Commensurate and incommensurate 1D interacting quantum systems.

Single-atom imaging resolution of many-body quantum systems in optical lattices is routinely achieved with quantum-gas microscopes. Key to their great versatility as quantum simulators is the ability to use engineered light potentials at the microscopic level. Here, we employ dynamically varying microscopic light potentials in a quantum-gas microscope to study commensurate and incommensurate 1D systems of interacting bosonic Rb atoms. Such incommensurate systems are analogous to doped insulating states that exhibit atom transport and compressibility. Initially, a commensurate system with unit filling and fixed atom number is prepared between two potential barriers. We deterministically create an incommensurate system by dynamically changing the position of the barriers such that the number of available lattice sites is reduced while retaining the atom number. Our systems are characterised by measuring the distribution of particles and holes as a function of the lattice filling, and interaction strength, and we probe the particle mobility by applying a bias potential. Our work provides the foundation for preparation of low-entropy states with controlled filling in optical-lattice experiments.

Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.

BACKGROUND: In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD. METHODS: Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD. The minimum immunological evaluation comprised a full blood examination and film, serum immunoglobulins (IgG, IgA and IgM), complement levels and function. Included participants were children in whom Streptococcus pneumoniae was isolated from a normally sterile site (cerebrospinal fluid, pleura, peritoneum and synovium). If isolated from blood, features of sepsis needed to be present. Children with predisposing factors for IPD (nephrotic syndrome, anatomical defect or malignancy) were excluded. RESULTS: Overall, there were 379 episodes of IPD of which 313 (83%) were eligible for inclusion and 143/313 (46%) had an immunologic evaluation. Of these, 17/143 (12%) were diagnosed with a clinically significant abnormality: hypogammaglobulinemia (n = 4), IgA deficiency (n = 3), common variable immunodeficiency (n = 2), asplenia (n = 2), specific antibody deficiency (n = 2), incontinentia pigmenti with immunologic dysfunction (n = 1), alternative complement deficiency (n = 1), complement factor H deficiency (n = 1) and congenital disorder of glycosylation (n = 1). The number needed to investigate to identify 1 child presenting with IPD with an immunologic abnormality was 7 for children under 2 years and 9 for those 2 years old and over. CONCLUSIONS: This study supports the routine immune evaluation of children presenting with IPD of any age, with consideration of referral to a pediatric immunologist.

A simplified, amplicon-based method for whole genome sequencing of human respiratory syncytial viruses.

BACKGROUND: Human Respiratory Syncytial Virus (RSV) infections pose a significant risk to human health worldwide, especially for young children. Whole genome sequencing (WGS) provides a useful tool for global surveillance to better understand the evolution and epidemiology of RSV and provide essential information that may impact on antibody treatments, antiviral drug sensitivity and vaccine effectiveness. OBJECTIVES: Here we report the development of a rapid and simplified amplicon-based one-step multiplex reverse-transcription polymerase chain reaction (mRT-PCR) for WGS of both human RSV-A and RSV-B viruses. STUDY DESIGN: Two mRT-PCR reactions for each sample were designed to generate amplicons for RSV WGS. This new method was tested and evaluated by sequencing 206 RSV positive clinical samples collected in Australia in 2020 and 2021 with RSV Ct values between 10 and 32. RESULTS: In silico analysis and laboratory testing revealed that the primers used in the new method covered most of the currently circulating RSV-A and RSV-B. Amplicons generated were suitable for both Illumina and Oxford Nanopore Technologies (ONT) NGS platforms. A success rate of 83.5% with a full coverage for the genome of 98 RSV-A and 74 RSV-B was achieved from all clinical samples tested. CONCLUSIONS: This assay is simple to set up, robust, easily scalable in sample preparation and relatively inexpensive, and as such, provides a valuable addition to existing NGS RSV WGS methods.

Clinical and Health System Impact of Biofire Filmarray Meningitis/Encephalitis Routine Testing of CSF in a Pediatric Hospital: An Observational Study.

