Influences of 23 different equations used to calculate gene copies of SARS-CoV-2 during wastewater-based epidemiology.

Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the use of wastewater-based surveillance (WBS) has increased dramatically along with associated infrastructure globally. However, due to the global nature of its application, and various workflow adaptations (e.g., sample collection, water concentration, RNA extraction kits), numerous methods for back-calculation of gene copies per volume (gc/L) of sewage have also emerged. Many studies have considered the comparability of processing methods (e.g., water concentration, RNA extraction); however, for equations used to calculate gene copies in a wastewater sample and subsequent influences on monitoring viral trends in a community and its association with epidemiological data, less is known. Due to limited information on how many formulas exist for the calculation of SARS-CoV-2 gene copies in wastewater, we initially attempted to quantify how many equations existed in the referred literature. We identified 23 unique equations, which were subsequently applied to an existing wastewater dataset. We observed a range of gene copies based on use of different equations, along with variability of AUC curve values, and results from correlation and regression analyses. Though a number of individual laboratories appear to have independently converged on a similar formula for back-calculation of viral load in wastewater, and share similar relationships with epidemiological data, differential influences of various equations were observed for variation in PCR volumes, RNA extraction volumes, or PCR assay parameters. Such observations highlight challenges when performing comparisons among WBS studies when numerous methodologies and back-calculation methods exist. To facilitate reproducibility among studies, the different gc/L equations were packaged as an R Shiny app, which provides end users the ability to investigate variability within their datasets and support comparisons among studies.

Diminished antimicrobial drug use in dogs with allergic dermatitis treated with oclacitinib.

Introduction: Dogs with allergic dermatitis often suffer concurrent skin and ear infections. The objective of this study was to retrospectively quantify the number of systemic and topical antimicrobial transactions in dogs with allergic dermatitis, following administration of oclacitinib or a glucocorticoid, compared to dogs that did not receive a pruritus therapy when there is an initial diagnosis of pyoderma. A secondary objective was to demonstrate that dogs on oclacitinib use fewer antimicrobials and concomitant therapies over time and have improved quality of life. Materials and methods: This was a retrospective case-control study using a large, centralized database to identify canine patients receiving pruritus therapy along with a concurrent diagnosis of pyoderma. For the second objective, 58 client-owned dogs diagnosed with allergic dermatitis were enrolled in a prospective owner and dog quality of life and treatment satisfaction (QoL&TS) study that also evaluated concomitant therapy use over time. In Part A, data consisted of anonymous transaction records from 1,134 hospitals across the United States, representing pyoderma visits between December 2018 and December 2019. Odds ratios comparing the relative odds of having additional antimicrobial agent transactions were calculated, given initial pruritus therapy compared to dogs that did not receive pruritus therapy. Parametric bootstrapping was used to calculate goodness-of-fit statistics. In part B, dogs entered the study on Day 0 and returned for examination on Days 14, 21, 30, and 60. Owner determination of QoL&TS was performed on Days 0, 1, 3, 14, 21, 30, and 60. On Days 0, 14, 21, and 60, a veterinarian assessed concomitant therapies and dermatitis severity scoring. Least Squares Means and Standard Errors for QoL&TS, and Dermatitis Vet VAS (Visual Analog Scale) Scores were calculated using a Linear Mixed Model Approach for Repeated Measures (α = 0.05). The percent reduction in therapies was also calculated. Results: Dogs that received oclacitinib (n = 5,132) or a glucocorticoid (n = 7,024) had reduced odds (OR: 0.8091; p = 0.0002 and OR: 0.7095; p < 0.0001, respectively) of having a follow up antimicrobial drug transaction after initial antimicrobial therapy compared to dogs with no pruritus therapy at the initial visit (n = 12,997). In part B, oclacitinib demonstrated a statistically significant improvement in QoL&TS scores over time QoL (p < 0.05). Veterinarian assessment showed a 70% reduction in dermatitis severity over time (p < 0.05), supporting oclacitinib's anti-inflammatory effects. Oclacitinib therapy was also associated with an 83% reduction in concomitant treatments, including a 100% reduction in systemic antimicrobial therapy over eight weeks. Discussion: Dogs receiving oclacitinib showed no increase in antimicrobial therapy transactions compared to glucocorticoid recipients at the initial pyoderma diagnosis. Having a pruritus therapy at the index pyoderma visit reduced the odds of subsequent antimicrobial transactions. In addition to reducing concomitant therapy usage, oclacitinib improved owner and pet QoL, suggesting a paradigm shift in treatment success that could reshape allergic pruritus therapy recommendations. The study provides empirical evidence of oclacitinib's reduction in antibacterial therapy, supporting its therapeutic value and antimicrobial stewardship.

