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

Circulating microparticles are increased amongst people presenting with HIV and advanced immune suppression in Malawi and correlate closely with arterial stiffness: a nested case control study

Background: We aimed to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with human immunodeficiency virus (HIV) and advanced immune suppression in Malawi, and whether they associated with arterial stiffness. Methods: Antiretroviral therapy (ART)-naïve adults with a new HIV diagnosis and CD4 <100 cells/µL had microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic blood pressure (BP) and diastolic BP in a 1:1 ratio.  Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers. Results: The median (IQ) total CMP count for 71 participants was 1 log higher in HIV compared to those without (p<0.0001) and was associated with arterial stiffness (spearman rho 0.47, p<0.001). In adjusted analysis, every log increase in circulating particles showed a 20% increase in cfPWV (95% confidence interval [CI] 4 – 40%, p=0.02). In terms of subsets, endothelial and platelet derived microparticles were most strongly associated with HIV. Endothelial derived E-selectin+ CMPs were 1.3log-fold higher and platelet derived CD42a+ CMPs were 1.4log-fold higher (both p<0.0001). Endothelial and platelet derived CMPs also correlated most closely with arterial stiffness (spearman rho: E-selectin+ 0.57 and CD42a 0.56, both p<0.0001). Conclusions: Circulating microparticles associate strongly with arterial stiffness among people living with HIV in Malawi. Endothelial damage and platelet microparticles are the predominant cell origin types and future translational studies could consider prioritising these pathways

Sequential Acquisition of T Cells and Antibodies to Nontyphoidal Salmonella in Malawian Children

Background Salmonella Typhimurium (STm) remain a prominent cause of bacteremia in sub-Saharan Africa. Complement-fixing antibodies to STm develop by 2 years of age. We hypothesized that STm-specific CD4+ T cells develop alongside this process. Methods Eighty healthy Malawian children aged 0–60 months were recruited. STm-specific CD4+ T cells producing interferon γ, tumor necrosis factor α, and interleukin 2 were quantified using intracellular cytokine staining. Antibodies to STm were measured by serum bactericidal activity (SBA) assay, and anti-STm immunoglobulin G antibodies by enzyme-linked immunosorbent assay. Results Between 2006 and 2011, STm bacteremias were detected in 449 children <5 years old. STm-specific CD4+ T cells were acquired in infancy, peaked at 14 months, and then declined. STm-specific SBA was detectable in newborns, declined in the first 8 months, and then increased to a peak at age 35 months. Acquisition of SBA correlated with acquisition of anti–STm–lipopolysaccharide (LPS) immunoglobulin G (r = 0.329 [95% confidence interval, .552–.062]; P = .01) but not anti–STm–outer membrane protein or anti–STm-flagellar protein (FliC). Conclusions Acquisition of STm-specific CD4+ T cells in early childhood is consistent with early exposure to STm or cross-reactive protein antigens priming this T-cell development. STm-specific CD4+ T cells seem insufficient to protect against invasive nontyphoidal Salmonella disease, but sequential acquisition of SBA to STm LPS is associated with a decline in its incidence

Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi

Objectives This study aimed to define the molecular basis of co-trimoxazole resistance in Malawian pneumococci under the dual selective pressure of widespread co-trimoxazole and sulfadoxine/pyrimethamine use. Methods We measured the trimethoprim and sulfamethoxazole MICs and analysed folA and folP nucleotide and translated amino acid sequences for 143 pneumococci isolated from carriage and invasive disease in Malawi (2002–08). Results Pneumococci were highly resistant to both trimethoprim and sulfamethoxazole (96%, 137/143). Sulfamethoxazole-resistant isolates showed a 3 or 6 bp insertion in the sulphonamide-binding site of folP. The trimethoprim-resistant isolates fell into three genotypic groups based on dihydrofolate reductase (encoded by folA) mutations: Ile-100-Leu (10%), the Ile-100-Leu substitution together with a residue 92 substitution (56%) and those with a novel uncharacterized resistance genotype (34%). The nucleotide sequence divergence and dN/dS of folA and folP remained stable from 2004 onwards. Conclusions S. pneumoniae exhibit almost universal co-trimoxazole resistance in vitro and in silico that we believe is driven by extensive co-trimoxazole and sulfadoxine/pyrimethamine use. More than one-third of pneumococci employ a novel mechanism of co-trimoxazole resistance. Resistance has now reached a point of stabilizing evolution. The use of co-trimoxazole to prevent pneumococcal infection in HIV/AIDS patients in sub-Saharan Africa should be re-evaluated

