Nematic phases and elastoresistivity from a multiorbital non-Fermi liquid.

We propose and study a two-orbital lattice extension of the Sachdev-Ye-Kitaev model in the large-N limit. The phase diagram of this model features a high-temperature isotropic non-Fermi liquid which undergoes first-order thermal transition into a nematic insulator or continuous thermal transition into a nematic metal phase, separated by a tunable tricritical point. These phases arise from spontaneous partial orbital polarization of the multiorbital non-Fermi liquid. We explore the spectral and transport properties of this model, including d.c. elastoresistivity, which exhibits a peak near nematic transition, as well as nonzero frequency elastoconductivity. Our work offers a useful perspective on nematic phases and transport in correlated multiorbital systems.

Survey of procedural and resuscitation requirements for paediatricians working in a non-tertiary centre: Implications for training.

AIM: There are minimal data to guide the continuing medical education (CME) of general paediatricians working in non-tertiary hospitals. The aim of this study was to determine the procedural and resuscitation skills required by non-tertiary paediatricians and the frequency with which these skills are utilised. METHODS: Over a 12-month period (December 2012 to December 2013), each of the 11 paediatricians involved in acute inpatient care at University Hospital Geelong (UHG) completed a weekly online survey regarding their inpatient clinical experience. This included procedures performed or directly supervised as well as their resuscitation involvement. RESULTS: Each of the 11 paediatricians who managed inpatients on a regular or semi-regular basis during the study period agreed to participate, and each completed all of the weekly surveys. There were seven UHG paediatricians with an inpatient appointment (each with a 0.27 full-time equivalent (FTE) paediatrician workload) and four paediatricians providing inpatient cover on a locum basis. Over the course of 12 months, each 0.27 FTE paediatrician was, on average, involved in 11.3 neonatal, 1.7 infant and 2.4 child resuscitations and performed 0.9 intubations. CONCLUSIONS: Paediatricians working at non-tertiary hospitals are required to perform and supervise critical procedural and resuscitation skills but have limited opportunities to maintain proficiency in such skills. General paediatric training and consultant paediatrician CME programmes should ensure the acquisition and maintenance of the procedural and resuscitation skills required for the management of seriously ill children in non-tertiary acute care settings.

Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.

Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Aß) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Aß levels was detected.

Per capita increase in hospital presentations and admissions among children since the 1990s.

AIM: Data regarding temporal trends in per capita paediatric hospital presentations and admissions are required to inform health system and workforce planning. METHODS: Emergency Department (ED) presentations and admissions to the University Hospital Geelong among patients aged 0 to 16 years over a 12-month period (2012-2013) were determined by review of hospital records and then compared with similar data collected during 1996/1997.1 During each period, the Geelong region was serviced by a single ED, enabling us to estimate per capita presentation and admission rates. RESULTS: Since 1996/1997, per capita paediatric presentations to the ED increased from 643 to 1837 per 10 000 (186%; 95% confidence interval 181% to 191%). Moreover, the proportion of paediatric ED presentations resulting in hospital admission increased from 12.3% to 18.3% (49%; 95% confidence interval 39% to 59%). CONCLUSIONS: There has been a substantial absolute and per capita increase in paediatric ED presentations and hospital admissions since the 1990s. These trends place an increasing burden on the public hospital system, and strategies are required to promote paediatric acute care in the ambulatory setting.

Combined effect of antiretroviral therapy and blockade of IDO in SIV-infected rhesus macaques.