Retrospective analyses of heartworm (Dirofilaria immitis) disease and ectoparasite preventive medication compliance in veterinary practices in the USA.

BACKGROUND: Compliance failure with administration of heartworm (HW) disease preventives has been reported as the main contributor to HW disease incidence in medicalized dogs. This study aimed to evaluate purchase compliance with different canine HW preventive products in the USA. METHODS: Anonymized transaction data from clinics throughout the USA served as the basis for two retrospective analyses. We first examined the monthly equivalent doses of HW preventive purchases from clinics that had implemented extended-release moxidectin injectables ProHeart® 6 (PH6) and/or ProHeart® 12 (PH12) compared to clinics that prescribed monthly HW preventatives (MHWP) only. In the second analysis, the purchase compliance in practices that dispensed only flea and tick (FT) and HW products separately but did not dispense combination products (dual-therapy practices) was compared to the purchase compliance with the combination product Simparica Trio® (sarolaner, moxidectin, and pyrantel chewable tablets), purchased in clinics having implemented combination therapy in their formulary (combination-therapy practices). In both analyses, the numbers of monthly doses dispensed annually per dog were calculated. RESULTS: Transaction data from 3,539,990 dogs in 4615 practices were included in the first analysis. In dogs administered PH12 or PH6, the numbers of monthly equivalent doses were 12 and 8.1, respectively. In both clinic types, the average annual number of MHWP doses totaled 7.3. In the second analysis, a total of 919 practices were identified as combination-therapy practices and 434 as dual-therapy-only practices. A total of 246,654 dogs (160,854 dogs in dual-therapy practices and 85,800 dogs in combination-therapy practices) were included in the calculation of the average annual number of monthly doses, which totaled 6.8 (HW preventive products) and 4.4 (FT products) in dual-therapy practices compared to 7.2 months for both FT and HW preventives with Simparica Trio® across both practice types. CONCLUSIONS: The injectable HW preventive PH12 is the only product that provides 12 months of heartworm disease prevention in a single veterinarian-administered injection. When choosing a monthly preventive, the combination therapy was associated with a greater purchase compliance compared with FT and HW products being dispensed separately.

Prevention and long-term outcomes of naturally occurring canine heartworm infection in primary care settings.

Background: This study had two objectives: first, to examine the association between the history of heartworm preventive purchase compliance and the risk of positive heartworm tests, and second to preliminarily investigate the long-term cardiac outcomes of heartworm disease in dogs that had undergone successful adulticidal therapy. Methods: A retrospective cohort study design was used for both analyses, using anonymous transaction data from Covetrus (retrospective analysis 1) and anonymized medical records from Banfield Pet Hospital (retrospective analysis 2), both including canine patients across the USA. The first analysis examined the relative risk (RR) of a positive heartworm test in dogs with lapses in heartworm preventive purchase history compared to dogs that had no history of a preventive purchase six to 24 months prior to the test. In the second analysis, a long-term evaluation of structured diagnostic codes pertaining to cardiac diseases and risk assessment of outcomes was performed in dogs that had previously been successfully treated for heartworm disease compared to dogs that never had a positive heartworm test. Results: 83,478 unique patients were included in the first analysis. Compared to 32,413 dogs with no history of a heartworm preventive purchase, 44,410 dogs with lapses in monthly preventive purchases had a reduced risk of testing positive for heartworm disease (RR = 0.36, p < 0.0001). Dogs (n = 6,655) with lapses in injectable heartworm preventive administration had a decreased risk of a positive test versus dogs with no preventive purchases (RR = 0.15, p < 0.0001), as well as versus dogs with lapses in monthly heartworm preventive purchases (RR = 0.28, p = 0.0024). In the second analysis, 6,138 patients treated for heartworm infection were found to have significantly (p < 0.001) elevated risks of right heart failure (RR = 3.59), left heart failure (RR = 1.83), or cardiomyopathy (RR = 2.79) compared to 4,022,752 patients that never had a positive heartworm test. Conclusion: This study highlights the importance of compliance with heartworm preventive guidelines, to reduce the risk of heartworm disease in dogs, which is not only a potentially life-threatening condition in the short-term but also associated with long-term negative cardiac outcomes.

