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This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer’s disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.
This paper is concerned with rapid distortion theory on transversely sheared mean flows that (among other things) can be used to analyse the unsteady motion resulting from the interaction of a turbulent shear flow with a solid surface. It expands on a previous analysis of Goldstein et al. (J. Fluid Mech., vol. 824, 2017, pp. 477–512) that uses a pair of conservation laws to derive upstream boundary conditions for planar mean flows and extends these findings to transversely sheared flows of arbitrary cross-section. The results, which turn out to be quite general, are applied to the specific case of a round jet interacting with the trailing edge of a flat plate and are used to calculate the radiated sound field, which is then compared with experimental data taken at the NASA Glenn Research Center.
Introduction: The Prehospital Evidence-Based Practice (PEP) program is an online, freely accessible, continuously updated Emergency Medical Services (EMS) evidence repository. This summary describes the research evidence for the identification and management of adult patients suffering from sepsis syndrome or septic shock. Methods: PubMed was searched in a systematic manner. One author reviewed titles and abstracts for relevance and two authors appraised each study selected for inclusion. Primary outcomes were extracted. Studies were scored by trained appraisers on a three-point Level of Evidence (LOE) scale (based on study design and quality) and a three-point Direction of Evidence (DOE) scale (supportive, neutral, or opposing findings based on the studies’ primary outcome for each intervention). LOE and DOE of each intervention were plotted on an evidence matrix (DOE x LOE). Results: Eighty-eight studies were included for 15 interventions listed in PEP. The interventions with the most evidence were related to identification tools (ID) (n = 26, 30%) and early goal directed therapy (EGDT) (n = 21, 24%). ID tools included Systematic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA) and other unique measures. The most common primary outcomes were related to diagnosis (n = 30, 34%), mortality (n = 40, 45%) and treatment goals (e.g. time to antibiotic) (n = 14, 16%). The evidence rank for the supported interventions were: supportive-high quality (n = 1, 7%) for crystalloid infusion, supportive-moderate quality (n = 7, 47%) for identification tools, prenotification, point of care lactate, titrated oxygen, temperature monitoring, and supportive-low quality (n = 1, 7%) for vasopressors. The benefit of prehospital antibiotics and EGDT remain inconclusive with a neutral DOE. There is moderate level evidence opposing use of high flow oxygen. Conclusion: EMS sepsis interventions are informed primarily by moderate quality supportive evidence. Several standard treatments are well supported by moderate to high quality evidence, as are identification tools. However, some standard in-hospital therapies are not supported by evidence in the prehospital setting, such as antibiotics, and EGDT. Based on primary outcomes, no identification tool appears superior. This evidence analysis can guide selection of appropriate prehospital therapies.
Introduction: In Nova Scotia, under the Paramedics Providing Palliative Care program, paramedics can now manage symptom crises in patients with palliative care goals and often at home without the need to transport to hospital. Growing recognition that non-cancer conditions benefit from a palliative approach is expanding the program. Our team previously found treatment of pain and breathlessness is not optimized, pain scores are underutilized, and paramedics were more comfortable (pre-launch) with a palliative approach in cancer versus non-cancer conditions. Our objective was to compare symptom management in cancer versus non-cancer subgroup. Methods: We conducted a retrospective cohort study. The Electronic Patient Care Record and Special Patient Program were queried for patients with palliative goals from July 1, 2015 to July 1, 2016. Descriptive analysis was conducted and results were compared with a t-test and Bonferroni correction (alpha = p < 0.007). Results: 1909 unique patients; 765/1909 (40.1%) cancer and 1144/1909 (59.9%) non-cancer. Female sex: cancer 357/765 (46.7%), non-cancer 538/1144 (47.0%). Mean age cancer: 73.3 (11.65), non-cancer 77.7 (12.80). Top non-cancer conditions: COPD (495/1144, 43.3%), CHF (322/1144, 28.1%), stroke (172/1144, 15.0%) and dementia (149/1144, 13.0%). Comorbidities for cancer patients (range): 0 to 3; non-cancer 0 to 5. Most common chief complaint (CC) for cancer and non-cancer: respiratory distress, 10.8% vs 21.5%. Overall, no difference in proportion treated cancer vs non-cancer, 11.5% vs 10.1%, p = 0.35. Some difference in individual therapies: morphine 83/765 (10.8%) vs 55/1144 (4.8%), p < 0.001, hydromorphone 9/765 (1.2%) vs 2/1144 (0.2%), p = 0.014, salbutamol 38/765 (5.0%) vs 5/1144 (0.4%), p < 0.001 and ipratropium 27/765 (3.5%) vs 134/1144 (11.7%), p < 0.001, in addition to any support with home medication which is not queriable. Pre-treatment pain scores were documented more often than post-treatment in both groups (58.7% vs 25.6% (p < 0.001), 57.4% vs 26.9% (p < 0.001)). Conclusion: Non-cancer patients represent an important proportion of palliative care calls for paramedics. Cancer and non-cancer patients had very similar CC and received similar treatment, although low proportions, despite pre-launch findings that non-cancer conditions were likely to be undertreated. Pain scores remain underutilized. Further research into the underlying reason(s) is required to improve the support of non-cancer patients by paramedics.
