Export Production in the Subarctic North Pacific over the Last 800 kyrs: No Evidence for Iron Fertilization?

The subarctic North Pacific is a high nitrate-low chlorophyll (HNLC) region, where phytoplankton growth rates, especially those of diatoms, are enhanced when micronutrient Fe is added. Accordingly, it has been suggested that glacial Fe-laden dust might have increased primary production in this region. This paper reviews published palaeoceanographic records of export production over the last 800 kyrs from the open North Pacific (north of ∼35°N). We find different patterns of export production change over time in the various domains of the North Pacific (NW and NE subarctic gyres, the marginal seas and the transition zone). However, there is no compelling evidence for an overall increase in productivity during glacials in the subarctic region, challenging the paradigm that dust-born Fe fertilization of this region has contributed to the glacial draw down of atmospheric CO 2 . Potential reasons for the lack of increased glacial export production include the possibility that Fe-fertilization rapidly drives the ecosystem towards limitation by another nutrient. This effect would have been exacerbated by an even more stable mixed layer compared to today.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41539/1/10872_2004_Article_5383267.pd

Living with a left ventricular assist device:Capturing recipients experiences using group concept mapping software

BackgroundLeft ventricular assist device (LVAD) implantation significantly impacts on a recipient's symptoms and quality of life. Capturing their experiences and post implant journey is an important part of clinical practice, research and device design evolution. Patient reported outcome measures (PROMs) are a useful tool for capturing that experience. However, patient reported outcome measures need to reflect recipients' experiences. Discussions with a patient partner group found that none of the frequently used cardiology PROMs captured their unique experiences.AimsTo capture the experiences and important issues for LVAD recipients. Develop a conceptual map of domains and items that should be reflected in patient reported outcomes.MethodsGroup concept mapping (GCM) web-based software was used to remotely capture and structure recipients' experiences across a wide geographical area. GCM is a semi-quantitative mixed method consisting of 3 stages: item generation, item sorting and rating (importance, relevance and frequency). Patient partners were involved in all aspects of the study design and development.Results18 LVAD recipients consented to take part. 101 statements were generated and multi-dimensional scaling, and hierarchical cluster analysis identified 9 clusters. Cluster themes included: Activities, Partner/family support, Travel, Mental wellbeing, Equipment and clothing, Physical and cognitive limitations, LVAD Restrictions, LVAD Challenges and positive impact of the LVAD (LVAD Positives). LVAD Positives were scored highest across all the rating variables, e.g., frequency (2.85), relevance (2.44) and importance (2.21). Other domains rated high for importance included physical and cognitive limitations (2.19), LVAD restrictions (2.11), Partner/family support (2.02), and Equipment and clothing (2.01).ConclusionOnline GCM software facilitated the inclusion of geographically dispersed recipients and provided useful insights into the experiences of LVAD recipients. The conceptual framework identifies important domains and items that should be prioritised and included in patient reported outcomes in future research, LVAD design evolution, and clinical practice

Heterogeneous seismic velocity structure of the upper lithosphere at Kane oceanic core complex, Mid-Atlantic Ridge

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 10 (2009): Q10001, doi:10.1029/2009GC002586.The Kane oceanic core complex (OCC) is a large, corrugated megamullion that was formed by a long-lived detachment fault at the axis of the Mid-Atlantic Ridge adjacent to Kane Fracture Zone between 2.1 and 3.3 Ma. We use refracted arrivals recorded along a 6-km-long hydrophone streamer during a multichannel seismic survey to constrain the shallow seismic velocity structure of the OCC. Results are presented in high-resolution traveltime seismic tomographic models along six lines that cover all of the main morphological features of the megamullion. The models show large lateral variability in P wave velocity within the upper ∼0.5–2.0 km of the lithosphere, and these variations correlate to first order with observed variations in lithology, documented by in situ basement samples and seafloor morphology. Lithological interpretation of the velocity models indicates that there is marked lateral variability in distribution of gabbroic intrusions, serpentinized peridotites, and basalts at scales of a few kilometers to ∼10 km. Serpentinized peridotites appear to dominate the central and older parts of the OCC. High-velocity gabbros are consistently (but not exclusively) present closer to the termination of the Kane detachment fault and toward the ends of the OCC. The structure of the lithosphere exhumed by the Kane detachment fault is far from the standard ophiolite-based Penrose model, and it does not show segment-centered magmatism that is commonly interpreted at slow spreading ridges. If the gabbros exhumed toward the termination of the OCC were emplaced deep (∼10 km) beneath the spreading axis, they may have constituted a weak zone that focused initiation of the Kane detachment fault. Alternately, as the OCC footwall was being exhumed the gabbros may have been emplaced because of dynamic changes in melt supply, changes in mantle fertility, or decompression melting. Late stage volcanism is clearly associated with a major high-angle normal fault that cuts the detachment surface; this volcanism may have been stimulated or enhanced by bending stresses in the bending footwall. The shape of the large-scale corrugated morphology of the OCC is nearly invariant in the dip direction across major changes in basement lithology, indicating that once established, the form of the Kane detachment fault was highly resistant to modification.This research was supported by NSF grants OCE-9987004 and OCE-0621660

