A discrete choice experiment to elicit preferences for a chronic disease screening programme in Queensland, Australia.

OBJECTIVE: Patient-centred care, increasingly highlighted in healthcare strategies, necessitates understanding public preferences for healthcare service attributes. We aimed to understand the preferences of the Australian population regarding the attributes of chronic disease screening programmes. STUDY DESIGN: The preferences were elicited using the discrete choice experiment (DCE) methodology. METHODS: A DCE was administered to a sample of the Australian general population. Respondents were asked to make choices, each offering two hypothetical screening scenarios defined by screening conduct, quality and accuracy of the test results, cost to the patient, wait time and source of information. Data were analysed using a panel mixed multinomial logit model. RESULTS: A strong preference for highly accurate screening tests and nurse-led screenings at local health clinics was evident. They expressed disutility for waiting time and out-of-pocket costs but were indifferent about the source of information. Their preference for a nurse-led programme was highlighted by the fact that they were willing to pay $81 and $88 to get a nurse-led programme when they were offered a general practitioner-led and a specialist-led programme, respectively. Furthermore, they were willing to pay $32 to reduce a week of waiting time and $205 for a 95% accurate test compared to a 75% accurate test. Preferences remained consistent irrespective of the respondent's place of residence. CONCLUSIONS: Our findings highlight the importance of diagnostic test accuracy and nurse-led service delivery in chronic disease screening programmes. These insights could guide the development of patient-centric services by enhancing test accuracy, reducing waiting times and promoting nurse-led care models.

A Novel Paradigm to Develop Regional Thoracoabdominal Criteria for Behind Armor Blunt Trauma Based on Original Data.

INTRODUCTION: For behind armor blunt trauma (BABT), recent prominent BABT standards for chest plate define a maximum deformation distance of 44 mm in clay. It was developed for soft body armor applications with limited animal, gelatin, and clay tests. The legacy criterion does not account for differing regional thoracoabdominal tolerances to behind armor-induced injury. This study examines the rationale and approaches used in the legacy BABT clay criterion and presents a novel paradigm to develop thoracoabdominal regional injury risk curves. MATERIALS AND METHODS: A review of the original military and law enforcement studies using animals, surrogates, and body armor materials was conducted, and a reanalysis of data was performed. A multiparameter model analysis describes survival-lethality responses using impactor/projectile (mass, diameter, and impact velocity) and specimen (weight and tissue thickness) variables. Binary regression risk curves with ±95% confidence intervals (CIs) and peak deformations from simulant tests are presented. RESULTS: Injury risk curves from 74 goat thorax tests showed that peak deflections of 44.7 mm (±95% CI: 17.6 to 55.4 mm) and 49.9 mm (±95% CI: 24.7 to 60.4 mm) were associated with the 10% and 15% probability of lethal outcomes. 20% gelatin and Roma Plastilina #1 clay were stiffer than goat. The clay was stiffer than 20% gelatin. Penetration diameters showed greater variations (on a test-by-test basis, difference 36-53%) than penetration depths (0-12%) across a range of projectiles and velocities. CONCLUSIONS: While the original authors stressed limitations and the importance of additional tests for refining the 44 mm recommendation, they were not pursued. As live swine tests are effective in developing injury criteria and the responses of different areas of the thoracoabdominal regions are different because of anatomy, structure, and function, a new set of swine and human cadaver tests are necessary to develop scaling relationships. Live swine tests are needed to develop incapacitation/lethal injury risk functions; using scaling relationships, human injury criteria can be developed.

Index Admission Cholecystectomy and Recurrence of Pediatric Gallstone Pancreatitis: Multicenter Cohort Analysis.

BACKGROUND: We aim to evaluate recurrence rates of gallstone pancreatitis in children undergoing early vs interval cholecystectomy. STUDY DESIGN: A multicenter, retrospective review of pediatric patients admitted with gallstone pancreatitis from 2010 through 2017 was performed. Children were evaluated based on timing of cholecystectomy. Early cholecystectomy was defined as surgery during the index admission, whereas the delayed group was defined as no surgery or surgery after discharge. Outcomes, recurrence rates, and complications were evaluated. RESULTS: Of 246 patients from 6 centers with gallstone pancreatitis, 178 (72%) were female, with mean age 13.5 ± 3.2 years and a mean body mass index of 28.9 ± 15.2. Most (90%) patients were admitted with mild pancreatitis (Atlanta Classification). Early cholecystectomy was performed in 167 (68%) patients with no difference in early cholecystectomy rates across institutions. Delayed group patients weighed less (61 kg vs. 72 kg, p = 0.003) and were younger (12 vs. 14 years, p = 0.001) than those who underwent early cholecystectomy. However, there were no differences in clinical, radiological, or laboratory characteristics between groups. There were 4 (2%) episodes of postoperative recurrent pancreatitis in the early group compared with 22% in the delayed group. More importantly, when cholecystectomy was delayed more than 6 weeks from index discharge, recurrence approached 60%. There were no biliary complications in any group. CONCLUSIONS: Cholecystectomy during the index admission for children with gallstone pancreatitis reduces recurrent pancreatitis. Recurrence proportionally increases with time when patients are treated with a delayed approach.

