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Nutrient management strategies that exploit nutrient elements' synergistic interaction to enhance nitrogen use efficiency (NUE) are needed for economic and environmental reasons. A field study was carried out during the 2020–2022 growing seasons at six locations in three countries: two each in the United States, Ghana, and Mali using three sulfur (S) sources with different bioavailability levels (micronized elemental S, untreated elemental S, and ammonium sulfate); applied at five S application rates: site‐specific recommended S rate (SR), 25%, 50%, 75%, and 125% of SR; and a single nitrogen (N) application rate (site‐specific recommended N rate) to comprehensively investigate the influence of S availability on NUE. Specific objectives were to evaluate the impact of S availability on corn (Zea mays L.) yield, N uptake, and NUE. Regardless of the S source and experimental site, the aboveground S and N uptake were strongly and positively correlated (r > 0.88). Increases in apparent N recovery efficiency and agronomic NUE occurred with corresponding increases in S application rate, irrespective of the site and S source. The combined data showed that the agronomic efficiency of applied N fertilizer sources could be enhanced significantly by increasing S availability in soils. With the rising N fertilizer costs in recent times, N losses from the applied fertilizer are a drain on farmers' income and of environmental concern. Thus, increasing NUE is a needed strategy to safeguard against excessive N application, increase farm profits, and minimize N losses to the environment that could disrupt the ecosystem function. Core Ideas: Nitrogen (N) losses from applied fertilizer are both a great economic drain and a major environmental concern. Exploiting the synergistic interaction of nutrient elements is needed to improve N use efficiency (NUE).Sulfur (S) and N uptake were strongly and positively correlated (r > 0.88).Increase in apparent N recovery efficiency and agronomic NUE occurred with an increasing S application rate.Increasing NUE is expected to increase returns on investment and safeguard against ecosystem degradation. [ABSTRACT FROM AUTHOR]

Objectives: To assess associations between breast cancer‐specific survival and timeliness of treatment, based on 2020 Australian guidelines for the treatment of early breast cancer. Design: Population‐based cohort study; analysis of linked Queensland Cancer Register, patient medical record, and National Death Index data, supplemented by telephone interviews. Setting, participants: Women aged 20–79 years diagnosed with invasive breast cancer during 1 March 2010 – 30 June 2013, followed to 31 December 2020. Main outcome measures: Breast cancer‐specific survival for women who received or did not receive treatment within the recommended timeframe, overall and for six treatment intervals; optimal cut‐points for each treatment interval; characteristics of women for whom treatment was not provided within the recommended timeframe. Results: Of 5426 eligible women, 4762 could be invited for interviews; complete data were available for 3044 women (56% of eligible women, 65% of invited women). Incomplete compliance with guideline interval recommendations was identified for 1375 women (45%); their risk of death from breast cancer during the follow‐up period was greater than for those for whom guideline compliance was complete (adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 1.04–1.96). Risk of death was greater for women for whom the diagnosis to surgery interval exceeded 29 days (aHR, 1.76; 95% CI, 1.19–2.59), the surgery to chemotherapy interval exceeded 36 days (aHR, 1.63; 95% CI, 1.13–2.36), or the chemotherapy to radiotherapy interval exceeded 31 days (aHR, 1.83; 95% CI, 1.19–2.80). Treatment intervals longer than recommended were more frequent for women for whom breast cancer was detected by public facility screening (adjusted odds ratio [aOR], 1.58; 95% CI, 1.22–2.04) or by symptoms (aOR, 1.39; 95% CI, 1.09–1.79) than when cancer had been detected in private facilities, and for women without private health insurance (aOR, 1.96; 95% CI, 1.66–2.32) or living outside major cities (aOR, 1.38; 95% CI, 1.18–1.62). Conclusions: Breast cancer‐specific survival was poorer for women for whom the diagnosis to surgery, surgery to chemotherapy, or chemotherapy to radiotherapy intervals exceeded guideline‐recommended limits. Our findings support 2020 Australian guideline recommendations regarding timely care. [ABSTRACT FROM AUTHOR]

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Introduction: Ever since the United States Food and Drug Administration (FDA) approved aducanumab and Centers for Medicare & Medicaid Service (CMS) restricted coverage for the drug, a crucial question has been how other payers will behave. This study examined how Medicaid and commercial plans cover aducanumab. Methods: We created a database of aducanumab coverage policies issued by Medicaid fee‐for‐service programs (50 states and DC) and 35 of the largest commercial plans (covering ∼ 84% of the commercially insured population). Results: We found that only 41% of Medicaid fee‐for‐service plans have issued a publicly available coverage policy for aducanumab and that there is wide variation in these coverage criteria. Although the majority of included commercial plans have issued an aducanumab coverage policy, only five plans covered aducanumab for their enrollees. Available coverage polices showed little consistency in how to measure sufficient treatment response. Discussion: Differences in coverage policies mean that Alzheimer's patients' access to aducanumab may vary across jurisdictions and across commercial insurers. Highlights: Less than half of state Medicaid fee‐for‐service plans issued a publicly available coverage policy for aducanumab.Available Medicaid coverage policies varied substantially in their coverage criteria.The majority of included commercial plans issued an aducanumab coverage policy; only five plans covered aducanumab.Available coverage polices showed little consistency in how to measure sufficient treatment response. [ABSTRACT FROM AUTHOR]

Background: Virtual healthcare services are usually provided from urban centres to outpatient clinics or underserved rural areas. This study utilises virtual pharmacy as an innovative model to provide services to a metropolitan hospital from a rural area. Aim: This study assesses the feasibility, and patient and staff acceptability of a Virtual Clinical Pharmacy Service (VCPS) in a tertiary metropolitan hospital ward with limited on‐site clinical pharmacy services. Method: Pharmacists from a rural health district provided telepharmacy services for nine weeks. Data on service provision and detection of medication‐related issues were captured in the electronic health record. Service acceptability was assessed through a staff focus group and patient acceptability by a patient‐reported experience measures (PREM) survey. Ethical approval was granted by the Greater Western Human Research Ethics Committee (Reference no: 2021/ETH00097). Results: The VCPS demonstrated high utilisation, with 535 clinical and medication reviews provided for 225 patients. Virtual medication reviews identified 151 medication‐related issues or recommendations. PREM surveys (n = 22) were supportive of the VCPS model. Staff valued the service and reported ease of access to specialist medication advice and confidence that patient medications were correct. Staff raised patient confidentiality in open wards and lack of experience using virtual healthcare as barriers to the implementation. Conclusion: Feasibility was demonstrated by high service utilisation, detection of medication‐related issues, and measures of acceptability from patients and staff. The VCPS offers a solution to enhance sustainability and service agility by delivery of clinical services when face‐to‐face is not practicable or available. Further research is required to demonstrate efficacy and to confirm patient acceptability. [ABSTRACT FROM AUTHOR]