Increased activity of IDO, which catalyzes the degradation of Trp into kynurenine (Kyn), is observed during HIV/SIV infection, and it may contribute to the persistence of HIV/SIV by suppressing antiviral T cell responses. We administered the IDO inhibitor 1-methyl-d-tryptophan (d-1mT) for 13 days to SIV-infected rhesus macaques receiving antiretroviral therapy (ART). d-1mT treatment increased the plasma levels of Trp, without reducing the levels of Kyn, suggesting only a partial effect on IDO enzymatic activity. Surprisingly, d-1mT significantly reduced the virus levels in plasma and lymph nodes of ART-treated animals with incomplete responsiveness to ART. In SIV-infected animals that were not receiving ART, d-1mT was ineffective in reducing the plasma viral load and had only a marginal effect on the plasma Kyn/Trp ratio. Increased IDO and TGF-beta mRNA expression in lymph nodes of ART-treated macaques after d-1mT treatment suggested that compensatory counterregulatory mechanisms were activated by d-1mT, which may account for the lack of effect on plasma Kyn. Finally, d-1mT did not interfere with the ART-induced T cell dynamics in lymph nodes (increased frequency of total CD4 T cells, increase of CD8 T cells expressing the antiapoptotic molecule Bcl2, and reduction of regulatory T cells). Thus, d-1mT appeared to synergize with ART in inhibiting viral replication and did not interfere with the beneficial immunologic effects of ART. Further studies are required to elucidate the immunologic or virologic mechanism by which d-1mT inhibited SIV replication in vivo.

Audit of vaccination status of health-care workers who tested positive for SARS-CoV-2.

Multiple SARS-CoV-2 vaccinations have shown excellent efficacy during clinical trials. However, post vaccine surveillance is important to confirm 'real-world' findings of vaccine efficacy and safety. It is therefore imperative to identify individuals that become infected with SARS-CoV-2 post vaccination. We investigated the vaccination status of staff that had tested positive in a cohort of healthcare workers in one large tertiary hospital in the UK. At the time of the investigation, 8th December 2020 to 13th March 2021, 11,871 staff had been vaccinated and 225 staff tested positive for SARS-CoV-2. This period coincided with the second wave of SARS-CoV-2 infections in the UK which was driven by the Alpha variant. No healthcare workers who were double vaccinated had a positive PCR test for SARS-CoV-2 during this study period confirming vaccination with Pfizer BioNTec BNT162b2 gives excellent protection against infection of this variant.

Development of a web-based training programme for respiratory physicians in Yorkshire.

This article describes the establishment of a web-based training programme for postgraduate respiratory trainees. A pilot survey assessed trainees' experiences of online learning. All trainees had used the internet for work-related purposes with commonly used resources being Google, national society websites and specialty journals. A modular training programme based on article review, multiple choice questions (MCQs) and a reflective feedback exercise was subsequently established and trainees' experiences reviewed at three and 15 months. Trainees found that topics covered were appropriate, contained novel information and subjectively impacted on practice. Common problems were technical difficulties accessing the site (37%) and journal articles (74%), ambiguity of MCQs and difficulty finding time during normal working hours to complete modules. Trainees felt that feedback from MCQs and discussion with colleagues and their educational supervisor were useful methods to support their learning, but did not find the self-reflection exercise helpful.

The compliance and cost-effectiveness of smartphone urinalysis albumin screening for people with diabetes in England.

BACKGROUND: People with diabetes are at increased risk of developing chronic kidney disease (CKD) and should undergo annual screening, but adherence is poor. A home urinalysis self-test has been developed to improve compliance with screening. The objective of this paper is to report on a clinical evaluation and economic analysis of home urinalysis self-testing. RESEARCH DESIGN AND METHODS: People with diabetes who had not undergone screening within the previous 18 months were recruited to a single-arm clinical evaluation to assess the uptake and compliance of home urinalysis self-testing. An economic evaluation assessed the likely cost-consequences of the use of home urinalysis self-testing over a lifetime time horizon. RESULTS: A total of 2,196 people with diabetes were contacted as part of the clinical evaluation. Of these, 695 people agreed to be sent a home urinalysis self-testing kit and 499 people completed and returned the test. Cost savings of £2,008 per person were estimated over a lifetime due to increased CKD diagnosis and reduced progression to end stage renal disease. CONCLUSIONS: Home urinalysis self-testing of ACR in people with diabetes is estimated to be a cost-effective use of NHS resources in England in people who would otherwise not comply with standard care.