BACKGROUND: Rapid cartridge-based molecular test panels targeting multiple pathogens are increasingly available, improve pathogen detection and reduce turn-around-time but are more expensive than standard testing. Confirmation that these test panels contribute to improved patient or health service outcomes is required. METHODS: In March 2021, our pediatric hospital laboratory implemented the BioFire Filmarray™ meningitis/encephalitis (M/E) panel as an additional routine test for all cerebrospinal fluid (CSF) samples collected from infants <90 days or from any patient in the emergency department. A retrospective chart review was done to ascertain changes in clinical outcomes, antimicrobial prescribing practices, and hospital length of stay, comparing two discrete 6-month periods: preimplementation (March-August 2019) and postimplementation (March-August 2021). RESULTS: Both pre- and postimplementation groups were similar at baseline, except the preimplementation group had a higher proportion of infants with enterovirus and parechovirus meningitis. There was no significant difference between the groups in terms of median length of stay (2.94 vs 3.47 days, p = 0.41), duration of antibiotic treatment (2.0 vs 2.3 days, p = 0.25), need for central venous access (12.9% vs 17%, p = 0.38) or hospital-in-the-home admission (9.4% vs 9%, p = 0.92). A similar proportion of infants received aciclovir (33% vs 31%), however, a reduction in duration was observed (1.36 vs 0.90 days, p = 0.03) in the postimplementation period. CONCLUSIONS: Introduction of the Biofire Filmarray™ M/E panel for routine testing of CSF samples reduced the duration of antiviral prescribing but had only a minor impact on antibiotic prescribing practices or health service outcomes in our pediatric hospital. The introduction of new laboratory testing needs to be supported by a comprehensive stewardship program to see optimal outcomes from new testing platforms.

Practical quantum advantage in quantum simulation.

The development of quantum computing across several technologies and platforms has reached the point of having an advantage over classical computers for an artificial problem, a point known as 'quantum advantage'. As a next step along the development of this technology, it is now important to discuss 'practical quantum advantage', the point at which quantum devices will solve problems of practical interest that are not tractable for traditional supercomputers. Many of the most promising short-term applications of quantum computers fall under the umbrella of quantum simulation: modelling the quantum properties of microscopic particles that are directly relevant to modern materials science, high-energy physics and quantum chemistry. This would impact several important real-world applications, such as developing materials for batteries, industrial catalysis or nitrogen fixing. Much as aerodynamics can be studied either through simulations on a digital computer or in a wind tunnel, quantum simulation can be performed not only on future fault-tolerant digital quantum computers but also already today through special-purpose analogue quantum simulators. Here we overview the state of the art and future perspectives for quantum simulation, arguing that a first practical quantum advantage already exists in the case of specialized applications of analogue devices, and that fully digital devices open a full range of applications but require further development of fault-tolerant hardware. Hybrid digital-analogue devices that exist today already promise substantial flexibility in near-term applications.

Density Matrix Renormalization Group for Continuous Quantum Systems.

We introduce a versatile and practical framework for applying matrix product state techniques to continuous quantum systems. We divide space into multiple segments and generate continuous basis functions for the many-body state in each segment. By combining this mapping with existing numerical density matrix renormalization group routines, we show how one can accurately obtain the ground-state wave function, spatial correlations, and spatial entanglement entropy directly in the continuum. For a prototypical mesoscopic system of strongly interacting bosons we demonstrate faster convergence than standard grid-based discretization. We illustrate the power of our approach by studying a superfluid-insulator transition in an external potential. We outline how one can directly apply or generalize this technique to a wide variety of experimentally relevant problems across condensed matter physics and quantum field theory.

Risk factors for healthcare-associated infection among children in a low-and middle-income country.