Purpose: Demonstrate that dental hygiene students' participation in a randomized controlled trial comparing the plaque‐removing capability of two toothbrushes provides a fuller understanding of the factors affecting the potential application of research to practice. Methods: All students (N = 18) in a baccalaureate dental hygiene class were engaged in the design of a randomized controlled trial using the Consolidated Standards of Reporting Trials (CONSORT) standard and then participated as subjects in a staggered, repeated measures trial using plaque removal as the dependent variable and brush type, brush head wear, and time in study as independent variables. A debriefing of student participation and lessons learned from analyzing the results was conducted. Results: The study found statistically significant differences in plaque removal capability. Brush type accounted for only 4% of the variance, while measures of brush head wear were inconsistent, and time in the study ("experimental fatigue") accounted for the most variance (9%). Students recognized and confirmed by their personal experiences that research that fails to focus on variance can create an overly optimistic impression of research effectiveness. There was strong agreement that subjects/patients vary widely and that performance depends on multiple factors. Conclusions: Dental hygiene students who participated as subjects in a randomized controlled trial comparing toothbrushes for plaque removal capacity felt that full analysis to account for all sources of variance and estimate the magnitude of measures of effect add to the value of reported research. Variation across patients is important in practice, if often overlooked as an "error" in the literature. [ABSTRACT FROM AUTHOR]

Background: Ridge preservation is performed by placing a biocompatible product, following tooth extraction, to maintain bone volume. However, current ridge preservation therapies do not always maintain the volume required for future implant placement. Variations in surgical technique and material selection contribute to determining clinical outcomes. The wide variety of grafting materials available and conflicting efficacy reports make selecting the appropriate graft materials challenging. To investigate how different commercially available ridge preservation products might perform clinically: Helistat (collagen control) (Material 1), OsteoGen Plug (Material 2), Bio-Oss Collagen (Material 3), and J-Bone (native bone) (Material 4) were evaluated.Methods: These products underwent field emission scanning electron microscopy, microcomputed tomography, helium pycnometry, and infrared spectra analysis. Human osteosarcomas were incubated on products and proliferation was monitored with CCK-8 and visualized with confocal microscopy. Scaffold osteoconductivity was evaluated through the cellular production of proteins osteocalcin, osteonectin, and osteopontin.Results: Results indicated that products varied in porosity and pore interconnectivity. Although Material 3 was chemically similar to Material 4, Material 2 demonstrated significantly better biocompatibility. Functionally, Material 1 and Material 2 elicited higher osteonectin release than Material 3 and Material 4 which suggests the latter products suppress endogenous osteonectin secretion. Furthermore, osteopontin secretion was minimal for all products, while osteocalcin was elevated. This seems to suggest that high levels of mineralization might be deleterious for bone regeneration.Conclusions: Although all products are marketed as effective preservation products, the results demonstrated high variability in physical, chemical, and biological effects; however, this study suggests a product with higher ratio of collagen to mineral component may have the most desirable effects for the use in alveolar ridge preservation. [ABSTRACT FROM AUTHOR]

Senescence is a cellular state in which cells undergo persistent cell cycle arrest in response to nonlethal stress. In the treatment of cancer, senescence induction is a potent method of suppressing tumour cell proliferation. In spite of this, senescent cancer cells and adjacent nontransformed cells of the tumour microenvironment can remain metabolically active, resulting in paradoxical secretion of pro‐inflammatory factors, collectively termed the senescence‐associated secretory phenotype (SASP). The SASP plays a critical role in tumorigenesis, affecting numerous processes including invasion, metastasis, epithelial‐to‐mesenchymal transition (EMT) induction, therapy resistance and immunosuppression. With increasing evidence, it is becoming clear that cell type, tissue of origin and the primary cellular stressor are key determinants in how the SASP will influence tumour development and progression, including whether it will be pro‐ or antitumorigenic. In this review, we will focus on recent evidence regarding therapy‐induced senescence (TIS) from anticancer agents, including chemotherapy, radiation, immunotherapy, and targeted therapies, and how each therapy can trigger the SASP, which in turn influences treatment efficacy. We will also discuss novel pharmacological manipulation of senescent cancer cells and the SASP, which offers an exciting and contemporary approach to cancer therapeutics. With future research, these adjuvant options may help to mitigate many of the negative side effects and protumorigenic roles that are currently associated with TIS in cancer. [ABSTRACT FROM AUTHOR]

Purpose/objectives: Identify barriers and opportunities regarding faculty participation in research. Methods: Sixty‐four faculty members of all ranks and days of employment completed a survey designed to reveal attitudes toward participation in research. Results: Among those responding, three‐quarters said they were actively engaged in research, and 45% of these identified no perceived barriers. Those reporting obstacles rank‐ordered 10 barriers, but no consistent patterns emerged. A factor analysis revealed three clusters of concerns: (a) school barriers, (b) personal barriers, and (c) team opportunities. A large number of comments were offered, and these tended to group by the three quantitatively identified factors. Conclusion: These findings were consistent with the view that lack of time and formal training in standardized research skills were not major impediments to scholarship. Instead, assistance in navigating administrative hurdles and participation on multiskilled teams appeared to offer the best prospect for helping faculty interested in research. [ABSTRACT FROM AUTHOR]