Transcatheter right ventricle decompression in neonates with pulmonary atresia and intact ventricular septum is technically challenging, with risk of cardiac perforation and death. Further, despite successful right ventricle decompression, re-intervention on the pulmonary valve is common. The association between technical factors during right ventricle decompression and the risks of complications and re-intervention are not well described.
This is a multicentre retrospective study among the participating centres of the Congenital Catheterization Research Collaborative. Between 2005 and 2015, all neonates with pulmonary atresia and intact ventricular septum and attempted transcatheter right ventricle decompression were included. Technical factors evaluated included the use and characteristics of radiofrequency energy, maximal balloon-to-pulmonary valve annulus ratio, infundibular diameter, and right ventricle systolic pressure pre- and post-valvuloplasty (BPV). The primary end point was cardiac perforation or death; the secondary end point was re-intervention.
A total of 99 neonates underwent transcatheter right ventricle decompression at a median of 3 days (IQR 2–5) of age, including 63 patients by radiofrequency and 32 by wire perforation of the pulmonary valve. There were 32 complications including 10 (10.5%) cardiac perforations, of which two resulted in death. Cardiac perforation was associated with the use of radiofrequency (p=0.047), longer radiofrequency duration (3.5 versus 2.0 seconds, p=0.02), and higher maximal radiofrequency energy (7.5 versus 5.0 J, p<0.01) but not with patient weight (p=0.09), pulmonary valve diameter (p=0.23), or infundibular diameter (p=0.57). Re-intervention was performed in 36 patients and was associated with higher post-intervention right ventricle pressure (median 60 versus 50 mmHg, p=0.041) and residual valve gradient (median 15 versus 10 mmHg, p=0.046), but not with balloon-to-pulmonary valve annulus ratio, atmospheric pressure used during BPV, or the presence of a residual balloon waist during BPV. Re-intervention was not associated with any right ventricle anatomic characteristics, including pulmonary valve diameter.
Technical factors surrounding transcatheter right ventricle decompression in pulmonary atresia and intact ventricular septum influence the risk of procedural complications but not the risk of future re-intervention. Cardiac perforation is associated with the use of radiofrequency energy, as well as radiofrequency application characteristics. Re-intervention after right ventricle decompression for pulmonary atresia and intact ventricular septum is common and relates to haemodynamic measures surrounding initial BPV.
This paper is concerned with rapid-distortion theory on transversely sheared mean flows which (among other things) can be used to analyse the unsteady motion resulting from the interaction of a turbulent shear flow with a solid surface. It extends previous analyses of Goldstein et al. (J. Fluid Mech., vol. 736, 2013a, pp. 532–569; NASA/TM-2013-217862, 2013b) which showed that the unsteady motion is completely determined by specifying two arbitrary convected quantities. The present paper uses a pair of previously derived conservation laws to derive upstream boundary conditions that relate these quantities to experimentally measurable flow variables. The result is dependent on the imposition of causality on an intermediate variable that appears in the conservation laws. Goldstein et al. (2013a) related the convected quantities to the physical flow variables at the location of the interaction, but the results were not generic and hard to reconcile with experiment. That problem does not occur in the present formulation, which leads to a much simpler and more natural result than the one given in Goldstein et al. (2013a). We also show that the present formalism yields better predictions of the sound radiation produced by the interaction of a two-dimensional jet with the downstream edge of a flat plate than the Goldstein et al. (2013a) result. The role of causality is also discussed.
