Raman and nuclear magnetic resonance investigation of alkali metal vapor interaction with alkene-based anti-relaxation coating.

The use of anti-relaxation coatings in alkali vapor cells yields substantial performance improvements compared to a bare glass surface by reducing the probability of spin relaxation in wall collisions by several orders of magnitude. Some of the most effective anti-relaxation coating materials are alpha-olefins, which (as in the case of more traditional paraffin coatings) must undergo a curing period after cell manufacturing in order to achieve the desired behavior. Until now, however, it has been unclear what physicochemical processes occur during cell curing, and how they may affect relevant cell properties. We present the results of nondestructive Raman-spectroscopy and magnetic-resonance investigations of the influence of alkali metal vapor (Cs or K) on an alpha-olefin, 1-nonadecene coating the inner surface of a glass cell. It was found that during the curing process, the alkali metal catalyzes migration of the carbon-carbon double bond, yielding a mixture of cis- and trans-2-nonadecene.

Efficacy of liposome-encapsulated ciprofloxacin in a murine model of Q fever.

Encapsulation of antibiotics may improve treatment of intracellular infections by prolonging antibiotic release and improving antibiotic uptake into cells. In this study, liposome-encapsulated ciprofloxacin for inhalation (CFI) was evaluated as a postexposure therapeutic for the treatment of Coxiella burnetii, the causative agent of Q fever. Intranasal treatment of male A/Jola (A/J) mice with CFI (50 mg/kg of body weight) once daily for 7 days protected mice against weight loss and clinical signs following an aerosol challenge with C. burnetii. In comparison, mice treated twice daily with oral ciprofloxacin or doxycycline (50 mg/kg) or phosphate-buffered saline (PBS) lost 15 to 20% body weight and exhibited ruffled fur, arched backs, and dehydration. Mice were culled at day 14 postchallenge. The weights and bacterial burdens of organs were determined. Mice treated with CFI exhibited reduced splenomegaly and reduced bacterial numbers in the lungs and spleen compared to mice treated with oral ciprofloxacin or doxycycline. When a single dose of CFI was administered, it provided better protection against body weight loss than 7 days of treatment with oral doxycycline, the current antibiotic of choice to treat Q fever. These data suggest that CFI has potential as a superior antibiotic to treat Q fever.

Long-lived heteronuclear spin-singlet states in liquids at a zero magnetic field.

We report an observation of long-lived spin-singlet states in a 13C-1H spin pair in a zero magnetic field. In 13C-labeled formic acid, we observe spin-singlet lifetimes as long as 37 s, about a factor of 3 longer than the T1 lifetime of dipole polarization in the triplet state. In contrast to common high-field experiments, the observed coherence is a singlet-triplet coherence with a lifetime T2 longer than the T1 lifetime of dipole polarization in the triplet manifold. Moreover, we demonstrate that heteronuclear singlet states formed between a 1H and a 13C nucleus can exhibit longer lifetimes than the respective triplet states even in the presence of additional spins that couple to the spin pair of interest. Although long-lived homonuclear spin-singlet states have been extensively studied, this is the first experimental observation of analogous singlet states in heteronuclear spin pairs.

Differences between seven measures of self-reported numbers of clients of female sex workers in southern India: implications for individual- and population-level analysis.

Quantifying sexual activity of sub-populations with high-risk sexual behaviour is important in understanding HIV epidemiology. This study examined inconsistency of seven outcomes measuring self-reported clients per month (CPM) of female sex workers (FSWs) in southern India and implications for individual/population-level analysis. Multivariate negative binomial regression was used to compare key social/environmental factors associated with each outcome. A transmission dynamics model was used to assess the impact of differences between outcomes on population-level FSW/client HIV prevalence. Outcomes based on 'clients per last working day' produced lower estimates than those based on 'clients per typical day'. Although the outcomes were strongly correlated, their averages differed by approximately two-fold (range 39.0-79.1 CPM). The CPM measure chosen did not greatly influence standard epidemiological 'risk factor' analysis. Differences across outcomes influenced HIV prevalence predictions. Due to this uncertainty, we recommend basing population-based estimates on the range of outcomes, particularly when assessing the impact of interventions.

Development of ELIP to Assess Physical Literacy for Emerging Adults: A Methodological and Epistemological Challenge.

Purpose: Following increased interest in physical literacy (PL), development of appropriate tools for assessment has become an important next step for its operationalization. To forward the development of such tools, the objective of this study was to build the foundations of the Évaluation de la Littératie Physique (ELIP), designed to help reduce existing tensions in approaches to PL assessment that may be resulting in a low uptake into applied settings. Methods: We followed two steps: (1) the development of the first version of ELIP by deploying a Delphi method (n = 30); and (2) the modification of items through cognitive interviews with emerging adults (n = 32). Results: The expert consensus highlighted four dimensions of PL to be assessed-physical; affective; cognitive; and social-with new perspectives, including a preference for broad motor tests over fitness. Conclusion: Results offer new insights into the assessment of emerging adults' PL, but ELIP still requires further work concerning validity, reliability, and sensitivity.