Small‐cell lung cancer (SCLC) occurs infrequently in never/former light smokers. We sought to study this rare clinical subset through next‐generation sequencing (NGS) and by characterizing a representative patient‐derived model. We performed targeted NGS, as well as comprehensive pathological evaluation, in 11 never/former light smokers with clinically diagnosed SCLC. We established a patient‐derived model from one such patient (DFCI168) harboring an NRASQ61K mutation and characterized the sensitivity of this model to MEK and TORC1/2 inhibitors. Despite the clinical diagnosis of SCLC, the majority (8/11) of cases were either of nonpulmonary origin or of mixed histology and included atypical carcinoid (n = 1), mixed non‐small‐cell lung carcinoma and SCLC (n = 4), unspecified poorly differentiated carcinoma (n = 1), or small‐cell carcinoma from different origins (n = 2). RB1 and TP53 mutations were found in four and five cases, respectively. Predicted driver mutations were detected in EGFR (n = 2), NRAS (n = 1), KRAS (n = 1), BRCA1 (n = 1), and ATM (n = 1), and one case harbored a TMPRSS2‐ERG fusion. DFCI168 (NRASQ61K) exhibited marked sensitivity to MEK inhibitors in vitro and in vivo. The combination of MEK and mTORC1/2 inhibitors synergized to prevent compensatory mTOR activation, resulting in prolonged growth inhibition in this model and in three other NRAS mutant lung cancer cell lines. SCLC in never/former light smokers is rare and is potentially a distinct disease entity comprised of oncogenic driver mutation‐harboring carcinomas morphologically and/or clinically mimicking SCLC. Comprehensive pathologic review integrated with genomic profiling is critical in refining the diagnosis and in identifying potential therapeutic options. [ABSTRACT FROM AUTHOR]

Objectives: To prepare more accurate population-based Australian birthweight centile charts by using the most recent population data available and by excluding pre-term deliveries by obstetric intervention of small for gestational age babies.Design: Population-based retrospective observational study.Setting: Australian Institute of Health and Welfare National Perinatal Data Collection.Participants: All singleton births in Australia of 23-42 completed weeks' gestation and with spontaneous onset of labour, 2004-2013. Births initiated by obstetric intervention were excluded to minimise the influence of decisions to deliver small for gestational age babies before term.Main Outcome Measures: Birthweight centile curves, by gestational age and sex.Results: Gestational age, birthweight, sex, and labour onset data were available for 2 807 051 singleton live births; onset of labour was spontaneous for 1 582 137 births (56.4%). At pre-term gestational ages, the 10th centile was higher than the corresponding centile in previous Australian birthweight charts based upon all births.Conclusion: Current birthweight centile charts probably underestimate the incidence of intra-uterine growth restriction because obstetric interventions for delivering pre-term small for gestational age babies depress the curves at earlier gestational ages. Our curves circumvent this problem by excluding intervention-initiated births; they also incorporate more recent population data. These updated centile curves could facilitate more accurate diagnosis of small for gestational age babies in Australia. [ABSTRACT FROM AUTHOR]

A new Mirai variant found recently was equipped with a dynamic update ability, which increases the level of difficulty for DDoS mitigation. Continuous development of 5G technology and an increasing number of Internet of Things (IoT) devices connected to the network pose serious threats to cyber security. Therefore, researchers have tried to develop better DDoS mitigation systems. However, the majority of the existing models provide centralized solutions either by deploying the system with additional servers at the host site, on the cloud, or at third party locations, which may cause latency. Since Internet service providers (ISP) are links between the internet and users, deploying the defense system within the ISP domain is the panacea for delivering an efficient solution. To cope with the dynamic nature of the new DDoS attacks, we utilized an unsupervised artificial neural network to develop a hierarchical two‐layered self‐organizing map equipped with a twofold feature selection for DDoS mitigation within the ISP domain. [ABSTRACT FROM AUTHOR]

Objectives: To report human papillomavirus (HPV) testing patterns and rates of oncogenic HPV-positivity for specimens submitted during the first 6 months after the National Cervical Screening Program switched from cytology- to primary HPV-based screening.Design, Participants: Retrospective cross-sectional review of 195 606 specimens submitted for HPV testing, 1 December 2017 - 31 May 2018.Setting: Large community-based general pathology laboratory in metropolitan Sydney.Main Outcome Measures: Prevalence of oncogenic HPV types (all, HPV16/18, non-HPV16/18) by reason for HPV test (primary screening, non-screening); for oncogenic HPV-positive women in the age band recommended for primary HPV screening (25-74 years), prevalence of cytologic abnormality and rates of 12-month follow-up and colposcopy recommendations.Results: 195 606 samples were received: 157 700 (80.6%) for primary screening, 37 906 (19.4%) for non-screening tests. Oncogenic HPV was detected in 8.1% of screening tests (95% CI, 7.9-8.2%) and 20.9% of non-screening tests (95% CI, 20.5-21.3%); 35.5% (95% CI, 34.7-36.4%) of women of recommended screening age with positive oncogenic HPV screening test results also had a cytologic abnormality. The proportion of HPV16/18-positive samples with high grade abnormality was 15.3% (95% CI, 14.2-16.6%); for samples positive for other oncogenic HPV types, the proportion was 6.3% (95% CI, 5.8-6.8%). Repeat HPV testing after 12 months was recommended for 5.4% (95% CI, 5.3-5.5%) and direct colposcopy for 2.6% (95% CI, 2.5-2.7%) of screened women aged 25-74 years.Conclusions: High grade cytologic abnormalities were more common in women positive for HPV16/18, supporting their higher risk classification. Colposcopy referral rates were higher than during primary cytology-based testing, as predicted by clinical trial and modelling data. The prevalence of HPV was much higher in non-screening than in primary screening samples. Our findings indicate the renewed program is performing as expected during the initial HPV screening round. [ABSTRACT FROM AUTHOR]

Synovial sarcoma is a slow-growing, intermediate- to high-grade neoplasm with extensive metastatic potential. Accurate diagnosis of synovial sarcoma may pose a challenge to providers because of its indolent growth and variable presentation. The findings of a soft-tissue, periarticular mass with calcifications in a young patient are highly suggestive of synovial sarcoma. Although different imaging modalities can aid in the diagnosis of synovial sarcoma, diagnostic certainty is typically only confirmed by biopsy and histologic analysis. We present a case describing the diagnostic workup of synovial sarcoma with an emphasis on imaging findings in a patient with increasing symptomatology spanning more than a decade.Level Of Evidence: V. [ABSTRACT FROM AUTHOR]