DUX4 expression activates JNK and p38 MAP kinases in myoblasts.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by misexpression of the DUX4 transcription factor in skeletal muscle that results in transcriptional alterations, abnormal phenotypes and cell death. To gain insight into the kinetics of DUX4-induced stresses, we activated DUX4 expression in myoblasts and performed longitudinal RNA sequencing paired with proteomics and phosphoproteomics. This analysis revealed changes in cellular physiology upon DUX4 activation, including DNA damage and altered mRNA splicing. Phosphoproteomic analysis uncovered rapid widespread changes in protein phosphorylation following DUX4 induction, indicating that alterations in kinase signaling might play a role in DUX4-mediated stress and cell death. Indeed, we demonstrate that two stress-responsive MAP kinase pathways, JNK and p38, are activated in response to DUX4 expression. Inhibition of each of these pathways ameliorated DUX4-mediated cell death in myoblasts. These findings uncover that the JNK pathway is involved in DUX4-mediated cell death and provide additional insights into the role of the p38 pathway, a clinical target for the treatment of FSHD.

The compliance and revenue benefits of ProHeart Vs monthly heartworm disease preventives in the US.

The aim of the current study was to understand how the canine heartworm disease preventive ProHeart® 12 (extended-release injectable moxidectin, PH 12), impacts heartworm preventive purchase compliance and veterinary practice revenue over time compared to monthly heartworm disease preventives. This was a preliminary observational purchase compliance and revenue study based on a retrospective review of transaction data from 4,615 general practices across the United States. The review period was from September 2018 to August 2020. Anonymous transaction records of over 13 million canine patients were analyzed. Of these, only 3.5 million (25.7%) patients purchased any heartworm preventive, as has been presented in other studies. Practices that implemented PH 12 demonstrated the most growth in canine heartworm prevention revenue, patients, and patient compliance levels during the 12-month observation period, compared to previous year. These practices saw year over year growth in percent patients receiving heartworm protection, as well as 10% and 15% growth in the proportion of preventive patients compliant for more than 6 months and 12 months respectively. In contrast, practices that did not bring on PH 12 and only dispensed monthly heartworm preventives saw a decline in the proportion of canine preventive patients that were compliant for more than 6 months. Similarly, PH 12 practices experienced 15% growth in preventive revenue, and practices that did not bring on PH 12 only experienced 3.9% growth in preventive revenue. PH 12 was single-handedly responsible for all growth in patients compliant for more than 6 months in this study. Growth in protection of canine patients with PH 12 proves a helpful tool where mitigation strategies have thus far failed to curb increasing canine heartworm disease prevalence in the US.

Evaluation of plasma N-terminal pro-B-type natriuretic peptide levels in healthy North American Salukis with normal echocardiographic measurements.

Measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels has been shown to have clinical significance for diagnosis and management of heart disease in dogs. Evaluation of current reference limits for specific breeds is necessary to ensure the test can accurately distinguish between healthy and diseased animals. The objective of this study is to evaluate the adequacy of currently established NT-proBNP reference limits for clinical use in healthy Salukis. Cardiac health of 33 clinically healthy Salukis was evaluated via echocardiography using available breed standards. Plasma concentrations of NT-proBNP were measured using a commercially available assay. A one-sided 97.5% upper reference limit for the NT-proBNP concentrations was calculated using non-parametric percentile method. The 97.5% upper reference limit was 769 pmol/L (90% CI, 547-1214 pmol/L) for the study dogs. This upper reference limit was within the currently established non-breed specific NT-proBNP upper reference limit of 900 pmol/L. No relationship between sex, age, or body weight on plasma levels of NT-proBNP was noted. Results of this study supports the use of currently available non-breed specific NT-proBNP cut-off values for clinical evaluation of healthy Salukis.

