PAAN/MIF nuclease inhibition prevents neurodegeneration in Parkinson's disease.

Parthanatos-associated apoptosis-inducing factor (AIF) nuclease (PAAN), also known as macrophage migration inhibitor factor (MIF), is a member of the PD-D/E(X)K nucleases that acts as a final executioner in parthanatos. PAAN's role in Parkinson's disease (PD) and whether it is amenable to chemical inhibition is not known. Here, we show that neurodegeneration induced by pathologic α-synuclein (α-syn) occurs via PAAN/MIF nuclease activity. Genetic depletion of PAAN/MIF and a mutant lacking nuclease activity prevent the loss of dopaminergic neurons and behavioral deficits in the α-syn preformed fibril (PFF) mouse model of sporadic PD. Compound screening led to the identification of PAANIB-1, a brain-penetrant PAAN/MIF nuclease inhibitor that prevents neurodegeneration induced by α-syn PFF, AAV-α-syn overexpression, or MPTP intoxication in vivo. Our findings could have broad relevance in human pathologies where parthanatos plays a role in the development of cell death inhibitors targeting the druggable PAAN/MIF nuclease.

Modulation of Capsid Dynamics in Bromoviruses by the Host and Heterologous Viral Replicase.

The three genomic and a single subgenomic RNA of Cowpea chlorotic mottle virus (CCMV), which is pathogenic to plants, is packaged into three morphologically indistinguishable icosahedral virions with T=3 symmetry. The two virion types, C1V and C2V, package genomic RNAs 1 (C1) and 2 (C2), respectively. The third virion type, C3+4V, copackages genomic RNA3 and its subgenomic RNA (RNA4). In this study, we sought to evaluate how the alteration of native capsid dynamics by the host and viral replicase modulate the general biology of the virus. The application of a series of biochemical, molecular, and biological assays revealed the following. (i) Proteolytic analysis of the three virion types of CCMV assembled individually in planta revealed that, while retaining the structural integrity, C1V and C2V virions released peptide regions encompassing the N-terminal arginine-rich RNA binding motif. In contrast, a minor population of the C3+4V virion type was sensitive to trypsin-releasing peptides encompassing the entire capsid protein region. (ii) The wild-type CCMV virions purified from cowpea are highly susceptible to trypsin digestion, while those from Nicotiana benthamiana remained resistant, and (iii) finally, the matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis evaluated the relative dynamics of C3+4V and B3+4V virions assembled under the control of the homologous versus heterologous replicase. The role of viral replicase in modulating the capsid dynamics was evident by the differential sensitivity to protease exhibited by B3+4V and C3+4V virions assembled under the homologous versus heterologous replicase. Our results collectively conclude that constant modulation of capsid dynamics by the host and viral replicase is obligatory for successful infection. IMPORTANCE Infectious virus particles or virions are considered static structures and undergo various conformational transitions to replicate and infect many eukaryotic cells. In viruses, conformational changes are essential for establishing infection and evolution. Although viral capsid fluctuations, referred to as dynamics or breathing, have been well studied in RNA viruses pathogenic to animals, such information is limited among plant viruses. The primary focus of this study is to address how capsid dynamics of plant-pathogenic RNA viruses, namely, Cowpea chlorotic mottle (CCMV) and Brome mosaic virus (BMV), are modulated by the host and viral replicase. The results presented have improved and transformed our understanding of the functional relationship between capsid dynamics and the general biology of the virus. They are likely to provide stimulus to extend similar studies to viruses pathogenic to eukaryotic organisms.

Direct generation of multicolor Bessel beams from a Pr3+: WPFG fiber laser.

Multicolor visible high-order Bessel (Bessel-vortex) beams which have a helical wavefront and a long confocal length have garnered significant interest for applications in materials processing and biomedical technologies. In this paper, we demonstrate the direct generation of multicolor (523, 605 and 637 nm) Bessel-vortex beams from a Pr3+-doped water-proof fluoro-aluminate glass (Pr3+: WPFG) fiber laser with an intracavity lens which induces chromatic and spherical aberration. The handedness of the generated Bessel-vortex beam is selectively controlled through lateral displacement of the intra-cavity lens.