Abstract: Managers require quantitative yet tractable tools that identify areas for restoration yielding effective benefits for targeted wildlife species and the ecosystems they inhabit. As a contemporary example of high national significance for conservation, the persistence of Greater Sage‐grouse (Centrocercus urophasianus) in the Great Basin is compromised by strongly interacting stressors of conifer expansion, annual grass invasion, and more frequent wildfires occurring in sagebrush ecosystems. Associated restoration treatments to a sagebrush‐dominated state are often costly and may yield relatively little ecological benefit to sage‐grouse if implemented without estimating how Sage‐grouse may respond to treatments, or do not consider underlying processes influencing sagebrush ecosystem resilience to disturbance and resistance to invasive species. Here, we describe example applications of a spatially explicit conservation planning tool (CPT) to inform prioritization of: (1) removal of conifers (i.e., pinyon‐juniper); and (2) wildfire restoration aimed at improving habitat conditions for the Bi‐State Distinct Population Segment of Sage‐grouse along the California–Nevada state line. The CPT measures ecological benefits to sage‐grouse for a given management action through a composite index comprised of resource selection functions and estimates of abundance and space use. For pinyon‐juniper removal, we simulated changes in land‐cover composition following the removal of sparse trees with intact understories, and ranked treatments on the basis of changes in ecological benefits per dollar‐unit of cost. For wildfire restoration, we formulated a conditional model to simulate scenarios for land cover changes (e.g., sagebrush to annual grass) given estimated fire severity and underlying ecosystem processes influencing resilience to disturbance and resistance to invasion by annual grasses. For both applications, we compared CPT rankings to land cover changes along with sagebrush resistance and resilience metrics. Model results demonstrated how the CPT can be an important step in identifying management projects that yield the highest quantifiable benefit to Sage‐grouse while avoiding costly misallocation of resources, and highlight the importance of considering changes in sage‐grouse ecological response and factors influencing sagebrush ecosystem resilience to disturbance and resistance to invasion. This unique framework can be adopted to help inform other management questions aimed at improving habitat for other species across sagebrush and other ecosystems. [ABSTRACT FROM AUTHOR]

Background: While previous studies have demonstrated the effect of Alzheimer's disease (AD) CSF testing in changing diagnosis, we lack an understanding of how this testing affects clinical management. Therefore, we assessed changes in clinical management associated with AD CSF biomarker testing when ordered as part of routine clinical management. Method: The 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT‐AD BC) study (NCT05002699) is a longitudinal study examining the impact of AD CSF testing on clinical management, personal utility and health care economics in British Columbia, Canada. After AD CSF testing was ordered as part of routine care (where the clinical scenario met the appropriate use criteria), the patient and their physician were eligible to participate in the study. The primary outcome was the change in management (pre‐ v. post‐biomarker results) in a composite measure including 1) AD drug therapy, 2) other relevant drug therapy, 3) other diagnostic procedures, and 4) referral or counselling. Result: Participants (n = 129) had a median age of 63 (IQR:58‐68); 49% were female. Cognitive impairment at baseline consisted of 7% with subjective cognitive impairment, 53% with mild cognitive impairment, and 40% with dementia. CSF biomarker profiles were consistent with an amyloid‐beta pathology (i.e., A+) in 72% of cases. Changes in clinical management because of testing occurred in 83% of cases including: referrals and counseling (57%), imaging (47%) and other diagnostic procedures (e.g., neuropsychological testing) (42%), and use of AD drug therapies (40%). For those with a non‐AD pre‐biomarkers diagnosis, 42% were changed to AD post‐biomarkers; for those with an AD pre‐biomarkers diagnosis, 18% were changed to non‐AD post‐biomarkers. Conclusion: This study has revealed substantial changes in clinical management as a direct result of AD CSF biomarker testing in routine care. An understanding of the implications of biomarker testing will in turn help us: improve appropriate utilization, understand the broader impacts on persons living with dementia and on the health care system, and prepare for expanded use of this testing with the availability of disease‐modifying therapeutics. [ABSTRACT FROM AUTHOR]

Background: The growing clinical use of the analysis of CSF amyloid‐beta peptides and tau proteins to assist in the diagnosis Alzheimer's disease (AD) highlights an urgent need to understand the impact of this testing on patients, as well as their care partners. We aimed to address this knowledge gap by examining the perspectives of patients who underwent CSF AD biomarker testing as part of routine care, and a family member ('care partner'). Method: Within the 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT‐AD BC) study (NCT05002699), we conducted semi‐structured telephone interviews with patients that meet the appropriate use criteria for AD CSF biomarker testing and separate interviews with their care partner. A subset of patients (n=33) and care partners (n=31) were interviewed post‐CSF biomarker disclosure and again ∼5 months (median: 4.9 [4.2‐5.3]) after the initial interview. Thematic content analysis was performed to understand the impact of AD biomarker testing on health behaviors, financial and care planning decisions, and resources and support needs. Result: Most patients (94%) rated their decision to undergo testing as "easy", with the remainder noting the decision was neither easy nor difficult. After result disclosure, a few patients (8%) reported feelings of concern, but the majority (80%) reported overall positive feelings from having more information about their brain health, certainty around their diagnosis, and the ability to plan ahead. Regarding actions patients planned to take after learning their test result, many expressed an intention to adopt or continue with healthy behaviors, such as exercise (42%). From the care partners' perspective, many expressed relief at having more diagnostic certainty post‐disclosure, and that this information would help them plan for future care needs. Post‐disclosure, care partners also relayed an increased awareness of future caregiving responsibilities and the need or desire to connect with community resources to help navigate this new role. Additional analyses investigated responses based on patients' amyloid status and disease severity. Conclusion: In summary, individuals undergoing AD CSF biomarker testing and their care partners found that CSF testing provided the information needed to help them make wellbeing decisions and plan their future. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with debilitating symptoms of dyspnoea and cough, resulting in respiratory failure, impaired quality of life and ultimately death. Diagnosing IPF can be challenging, as it often shares many features with other interstitial lung diseases. In this article, we summarise recent joint position statements on the diagnosis and management of IPF from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia, specifically tailored for physicians across Australia and New Zealand. Main suggestions: A comprehensive multidisciplinary team meeting is suggested to establish a prompt and precise IPF diagnosis. Antifibrotic therapies should be considered to slow disease progression. However, enthusiasm should be tempered by the lack of evidence in many IPF subgroups, particularly the broader disease severity spectrum. Non-pharmacological interventions including pulmonary rehabilitation, supplemental oxygen, appropriate treatment of comorbidities and disease-related symptoms remain crucial to optimal management. Despite recent advances, IPF remains a fatal disease and suitable patients should be referred for lung transplantation assessment. [ABSTRACT FROM AUTHOR]

