Managing COVID-19 within and across health systems: why we need performance intelligence to coordinate a global response.

BACKGROUND: The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems' decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic. DISCUSSION: A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance. CONCLUSION: Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution.

Verification of a Many-Ion Simulator of the Dicke Model Through Slow Quenches across a Phase Transition.

We use a self-assembled two-dimensional Coulomb crystal of ∼70 ions in the presence of an external transverse field to engineer a simulator of the Dicke Hamiltonian, an iconic model in quantum optics which features a quantum phase transition between a superradiant (ferromagnetic) and a normal (paramagnetic) phase. We experimentally implement slow quenches across the quantum critical point and benchmark the dynamics and the performance of the simulator through extensive theory-experiment comparisons which show excellent agreement. The implementation of the Dicke model in fully controllable trapped ion arrays can open a path for the generation of highly entangled states useful for enhanced metrology and the observation of scrambling and quantum chaos in a many-body system.

Amplitude Sensing below the Zero-Point Fluctuations with a Two-Dimensional Trapped-Ion Mechanical Oscillator.

We present a technique to measure the amplitude of a center-of-mass (c.m.) motion of a two-dimensional ion crystal of ∼100 ions. By sensing motion at frequencies far from the c.m. resonance frequency, we experimentally determine the technique's measurement imprecision. We resolve amplitudes as small as 50 pm, 40 times smaller than the c.m. mode zero-point fluctuations. The technique employs a spin-dependent, optical-dipole force to couple the mechanical oscillation to the electron spins of the trapped ions, enabling a measurement of one quadrature of the c.m. motion through a readout of the spin state. We demonstrate sensitivity limits set by spin projection noise and spin decoherence due to off-resonant light scattering. When performed on resonance with the c.m. mode frequency, the technique demonstrated here can enable the detection of extremely weak forces (<1 yN) and electric fields (<1 nV/m), providing an opportunity to probe quantum sensing limits and search for physics beyond the standard model.

Integrated on-chip mass spectrometry reaction monitoring in microfluidic devices containing porous polymer monolithic columns.

Chip-based microfluidics enable the seamless integration of different functions into single devices. Here, we present microfluidic chips containing porous polymer monolithic columns as a means to facilitate chemical transformations as well as both downstream chromatographic separation and mass spectrometric analysis. Rapid liquid phase lithography prototyping creates the multifunctional device economically.

High-intensity functional training improves functional movement and body composition among cancer survivors: a pilot study.

This pilot study investigated feasibility and preliminary efficacy of a high-intensity functional training (HIFT) group-exercise programme among adult cancer survivors within 5 years of last cancer treatment. Eight participants were assigned to a 5-week, 3 days/week HIFT intervention with four testing sessions and 12 workouts along with mobility and stretching exercises. Feasibility was assessed by initiation, adherence, and acceptability. Efficacy was determined by changes from baseline to post-test in health-related quality of life, body composition and functional movement. The recruitment rate was 80% and the adherence rate was 75%. Significant improvements were found for emotional functioning (P = 0.042) and body composition (lean mass +3.8 ± 2.1 kg, P = 0.008; fat mass -3.3 ± 1.0 kg, P = 0.001; body fat percentage -4.7 ± 1.2%, P < 0.001). Participants also significantly improved on five of seven functional movements: balance (P = 0.032), carrying a weighted object (P = 0.004), lower body strength and power (P = 0.009), aerobic capacity and endurance (P = 0.039), and perceived difficulty for flexibility (P = 0.012). Five weeks of HIFT training was well-received and feasible for most cancer survivors, and effective for improving emotional functioning, body composition and functional movement.

Sensitivity of the Kß″ X-ray Emission Line to Coordination Changes in GeO2 and TiO2.

The hard X-ray Kß″ emission line shows sensitivity with respect to a wide range of cation-ligand coordination, which we investigate in the cases of GeO2 and TiO2 on the basis of ab initio spectral calculations on amorphous and crystalline structures. In compressed amorphous GeO2, the sampling of a large number of instantaneous coordination polyhedra from an ab initio molecular dynamics trajectory reveals that the functional relation between the Kß″ shift and coordination is close to linear between 4-fold and 7-fold coordination. A similar sensitivity of the Kß″ emission line exists in the coordination range between six and nine of crystalline high-pressure TiO2 polymorphs. Our results demonstrate the potential of the Kß″ emission line in research on the structure of amorphous oxide material.

