Emerging dominance of summer rainfall driving High Arctic terrestrial-aquatic connectivity.

Hydrological transformations induced by climate warming are causing Arctic annual fluvial energy to shift from skewed (snowmelt-dominated) to multimodal (snowmelt- and rainfall-dominated) distributions. We integrated decade-long hydrometeorological and biogeochemical data from the High Arctic to show that shifts in the timing and magnitude of annual discharge patterns and stream power budgets are causing Arctic material transfer regimes to undergo fundamental changes. Increased late summer rainfall enhanced terrestrial-aquatic connectivity for dissolved and particulate material fluxes. Permafrost disturbances (<3% of the watersheds' areal extent) reduced watershed-scale dissolved organic carbon export, offsetting concurrent increased export in undisturbed watersheds. To overcome the watersheds' buffering capacity for transferring particulate material (30 ± 9 Watt), rainfall events had to increase by an order of magnitude, indicating the landscape is primed for accelerated geomorphological change when future rainfall magnitudes and consequent pluvial responses exceed the current buffering capacity of the terrestrial-aquatic continuum.

Safety of Consecutive Bilateral Decubitus Digital Subtraction Myelography in Patients with Spontaneous Intracranial Hypotension and Occult CSF Leak.

BACKGROUND AND PURPOSE: Digital subtraction myelography performed with the patient in the lateral decubitus position has the potential for increased sensitivity over prone-position myelography in the detection of spinal CSF-venous fistulas, a well-established cause of spontaneous intracranial hypotension. We report on the safety of performing routine, consecutive-day right and left lateral decubitus digital subtraction myelography in these patients. MATERIALS AND METHODS: In this retrospective case series, all patients undergoing consecutive-day lateral decubitus digital subtraction myelography for suspected spinal CSF leak between September 2018 and September 2019 were identified. Chart review was performed to identify any immediate or delayed adverse effects associated with the procedures. Procedural parameters were also analyzed due to inherent variations associated with the positive-pressure myelography technique that was used. RESULTS: A total of 60 patients underwent 68 pairs of consecutive-day lateral decubitus digital subtraction myelographic examinations during the study period. No major adverse effects were recorded. Various minor adverse effects were observed, including pain requiring analgesics (27.2%), nausea/vomiting requiring antiemetics (8.1%), and transient neurologic effects such as syncope, vertigo, altered mental status, and autonomic dysfunction (5.1%). Minor transient neurologic effects were correlated with increasing volumes of intrathecal saline injectate used for thecal sac prepressurization. CONCLUSIONS: In patients with spontaneous intracranial hypotension and suspected spontaneous spinal CSF leak, consecutive-day lateral decubitus digital subtraction myelography demonstrates an acceptable risk profile without evidence of neurotoxic effects from cumulative intrathecal contrast doses. Higher intrathecal saline injectate volumes may correlate with an increased incidence of minor transient periprocedural neurologic effects.

Differential impact of thermal and physical permafrost disturbances on High Arctic dissolved and particulate fluvial fluxes.

Climate warming and changing precipitation patterns have thermally (active layer deepening) and physically (permafrost-thaw related mass movements) disturbed permafrost-underlain watersheds across much of the Arctic, increasing the transfer of dissolved and particulate material from terrestrial to aquatic ecosystems. We examined the multiyear (2006-2017) impact of thermal and physical permafrost disturbances on all of the major components of fluvial flux. Thermal disturbances increased the flux of dissolved organic carbon (DOC), but localized physical disturbances decreased multiyear DOC flux. Physical disturbances increased major ion and suspended sediment flux, which remained elevated a decade after disturbance, and changed carbon export from a DOC to a particulate organic carbon (POC) dominated system. As the magnitude and frequency of physical permafrost disturbance intensifies in response to Arctic climate change, disturbances will become an increasingly important mechanism to deliver POC from terrestrial to aquatic ecosystems. Although nival runoff remained the primary hydrological driver, the importance of pluvial runoff as driver of fluvial flux increased following both thermal and physical permafrost disturbance. We conclude the transition from a nival-dominated fluvial regime to a regime where rainfall runoff is proportionately more important will be a likely tipping point to accelerated High Arctic change.

Effects of whole body vibration on spinal proprioception in healthy individuals.