Optical skyrmions in the Bessel profile.

Optical skyrmions formed in terms of polarization are topological quasi-particles, and they have garnered much interest in the optical community owing to their unique inhomogeneous polarization structure and simplicity in their experimental realization. These structures belong to the Poincaré beams satisfying the stable topology. We theoretically investigated the non-diffracting and self-healing Poincaré beams based on the superposition of two orthogonal Bessel modes by the longitudinal mode matching technique. These Poincaré beams are topologically protected, and we suggest them as optical skyrmions in the corresponding Stokes vector fields. These optical skyrmions are quasi-skyrmions, and their range of propagation depends on the range of superposed Bessel modes. We have shown longitudinal mode matching of superposed Bessel beams is a necessary condition for the generation of propagation-invariant and non-diffracting skyrmions. The proposed longitudinal mode matching technique facilitates the generation of skyrmions with tunable position and range without any on-axis intensity modulations along the propagation axis. A suitable experimental configuration is suggested to realize variable order skyrmions in Bessel modes. The suggested experimental configuration can produce optical skyrmions even in ultra-short laser pulses with high mode conversion efficacy. This work can provide a new direction for the generation of skyrmions with completely new textures and features with reference to existing skyrmions originating from Laguerre-Gaussian modes.

Red, orange, and dual wavelength vortex emission from Pr:WPFGF fiber laser using a microscope slide output coupler.

Visible vortex beams have a large array of applications; however, the sources are often large or complex. Here, we present a compact vortex source with red, orange, and dual wavelength emission. This Pr:Waterproof Fluoro-Aluminate Glass fiber laser uses a standard microscope slide as an interferometric output coupler, yielding high quality first order vortex modes in a compact setup. We further demonstrate the broad (∼5 nm) emission bands in the orange (610 nm), red (637 nm) and near-infrared regions (698 nm), with the potential for green (530 nm) and cyan (485 nm) emission. This is a low-cost, compact and accessible device giving high quality modes for visible vortex applications.

Synthesis, Structural and Fluorescence Investigations of Novel Li2Ba5W3O15:Sm3+ Phosphors for Photonic Device Applications.

In the current study, Sm3+ ions doped Lithium Barium Tungstate (Li2Ba5W3O15) (LBW) phosphors with the ability to emit orange-red light were made using the traditional high-temperature solid-state reaction technique. The structure and phase of the as-synthesized phosphor samples were examined via X-ray diffraction (XRD) patterns. The diffraction peaks of the undoped LBW and Sm3+ ions doped LBW phosphors closely resemble those of the Joint Committee on Powder Diffraction Standards (JCPDS) pattern with card number 01-072-1717. Scanning electron microscopy (SEM) was employed for the analysis of the morphological characteristics of the synthesized phosphor material. Fourier Transform Infrared (FT-IR) spectroscopy was used to study several vibrational and molecular bands present in the host matrix. Using diffuse reflectance spectra (DRS), the optical band gap values (Eg) were evaluated by applying Tauc's method. The photoluminescence (PL) spectra characteristics at λex = 336 nm indicate the emission of dopant ions (Sm3+) in the deep orange-red region corresponding to 4G5/2 → 6H5/2 transition (at 581 nm) with concentration quenching after 2 mol % of Sm3+ ions. Using the PL spectra, the CIE chromaticity coordinates of LBWS2.0 phosphor were estimated and found in the deep visible orange-red area, indicating the potential use of the prepared phosphor material for phosphor-converted white light emitting diodes (w-LEDs) applications. Double exponential behaviour can be seen in the PL decay spectral profiles obtained under λem = 581 nm and λex = 336 nm. The experimental lifetimes (τexp) decrease as the concentration of Sm3+ ions rise. The temperature-dependent PL (TDPL) and activation energy results show that the as-synthesized phosphor has considerably superior thermal stability. The results of the current research contemplate us the applicability of Sm3+ ions doped LBW phosphor for photonic devices such as w-LEDs.

Structural Investigation and Optical Properties of Dysprosium (Dy3+) Ions Doped Oxyfluoro Antimony Borate Glasses for Photonics Applications.