Glacial-interglacial modulation of the marine nitrogen cycle by high-latitude O2 supply to the global thermocline

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 19 (2004): PA4007, doi:10.1029/2003PA001000.An analysis of sedimentary nitrogen isotope records compiled from widely distributed marine environments emphasizes the global synchrony of denitrification changes and provides evidence for a strong temporal coupling of these variations to changes in nitrogen fixation as previously inferred. We explain the global coherence of these records by a simple physical control on the flux of dissolved oxygen to suboxic zones and the coupling to fixation via the supply of phosphorus to diazotrophs in suitable environments. According to our hypothesis, lower glacial-stage sea surface temperature increased oxygen solubility, while stronger winds in high-latitude regions enhanced the rate of thermocline ventilation. The resultant colder, rapidly flushed thermocline lessened the spatial extent of denitrification and, consequently, N fixation. During warm periods, sluggish circulation of warmer, less oxygen rich thermocline waters caused expansion of denitrification zones and a concomitant increase in N fixation. Local fluctuations in export productivity would have modulated this global signal.Financial support for this work was provided by the Natural Sciences and Engineering Research Council of Canada and by a WHOI postdoctoral fellowship to MK

Evaluation of the clinical and cost effectiveness of intermediate care clinics for diabetes (ICCD): A multicentre cluster randomised controlled trial

Background Configuring high quality care for the rapidly increasing number of people with type 2 diabetes (T2D) is a major challenge worldwide for both providers and commissioners. In the UK, about two thirds of people with T2D are managed entirely in primary care, with wide variation in management strategies and achievement of targets. Pay for performance, introduced in 2004, initially resulted in improvements but disparities exist in ethnic minorities and the improvements are levelling off. Community based, intermediate care clinics for diabetes (ICCDs) were considered one solution and are functioning across the UK. However, there is no randomised trial evidence for the effectiveness of such clinics. Trial Design, Methods and Findings This is a cluster-randomised trial, involving 3 primary care trusts, with 49 general practices randomised to usual care (n = 25) or intervention (ICCDs; n = 24). All eligible adult patients with T2D were invited; 1997 were recruited and 1280 followed-up after 18-months intervention. Primary outcome: achievement of all three of the NICE targets [(HbA1c≤7.0%/53 mmol/mol; Blood Pressure <140/80 mmHg; cholesterol <154 mg/dl (4 mmol/l)]. Primary outcome was achieved in 14.3% in the intervention arm vs. 9.3% in the control arm (p = 0.059 after adjustment for covariates). The odds ratio (95% CI) for achieving primary outcome in the intervention group was 1.56 (0.98, 2.49). Primary care and community clinic costs were significantly higher in the intervention group, but there were no significant differences in hospital costs or overall healthcare costs. An incremental cost-effectiveness ratio (ICER) of +£7,778 per QALY gained, indicated ICCD was marginally more expensive at producing health gain. Conclusions Intermediate care clinics can contribute to improving target achievement in patients with diabetes. Further work is needed to investigate the optimal scale and organisational structure of ICCD services and whether, over time, their role may change as skill levels in primary care increase. Trial Registration ClinicalTrials.gov NCT00945204; National Research Register (NRR) M0014178167.National Institute of Health Research Project number: SDO/110/2005. Initial service for support costs was provided by Department of health.NHS Leicester City, Thames Valley Diabetes Research Network (TVDRN), West Midlands South Comprehensive Local Research Network (CLRN), Primary Care Research Network (PCRN) and DIERT charity provided additional support for the successful completion of the study

A comparison of five surface mixed layer models with a year of observations in the North Atlantic

Five upper ocean mixed layer models driven by ERA-Interim surface forcing are compared with a year of hydrographic observations of the upper 1000 m, taken at the Porcupine Abyssal Plain observatory site using profiling gliders. All the models reproduce sea surface temperature (SST) fairly well, with annual mean warm biases of 0.11  ° C (PWP model), 0.24  ° C (GLS), 0.31  ° C (TKE), 0.91  ° C (KPP) and 0.36  ° C (OSMOSIS). The main exception is that the KPP model has summer SSTs which are higher than the observations by nearly 3 ° . Mixed layer salinity (MLS) is not reproduced well by the models and the biases are large enough to produce a non-trivial density bias in the Eastern North Atlantic Central Water which forms in this region in winter. All the models develop mixed layers which are too deep in winter, with average winter mixed layer depth (MLD) biases between 160 and 228 m. The high variability in winter MLD is reproduced more successfully by model estimates of the depth of active mixing and/or boundary layer depth than by model MLD based on water column properties. After the spring restratification event, biases in MLD are small and do not appear to be related to the preceding winter biases. There is a very clear relationship between MLD and local wind stress in all models and in the observations during spring and summer, with increased wind speeds leading to deepening mixed layers, but this relationship is not present during autumn and winter. We hypothesize that the deepening of the MLD in autumn is so strongly driven by the annual cycle in surface heat flux that the winds are less significant in the autumn. The surface heat flux drives a diurnal cycle in MLD and SST from March onwards, though this effect is much more significant in the models than in the observations. We are unable to identify one model as definitely better than the others. The only clear differences between the models are KPP’s inability to accurately reproduce summer SSTs, and the OSMOSIS model’s more accurate reproduction of MLS

