Iron (Fe) is an essential trace element for marine life. Extremely low Fe concentrations limit primary production and nitrogen fixation in large parts of the oceans and consequently influence ocean ...ecosystem functioning. The importance of Fe for ocean ecosystems makes Fe one of the core chemical trace elements in the international GEOTRACES program. Despite the recognized importance of Fe, our present knowledge of its supply and biogeochemical cycle has been limited by mostly fragmentary datasets. Here, we present highly accurate dissolved Fe (DFe) values measured at an unprecedented high intensity (1407 samples) along the longest full ocean depth transect (17,500 kilometers) covering the entire western Atlantic Ocean. DFe measurements along this transect unveiled details about the supply and cycling of Fe. External sources of Fe identified included off-shelf and river supply, hydrothermal vents and aeolian dust. Nevertheless, vertical processes such as the recycling of Fe resulting from the remineralization of sinking organic matter and the removal of Fe by scavenging still dominated the distribution of DFe. In the northern West Atlantic Ocean, Fe recycling and lateral transport from the eastern tropical North Atlantic Oxygen Minimum Zone (OMZ) dominated the DFe-distribution. Finally, our measurements showed that the North Atlantic Deep Water (NADW), the major driver of the so-called ocean conveyor belt, contains excess DFe relative to phosphate after full biological utilization and is therefore an important source of Fe for biological production in the global ocean.
Extremely dense breast tissue is a risk factor for breast cancer and limits the detection of cancer with mammography. Data are needed on the use of supplemental magnetic resonance imaging (MRI) to ...improve early detection and reduce interval breast cancers in such patients.
In this multicenter, randomized, controlled trial in the Netherlands, we assigned 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography to a group that was invited to undergo supplemental MRI or to a group that received mammography screening only. The groups were assigned in a 1:4 ratio, with 8061 in the MRI-invitation group and 32,312 in the mammography-only group. The primary outcome was the between-group difference in the incidence of interval cancers during a 2-year screening period.
The interval-cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group, for a difference of 2.5 per 1000 screenings (95% confidence interval CI, 1.0 to 3.7; P<0.001). Of the women who were invited to undergo MRI, 59% accepted the invitation. Of the 20 interval cancers that were diagnosed in the MRI-invitation group, 4 were diagnosed in the women who actually underwent MRI (0.8 per 1000 screenings) and 16 in those who did not accept the invitation (4.9 per 1000 screenings). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings (95% CI, 13.3 to 20.5). The positive predictive value was 17.4% (95% CI, 14.2 to 21.2) for recall for additional testing and 26.3% (95% CI, 21.7 to 31.6) for biopsy. The false positive rate was 79.8 per 1000 screenings. Among the women who underwent MRI, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening.
The use of supplemental MRI screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone during a 2-year screening period. (Funded by the University Medical Center Utrecht and others; DENSE ClinicalTrials.gov number, NCT01315015.).
Summary
In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical ...density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites.
Introduction
To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters.
Methods
Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history.
Results
After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters.
Conclusions
In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.
Vitamin K occurs in the diet as phylloquinone and menaquinones. Observational studies have shown that both phylloquinone and menaquinone intake might reduce cardiovascular disease (CVD) risk. ...However, the effect of vitamin K on vascular calcification is unknown.
The aim of this study was to assess if menaquinone supplementation, compared to placebo, decreases vascular calcification in people with type 2 diabetes and known CVD.
In this double-blind, randomized, placebo-controlled trial, we randomly assigned men and women with type 2 diabetes and CVD to 360 µg/d menaquinone-7 (MK-7) or placebo for 6 mo. Femoral arterial calcification at baseline and 6 mo was measured with 18sodium fluoride positron emission tomography (18F-NaF PET) scans as target-to-background ratios (TBRs), a promising technique to detect active calcification. Calcification mass on conventional computed tomography (CT) scan was measured as secondary outcome. Dephosphorylated–uncarboxylated matrix Gla protein (dp-ucMGP) concentrations were measured to assess compliance. Linear regression analyses were performed with either TBR or CT calcification at follow-up as the dependent variable, and treatment and baseline TBR or CT calcification as independent variables.
We randomly assigned 35 patients to the MK-7 group (33 completed follow-up) and 33 to the placebo group (27 completed follow-up). After the 6-mo intervention, TBR tended to increase in the MK-7 group compared with placebo (0.25; 95% CI: −0.02, 0.51; P = 0.06), although this was not significant. Log-transformed CT calcification mass did not increase in the intervention group compared with placebo (0.50; 95% CI: −0.23, 1.36; P = 0.18). MK-7 supplementation significantly reduced dp-ucMGP compared with placebo (−205.6 pmol/L; 95% CI: −255.8, −155.3 pmol/L). No adverse events were reported.
MK-7 supplementation tended to increase active calcification measured with 18F-NaF PET activity compared with placebo, but no effect was found on conventional CT. Additional research investigating the interpretation of 18F-NaF PET activity is necessary. This trial was registered at clinicaltrials.gov as NCT02839044.
