The challenges of defining the human nasopharyngeal resistome

The nasopharynx is an important microbial reservoir for the emergence and spread of antibiotic-resistant organisms. The nasopharyngeal resistome is an extensive, adaptable reservoir of antibiotic-resistance genes (ARGs) within this niche. Metagenomic sequencing decodes the genetic material of all organisms within a sample using next-generation technologies, permitting unbiased discovery of novel ARGs and associated mobile genetic elements (MGEs). The challenges of sequencing a low-biomass bacterial sample have limited exploration of the nasopharyngeal resistome. Here, we explore the current understanding of the nasopharyngeal resistome, particularly the role of MGEs in propagating antimicrobial resistance (AMR), explore the advantages and limitations of metagenomic sequencing technologies and bioinformatic pipelines for nasopharyngeal resistome analysis, and highlight the key outstanding questions for future research

Artificial ferroic systems: novel functionality from structure, interactions and dynamics

Lithographic processing and film growth technologies are continuing to advance, so that it is now possible to create patterned ferroic materials consisting of arrays of sub-1 μm elements with high definition. Some of the most fascinating behaviour of these arrays can be realised by exploiting interactions between the individual elements to create new functionality. The properties of these artificial ferroic systems differ strikingly from those of their constituent components, with novel emergent behaviour arising from the collective dynamics of the interacting elements, which are arranged in specific designs and can be activated by applying magnetic or electric fields. We first focus on artificial spin systems consisting of arrays of dipolar-coupled nanomagnets and, in particular, review the field of artificial spin ice, which demonstrates a wide range of fascinating phenomena arising from the frustration inherent in particular arrangements of nanomagnets, including emergent magnetic monopoles, domains of ordered macrospins, and novel avalanche behaviour. We outline how demagnetisation protocols have been employed as an effective thermal anneal in an attempt to reach the ground state, comment on phenomena that arise in thermally activated systems and discuss strategies for selectively generating specific configurations using applied magnetic fields. We then move on from slow field and temperature driven dynamics to high frequency phenomena, discussing spinwave excitations in the context of magnonic crystals constructed from arrays of patterned magnetic elements. At high frequencies, these arrays are studied in terms of potential applications including magnetic logic, linear and non-linear microwave optics, and fast, efficient switching, and we consider the possibility to create tunable magnonic crystals with artificial spin ice. Finally, we discuss how functional ferroic composites can be incorporated to realise magnetoelectric effects. Specifically, we discuss artificial multiferroics (or multiferroic composites), which hold promise for new applications that involve electric field control of magnetism, or electric and magnetic field responsive devices for high frequency integrated circuit design in microwave and terahertz signal processing. We close with comments on how enhanced functionality can be realised through engineering of nanostructures with interacting ferroic components, creating opportunities for novel spin electronic devices that, for example, make use of the transport of magnetic charges, thermally activated elements, and reprogrammable nanomagnet systems

Switchable Adhesion of Soft Composites Induced by a Magnetic Field

Switchable adhesives have the potential to improve the manufacturing and recycling of parts and to enable new modes of motility for soft robots. Here, we demonstrate magnetically-switchable adhesion of a two-phase composite to non-magnetic objects. The composite's continuous phase is a silicone elastomer, and the dispersed phase is a magneto-rheological fluid. The composite is simple to prepare, and to mould to different shapes. When a magnetic field is applied, the magneto-rheological fluid develops a yield stress, which dramatically enhances the composite's adhesive properties. We demonstrate up to a nine-fold increase of the pull-off force of non-magnetic objects in the presence of a 250 mT field

Acute Bacterial Meningitis

Purpose of review Community-acquired bacterial meningitis is a continually changing disease. This review summarises both dynamic epidemiology and emerging data on pathogenesis. Updated clinical guidelines are discussed, new agents undergoing clinical trials intended to reduce secondary brain damage are presented. Recent findings Conjugate vaccines are effective against serotype/serogroup-specific meningitis but vaccine escape variants are rising in prevalence. Meningitis occurs when bacteria evade mucosal and circulating immune responses and invade the brain: directly, or across the blood–brain barrier. Tissue damage is caused when host genetic susceptibility is exploited by bacterial virulence. The classical clinical triad of fever, neck stiffness and headache has poor diagnostic sensitivity, all guidelines reflect the necessity for a low index of suspicion and early Lumbar puncture. Unnecessary cranial imaging causes diagnostic delays. cerebrospinal fluid (CSF) culture and PCR are diagnostic, direct next-generation sequencing of CSF may revolutionise diagnostics. Administration of early antibiotics is essential to improve survival. Dexamethasone partially mitigates central nervous system inflammation in high-income settings. New agents in clinical trials include C5 inhibitors and daptomycin, data are expected in 2025. Summary Clinicians must remain vigilant for bacterial meningitis. Constantly changing epidemiology and emerging pathogenesis data are increasing the understanding of meningitis. Prospects for better treatments are forthcoming

A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.

