a significant reduction in diastolic passive force upon stretch, and ∼50% reduction of the magnitude of the SFR; the rate of SFR development was unaffected. The sustained SL stretch was identical in both muscle groups. Therefore, our data suggest that cytoskeletal strain may underlie directly the cellular mechanisms that lead to the increased intracellular [Ca2+]i that causes the SFR, possibly by involving cardiac myocyte integrin signaling pathways.

Individuals and teams engaging in the scholarship of teaching and learning (SoTL) in multidisciplinary higher education settings must make decisions regarding choice of research methodology and methods. These decisions are guided by the research context and the goals of the inquiry. With reference to our own recent experiences investigating pedagogical and curricular practices in a pharmacy program, we outline case study methodology as one of the many options available for SoTL inquiry. Case study methodology has the benefits of flexibility in terms of the types of research questions that can be addressed and the data collection methods that can be employed. Conducted with proper attention to the context of the case(s) selected, ethical treatment of participants, and data management, case studies also have the necessary rigour to be credible and generalizable. In the matter of generalization, however, we recommend that the readers of a case study draw their own conclusions about the applicability of the findings to other settings.

Abstract Background Improved knowledge on vector-borne pathogens in wildlife will help determine their effect on host species at the population and individual level and whether these are affected by anthropogenic factors such as global climate change and landscape changes. Here, samples from brown hyenas (Parahyaena brunnea) from Namibia (BHNA) and spotted hyenas (Crocuta crocuta) from Namibia (SHNA) and Tanzania (SHTZ) were screened for vector-borne pathogens to assess the frequency and genetic diversity of pathogens and the effect of ecological conditions and host taxonomy on this diversity. Methods Tissue samples from BHNA (n = 17), SHNA (n = 19) and SHTZ (n = 25) were analysed by PCRs targeting Anaplasmataceae, Rickettsia spp., piroplasms, specifically Babesia lengau-like piroplasms, Hepatozoidae and filarioids. After sequencing, maximum-likelihood phylogenetic analyses were conducted. Results The relative frequency of Anaplasmataceae was significantly higher in BHNA (82.4%) and SHNA (100.0%) than in SHTZ (32.0%). Only Anaplasma phagocytophilum/platys-like and Anaplasma bovis-like sequences were detected. Rickettsia raoultii was found in one BHNA and three SHTZ. This is the first report of R. raoultii from sub-Saharan Africa. Babesia lengau-like piroplasms were found in 70.6% of BHNA, 88.9% of SHNA and 32.0% of SHTZ, showing higher sequence diversity than B. lengau from South African cheetahs (Acinonyx jubatus). In one SHTZ, a Babesia vogeli-like sequence was identified. Hepatozoon felis-like parasites were identified in 64.7% of BHNA, 36.8% of SHNA and 44.0% of SHTZ. Phylogenetic analysis placed the sequences outside the major H. felis cluster originating from wild and domestic felids. Filarioids were detected in 47.1% of BHNA, 47.4% of SHNA and 36.0% of SHTZ. Phylogenetic analysis revealed high genetic diversity and suggested the presence of several undescribed species. Co-infections were frequently detected in SHNA and BHNA (BHNA median 3 pathogens, range 1–4; SHNA median 3 pathogens, range 2–4) and significantly rarer in SHTZ (median 1, range 0–4, 9 individuals uninfected). Conclusions The frequencies of all pathogens groups were high, and except for Rickettsia, multiple species and genotypes were identified for each pathogen group. Ecological conditions explained pathogen identity and diversity better than host taxonomy. Graphic Abstract

Abstract Host immune defenses are important components of host–parasite interactions that affect the outcome of infection and may have fitness consequences for hosts when increased allocation of resources to immune responses undermines other essential life processes. Research on host–parasite interactions in large free‐ranging wild mammals is currently hampered by a lack of verified noninvasive assays. We successfully adapted existing assays to measure innate and adaptive immune responses produced by the gastrointestinal mucosa in spotted hyena (Crocuta crocuta) feces, including enzyme‐linked immunosorbent assays (ELISAs), to quantify fecal immunoglobulins (total IgA, total IgG) and total fecal O‐linked oligosaccharides (mucin). We investigated the effect of infection load by an energetically costly hookworm (Ancylostoma), parasite richness, host age, sex, year of sampling, and clan membership on immune responses and asked whether high investment in immune responses during early life affects longevity in individually known spotted hyenas in the Serengeti National Park, Tanzania. Fecal concentrations of IgA, IgG, and mucin increased with Ancylostoma egg load and were higher in juveniles than in adults. Females had higher mucin concentrations than males. Juvenile females had higher IgG concentrations than juvenile males, whereas adult females had lower IgG concentrations than adult males. High IgA concentrations during the first year of life were linked to reduced longevity after controlling for age at sampling and Ancylostoma egg load. Our study demonstrates that the use of noninvasive methods can increase knowledge on the complex relationship between gastrointestinal parasites and host local immune responses in wild large mammals and reveal fitness‐relevant effects of these responses.