The Emirates Mars Mission.

The Emirates Mars Mission (EMM) was launched to Mars in the summer of 2020, and is the first interplanetary spacecraft mission undertaken by the United Arab Emirates (UAE). The mission has multiple programmatic and scientific objectives, including the return of scientifically useful information about Mars. Three science instruments on the mission's Hope Probe will make global remote sensing measurements of the Martian atmosphere from a large low-inclination orbit that will advance our understanding of atmospheric variability on daily and seasonal timescales, as well as vertical atmospheric transport and escape. The mission was conceived and developed rapidly starting in 2014, and had aggressive schedule and cost constraints that drove the design and implementation of a new spacecraft bus. A team of Emirati and American engineers worked across two continents to complete a fully functional and tested spacecraft and bring it to the launchpad in the middle of a global pandemic. EMM is being operated from the UAE and the United States (U.S.), and will make its data freely available.

An innovative antimicrobial stewardship programme for children in remote and regional areas in Queensland, Australia: optimising antibiotic use through timely intravenous-to-oral switch.

OBJECTIVES: Little is known about the benefits of timely switch from intravenous (IV) to oral antibiotic therapy in children. We evaluated the appropriateness of IV-to-oral switch of antibiotic therapy in remote and regional areas of Australia following the implementation of a multifaceted package of interventions. METHODS: The intervention package, including clinician guidelines, medication review stickers, patient information leaflets and educational resources, was implemented in seven facilities in Queensland, Australia. Children with community-acquired pneumonia and skin and soft-tissue infections were switched to oral therapy if they met the required 'IV-to-oral switch' criteria. Data were collected for a 7-month period from May to November for the baseline (2018) and intervention (2019) phases. RESULTS: A total of 357 patients were enrolled in the study, including 178 in the baseline phase and 179 in the intervention phase. The percentage of patients who switched to oral therapy or stopped IV antibiotics, within 24 h of eligibility, increased from 87.6% (156/178) in the baseline phase to 97.2% (174/179) in the intervention phase (P = 0.003). The average number of extra IV days decreased from 0.45 days in the baseline period to 0.18 days in the intervention period (P < 0.001). The median patient length of stay was 2 days for both phases. The only adverse events recorded were line-associated infiltration, with a decrease from 34.3% (61/178) (baseline) to 17.9% (32/179) (intervention) (P < 0.001). CONCLUSION: A multifaceted intervention package to enhance timely IV-to-oral switch of antibiotic therapy for children in remote and regional facilities is effective.

Multifocal Skull Base Defects With Associated Spontaneous Cerebrospinal Fluid Leaks.

OBJECTIVE: Spontaneous cerebrospinal fluid (CSF) leaks are thought to arise due to elevated intracranial pressure which is distributed across the skull base, potentially predisposing the development of multifocal CSF leaks. The aims of this study are to evaluate the characteristics of this population at presentation and surgical outcomes. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Patients 18 years or older with spontaneous CSF leak diagnosis were eligible for study inclusion. Multifocal spontaneous CSF leak was defined as leaks originating from more than one skull base defect at anatomically distinct subsites. INTERVENTION: None. MAIN OUTCOME MEASURE: Clinical presentation and surgical outcome. RESULTS: Two hundred ninety-three patients with diagnosis of spontaneous CSF leak were identified. Of these, 11 (3.8%) were characterized as having multifocal spontaneous CSF leaks. Mean body mass index was significantly higher in multifocal CSF leak patients (31.5 ±â€Š8.5 vs 46.2 ±â€Š9.9, p < 0.0001). There was also higher prevalence of women (100% vs 63.8%, p = 0.012) and African-Americans (63.6% vs 23.4%, p = 0.003). The overall success rate of CSF leak repair was 95%. Fifty percent of patients developed headaches or blurry vision after surgical repair, and two patients required ventriculoperitoneal shunting. CONCLUSIONS: Multifocal spontaneous CSF leaks are rare and occurred in 3.8% of patients with spontaneous CSF. These patients were morbidly obese and more likely to be female and African American. Surgical repair conferred excellent outcomes. However, these patients have high risk of developing symptoms suggestive of elevated intracranial pressure postoperatively and should be counseled accordingly.

Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.

BACKGROUND: A growing number of studies clearly demonstrate a substantial association between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD), although little is known about the shared genetics that contribute to this association. METHODS: We conducted a large-scale cross-trait genome-wide association study to investigate genetic overlap between COPD (Ncase = 12,550, Ncontrol = 46,368) from the International COPD Genetics Consortium and four primary cardiac traits: resting heart rate (RHR) (N = 458,969), high blood pressure (HBP) (Ncase = 144,793, Ncontrol = 313,761), coronary artery disease (CAD)(Ncase = 60,801, Ncontrol = 123,504), and stroke (Ncase = 40,585, Ncontrol = 406,111) from UK Biobank, CARDIoGRAMplusC4D Consortium, and International Stroke Genetics Consortium data. RESULTS: RHR and HBP had modest genetic correlation, and CAD had borderline evidence with COPD at a genome-wide level. We found evidence of local genetic correlation with particular regions of the genome. Cross-trait meta-analysis of COPD identified 21 loci jointly associated with RHR, 22 loci with HBP, and 3 loci with CAD. Functional analysis revealed that shared genes were enriched in smoking-related pathways and in cardiovascular, nervous, and immune system tissues. An examination of smoking-related genetic variants identified SNPs located in 15q25.1 region associated with cigarettes per day, with effects on RHR and CAD. A Mendelian randomization analysis showed a significant positive causal effect of COPD on RHR (causal estimate = 0.1374, P = 0.008). CONCLUSION: In a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.

A Case Report in Hemorrhagic Stroke: A Complex Disease Process and Requirement for a Multimodal Treatment Approach.

Intracerebral hemorrhage (ICH) with or without intraventricular hemorrhage (IVH) is a highly morbid disease process due to the mass effect and secondary injury that occurs upon the surrounding brain. Historically, surgical evacuation has failed to demonstrate improved outcomes in comparison to standard medical therapy likely due to the significant brain trauma when accessing the clot. Recent minimally invasive techniques have proposed a way to improve outcomes by reducing this injury. We report here a 62-year-old male with ICH and IVH with acute neurological deterioration due to hydrocephalus was found to have no improvement following external ventricular drainage. A repeat non-contrasted computed tomography (CT) head was obtained which demonstrated the worsening mass effect from peri-hematoma edema. Surgical intervention was employed that uses a variety of techniques (endoscopic and exoscopic visualization, stereotactic trans-sulcal approach and side cutting aspiration, and intraventricular thrombolytic therapy) to reduce cerebral trauma while effectively removing both ICH and IVH. The surgical intervention reduces the mass effect and associated secondary injury, lessens the likelihood of shunt placement and length of stay, and improves long-term morbidity. We conclude that the effectiveness of surgical management of ICH could potentially be improved by employing a multifaceted approach to address the different characteristics of the hemorrhagic stroke.

Discovery of diffuse aurora on Mars.

Planetary auroras reveal the complex interplay between an atmosphere and the surrounding plasma environment. We report the discovery of low-altitude, diffuse auroras spanning much of Mars' northern hemisphere, coincident with a solar energetic particle outburst. The Imaging Ultraviolet Spectrograph, a remote sensing instrument on the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft, detected auroral emission in virtually all nightside observations for ~5 days, spanning nearly all geographic longitudes. Emission extended down to ~60 kilometer (km) altitude (1 microbar), deeper than confirmed at any other planet. Solar energetic particles were observed up to 200 kilo--electron volts; these particles are capable of penetrating down to the 60 km altitude. Given minimal magnetic fields over most of the planet, Mars is likely to exhibit auroras more globally than Earth.

MAVEN observations of the response of Mars to an interplanetary coronal mass ejection.

Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere.

Early MAVEN Deep Dip campaign reveals thermosphere and ionosphere variability.

The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability.

Costing the Australian National Hand Hygiene Initiative.