OBJECTIVE: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes. DESIGN: This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day. RESULTS: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]). CONCLUSION: There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis

Impairment of pneumococcal antigen specific isotype-switched IgG memory B-cell immunity in HIV infected Malawian adults

Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19+ CD27+ IgM+ IgD+) depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.Oluwadamilola H. Iwajomo, Adam Finn, Abiodun D. Ogunniyi, Neil A. Williams, Robert S. Heyderma

Focus on artificial frustrated systems

Frustration in physics is the inability of a system to simultaneously satisfy all the competing pairwise interactions within it. The past decade has seen an explosion of activity involving engineering frustration in artificial systems built using nanotechnology. The most common are the artificial spin ices that comprise arrays of nanomagnets with competing magnetostatic interactions. As well as being physical embodiments of idealized statistical mechanical models in which properties can be tuned by design, artificial spin ices can be studied using magnetic microscopy, allowing all the details of the microstates of these systems to be interrogated, both in equilibrium and when perturbed away from it. This 'focus on' collection brings together reports on the latest results from leading groups around the globe in this fascinating and fast-moving field

Non-adiabatic spin torque investigated using thermally activated magnetic domain wall dynamics

Using transmission electron microscopy, we investigate the thermally activated motion of domain walls (DWs) between two positions in permalloy (Ni80Fe20) nanowires at room temperature. We show that this purely thermal motion is well described by an Arrhenius law, allowing for a description of the DW as a quasi-particle in a 1D potential landscape. By injecting small currents, the potential is modified, allowing for the determination of the non-adiabatic spin torque: the non-adiabatic coefficient is 0.010 +/- 0.004 for a transverse DW and 0.073 +/- 0.026 for a vortex DW. The larger value is attributed to the higher magnetization gradients present

Response of breast carcinoma to endocrine therapy predicted using immunostained pelleted fine needle aspirates.

Fine needle aspirates from 82 patients with breast carcinoma were fixed in methacarn, double embedded in agar or gelatin, and then in paraffin wax. Sequential sections were stained with monoclonal antibodies to the oestrogen receptor-related protein P29 (antibody D5), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and cytokeratin (CAM 5.2). Sixty-one of 82 (74%) aspirates provided sections suitable for immunostaining. Twenty-six (43%) were D5 positive, 23 (38%) CEA positive, 59 (97%) EMA positive, and 54 (89%) CAM 5.2 positive. Twenty-six of these patients were treated with some form of endocrine therapy. Twelve (46%) showed positive staining for D5. Eleven (92%) of the 12 D5-positive patients responded or had static disease, and 8% progressed. Of the 14 D5-negative tumours 43% responded or remained static, and 57% progressed. The difference in response between the D5-positive and the D5-negative tumours was significant (P less than 0.05, Fisher's exact test). There was no correlation between staining for CEA, EMA or cytokeratin and response to endocrine therapy

Strain-dependent magnetic configurations in manganite-titanate heterostructures probed with soft X-ray techniques

We present a detailed study on the strain-induced magnetic domain structure of a (La,Sr)MnO3 thin film epitaxially grown on a BaTiO3 substrate through the use of polarization-dependent X-ray photoemission electron microscopy and X-ray absorption spectroscopy. Angular-dependent measurements allow us to detect vector magnetization on a single-domain scale, and we relate the strain-induced changes in magnetic anisotropy of the ferromagnetic film to the ferroelectric domain structure of the underlying substrate using X-ray magnetic circular and linear dichroism spectro-microscopy. Comparisons to measurements on a nearly strain free film of (La,Sr)MnO3 grown on a (La,Sr)(Al,Ta)O3 substrate illustrate that the BaTiO3 ferroelectric domain structure imprints specific domain sizes and wall orientations in the (La,Sr)MnO3/BaTiO3 artificial multiferroic heterostructure. Furthermore, a change of the BaTiO3 ferroelectric domain structure either with temperature or with applied electric field results in a corresponding change in the (La,Sr)MnO3 ferromagnetic domain structure, thus showing a possible route to obtain room-temperature electric field control of magnetic anisotropy at the nanoscal