People with pancreatic cancer have poor survival, and management is challenging. Pancreatic cancer patients' perceptions of their care coordination and its association with their outcomes have not been well-studied. Our objective was to determine if perception of care coordination is associated with patient-reported outcomes or survival.
People with pancreatic cancer who were 1–8 months postdiagnosis (52 with completed resection and 58 with no resection) completed a patient-reported questionnaire that assessed their perceptions of care coordination, quality of life, anxiety, and depression using validated instruments. Mean scores for 15 care-coordination items were calculated and then ranked from highest (best experience) to lowest (worst experience). Associations between care-coordination scores (including communication and navigation domains) and patient-reported outcomes and survival were investigated using general linear regression and Cox regression, respectively. All analyses were stratified by whether or not the tumor had been resected.
In both groups, the highest-ranked care-coordination items were: knowing who was responsible for coordinating care, health professionals being informed about their history, and waiting times. The worst-ranked items related to: how often patients were asked about visits with other health professionals and how well they and their family were coping, knowing the symptoms they should monitor, having sufficient emotional help from staff, and access to additional specialist services. For people who had a resection, better communication and navigation scores were significantly associated with higher quality of life and less anxiety and depression. However, these associations were not statistically significant for those with no resection. Perception of cancer care coordination was not associated with survival in either group.
Significance of results:
Our results suggest that, while many core clinical aspects of care are perceived to be done well for pancreatic cancer patients, improvements in emotional support, referral to specialist services, and self-management education may improve patient-reported outcomes.
Introduction: Collaborative Emergency Centres (CECs) provide access to care in rural communities. After hours, registered nurses (RNs) and paramedics work together in the ED with telephone support by an emergency medical services (EMS) physician. The safety of such a model is unknown. Relapse visits are often used as a proxy measure for safety in emergency medicine. The primary outcome of this study is to measure unscheduled relapses to emergency care. Methods: The electronic patient care record (ePCR) database was queried for all patients who visited two CECs from April 1, 2012 to April 1, 2013. Abstracted data included demographics, time, acuity score, clinical impression, chief complaint, and disposition. Records were searched for each discharged CEC patient to identify unscheduled relapses to emergency care, defined as presenting back to EMS, CEC, or any other ED within the Health Authority within 48 hours of CEC discharge. Results: There were 894 CEC visits, of which 66 were excluded due to missing data. The dispositions from CEC were: 131/828 (15.8%) transferred to regional ED; 264/828 (31.9%) discharged home; 488/828 (58.9%) discharged with follow up visit booked; and 11/82 (1.2%) left the CEC without being seen. There was 37/828 (4.5%) visits which relapsed back to emergency care, all of whom were discharged from CEC or left without being seen: 3/828 (0.4%) relapsed back to EMS (two taken to regional ED and one to CEC); 16/828 (1.9%) relapsed to regional ED (by walking-in); and 18/828 (2.2%) had a relapse to the CEC (walk-in). 516/828 (62.3%) CEC visits were resolved in a single visit. Conclusion: This study was based on only two of the 7 operating CECs due to accessing paper-based charts for multiple health regions. We also acknowledge the limitations of using relapse as a proxy for safety, and that low volumes and acuity will make detection of adverse events challenging. Albeit a proxy measure, the rate of patients who relapse to emergency care was under 5% in this case series of two CECs. Most patients had their concern resolved in a single visit to a CEC. Further research is underway to determine the effectiveness, optimal utilization and safety of this collaborative model of rural emergency care.