Dysprosium oxide-doped glasses with a composition of 60B2O3-10Sb2O3-10Al2O3-10NaF-(10-x) LiF-xDy2O3 (x = 0.1,0.5, 1.0,1.5,2.0,2.5 mol%) were prepared using a conventional melt-quenching technique. The glasses were characterized through various analytical investigations, including X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, refractive index, density, optical absorption, excitation, photoluminescence (PL) studies, decay measurements and radiation shielding parameters. The XRD and FT-IR confirms the glassy nature and functional groups present in the titled glass. The absorption spectra were used to determine the oscillator strength of the Dy3+ absorption transitions as well as the bond created with the O-2 ion in the titled glass network. The degree of the suitability of developed glasses for lasing applications was demonstrated by radiative parameters determined using Judd-Ofelt theory. In the prepared glass samples, the optical bandgap measurements indicate the presence of non-bridging oxygen (NBOs), localization of charges and donor centers in the titled glasses. Due to the de-excitation of 4F9/2 to the corresponding 6H15/2,6H13/2 and 6H11/2 states, the PL emission spectrum shows two main strong emissions at blue(480nm), yellow (575nm) and one less emission at red (663nm). The CIE coordinates determined using PL emission spectra reveal the coordinates that are falling within the white light region. Various shielding parameters such as mass attenuation coefficient, mean free path, effective atomic number were estimated to understand the radiative shielding nature of the titled glasses. Within the addition of Dy2O3, it was found that the shielding parameters values of the titled glass samples are increasing. The Mass Attenuation Coefficient, Half Value Layer and Mean Free Path of the as prepared glasses has been compared with different types of concretes to understand the shielding effectiveness of prepared glass.

Direct generation of lower-order cylindrical vector vortex modes from an end-pumped Pr3+:LiYF4 laser.

We report the direct generation of vector vortex laser modes at 640 nm from a compact, diode end-pumped continuous-wave P r 3+:L i Y F 4 (YLF) laser that utilizes an intracavity lens and diaphragm. On-axis displacement of the intracavity lens, combined with appropriate choice of the intracavity diaphragm, enables selective generation of a desired radial and azimuthal vector laser mode. Such compact, vector vortex laser sources based on P r 3+:Y L F in the visible wavelength region are a significant enabling technology for a wide range of applications.

Efficacy and safety of 0.05% micellar nano-particulate (MNP) cyclosporine ophthalmic emulsion in the treatment of moderate-to-severe keratoconjunctivitis sicca: a 12-week, multicenter, randomized, active-controlled trial.

BACKGROUND: Keratoconjunctivitis sicca or dry eye disease (DED) is a multifactorial disorder underpinned by a complex inflammatory cycle. Introduction of topical cyclosporine has been a significant advance in the management of DED. In recent years advancements in formulation technology have led to development of micellar nano-particulate (MNP) cyclosporine formulations that promise better penetration into ocular target tissues and potential for reduced ocular surface irritation. METHODS: We compared two dosing regimes of a proprietary MNP cyclosporine emulsion with the widely marketed topical cyclosporine formulation Restasis™ in a multicenter parallel-group randomised trial in patients with DED. Patients were randomised to one of 3 treatment groups with 90 patients eligible for the per protocol analysis: 30 in the higher dose test arm A; 32 in the lower dose test arm B; and 28 in the Restasis™ control arm C. All scored efficacy endpoints were tested for significance by comparing the mean change in scores from baseline in the test groups with that in the control group at 12 weeks, using the Student's t test. Wilcoxon's rank sum test was used to test individual symptom scores and clinician's global evaluation of treatment grades. RESULTS: Corneal fluorescein staining score, the primary efficacy endpoint, decreased by 6.8 ± 4.0, 5.7 ± 3.9, and 4.6 ± 3.6 points in the 3 groups respectively, indicating superior efficacy in test arm A in comparison to control arm C (p = 0.0026). Schirmer's tear test, conjunctival lissamine staining score, ocular surface disease index, and individual dry eye symptom scores also favoured higher dose MNP cyclosporine over Restasis™. The study failed to differentiate the treatment arms in terms of clinician's global evaluation of treatment, use of tear substitutes, best corrected visual acuity or safety and toleration. CONCLUSION: The results indicate that the dose of 1 drop of a 0.05% w/v ophthalmic emulsion of MNP cyclosporine administered topically twice daily yields better outcomes at 12 weeks than the lower dose tested in the study, and is more efficacious than an equivalent dose of Restasis™, the active control used in the study. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Registry of India on 29/03/2019, and was assigned registration number CTRI/2019/03/018319.