Fast camera spatial characterization of photonic polarization entanglement.

Scalable technologies to characterize the performance of quantum devices are crucial to creating large quantum networks and quantum processing units. Chief among the resources of quantum information processing is entanglement. Here we describe the full temporal and spatial characterization of polarization-entangled photons produced by Spontaneous Parametric Down Conversions using an intensified high-speed optical camera, Tpx3Cam. This novel technique allows for precise determination of Bell inequality parameters with minimal technical overhead, and for new characterization methods for the spatial distribution of entangled quantum information. The fast-optical camera could lead to multiple applications in Quantum Information Science, opening new perspectives for the scalability of quantum experiments.

Antiretroviral activity of the aminothiol WR1065 against Human Immunodeficiency virus (HIV-1) in vitro and Simian Immunodeficiency virus (SIV) ex vivo.

BACKGROUND: WR1065 is the free-thiol metabolite of the cytoprotective aminothiol amifostine, which is used clinically at very high doses to protect patients against toxicity induced by radiation and chemotherapy. In an earlier study we briefly reported that the aminothiol WR1065 also inhibits HIV-1 replication in phytohemagglutinin (PHA)-stimulated human T-cell blasts (TCBs) infected in culture for 2 hr before WR1065 exposure. In this study we expanded the original observations to define the dose-response curve for that inhibition, and address the question of additive effects for the combination of WR1065 plus Zidovudine (AZT). Here we also explored the effect of WR1065 on SIV by examining TCBs taken from macaques with well-established infections several months with SIV. RESULTS: TCBs from healthy human donors were infected for 2 hr with HIV-1, and viral replication (p24) was measured after 72 hr of incubation with or without WR1065, AZT, or both drugs. HIV-1 replication, in HIV-1-infected human TCBs, was inhibited by 50% at 13 microM WR1065, a dose at which 80% of the cells were viable. Cell cycle parameters were the same or equivalent at 0, 9.5 and 18.7 microM WR1065, showing no drug-related toxicity. Combination of AZT with WR1065 showed that AZT retained antiretroviral potency in the presence of WR1065. Cultured CD8+ T cell-depleted PHA-stimulated TCBs from Macaca mulatta monkeys chronically infected with SIV were incubated 17 days with WR1065, and viral replication (p27) and cell viability were determined. Complete inhibition (100%) of SIV replication (p27) was observed when TCBs from 3 monkeys were incubated for 17 days with 18.7 microM WR1065. A lower dose, 9.5 microM WR1065, completely inhibited SIV replication in 2 of the 3 monkeys, but cells from the third macaque, with the highest viral titer, only responded at the high WR1065 dose. CONCLUSION: The study demonstrates that WR1065 and the parent drug amifostine, the FDA-approved drug Ethyol, have antiretroviral activity. WR1065 was active against both an acute infection of HIV-1 and a chronic infection of SIV. The data suggest that the non-toxic drug amifostine may be a useful antiretroviral agent given either alone or in combination with other drugs as adjuvant therapy.

The Impact of a Newly Established Multidisciplinary Team on the Interventional Treatment of Patients With Emphysema.

BACKGROUND: The emphysema interventional treatment involves mainly lung volume reduction surgery (LVRS) and endobronchial valve (EBV) implantation. Few institutes discuss these cases at a dedicated emphysema multidisciplinary team (MDT) meeting. OBJECTIVES: To investigate the impact of a newly established dedicated emphysema MDT meeting on the interventional treatment of such patients. METHODS: During a study period of 4 years, the outcome of 44 patients who underwent intervention according to the proposal of the emphysema MDT (group A) was compared with the outcome of 44 propensity score matched patients (group B) treated without the emphysema MDT proposal. RESULTS: More LVRS and less EBV insertions were performed in group A (P = .009). In group B, the interventions were performed sooner than in group A (P = .003). Postoperative overall morbidity and length of in-hospital stay were similar in the 2 groups (P = .918 and .758, respectively). Improvement of breathing ability was reported in more patients from group A (P = .012). In group B, the total number of re-interventions was higher (P = .001) and the time to re-intervention had the tendency to be less (P = .069). Survival was similar between the 2 groups (P = .884). Intervention without discussion at the MDT and EBV as initial intervention was an independent predictor of re-intervention. CONCLUSIONS: Interventional treatment for patients with chronic obstructive pulmonary disease (COPD) after discussion at a dedicated MDT involved more LVRS performed, required fewer interventions for their disease, and had longer re-intervention-free intervals and better breathing improvement.