The prenatal environment is now recognized as a key driver of non-communicable disease risk later in life. Within the developmental origins of health and disease (DOHaD) paradigm, studies are increasingly identifying links between maternal morbidity during pregnancy and disease later in life for offspring. Nutrient restriction, metabolic disorders during gestation, such as diabetes or obesity, and maternal immune activation provoked by infection have been linked to adverse health outcomes for offspring later in life. These factors frequently co-occur, but the potential for compounding effects of multiple morbidities on DOHaD-related outcomes has not received adequate attention. This is of particular importance in low- or middle-income countries (LMICs), which have ongoing high rates of infectious diseases and are now experiencing transitions from undernutrition to excess adiposity. The purpose of this scoping review is to summarize studies examining the effect and interaction of co-occurring metabolic or nutritional stressors and infectious diseases during gestation on DOHaD-related health outcomes. We identified nine studies in humans – four performed in the United States and five in LMICs. The most common outcome, also in seven of nine studies, was premature birth or low birth weight. We identified nine animal studies, six in mice, two in rats and one in sheep. The interaction between metabolic/nutritional exposures and infectious exposures had varying effects including synergism, inhibition and independent actions. No human studies were specifically designed to assess the interaction of metabolic/nutritional exposures and infectious diseases. Future studies of neonatal outcomes should measure these exposures and explicitly examine their concerted effect.
The Arcminute Cosmology Bolometer Array Receiver (Acbar) is a multifrequency millimeter-wave receiver optimized for observations of the Cosmic Microwave Background (CMB) and the Sunyaev-Zel'dovich (SZ) effect in clusters of galaxies. Acbar was installed on the 2.1 m Viper telescope at the South Pole in January 2001 and the results presented here incorporate data through July 2002. The power spectrum of the CMB at 150 GHz over the range ℓ = 150 — 3000 measured by Acbar is presented along with estimates for the values of the cosmological parameters within the context of ΛCDM models. The inclusion of ΩΛ greatly improves the fit to the power spectrum. Three-frequency images of the SZ decrement/increment are also presented for the galaxy cluster 1E0657–67.
The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth’s magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space – magnetosheath, shock, foreshock and pristine solar wind – featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the ‘Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)’. THOR has been selected by European Space Agency (ESA) for the study phase.
Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.
Methods and results
This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].
Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
Introduction: Paramedics are sometimes called for crisis management and relief of symptoms or for patients receiving palliative care. To address the mismatch between the system protocols and resources, and patient’s goals of care, a new protocol, new medications, and an 8-hour training program Learning Essentials Approach to Palliative Care (LEAP) were implemented in our provincial EMS system. Methods: Prior to attending their training session paramedics received an invitation to complete an online survey regarding their comfort, confidence, and attitudes toward delivering palliative care. Comfort and confidence questions were scored on a 4-point Likert scale, while attitudes toward specific aspects of care were scored on a 7-point Likert scale. Descriptive statistics were calculated. Identifiers will permit linkage of these responses to a repeat survey post-implementation. Results: 188 (58%) paramedics completed the survey of the 325 who opened the link. 134 (68%) were male with a mean age of 38.5 years. 95 (50%) were primary care paramedics. The average experience as a paramedic was 12.7 years, with an estimated mean number of palliative calls per year of 9.6 each. On a 4 point scale, most (156, 83%) were comfortable with providing care to someone with palliative goals, and 130 (69.1%) were comfortable providing care without transport. Only 82 (43.6%) were confident they had the tools to deliver this care, and 76 (40.4%) were confident they could do so without transport to hospital. On a 7 point scale, paramedics disagreed with the statement “caring for dying persons is not a worthwhile experience for me”, median 7 (IQR 5-7). Paramedics also disagreed with the statement “Dying persons make me feel uneasy”, median 5 (IQR 4-6). Conclusion: Prior to the implementation of the new protocol, medications, and training, most paramedics were comfortable with the concept of providing care with palliative goals and felt that caring for dying persons is a worthwhile experience, but they were not confident that they have the tools and resources to do so. This suggests paramedics would be open to system improvements to meet an unmet healthcare need for crisis management of patients with palliative goals of care.
To describe the burden of extended-spectrum β-lactamase (ESBL) Enterobacteriaceae in veterans with spinal cord injury or disorder (SCI/D), to identify risk factors for ESBL acquisition, and to assess impact on clinical outcomes
Retrospective case-case-control study
PATIENTS AND SETTING
Veterans with SCI/D and utilization at a Veterans’ Affairs medical center from January 1, 2012, to December 31, 2013.