BACKGROUND: Low back pain (LBP) is a common health problem with high reoccurrence rate. As patients with LBP are often found to be proprioception impaired, new proprioception exercises should be explored. Whole body vibration (WBV) has been proven to improve muscle function and proprioception. OBJECTIVE: The aim of this study was to determine the effects of WBV on spinal proprioception when WBV was administered in standing and seated postures. METHODS: Twenty healthy male individuals (mean age: 23.2±1.2 years) were recruited and randomly assigned to two WBV groups: WBV in standing or WBV in seated posture. Their body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination during dynamic motion in flexion and extension were assessed before, immediately after, 30 minutes after and 1 hour after 5 minutes of WBV (18 Hz, 6 mm amplitude) exposure. A Mixed ANOVA was used to analyze the effects of group and time factors on these four outcome measures. RESULTS: There were no significant interaction (group and time) and group effects on all outcome measures. Participants were found to have significant different time effect on body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination. CONCLUSIONS: WBV could significantly improve spinal proprioception including body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination in healthy individuals. WBV protocol is recommended to confirm its clinical application for improving spinal proprioception and its effects on patients with LBP is warranted.

The Joule heating problem in silver nanowire transparent electrodes.

Silver nanowire transparent electrodes have shown considerable potential to replace conventional transparent conductive materials. However, in this report we show that Joule heating is a unique and serious problem with these electrodes. When conducting current densities encountered in organic solar cells, the average surface temperature of indium tin oxide (ITO) and silver nanowire electrodes, both with sheet resistances of 60 ohms/square, remains below 35 °C. However, in contrast to ITO, the temperature in the nanowire electrode is very non-uniform, with some localized points reaching temperatures above 250 °C. These hotspots accelerate nanowire degradation, leading to electrode failure after 5 days of continuous current flow. We show that graphene, a commonly used passivation layer for these electrodes, slows nanowire degradation and creates a more uniform surface temperature under current flow. However, the graphene does not prevent Joule heating in the nanowires and local points of high temperature ultimately shift the failure mechanism from nanowire degradation to melting of the underlying plastic substrate. In this paper, surface temperature mapping, lifetime testing under current flow, post-mortem analysis, and modelling illuminate the behaviour and failure mechanisms of nanowires under extended current flow and provide guidelines for managing Joule heating.

Rapid Proteomics to Prospect and Validate Novel Bacterial Metabolism Induced by Environmental Burden.

Understanding the pathophysiology of genes and enzymes involved in caffeine metabolism can have extracurricular benefits, such as providing distinct methylxanthines as intermediates for pharmaceutical synthesis, and also improve environmental waste remediation. The strains Pseudomonas putida CBB5 and CES may provide insights into these applications because they may both be induced to degrade caffeine, yet the latter thrives in concentrations >8.0gL-1; threefold higher than any other bacteria. We took a novel approach toward identifying the enzymatic pathways in both Pseudomonas sp. CES and a deletion mutation of strain CBB5, which largely circumvented the need for exhaustive isolation of enzymes and the stepwise reconstitution of their activities to determine caffeine response elements. Here, we describe two optimized, rapid alternative strategies based on multiplexed SIL assays and demonstrate their application by discovering caffeine-degrading enzymes in the CES strain based on quantitative comparison between enriched lysate fractions drawn from bacterial proteomes grown in the absence and presence of caffeine. Comparisons were made using stable isotope dimethyl labeling and expression differences were substantiated by reciprocal labeling experiments. The role of the identified proteins in caffeine degradation was independently verified by genetic sequencing. Multiple new components of N-demethylase system were discovered within a fraction of the lysate enriched specifically for this activity. We also describe how to expand the biological context (and reduce systemic bias) by adapting the protocol for total lysate analysis. We combined off-line prefractionation with the speed and resolution advantages of the Orbitrap LUMOS. The global protocol revealed 2406 proteins 1789 of which were quantified between treatments revealing, among other insights, a new antagonistic degradation pathway for vanillin that is completely suppressed by caffeine treatment.

Developmental programming, adiposity, and reproduction in ruminants.

Although sheep have been widely adopted as an animal model for examining the timing of nutritional interventions through pregnancy on the short- and long-term outcomes, only modest programming effects have been seen. This is due in part to the mismatch in numbers of twins and singletons between study groups as well as unequal numbers of males and females. Placental growth differs between singleton and twin pregnancies which can result in different body composition in the offspring. One tissue that is especially affected is adipose tissue which in the sheep fetus is primarily located around the kidneys and heart plus the sternal/neck region. Its main role is the rapid generation of heat due to activation of the brown adipose tissue-specific uncoupling protein 1 at birth. The fetal adipose tissue response to suboptimal maternal food intake at defined stages of development differs between the perirenal abdominal and pericardial depots, with the latter being more sensitive. Fetal adipose tissue growth may be mediated in part by changes in leptin status of the mother which are paralleled in the fetus. Then, over the first month of life plasma leptin is higher in females than males despite similar adiposity, when fat is the fastest growing tissue with the sternal/neck depot retaining uncoupling protein 1, whereas other depots do not. Future studies should take into account the respective effects of fetal number and sex to provide more detailed insights into the mechanisms by which adipose and related tissues can be programmed in utero.