Vasoactive agents in acute mesenteric ischaemia in critical care. A systematic review.

Background: Acute mesenteric ischaemia (AMI) is a surgical emergency which has an associated high mortality.  The mainstay of active treatment includes early surgical intervention, with resection of non-viable bowel, and revascularisation of the ischaemic bowel where possible. Due to the physiological insult of AMI however, perioperative care often involves critical care and the use of vasoactive agents to optimise end organ perfusion. A number of these vasoactive agents are currently available with varied mechanism of action and effects on splanchnic blood flow. However, specific guidance on which is the optimal vasoactive drug to use in these settings is limited. This systematic review aimed to evaluate the current evidence comparing vasoactive drugs in AMI. Methods: A systematic search of Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review was performed on the 5th of November 2020 to identify randomised clinical trials comparing different vasoactive agents in AMI on outcomes including mortality. The search was performed through the Royal College of Surgeons of England (RCSEng) search support library. Results were analysed using the Rayyan platform, and independently screened by four investigators. Results: 614 distinct papers were identified. After screening, there were no randomised clinical trials meeting the inclusion criteria. Conclusions: This review identifies a gap in literature, and therefore recommends an investigation into current practice and clinician preference in relation to vasoactive agents in AMI. Multicentre randomised controlled trials comparing these medications on clinical outcomes will therefore be required to address this question.

p38 MAPKs - roles in skeletal muscle physiology, disease mechanisms, and as potential therapeutic targets.

p38 MAPKs play a central role in orchestrating the cellular response to stress and inflammation and in the regulation of myogenesis. Potent inhibitors of p38 MAPKs have been pursued as potential therapies for several disease indications due to their antiinflammatory properties, although none have been approved to date. Here, we provide a brief overview of p38 MAPKs, including their role in regulating myogenesis and their association with disease progression. Finally, we discuss targeting p38 MAPKs as a therapeutic approach for treating facioscapulohumeral muscular dystrophy and other muscular dystrophies by addressing multiple pathological mechanisms in skeletal muscle.

Pharmacoeconomic Analysis of Heartworm Preventive Compliance and Revenue in Veterinary Practices in the United States.

Background: Heartworm disease (HWD) is a potentially fatal condition caused by the nematode Dirofilaria immitis. It is endemic in North America, and the American Heartworm Society recommends that owned dogs be on a Food and Drug Administration-approved HWD preventive year-round. The objective of this study was to compare the 12-month HWD preventive purchase compliance rates of injectable moxidectin (ProHeart® 6) and the dose equivalent in monthly HWD preventives and their associated economic value to the veterinary hospital. Methods: This study used retrospective anonymized transactional data of 7,926,392 unique dogs from 3,737 companion animal practices across the US for the period 2014-2017. Compliance was defined using American Heartworm Society guidelines. Comparisons were purchases of a 6-month moxidectin injection or six doses of any monthly HWD or HWD combination preventive product, tracked for the next preventive purchase 5-7 months later. Total revenue, HWD prevention cost, 12-month repurchase compliance, and patient retention were calculated. Data were expressed on an annualized basis. Compliance comparisons were calculated based on proportion analysis with the SAS ProbNorm function (SAS 9.4, Cary, NC), using a two-sided t-test, at the 5% level of significance (P < 0.05). Results: At 51.7%, annual compliance with injectable moxidectin was higher than the dose equivalent in monthly HWD preventives, which was 24.4% (P = 0.0001). Eighty-five percent of patients on injectable moxidectin recorded additional transactions during the first visit (average invoice of $161), compared with only 55% of pet owners who purchased monthly HWD prevention (average invoice $141) or monthly HWD combination (average invoice of $171). The average costs of 6 months of HWD preventives were as follows: injectable moxidectin, $48 (29.7% of the total visit invoice); monthly HWD prevention, $45 (31.0% of the total invoice); and monthly HWD combination, 95 (55.6% of the total visit invoice). Finally, dogs receiving injectable moxidectin had a higher proportion of patients with repeat injections within 12 months between 2014 and 2017, with 68% retention rate after 4 years. In comparison, the six-dose monthly HWD cohort retention rate dropped to 55% by 2017. Conclusions: Dogs receiving injectable moxidectin had higher HWD preventive compliance, generated more practice revenue, and had a higher rate of practice retention compared with monthly HWD products.