Abstract: We compared two bycatch reduction device (BRD) models that were designed to maintain the catch of commercially harvestable blue crabs Callinectes sapidus while excluding diamondback terrapins Malaclemys terrapin. The Virginia BRD (VA BRD) model was a thick‐plastic, 5.1‐ × 15.3‐cm, rectangular red frame. The South Carolina BRD (SC BRD) model was a thin‐plastic, 5.1–6.4‐ × 7.3‐cm, curved rectangular red frame. Baited crab traps were fished in groups of three (no BRD, VA BRD, and SC BRD) within tidal creeks in Virginia and South Carolina. In Virginia, legal‐sized blue crabs from traps with BRDs were 2 mm smaller than those from traps without BRDs. In South Carolina, significantly fewer and smaller crabs were captured in traps with SC BRDs relative to traps with VA BRDs or traps without BRDs. Shorter soak times in South Carolina may have reduced traffic flow of crabs into traps fitted with BRDs, an effect that was overcome by longer soak times in Virginia. Of the 29 diamondback terrapins captured during the Virginia study, 23 were captured in traps without BRDs, 3 were captured in traps with VA BRDs, and 3 were caught in traps with SC BRDs. The BRDs are needed for the blue crab fishery to decrease diamondback terrapin mortality in hot spots where crabbing and terrapin habitat overlap. [ABSTRACT FROM AUTHOR]

Objectives: To estimate cumulative live birth rates (CLBRs) following repeated assisted reproductive technology (ART) ovarian stimulation cycles, including all fresh and frozen/thaw embryo transfers (complete cycles).Design, Setting and Participants: Prospective follow-up of 56 652 women commencing ART in Australian and New Zealand during 2009-2012, and followed until 2014 or the first treatment-dependent live birth.Main Outcome Measures: CLBRs and cycle-specific live birth rates were calculated for up to eight cycles, stratified by the age of the women (< 30, 30-34, 35-39, 40-44, > 44 years). Conservative CLBRs assumed that women discontinuing treatment had no chance of achieving a live birth if had they continued treatment; optimal CLBRs assumed that they would have had the same chance as women who continued treatment.Results: The overall CLBR was 32.7% (95% CI, 32.2-33.1%) in the first cycle, rising by the eighth cycle to 54.3% (95% CI, 53.9-54.7%) (conservative) and 77.2% (95% CI, 76.5-77.9%) (optimal). The CLBR decreased with age and number of complete cycles. For women who commenced ART treatment before 30 years of age, the CLBR for the first complete cycle was 43.7% (95% CI, 42.6-44.7%), rising to 69.2% (95% CI, 68.2-70.1%) (conservative) and 92.8% (95% CI, 91.6-94.0) (optimal) for the seventh cycle. For women aged 40-44 years, the CLBR was 10.7% (95% CI, 10.1-11.3%) for the first complete cycle, rising to 21.0% (95% CI, 20.2-21.8%) (conservative) and 37.9% (95% CI, 35.9-39.9%) (optimal) for the eighth cycle.Conclusion: CLBRs based on complete cycles are meaningful estimates of ART success, reflecting contemporary clinical practice and encouraging safe practice. These estimates can be used when counselling patients and to inform public policy on ART treatment. [ABSTRACT FROM AUTHOR]

Objectives: To calculate cost savings to the Australian federal and state governments from the reduction in twin and triplet birth rates for infants conceived by assisted reproductive technology (ART) since 2002, and to determine the number of ART treatment programs theoretically funded by means of these savings.Design and Setting: Costing model using data from the Australia and New Zealand Assisted Reproduction Database, the National Perinatal Data Collection and Medicare Australia on ART treatment cycles undertaken in Australia between 2002 and 2008.Main Outcome Measures: Annual savings in maternal and infant inpatient birth-admission costs resulting from the reduction in ART multiple birth rate; theoretical number of ART treatment programs funded and infants born by means of these savings.Results: The reduction in the ART multiple birth rate from 18.8% in 2002 to 8.6% in 2008 resulted in estimated savings to government of $47.6 million in birth-admission costs alone. Theoretically, these savings funded 7042 ART treatment programs comprising one fresh plus one frozen embryo transfer cycle, equating to the birth of 2841 babies. Fifty-five per cent of the increased use of ART services since 2002 has been theoretically funded by the reduction in multiple birth infants.Conclusions: Against a backdrop of supportive public funding of ART in Australia, a voluntary shift to single embryo transfer by fertility clinicians and ART patients has resulted in substantial savings in hospital costs. Much of the growth in ART use has been theoretically cross-subsidised by the move to safer embryo transfer practices. [ABSTRACT FROM AUTHOR]

