Influence of Four Veterinary Antibiotics on Constructed Treatment Wetland Nitrogen Transformation

The use of wetlands as a treatment approach for nitrogen in runoff is a common practice in agroecosystems. However, nitrate is not the sole constituent present in agricultural runoff and other biologically active contaminants have the potential to affect nitrate removal efficiency. In this study, the impacts of the combined effects of four common veterinary antibiotics (chlortetracycline, sulfamethazine, lincomycin, monensin) on nitrate-N treatment efficiency in saturated sediments and wetlands were evaluated in a coupled microcosm/mesocosm scale experiment. Veterinary antibiotics were hypothesized to significantly impact nitrogen speciation (e.g., nitrate and ammonium) and nitrogen uptake and transformation processes (e.g., plant uptake and denitrification) within the wetland ecosystems. To test this hypothesis, the coupled study had three objectives: 1. assess veterinary antibiotic impact on nitrogen cycle processes in wetland sediments using microcosm incubations, 2. measure nitrate-N reduction in water of floating treatment wetland systems over time following the introduction of veterinary antibiotic residues, and 3. identify the fate of veterinary antibiotics in floating treatment wetlands using mesocosms. Microcosms containing added mixtures of the veterinary antibiotics had little to no effect at lower concentrations but stimulated denitrification potential rates at higher concentrations. Based on observed changes in the nitrogen loss in the microcosm experiments, floating treatment wetland mesocosms were enriched with 1000 μg L−1 of the antibiotic mixture. Rates of nitrate-N loss observed in mesocosms with the veterinary antibiotic enrichment were consistent with the microcosm experiments in that denitrification was not inhibited, even at the high dosage. In the mesocosm experiments, average nitrate-N removal rates were not found to be impacted by the veterinary antibiotics. Further, veterinary antibiotics were primarily found in the roots of the floating treatment wetland biomass, accumulating approximately 190 mg m−2 of the antibiotic mixture. These findings provide new insight into the impact that veterinary antibiotic mixtures may have on nutrient management strategies for large-scale agricultural operations and the potential for veterinary antibiotic removal in these wetland

Benefits and challenges of electronic prescribing for general practitioners and pharmacists in regional Australia

Objective: To explore the benefits and challenges of electronic prescribing (e-prescribing) for general practitioners (GPs) and pharmacists in regional New South Wales (NSW). Methods: This qualitative study utilised semistructured interviews conducted virtually or in-person between July and September 2021. Setting and Participants: General practitioners and pharmacists practising in Bathurst NSW. Main Outcomes: Self-reported perceived and experienced benefits and challenges of e-prescribing. Results: Two GPs and four pharmacists participated in the study. Reported benefits of e-prescribing included improvement in the prescribing and dispensing process, patient adherence, and prescription safety and security. The increased convenience for the patients was appreciated particularly during the COVID-19 pandemic. Challenges discussed were how the system was perceived to be unsafe and insecure, costs of messaging and updating general practice software, utilisation of new systems and patient awareness. Pharmacists reported the need for education to patients and staff to minimise the impact of inexperience with the novel technology on workflow efficacy. Conclusion: This study provided first insight and information on the perspectives of GPs and pharmacists 12 months after the implementation of e-prescribing. Further nationwide studies are required to consolidate these findings; provide comparisons with the system's progress since conception; determine whether metropolitan and rural health care professionals share similar perspectives; and shed light on where additional government support may be required

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients

Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections. We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9$1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1$1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8$50,000 per life-year saved. Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development

DNA Double-Strand Break Repair Genes and Oxidative Damage in Brain Metastasis of Breast Cancer

Background Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood. Methods Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis–specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group). Results Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression. Conclusions BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species–mediated genotoxic stress in the metastatic brain

Quantifying trends in disease impact to produce a consistent and reproducible definition of an emerging infectious disease.

The proper allocation of public health resources for research and control requires quantification of both a disease's current burden and the trend in its impact. Infectious diseases that have been labeled as "emerging infectious diseases" (EIDs) have received heightened scientific and public attention and resources. However, the label 'emerging' is rarely backed by quantitative analysis and is often used subjectively. This can lead to over-allocation of resources to diseases that are incorrectly labelled "emerging," and insufficient allocation of resources to diseases for which evidence of an increasing or high sustained impact is strong. We suggest a simple quantitative approach, segmented regression, to characterize the trends and emergence of diseases. Segmented regression identifies one or more trends in a time series and determines the most statistically parsimonious split(s) (or joinpoints) in the time series. These joinpoints in the time series indicate time points when a change in trend occurred and may identify periods in which drivers of disease impact change. We illustrate the method by analyzing temporal patterns in incidence data for twelve diseases. This approach provides a way to classify a disease as currently emerging, re-emerging, receding, or stable based on temporal trends, as well as to pinpoint the time when the change in these trends happened. We argue that quantitative approaches to defining emergence based on the trend in impact of a disease can, with appropriate context, be used to prioritize resources for research and control. Implementing this more rigorous definition of an EID will require buy-in and enforcement from scientists, policy makers, peer reviewers and journal editors, but has the potential to improve resource allocation for global health

