Patient experiences during the planned perioperative care pathway: An integrative review.

AIMS: This integrative review aimed to synthesize evidence about the patients' experiences during the planned perioperative care pathway. DESIGN: Integrative review. DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline Ovid, Scopus, and American Psychological Association (APA) PsychINFO. Original, peer-reviewed studies published in English between 2012 and 2023 exploring patient experiences during the planned perioperative care pathway were reviewed. METHODS: This review was guided by the Whittemore and Knafl method and followed PRISMA guidelines to search the literature. Twenty-two articles were selected for the final study. RESULTS: Three themes emerged: Sharing of information is empowering; interpersonal relationships are valued by patients, and hospital systems and care co-ordination influence the patient experience. CONCLUSIONS: The quality and consistency of the information patients receive can both support and undermine patient confidence in health professionals. The quality of relationships that participants experience and effective communication with health professionals can support or compromise the quality of the patients' perioperative experience. The nature of the hospital systems and care co-ordination in hospital has implications for the quality of recovery from surgery. IMPACT: This review evaluates whether national and international health services and organizations, adhering to the WHO guidelines, have developed and implemented intentionally focused perioperative care with the aims to achieving effective and sustainable surgical outcomes through increased patient satisfaction. NO PATIENT OR PUBLIC CONTRIBUTION: This article is an integrative review and does not include patient or public contribution.

Establishing a pediatric interventional radiology inpatient consult service.

OBJECTIVE: To delineate pediatric interventional radiology (IR) inpatient consult growth and resulting collections after implementation of a pediatric IR consult service. METHODS: An inpatient IR consult process was created at a single academic children's hospital in October 2019. IR consult note templates were created in Epic (Epic Systems Corporation, Verona, Wisconsin) and utilized by 4 IR physicians. Automatic charge generation was linked to differing levels of evaluation and management (E&M) service relating to current procedural terminology (CPT) inpatient consult codes 99251-99255. The children's hospital informatics division identified IR consult notes entered from the implementation of the consult service: October 2019 to January 2022. The university radiology department billing office provided IR service E&M charge, payment, and relative value units (RVU) information during this study period. A chart review was performed to determine the IR procedure conversion rate. Mann-Whitney and a two-sample t-test statistical analyses compared use of the 25-modifier, monthly consult growth and monthly payment growth. P-value < 0.05 was considered statistically significant.  RESULTS: Within this 27-month period, a total of 2153 inpatient IR consults were performed during 1757 Epic hospital encounters; monthly consult peak was reached 5 months into the study period. Consult level breakdown by CPT codes: 99251-8.7%, 99252-81.7%, and 99253-8.8%. 69.7% of IR consults had consult-specific billing with payments in 96.4% resulting in $143,976 new revenue. From 2020 to 2021, IR consult volume trended upward by 13.4% (P =0.069), and consult-specific payments increased by 84.1% (P<0.001). IR consult procedure conversion rate was 96.5%. CONCLUSION: An inpatient pediatric IR consult service was quickly established and maintained by four physicians over a 27-month study period. Annual IR consult volume trended upward and consult-specific payments increased, resulting in previously uncaptured IR service revenue.

Efficacy of standardizing fibrinolytic therapy for parapneumonic effusion.