Culture-independent characterization of bacteria and fungi in a poultry bioaerosol using pyrosequencing: a new approach.

Work in animal production facilities often results in exposure to organic dusts. Previous studies have documented decreases in pulmonary function and lung inflammation among workers exposed to organic dust in the poultry industry. Bacteria and fungi have been reported as components of the organic dust produced in poultry facilities. To date, little is known about the diversity and concentration of bacteria and fungi inside poultry buildings. All previous investigations have utilized culture-based methods for analysis that identify only biota cultured on selected media. The bacterial tag-encoded flexible (FLX) amplicon pyrosequencing (bTEFAP) and fungal tag-encoded flexible (FLX) amplicon pyrosequencing (fTEFAP) are modern and comprehensive approaches for determining biodiversity of microorganisms and have not previously been used to provide characterization of exposure to microorganisms in an occupational environment. This article illustrates the potential application of this novel technique in occupational exposure assessment as well as other settings. An 8-hr area sample was collected using an Institute of Medicine inhalable sampler attached to a mannequin in a poultry confinement building. The sample was analyzed using bTEFAP and fTEFAP. Of the bacteria and fungi detected, 116 and 39 genera were identified, respectively. Among bacteria, Staphylococcus cohnii was present in the highest proportion (23%). The total inhalable bacteria concentration was estimated to be 7503 cells/m³. Among the fungi identified, Sagenomella sclerotialis was present in the highest proportion (37%). Aspergillus ochraceus and Penicillium janthinellum were also present in high proportions. The total inhalable fungi concentration was estimated to be 1810 cells/m³. These estimates are lower than what has been reported by others using standard epifluorescence microscope methods. However, no study has used non-culture-based techniques, such as bTEFAP and fTEFAP, to evaluate bacteria and fungi in the inhalable fraction of a bioaerosol in a broiler production environment. Furthermore, the impact of this bTEFAP and fTEFAP technology has yet to be realized by the scientific community dedicated to evaluating occupational and environmental bioaerosol exposure.

Phase-coherent sensing of the center-of-mass motion of trapped-ion crystals.

Trapped ions are sensitive detectors of weak forces and electric fields that excite ion motion. Here measurements of the center-of-mass motion of a trapped-ion crystal that are phase coherent with an applied weak external force are reported. These experiments are conducted far from the trap motional frequency on a two-dimensional trapped-ion crystal of approximately 100 ions, and determine the fundamental measurement imprecision of our protocol free from noise associated with the center-of-mass mode. The driven sinusoidal displacement of the crystal is detected by coupling the ion crystal motion to the internal spin degree of freedom of the ions using an oscillating spin-dependent optical dipole force. The resulting induced spin precession is proportional to the displacement amplitude of the crystal, and is measured with near-projection-noise-limited resolution. A 49 pm displacement is detected with a signal-to-noise ratio of 1 in a single experimental determination, which is an order-of-magnitude improvement over prior phase-incoherent experiments. This displacement amplitude is 40 times smaller than the zero-point fluctuations. With our repetition rate, an 8.4   pm / Hz displacement sensitivity is achieved, which implies 12   ( yN/ion ) / Hz and 77   ( µ V/m ) / Hz sensitivities to forces and electric fields, respectively. This displacement sensitivity, when applied on-resonance with the center-of-mass mode, indicates the possibility of weak force and electric field detection below 10-3 yN/ion and 1 nV/m, respectively.

Li 1s core exciton in LiH studied by x-ray Raman scattering spectroscopy.

The Li 1s core excitation spectra in LiH was studied by means of x-ray Raman scattering (XRS) spectroscopy in a wide range of momentum transfers q. The analysis of the near-edge region of the measured spectra in combination with q-dependent ab initio calculations of XRS spectra based on the Bethe-Salpeter equation (BSE) reveals that the prominent peak at the excitation onset arises from two main contributions, namely a pre-edge peak associated to a p-type core exciton and strong transitions to empty states near the bottom of the conduction band, which is in contrast to previous experimental studies that attributed that feature to a single excitonic peak. The p-like angular symmetry of the core exciton is supported by BSE calculations of the relative contributions to the XRS spectra from monopole and dipole transitions and by the observed decrease of its normalised intensity for increasing momentum transfers. Higher energy spectral features in the measured XRS spectra are well reproduced by BSE, as well as by real-space multiple-scattering calculations.