KElt-18b: Puffy planet, hot host, probably perturbed

We report the discovery of KELT-18b, a transiting hot Jupiter in a 2.87-day orbit around the bright (V = 10.1), hot, F4V star BD+60 1538 (TYC 3865-1173-1). We present follow-up photometry, spectroscopy, and adaptive optics imaging that allow a detailed characterization of the system. Our preferred model fits yield a host stellar temperature of K and a mass of, situating it as one of only a handful of known transiting planets with hosts that are as hot, massive, and bright. The planet has a mass of, a radius of, and a density of, making it one of the most inflated planets known around a hot star. We argue that KELT-18b\u27s high temperature and low surface gravity, which yield an estimated ∼600 km atmospheric scale height, combined with its hot, bright host, make it an excellent candidate for observations aimed at atmospheric characterization. We also present evidence for a bound stellar companion at a projected separation of ∼1100 au, and speculate that it may have contributed to the strong misalignment we suspect between KELT-18\u27s spin axis and its planet\u27s orbital axis. The inferior conjunction time is 2457542.524998 ± 0.000416 (BJDTDB) and the orbital period is 2.8717510 ± 0.0000029 days. We encourage Rossiter-McLaughlin measurements in the near future to confirm the suspected spin-orbit misalignment of this system

Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

system. mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging.Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma

Hearing loss and cognition: A protocol for ensuring speech understanding before neurocognitive assessment

INTRODUCTION: Many neurocognitive evaluations involve auditory stimuli, yet there are no standard testing guidelines for individuals with hearing loss. The ensuring speech understanding (ESU) test was developed to confirm speech understanding and determine whether hearing accommodations are necessary for neurocognitive testing. METHODS: Hearing was assessed using audiometry. The probability of ESU test failure by hearing status was estimated in 2679 participants (mean age: 81.4 ± 4.6 years) using multivariate logistic regression. RESULTS: Only 2.2% (N = 58) of participants failed the ESU test. The probability of failure increased with hearing loss severity; similar results were observed for those with and without mild cognitive impairment or dementia. DISCUSSION: The ESU test is appropriate for individuals who have variable degrees of hearing loss and cognitive function. This test can be used prior to neurocognitive testing to help reduce the risk of hearing loss and compromised auditory access to speech stimuli causing poorer performance on neurocognitive evaluation

KELT-16b: A Highly Irradiated, Ultra-short Period Hot Jupiter Nearing Tidal Disruption

We announce the discovery of KELT-16b, a highly irradiated, ultra-short period hot Jupiter transiting the relatively bright ($V = 11.7$) star TYC 2688-1839-1. A global analysis of the system shows KELT-16 to be an F7V star with $T_\textrm{eff} = 6236\pm54$ K, $\log{g_\star} = 4.253_{-0.036}^{+0.031}$, [Fe/H] = -0.002$_{-0.085}^{+0.086}$, $M_\star = 1.211_{-0.046}^{+0.043} M_\odot$, and $R_\star = 1.360_{-0.053}^{+0.064} R_\odot$. The planet is a relatively high mass inflated gas giant with $M_\textrm{P} = 2.75_{-0.15}^{+0.16} M_\textrm{J}$, $R_\textrm{P} = 1.415_{-0.067}^{+0.084} R_\textrm{J}$, density $\rho_\textrm{P} = 1.20\pm0.18$ g cm$^{-3}$, surface gravity $\log{g_\textrm{P}} = 3.530_{-0.049}^{+0.042}$, and $T_\textrm{eq} = 2453_{-47}^{+55}$ K. The best-fitting linear ephemeris is $T_\textrm{C} = 2457247.24791\pm0.00019$ BJD$_{tdb}$ and $P = 0.9689951 \pm 0.0000024$ d. KELT-16b joins WASP-18b, -19b, -43b, -103b, and HATS-18b as the only giant transiting planets with $P < 1$ day. Its ultra-short period and high irradiation make it a benchmark target for atmospheric studies by HST, Spitzer, and eventually JWST. For example, as a hotter, higher mass analog of WASP-43b, KELT-16b may feature an atmospheric temperature-pressure inversion and day-to-night temperature swing extreme enough for TiO to rain out at the terminator. KELT-16b could also join WASP-43b in extending tests of the observed mass-metallicity relation of the Solar System gas giants to higher masses. KELT-16b currently orbits at a mere $\sim$ 1.7 Roche radii from its host star, and could be tidally disrupted in as little as a few $\times 10^{5}$ years (for a stellar tidal quality factor of $Q_*' = 10^5$). Finally, the likely existence of a widely separated bound stellar companion in the KELT-16 system makes it possible that Kozai-Lidov oscillations played a role in driving KELT-16b inward to its current precarious orbit.Comment: 16 pages, 18 Figures, 7 Tables, Accepted for publication in A

Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. Methods We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. Findings Globally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1-7·8), from 65·6 years (65·3-65·8) in 1990 to 73·0 years (72·7-73·3) in 2017. The increase in years of life varied from 5·1 years (5·0-5·3) in high SDI countries to 12·0 years (11·3-12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1-33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8-15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9-6·7), from 57·0 years (54·6-59·1) in 1990 to 63·3 years (60·5-65·7) in 2017. The increase varied from 3·8 years (3·4-4·1) in high SDI countries to 10·5 years (9·8-11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4-1·7) in Saint Vincent and the Grenadines (62·4 years [59·9-64·7] in 1990 to 63·5 years [60·9-65·8] in 2017) to 23·7 years (21·9-25·6) in Eritrea (30·7 years [28·9-32·2] in 1990 to 54·4 years [51·5-57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6-2·3) in Algeria to 11·9 years (10·9-12·9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75·8 years [72·4-78·7]) and males (72·6 years [69·8-75·0]) and the lowest estimates were in Central African Republic (47·0 years [43·7-50·2] for females and 42·8 years [40·1-45·6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41·3% (38·8-43·5) for communicable diseases and by 49·8% (47·9-51·6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40·1% (36·8-43·0), although age-standardised DALY rates decreased by 18·1% (16·0-20·2)