PDL-1 upregulation on monocytes and T cells by HIV via type I interferon: restricted expression of type I interferon receptor by CCR5-expressing leukocytes.

The programmed death (PD)-1 interacts with its ligand (PDL-1) delivering a negative signal to T cells. During human immunodeficiency virus (HIV)-1 infection PD-1 and PDL-1 expressions are increased. Here we show that monocytes and CCR5(+) T cells of HIV-uninfected donors upregulated PDL-1 upon in vitro exposure to HIV. HIV-induced PDL-1 required interferon (IFN)-alpha, but not IFN-gamma, production. Inhibition of endocytosis, required for HIV-induced IFN-alpha production, prevented PDL-1 upregulation. IFN-alpha-inducing Toll-like receptor (TLR) agonists increased PDL-1 on monocytes and CCR5(+) T cells. CD80 and CD86 were also increased on monocytes and CCR5(+) T cells after HIV exposure, but only CD80 was IFN-alpha-dependent. IFN-alpha-receptor subunit 2 (IFNAR2), was expressed only by CCR5(+) T cells and monocytes, explaining why these leukocytes responded to HIV-induced IFN-alpha. Finally, T cell proliferation was improved by PDL-1 blockade in HIV-treated PBMC. In the setting of HIV infection, IFN-alpha may negatively affect T cell responses by inducing PDL-1.

A study of the chemical composition of traditional eye cosmetics ("kohls") used in Qatar and Yemen.

This study looks at the chemical composition of traditional eye cosmetics ("kohls") used in Qatar and Yemen. Of especial interest was how many samples in each country contain the toxic element lead. In Qatar 19 observably different kohl samples were obtained, and in Yemen ten such samples obtained. The analytical techniques of scanning electron microscopy (SEM) and X-ray powder diffraction (XRPD) were used to study the samples. For the samples from Qatar, six of the 19 (32%) contained galena (lead sulfide, PbS)--all as the main component. However, for the samples from Yemen, five of the ten (50%) samples contained galena as the main component, with another three having it present as a minor component. Overall, the other main components were found to be: amorphous carbon (3), iron oxides (hematite, Fe2O3; and goethite, FeO(OH)) (1), quartz (SiO2) (1), sassolite (H3BO3) (5), talc (Mg3Si4O10(OH)2) (1), and zincite (ZnO) (7).

Scalp electrical recording during paralysis: quantitative evidence that EEG frequencies above 20 Hz are contaminated by EMG.

OBJECTIVE: To identify the possible contribution of electromyogram (EMG) to scalp electroencephalogram (EEG) rhythms at rest and induced or evoked by cognitive tasks. METHODS: Scalp EEG recordings were made on two subjects in presence and absence of complete neuromuscular blockade, sparing the dominant arm. The subjects undertook cognitive tasks in both states to allow direct comparison of electrical recordings. RESULTS: EEG rhythms in the paralysed state differed significantly compared with the unparalysed state, with 10- to 200-fold differences in the power of frequencies above 20 Hz during paralysis. CONCLUSIONS: Most of the scalp EEG recording above 20 Hz is of EMG origin. Previous studies measuring gamma EEG need to be re-evaluated. SIGNIFICANCE: This has a significant impact on measurements of gamma rhythms from the scalp EEG in unparalysed humans. It is to be hoped that signal separation methods will be able to rectify this situation.