Cell adaptation to aneuploidy by the environmental stress response dampens induction of the cytosolic unfolded-protein response.

Aneuploid yeast cells are in a chronic state of proteotoxicity, yet do not constitutively induce the cytosolic unfolded protein response, or heat shock response (HSR) by heat shock factor 1 (Hsf1). Here, we demonstrate that an active environmental stress response (ESR), a hallmark of aneuploidy across different models, suppresses Hsf1 induction in models of single-chromosome gain. Furthermore, engineered activation of the ESR in the absence of stress was sufficient to suppress Hsf1 activation in euploid cells by subsequent heat shock while increasing thermotolerance and blocking formation of heat-induced protein aggregates. Suppression of the ESR in aneuploid cells resulted in longer cell doubling times and decreased viability in the presence of additional proteotoxicity. Last, we show that in euploids, Hsf1 induction by heat shock is curbed by the ESR. Strikingly, we found a similar relationship between the ESR and the HSR using an inducible model of aneuploidy. Our work explains a long-standing paradox in the field and provides new insights into conserved mechanisms of proteostasis with potential relevance to cancers associated with aneuploidy.

Assessing the role of the universal addition of CT thorax to CT abdomen and pelvis in the COVID era. A retrospective multicentre cohort study.

OBJECTIVE: The SARS-CoV2 infection is associated with high mortality for individuals who undergo emergency surgery. The United Kingdom surgical associations and Colleges of Surgeons collectively recommended the addition of CT Thorax to all emergency CT abdomen/pelvis imaging in order to help identify possible COVID-19 patients. Early identification of these patients would lead to optimal treatment strategies for the patient and protection for staff members. However, an extension of CT would be associated with increased irradiation doses for the patient, and its diagnostic relevance was unclear. METHODS: This was a retrospective observational review looking at all surgical admissions that required a CT Thorax/Abdomen/Pelvis across 7 weeks during the COVID-19 pandemic, across four Scottish Hospitals. CT thorax investigations (of non-surgical patients) were also re-assessed by a single radiologist to assess the extent of pathology identified at the lung bases (and therefore would be included in a standard CT abdomen and pelvis). RESULTS: Of 216 patients identified who had a CT thorax/Abdomen/Pelvis during the timeframe, 5 were diagnosed with COVID-19. During this timeframe, 77 patients underwent solely CT thorax. Across the entire cohort, 98% of COVID pathology was identified at the lung bases. The estimated sensitivity and specificity of CT thorax was 60 and 86.4% respectively. CONCLUSIONS: In a region with relatively low prevalence of SARS-COV2 infection, inclusion of CT Thorax in surgical admission imaging does not significantly contribute to identification and management of SARS-COV2 patients. We therefore suggest that imaging the lung bases can be sufficient to raise clinical suspicion of COVID-19. ADVANCES IN KNOWLEDGE: This paper adds further evidence to that from other single UK centres that the addition of CT chest for all patients does not yield any further diagnostic information regarding coronavirus. Additionally, rapid SARS-CoV-2 testing in the UK (which is currently widely available) further demonstrates that inclusion of the entire chest during CT examination of the acute abdomen is not required.

Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells.

Aneuploidy, a condition characterized by chromosome gains and losses, causes reduced fitness and numerous cellular stresses, including increased protein aggregation. Here, we identify protein complex stoichiometry imbalances as a major cause of protein aggregation in aneuploid cells. Subunits of protein complexes encoded on excess chromosomes aggregate in aneuploid cells, which is suppressed when expression of other subunits is coordinately altered. We further show that excess subunits are either degraded or aggregate and that protein aggregation is nearly as effective as protein degradation at lowering levels of excess proteins. Our study explains why proteotoxic stress is a universal feature of the aneuploid state and reveals protein aggregation as a form of dosage compensation to cope with disproportionate expression of protein complex subunits.