Childhood trauma, midbrain activation and psychotic symptoms in borderline personality disorder.

Childhood trauma is believed to contribute to the development of borderline personality disorder (BPD), however the mechanism by which childhood trauma increases risk for specific symptoms of the disorder is not well understood. Here, we explore the relationship between childhood trauma, brain activation in response to emotional stimuli and psychotic symptoms in BPD. Twenty individuals with a diagnosis of BPD and 16 healthy controls were recruited to undergo a functional MRI scan, during which they viewed images of faces expressing the emotion of fear. Participants also completed the childhood trauma questionnaire (CTQ) and a structured clinical interview. Between-group differences in brain activation to fearful faces were limited to decreased activation in the BPD group in the right cuneus. However, within the BPD group, there was a significant positive correlation between physical abuse scores on the CTQ and BOLD signal in the midbrain, pulvinar and medial frontal gyrus to fearful (versus neutral) faces. In addition there was a significant correlation between midbrain activation and reported psychotic symptoms in the BPD group (P<0.05). These results show that physical abuse in childhood is, in individuals with BPD, associated with significantly increased activation of a network of brain regions including the midbrain in response to emotional stimuli. Sustained differences in the response of the midbrain to emotional stimuli in individuals with BPD who suffered childhood physical abuse may underlie the vulnerability of these patients to developing psychotic symptoms.

Impulsivity in borderline personality disorder.

BACKGROUND: Impulsivity is a core feature of borderline personality disorder (BPD) and is most frequently measured using self-rating scales. There is a need to find objective, valid and reliable measures of impulsivity. This study aimed to examine performance of participants with BPD compared with healthy controls on delay and probabilistic discounting tasks and the stop-signal task (SST), which are objective measures of choice and motor impulsivity, respectively. METHOD: A total of 20 participants with BPD and 21 healthy control participants completed delay and probabilistic discounting tasks and the SST. They also completed the Barratt Impulsiveness Scale (BIS), a self-rating measure of impulsivity. RESULTS: Participants with BPD showed significantly greater delay discounting than controls, manifest as a greater tendency to accept the immediately available lesser reward rather than waiting longer for a greater reward. Similarly they showed significantly greater discounting of rewards by the probability of payout, which correlated with past childhood trauma. Participants with BPD were found to choose the more certain and/or immediate rewards, irrespective of the value. On the SST the BPD and control groups did not differ significantly, demonstrating no difference in motor impulsivity. There was no significant difference between groups on self-reported impulsivity as measured by the BIS. CONCLUSIONS: Measures of impulsivity show that while motor impulsivity was not significantly different in participants with BPD compared with controls, choice or reward-related impulsivity was significantly affected in those with BPD. This suggests that choice impulsivity but not motor impulsivity is a core feature of BPD.

A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

BACKGROUND: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies. PATIENTS AND METHODS: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload. RESULTS: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival. CONCLUSIONS: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

The developmental transition of ovine adipose tissue through early life.

AIM: Hypothermia induced by cold exposure at birth is prevented in sheep by the rapid onset of non-shivering thermogenesis in brown adipose tissue (BAT). Changes in adipose tissue composition in early life are therefore essential for survival but also influence adiposity in later life and were thus examined in detail during early development. METHODS: Changes in adipose composition were investigated by immunohistochemistry and qRT-PCR between the period from the first appearance of adipose in the mid gestation foetus, through birth and up to 1 month of age. RESULTS: We identified four distinct phases of development, each associated with pronounced changes in tissue histology and in distribution of the BAT specific uncoupling protein (UCP)1. At mid gestation, perirenal adipose tissue exhibited a dense proliferative, structure marked by high expression of KI-67 but with no UCP1 or visible lipid droplets. By late gestation large quantities of UCP1 were present, lipid storage was evident and expression of BAT-related genes were abundant (e.g. prolactin and ß3 receptors). Subsequently, within 12 h of birth, the depot was largely depleted of lipid and expression of genes such as UCP1, PGC1α, CIDEA peaked. By 30 days UCP1 was undetectable and the depot contained large lipid droplets; however, genes characteristic of BAT (e.g. PRDM16 and BMP7) and most characteristic of white adipose tissue (e.g. leptin and RIP140) were still abundant. CONCLUSION: Adipose tissue undergoes profound compositional changes in early life, of which an increased understanding could offer potential interventions to retain BAT in later life.