BACKGROUND: While chest tube placement with pleural fibrinolytic medication is the established treatment of pediatric empyema, treatment failure is reported in up to 20% of these children. OBJECTIVE: Standardizing fibrinolytic administration among interventional radiology (IR) physicians to improve patient outcomes in pediatric parapneumonic effusion. MATERIALS AND METHODS: We introduced a hospital-wide clinical pathway for parapneumonic effusion (1-2 mg tissue plasminogen activator [tPA] twice daily based on pleural US grade); we then collected prospective data for IR treatment May 2017 through February 2020. These data included demographics, co-morbidities, pediatric intensive care unit (PICU) admission, pleural US grade, culture results, daily tPA dose average, twice-daily dose days, skipped dose days, pleural therapy days, need for chest CT/a second IR procedure/surgical drainage, and length of stay. We compared the prospective data to historical controls with IR treatment from January 2013 to April 2017. RESULTS: Sixty-three children and young adults were treated after clinical pathway implementation. IR referrals increased (P = 0.02) and included higher co-morbidities (P = 0.005) and more PICU patients (P = 0.05). Mean doses per day increased from 1.5 to 1.9 (P < 0.001), twice-daily dose days increased from 38% to 79% (P < 0.001) and median pleural therapy days decreased from 3.5 days to 2.5 days (P = 0.001). No IR patients needed surgical intervention. No statistical differences were observed for gender/age/weight, US grade, need for a second IR procedure or length of stay. US grade correlated with greater positive cultures, need for chest CT/second IR procedure, and pleural therapy days. CONCLUSION: Interventional radiology physician standardization improved on a clinical pathway for fibrinolysis of parapneumonic effusion. Despite higher patient complexity, pleural therapy duration decreased. There were no chest tube failures needing surgical drainage.

Analyzing coagulation dynamics during treatment of vascular malformations with thromboelastography.

BACKGROUND/OBJECTIVES: Slow-flow vascular malformations are abnormal vessels that can lead to activation and consumption of coagulation factors and thrombosis, known as localized intravascular coagulopathy (LIC). Most clinical and research evidence of vascular malformation hemostasis relies on conventional coagulation studies, which may not provide a complete picture. Thromboelastograpy (TEG) is a tool that can provide real-time assessment of a patient's coagulation dynamics, and may allow for a more individualized treatment approach. We hypothesized that patients with slow-flow vascular malformations will have changes in TEG parameters peri-procedure that will help predict blood product or medication administration. DESIGN/METHODS: Institutional Review Board approved prospective study of patients with slow-flow vascular malformations undergoing a sedated, minor procedure. TEG and conventional coagulation studies were obtained preprocedure, 15 min, and when possible, at 30 min after the start of the procedure. RESULTS: Twenty-five patients were enrolled. Median age was 15 years (range 3-47 years). Procedures included laser and/or sclerotherapy. There were no changes in TEG parameters from baseline to 15 min or 30 min. The following decreased from baseline to 15 min: fibrinogen 313 to 287 mg/dL (P = .001), D-dimer 1.3 to 1.1 mg/L (P = .02), hemoglobin 12.8 to 11.8 g/dL (P = .001), and platelet count 272 000 to 256 000 (P = .006). No patient had a bleeding/thrombotic complication during or within 1 week postprocedure. CONCLUSION: We saw no change in TEG parameters or bleeding or clotting complications despite significant numerical changes in conventional coagulation profiles, suggesting that conventional studies may not be as useful in determining risks of bleeding or thrombotic complications peri-procedure for minor procedures.

Processes of consent in research for adults with impaired mental capacity nearing the end of life: systematic review and transparent expert consultation (MORECare_Capacity statement).

BACKGROUND: Involving adults lacking capacity (ALC) in research on end of life care (EoLC) or serious illness is important, but often omitted. We aimed to develop evidence-based guidance on how best to include individuals with impaired capacity nearing the end of life in research, by identifying the challenges and solutions for processes of consent across the capacity spectrum. METHODS: Methods Of Researching End of Life Care_Capacity (MORECare_C) furthers the MORECare statement on research evaluating EoLC. We used simultaneous methods of systematic review and transparent expert consultation (TEC). The systematic review involved four electronic databases searches. The eligibility criteria identified studies involving adults with serious illness and impaired capacity, and methods for recruitment in research, implementing the research methods, and exploring public attitudes. The TEC involved stakeholder consultation to discuss and generate recommendations, and a Delphi survey and an expert 'think-tank' to explore consensus. We narratively synthesised the literature mapping processes of consent with recruitment outcomes, solutions, and challenges. We explored recommendation consensus using descriptive statistics. Synthesis of all the findings informed the guidance statement. RESULTS: Of the 5539 articles identified, 91 met eligibility. The studies encompassed people with dementia (27%) and in palliative care (18%). Seventy-five percent used observational designs. Studies on research methods (37 studies) focused on processes of proxy decision-making, advance consent, and deferred consent. Studies implementing research methods (30 studies) demonstrated the role of family members as both proxy decision-makers and supporting decision-making for the person with impaired capacity. The TEC involved 43 participants who generated 29 recommendations, with consensus that indicated. Key areas were the timeliness of the consent process and maximising an individual's decisional capacity. The think-tank (n = 19) refined equivocal recommendations including supporting proxy decision-makers, training practitioners, and incorporating legislative frameworks. CONCLUSIONS: The MORECare_C statement details 20 solutions to recruit ALC nearing the EoL in research. The statement provides much needed guidance to enrol individuals with serious illness in research. Key is involving family members early and designing study procedures to accommodate variable and changeable levels of capacity. The statement demonstrates the ethical imperative and processes of recruiting adults across the capacity spectrum in varying populations and settings.

