Iron (Fe) is an essential micronutrient for marine microbial organisms, and low supply controls productivity in large parts of the world's ocean. The high latitude North Atlantic is seasonally Fe ...limited, but Fe distributions and source strengths are poorly constrained. Surface ocean dissolved Fe (DFe) concentrations were low in the study region (<0.1 nM) in summer 2010, with significant perturbations during spring 2010 in the Iceland Basin as a result of an eruption of the Eyjafjallajökull volcano (up to 2.5 nM DFe near Iceland) with biogeochemical consequences. Deep water concentrations in the vicinity of the Reykjanes Ridge system were influenced by pronounced sediment resuspension, with indications for additional inputs by hydrothermal vents, with subsequent lateral transport of Fe and manganese plumes of up to 250-300 km. Particulate Fe formed the dominant pool, as evidenced by 4-17 fold higher total dissolvable Fe compared with DFe concentrations, and a dynamic exchange between the fractions appeared to buffer deep water DFe. Here we show that Fe supply associated with deep winter mixing (up to 103 nmol m
d
) was at least ca. 4-10 times higher than atmospheric deposition, diffusive fluxes at the base of the summer mixed layer, and horizontal surface ocean fluxes.
Recently, remarkable advances have been made in coupling a number of high-Q modes of nano-mechanical systems to high-finesse optical cavities, with the goal of reaching regimes in which quantum ...behavior can be observed and leveraged toward new applications. To reach this regime, the coupling between these systems and their thermal environments must be minimized. Here we propose a novel approach to this problem, in which optically levitating a nano-mechanical system can greatly reduce its thermal contact, while simultaneously eliminating dissipation arising from clamping. Through the long coherence times allowed, this approach potentially opens the door to ground-state cooling and coherent manipulation of a single mesoscopic mechanical system or entanglement generation between spatially separate systems, even in room-temperature environments. As an example, we show that these goals should be achievable when the mechanical mode consists of the center-of-mass motion of a levitated nanosphere.
The prevalence of clinically-relevant bacterial strains resistant to current antibiotic therapies is increasing and has been recognized as a major health threat. For example, multidrug-resistant ...tuberculosis and methicillin-resistant Staphylococcus aureus are of global concern. Novel methodologies are needed to identify new targets or novel compounds unaffected by pre-existing resistance mechanisms. Recently, water-in-oil picodroplets have been used as an alternative to conventional high-throughput methods, especially for phenotypic screening. Here we demonstrate a novel microfluidic-based picodroplet platform which enables high-throughput assessment and isolation of antibiotic-resistant bacteria in a label-free manner. As a proof-of-concept, the system was used to isolate fusidic acid-resistant mutants and estimate the frequency of resistance among a population of Escherichia coli (strain HS151). This approach can be used for rapid screening of rare antibiotic-resistant mutants to help identify novel compound/target pairs.
The integration of nanophotonics and atomic physics has been a long-sought goal that would open new frontiers for optical physics, including novel quantum transport and many-body phenomena with ...photon-mediated atomic interactions. Reaching this goal requires surmounting diverse challenges in nanofabrication and atomic manipulation. Here we report the development of a novel integrated optical circuit with a photonic crystal capable of both localizing and interfacing atoms with guided photons. Optical bands of a photonic crystal waveguide are aligned with selected atomic transitions. From reflection spectra measured with average atom number N=1.1+/-0.4, we infer that atoms are localized within the waveguide by optical dipole forces. The fraction of single-atom radiative decay into the waveguide is Γ1D/Γ'≃(0.32±0.08), where Γ1D is the rate of emission into the guided mode and Γ' is the decay rate into all other channels. Γ1D/Γ' is unprecedented in all current atom-photon interfaces.
Mountains are the water towers of the world, supplying a substantial part of both natural and anthropogenic water demands
. They are highly sensitive and prone to climate change
, yet their ...importance and vulnerability have not been quantified at the global scale. Here we present a global water tower index (WTI), which ranks all water towers in terms of their water-supplying role and the downstream dependence of ecosystems and society. For each water tower, we assess its vulnerability related to water stress, governance, hydropolitical tension and future climatic and socio-economic changes. We conclude that the most important (highest WTI) water towers are also among the most vulnerable, and that climatic and socio-economic changes will affect them profoundly. This could negatively impact 1.9 billion people living in (0.3 billion) or directly downstream of (1.6 billion) mountainous areas. Immediate action is required to safeguard the future of the world's most important and vulnerable water towers.
Vaginal microbiota composition is associated with spontaneous preterm birth (sPTB), depending on ethnicity. Host-microbiota interactions are thought to play an important underlying role in this ...association between ethnicity, vaginal microbiota and sPTB.