The nonnucleoside reverse transcriptase inhibitor MIV-150 in carrageenan gel prevents rectal transmission of simian/human immunodeficiency virus infection in macaques.

Development of a microbicide that prevents rectal transmission of human immunodeficiency virus (HIV) is a vital component in reducing HIV spread. We recently demonstrated that a formulation of the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan reduced vaginal infection of macaques with simian immunodeficiency virus SIVmac239 with HIV-1(HxB2) reverse transcriptase (SHIV-RT). Herein, we performed the first testing of MIV-150-carrageenan against rectal infection. Rhesus macaques were treated rectally with MIV-150-carrageenan or methyl cellulose (MC) placebo gel up to 4 h prior to rectal challenge with 10³ or 10(4) 50% tissue culture infective doses (TCID50) of SHIV-RT. Infection was assessed by measuring plasma virus RNA as well as T and B cell responses. MIV-150-carrageenan protected all animals challenged with 10³ TCID(50 when gel was applied either 30 min or 4 h prior to challenge, while 100% of the MC-treated animals became infected (n = 4 each; P < 0.03). Partial protection (2 of 4 animals) by MIV-150-carrageenan was observed for rectal challenge with 10-fold more virus applied 4 h after the gel. Sequencing of the RT gene from plasma virus RNA isolated at peak viremia confirmed that both of these animals (like infected MC controls) were infected with wild-type virus. Infection correlated with the development of SIV-specific T and B cell responses. MIV-150 was detected in the rectal fluids and tissues 4 h after gel application but was not detected in the blood at any time (0.5 to 24 h). These data are promising for the development of NNRTI-containing gels to prevent rectal HIV transmission.

Liquid-state nuclear spin comagnetometers.

We discuss nuclear spin comagnetometers based on ultralow-field nuclear magnetic resonance in mixtures of miscible solvents, each rich in a different nuclear spin. In one version thereof, Larmor precession of protons and 19F nuclei in a mixture of thermally polarized pentane and hexafluorobenzene is monitored via a sensitive alkali-vapor magnetometer. We realize transverse relaxation times in excess of 20 s and suppression of magnetic field fluctuations by a factor of 3400. We estimate it should be possible to achieve single-shot sensitivity of about 5×10(-9) Hz, or about 5×10(-11) Hz in ≈1 day of integration. In a second version, spin precession of protons and 129Xe nuclei in a mixture of pentane and hyperpolarized liquid xenon is monitored using superconducting quantum interference devices. Application to spin-gravity experiments, electric dipole moment experiments, and sensitive gyroscopes is discussed.

Food for all: designing sustainable and secure future seafood systems.

Food from the sea can make a larger contribution to healthy and sustainable diets, and to addressing hunger and malnutrition, through improvements in production, distribution and equitable access to wild harvest and mariculture resources and products. The supply and consumption of seafood is influenced by a range of 'drivers' including ecosystem change and ocean regulation, the influence of corporations and evolving consumer demand, as well as the growing focus on the importance of seafood for meeting nutritional needs. These drivers need to be examined in a holistic way to develop an informed understanding of the needs, potential impacts and solutions that align seafood production and consumption with relevant 2030 Sustainable Development Goals (SDGs). This paper uses an evidence-based narrative approach to examine how the anticipated global trends for seafood might be experienced by people in different social, geographical and economic situations over the next ten years. Key drivers influencing seafood within the global food system are identified and used to construct a future scenario based on our current trajectory (Business-as-usual 2030). Descriptive pathways and actions are then presented for a more sustainable future scenario that strives towards achieving the SDGs as far as technically possible (More sustainable 2030). Prioritising actions that not only sustainably produce more seafood, but consider aspects of access and utilisation, particularly for people affected by food insecurity and malnutrition, is an essential part of designing sustainable and secure future seafood systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-021-09663-x.

Near-zero-field nuclear magnetic resonance.

We investigate nuclear magnetic resonance (NMR) in near zero field, where the Zeeman interaction can be treated as a perturbation to the electron mediated scalar interaction (J coupling). This is in stark contrast to the high-field case, where heteronuclear J couplings are normally treated as a small perturbation. We show that the presence of very small magnetic fields results in splitting of the zero-field NMR lines, imparting considerable additional information to the pure zero-field spectra. Experimental results are in good agreement with first-order perturbation theory and with full numerical simulation when perturbation theory breaks down. We present simple rules for understanding the splitting patterns in near-zero-field NMR, which can be applied to molecules with nontrivial spectra.