Genome organization and interaction with capsid protein in a multipartite RNA virus.

We report the asymmetric reconstruction of the single-stranded RNA (ssRNA) content in one of the three otherwise identical virions of a multipartite RNA virus, brome mosaic virus (BMV). We exploit a sample consisting exclusively of particles with the same RNA content-specifically, RNAs 3 and 4-assembled in planta by agrobacterium-mediated transient expression. We find that the interior of the particle is nearly empty, with most of the RNA genome situated at the capsid shell. However, this density is disordered in the sense that the RNA is not associated with any particular structure but rather, with an ensemble of secondary/tertiary structures that interact with the capsid protein. Our results illustrate a fundamental difference between the ssRNA organization in the multipartite BMV viral capsid and the monopartite bacteriophages MS2 and Qß for which a dominant RNA conformation is found inside the assembled viral capsids, with RNA density conserved even at the center of the particle. This can be understood in the context of the differing demands on their respective lifecycles: BMV must package separately each of several different RNA molecules and has been shown to replicate and package them in isolated, membrane-bound, cytoplasmic complexes, whereas the bacteriophages exploit sequence-specific "packaging signals" throughout the viral RNA to package their monopartite genomes.

Microencapsulation of n-tetradecane with poly (methyl methacrylate-co-methacrylic acid) shell by seeded emulsion polymerisation and its thermal energy storage characteristics.

This study aims to enhance the latent heat storage properties of the microcapsules by altering the amount of crosslinking agent from 3 to 20%w/w, the core-to-shell ratio from 1:1 to 2:1, and the amount of initiator from 1 to 3%. The phase change material n-tetradecane (C-14) was microencapsulated by using poly (methyl methacrylate -co- methacrylic acid) as a shell material through an oil by water-seeded emulsion polymerisation technique. The structural, morphological, and thermal properties of microcapsules were evaluated by using Fourier transform infrared spectroscopy, optical microscopy, scanning electron microscopy, differential scanning calorimetry analysis, and thermogravimetric analysis. The average particle size of the microcapsules ranges from 01 to 15 µm. The results showed that the microcapsules have a higher melting enthalpy value of 127.3 ± 0.06 J/g with a microencapsulation efficiency of 66.72% when a 20% w/w crosslinker was used. The thermal stability of the phase change material (PCM) was increased by ∼30 ± 2 °C by encapsulation.

Physiologically Based Pharmacokinetic Modeling To Guide Management of Drug Interactions between Elexacaftor-Tezacaftor-Ivacaftor and Antibiotics for the Treatment of Nontuberculous Mycobacteria.

Nontuberculous mycobacteria (NTM) are the pathogens of concern in people with cystic fibrosis (pwCF) due to their association with deterioration of lung function. Treatment requires the use of a multidrug combination regimen, creating the potential for drug-drug interactions (DDIs) with cystic fibrosis transmembrane conductance regulator (CFTR)-modulating therapies, including elexacaftor, tezacaftor, and ivacaftor (ETI), which are eliminated mainly through cytochrome P450 (CYP) 3A-mediated metabolism. An assessment of the DDI risk for ETI coadministered with NTM treatments, including rifabutin, clofazimine, and clarithromycin, is needed to provide appropriate guidance on dosing. The CYP3A-mediated DDIs between ETI and the NTM therapies rifabutin, clarithromycin, and clofazimine were evaluated using physiologically based pharmacokinetic (PBPK) modeling by incorporating demographic and physiological "system" data with drug physicochemical and in vitro parameters. Models were verified and then applied to predict untested scenarios to guide continuation of ETI during antibiotic treatment, using ivacaftor as the most sensitive CYP3A4 substrate. The predicted area under the concentration-time curve (AUC) ratios of ivacaftor when coadministered with rifabutin, clofazimine, or clarithromycin were 0.31, 2.98, and 9.64, respectively, suggesting moderate and strong interactions. The simulation predicted adjusted dosing regimens of ETI administered concomitantly with NTM treatments, which required delayed resumption of the standard dose of ETI once the NTM treatments were completed. The dosing transitions were determined based on the characteristics of the perpetrator drugs, including the mechanism of CYP3A modulation and their elimination half-lives. This study suggests increased doses of elexacaftor/tezacaftor/ivacaftor 200/100/450 mg in the morning and 100/50/375 mg in the evening when ETI is coadministered with rifabutin and reduced doses of elexacaftor/tezacaftor 200/100 mg every 48 h (q48h) and ivacaftor 150 mg daily or a dose of elexacaftor/tezacaftor/ivacaftor 200/100/150 mg q72h when coadministered with clofazimine or clarithromycin, respectively. Importantly, the PBPK simulations provide evidence in support of the use of treatments for NTM in pwCF receiving concomitant dose-adjusted ETI therapy.