In a prospective cohort of nulliparous pregnant women, we assessed vaginal microbiota composition, vaginal immunoglobulins (Igs), and local inflammatory markers. We performed a nested case-control study with 19 sPTB cases, matched based on ethnicity and midwifery practice to 19 term controls.
Of the 294 included participants, 23 pregnancies ended in sPTB. We demonstrated that Lactobacillus iners-dominated microbiota, diverse microbiota, and ethnicity were all independently associated with sPTB. Microbial Ig coating was associated with both microbiota composition and ethnicity, but a direct association with sPTB was lacking. Microbial IgA and IgG coating were lowest in diverse microbiota, especially in women of any ethnic minority. When correcting for microbiota composition, increased microbial Ig coating correlated with increased inflammation.
In these nulliparous pregnant women, vaginal microbiota composition is strongly associated with sPTB. Our results support that vaginal mucosal Igs might play a pivotal role in microbiota composition, microbiota-related inflammation, and vaginal community disparity within and between ethnicities. This study provides insight in host-microbe interaction, suggesting that vaginal mucosal Igs play an immunomodulatory role similar to that in the intestinal tract. Video Abstract.
Do parental characteristics and treatment with ART affect perinatal outcomes in singleton pregnancies?
Both parental and ART treatment characteristics affect perinatal outcomes in singleton ...pregnancies.
Previous studies have shown that singleton pregnancies resulting from ART are at risk of preterm birth. ART children are lighter at birth after correction for duration of gestation and at increased risk of congenital abnormalities compared to naturally conceived children. This association is confounded by parental characteristics that are also known to affect perinatal outcomes. It is unclear to which extent parental and ART treatment characteristics independently affect perinatal outcomes.
All IVF clinics in the Netherlands (n = 13) were requested to provide data on all ART treatment cycles (IVF, ICSI and frozen-thawed embryo transfers (FET)), performed between 1 January 2000, and 1 January 2011, which resulted in a pregnancy. Using probabilistic data-linkage, these data (n = 36 683) were linked to the Dutch Perinatal Registry (Perined), which includes all children born in the Netherlands in the same time period (n = 2 548 977).
Analyses were limited to singleton pregnancies that resulted from IVF, ICSI or FET cycles. Multivariable models for linear and logistic regression were fitted including parental characteristics as well as ART treatment characteristics. Analyses were performed separately for fresh cycles and for fresh and FET cycles combined. We assessed the impact on the following perinatal outcomes: birth weight, preterm birth below 37 or 32 weeks of gestation, congenital malformations and perinatal mortality.
The perinatal outcomes of 31 184 out of the 36 683 ART treatment cycles leading to a pregnancy were retrieved through linkage with the Perined (85% linkage). Of those, 23 671 concerned singleton pregnancies resulting from IVF, ICSI or FET. Birth weight was independently associated with both parental and ART treatment characteristics. Characteristics associated with lower birth weight included maternal hypertensive disease, non-Dutch maternal ethnicity, nulliparity, increasing duration of subfertility, hCG for luteal phase support (compared to progesterone), shorter embryo culture duration, increasing number of oocytes retrieved and fresh embryo transfer. The parental characteristic with the greatest effect size on birth weight was maternal diabetes (adjusted difference 283 g, 95% CI 228-338). FET was the ART treatment characteristic with the greatest effect size on birth weight (adjusted difference 100 g, 95% CI 84-117) compared to fresh embryo transfer. Preterm birth was more common among mothers of South-Asian ethnicity. Preterm birth was less common among multiparous women and women with 'male factor' as treatment indication (compared to 'tubal factor').
Due to the retrospective nature of our study, we cannot prove causality. Further limitations of our study were the inability to adjust for mothers giving birth more than once in our dataset, missing values for several variables and limited information on parental lifestyle and general health.
Multiple parental and ART treatment characteristics affect perinatal outcomes, with birth weight being influenced by the widest range of factors. This highlights the importance of assessing both parental and ART treatment characteristics in studies that focus on the health of ART-offspring, with the purpose of modifying these factors where possible. Our results further support the hypothesis that the embryo is sensitive to its early environment.
This study was funded by Foreest Medical School, Alkmaar, the Netherlands (grants: FIO 1307 and FIO 1505). B.W.M. reports grants from NHMRC and consultancy for ObsEva, Merck KGaA, iGenomics and Guerbet. F.B. reports research support grants from Merck Serono and personal fees from Merck Serono. A.C. reports travel support from Ferring BV. and Theramex BV. and personal fees from UpToDate (Hyperthecosis), all outside the remit of the current work. The remaining authors report no conflict of interests.