E-cigarettes likely represent a lower risk to health than traditional combustion cigarettes, but they are not innocuous. Recently reported emission rates of potentially harmful compounds were used to assess intake and predict health impacts for vapers and bystanders exposed passively. Vapers' toxicant intake was calculated for scenarios in which different e-liquids were used with various vaporizers, battery power settings and vaping regimes. For a high rate of 250 puff day-1 using a typical vaping regime and popular tank devices with battery voltages from 3.8 to 4.8 V, users were predicted to inhale formaldehyde (up to 49 mg day-1), acrolein (up to 10 mg day-1) and diacetyl (up to 0.5 mg day-1), at levels that exceeded U.S. occupational limits. Formaldehyde intake from 100 daily puffs was higher than the amount inhaled by a smoker consuming 10 conventional cigarettes per day. Secondhand exposures were predicted for two typical indoor scenarios: a home and a bar. Contributions from vaping to air pollutant concentrations in the home did not exceed the California OEHHA 8-h reference exposure levels (RELs), except when a high emitting device was used at 4.8 V. In that extreme scenario, the contributions from vaping amounted to as much as 12 μg m-3 formaldehyde and 2.6 μg m-3 acrolein. Pollutant concentrations in bars were modeled using indoor volumes, air exchange rates and the number of hourly users reported in the literature for U.S. bars in which smoking was allowed. Predicted contributions to indoor air levels were higher than those in the residential scenario. Formaldehyde (on average 135 μg m-3) and acrolein (28 μg m-3) exceeded the acute 1-h exposure REL for the highest emitting vaporizer/voltage combination. Predictions for these compounds also exceeded the 8-h REL in several bars when less intense vaping conditions were considered. Benzene concentrations in a few bars approached the 8-h REL, and diacetyl levels were close to the lower limit for occupational exposures. The integrated health damage from passive vaping was derived by computing disability-adjusted life years (DALYs) lost due to exposure to secondhand vapor. Acrolein was the dominant contributor to the aggregate harm. DALYs for the various device/voltage combinations were lower than-or comparable to-those estimated for exposures to secondhand and thirdhand tobacco smoke.

Infanticide by adult females includes any substantial contribution to the demise of young and inevitably imposes fitness costs on the victim’s genetic fathers, thereby generating sexual conflict with them. Few if any studies have quantified the impact of infanticide by females on male reproductive success, the magnitude of sexual conflict this causes and possible counterstrategies males use against infanticidal females. We examine these topics in spotted hyena (Crocuta crocuta) clans, where females socially dominate breeding males and strong female mate-choice is independent of male social status. We consider two causes of infanticide by females, violent attacks on cubs and fatal maternal neglect. Violent attacks are predicted during periods of social instability at the top of the female linear dominance hierarchy and victims are expected to predominantly have mothers above median rank. Fatal maternal neglect, when starving litters are abandoned, is associated with monopolization of food in clan territories by high-ranking females, and victims are predicted to have mothers below median rank. Female perpetrators of violent attacks are expected to reduce the reproductive success of the fathers of their victims more than perpetrators of fatal maternal neglect. We tested these predictions using 30 + years of data (54 recorded violent attacks, 43 cases of fatal maternal neglect, DNA profiling of 1,671 individuals). Using long-term observations at communal dens we investigated whether males use counterstrategies against infanticide reported in other mammals. Due to female social dominance over breeding males, strong female mate-choice and prolonged offspring dependence on lactation in spotted hyenas, we predicted that these counterstrategies were unlikely to be used by males against females, thus no incidences of them were likely to be observed. Our results revealed that breeding males lost cubs to violent attacks at all stages of their reproductive tenure and to perpetrators with whom they did not sire offspring. Amongst known sources of paternity loss, violent attacks comprised 12.2% and maternal neglect 9.8% of cases. Violent attacks significantly reduced offspring production rates of breeding males, suggesting that infanticide by females generates sexual conflict. As predicted, no evidence of males using counterstrategies against infanticide by females were observed.