Characterizing Elevated Urban Air Pollutant Spatial Patterns with Mobile Monitoring in Houston, Texas.

Diverse urban air pollution sources contribute to spatially variable atmospheric concentrations, with important public health implications. Mobile monitoring shows promise for understanding spatial pollutant patterns, yet it is unclear whether uncertainties associated with temporally sparse sampling and instrument performance limit our ability to identify locations of elevated pollution. To address this question, we analyze 9 months of repeated weekday daytime on-road mobile measurements of black carbon (BC), particle number (PN), and nitrogen oxide (NO, NO2) concentrations within 24 census tracts across Houston, Texas. We quantify persistently elevated, intermittent, and extreme concentration behaviors at 50 m road segments on surface streets and 90 m segments on highways relative to median statistics across the entire sampling domain. We find elevated concentrations above uncertainty levels (±40%) within portions of every census tract, with median concentration increases ranging from 2 to 3× for NO2, and >9× for NO. In contrast, PN exhibits elevated concentrations of 1.5-2× the domain-wide median and distinct spatial patterns relative to other pollutants. Co-located elevated concentrations of primary combustion tracers (BC and NOx) near 30% of metal recycling and concrete batch plant facilities within our sampled census tracts are comparable to those measured within 200 m of highways. Our results demonstrate how extensive mobile monitoring across multiple census tracts can quantitatively characterize urban air pollution source patterns and are applicable to developing effective source mitigation policies.

Survival of Japanese beetle, Popillia japonica Newman, larvae in field plots when infected with a microsporidian pathogen, Ovavesicula popilliae.

Japanese beetle, Popillia japonica Newman, is an important invasive pest that causes significant damage to golf courses, blueberries, raspberries, hops and many other crops and ornamentals in the eastern United States. This study was conducted to determine the survival of Ovavesicula popilliae-infected larvae compared with uninfected larvae from October to May. Larvae were collected from two sites, one where O. popilliae was active and one where it had not yet been detected. Larvae were placed into plastic sleeve-pots containing 15 cm-diameter cores of turfgrass with roots and soil intact. Larvae collected from both locations were put into sleeve-pots at both locations to account for soil and site factors. Results of this experiment in both years confirm that Japanese beetle larvae infected with O. popilliae do not survive well from October to May. We estimate that at an epizootic location where the pathogen has been active for several years, at least 76.5% of the Japanese beetle larvae infected in October do not survive until May. When the observed amount of population reduction (27-29%) due to natural pathogen infection of larvae in our field plots is combined with a 50% reduction in eggs produced by infected females as previously reported, annual population declines due to O. popilliae would average 40% (assuming a typical adult female infection rate of 25%). This rate of population reduction is consistent with previous reports of Japanese beetle population decline over a period of several years at O. popilliae epizootic sites.

Geographic distribution of Ovavesicula popilliae in the United States and sensitivity of visual diagnosis compared with qPCR detection.