Mechanics of spontaneously formed nanoblisters trapped by transferred 2D crystals.

Layered systems of 2D crystals and heterostructures are widely explored for new physics and devices. In many cases, monolayer or few-layer 2D crystals are transferred to a target substrate including other 2D crystals, and nanometer-scale blisters form spontaneously between the 2D crystal and its substrate. Such nanoblisters are often recognized as an indicator of good adhesion, but there is no consensus on the contents inside the blisters. While gas-filled blisters have been modeled and measured by bulge tests, applying such models to spontaneously formed nanoblisters yielded unrealistically low adhesion energy values between the 2D crystal and its substrate. Typically, gas-filled blisters are fully deflated within hours or days. In contrast, we found that the height of the spontaneously formed nanoblisters dropped only by 20-30% after 3 mo, indicating that probably liquid instead of gas is trapped in them. We therefore developed a simple scaling law and a rigorous theoretical model for liquid-filled nanoblisters, which predicts that the interfacial work of adhesion is related to the fourth power of the aspect ratio of the nanoblister and depends on the surface tension of the liquid. Our model was verified by molecular dynamics simulations, and the adhesion energy values obtained for the measured nanoblisters are in good agreement with those reported in the literature. This model can be applied to estimate the pressure inside the nanoblisters and the work of adhesion for a variety of 2D interfaces, which provides important implications for the fabrication and deformability of 2D heterostructures and devices.

Can anti-gravity running improve performance to the same degree as over-ground running?

This study examined the changes in running performance, maximal blood lactate concentrations and running kinematics between 85%BM anti-gravity (AG) running and normal over-ground (OG) running over an 8-week training period. Fifteen elite male developmental cricketers were assigned to either the AG or over-ground (CON) running group. The AG group (n = 7) ran twice a week on an AG treadmill and once per week over-ground. The CON group (n = 8) completed all sessions OG on grass. Both AG and OG training resulted in similar improvements in time trial and shuttle run performance. Maximal running performance showed moderate differences between the groups, however the AG condition resulted in less improvement. Large differences in maximal blood lactate concentrations existed with OG running resulting in greater improvements in blood lactate concentrations measured during maximal running. Moderate increases in stride length paired with moderate decreases in stride rate also resulted from AG training. The use of AG training to supplement regular OG training for performance should be used cautiously, as extended use over long periods of time could lead to altered stride mechanics and reduced blood lactate.

Interface-Governed Deformation of Nanobubbles and Nanotents Formed by Two-Dimensional Materials.

Nanoblisters such as nanobubbles and nanotents formed by two-dimensional (2D) materials have been extensively exploited for strain engineering purposes as they can produce self-sustained, nonuniform in-plane strains through out-of-plane deformation. However, deterministic measure and control of strain fields in these systems are challenging because of the atomic thinness and unconventional interface behaviors of 2D materials. Here, we experimentally characterize a simple and unified power law for the profiles of a variety of nanobubbles and nanotents formed by 2D materials such as graphene and MoS_{2} layers. Using membrane theory, we analytically unveil what sets the in-plane strains of these blisters regarding their shape and interface characteristics. Our analytical solutions are validated by Raman spectroscopy measured strain distributions in bulged graphene bubbles supported by strong and weak shear interfaces. We advocate that both the strain magnitudes and distributions can be tuned by 2D material-substrate interface adhesion and friction properties.

Out-of-Plane Electromechanical Response of Monolayer Molybdenum Disulfide Measured by Piezoresponse Force Microscopy.