BACKGROUND: Healthcare-associated infections (HAI) are one of significant causes of morbidity and mortality. Evaluating risk factors associated with HAI are important to improve clinical outcomes. We aimed to evaluate the risk factors of HAI in children in a low-to middle-income country. METHODS: A prospective cohort study was conducted during 43 months at a teaching hospital in Yogyakarta, Indonesia. All consecutive patients admitted to pediatric ICU and pediatric wards > 48 h were eligible. Those eligible patients were observed daily to identify the presence of HAI based on CDC criteria. The risk factors of HAI were identified. Multivariable logistic regression was used to identify independent risk factors. RESULTS: Total of 2612 patients were recruited. Of 467 were diagnosed as HAI. The cumulative incidence of HAI was 17.9%. In the multivariable analysis; length of stay > 7 days, severe sepsis, use of urine catheter, central venous catheter (CVC), non-standardized antibiotics, and aged < 1 year were independently associated with increased risk of HAI with adjusted OR (95%CI): 5.6 (4.3-7.3), 1.9 (1.3-2.9), 1.9 (1.3-2.6), 1.8 (1.1-2.9), 1.6 (1.2-2.0), and 1.4 (1.1-1.8), respectively. CONCLUSIONS: This study found that length of stay > 7 days, use of urine catheter and CVC, non-standardized antibiotic use, aged < 1 year, and had a diagnosis of severe sepsis increased risk of HAI.

The 2018 annual cost burden for children under five years of age hospitalised with respiratory syncytial virus in Australia.

ABSTRACT: Respiratory syncytial virus (RSV) is one of the principal causes of acute bronchiolitis and respiratory tract infections in young children. Routine RSV surveillance in Australian children is limited; vaccines are in late stage development; prophylactic monoclonal antibody (mAb) treatment is available but expensive; and there has been uncertainty around the cost burden. The objective of this study was to determine the annual cost burden for children under five years of age hospitalised with RSV in a single health service in 2018, with national extrapolation based on published Australian prevalence data. The methods utilised individual patient-level cost data prospectively collected for hospitalised children under five years of age in a tertiary Melbourne paediatric hospital. Results were extrapolated to all Australian children under five years of age to determine the national annual health cost burden, from a healthcare sector perspective over a 12 month time horizon. The results included 363 children with a mean age of 9.2 months (standard deviation, SD: 8.5 months). The mean cost per child was $17,120 (SD: $37,562), with a combined health service cost of $6,214,439. The reported Australian hospitalisation rate for RSV in the target age group ranged from 2.2 to 4.5 per 1,000 children under five years of age, resulting in a 2018 extrapolated cost range of $59,218,844-$121,129,453 for the estimated 3,459-7,075 children affected (combined index and all-cause six-month readmissions). This study concluded that RSV represents a significant cost burden to Australia's health care system. These data are important for future health economic assessments of preventative therapies, such as new RSV mAb treatments and maternal/childhood RSV vaccines, and provides valuable insights to inform health care planning and health policy.

Identifying a therapeutic target for vancomycin against staphylococci in young infants.

OBJECTIVES: To determine the therapeutic target of vancomycin in young infants with staphylococcal infections. METHODS: Retrospective data were collected for infants aged 0 to 90 days with CoNS or MRSA bacteraemia over a 4 year period at the Royal Children's Hospital Melbourne, Australia. Vancomycin broth microdilution MICs were determined. A published pharmacokinetic model was externally validated using the study dataset and a time-to-event (TTE) pharmacodynamic model developed to link the AUC of vancomycin with the event being the first negative blood culture. Simulations were performed to determine the trough vancomycin concentration that correlates with a 90% PTA of the target AUC24. RESULTS: Thirty infants, 28 with CoNS and 2 with MRSA bacteraemia, who had 165 vancomycin concentrations determined were included. The vancomycin broth microdilution MIC was determined for 24 CoNS and 1 MRSA isolate, both with a median MIC of 1 mg/L (CoNS range = 0.5-4.0). An AUC0-24 target of ≥300 mg/L·h or AUC24-48 of ≥424 mg/L·h. increased the chance of bacteriological cure by 7.8- and 7.3-fold, respectively. However, AUC0-24 performed best in the pharmacokinetic-pharmacodynamic model. This correlates with 24 to 48 h trough concentrations of >15-18 mg/L and >10-15 mg/L for 6- and 12-hourly dosing, respectively, and can be used to guide vancomycin therapy in this population. CONCLUSIONS: An AUC0-24 ≥300 mg/L·h or AUC24-48 ≥424 mg/L·h was associated with an increase in bacteriological cure in young infants with staphylococcal bloodstream infections.

Feasibility and acceptability of targeted salivary cytomegalovirus screening through universal newborn hearing screening.