A map of transcriptional heterogeneity and regulatory variation in human microglia.

Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease

De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies

Epileptic encephalopathies (EEs) are the most clinically important group of severe early-onset epilepsies. Next-generation sequencing has highlighted the crucial contribution of de novo mutations to the genetic architecture of EEs as well as to their underlying genetic heterogeneity. Our previous whole-exome sequencing study of 264 parent-child trios revealed more than 290 candidate genes in which only a single individual had a de novo variant. We sought to identify additional pathogenic variants in a subset (n = 27) of these genes via targeted sequencing in an unsolved cohort of 531 individuals with a diverse range of EEs. We report 17 individuals with pathogenic variants in seven of the 27 genes, defining a genetic etiology in 3.2% of this unsolved cohort. Our results provide definitive evidence that de novo mutations in SLC1A2 and CACNA1A cause specific EEs and expand the compendium of clinically relevant genotypes for GABRB3. We also identified EEs caused by genetic variants in ALG13, DNM1, and GNAO1 and report a mutation in IQSEC2. Notably, recurrent mutations accounted for 7/17 of the pathogenic variants identified. As a result of high-depth coverage, parental mosaicism was identified in two out of 14 cases tested with mutant allelic fractions of 5%–6% in the unaffected parents, carrying significant reproductive counseling implications. These results confirm that dysregulation in diverse cellular neuronal pathways causes EEs, and they will inform the diagnosis and management of individuals with these devastating disorders

Psychiatric and medical comorbidities of eating disorders : findings from a rapid review of the literature

Background: Eating disorders (EDs) are potentially severe, complex, and life-threatening illnesses. The mortality rate of EDs is signifcantly elevated compared to other psychiatric conditions, primarily due to medical complications and suicide. The current rapid review aimed to summarise the literature and identify gaps in knowledge relating to any psychiatric and medical comorbidities of eating disorders. Methods: This paper forms part of a rapid review) series scoping the evidence base for the feld of EDs, conducted to inform the Australian National Eating Disorders Research and Translation Strategy 2021–2031, funded and released by the Australian Government. ScienceDirect, PubMed and Ovid/Medline were searched for English-language studies focused on the psychiatric and medical comorbidities of EDs, published between 2009 and 2021. High-level evidence such as meta-analyses, large population studies and Randomised Control Trials were prioritised. Results: A total of 202 studies were included in this review, with 58% pertaining to psychiatric comorbidities and 42% to medical comorbidities. For EDs in general, the most prevalent psychiatric comorbidities were anxiety (up to 62%), mood (up to 54%) and substance use and post-traumatic stress disorders (similar comorbidity rates up to 27%). The review also noted associations between specifc EDs and non-suicidal self-injury, personality disorders, and neurodevelopmental disorders. EDs were complicated by medical comorbidities across the neuroendocrine, skeletal, nutritional, gastrointestinal, dental, and reproductive systems. Medical comorbidities can precede, occur alongside or emerge as a complication of the ED. Conclusions: This review provides a thorough overview of the comorbid psychiatric and medical conditions cooccurring with EDs. High psychiatric and medical comorbidity rates were observed in people with EDs, with comorbidities contributing to increased ED symptom severity, maintenance of some ED behaviours, and poorer functioning as well as treatment outcomes. Early identifcation and management of psychiatric and medical comorbidities in people with an ED may improve response to treatment and overall outcomes

Felony Murder and Capital Punishment: an Examination of the Deterrence Question

A proper test of the deterrent effect of the death penalty must consider capital homicides. However, the criterion variable in most investigations has been total homicides—most of which bear no legal or theoretical relationship to capital punishment. To address this fundamental data problem, this investigation used Federal Bureau of Investigation data for 1976–1987 to examine the relationship between capital punishment and felony murder, the most common type of capital homicide. We conducted time series analyses of monthly felony murder rates, the frequency of executions, and the amount and type of television coverage of executions over the period. The analyses revealed occasional departures (for vehicle theft and narcotics killings) from the null hypotheses. However, on balance, and in line with the vast majority of capital punishment studies, this investigation found no consistent evidence that executions and the television coverage they receive are associated significantly with rates for total, index, or different types of felony murder