Abstract Little is known about potential cascading effects of climate change on the ability of predators to exploit mobile aggregations of prey with a spatiotemporal distribution largely determined by climatic conditions. If predators employ central‐place foraging when rearing offspring, the ability of parents to locate sufficient prey could be reduced by climate change. In the Serengeti National Park, Tanzania, migratory species dominate mammalian herbivore biomass. These migratory herds exploit nutrient‐rich vegetation on the southern plains in the rainy season and surface water in the northwest in the dry season. Female spotted hyenas Crocuta crocuta breed throughout the year and use long‐distance central‐place‐foraging “commuting trips” to migratory herds to fuel lactation for ≥12 months. Changes in rainfall patterns that alter prey movements may decrease the ability of mothers to locate profitable foraging areas and thus increase their overall commuting effort, particularly for high‐ranking females that have priority of access to food resources within their clan territory and thus less commuting experience. In hyena clan territories, this may be reflected by a decrease in migratory herd presence and a decrease in the presence of lactating females, as maternal den presence represents the opposite of commuting effort. We investigated the strength of the relationship between rainfall volume, migratory herd presence in three hyena clan territories, and the responses of lactating females to this climate/prey relationship in terms of maternal den presence, using an observation‐based dataset spanning three decades. The probability of migratory herd presence in hyena clan territories increased with the amount of rainfall 2 months earlier, and maternal den presence increased with migratory herd presence. Rainfall volume substantially increased over 30 years, whereas the presence of migratory herds in hyena clans and the strength of the relationship between rainfall and migratory herd presence decreased. Hyenas thus adjusted well to the climate change‐induced decreased the presence of migratory herds in their territories, since maternal den presence did not decrease over 30 years and still matched periods of high prey abundance, irrespective of female social status. These results suggest a high plasticity in the response of this keystone predator to environmental variability.

Protozoan parasites, such as Plasmodium, Leishmania, Toxoplasma, Cryptosporidium, and Trypanosoma, are causative agents of health-threatening diseases in both humans and animals, leading to significant health risks and socioeconomic losses globally. The development of effective therapeutic and prevention strategies for protozoan-caused diseases requires a full understanding of the pathogenesis and protective events occurring in infected hosts. Interferons (IFNs) are a family of cytokines with diverse biological effects in host antimicrobial defense and disease pathogenesis, including protozoan parasite infection. Type II IFN (IFN-γ) has been widely recognized as the essential defense cytokine in intracellular protozoan parasite infection, whereas recent studies also revealed the production and distinct function of type I and III IFNs in host defense against these parasites. Decoding the complex network of the IFN family in host–parasite interaction is critical for exploring potential new therapeutic strategies against intracellular protozoan parasite infection. Here, we review the complex effects of IFNs on the host defense against intracellular protozoan parasites and the crosstalk between distinct types of IFN signaling during infections.

Sexual dimorphism is seen in many dioecious plant and animal species, which may influence their trophic interactions. The differences in trophic interactions derived from sexual dimorphism in plants may influence herbivorous performance and population dynamics. Both silkworm (Bombyx mori L.) and mulberry (Morus alba L.) usually exhibit sexual dimorphism. However, few studies have been conducted on the effect of sex-related silkworm and mulberry pairings on cocoon and silk qualities, which are crucial in sericulture. Here, we compared the differences in cocoon and silk qualities under four feeding combinations (FS-FL: female silkworm fed with leaves from female mulberry trees; MS-FL: male silkworm fed with leaves from female mulberry trees; FS-ML: female silkworm fed with leaves from male mulberry trees; MS-ML: male silkworm fed with leaves from male mulberry trees). The results showed that silkworms exhibited male-biased herbivory with more male mulberry leaves digested. The FS-ML group had higher silk weight and silk ratio of fresh cocoons than the FS-FL group, and the MS-ML group had lower coarse points than the MS-FL group. Compared with groups FS-ML and FS-FL, both MS-FL and MS-ML had smaller cocoons with longer silk lengths and a higher silk ratio of the fresh cocoons. In addition, the Entropy Weight-TOPSIS method showed the cocoon quality rank as FS-ML > FS-FL > MS-FL > MS-ML, whereas silk quality rank was MS-ML > FS-FL > FS-ML > MS-FL. These results indicate that the quality of cocoon and silk is related to the interaction of silkworm and mulberry at the sex level. Furthermore, female silkworms fed with female and male tree leaves have a higher total yield in cocoon production, while male silkworms fed with male tree leaves produced higher silk quality.