Patients with a positive culture for ESBL Klebsiella pneumoniae, Escherichia coli, or Proteus mirabilis were matched with patients with non-ESBL organisms by organism, facility, and level of care and to uninfected controls by facility and level of care. Inpatients were also matched by time at risk. Univariate and multivariate matched models were assessed for differences in risk factors and outcomes.
A total of 492 cases (62.6% outpatients) were matched 1:1 with each comparison group. Recent prior use of fluoroquinolones and prior use of third- and fourth-generation cephalosporins were independently associated with ESBL compared to the non-ESBL group (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.77–3.84; P<.001 for fluoroquinolones and aOR, 3.86; 95% CI, 2.06–7.25; P<.001 for third- and fourth-generation cephalosporins) and the control group (aOR, 2.10; 95% CI, 1.29–3.43; P = .003 for fluoroquinolones; and aOR, 3.31; 95% CI, 1.56–7.06; P=.002 for third- and fourth-generation cephalosporins). Although there were no differences in mortality rate, the ESBL group had a longer post-culture length of stay (LOS) than the non-ESBL group (incidence rate ratio, 1.36; 95% CI, 1.13–1.63; P=.001).
All SCI/D patients with ESBL were more likely to have had recent exposure to fluoroquinolones or third- and fourth-generation cephalosporins, and hospitalized patients were more likely to have increased post-culture LOS. Programs targeted toward reduced antibiotic use in SCI/D patients may prevent subsequent ESBL acquisition.
Plasmas are ubiquitous in nature, surround our local geospace environment, and permeate the universe. Plasma phenomena in space give rise to energetic particles, the aurora, solar flares and coronal mass ejections, as well as many energetic phenomena in interstellar space. Although plasmas can be studied in laboratory settings, it is often difficult, if not impossible, to replicate the conditions (density, temperature, magnetic and electric fields, etc.) of space. Single-point space missions too numerous to list have described many properties of near-Earth and heliospheric plasmas as measured both in situ and remotely (see http://www.nasa.gov/missions/#.U1mcVmeweRY for a list of NASA-related missions). However, a full description of our plasma environment requires three-dimensional spatial measurements. Cluster is the first, and until data begin flowing from the Magnetospheric Multiscale Mission (MMS), the only mission designed to describe the three-dimensional spatial structure of plasma phenomena in geospace. In this paper, we concentrate on some of the many plasma phenomena that have been studied using data from Cluster. To date, there have been more than 2000 refereed papers published using Cluster data but in this paper we will, of necessity, refer to only a small fraction of the published work. We have focused on a few basic plasma phenomena, but, for example, have not dealt with most of the vast body of work describing dynamical phenomena in Earth's magnetosphere, including the dynamics of current sheets in Earth's magnetotail and the morphology of the dayside high latitude cusp. Several review articles and special publications are available that describe aspects of that research in detail and interested readers are referred to them (see for example, Escoubet et al. 2005Multiscale Coupling of Sun-Earth Processes, p. 459, Keith et al. 2005Sur. Geophys.26, 307–339, Paschmann et al. 2005Outer Magnetospheric Boundaries: Cluster Results, Space Sciences Series of ISSI. Berlin: Springer, Goldstein et al. 2006Adv. Space Res.38, 21–36, Taylor et al. 2010The Cluster Mission: Space Plasma in Three Dimensions, Springer, pp. 309–330 and Escoubet et al. 2013Ann. Geophys.31, 1045–1059).
Continued monitoring of the seriousness of influenza viruses is a public health priority. We applied time-series regression models to data on cardio-respiratory mortality rates in Hong Kong from 2001 to 2011. We used surveillance data on outpatient consultations for influenza-like illness, and laboratory detections of influenza types/subtypes to construct proxy measures of influenza activity. In the model we allowed the regression coefficients for influenza to drift over time, and adjusted for temperature and humidity. The regression coefficient for influenza A(H3N2) increased significantly in 2005. The regression coefficients for influenza A(H1N1) and B were relatively stable over the period. Our model suggested an increase in seriousness of A(H3N2) in 2005, the year after the appearance of the A/Fujian/411/2002(H3N2)-like virus when the drifted A/California/7/2004(H3N2)-like virus appeared. Ongoing monitoring of mortality and influenza activity could permit identification of future changes in seriousness of influenza virus infections.