The Japanese beetle (Popillia japonica) is one of the most destructive invasive pests in North America, causing significant economic impact to many fruit crops, turfgrass and the nursery industry. A microsporidian pathogen of Japanese beetle, Ovavesicula popilliae, discovered in 1985, proliferates in the Malpighian tubules of larvae and adults, disrupting waste-removal, mineral filtering, and fluid balance in heavily infected individuals. Most infected larvae do not survive from fall to spring, and egg production by infected females is reduced by 50%. Ovavesicula popilliae is promising as a classical biological control agent for Japanese beetle, but outside of surveys completed in Connecticut and Michigan little is known about its geographic distribution in North America. The objective of this research is to obtain a better understanding of the distribution of O. popilliae in North America. Japanese beetles were collected at 59 locations in a total of 19 different states in the USA for pathogen analysis. Overall, the proportion of Japanese beetle adults infected by O. popilliae was much greater in Michigan, Ohio, Tennessee and four states in the northeastern USA compared with sites located west of the Mississippi River (18.6 ± 13.3% and 0.6 ± 1.2%, respectively). Nucleotide sequences of the gene encoding a small subunit of nuclear ribosomal RNA (ssrDNA), obtained from GenBank for O. popilliae was used to develop a highly specific qPCR test for O. popilliae DNA. A subsample of 110 individual Japanese beetles were visually diagnosed first, then analyzed via qPCR. Visual diagnosis and qPCR detection agreed for 80.9% of the beetles tested. The qPCR assay is more sensitive than visual diagnosis (56 visually positive, 73 qPCR positive), is highly specific for O. popilliae, and will be useful for detecting the pathogen in large batches of beetles, or in beetle frass.

Phonation threshold pressure using a 3-mass model of phonation with empirical pressure values.

Understanding the control parameters that influence phonation threshold pressure can have important implications for ease of phonation. Using a computer model of phonation can aid in studying parameters not easily controllable through human experimental work and may provide a means of explaining variations seen across human participants. A vertical 3-mass computer model of phonation with empirical driving pressures was used to obtain phonation threshold pressures for a variety of prephonatory conditions that may be realistically produced by humans. The resulting phonation threshold pressures are reasonable compared to results from human studies and may extend beyond the range of phonatory control parameters studied in human experiments. In addition, the present work adds a formula for calculating phonation threshold pressure based on the prephonatory glottal angle, the tension of the vocal folds, and the prephonatory diameter. Of special interest is that, as the prephonatory angle of convergence increases from 0 degrees (the rectangular glottis condition), the phonation threshold pressure increases in a nearly linear fashion.

Staphylococcus debuckii sp. nov., a coagulase-negative species from bovine milk.

A novel type strain, designated SDB 2975T (=CECT 9737T=DSM 105892T), of the novel species Staphylococcus debuckii sp. nov. isolated from bovine milk is described. The novel species belongs to the genus Staphylococcus and showed resistance to tetracycline and was oxidase- and coagulase-negative, catalase-positive, and Gram-stain-positive. Phylogenetic relationships of Staphylococcus debuckii SDB 2975T to other staphylococcal species were inferred from 16S rRNA gene and whole-genome-based phylogenetic reconstruction. The 16S rRNA gene comparisons showed that the strain is closely related to Staphylococcus condimenti (99.73 %), Staphylococcus piscifermentans (99.66 %), Staphylococcus carnosus (99.59 %) and Staphylococcus simulans (98.03 %). Average nucleotide identity (ANI) values between S.taphylococcus debuckii SDB 2975T and its closely related Staphylococcus species were 83.96, 94.5, 84.03 and 78.09 %, respectively, and digital DNA-DNA hybridization (dDDH) values were 27.70, 58.02, 27.70 and 22.00 %, respectively. The genome of Staphylococcus debuckii SDB 2975T was sequenced with PacBio and Illumina technologies and is 2 691 850 bp long, has a G+C content of 36.6 mol% and contains 2678 genes and 80 RNAs, including six copies of each5S rRNA, 16S rRNA and 23S rRNA genes. Biochemical profiling and a newly developed PCR assay enabled differentiation of Staphylococcus debuckii SDB 2975T and three other SDB strains from its closest staphylococcal species. Differentiation was also achieved by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). Genes unique to Staphylococcus debuckii were identified and a PCR-based assay was developed to differentiate Staphylococcus debuckii from other staphylococcal species. In conclusion, the results of phylogenetic analysis along with the ANI values <95 %, and dDDH values <70 % from closely related species along with the phenotypic and biochemical characteristics and specific MALDI-TOF profiles demonstrated that Staphylococcus debuckii SDB 2975T represents a novel species within the genus Staphylococcus, named Staphylococcus debuckii sp. nov. (SDB 2975T=CECT 9737T=DSM 105892T).