Maternal and fetal outcomes of primary immune thrombocytopenia during pregnancy: A retrospective study.

OBJECTIVE: We reviewed outcomes of 52 pregnancies in 45 women with immune thrombocytopenic purpura who delivered at Auckland Hospital with an antenatal platelet count of <100 × 109/L. OUTCOME MEASURES: Primary outcomes were maternal platelet count at delivery and treatment response. Secondary outcomes included post-partum haemorrhage (PPH). RESULTS: Most women had thrombocytopenia at delivery. Treatment with prednisone was given in 14 (27%) pregnancies with responses considered safe for delivery in 11 pregnancies (79%). Women in eight pregnancies also received intravenous immunoglobulin; in five pregnancies (63%) a platelet response acceptable for delivery was achieved.Seventeen pregnancies (33%) were complicated by a PPH ≥500 mL. Ten pregnancies (19%) were complicated by a PPH ≥1000 mL. PPH was reported in all women with a platelet count <50 × 109/L at delivery. CONCLUSIONS: There were no antenatal bleeding complications but PPH was common among women with platelet counts <50 × 109/L at the time of birth.

Quantitative first-principles calculations of valence and core excitation spectra of solid C60.

We present calculated valence and C 1s near-edge excitation spectra of solid C60 and experimental results measured with high-resolution electron energy-loss spectroscopy. The near-edge calculations are carried out using three different methods: solution of the Bethe-Salpeter equation (BSE) as implemented in the OCEAN suite (Obtaining Core Excitations with ab initio methods and the NIST BSE solver), the excited-electron core-hole approach (XCH), and the constrained-occupancy method using the Stockholm-Berlin core-excitation code, StoBe. The three methods give similar results and are in good agreement with experiment, though the BSE results are the most accurate. The BSE formalism is also used to carry out valence level calculations using the NIST Bethe-Salpeter Equation solver (NBSE). Theoretical results include self-energy corrections to the band gap and band widths, lifetime-damping effects, and Debye-Waller effects in the core-excitation case. A comparison of spectral features to those observed experimentally illustrates the sensitivity of certain features to computational details, such as self-energy corrections to the band structure and core-hole screening.

Preferential increase of glutathione S-transferase class alpha transcripts in cultured human hepatocytes by phenobarbital, 3-methylcholanthrene, and dithiolethiones.

In rodents, a diversity of compounds are able to protect against acute and chronic toxicities of various xenobiotics including carcinogens, at least in part through induction of drug-metabolizing enzymes including glutathione S-transferase (GST) enzymes. We have posed the question as to whether or not these compounds also induce GSTs in human liver. Primary human hepatocyte cultures were exposed to phenobarbital, 3-methylcholanthrene, and two dithiolethiones [1,2-dithiole-3-thione and its 5-(2-pyrazinyl)-4-methyl derivative, oltipraz], and steady-state mRNA levels of GST classes alpha, mu, and pi were determined by Northern blot analysis. After 3 daily treatments, the two dithiolethiones were the most potent inducers; phenobarbital was also effective but to a lesser extent and 3-methylcholanthrene increased GST mRNA in only 2 of the 6 samples, although it stimulated cytochrome P-450 1A2 mRNA in all cell preparations. Whatever the compound only GSTA1 and/or A2 transcripts were induced. GST M1 mRNAs were not responsive or only slightly responsive, and GST P1 mRNAs, which were mostly undetectable in control cells, were not affected by treatment with any of the four chemicals. Large individual variations were observed in the level of induction of GST A1 and/or A2 mRNAs, and no sex difference could be demonstrated. These results clearly indicate that phenobarbital, 3-methylcholanthrene, and dithiolethiones are able to markedly increase mRNA levels of GST in human hepatocytes and that the GST alpha class is preferentially involved.

Tissue engineering with gellan gum.