AIM: This study aimed to determine the feasibility and parental acceptability of screening for congenital cytomegalovirus (cCMV) through saliva polymerase chain reaction in infants who did not pass their newborn hearing screening. Additionally, the utility (i.e. time to diagnosis and treatment) of this enhanced clinical pathway was evaluated. METHODS: The study was conducted through the Victorian Infant Hearing Screening Programme (VIHSP) across four maternity hospitals in Melbourne, Australia, during June 2019-March 2020. Parents were approached by VIHSP staff about obtaining a test for cytomegalovirus (CMV) at the time of their baby's second positive ('refer') result on the VIHSP screen. Participating parents collected a saliva swab for CMV polymerase chain reaction from their infants. Feasibility was determined by the proportion of 'referred' infants whose parents completed the salivary CMV screening test ≤21 days of life. Acceptability was measured through parent survey. RESULTS: Of 126 eligible families, 96 (76.0%) had salivary screening swabs taken ≤21 days of life. Most families (>92.0%) indicated that screening was acceptable, straightforward and thought testing their baby for cCMV was a good idea. One infant screened positive on day 30, was diagnosed with cCMV via confirmatory testing by day 31 and commenced valganciclovir on day 32. CONCLUSIONS: Obtaining a saliva sample to screen for cCMV in infants who do not pass their newborn hearing screen is feasible and appears acceptable to parents. This targeted cCMV screening method could be an option where mothers are rapidly discharged from hospital, especially in the context of the COVID-19 pandemic.

Breastfeeding and Risk of Late-Onset Group B Streptococcal Disease.

BACKGROUND: Group B Streptococcus (GBS) is a major contributor to neonatal sepsis worldwide. Late-onset group B Streptococcus disease (LOGBS) and its risk factors remain poorly understood. The isolation of GBS from breast milk has been described in cases of LOGBS. This potential association has raised concerns for mothers and clinicians regarding the safety of ongoing breastfeeding. In this study, we aimed to investigate whether exposure to breast milk is associated with increased risk of LOGBS. METHODS: A case-control study of LOGBS was conducted across 4 hospital networks in Victoria, Australia, including the 2 major tertiary pediatric centers in the state, to evaluate 11 years of data (2007-2017). Cases were captured initially from microbiology databases and recaptured with International Classification of Diseases discharge coding. Each case patient was matched with 4 controls to assess feeding status. Patients were matched for chronological age, gestation, discharge status, recruitment site, and calendar year. RESULTS: We identified 92 cases of LOGBS: 73 cases on initial capture and 76 cases on the recapture analysis. Case patients were matched with 368 controls: 4 controls to each patient. Seventy-two patients were exposed to breast milk at the time of LOGBS (78.3%), compared with 274 controls (74.5%; odds ratio 1.2 [95% confidence interval 0.7-2.3]). CONCLUSIONS: Breastfeeding was not associated with increased risk of LOGBS. Breast milk should not be tested for GBS during a first episode of LOGBS.

COVID-19 public health measures and respiratory viruses in children in Melbourne.

AIM: To describe the epidemiology of respiratory viruses in children before and during the 2020 SARS-CoV-2 pandemic and the relationship to public health measures instituted by the Victorian government. METHODS: Retrospective audit of respiratory viruses at a tertiary paediatric hospital in Melbourne from January 2015 up to week 47, 2020 in children under 18 years of age. The proportion of positive cases in weeks 1-47 in 2015-2019 (period 1) were compared to weeks 1-47, 2020 (period 2), and reviewed in the context of public health restrictions in Victoria. RESULTS: An annual average of 4636 tests were performed in period 1 compared to 3659 tests in period 2. Proportions of positive influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human parainfluenza virus were significantly reduced in period 2 compared to period 1: 77.3, 89.4, 68.6 and 66.9% reductions, respectively (all P < 0.001). From week 12-47, 2020, 28 893 SARS-CoV-2 tests were performed with a 0.64% positivity rate. Influenza viruses were not detected after week 17, RSV was not detected after week 35. CONCLUSIONS: Strict public health measures and border closures were successful in eliminating community transmission of SARS-CoV-2 in Melbourne. This was associated with a significant reduction in other respiratory virus infections in children. Identifying sustainable and effective ongoing public health interventions to reduce transmission of RSV and influenza could result in reduced morbidity and mortality in children and requires further research.