Two-dimensional (2D) materials have recently been theoretically predicted and experimentally confirmed to exhibit electromechanical coupling. Specifically, monolayer and few-layer molybdenum disulfide (MoS2) have been measured to be piezoelectric within the plane of their atoms. This work demonstrates and quantifies a nonzero out-of-plane electromechanical response of monolayer MoS2 and discusses its possible origins. A piezoresponse force microscope was used to measure the out-of-plane deformation of monolayer MoS2 on Au/Si and Al2O3/Si substrates. Using a vectorial background subtraction technique, we estimate the effective out-of-plane piezoelectric coefficient, d33eff, for monolayer MoS2 to be 1.03 ± 0.22 pm/V when measured on the Au/Si substrate and 1.35 ± 0.24 pm/V when measured on Al2O3/Si. This is on the same order as the in-plane coefficient d11 reported for monolayer MoS2. Interpreting the out-of-plane response as a flexoelectric response, the effective flexoelectric coefficient, µeff*, is estimated to be 0.10 nC/m. Analysis has ruled out the possibility of elastic and electrostatic forces contributing to the measured electromechanical response. X-ray photoelectron spectroscopy detected some contaminants on both MoS2 and its substrate, but the background subtraction technique is expected to remove major contributions from the unwanted contaminants. These measurements provide evidence that monolayer MoS2 exhibits an out-of-plane electromechanical response and our analysis offers estimates of the effective piezoelectric and flexoelectric coefficients.

Aneuploidy Causes Non-genetic Individuality.

Phenotypic variability is a hallmark of diseases involving chromosome gains and losses, such as Down syndrome and cancer. Allelic variances have been thought to be the sole cause of this heterogeneity. Here, we systematically examine the consequences of gaining and losing single or multiple chromosomes to show that the aneuploid state causes non-genetic phenotypic variability. Yeast cell populations harboring the same defined aneuploidy exhibit heterogeneity in cell-cycle progression and response to environmental perturbations. Variability increases with degree of aneuploidy and is partly due to gene copy number imbalances, suggesting that subtle changes in gene expression impact the robustness of biological networks and cause alternate behaviors when they occur across many genes. As inbred trisomic mice also exhibit variable phenotypes, we further propose that non-genetic individuality is a universal characteristic of the aneuploid state that may contribute to variability in presentation and treatment responses of diseases caused by aneuploidy.

Prevalence, knowledge and attitudes relating to ß-alanine use among professional footballers.

OBJECTIVES: To investigate ß-alanine supplementation use and level of knowledge amongst professional footballers. DESIGN: Cross-sectional survey of Australian professional football players. METHODS: Questionnaires assessing ß-alanine supplementation behaviours, level of knowledge and sources of information were completed by professional rugby union (RU) (n=87), rugby league (RL) (n=180) and Australian Rules Football (ARF) (n=303) players. RESULTS: Approximately 61% of athletes reported ß-alanine use, however use by ARF football players (44%) was lower than that of RU (80%) and RL players (80%). The majority of respondents were not using ß-alanine in accordance with recommendations. Only 35% of the participants were able to correctly identify the potential benefits of ß-alanine supplementation. The main information sources that influenced players' decision to use ß-alanine were strength and conditioning coach (71%) and dietitian (52%). Forty-eight per cent of athletes never read labels prior to supplementing and only 11% completed their own research on ß-alanine. Compared to RL and ARF players, RU players had both a greater knowledge of ß-alanine supplementation and better supplementation practices. CONCLUSIONS: Despite over half the surveyed professional footballers using ß-alanine, the majority of athletes used ß-alanine in a manner inconsistent with recommendations. A better understanding of the environment and culture within professional football codes is required before supplement use becomes consistent with evidence based supplement recommendations.

Comparison of photoinduced reorientation of ortho-, meta-, and para-methyl red-doped nematic liquid crystals on rubbed polyimide.

We compare the photoinduced reorientation of the easy axis on rubbed polyimide surfaces for the nematic E7 doped with three isomers of methyl red; ortho, meta, and para. Using optical techniques, the angle and the pitch of the director at the polymer surface were measured before, during, and after photoexcitation of the dye. Optical absorbances were also measured before and after photoexcitation. Extrapolation lengths, hence anchoring energies, were determined with the on/off application of a magnetic field for meta- and para-methyl red-doped nematics. Because of an elastic reorientation of the easy axis in the presence of the magnetic field, we could not determine the extrapolation length of the ortho-methyl red-doped nematic. Our results confirm that photoinduced reorientation is facilitated by desorption of all dyes from the polymer surface. While there is little evidence of weak photoinduced adsorption of meta- and para-methyl red to the surface during photoexcitation, there is strong evidence of photoinduced adsorption of ortho-methyl red, which is long lasting.