Background There is increasing data that show a persistently impaired pulmonary function upon recovery after severe infection. Little is known however about the extent, recovery and determinants of ...pulmonary impairment across the full spectrum of COVID-19 severity over time. Methods In a well characterized, prospective cohort of both hospitalised and non-hospitalised individuals with SARS-CoV-2 infection, the RECoVERED study, pulmonary function (diffusing capacity for carbon monoxide (DLCO)) and spirometry) was measured until one year after disease onset. Additionally, data on sociodemographics, clinical characteristics, symptoms, and health-related quality of life (HRQL) were collected. Pulmonary function and these determinants were modelled over time using mixed-effect linear regression. Determinants of pulmonary function impairment at 12 months after disease onset were identified using logistic regression. Findings Between May 2020 and December 2021, 301 of 349 participants underwent at least one pulmonary function test. After one year of follow-up, 25% of the participants had an impaired pulmonary function which translates in 11%, 22%, and 48% of the participants with mild, moderate and severe/critical COVID-19. Improvement in DLCO among the participants continued over the period across one, six and twelve months. Being older, having more than three comorbidities (p<0·001) and initial severe/critical disease (p<0·001) were associated with slower improvement of pulmonary function over time, adjusted for age and sex. HRQL improved over time and at 12 months was comparable to individuals without impaired pulmonary function. Interpretation The prevalence of impaired pulmonary function after twelve months of follow-up, was still significant among those with initially moderate or severe/critical COVID-19. Pulmonary function increased over time in most of the severity groups. These data imply that guidelines regarding revalidation after COVID-19 should target individuals with moderate and severe/critical disease severities.
We present cosmological parameter constraints from a tomographic weak gravitational lensing analysis of ~450 deg super( 2) of imaging data from the Kilo Degree Survey (KiDS). For a flat ... cold dark ...matter (...CDM) cosmology with a prior on H sub( 0) that encompasses the most recent direct measurements, we find S sub( 8) ... = 0.745 plus or minus 0.039. This result is in good agreement with other low-redshift probes of large-scale structure, including recent cosmic shear results, along with pre-Planck cosmic microwave background constraints. A 2.3... tension in S sub( 8) and 'substantial discordance' in the full parameter space is found with respect to the Planck 2015 results. We use shear measurements for nearly 15 million galaxies, determined with a new improved 'self-calibrating' version of lensfit validated using an extensive suite of image simulations. Four-band ugri photometric redshifts are calibrated directly with deep spectroscopic surveys. The redshift calibration is confirmed using two independent techniques based on angular cross-correlations and the properties of the photometric redshift probability distributions. Our covariance matrix is determined using an analytical approach, verified numerically with large mock galaxy catalogues. We account for uncertainties in the modelling of intrinsic galaxy alignments and the impact of baryon feedback on the shape of the non-linear matter power spectrum, in addition to the small residual uncertainties in the shear and redshift calibration. The cosmology analysis was performed blind. Our high-level data products, including shear correlation functions, covariance matrices, redshift distributions, and Monte Carlo Markov chains are available at http://kids.strw.leidenuniv.nl. (ProQuest: ... denotes formulae/symbols omitted.)
Extracellular vesicles (EVs) form an endogenous transport system for intercellular transfer of biological cargo, including RNA, that plays a pivotal role in physiological and pathological processes. ...Unfortunately, whereas biological effects of EV-mediated RNA transfer are abundantly studied, regulatory pathways and mechanisms remain poorly defined due to a lack of suitable readout systems. Here, we describe a highly-sensitive CRISPR-Cas9-based reporter system that allows direct functional study of EV-mediated transfer of small non-coding RNA molecules at single-cell resolution. Using this CRISPR operated stoplight system for functional intercellular RNA exchange (CROSS-FIRE) we uncover various genes involved in EV subtype biogenesis that play a regulatory role in RNA transfer. Moreover we identify multiple genes involved in endocytosis and intracellular membrane trafficking that strongly regulate EV-mediated functional RNA delivery. Altogether, this approach allows the elucidation of regulatory mechanisms in EV-mediated RNA transfer at the level of EV biogenesis, endocytosis, intracellular trafficking, and RNA delivery.
Objectives
To present the results of a systematic literature search aimed at determining to what extent the radiation dose can be reduced with iterative reconstruction (IR) for cardiopulmonary and ...body imaging with computed tomography (CT) in the clinical setting and what the effects on image quality are with IR versus filtered back-projection (FBP) and to provide recommendations for future research on IR.
Methods
We searched Medline and Embase from January 2006 to January 2012 and included original research papers concerning IR for CT.
Results
The systematic search yielded 380 articles. Forty-nine relevant studies were included. These studies concerned: the chest(
n
= 26), abdomen(
n
= 16), both chest and abdomen(
n
= 1), head(
n
= 4), spine(
n
= 1), and no specific area (
n
= 1). IR reduced noise and artefacts, and it improved subjective and objective image quality compared to FBP at the same dose. Conversely, low-dose IR and normal-dose FBP showed similar noise, artefacts, and subjective and objective image quality. Reported dose reductions ranged from 23 to 76 % compared to locally used default FBP settings. However, IR has not yet been investigated for ultra-low-dose acquisitions with clinical diagnosis and accuracy as endpoints.