Transparency in the eye region of an ostracod carapace ( Macrocypridina castanea, Myodocopida).

Many myodocopid ostracods are unusual in that they have well-developed compound eyes yet must view their environment through a shell. The cypridinid Macrocypridina castanea is relatively large among ostracods (about 5-10 mm) and is a pelagic predator. This species possess highly pigmented shells with a transparent region lying just above the eye. Here we examine the ultrastructure and transparency of this window using electron microscopy, serial-block face scanning electron microscopy and X-ray diffraction analysis and optical modelling. An internal, laminar stack was identified within the window region of the shell that formed a more regular half-wave reflector than in non-window regions, and where the distance between molecules in the chitin-protein fibrils decreases as compared to the non-window area. This results in excellent transmission properties-at around 99% transmission-for wavelengths between 350 and 630 nm due to its half-wave reflector organization. Therefore, blue light, common in the mid and deep sea, where this species inhabits, would be near-optimally transmitted as a consequence of the sub-micrometre structuring of the shell, thus optimizing the ostracod's vision. Further, pore canals were identified in the shell that may secrete substances to prevent microbial growth, and subsequently maintain transparency, on the shell surface. This article is part of the theme issue 'Bioinspired materials and surfaces for green science and technology'.

Polymerase chain reaction blood tests for the diagnosis of invasive aspergillosis in immunocompromised people.

BACKGROUND: This is an update of the original review published in the Cochrane Database of Systematic Reviews Issue 10, 2015.Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mould infection in immunocompromised people. Early diagnosis of IA and prompt administration of appropriate antifungal treatment are critical to the survival of people with IA. Antifungal drugs can be given as prophylaxis or empirical therapy, instigated on the basis of a diagnostic strategy (the pre-emptive approach) or for treating established disease. Consequently, there is an urgent need for research into both new diagnostic tools and drug treatment strategies. Increasingly, newer methods such as polymerase chain reaction (PCR) to detect fungal nucleic acids are being investigated. OBJECTIVES: To provide an overall summary of the diagnostic accuracy of PCR-based tests on blood specimens for the diagnosis of IA in immunocompromised people. SEARCH METHODS: We searched MEDLINE (1946 to June 2015) and Embase (1980 to June 2015). We also searched LILACS, DARE, Health Technology Assessment, Web of Science and Scopus to June 2015. We checked the reference lists of all the studies identified by the above methods and contacted relevant authors and researchers in the field. For this review update we updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3) in the Cochrane Library; MEDLINE via Ovid (June 2015 to March week 2 2018); and Embase via Ovid (June 2015 to 2018 week 12). SELECTION CRITERIA: We included studies that: i) compared the results of blood PCR tests with the reference standard published by the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG); ii) reported data on false-positive, true-positive, false-negative and true-negative results of the diagnostic tests under investigation separately; and iii) evaluated the test(s) prospectively in cohorts of people from a relevant clinical population, defined as a group of individuals at high risk for invasive aspergillosis. Case-control and retrospective studies were excluded from the analysis. DATA COLLECTION AND ANALYSIS: Authors independently assessed quality and extracted data. For PCR assays, we evaluated the requirement for either one or two consecutive samples to be positive for diagnostic accuracy. We investigated heterogeneity by subgroup analyses. We plotted estimates of sensitivity and specificity from each study in receiver operating characteristics (ROC) space and constructed forest plots for visual examination of variation in test accuracy. We performed meta-analyses using the bivariate model to produce summary estimates of sensitivity and specificity. MAIN RESULTS: We included 29 primary studies (18 from the original review and 11 from this update), corresponding to 34 data sets, published between 2000 and 2018 in the meta-analyses, with a mean prevalence of proven or probable IA of 16.3 (median prevalence 11.1% , range 2.5% to 57.1%). Most patients had received chemotherapy for haematological malignancy or had undergone hematopoietic stem cell transplantation. Several PCR techniques were used among the included studies. The sensitivity and specificity of PCR for the diagnosis of IA varied according to the interpretative criteria used to define a test as positive. The summary estimates of sensitivity and specificity were 79.2% (95% confidence interval (CI) 71.0 to 85.5) and 79.6% (95% CI 69.9 to 86.6) for a single positive test result, and 59.6% (95% CI 40.7 to 76.0) and 95.1% (95% CI 87.0 to 98.2) for two consecutive positive test results. AUTHORS' CONCLUSIONS: PCR shows moderate diagnostic accuracy when used as screening tests for IA in high-risk patient groups. Importantly the sensitivity of the test confers a high negative predictive value (NPV) such that a negative test allows the diagnosis to be excluded. Consecutive positives show good specificity in diagnosis of IA and could be used to trigger radiological and other investigations or for pre-emptive therapy in the absence of specific radiological signs when the clinical suspicion of infection is high. When a single PCR positive test is used as the diagnostic criterion for IA in a population of 100 people with a disease prevalence of 16.3% (overall mean prevalence), three people with IA would be missed (sensitivity 79.2%, 20.8% false negatives), and 17 people would be unnecessarily treated or referred for further tests (specificity of 79.6%, 21.4% false positives). If we use the two positive test requirement in a population with the same disease prevalence, it would mean that nine IA people would be missed (sensitivity 59.6%, 40.4% false negatives) and four people would be unnecessarily treated or referred for further tests (specificity of 95.1%, 4.9% false positives). Like galactomannan, PCR has good NPV for excluding disease, but the low prevalence of disease limits the ability to rule in a diagnosis. As these biomarkers detect different markers of disease, combining them is likely to prove more useful.