Two-photon microscopy with enhanced resolution and signal-to-background ratio using hollow Gaussian beam excitation.

Two-photon microscopy (TPM) offers deeper imaging depth inside the scattering medium, however, it suffers from limited resolution owing to the longer excitation wavelength. We demonstrate the use of a hollow Gaussian beam (HGB) at the therapeutic window to improve the resolution and signal-to-background ratio (SBR). The HGB was produced by omitting the azimuthal phase term from the vortex mode, and the excitation point spread function (PSF) can be readily tuned by the mode order. The performance of the TPM with HGB was evaluated by experimentally imaging 100 nm fluorescent beads to estimate the PSF. The HGB improved the lateral resolution of the TPM by 36% in contrast to the conventional TPM. The HGB also furnishes an improvement of SBR by eliminating the out-of-focus light owing to its ring shape. Furthermore, we have used a translating lens-based module for additional lateral resolution tuning and reduced the resolution further down to 44% with respect to conventional TPM. Finally, we have performed imaging with merely two-dimensional scanning of a 50 µm thick mouse brain slice (Thy-YFP H-line) using the developed TPM with HGB. Our compact, robust, and low-cost design of the HGB generation scheme can easily be integrated into the commercial TPM to accommodate the improvements.

Industrialization and food safety for the Tsleil-Waututh Nation: An analysis of chemical levels in shellfish in Burrard Inlet.

While Indigenous food systems remain critical for community well-being, traditionally harvested foods are a potential source of toxic exposures. The Tsleil-Waututh Nation (TWN) is seeking to restore shellfish harvesting in Burrard Inlet (British Columbia [BC], Canada), where the cumulative effects of industrial activity have nearly eliminated safe harvesting. The Trans Mountain Expansion project would triple the capacity to transport oil through the inlet, threatening TWN's progress to restore shellfish harvesting. To inform ongoing efforts we assessed contamination by heavy metals (arsenic, cadmium, lead, and mercury) and 48 polycyclic aromatic hydrocarbons (PAHs) congeners in different shellfish species (Softshell clams, Varnish clams, and Dungeness crab) in three areas. We compared our results against local screening values (SVs) established by the TWN and BC Ministry of Environment and Climate Change Strategy, as well as provincial and national benchmarks. In total, we analyzed 18 composite samples of Softshell clams and Varnish clams (5 individuals per sample), as well as 17 individual crabs. We found chemical contamination in all species at all sites. PAHs were most frequently detected in Softshell clams, highest in the site closest to the pipeline terminus. Clams presented higher levels of contamination than crabs for PAHs, but not for heavy metals. For Softshell and Varnish clams, all heavy metals across study sites exceeded at least one of the population-specific SVs. Of the 14 PAHs detected, benzo(a)pyrene presented a median concentration in Softshell clams of 3.25 µ/kg, exceeding local SV for subsistence fisher. Our results call for further assessment of human health impacts related to food harvesting within Burrard Inlet and establishing a long-term coordinated program co-led by the TWN to monitor contamination and inform future harvesting programs. The study draws attention to the need to consider locally-relevant toxicity benchmarks, and include potential health impacts of food contamination in appraising development project proposals.