Engineering complex tissues for research and clinical applications relies on high-performance biomaterials that are amenable to biofabrication, maintain mechanical integrity, support specific cell behaviours, and, ultimately, biodegrade. In most cases, complex tissues will need to be fabricated from not one, but many biomaterials, which collectively fulfill these demanding requirements. Gellan gum is an anionic polysaccharide with potential to fill several key roles in engineered tissues, particularly after modification and blending. This review focuses on the present state of research into gellan gum, from its origins, purification and modification, through processing and biofabrication options, to its performance as a cell scaffold for both soft tissue and load bearing applications. Overall, we find gellan gum to be a highly versatile backbone material for tissue engineering research, upon which a broad array of form and functionality can be built.

Pinocytic loading of cytochrome c into intact cells specifically induces caspase-dependent permeabilization of mitochondria: evidence for a cytochrome c feedback loop.

Previous studies introduced cytochrome c into intact cells via the disruptive techniques of microinjection or electroporation to provide support for the hypothesis that, in whole cells, cytochrome c release from mitochondria triggers caspase activation and other degradative changes. However, the types of measurements that could be undertaken with these techniques was limited. We used the simple and relatively gentle technique of pinocytic loading to demonstrate that, in intact cells, cytosolic cytochrome c specifically induced activation of caspase-3- and -9-like enzymes, and a loss of mitochondrial polarization coincident with an increase in mitochondrial permeability. Our results support the prediction from in vitro studies that activation of caspases-3 and -9 is downstream of cytochrome c release and provide the first direct evidence that, in whole cells, cytochrome c-dependent caspase-activation can exert a feedback effect to elicit mitochondrial permeabilization and collapse of the mitochondrial trans-membrane potential.

Peptide modification of purified gellan gum.

Gellan gum (GG) is an anionic polysaccharide with potential as a biopolymer for additive manufacturing (3D-bioprinting) and tissue engineering. Previous studies have shown GG to be highly cytocompatible, but lacking specific attachment sites required for anchorage-dependent cells. In this work, we modify purified-GG polymer with a short peptide containing the arginine-glycine-aspartic acid (RGD) sequence that is known to enhance integrin-mediated cell attachment. Radiolabelling of the peptide was used in optimisation of the conjugation procedure to achieve an overall efficiency of 40%. The purification of divalent cations from commercial GG samples was found to be critical for successful conjugation. Rheological studies revealed that the peptide coupling did not prevent gelation behaviour. C2C12 cells showed improved attachment on the surface of and encapsulated within RGD-GG hydrogels, differentiating to multinucleated myofibers after 5-7 days. PC12 cells showed minimal interactions with both GG and RGD-GG, with formation of cell clusters and impedance of terminal differentiation and neurite extension.

Impact of field-transmitted electrocardiography on time to in-hospital thrombolytic therapy in acute myocardial infarction.

To assess the impact of a field-transmitted electrocardiogram (ECG) on patients with possible acute myocardial infarction, randomized and open trials were performed with a portable electrocardiographic system coupled with a cellular phone programmed to automatically transmit ECGs to the base hospital. Consecutive patients served by the 6 units of the Salt Lake City Emergency Rescue System were studied; 71 patients were randomized to in-field ECG (n = 34) versus no ECG (n = 37). Time on scene was 16.4 +/- 9.7 minutes for the ECG group versus 16.1 +/- 7.0 minutes for the non ECG group (difference not significant). Time of transport averaged 18.2 +/- 9.9 and 17.6 +/- 13.1 minutes, respectively (difference not significant). Six of 34 patients with in-field ECG showed acute myocardial infarction, qualified for and received thrombolytic therapy at 48 +/- 12 minutes after hospital arrival (range 30 to 60) compared with 103 +/- 44 minutes (p less than 0.01) for 51 historical control patients and 68 +/- 29 minutes for 6 concurrent control patients without in-field ECG. Thus, in-field ECG causes negligible delays in paramedic time, leads to significant decreases in time to in-hospital thrombolysis and may make in-field therapy feasible. In-field ECG may be an important addition to reperfusion strategies.

Androgen and oestrogen responsiveness of stromal cells derived from the human hyperplastic prostate: oestrogen regulation of the androgen receptor.

