Vectorial Control of Magnetization by Light

Coherent light-matter interactions have recently extended their applications to the ultrafast control of magnetization in solids. An important but unrealized technique is the manipulation of magnetization vector motion to make it follow an arbitrarily designed multi-dimensional trajectory. Furthermore, for its realization, the phase and amplitude of degenerate modes need to be steered independently. A promising method is to employ Raman-type nonlinear optical processes induced by femtosecond laser pulses, where magnetic oscillations are induced impulsively with a controlled initial phase and an azimuthal angle that follows well defined selection rules determined by the materials' symmetries. Here, we emphasize the fact that temporal variation of the polarization angle of the laser pulses enables us to distinguish between the two degenerate modes. A full manipulation of two-dimensional magnetic oscillations is demonstrated in antiferromagnetic NiO by employing a pair of polarization-twisted optical pulses. These results have lead to a new concept of vectorial control of magnetization by light

Proton acceleration enhanced by a plasma jet in expanding foils undergoing relativistic transparency

Ion acceleration driven by the interaction of an ultraintense (2x10^20 Wcm^-2) laser pulse with an ultrathin (40nm) foil target is experimentally and numerically investigated. Protons accelerated by sheath fields and via laser radiation pressure are angularly separated and identified based on their directionality and signature features (e.g. transverse instabilities) in the measured spatial-intensity distribution. A low divergence, high energy proton component is also detected when the heated target electrons expand and the target becomes relativistically transparent during the interaction. 2D and 3D particle-in-cell (PIC) simulations indicate that under these conditions a plasma jet is formed at the target rear, supported by a self-generated azimuthal magnetic field, which extends into the expanded layer of sheath-accelerated protons. Electrons trapped within this jet are directly accelerated to super-thermal energies by the portion of the laser pulse transmitted through the target. The resulting streaming of the electrons into the ion layers enhances the energy of protons in the vicinity of the jet. Through the addition of a controlled prepulse, the maximum energy of these protons is demonstrated experimentally and numerically to be sensitive to the picosecond rising edge prole of the laser pulse

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Comment on “The extent of forest in dryland biomes”

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.Bastin et al. (Reports, 12 May 2017, p. 635) infer forest as more globally extensive than previously estimated using tree cover data. However, their forest definition does not reflect ecosystem function or biotic composition. These structural and climatic definitions inflate forest estimates across the tropics and undermine conservation goals, leading to inappropriate management policies and practices in tropical grassy ecosystems

The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients

Background: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Findings: Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. Interpretation: Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. Funding: JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care

Benthic pH gradients across a range of shelf sea sediment types linked to sediment characteristics and seasonal variability

This study used microelectrodes to record pH profiles in fresh shelf sea sediment cores collected across a range of different sediment types within the Celtic Sea. Spatial and temporal variability was captured during repeated measurements in 2014 and 2015. Concurrently recorded oxygen microelectrode profiles and other sedimentary parameters provide a detailed context for interpretation of the pH data. Clear differences in profiles were observed between sediment type, location and season. Notably, very steep pH gradients exist within the surface sediments (10–20 mm), where decreases greater than 0.5 pH units were observed. Steep gradients were particularly apparent in fine cohesive sediments, less so in permeable sandier matrices. We hypothesise that the gradients are likely caused by aerobic organic matter respiration close to the sediment–water interface or oxidation of reduced species at the base of the oxic zone (NH4+, Mn2+, Fe2+, S−). Statistical analysis suggests the variability in the depth of the pH minima is controlled spatially by the oxygen penetration depth, and seasonally by the input and remineralisation of deposited organic phytodetritus. Below the pH minima the observed pH remained consistently low to maximum electrode penetration (ca. 60 mm), indicating an absence of sub-oxic processes generating H+ or balanced removal processes within this layer. Thus, a climatology of sediment surface porewater pH is provided against which to examine biogeochemical processes. This enhances our understanding of benthic pH processes, particularly in the context of human impacts, seabed integrity, and future climate changes, providing vital information for modelling benthic response under future climate scenarios

Differences in reproductive risk factors for breast cancer in middle-aged women in Marin County, California and a sociodemographically similar area of Northern California

<p>Abstract</p> <p>Background</p> <p>The Northern California county of Marin (MC) has historically had high breast cancer incidence rates. Because of MC's high socioeconomic status (SES) and racial homogeneity (non-Hispanic White), it has been difficult to assess whether these elevated rates result from a combination of established risk factors or other behavioral or environmental factors. This survey was designed to compare potential breast cancer risks and incidence rates for a sample of middle-aged MC women with those of a demographically similar population.</p> <p>Methods</p> <p>A random sample of 1500 middle-aged female members of a large Northern California health plan, half from Marin County (MC) and half from a comparison area in East/Central Contra Costa County (ECCC), were mailed a survey covering family history, reproductive history, use of oral contraceptives (OC) and hormone replacement therapy (HRT), behavioral health risks, recency of breast screening, and demographic characteristics. Weighted data were used to compare prevalence of individual breast cancer risk factors and Gail scores. Age-adjusted cumulative breast cancer incidence rates (2000–2004) were also calculated for female health plan members aged 40–64 residing in the two geographic areas.</p> <p>Results</p> <p>Survey response was 57.1% (n = 427) and 47.9% (n = 359) for MC and ECCC samples, respectively. Women in the two areas were similar in SES, race, obesity, exercise frequency, current smoking, ever use of OCs and HRT, age at onset of menarche, high mammography rates, family history of breast cancer, and Gail scores. However, MC women were significantly more likely than ECCC women to be former smokers (43.6% vs. 31.2%), have Ashkenazi Jewish heritage (12.8% vs. 7.1%), have no live births before age 30 (52.7% vs. 40.8%), and be nulliparous (29.2% vs. 15.4%), and less likely to never or rarely consume alcohol (34.4% vs. 41.9%). MC and ECCC women had comparable 2000–2004 invasive breast cancer incidence rates.</p> <p>Conclusion</p> <p>The effects of reproductive risks factors, Ashkenazi Jewish heritage, smoking history, and alcohol consumption with regard to breast cancer risk in Marin County should be further evaluated. When possible, future comparisons of breast cancer incidence rates between regions should adjust for differences in income and education in addition to age and race/ethnicity, preferably by using a sociodemographically similar comparison group.</p