Complications in Device Therapy: Spectrum, Prevalence, and Management.

PURPOSE OF REVIEW: Cardiac implantable electronic device implant numbers are continually increasing due to the expanding indications and ageing population. This review explores the complications associated with device therapy and discusses ways to minimise and manage such complications. RECENT FINDINGS: Complications related to device therapy contribute to mortality and morbidity. Recent publications have detailed clear guidelines for appropriate cardiac device selection, as well as consensus documents discussing care quality and optimal implantation techniques. There have also been advances in device technologies that may offer alternative options to patients at high risk of/or already having encountered a complication. Adherence to guidelines, appropriate training, and selection of device, in addition to good surgical technique are key in reducing the burden of complications and improving acceptability of device therapy.

Rising Mental Health Incidence Among Adolescents in Westchester, NY.

CONTEXT: Many governments have publicly released healthcare data, which can be mined for insights about disease conditions, and their impact on society. METHODS: We present a big-data analytics approach to investigate data in the New York Statewide Planning and Research Cooperative System (SPARCS) consisting of 20 million patient records. FINDINGS: Whereas the age group 30-48 years exhibited an 18% decline in mental health (MH) disorders from 2009 to 2016, the age group 0-17 years showed a 5.4% increase. MH issues amongst the age group 0-17 years comprise a significant expenditure in New York State. Within this age group, we find a higher prevalence of MH disorders in females and minority populations. Westchester County has seen a 32% increase in incidences and a 41% increase in costs. CONCLUSIONS: Our approach is scalable to data from multiple government agencies and provides an independent perspective on health care issues, which can prove valuable to policy and decision-makers.

Unravelling the Stability and Capsid Dynamics of the Three Virions of Brome Mosaic Virus Assembled Autonomously In Vivo.

Viral capsids are dynamic assemblies that undergo controlled conformational transitions to perform various biological functions. The replication-derived four-molecule RNA progeny of Brome mosaic virus (BMV) is packaged by a single capsid protein (CP) into three types of morphologically indistinguishable icosahedral virions with T=3 quasisymmetry. Type 1 (B1V) and type 2 (B2V) virions package genomic RNA1 and RNA2, respectively, while type 3 (B3+4V) virions copackage genomic RNA3 (B3) and its subgenomic RNA4 (sgB4). In this study, the application of a robust Agrobacterium-mediated transient expression system allowed us to assemble each virion type separately in planta Experimental approaches analyzing the morphology, size, and electrophoretic mobility failed to distinguish between the virion types. Thermal denaturation analysis and protease-based peptide mass mapping experiments were used to analyze stability and the conformational dynamics of the individual virions, respectively. The crystallographic structure of the BMV capsid shows four trypsin cleavage sites (K65, R103, K111, and K165 on the CP subunits) exposed on the exterior of the capsid. Irrespective of the digestion time, while retaining their capsid structural integrity, B1V and B2V released a single peptide encompassing amino acids 2 to 8 of the N-proximal arginine-rich RNA binding motif. In contrast, B3+4V capsids were unstable with trypsin, releasing several peptides in addition to the peptides encompassing four predicted sites exposed on the capsid exterior. These results, demonstrating qualitatively different dynamics for the three types of BMV virions, suggest that the different RNA genes they contain may have different translational timing and efficiency and may even impart different structures to their capsids.IMPORTANCE The majority of viruses contain RNA genomes protected by a shell of capsid proteins. Although crystallographic studies show that viral capsids are static structures, accumulating evidence suggests that, in solution, virions are highly dynamic assemblies. The three genomic RNAs (RNA1, -2, and -3) and a single subgenomic RNA (RNA4) of Brome mosaic virus (BMV), an RNA virus pathogenic to plants, are distributed among three physically homogeneous virions. This study examines the thermal stability by differential scanning fluorimetry (DSF) and capsid dynamics by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analyses following trypsin digestion of the three virions assembled separately in vivo using the Agrobacterium-mediated transient expression approach. The results provide compelling evidence that virions packaging genomic RNA1 and -2 are distinct from those copackaging RNA3 and -4 in their stability and dynamics, suggesting that RNA-dependent capsid dynamics play an important biological role in the viral life cycle.