Stromal cells derived from collagenase-digested benign hyperplastic adult prostates were isolated and grown in culture. Androgen and oestrogen receptor status were determined and growth in response to mibolerone (a synthetic androgen) and oestradiol-17 beta was measured. In addition, the ability of oestrogens to regulate the androgen receptor in stromal cells was investigated. [3H]Thymidine incorporation into DNA was stimulated by mibolerone in primary and secondary cultures, but sensitivity was lost with subsequent passages. Androgen stimulation of [3H]thymidine incorporation was consistently inhibited by the anti-androgen cyproterone acetate. Oestradiol-17 beta also stimulated [3H]thymidine incorporation into DNA, and this effect was inhibited by the anti-oestrogen tamoxifen. Sensitivity to oestradiol was lost with subsequent passages. A combination of mibolerone and oestradiol was not synergistic in increasing [3H]thymidine incorporation into DNA, but maximal stimulation occurred at 100-fold lower concentrations of mibolerone and oestradiol when the two hormones were applied in combination. Specific high-affinity [3H]mibolerone- and [3H]oestradiol-binding sites were demonstrated by radioligand binding in intact cells. The affinity for oestradiol binding to its receptor exceeded that quantified for mibolerone binding to the androgen receptor, whilst the number of oestradiol-binding sites was approximately tenfold less than that quantified for mibolerone. Treatment with oestradiol down-regulated the number of [3H]mibolerone binding sites 1.7-fold (P < 0.005) as early as day 2 after oestradiol treatment. In conclusion, we successfully cultured stromal cells derived from hyperplastic prostates which retained sensitivity to androgen and oestrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of an important thyrotrophin binding site on the human thyrotrophin receptor using monoclonal antibodies.

A thyrotrophin (TSH) binding site has been identified on the extracellular domain of the human thyrotrophin receptor (hTSHR) using monoclonal antibodies that recognise the native hTSHR. These antibodies were produced by immunising BALB/c mice with denatured recombinant material, selected by their reaction with recombinant hTSHR expressed on heterologous cell lines using flow cytofluorimetric analysis, and characterised by immunoblotting and immunoprecipitation. The epitopes the monoclonal antibodies recognise were determined using multiple overlapping synthetic peptides. All of the antibodies reacted with epitopes within the region 335-390; these epitopes must be accessible on the external surface of the native hTSHR. None of the antibodies stimulated cAMP production of recombinant hTSHR cell lines. The epitopes of two antibodies (residues 337-342 and 355-358) are in the small peptide thought to be removed by proteolytic processing of hTSHR. A further five different antibodies (determined from their variable region sequences) all reacted with residues 381-384 emphasising the immunogenicity of this region. The functional importance of residues 381-384 as a TSH binding site was shown by the fact that some of these monoclonal antibodies caused inhibition of radiolabelled TSH binding of 80-90% at 1 microg/ml and greater than 50% inhibition at 0.1 microg/ml (0.65 nM--i.e. comparable in effectiveness with TSH itself). Residues 381-384 may form part of the target regions recognised by inhibitory autoantibodies found in Graves' disease.

Validation of a photographic method of measuring corneal diameter.

A photographic method for measuring corneal diameter using the Medical-Nikkor f200 mm lens is described. Measurements were compared with those obtained by calipers (46 eyes of 25 patients) and by placing a ruler either near the eye (123 eyes of 64 patients) or on the nose (98 eyes of 55 patients). Over all we found good correlation between photographic and caliper measurements (r = 0.94). No significant correlation was found between photographic measurements and estimates made with the ruler either near the eye or on the nose (r = 0.65 and 0.31 respectively). Modifications to our system are suggested which may provide an accurate, simple, non-invasive method of measuring corneal diameter in ophthalmic clinics.

Olfactory and nonolfactory odor detection in pigeons: elucidation by a cardiac acceleration paradigm.

A technique for the Pavlovian conditioning of cardiac acceleration in response to odorants was developed and used to compare the sensitivity of pigeons to four odorants before and after resection of the olfactory nerves. This method provided quite reliable psychophysical functions yet required relatively little training time. Thresholds of normal pigeons to n-amyl acetate, n-butyl acetate, benzaldehyde and butanol were approximately 10(-4), 10(-5), 10(-3.3) and 10(-4.3) of vapor saturation, respectively. Following resection surgery, sensitivity decreased by 2 to 4 log units. When transection of the ophthalmic branch of the trigeminal nerve was combined with olfactory nerve resection, little evidence of a further decline in odor sensitivity was seen. Based on these results each of these compounds could be used, at concentrations below the postoperative threshold, to study, in isolation, both normal and reconstituting olfactory systems in the pigeon.