Wind disturbance can create large forest blowdowns, which greatly reduces live biomass and adds uncertainty to the strength of the Amazon carbon sink. Observational studies from within the central Amazon have quantified blowdown size and estimated total mortality but have not determined which trees are most likely to die from a catastrophic wind disturbance. Also, the impact of spatial dependence upon tree mortality from wind disturbance has seldom been quantified, which is important because wind disturbance often kills clusters of trees due to large treefalls killing surrounding neighbors. We examine (1) the causes of differential mortality between adult trees from a 300-ha blowdown event in the Peruvian region of the northwestern Amazon, (2) how accounting for spatial dependence affects mortality predictions, and (3) how incorporating both differential mortality and spatial dependence affect the landscape level estimation of necromass produced from the blowdown. Standard regression and spatial regression models were used to estimate how stem diameter, wood density, elevation, and a satellite-derived disturbance metric influenced the probability of tree death from the blowdown event. The model parameters regarding tree characteristics, topography, and spatial autocorrelation of the field data were then used to determine the consequences of non-random mortality for landscape production of necromass through a simulation model. Tree mortality was highly non-random within the blowdown, where tree mortality rates were highest for trees that were large, had low wood density, and were located at high elevation. Of the differential mortality models, the non-spatial models overpredicted necromass, whereas the spatial model slightly underpredicted necromass. When parameterized from the same field data, the spatial regression model with differential mortality estimated only 7.5% more dead trees across the entire blowdown than the random mortality model, yet it estimated 51% greater necromass. We suggest that predictions of forest carbon loss from wind disturbance are sensitive to not only the underlying spatial dependence of observations, but also the biological differences between individuals that promote differential levels of mortality. [ABSTRACT FROM AUTHOR]

This Month Use of alcohol (ethanol)-based hand rubs (ABHRs) during pregnancy Key words: alcohol, ethanol, hand rub, ABHR, hand sanitizer . Working when experiencing a shingles infection Key words: shingles, varicella, zoster, employee health . Cleaning rigid containers Key words: rigid container, container, instrument pan . [ABSTRACT FROM AUTHOR]

This Month Increasing ambient room temperature Key words: OR temperature, core temperature, unplanned hypothermia, ambient room temperature, thermoregulation. Clinical alarm management Key words: alarm fatigue, clinical alarms, alert alarms. [ABSTRACT FROM AUTHOR]

Background: Recently we demonstrated that local genomic ancestry (LA) drives the difference in AD risk between European (EU) and African (AF) carriers of APOEε4/4. As a follow‐up study using single‐nuclei RNAseq, we found that AD APOEε4 homozygotes with EU Local Ancestry (LA) had a significantly increased APOEε4 expression compared to AD APOEε4/4 homozygotes with AF LA. In two of the EU LA patients, an astrocyte cluster with the highest APOEε4 expression was observed and expressed a panel of genes consistent with A1 reactive astrocytes (A1RA). No such cluster was seen in the AF LA. As a previous study in mice suggested that APOEε4 expression was a contributor to the development of A1RA, we sought to explore the relationship of increased APOEε4 expression and A1RA using inducible pluripotent stem cells (iPSC)‐derived astrocytes. Method: APOEε4/4 astrocytes from one European and one African LA were derived from iPSC lines. The astrocytes were brought to maturity (Day 54 in‐vitro), and then each group was treated with either a cytokine cocktail (IL‐1a, hTNFa, C1q) or overexpressed with APOEε4 by lentiviral transduction for 14‐days (two replicates per line). mRNA was extracted and qPCR was performed to measure changes in APOEε4 and markers of A1RA (C3, GBP2, IFITM3). Result: iPSCs were validated by immunocytochemistry (ICC) and qPCR for Nanog, SOX2 and OCT4 and subsequently differentiated into astrocytes. Astrocyte validation was performed by GFAP and βS100 ICC. Astrocytes treated with the cytokine cocktail had a 100‐ and 600‐fold increase in C3 in EU and AF LA astrocytes respectively, as well as significant increase in GBP2 and IFITM3 compatible with A1RA. When overexpressing APOEε4, a significant increase in C3 was observed in the EU LA astrocytes, while no increase was observed in the AF LA astrocytes. Conclusion: Our preliminary results support the hypothesis that APOEe4 overexpression can increase the conversion of astrocytes to the toxic A1RA state in EU LA astrocytes. It is intriguing that this effect was not seen in the African LA astrocytes. By increasing the sample size, we will increase the significance of the association between APOEe4 overexpression and A1RA induction in EU LA astrocytes compared to their AF counterparts. [ABSTRACT FROM AUTHOR]

This month Using an automated washer or washer/disinfector that includes a lubrication cycle to process implants Key words: surgical implants, lubrication, critical water . Using items packaged in impervious packages if dropped Key words: impervious package, dropped items, event-related sterility . Using a normal saline solution rather than sterile water to wipe instruments and flush lumens during surgical procedures Key words: normal saline solution, sterile water, lumens, gross soil . Wicking versus blotting excess skin antiseptics in a gel form Key words: wicking, blotting, skin antiseptics. Silver-based dressings and risk of patient injury if left in place during a surgical procedure Key words: silver-based dressings, surgical procedures, patient injuries . [ABSTRACT FROM AUTHOR]

Introduction Cerebrospinal fluid (CSF) amyloid-β 1–42 (Aβ 42 ) is an important biomarker for Alzheimer's disease, both in diagnostics and to monitor disease-modifying therapies. However, there is a great need for standardization of methods used for quantification. To overcome problems associated with immunoassays, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a critical orthogonal alternative. Methods We compared results for CSF Aβ 42 quantification in a round robin study performed in four laboratories using similar sample preparation methods and LC-MS instrumentation. Results The LC-MS results showed excellent correlation between laboratories ( r 2 >0.98), high analytical precision, and good correlation with enzyme-linked immunosorbent assay ( r 2 >0.85). The use of a common reference sample further decreased interlaboratory variation. Discussion Our results indicate that LC-MS is suitable for absolute quantification of Aβ 42 in CSF and highlight the importance of developing a certified reference material. [ABSTRACT FROM AUTHOR]

Yeast starter cultures for winemaking have traditionally been developed from successful fermentation isolates. Over the past 10-20 years there has been a move to harness genetic techniques to improve production strains. The approaches to achieve this have been similar to those applied in the agricultural sector for crop and livestock development. Thus, domestication of wine yeasts now involves hybridisation, mutagenesis, selection and screening. There is also a growing interest in tapping into isolates of non-Saccharomyces yeasts to develop novel starter cultures that bring complexity and potentially enhance regionality of wines. This review will cover these developments and will look to the future opportunities arising from the application of genetic engineering and synthetic biology approaches for the introduction of novel phenotypes that are outside of the reach of traditional methods. [ABSTRACT FROM AUTHOR]