Suboptimal maternal nutrition during early fetal kidney development specifically promotes renal lipid accumulation following juvenile obesity in the offspring.

Reduced maternal food intake between early-to-mid gestation results in tissue-specific adaptations in the offspring following juvenile-onset obesity that are indicative of insulin resistance. The aim of the present study was to establish the extent to which renal ectopic lipid accumulation, as opposed to other markers of renal stress, such as iron deposition and apoptosis, is enhanced in obese offspring born to mothers nutrient restricted (NR) throughout early fetal kidney development. Pregnant sheep were fed either 100% (control) or NR (i.e. fed 50% of their total metabolisable energy requirement from 30-80 days gestation and 100% at all other times). At weaning, offspring were made obese and, at approximately 1 year, kidneys were sampled. Triglyceride content, HIF-1α gene expression and the protein abundance of the outer-membrane transporter voltage-dependent anion-selective channel protein (VDAC)-I on the kidney cortex were increased in obese offspring born to NR mothers compared with those born to controls, which exhibited increased iron accumulation within the tubular epithelial cells and increased gene expression of the death receptor Fas. In conclusion, suboptimal maternal nutrition coincident with early fetal kidney development results in enhanced renal lipid deposition following juvenile obesity and could accelerate the onset of the adverse metabolic, rather than cardiovascular, symptoms accompanying the metabolic syndrome.

Evaluation of perifacet injections and paraspinal muscle rehabilitation in treatment of low back pain. A randomised controlled trial.

BACKGROUND: Lumbar paraspinal muscle dysfunction and Low Back Pain are strongly correlated. The best treatment for non-specific Low Back Pain is still controversial. OBJECTIVE: To evaluate the efficacy of lumbar multifidus muscle retraining exercises and perifacet multifidus injections in the treatment of Low Back Pain. MATERIAL AND METHODS: 63 patients with non-specific LBP, with or without leg pain, and magnetic resonance images of paraspinal muscle degeneration only, were randomised to one of three treatment groups: A- Back education and standard physiotherapy for 10 weeks, B- Back education and gym ball exercise for 10 weeks or C- Perifacet injection into the lumbar multifidus muscle with methylprednisolone. The Oswestry Disability Index was used as the primary outcome measure and the SF-36, modified Zung depression index, modified somatic perception and McGill pain questionnaires were used as secondary outcome measures. RESULTS: 56 patients completed the trial. The Oswestry Disability Index improved in general from a mean of 29.9 to 25.9, but there were no statistically significant differences between the groups. Low back pain improved most in group C (P<0.02), while physical activities and social functioning were improved the most in group B (P<0.03). CONCLUSION: Perifacet injection and back education including a gym ball exercise program may be more effective than back education alone in relieving pain and improving physical capacity respectively. Back education including gym ball exercise could be used for non-specific Low Back Pain, as the ultimate goal should be to restore function.

Adipose tissue and fetal programming.

Adipose tissue function changes with development. In the newborn, brown adipose tissue (BAT) is essential for ensuring effective adaptation to the extrauterine environment, and its growth during gestation is largely dependent on glucose supply from the mother to the fetus. The amount, location and type of adipose tissue deposited can also determine fetal glucose homeostasis. Adipose tissue first appears at around mid-gestation. Total adipose mass then increases through late gestation, when it comprises a mixture of white and brown adipocytes. BAT possesses a unique uncoupling protein, UCP1, which is responsible for the rapid generation of large amounts of heat at birth. Then, during postnatal life some, but not all, depots are replaced by white fat. This process can be utilised to investigate the physiological conversion of brown to white fat, and how it is re-programmed by nutritional changes in pre- and postnatal environments. A reduction in early BAT deposition may perpetuate through the life cycle, thereby suppressing energy expenditure and ultimately promoting obesity. Normal fat development profiles in the offspring are modified by changes in maternal diet at defined stages of pregnancy, ultimately leading to adverse long-term outcomes. For example, excess macrophage accumulation and the onset of insulin resistance occur in an adipose tissue depot-specific manner in offspring born to mothers fed a suboptimal diet from early to mid-gestation. In conclusion, the growth of the different fetal adipose tissue depots varies according to maternal diet and, if challenged in later life, this can contribute to insulin resistance and impaired glucose homeostasis.

Effect of two sitting postures on lumbar sagittal alignment and intervertebral discs in runners.