BACKGROUND: The Australian National Hand Hygiene Initiative (NHHI) is a major patient safety programme co-ordinated by Hand Hygiene Australia (HHA) and funded by the Australian Commission for Safety and Quality in Health Care. The annual costs of running this programme need to be understood to know the cost-effectiveness of a decision to sustain it as part of health services. AIM: To estimate the annual health services cost of running the NHHI; the set-up costs are excluded. METHODS: A health services perspective was adopted for the costing and collected data from the 50 largest public hospitals in Australia that implemented the initiative, covering all states and territories. The costs of HHA, the costs to the state-level infection-prevention groups, the costs incurred by each acute hospital, and the costs for additional alcohol-based hand rub are all included. FINDINGS: The programme cost AU$5.56 million each year (US$5.76, £3.63 million). Most of the cost is incurred at the hospital level (65%) and arose from the extra time taken for auditing hand hygiene compliance and doing education and training. On average, each infection control practitioner spent 5h per week on the NHHI, and the running cost per annum to their hospital was approximately AU$120,000 in 2012 (US$124,000, £78,000). CONCLUSION: Good estimates of the total costs of this programme are fundamental to understanding the cost-effectiveness of implementing the NHHI. This paper reports transparent costing methods, and the results include their uncertainty.

The impact of hemodynamic stress on sensory signal processing in the rodent lateral geniculate nucleus.

Hemodynamic stress via hypotensive challenge has been shown previously to cause a corticotropin-releasing factor (CRF)-mediated increase in tonic locus coeruleus (LC) activity and consequent release of norepinephrine (NE) in noradrenergic terminal fields. Although alterations in LC-NE can modulate the responsiveness of signal processing neurons along sensory pathways, little is understood regarding how continuous CRF-mediated activation of LC-NE output due to physiologically relevant stressor affects downstream target cell physiology. The goal of the present study was to investigate the effects of a physiological stressor [hemodynamic stress via sodium nitroprusside (SNP) i.v.] on stimulus evoked responses of sensory processing neurons that receive LC inputs. In rat, the dorsal lateral geniculate nucleus (dLGN) of the thalamus is the primary relay for visual information and is a major target of the LC-NE system. We used extracellular recording techniques in the anesthetized rat monitor single dLGN neuron activity during repeated presentation of light stimuli before and during hemodynamic stress. A significant decrease in magnitude occurred, as well as an increase in latency of dLGN stimulus-evoked responses were observed during hemodynamic stress. In another group of animals the CRF antagonist DpheCRF12-41 was infused onto the ipsilateral LC prior to SNP administration. This infusion blocked the hypotension-induced changes in dLGN stimulus-evoked discharge. These results show that CRF-mediated increases in LC-NE due to hemodynamic stress disrupts the transmission of information along thalamic-sensory pathways by: (1) initially reducing signal transmission during onset of the stressor and (2) decreasing the speed of stimulus evoked sensory transmission.

Is it possible to detect dendrite currents using presently available magnetic resonance imaging techniques?

The action currents of a dendrite, peripheral nerve or skeletal muscle create their own magnetic field. Many investigators have attempted to detect neural and dendritic currents directly using magnetic resonance imaging that can cause the phase of the spins to change. Our goal in this paper is to use the calculated magnetic field of a dendrite to estimate the resulting phase shift in the magnetic resonance signal. The field produced by a dense collection of simultaneously active dendrites may be just detectable under the most ideal circumstances, but in almost every realistic case the field cannot be detected using current MRI technology.

Autophagy facilitates major histocompatibility complex class I expression induced by IFN-γ in B16 melanoma cells.

The reduction or loss of MHC-I antigen surface expression in human and murine tumor cells is partly attributable to the dysregulation of various components of the MHC-I antigen-processing machinery. Accumulating evidence suggests that autophagy, besides its vital role in maintaining the cellular homeostasis, plays an important role in MHC-II surface expression. Here, we report that autophagy is a negative regulator of MHC-I antigen expression in B16 melanoma cells; however, in the presence of IFN-γ, it is converted to a positive regulator. We show that autophagy not only participates in the degradation of MHC-I antigen but also plays a role in the generation of MHC-I-binding peptides. For these two processes, IFN-γ interferes with MHC-I antigen degradation, rather than affecting peptide generation. Using B16 melanoma mouse model, we further show that autophagy may enhance the cytolysis of CTL to melanoma cells at the early stage of melanoma, but impairs the cytolysis at the late stage. Such different consequences may be explained by the different levels of IFN-γ during tumor progression. Taken together, our findings demonstrate that autophagy is involved in the regulation of MHC-I antigen expression, through which autophagy can play different roles in tumor immunity.

Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors.

In the present study, we have evaluated a boronated dendrimer-epidermal growth factor (BD-EGF) bioconjugate as a molecular targeting agent for boron neutron capture therapy (BNCT) of the human EGFR gene-transfected F98 rat glioma, designated F98(EGFR). EGF was chemically linked to a heavily boronated polyamidoamine dendrimer (BD) by means of the heterobifunctional reagent, mMBS. Biodistribution studies were carried out at 6 h and 24 h following intratumoral (i.t.) injection or intracerebral (i.c.) convection enhanced delivery (CED) of (125)I-labeled or unlabeled BD-EGF (40 microg (10)B/10 microg EGF) to F98 glioma bearing rats. At 24 h. there was 43% more radioactivity in EGFR(+) tumors following CED compared to i.t. injection, and a doubling of the tumor boron concentration (22.3 microg/g vs. 11.7 microg/g). CED of BD-EGF resulted in a 7.2x increase in the volume of distribution within the infused cerebral hemisphere and a 1.9x increase in tumor uptake of BD-EGF compared with i.t. injection. Based on these favorable biodistribution data, BNCT was carried out at the Massachusetts Institute of Technology nuclear reactor 14 days following i.c. tumor implantation and 24 h. after CED of BD-EGF. These animals had a MST of 54.1 +/- 4.7 days compared to 43.0 +/- 2.8 days following i.t. injection. Rats that received BD-EGF by CED in combination with i.v. boronophenylalanine (BPA), which has been used in both experimental and clinical studies, had a MST of 86.0 +/- 28.1 days compared to 39.8 +/- 1.6 days for i.v. BPA alone (P < 0.01), 30.9 +/- 1.4 days for irradiated controls and 25.1 +/- 1.0 days for untreated controls (overall P < 0.0001). These data have demonstrated that the efficacy of BNCT was significantly increased (P < 0.006), following i.c CED of BD-EGF compared to i.t injection, and that the survival data were equivalent to those previously reported by us using the boronated anti-human-EGF mAb, C225 (cetuximab).

Plasma acceleration above martian magnetic anomalies.

Auroras are caused by accelerated charged particles precipitating along magnetic field lines into a planetary atmosphere, the auroral brightness being roughly proportional to the precipitating particle energy flux. The Analyzer of Space Plasma and Energetic Atoms experiment on the Mars Express spacecraft has made a detailed study of acceleration processes on the nightside of Mars. We observed accelerated electrons and ions in the deep nightside high-altitude region of Mars that map geographically to interface/cleft regions associated with martian crustal magnetization regions. By integrating electron and ion acceleration energy down to the upper atmosphere, we saw energy fluxes in the range of 1 to 50 milliwatts per square meter per second. These conditions are similar to those producing bright discrete auroras above Earth. Discrete auroras at Mars are therefore expected to be associated with plasma acceleration in diverging magnetic flux tubes above crustal magnetization regions, the auroras being distributed geographically in a complex pattern by the many multipole magnetic field lines extending into space.

Archaeal diversity in ODP legacy borehole 892b and associated seawater and sediments of the Cascadia Margin.

The Cascadia Margin is a region of active accretionary tectonics characterized by high methane flux accompanied by the formation of sedimentary gas hydrates, carbonate nodules, and carbonate pavements. Several sediment cores have been obtained from this region by the Ocean Drilling Project (ODP), and in some cases the boreholes have been sealed off, serving as sites for long-term observatories. We characterized geochemical parameters and diversity of Archaea in one such "legacy" borehole, ODP site 892b, as well as in bottom water immediately above the borehole and in two nearby sediments. The methane concentrations in the samples varied over five orders of magnitude, from approximately 25 to 35 nM in the bottom water to approximately 1.4mM in one of the sediment samples. Despite these differences, the Archaeal community in all samples was dominated by gene sequences related to the methanogenic Archaea, a finding that correlates with studies of other environments characterized by high methane flux. The archaeal phylotype richness in borehole ODP 892b was limited to two phylotypes; one specifically related to Methanosaeta spp., the other to the anaerobic methane oxidizing ANME-1 group. Although some similar groups were observed in nearby sediment and seawater samples, their archaeal phylotype richness was significantly higher than in the borehole. The possible presence of a dynamic microbial community in the Cascadia Margin sub-surface and its potential roles in methanogenesis, anaerobic oxidation of methane, and authigenic precipitation of carbonate in the Cascadia Margin are discussed.