Recent measurements with a synthetic two-layer model of the vocal folds and extension of Titze's surface wave model to a body-cover model.

The experiments of Mendelsohn and Zhang in 2011 (J. Acoust. Soc. Am. 130, 2961-2968) with six synthetic, two-layer models of the vocal folds were undertaken to better understand the role that the body layer plays in determining the properties of phonation. This rich data set provides an opportunity to extend Titze's surface wave model to a body-cover model. Much of Mendelsohn and Zhang's data can be interpreted with this model by assuming that the ratio of the spring constants of the two oscillators is that of the ratio of the Young's moduli for the two layers, and that the ratio of the masses of the oscillators is proportional to the ratio of the depths of the two layers.

MEF2 transcription factors in human placenta and involvement in cytotrophoblast invasion and differentiation.

Development of the human placenta and its trophoblast cell types is critical for a successful pregnancy. Defects in trophoblast invasion and differentiation are associated with adverse pregnancy outcomes, including preeclampsia. The members of myocyte enhancer factor-2 (MEF2) family of transcription factors are key regulators of cellular proliferation, differentiation, and invasion in various cell types and tissues and might play a similarly important role in regulating trophoblast proliferation, invasion, and differentiation during human placental development. In the present study, using human cytotrophoblast cell lines (HTR8/SVneo and BeWo) and primary human cytotrophoblasts (CTBs), we show that members of the MEF2 family are differentially expressed in human placental CTBs, with MEF2B and MEF2D being highly expressed in first trimester extravillous CTBs. Overexpression of MEF2D results in cytotrophoblast proliferation and enhances the invasion and migration of extravillous-like HTR8/SVneo cells. This invasive property is blocked by overexpression of a dominant negative MEF2 (dnMEF2). In contrast, MEF2A is the principal MEF2 isoform expressed in term CTBs, MEF2C and MEF2D being expressed more weakly, and MEF2B expression being undetected. Overexpression of MEF2A induces cytotrophoblast differentiation and syncytium formation in BeWo cells. During in vitro differentiation of primary CTBs, MEF2A expression is associated with CTB differentiation into syncytiotrophoblast. Additionally, the course of p38 MAPK and ERK5 activities parallels the increase in MEF2A expression. These findings suggest individual members of MEF2 family distinctively regulate cytotrophoblast proliferation, invasion, and differentiation. Dysregulation of expression of MEF2 family or of their upstream signaling pathways may be associated with placenta-related pregnancy disorders.