Laboratory evidence of disseminated intravascular coagulation is associated with a fatal outcome in children with cerebral malaria despite an absence of clinically evident thrombosis or bleeding

Background A procoagulant state is implicated in cerebral malaria (CM ) pathogenesis, but whether disseminated intravascular coagulation (DIC ) is present or associated with a fatal outcome is unclear. Objectives To determine the frequency of overt DIC , according to ISTH criteria, in children with fatal and non‐fatal CM . Methods/patients Malawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy‐positive CM (n = 140), retinopathy‐negative CM (n = 36), non‐malarial coma (n = 14), uncomplicated malaria (UM ), (n = 91), mild non‐malarial febrile illness (n = 85), and healthy controls (n = 36). Assays in the ISTH DIC criteria were performed, and three fibrin‐related markers, i.e. protein C, antithrombin, and soluble thrombomodulin, were measured. Results and conclusions Data enabling assignment of the presence or absence of ‘overt DIC ’ were available for 98 of 140 children with retinopathy‐positive CM . Overt DIC was present in 19 (19%), and was associated with a fatal outcome (odds ratio [OR] 3.068; 95% confidence interval [CI] 1.085–8.609; P = 0.035]. The levels of the three fibrin‐related markers and soluble thrombomodulin were higher in CM patients than in UM patients (all P < 0.001). The mean fibrin degradation product level was higher in fatal CM patients (71.3 μg mL−1 [95% CI 49.0–93.6]) than in non‐fatal CM patients (48.0 μg mL−1 [95% CI 37.7–58.2]; P = 0.032), but, in multivariate logistic regression, thrombomodulin was the only coagulation‐related marker that was independently associated with a fatal outcome (OR 1.084 for each ng mL−1 increase [95% CI 1.017–1.156]; P = 0.014). Despite these laboratory derangements, no child in the study had clinically evident bleeding or thrombosis. An overt DIC score and high thrombomodulin levels are associated with a fatal outcome in CM , but infrequently indicate a consumptive coagulopathy

Emergent dynamic chirality in a thermally driven artificial spin ratchet

Modern nanofabrication techniques have opened the possibility to create novel functional materials, whose properties transcend those of their constituent elements. In particular, tuning the magnetostatic interactions in geometrically frustrated arrangements of nanoelements called artificial spin ice1, 2 can lead to specific collective behaviour3, including emergent magnetic monopoles4, 5, charge screening6, 7 and transport8, 9, as well as magnonic response10, 11, 12. Here, we demonstrate a spin-ice-based active material in which energy is converted into unidirectional dynamics. Using X-ray photoemission electron microscopy we show that the collective rotation of the average magnetization proceeds in a unique sense during thermal relaxation. Our simulations demonstrate that this emergent chiral behaviour is driven by the topology of the magnetostatic field at the edges of the nanomagnet array, resulting in an asymmetric energy landscape. In addition, a bias field can be used to modify the sense of rotation of the average magnetization. This opens the possibility of implementing a magnetic Brownian ratchet13, 14, which may find applications in novel nanoscale devices, such as magnetic nanomotors, actuators, sensors or memory cells

The UK's Global Health Respiratory Network: Improving respiratory health of the world's poorest through research collaborations.

Respiratory disorders are responsible for considerable morbidity, health care utilisation, societal costs and approximately one in five deaths worldwide [1-4]. Yet, despite this substantial health and societal burden – which particularly affects the world’s poorest populations and as such is a major contributor to global health inequalities – respiratory disorders have historically not received the policy priority they warrant. For example, despite causing an estimated 1000 deaths per day, less than half of the world’s countries collect data on asthma prevalence (http://www.globalasthmareport.org/). This is true for both communicable and non-communicable respiratory disorders, many of which are either amenable to treatment or preventable