Conclusion
Benefits of IR include improved subjective and objective image quality as well as radiation dose reduction while preserving image quality. Future studies need to address the value of IR in ultra-low-dose CT with clinically relevant endpoints.
Key Points
•
Iterative reconstruction improves image quality of CT images at equal acquisition parameters.
•
IR preserves image quality compared to normal-dose filtered back-projection.
•
The reduced radiation dose made possible by IR is advantageous for patients.
•
IR has not yet been investigated with clinical diagnosis and accuracy as endpoints.
Methane (CH4) is produced in many natural systems that are vulnerable to change under a warming climate, yet current CH4 budgets, as well as future shifts in CH4 emissions, have high uncertainties. ...Climate change has the potential to increase CH4 emissions from critical systems such as wetlands, marine and freshwater systems, permafrost, and methane hydrates, through shifts in temperature, hydrology, vegetation, landscape disturbance, and sea level rise. Increased CH4 emissions from these systems would in turn induce further climate change, resulting in a positive climate feedback. Here we synthesize biological, geochemical, and physically focused CH4 climate feedback literature, bringing together the key findings of these disciplines. We discuss environment‐specific feedback processes, including the microbial, physical, and geochemical interlinkages and the timescales on which they operate, and present the current state of knowledge of CH4 climate feedbacks in the immediate and distant future. The important linkages between microbial activity and climate warming are discussed with the aim to better constrain the sensitivity of the CH4 cycle to future climate predictions. We determine that wetlands will form the majority of the CH4 climate feedback up to 2100. Beyond this timescale, CH4 emissions from marine and freshwater systems and permafrost environments could become more important. Significant CH4 emissions to the atmosphere from the dissociation of methane hydrates are not expected in the near future. Our key findings highlight the importance of quantifying whether CH4 consumption can counterbalance CH4 production under future climate scenarios.
Plain Language Summary
Methane is a powerful greenhouse gas, second only to carbon dioxide in its importance to climate change. Methane production in natural environments is controlled by factors that are themselves influenced by climate. Increased methane production can warm the Earth, which can in turn cause methane to be produced at a faster rate ‐ this is called a positive climate feedback. Here we describe the most important natural environments for methane production that have the potential to produce a positive climate feedback. We discuss how these feedbacks may develop in the coming centuries under predicted climate warming using a cross‐disciplinary approach. We emphasize the importance of considering methane dynamics at all scales, especially its production and consumption and the role microorganisms play in both these processes, to our understanding of current and future global methane emissions. Marrying large‐scale geophysical studies with site‐scale biogeochemical and microbial studies will be key to this.
Key Points
The key drivers of methane production and consumption are assessed for wetlands, marine and freshwaters, permafrost regions, and methane hydrates
The balance of microbial controlled methane production and consumption are critical to methane climate feedbacks in all environments
Wetlands and freshwater systems are likely to drive the methane climate feedback from natural settings in the coming century
Worldwide, over 500,000 people are diagnosed with head and neck cancer each year, a disease with major impact on life expectancy and quality of life. The purpose of the Netherlands Quality of life ...and Biomedical Cohort study (NET-QUBIC) is to advance interdisciplinary research that aims to optimize diagnosis, treatment, and supportive care for head and neck cancer patients and their informal caregivers.
Using an extensive assessment protocol (electronic clinical record form, patient reported outcome measures and fieldwork (interviews and physical tests)), clinical data and data on quality of life, demographic and personal factors, psychosocial (depression, anxiety, fatigue, pain, sleep, mental adjustment to cancer, posttraumatic stress), physical (speech, swallowing, oral function, malnutrition, physical fitness, neurocognitive function, sexual function), lifestyle (physical activity, nutrition, smoking, alcohol, drugs), and social factors (social function, social support, work, health care use, and costs) are collected and stored in the data warehouse. A longitudinal biobank is built with tumor tissue, blood and blood components, saliva samples, and oral rinses. An infrastructure for fieldwork and laboratory protocols is established at all participating centers. All patients fill out patient reported outcome measures before treatment and at 3, 6, 12, 24, 36, 48, and 60 months follow-up. The interviews, physical tests and biological sample collection are at baseline and 6, 12, and 24 months follow-up. The protocol for caregivers includes blood sampling and oral rinses at baseline and a tailored list of questionnaires, administered at the same time points as the patients. In total, 739 HNC patients and 262 informal caregivers have been included in 5 out of the 8 HNC centers in the Netherlands.
By granting access to researchers to the NET-QUBIC data warehouse and biobank, we enable new research lines in clinical (e.g. treatment optimization in elderly patients), biological (e.g. liquid biopsy analysis for relapse detection), health related quality of life (e.g. the impact of toxicity on quality of life), and interrelated research (e.g. health related quality of life in relation to biomarkers and survival).
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