Successful stepdown treatment of pulmonary histoplasmosis with thrice-weekly liposomal amphotericin B in a hospital-associated, outpatient infusion centre: A case report.

WHAT IS KNOWN AND OBJECTIVE: Amphotericin is the preferred treatment for pulmonary histoplasmosis during pregnancy. The long half-life of amphotericin supports less than daily administration. CASE SUMMARY: A 28-year-old pregnant woman diagnosed with recurrent pulmonary histoplasmosis was initiated on liposomal amphotericin 250 mg (4 mg/kg) intravenously daily. After 2 weeks, the patient was discharged and successfully received 250 mg thrice weekly at a hospital-associated outpatient infusion centre. After 6 weeks of outpatient treatment, a chest X-ray demonstrated no remaining disease and therapy was discontinued. WHAT IS NEW AND CONCLUSION: Administration of thrice-weekly liposomal amphotericin in a hospital-associated, outpatient infusion centre may be a promising option for stepdown treatment in patients unable to take itraconazole.

Proform-Antecedent Linking in Individuals with Agrammatic Aphasia: A Test of the Intervener Hypothesis.

PURPOSE: To evaluate processing and comprehension of pronouns and reflexives in individuals with agrammatic (Broca's) aphasia and age-matched control participants. Specifically, we evaluate processing and comprehension patterns in terms of a specific hypothesis -- the Intervener Hypothesis - that posits that the difficulty of individuals with agrammatic (Broca's) aphasia results from similarity-based interference caused by the presence of an intervening NP between two elements of a dependency chain. METHODS: We used an eye tracking-while-listening paradigm to investigate real-time processing (Experiment 1) and a sentence-picture matching task to investigate final interpretive comprehension (Experiment 2) of sentences containing proforms in complement phrase and subject relative constructions. RESULTS: Individuals with agrammatic aphasia demonstrated a greater proportion of gazes to the correct referent of reflexives relative to pronouns and significantly greater comprehension accuracy of reflexives relative to pronouns. CONCLUSIONS: These results provide support for the Intervener Hypothesis, previous support for which comes from studies of Wh- questions and unaccusative verbs, and we argue that this account provides an explanation for the deficits of individuals with agrammatic aphasia across a growing set of sentence constructions. The current study extends this hypothesis beyond filler-gap dependencies to referential dependencies and allows us to refine the hypothesis in terms of the structural constraints that meet the description of the Intervener Hypothesis.

Carotenoid Lutein Selectively Inhibits Breast Cancer Cell Growth and Potentiates the Effect of Chemotherapeutic Agents through ROS-Mediated Mechanisms.

Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found that among several carotenoids (including ß-carotene, lutein, and astaxanthin), lutein significantly inhibits breast cancer cell growth by inducing cell-cycle arrest and caspase-independent cell death, but it has little effect on the growth of primary mammary epithelial cells (PmECs). Moreover, lutein-mediated growth inhibition of breast cancer cells is quantitatively similar to that induced by chemotherapeutic taxanes, paclitaxel and docetaxel, and exposure to lutein plus taxanes additively inhibits breast cancer cell growth. Analysis of mechanisms showed that lutein treatment significantly increases the intracellular reactive oxygen species (ROS) production in triple-negative breast cancer (TNBC) cells, but not in normal PmECs. Lutein-induced growth inhibition is also attenuated by the radical oxygen scavenger N-acetyl cysteine, suggesting a role for ROS generation in the growth inhibitory effect of lutein on TNBC cells. Additionally, we found that the p53 signaling pathway is activated and HSP60 levels are increased by lutein treatment, which may contribute partly to the induction of growth inhibition in TNBC cells. Our findings show that lutein promotes growth inhibition of breast cancer cells through increased cell type-specific ROS generation and alternation of several signaling pathways. Dietary lutein supplementation may be a promising alternative and/or adjunct therapeutic candidate against breast cancer.