Direct generation of 523†nm orbital Poincaré mode from a diode-pumped Pr3+:LiYF4 laser with an off-axis optical needle pumping geometry.

We demonstrate an ultra-compact (8 mm-long) green orbital Poincaré Pr3+:LiYF4 (YLF) laser, in which the intracavity lasing modes are represented as eigenmodes on an equivalent orbital Poincaré sphere (eOPS). This is achieved through the simple application of an 'optical-needle' pumping geometry in conjunction with off-axis laser mode-manipulation. Optical vortices that are produced and mapped on north and south poles of the eOPS exhibit a maximum output power of 304 mW with a pump-to-laser-output slope efficiency of 12%. In addition, higher-order structured modes, including Ince Gaussian (IG), helical IG (HIG), Hermite-Laguerre Gaussian (HLG) and vortex lattices, can be directly generated from the laser cavity.

Nonlinear frequency conversion of 3D optical bottle beams generated using a single axicon.

We demonstrate a novel experimental scheme to generate and study the nonlinear frequency conversion of a three-dimensional (3D) optical Bessel bottle beam (BBB). Using a single axicon and standard optical components and controlling the spot size and divergence of the input Gaussian beam to the axicon, we have generated stable micron-size, high-power optical BBB with tunable spatial characteristics. The BBB has a series of low-intensity regions surrounded by high intensity with diameters of ∼30µm and 17 µm, respectively, at a variable period of 2.3 to 6.4 mm along with the beam propagation. Using the single-pass second harmonic generation (SHG) of femtosecond BBB at 1064 nm in a bismuth triborate nonlinear crystal, we have generated BBB at 532 nm with output power as high as 75 mW and single-pass SHG efficiency of 1.9%. We also observed the self-healing of the BBB at both pump and SHG wavelengths. It is interesting to note that the pump beam truncation shows self-healing in the SHG beam. Such observation proves the direct transfer of the pump's spatial characteristics to the SHG beam in the nonlinear process, potentially useful for imaging even in the turbid medium in biology. This generic scheme can be used at different wavelengths and timescales (continuous-wave to ultrafast).

Dietary diversity scores, nutrient intakes and biomarkers vitamin B12, folate and Hb in rural youth from the Pune Maternal Nutrition Study.

Hidden hunger is widespread in India. Individual dietary diversity score (IDDS) is a measure of the nutrient adequacy of the diet. The FAO has set guidelines for the measurement of dietary diversity: the IDDS and the minimum dietary diversity score for women (MDD-W) to assess nutritional deficiency, but validation against nutritional biomarkers is required. Using available data among rural youth (17 years) from the Pune Maternal Nutrition Study, the validity of DDS was assessed to measure deficiencies of vitamin B12, folate and Hb. Of the 355 boys and 305 girls, 19 % were classified as underweight, 57 % as vitamin B12 deficient (<150 pmol/l) and 22 % as anaemic (<120/130 g/l). Cereals, legumes and 'other-vegetables' were the most frequently consumed foods. More boys than girls consumed milk, flesh, eggs and micronutrient-dense foods. Median IDDS of 4 (interquartile range (IQR) 3-4) and MDD-W of 6 (IQR 5-7) were low. Youth with vitamin B12 deficiency had a higher likelihood of an IDDS ≤ 4 (1·89; 95 % CI 1·24, 2·87) or an MDD-W ≤ 5 (1·40; 95 % CI 1·02, 1·94). Youth with anaemia were more likely to have an IDDS ≤ 4 (1·76; 95 % CI 1·01, 3·14) adjusted for socio-economic scores, BMI, energy intake and sex. Folate deficiency was low (3 %) and was not associated with either score. Youth with lowest plasma vitamin B12 and Hb infrequently or never consumed dairy products/non-vegetarian foods. These rural Indian youth were underweight, had low DDS and consumed foods low in good-quality proteins and micronutrients. Associations of DDS with circulating micronutrients indicate that DDS is a valid measure to predict vitamin B12 deficiency and anaemia.