Abstract Mutualism benefits partner species, and theory predicts these partnerships can affect the abundance, diversity, and composition of partner and non‐partner species. We used 16 years of monitoring data to determine the ant partner species of tree cholla cacti (Cylindropuntia imbricata), which reward ants with extrafloral nectar in exchange for anti‐herbivore defense. These long‐term data revealed one dominant ant partner (Liometopum apiculatum) and two less common partners (Crematogaster opuntiae and Forelius pruinosus). We then used short‐term characterization of the terrestrial ant community by pitfall trapping to sample partner and non‐partner ant species across ten plots of varying cactus density. We found that the dominant ant partner tended a higher proportion cacti in plots of higher cactus density, and was also found at higher occurrence within the pitfall traps in higher density plots, suggesting a strong positive feedback that promotes ant partner occurrence where plant partners are available. Despite the strong association and increased partner occurrence, ant community‐wide effects from this mutualism appear limited. Of the common ant species, the occurrence of a single non‐partner ant species was negatively associated with cactus density and with the increased presence of L. apiculatum. Additionally, the composition and diversity of the ant community in our plots were insensitive to cactus density variation, indicating that positive effects of the mutualism on the dominant ant partner did not have cascading impacts on the ant community. This study provides novel evidence that exclusive mutualisms, even those with a strong positive feedback, may be limited in the scope of their community‐level effects.

Use of electronic cigarettes has grown exponentially over the past few years, raising concerns about harmful emissions. This study quantified potentially toxic compounds in the vapor and identified key parameters affecting emissions. Six principal constituents in three different refill "e-liquids" were propylene glycol (PG), glycerin, nicotine, ethanol, acetol, and propylene oxide. The latter, with mass concentrations of 0.4-0.6%, is a possible carcinogen and respiratory irritant. Aerosols generated with vaporizers contained up to 31 compounds, including nicotine, nicotyrine, formaldehyde, acetaldehyde, glycidol, acrolein, acetol, and diacetyl. Glycidol is a probable carcinogen not previously identified in the vapor, and acrolein is a powerful irritant. Emission rates ranged from tens to thousands of nanograms of toxicants per milligram of e-liquid vaporized, and they were significantly higher for a single-coil vs a double-coil vaporizer (by up to an order of magnitude for aldehydes). By increasing the voltage applied to a single-coil device from 3.3 to 4.8 V, the mass of e-liquid consumed doubled from 3.7 to 7.5 mg puff(-1) and the total aldehyde emission rates tripled from 53 to 165 μg puff(-1), with acrolein rates growing by a factor of 10. Aldehyde emissions increased by more than 60% after the device was reused several times, likely due to the buildup of polymerization byproducts that degraded upon heating. These findings suggest that thermal degradation byproducts are formed during vapor generation. Glycidol and acrolein were primarily produced by glycerin degradation. Acetol and 2-propen-1-ol were produced mostly from PG, while other compounds (e.g., formaldehyde) originated from both. Because emissions originate from reaction of the most common e-liquid constituents (solvents), harmful emissions are expected to be ubiquitous when e-cigarette vapor is present.

Universities around the world increasingly recognize the importance of offering high quality, high-engagement student learning experiences in their undergraduate and graduate programs. While the SoTL movement and literature has gained considerable recognition and momentum over the past two decades, much less inquiry has focused on institutional and program-level educational reforms. This paper calls for a more expansive view and strategic use of SoTL inquiry in order to make substantive contributions to curriculum renewal, educational leadership practices, and, most importantly, the quality of undergraduate and graduate degree programs. Theoretical underpinnings, emerging trends, challenges, and strategic supports to enhance the effectiveness and efficiency of curricula within and across diverse disciplinary contexts are discussed.