Deterministic Fast Scrambling with Neutral Atom Arrays.

Fast scramblers are dynamical quantum systems that produce many-body entanglement on a timescale that grows logarithmically with the system size N. We propose and investigate a family of deterministic, fast scrambling quantum circuits realizable in near-term experiments with arrays of neutral atoms. We show that three experimental tools-nearest-neighbor Rydberg interactions, global single-qubit rotations, and shuffling operations facilitated by an auxiliary tweezer array-are sufficient to generate nonlocal interaction graphs capable of scrambling quantum information using only O(logN) parallel applications of nearest-neighbor gates. These tools enable direct experimental access to fast scrambling dynamics in a highly controlled and programmable way and can be harnessed to produce highly entangled states with varied applications.

Rapid detection of human respiratory syncytial virus A and B by duplex real-time RT-PCR.

Respiratory syncytial virus (RSV) is a common cause of acute respiratory disease worldwide, especially in young children. The World Health Organization (WHO) has initiated an RSV Surveillance Pilot program that aims to perform worldwide RSV surveillance, requiring the development of reliable and rapid molecular methods to detect and identify RSV. A duplex real-time RT-PCR assay developed for simultaneous detection of both A and B subtypes of RSV was included as part of this program. This duplex assay targeted a conserved region of the RSV polymerase gene and was validated for analytical sensitivity, specificity, reproducibility and clinical performance with a wide range of respiratory specimens. The assay was highly specific for RSV and did not react with non-RSV respiratory pathogens, including the SARS-CoV-2 virus.

Candidemia in Children: A 16-year Longitudinal Epidemiologic Study.

BACKGROUND: Candida species are the most common cause of systemic fungal infections in children. Risk factors for candidemia vary in different patient populations, posing challenges for clinical prediction of infection. We describe the epidemiology and clinical disease of candidemia in children admitted to a tertiary pediatric hospital. METHODS: Retrospective audit of children ≤18 years of age with candidemia at a tertiary pediatric hospital over a 16-year period. RESULTS: There were 139 episodes of candidemia in 124 children. A central venous catheter was present in 94% of episodes, prior antibiotic exposure in 86% and parenteral nutrition in 43%. During the study period, the proportion of candidemia due to non-albicans Candida spp. increased primarily due to a rise in C. krusei. Colonization with Candida spp. in the 30 days before developing candidemia was identified in 40% of episodes and the species was concordant in 60%. Infection at other sites was rare, including pulmonary dissemination (9/38, 24%), renal fungal disease (9/114, 8%), fungal endophthalmitis (8/102, 8%) and hepatosplenic nodules (5/92, 5%). Overall, 8/127 (6%) isolates were fluconazole-resistant (7 C. krusei and 1 C. glabrata) and 7/127 (6%) had intermediate susceptibility to fluconazole. The overall 30-day mortality was 12% and significant risk factors for mortality on multivariate analysis were male sex, liver disease and mucositis. CONCLUSIONS: Our study outlines low rates of disseminated candidiasis and low mortality associated with candidemia at our institution. Additionally, it suggests that prior colonization may be an important risk factor, however, this should be validated in large prospective controlled studies.

A case report describing the immune response of an infant with congenital heart disease and severe COVID-19.

Background: Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. Methods: We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. Results: Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. Conclusions: These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups.

Collisionally Inhomogeneous Bose-Einstein Condensates with a Linear Interaction Gradient.

We study the evolution of a collisionally inhomogeneous matter wave in a spatial gradient of the interaction strength. Starting with a Bose-Einstein condensate with weak repulsive interactions in quasi-one-dimensional geometry, we monitor the evolution of a matter wave that simultaneously extends into spatial regions with attractive and repulsive interactions. We observe the formation and the decay of solitonlike density peaks, counterpropagating self-interfering wave packets, and the creation of cascades of solitons. The matter-wave dynamics is well reproduced in numerical simulations based on the nonpolynomial Schrödinger equation with three-body loss, allowing us to better understand the underlying behavior based on a wavelet transformation. Our analysis provides new understanding of collapse processes for solitons, and opens interesting connections to other nonlinear instabilities.