N/A.
We use both large and small animal models in our pre-clinical evaluation of gene transfer agents (GTAs) for cystic fibrosis (CF) gene therapy. Here, we report the use of a large animal model to ...assess three non-viral GTAs: 25 kDa-branched polyethyleneimine (PEI), the cationic liposome (GL67A) and compacted DNA nanoparticle formulated with polyethylene glycol-substituted lysine 30-mer. GTAs complexed with plasmids expressing human cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA were administered to the sheep lung (n=8 per group) by aerosol. All GTAs gave evidence of gene transfer and expression 1 day after treatment. Vector-derived mRNA was expressed in lung tissues, including epithelial cell-enriched bronchial brushing samples, with median group values reaching 1-10% of endogenous CFTR mRNA levels. GL67A gave the highest levels of expression. Human CFTR protein was detected in small airway epithelial cells in some animals treated with GL67A (two out of eight) and PEI (one out of eight). Bronchoalveolar lavage neutrophilia, lung histology and elevated serum haptoglobin levels indicated that gene delivery was associated with mild local and systemic inflammation. Our conclusion was that GL67A was the best non-viral GTA currently available for aerosol delivery to the sheep lung, led to the selection of GL67A as our lead GTA for clinical trials in CF patients.
Bordetella hinzii has emerged as an unusual cause of infection in immunocompromised patients, previously linked to zoonotic transmission. Antimicrobial susceptibility and genetic diversity of ...B. hinzii are poorly understood. This study reports phenotypic and genomic characteristics of the first four Australian isolates of B. hinzii obtained from elderly immunocompromised patients. Bordetella hinzii isolates were identified by MALDI-TOF and whole genome sequencing (WGS). Antibiotic susceptibility testing was performed using disk diffusion or E-test. Genomes of B. hinzii were analysed in global context. A phylogenetic tree was constructed of all isolates using Roary and a maximum-likelihood tree was generated from the core-snp alignment. Bordetella hinzii minimum inhibitory concentrations (MICs) were largely uniform with high MICs to ampicillin, ceftriaxone and ciprofloxacin and low MICs to meropenem and piperacillin-tazobactam. Genomic analysis of isolate sequences divided strains analysed into two phylogenetically distinct groups, with one Australian B. hinzii isolate (AUS-4) assigned to Group 1, and the remaining isolates (AUS1-AUS3 and AUS-5) to Group 2. Single nucleotide polymorphism (SNP) analysis revealed two isolates, AUS-1 and AUS-2, were closely related with 14 SNP differences between them. All other Australian isolates were unrelated to each and all other isolates from the international dataset. Bordetella hinzii appears to pose a risk to immunocompromised individuals but remains susceptible to extended spectrum β-lactam and carbapenem antibiotics. Genomic analysis suggested a dissemination of genetically distinct strains.
To assess the association between ketonuria and hyperemesis gravidarum (HG) disease severity.
We included pregnant women hospitalised for HG who participated in the Maternal and Offspring outcomes ...after Treatment of HyperEmesis by Refeeding (MOTHER) trial and women who were eligible, chose not to be randomised and agreed to participate in the observational cohort. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. The presence of ketonuria was not required for study entry. Ketonuria was measured at hospital admission with a dipstick, which distinguishes 5 categories: negative and 1+ through 4 + . The outcome measures were multiple measures of HG disease severity at different time points: 1) At hospital admission (study entry): severity of nausea and vomiting, quality of life and weight change compared to pre-pregnancy weight, 2) One week after hospital admission: severity of nausea and vomiting, quality of life and weight change compared to admission, 3) Duration of index hospital admission and readmission for HG at any time point
215 women where included. Ketonuria was not associated with severity of nausea and vomiting, quality of life or weight loss at hospital admission, nor was the degree of ketonuria at admission associated with any of the outcomes 1 week after hospital admission. The degree of ketonuria was also not associated with the number of readmissions. However, women with a higher degree of ketonuria had a statistically significant longer duration of hospital stay (per 1+ ketonuria, difference: 0.27 days, 95 % CI: 0.05 to 0.48).
There was no association between the degree of ketonuria at admission and severity of symptoms, quality of life, maternal weight loss, or number of readmissions, suggesting that ketonuria provides no information about disease severity or disease course. Despite this, women with a higher degree of ketonuria at admission were hospitalised for longer. This could suggest that health care professionals base length of hospital stay on the degree of ketonuria. Based on the lack of association between ketonuria and disease severity, we suggest it has no additional value in the clinical management of HG.
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