PURPOSE: We evaluated in vivo changes in lumbar lordosis and intervertebral discs in runners and assessed the relationship between these changes and degenerative disc disease in runners with and without a history of low back pain. MATERIALS AND METHODS: Using open upright magnetic resonance (MR) imaging, we prospectively studied changes in lumbar lordosis and intervertebral discs of 25 elite long-distance runners in two sitting postures (neutral and extended) before and after 1 h of running and compared the results with disc height and dehydration/degeneration. Seventeen of the 25 runners had a history of low back pain. RESULTS: After 1 h of running, mean lordosis in neutral posture reduced by 4°; reduction was significant in runners with a history of low back pain. A significant reduction in mean lordosis in extension was not observed. Mean disc height significantly reduced in both postures, without, however, any statistical significance between runners with and without a history low back pain in any posture. Variable degrees of disc dehydration/degeneration were observed in 23 runners (57 discs), more commonly at L5-S1. A significant difference of disc dehydration/degeneration between runners with and without a history of low back pain was not observed. CONCLUSIONS: Intervertebral discs undergo significant strain after 1 h of running that in the long term may lead to low back pain and degenerative disc disease. Runners, especially those with low back pain and degenerative disc disease, should be evaluated after training to preserve the normal lumbar lordosis.

Warfarin anticoagulation: a survey of patients' knowledge of their treatment.

INTRODUCTION: Warfarin is used for the treatment of thromboembolic disease. It requires careful and sustained monitoring due to its narrow therapeutic index and potentially life-threatening complications. Patient education and knowledge is, therefore, vital. AIMS: To assess, in a specialised anticoagulation clinic, the extent of patients' knowledge of their warfarin treatment. METHODS: Ethical approval was obtained. All patients, aged over 18 years, attending our anticoagulation clinic during our study period were asked to participate. RESULTS: We enrolled 181 patients, 47.9% of respondents were unaware of any potential drug interactions, 57.7% of patients were unaware of any potential side effects, 20% of patients had experienced side effects, 10.9% of patients had been hospitalised due to side effects, 58% of which were due to Haemorrhage and 79% of patients kept a personal record of their INR. CONCLUSIONS: Patients' understanding of warfarin treatment was poor, despite their high level of compliance.

Intervertebral disc changes after 1 h of running: a study on athletes.

The lumbar spines of 25 long-distance runners were examined using an upright magnetic resonance imaging scanner. All volunteer runners were scanned before and after running for 1 h. Scanning was performed with the runners seated upright (neutral), leaning forwards (flexion) and leaning backwards (extension). All measured discs showed a reduction in disc height after 1 h of running. A significant reduction in disc height was observed in all three body positions (neutral, flexion and extension) after 1 h of running. The results showed that, in flexion, extension and neutral positions, intervertebral discs undergo significant strain after 1 h of running. The lowest disc-height reduction was found at the L5 - S1 space in the neutral position; the same space had the highest percentage of disc degeneration.

Accuracy of polar F6 in estimating the energy cost of aerobic dance bench stepping in college-age females.

AIM: This study: 1) examined the accuracy of the Polar F6 for estimating energy expenditure (EE) in a sample of college-age women during aerobic dance bench stepping (ADBS) using predicted maximal oxygen consumption (VO2max) and maximal heart rate (HRmax), and 2) determined whether the use of actual measures of VO2max and HRmax improves the accuracy of the Polar F6 for estimating EE. METHODS: Thirty-two females had their VO2max and HRmax predicted by the Polar F6 heart rate monitor (HRM), and then performed a graded maximal exercise treadmill test to determine their actual VO2max and HRmax. The participants then followed a 20-min ADBS routine while stepping up and down off of a 15.24-cm bench at a cadence of 126 beats.min-1. During ADBS, the participants wore two F6 HRM that simultaneously collected data. To estimate EE, one HRM utilized their predicted VO2max and HRmax (PHRM) while the other HRM utilized their actual VO2max and HRmax (AHRM). RESULTS: The predicted HRmax significantly overestimated actual HRmax by 3.75 beats.min-1 on average, and the predicted VO2max overestimated actual VO2max by 2.63 ml.kg-1.min-1 on average (P<0.01). However, there were no significant differences between the PHRM and AHRM (P≥0.05). When compared to indirect calorimetry, the PHRM and AHRM significantly overestimated average EE by 28% (2.4 kcal.min-1) and 27% (2.0 kcal.min-1), respectively (P<0.05). CONCLUSIONS: Even when using actual measures of VO2max and HRmax, the Polar F6 is inaccurate in estimating EE during ADBS for college-age females.