Using surveillance data for action: lessons learnt from the second generation HIV/AIDS surveillance project in Pakistan.

Although many countries are now collecting useful, high-quality HIV surveillance data, more efforts are put into the collection of data than into ensuring it is deployed effectively. The Canada-Pakistan HIV/AIDS surveillance project has strengthened and expanded the existing national AIDS control programme surveillance system in Pakistan through a comprehensive estimate of the size and location of some of the most at-risk populations (sex workers and injection drug users) and annual assessments of their sociodemographic characteristics, behaviours and HIV prevalence. The country now uses second generation surveillance data at a broad level to lobby for policy change, mobilize resources, improve programming and measure the success of prevention through an integrated national effort. This article aims to share the experiences and lessons learnt in the development of a second generation surveillance system for HIV/AIDS in Pakistan.

Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques.

To determine the role of CD8(+) T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8(+) T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.

["Responsiveness" in psychiatric outpatient care and in hostel management]. / "Responsiveness" in der psychiatrischen ambulanten Versorgung und in der Heimversorgung.

OBJECTIVE: Responsiveness is a concept developed by the World Health Organisation (WHO) to evaluate health system performance. It measures how well a health system meets its users' legitimate expectations in non-medical related service aspects. Responsiveness consists of the categories "patient orientation" and "respect for persons". It is operationalised by nine (8+1) domains. This project aims to explore the responsiveness concept as a possibility to evaluate the performance of mental health care. METHOD: Face to face interviews with users of outpatient and hostel mental health services by means of a standardised instrument, developed by WHO were carried out. RESULTS: Overall responsiveness in outpatient care was rated by a lower proportion of users negative than responsiveness in hostel care (15 vs. 20%). Socio-demographic characteristics were related only to responsiveness ratings in hostel care when legal guardianship was considered. Domains indicated as most important (attention, participation) in out-patient care did not perform well there. In hostel care the domains attention and respect were rated as most important. These domains performed well. DISCUSSION AND CONCLUSIONS: The results are in line with the literature and adequately reflect the realities in mental health care. The responsiveness concept offers a systematic approach for considering the categories "patient orientation" and "respect for persons" as quality criteria in mental health care. Evaluating mental health service provision using the concept of responsiveness, indicates where to launch reforms in health care.

Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil.

Soil ecosystems harbor diverse microorganisms and yet remain only partially characterized as neither single-cell sequencing nor whole-community sequencing offers a complete picture of these complex communities. Thus, the genetic and metabolic potential of this "uncultivated majority" remains underexplored. To address these challenges, we applied a pooled-cell-sorting-based mini-metagenomics approach and compared the results to bulk metagenomics. Informatic binning of these data produced 200 mini-metagenome assembled genomes (sorted-MAGs) and 29 bulk metagenome assembled genomes (MAGs). The sorted and bulk MAGs increased the known phylogenetic diversity of soil taxa by 7.2% with respect to the Joint Genome Institute IMG/M database and showed clade-specific sequence recruitment patterns across diverse terrestrial soil metagenomes. Additionally, sorted-MAGs expanded the rare biosphere not captured through MAGs from bulk sequences, exemplified through phylogenetic and functional analyses of members of the phylum Bacteroidetes Analysis of 67 Bacteroidetes sorted-MAGs showed conserved patterns of carbon metabolism across four clades. These results indicate that mini-metagenomics enables genome-resolved investigation of predicted metabolism and demonstrates the utility of combining metagenomics methods to tap into the diversity of heterogeneous microbial assemblages.IMPORTANCE Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented Bacteroidetes phylum provided insights into conserved and clade-specific patterns of carbon metabolism.

Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs.

Infection of macaques with chimeric simian-human immunodeficiency virus (SHIV) provides an excellent in vivo model for examining the influence of envelope on HIV-1 pathogenesis. Infection with a pathogenic CCR5 (R5)-specific enveloped virus, SHIVSF162P, was compared with infection with the CXCR4 (X4)-specific SHIVSF33A.2. Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes. SHIVSF162P caused a dramatic loss of CD4+ intestinal T cells followed by a gradual depletion in peripheral CD4+ T cells, whereas infection with SHIVSF33A.2 caused a profound loss in peripheral T cells that was not paralleled in the intestine. These results suggest a critical role of co-receptor utilization in viral pathogenesis and provide a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV-1 envelope protein.

Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis.

Resistance to isoniazid in Mycobacterium tuberculosis can be mediated by substitution of alanine for serine 94 in the InhA protein, the drug's primary target. InhA was shown to catalyze the beta-nicotinamide adenine dinucleotide (NADH)-specific reduction of 2-trans-enoyl-acyl carrier protein, an essential step in fatty acid elongation. Kinetic analyses suggested that isoniazid resistance is due to a decreased affinity of the mutant protein for NADH. The three-dimensional structures of wild-type and mutant InhA, refined to 2.2 and 2.7 angstroms, respectively, revealed that drug resistance is directly related to a perturbation in the hydrogen-bonding network that stabilizes NADH binding.