The outcome of patients in traumatic cardiac arrest presenting to deployed military medical treatment facilities: data from the UK Joint Theatre Trauma Registry.

BACKGROUND: The UK military was continuously engaged in armed conflict in Iraq and Afghanistan between 2003 and 2014, resulting in 629 UK fatalities. Traumatic cardiac arrest (TCA) is a precursor to traumatic death, but data on military outcomes are limited. In order to better inform military treatment protocols, the aim of this study was to define the epidemiology of TCA in the military population with a particular focus on survival rates and injury patterns. METHODS: A retrospective database analysis of the UK Joint Theatre Trauma Registry was undertaken. Patients who were transported to a UK deployed hospital between 2003 and 2014 and suffered TCA were included. Those patients injured by asphyxiation, electrocution, burns without other significant trauma and drowning were excluded. Data included mechanism of injury, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) for each body region and survival to deployed (Role 3) field hospital discharge. RESULTS: 424 TCA patients were identified during the study period; median age was 23 years, with a median ISS of 45. The most common mechanism of injury was explosive (55.7%), followed by gunshot wound (38.9%), road traffic collision (3.5%), crush (1.7%) and fall (0.2%). 45 patients (10.6% (95% CI 8.0% to 13.9%)) survived to deployed (Role 3) hospital discharge. The most prevalent body region with a severe to maximum AIS injury was the head, followed by the lower limbs, thorax and abdomen. Haemorrhage secondary to abdominal and lower limb injury was associated with survival; traumatic brain injury was associated with death. CONCLUSIONS: This study has shown that short-term survival from TCA in a military population is 10.6%. With appropriate and aggressive early management, although unlikely, survival is still potentially possible in military patients who suffer traumatic cardiac arrest.

Maternal and pediatric health and disease: integrating biopsychosocial models and epigenetics.

The concepts of allostasis (stability through adaptation) and accumulated life stress (McEwen's allostatic load) aim to understand childhood and adult outcomes. Chronic malnutrition, changes in social condition, and adverse early-life experiences may program phenotypes and contribute to long-lasting disease risk. However, integration of life course approaches, social and economic contexts, and comparison among different biopsychosocial models has not generally been explored. This review critically examines the literature and evaluates recent insights into how environmental stress can alter lifelong hypothalamic-pituitary-adrenal axis and immune system responsiveness and induce metabolic and neurodevelopmental maladaptation. Models of biopsychosocial stress overlap but may consider different conditions. Concepts include allostasis, which incorporates hormonal responses to predictable environmental changes, and Geronimus's "weathering," which aims to explain how socially structured, repeated stress can accumulate and increase disease vulnerability. Weathering emphasizes roles of internalized/interpersonal racism in outcomes disparities. For Mexican immigrants and Mexican Americans, the "acculturation" framework has proven especially useful to explore disparities, including preterm birth and neuropsychiatric risks in childhood. Complexities of stress assessments and recent research into epigenetic mechanisms mediating effects of physical, nutritional, psychological, and social stress are reviewed.

Sustaining careers of physician-scientists in neonatology and pediatric critical care medicine: formulating supportive departmental policies.

Understanding mechanisms of childhood disease and development of rational therapeutics are fundamental to progress in pediatric intensive care specialties. However, Division Chiefs and Department Chairs face unique challenges when building effective laboratory-based research programs in Neonatal and Pediatric Intensive Care, owing to high clinical demands necessary to maintain competence as well as financial pressures arising from fund flow models and the current extramural funding climate. Given these factors, the role of institutional support that could facilitate successful transition of promising junior faculty to independent research careers is ever more important. Would standardized guidelines of such support provide greater consistency among institutions? We addressed preliminary questions during a national focus group, a workshop and a survey of junior and senior academicians to solicit recommendations for optimal levels of protected time and resources when starting an independent laboratory. The consensus was that junior faculty should be assigned no more than 8 wk clinical service and should obtain start-up funds of $500K-1M exclusive of a 5-y committed salary support. Senior respondents placed a higher premium on protected time than junior faculty.