This Month Complementary care interventions for pediatric patients Key words: pediatric, complementary care, music, hypnosis, acupressure, play therapy, pain, anxiety. Cleaning personal eyewear Key words: personal eyewear, eye protection, cleaning, bloodborne pathogen exposure. Education requirements for advanced practice RN (APRN) first assistants Key words: advanced practice registered nurse, APRN, registered nurse first assistant, RNFA. Degree requirements for entrance to an RN first assistant (RNFA) program Key words: registered nurse first assistant, RNFA, first assistant. Wearing an arm cast in the perioperative setting Key words: arm cast, workplace safety, work restrictions, hand hygiene. [ABSTRACT FROM AUTHOR]

Extending the time before harvest-and therefore increasing grape maturity-enhances ripe fruit wine flavours and wine colour intensity, and also decreases unripe green and vegetal wine flavours. Greater maturity, however, increases sugar concentration, which in turn leads to wines with elevated ethanol concentration. High ethanol concentration can reduce the complexity of a wine by suppressing aroma intensity, while also increasing the perception of 'hotness' and 'bitterness'. In addition, health and economic considerations combined with market demand have the wine industry actively seeking ways to facilitate the production of wines with lower alcohol concentration. This review summarises the latest research aimed at reducing wine alcohol concentration, including viticultural practices, pre-fermentation and winemaking practices, microbiological strategies, and post-fermentation approaches and processing technologies. The effect of these practices on wine flavour is also discussed. [ABSTRACT FROM AUTHOR]

Deacidification of wines by malolactic fermentation (MLF) is an essential step in the production of most red, many white and some sparkling base wines. While this secondary fermentation can occur spontaneously, the majority of winemakers, particularly in new world winemaking regions, prefer to minimise the risk of a failed or sluggish MLF by inoculating with a reliable, commercially available starter culture. This review focuses on the scientific literature underpinning growing trends in the application of MLF starters. It considers the literature on co-inoculation regimes, where MLF bacteria are inoculated into a ferment prior to completion of alcoholic fermentation and what benefits this might bring relative to sequential inoculation, when bacteria are added after completion of primary fermentation. It also considers the benefits of the growing trend of using bacteria other than the traditional Oenococcus oeni for induction of MLF, and of developing starter cultures from regional isolates of MLF bacteria to enhance regional identity of wines. [ABSTRACT FROM AUTHOR]

The goal of this article is to describe the broad curricular constructs surrounding teaching and learning about social media in dental education. This analysis takes into account timing, development, and assessment of the knowledge, skills, attitudes, and behaviors needed to effectively use social media tools as a contemporary dentist. Three developmental stages in a student's path to becoming a competent professional are described: from undergraduate to dental student, from the classroom and preclinical simulation laboratory to the clinical setting, and from dental student to licensed practitioner. Considerations for developing the dental curriculum and suggestions for effective instruction at each stage are offered. In all three stages in the future dentist's evolution, faculty members need to educate students about appropriate professional uses of social media. Faculty members should provide instruction on the beneficial aspects of this communication medium and help students recognize the potential pitfalls associated with its use. The authors provide guidelines for customizing instruction to complement each stage of development, recognizing that careful timing is not only important for optimal learning but can prevent inappropriate use of social media as students are introduced to novel situations. [ABSTRACT FROM AUTHOR]

Social media consist of powerful tools that impact not only communication but relationships among people, thus posing an inherent challenge to the traditional standards of who we are as dental educators and what we can expect of each other. This article examines how the world of social media has changed dental education. Its goal is to outline the complex issues that social media use presents for academic dental institutions and to examine these issues from personal, professional, and legal perspectives. After providing an update on social media, the article considers the advantages and risks associated with the use of social media at the interpersonal, professional, and institutional levels. Policies and legal issues of which academic dental institutions need to be aware from a compliance perspective are examined, along with considerations and resources needed to develop effective social media policies. The challenge facing dental educators is how to capitalize on the benefits that social media offer, while minimizing risks and complying with the various forms of legal constraint. [ABSTRACT FROM AUTHOR]

Asset management and accrual accounting are staple best practices for private business capital planning. Surprising to some, it wasn't always that way for public tangible assets like water infrastructure. Water infrastructure assets require specialized performance and reporting of asset conditions to address critical needs. [ABSTRACT FROM AUTHOR]

Despite articles advising health care professionals about how to read the literature and surveys of time spent reading, there have been no studies of what dentists or dental educators actually recall from the formal and informal literature. The aim of this study was to begin to develop data on this subject with convenience samples of 62 clinical faculty members at one U.S. dental school and a group of 33 dental editors. Members of the two groups were surveyed about their interest in and familiarity with a sample of items from the Journal of the American Dental Association and the ADA News, including research articles, editorials, advertisements, and announcements about programs and people. The participants also completed a multiple-choice test about the essential feature of each item, a measure that reflected the degree of retention of content from reading prior to the study. The results showed that both groups had the greatest interest in content that presented scientific findings or responsible opinion. By contrast, they rated the advertisements and announcements as uninteresting and did not recall their content well. Based on the findings that reading an item produced better recall if the item was of interest, a hierarchical model for learning from the literature is hypothesized, one that is supported by the social psychology literature. [ABSTRACT FROM AUTHOR]

Tumor cells have unstable genomes relative to non-tumor cells. Decreased DNA integrity resulting from tumor cell instability is important in generating favorable therapeutic indices, and intact DNA repair mediates resistance to therapy. Targeting DNA repair to promote the action of anti-cancer agents is therefore an attractive therapeutic strategy. BRCA2 is involved in homologous recombination repair. BRCA2 defects increase cancer risk but, paradoxically, cancer patients with BRCA2 mutations have better survival rates. We queried TCGA data and found that BRCA2 alterations led to increased survival in patients with ovarian and endometrial cancer. We developed a BRCA2-targeting second-generation antisense oligonucleotide (ASO), which sensitized human lung, ovarian, and breast cancer cells to cisplatin by as much as 60%. BRCA2 ASO treatment overcame acquired cisplatin resistance in head and neck cancer cells, but induced minimal cisplatin sensitivity in non-tumor cells. BRCA2 ASO plus cisplatin reduced respiration as an early event preceding cell death, concurrent with increased glucose uptake without a difference in glycolysis. BRCA2 ASO and cisplatin decreased metastatic frequency in vivo by 77%. These results implicate BRCA2 as a regulator of metastatic frequency and cellular metabolic response following cisplatin treatment. BRCA2 ASO, in combination with cisplatin, is a potential therapeutic anti-cancer agent. [ABSTRACT FROM AUTHOR]