High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress. Nevertheless, the spatial interaction of acidic stores with other parts of the calcium signalling apparatus in cardiac myocytes is unknown. We present evidence that lysosomes are intimately associated with the sarcoplasmic reticulum (SR) in ventricular myocytes; a median separation of 20 nm in 2D electron microscopy and 3.3 nm in 3D electron tomography indicates a genuine signalling microdomain between these organelles. Fourier analysis of immunolabelled lysosomes suggests a sarcomeric pattern (dominant wavelength 1.80 μm). Furthermore, we show that lysosomes form close associations with mitochondria (median separation 6.2 nm in 3D studies) which may provide a basis for the recently-discovered role of NAADP in reperfusion-induced cell death. The trigger hypothesis for NAADP action proposes that calcium release from acidic stores subsequently acts to enhance calcium release from the SR. This work provides structural evidence in cardiac myocytes to indicate the formation of microdomains between acidic and SR calcium stores, supporting emerging interpretations of NAADP physiology and pharmacology in heart

Evasion of IFN-γ Signaling by Francisella novicida Is Dependent upon Francisella Outer Membrane Protein C

Francisella tularensis is a Gram-negative facultative intracellular bacterium and the causative agent of the lethal disease tularemia. An outer membrane protein (FTT0918) of F. tularensis subsp. tularensis has been identified as a virulence factor. We generated a F. novicida (F. tularensis subsp. novicida) FTN_0444 (homolog of FTT0918) fopC mutant to study the virulence-associated mechanism(s) of FTT0918.The ΔfopC strain phenotype was characterized using immunological and biochemical assays. Attenuated virulence via the pulmonary route in wildtype C57BL/6 and BALB/c mice, as well as in knockout (KO) mice, including MHC I, MHC II, and µmT (B cell deficient), but not in IFN-γ or IFN-γR KO mice was observed. Primary bone marrow derived macrophages (BMDM) prepared from C57BL/6 mice treated with rIFN-γ exhibited greater inhibition of intracellular ΔfopC than wildtype U112 strain replication; whereas, IFN-γR KO macrophages showed no IFN-γ-dependent inhibition of ΔfopC replication. Moreover, phosphorylation of STAT1 was downregulated by the wildtype strain, but not the fopC mutant, in rIFN-γ treated macrophages. Addition of NG-monomethyl-L-arginine, an NOS inhibitor, led to an increase of ΔfopC replication to that seen in the BMDM unstimulated with rIFN-γ. Enzymatic screening of ΔfopC revealed aberrant acid phosphatase activity and localization. Furthermore, a greater abundance of different proteins in the culture supernatants of ΔfopC than that in the wildtype U112 strain was observed.F. novicida FopC protein facilitates evasion of IFN-γ-mediated immune defense(s) by down-regulation of STAT1 phosphorylation and nitric oxide production, thereby promoting virulence. Additionally, the FopC protein also may play a role in maintaining outer membrane stability (integrity) facilitating the activity and localization of acid phosphatases and other F. novicida cell components

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Hypoxia has been associated with poor local tumour control and relapse in many cancer sites, including carcinoma of the prostate. This translational study tests whether breathing carbogen gas improves the oxygenation of human prostate carcinoma xenografts in mice and in human patients with prostate cancer. A total of 23 DU145 tumour-bearing mice, 17 PC3 tumour-bearing mice and 17 human patients with prostate cancer were investigated. Intrinsic susceptibility-weighted MRI was performed before and during a period of carbogen gas breathing. Quantitative R2* pixel maps were produced for each tumour and at each time point and changes in R2* induced by carbogen were determined. There was a mean reduction in R2* of 6.4% (P=0.003) for DU145 xenografts and 5.8% (P=0.007) for PC3 xenografts. In all, 14 human subjects were evaluable; 64% had reductions in tumour R2* during carbogen inhalation with a mean reduction of 21.6% (P=0.0005). Decreases in prostate tumour R2* in both animal models and human patients as a result of carbogen inhalation suggests the presence of significant hypoxia. The finding that carbogen gas breathing improves prostate tumour oxygenation provides a rationale for testing the radiosensitising effects of combining carbogen gas breathing with radiotherapy in prostate cancer patients