Diminishing returns from mutation supply rate in asexual populations.

Mutator genotypes with increased mutation rates may be especially important in microbial evolution if genetic adaptation is generally limited by the supply of mutations. In experimental populations of the bacterium Escherichia coli, the rate of evolutionary adaptation was proportional to the mutation supply rate only in particular circumstances of small or initially well-adapted populations. These experiments also demonstrate a "speed limit" on adaptive evolution in asexual populations, one that is independent of the mutation supply rate.

The 1.9 A structure of the branched-chain amino-acid transaminase (IlvE) from Mycobacterium tuberculosis.

Unlike mammals, bacteria encode enzymes that synthesize branched-chain amino acids. The pyridoxal 50-phosphate-dependent transaminase performs the final biosynthetic step in these pathways, converting keto acid precursors into -amino acids. The branched-chain amino-acid transaminase from Mycobacterium tuberculosis (MtIlvE) has been crystallized and its structure has been solved at 1.9 angstrom resolution. The MtIlvE monomer is composed of two domains that interact to form the active site. The biologically active form of IlvE is a homodimer in which each monomer contributes a substrate-specificity loop to the partner molecule. Additional substrate selectivity may be imparted by a conserved N-terminal Phe30 residue, which has previously been observed to shield the active site in the type IV fold homodimer. The active site of MtIlvE contains density corresponding to bound PMP, which is likely to be a consequence of the presence of tryptone in the crystallization medium. Additionally, two cysteine residues are positioned at the dimer interface for disulfide-bond formation under oxidative conditions. It is unknown whether they are involved in any regulatory activities analogous to those of the human mitochondrial branched-chain amino-acid transaminase.

Creation and piloting of a new hospital capacity assessment tool in a major urban area.

OBJECTIVES: Crowded hospital emergency departments (EDs) can undermine the ability of a region's safety net to provide safe, timely care. However, data to measure hospital capacity community-wide is generally unavailable. This study aimed to assess hospital crowding, capacity and patient flow in an urban community using the newly developed hospital capacity assessment tool (HCAT). STUDY DESIGN: A survey of the eight acute care hospitals in the District of Columbia (DC) with active EDs. METHODS: Existing emergency care assessment tools were reviewed. Eighteen of the 57 questions on the HCAT were adapted from existing hospital surveys, while the remaining 39 questions were constructed de novo for use in this assessment. Hospitals were provided with paper and electronic versions of the HCAT. RESULTS: All eight DC hospitals completed the HCAT; however, three hospitals were unable to answer many of the questions due to a lack of regular data collection. The HCAT data shows throughput times in DC hospitals that are substantially longer than national averages. CONCLUSIONS: The HCAT is a promising tool for evaluating community-wide emergency care. Findings from the HCAT allowed for the introduction of new ED performance data into the local decision-making process.

Impact of a sports project centered on scuba diving for adolescents with type 1 diabetes mellitus: New guidelines for adolescent recreational diving, a modification of the French regulations.

BACKGROUND: Recreational scuba diving has been authorized for type 1 diabetics over 18 years old - the age of majority in France - since 2004, but it remained forbidden for younger diabetics by the French underwater federation (FFESSM). Here, we present a study to evaluate: - the conditions under which diving could be authorized for 14- to 18 year olds with type 1 diabetes; - the value of continuous glucose monitoring (CGM) while diving. A secondary objective was to monitor the impact of diving on the teenagers' quality of life. SUBJECT AND METHODS: Sixteen adolescents (14-17.5 years old) were included. Diabetes was known for 6 years (range, 1-14) and Hb1Ac was 9.0% (range, 7.7-11.9). The study was conducted in Mayotte with both capillary glycemia (CG) and CGM measurements taken during five dives. RESULTS: The average CG prior to diving was 283mg/dL and decreased by 75±76mg/dL during the dive. No hypoglycemia occurred during the dives and four episodes occurred after. Glycemia variations during dives and for the overall duration of the study were greater than for adults, most likely due to the general adolescent behavior, notably regarding diet and diabetes management. CGM was greatly appreciated by the adolescents. They had an overall satisfactory quality of life. No significant variations were observed during the entire course of the study. CONCLUSIONS: Although in need of further studies, these preliminary results show that CGM can be used while diving. CGM records show a continuous decrease of glycemia during dives. Based on these results, the French underwater federation has now authorized diving for adolescent type 1 diabetics following a specific diving protocol that includes HbA1c<8.5%, autonomous management of diabetes by the adolescent, reduction of insulin doses, and target glycemia prior to the dive>250mg/dL.