Background Spatiotemporal (ST) mapping has mainly been applied to ex vivo preparations of the gut. We report the results of ST mapping of the spontaneous and remifentanil-induced motility of circular and longitudinal muscles of the distal ileum in the postprandial anaesthetized pig. Methods Spatiotemporal maps of strain rate were derived from image sequences of an exteriorized loop of ileum on a superfusion tray at laparotomy. Parameters were obtained by direct measurement from these maps, and by auto- and cross-correlation of map segments. Key Results Localized domains of standing longitudinal and circular activity that alternated between neighboring domains occurred spontaneously and both were promptly extinguished following intraluminal dosage with lidocaine. Longitudinal or circular contractions within a domain typically occurred at times that would coincide with every second or third cycle of the slow wave but propagated within the domain at a rate consistent with that reported within spike patches. Shortly after intravenous administration of remifentanil, longitudinal and circular contractions at the reported slow wave frequency propagated over longer distances at a high speed before slowing to a rate similar to that reported for slow waves. Conclusions & Inferences ST mapping based on cross-correlation is a robust tool for the analysis of intestinal movement and minimizing movement artefacts. We propose that the ST pattern of standing longitudinal and circular contractions arises from variation in the refractory period of smooth muscle, and hence, in its response to successive slow waves with neural stimuli influencing the former and having a mainly permissive role. [ABSTRACT FROM AUTHOR]

ABSTRACT Geographic information system (GIS) based distance weighted models were applied to determine critical areas of agricultural influence in nine agriculturally dominated, prairie subcatchments in southern Manitoba, Canada. Models were generated using a range of coefficients to represent nutrient overland and in-stream attenuation between agricultural source areas and stream sampling stations. Coefficients were also used to represent increased attenuation during overland travel through areas with natural vegetation. Water samples collected at intervals throughout the open water season were used to establish associations between areas of influence and in-stream total nitrogen and phosphorus concentrations in each season and under different flow conditions. Critical areas of influence varied seasonally with areas of influence expanding with individual rainfall events. Inclusion of natural vegetated areas on the landscape resulted in substantial increases in model power for only one scenario. Agriculture in areas within approximately 100 m of the stream channel appears to be the most critical driver of in-stream nutrient conditions during most seasons and under most flow conditions. Best management practices, such as vegetated buffer strips, should be most effective in controlling nutrient losses to southern Manitoba streams when situated within stream corridor, as opposed to upland areas, which appear to have minimal impact on in-stream conditions. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Recent work suggests that mixing in the small intestine takes place in central luminal and peripheral compartments. However, while movements of villi have been described, the mechanisms by which peripheral mixing are engendered remain unclear. Methods We examined the disposition and movement of mucosa and associated villi during contractions of the everted terminal ileum of the brushtail possum. We then simulated the effect of these movements on peripheral mixing. Key Results Compression of the intestinal mucosa by phasic longitudinal or radial contractions created short-lived microfolds, which were of similar scale to the attached villi. The packing density of the villous tips increased in the concavities and decreased on the crests of these microfolds. Simulations showed that these caused liquid digesta to be expelled from, or drawn into, intervillous spaces, significantly augmenting peripheral, but not bulk, luminal mixing. Conclusions & Inferences We describe a mechanism by which peripheral mixing may be engendered by mucosal microfolds without requiring the coordinated contraction of individual villi or groups of villi. [ABSTRACT FROM AUTHOR]

1. Stream metabolism is increasingly used for monitoring and assessment of the biological condition of aquatic ecosystems. However, distal environmental drivers, such as land use, are typically not well connected to the proximate controls, such as stream chemistry, that are usually invoked as driving metabolism. This is particularly true for North American prairie streams and for grassland streams worldwide. 2. Stream metabolism was measured at the outflow of 19 subcatchments of the Red River in southern Manitoba, Canada. Subcatchments represented gradients of nutrient-producing human activities present in the region, that is, wastewater treatment (WWT), livestock production and crop cultivation. Stream metabolism was estimated at all sites using diel changes in dissolved oxygen (DO) concentration over 1 week in the middle of summer. Environmental parameters hypothesised to control stream metabolism were sampled across three spatial scales (stream reach, stream segment and catchment). Model selection using Akaike's information criterion (AIC) was used to determine linkages between environmental parameters and measures of stream metabolism. 3. Estimated rates of metabolism were within the range of past studies of metabolism in prairie streams, although most streams had negative values of net ecosystem metabolism. However, production-to-respiration ratios were >0.5, at all but three sites suggesting that autochthonous production was an important source of organic matter. 4. The a priori model that best predicted gross primary production (GPP) was the intensity of nutrient-producing human activities (i.e. WWT, livestock and crop cultivation) measured at the catchment scale. Ecosystem respiration (ER) was best predicted by the a priori model comprised of GPP, total nitrogen (TN) and total phosphorus (TP). However, model averaging revealed that prediction of ER could be improved by including riparian cover and removing TP from the model. The positive association between GPP and ER suggested that heterotrophic compartments of the ecosystem were modest contributors to variation in respiration rates. 5. Overall, this study suggests that variation of metabolism in prairie streams of southern Manitoba is controlled by human activities occurring at the catchment scale, a finding consistent with current hierarchically structured riverine paradigms. Moreover, increased understanding of the hierarchical structure of stream metabolism drivers will help to ensure that assessment results can be used more effectively to inform management strategies for prairie ecosystems. [ABSTRACT FROM AUTHOR]