Seasonal variability of ocean circulation near the Dotson Ice Shelf, Antarctica.

Recent rapid thinning of West Antarctic ice shelves are believed to be caused by intrusions of warm deep water that induce basal melting and seaward meltwater export. This study uses data from three bottom-mounted mooring arrays to show seasonal variability and local forcing for the currents moving into and out of the Dotson ice shelf cavity. A southward flow of warm, salty water had maximum current velocities along the eastern channel slope, while northward outflows of freshened ice shelf meltwater spread at intermediate depth above the western slope. The inflow correlated with the local ocean surface stress curl. At the western slope, meltwater outflows followed the warm influx along the eastern slope with a ~2-3 month delay. Ocean circulation near Dotson Ice Shelf, affected by sea ice distribution and wind, appears to significantly control the inflow of warm water and subsequent ice shelf melting on seasonal time-scales.

Pathways and modification of warm water flowing beneath Thwaites Ice Shelf, West Antarctica.

Thwaites Glacier is the most rapidly changing outlet of the West Antarctic Ice Sheet and adds large uncertainty to 21st century sea-level rise predictions. Here, we present the first direct observations of ocean temperature, salinity, and oxygen beneath Thwaites Ice Shelf front, collected by an autonomous underwater vehicle. On the basis of these data, pathways and modification of water flowing into the cavity are identified. Deep water underneath the central ice shelf derives from a previously underestimated eastern branch of warm water entering the cavity from Pine Island Bay. Inflow of warm and outflow of melt-enriched waters are identified in two seafloor troughs to the north. Spatial property gradients highlight a previously unknown convergence zone in one trough, where different water masses meet and mix. Our observations show warm water impinging from all sides on pinning points critical to ice-shelf stability, a scenario that may lead to unpinning and retreat.

Diagnosing Carotid Near-Occlusion with Phase-Contrast MRI.

Carotid near-occlusion is a frequently overlooked diagnosis when CTA examinations are assessed in routine practice. To evaluate the potential value of phase-contrast MR imaging in identifying near-occlusion, we examined 9 carotid near-occlusions and 20 cases of conventional ≥50% carotid stenosis (mean stenosis degree, 65%) with phase-contrast MR imaging. Mean ICA flow was lower in near-occlusions (52 mL/min) than in conventional ≥50% stenosis (198 mL/min, P < .001). ICA flow of ≤110 mL/min was 100% sensitive and specific for near-occlusion. Phase-contrast MR imaging is a promising tool for diagnosing carotid near-occlusion.

Ice front blocking of ocean heat transport to an Antarctic ice shelf.

Mass loss from the Antarctic Ice Sheet to the ocean has increased in recent decades, largely because the thinning of its floating ice shelves has allowed the outflow of grounded ice to accelerate1,2. Enhanced basal melting of the ice shelves is thought to be the ultimate driver of change2,3, motivating a recent focus on the processes that control ocean heat transport onto and across the seabed of the Antarctic continental shelf towards the ice4-6. However, the shoreward heat flux typically far exceeds that required to match observed melt rates2,7,8, suggesting that other critical controls exist. Here we show that the depth-independent (barotropic) component of the heat flow towards an ice shelf is blocked by the marked step shape of the ice front, and that only the depth-varying (baroclinic) component, which is typically much smaller, can enter the sub-ice cavity. Our results arise from direct observations of the Getz Ice Shelf system and laboratory experiments on a rotating platform. A similar blocking of the barotropic component may occur in other areas with comparable ice-bathymetry configurations, which may explain why changes in the density structure of the water column have been found to be a better indicator of basal melt rate variability than the heat transported onto the continental shelf9. Representing the step topography of the ice front accurately in models is thus important for simulating ocean heat fluxes and induced melt rates.

Increase of frontal neuronal activity in chronic neglect after training in virtual reality.

OBJECTIVES: A third of patients with stroke acquire spatial neglect associated with poor rehabilitation outcome. New effective rehabilitation interventions are needed. Scanning training combined with multisensory stimulation to enhance the rehabilitation effect is suggested. In accordance, we have designed a virtual-reality based scanning training that combines visual, audio and sensori-motor stimulation called RehAtt® . Effects were shown in behavioural tests and activity of daily living. Here, we use fMRI to evaluate the change in brain activity during Posner's Cuing Task (attention task) after RehAtt® intervention, in patients with chronic neglect. METHODS: Twelve patients (mean age = 72.7 years, SD = 6.1) with chronic neglect (persistent symptoms >6 months) performed the interventions 3 times/wk during 5 weeks, in total 15 hours. Training effects on brain activity were evaluated using fMRI task-evoked responses during the Posner's cuing task before and after the intervention. RESULTS: Patients improved their performance in the Posner fMRI task. In addition, patients increased their task-evoked brain activity after the VR interventions in an extended network including pre-frontal and temporal cortex during attentional cueing, but showed no training effects during target presentations. CONCLUSIONS: The current pilot study demonstrates that a novel multisensory VR intervention has the potential to benefit patients with chronic neglect in respect of behaviour and brain changes. Specifically, the fMRI results show that strategic processes (top-down control during attentional cuing) were enhanced by the intervention. The findings increase knowledge of the plasticity processes underlying positive rehabilitation effects from RehAtt® in chronic neglect.

Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus.

OBJECTIVES: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology. MATERIALS AND METHODS: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age). RESULTS: Aqueduct stroke volume was higher in INPH than healthy (148±95 vs 90±50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays. CONCLUSIONS: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear.

Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: a study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party.

Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel.

Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-Labeling in Healthy Volunteers.

BACKGROUND AND PURPOSE: The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. MATERIALS AND METHODS: Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than ±10 mL/min/100 g. RESULTS: pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean ± 2 standard deviations) were -4 ± 14 mL/min/100 g in the young subjects and 6 ± 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 ± 8 mL/min/100 g; elderly, 54 ± 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 ± 10 mL/min/100 g; elderly, 48 ± 10 mL/min/100 g; P < .001). CONCLUSIONS: The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.

Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience.

The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8;21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients <80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both P<0.001), followed by sex (P=0.0135) and a karyotype including -7/del(7q) (P=0.048).

Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP.

OBJECTIVE: Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. METHOD: Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. RESULTS: The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. CONCLUSIONS: Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.

Impact of technology on cytology outcome in cervical cancer screening of young and older women.

Little is known about age-dependent variation in outcomes of cervical cytology with modern technologies. This population-based study evaluated age-dependent changes after routine implementation of ThinPrep and SurePath technology in two independent laboratories, and controlled for time trends in a third laboratory using manually read conventional cytology continually. Data were collected from the Danish National Health Care Registers. For each laboratory, we compared proportions of abnormal cytology defined as atypical squamous cells of undetermined significance or worse (ASCUS+) by age and technology phase. The study included 489,960 cytological samples with no recent abnormality from women aged 23-59 years, routinely screened between 1998 and 2007. Implementation of SurePath liquid-based cytology (LBC) was followed by an increase in abnormal cytology in women aged 23-29 years from 4.6 to 6.1%, relative proportion (RP): 1.31 [95% confidence interval (CI): 1.08-1.61], and a decrease in women aged 45-59 years from 2.9 to 2.0%, RP: 0.71 (95% CI: 0.60-0.83). Implementation of ThinPrep LBC was followed by a decrease in abnormal cytology both in women aged 23-29 years from 7.7 to 6.8%, RP: 0.89 (95% CI: 0.78-1.02) and in women aged 45-59 years from 3.4 to 1.0%, RP: 0.30 (95% CI: 0.24-0.37). With implementation of imaging-assisted reading, regardless of the brand of technology, the proportion of abnormality increased by around 30% in all age groups (range from 19 to 41%). In the laboratory with unchanged technology no trends in abnormality proportions were observed. The impact of LBC implementation on cytological abnormality proportions varied considerably across age groups.

Synergy effects of HbA1c and variants of APOE and BDNFVal66Met explains individual differences in memory performance.

We aimed at exploring if synergy effects of Brain-Derived Neurotrophic Factor (BDNF) Val(66)Met, Apolipoprotein E (APOE) and HbA1c (glycated haemoglobin) could explain individual differences in memory performance over 10 years in a population based sample of nondemented adults (N=888, 35-85 years at baseline). Episodic memory was affected by such agents, wheras semantic memory was spared. Both age and HbA1c were associated with episodic memory decline. BDNF(66)Met carriers with higher HbA1c levels evidenced slope decline in episodic recall. We found support for joint effects of BDNFVal(66)Met×APOE×HbA1c and BDNFVal(66)Met×APOE×age on rates of episodic memory change over ten years, after controlling for age, sex, education and cardiovascular diseases. We conclude that variants of genetic polymorphisms act in synergy with long-term blood glucose control in shaping patterns of cognitive aging.

Measuring pulsatile flow in cerebral arteries using 4D phase-contrast MR imaging.

BACKGROUND AND PURPOSE: 4D PCMRI can be used to quantify pulsatile hemodynamics in multiple cerebral arteries. The aim of this study was to compare 4D PCMRI and 2D PCMRI for assessments of pulsatile hemodynamics in major cerebral arteries. MATERIALS AND METHODS: We scanned the internal carotid artery, the anterior cerebral artery, the basilar artery, and the middle cerebral artery in 10 subjects with a single 4D and multiple 2D PCMRI acquisitions by use of a 3T system and a 32-channel head coil. We assessed the agreement regarding net flow and the volume of arterial pulsatility (ΔV) for all vessels. RESULTS: 2D and 4D PCMRI produced highly correlated results, with r = 0.86 and r = 0.95 for ΔV and net flow, respectively (n = 69 vessels). These values increased to r = 0.93 and r = 0.97, respectively, during investigation of a subset of measurements with <5% variation in heart rate between the 4D and 2D acquisition (n = 31 vessels). Significant differences were found for ICA and MCA net flow (P = .004 and P < .001, respectively) and MCA ΔV (P = .006). However, these differences were attenuated and no longer significant when the subset with stable heart rate (n = 31 vessels) was analyzed. CONCLUSIONS: 4D PCMRI provides a powerful methodology to measure pulsatility of the larger cerebral arteries from a single acquisition. A large part of differences between measurements was attributed to physiologic variations. The results were consistent with 2D PCMRI.

Evaluation of automatic measurement of the intracranial volume based on quantitative MR imaging.

BACKGROUND AND PURPOSE: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation. MATERIALS AND METHODS: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded. RESULTS: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P > .25). The mean difference between the reference and automatic measurement was -4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were -0.47 ± 17.95 mL (-0.01 ± 1.24%) and -1.26 ± 17.68 mL (-0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were <1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds). CONCLUSIONS: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.

Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry.

Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100,000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients <40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

Allogeneic haematopoietic stem-cell transplantation with reduced intensity conditioning for advanced stage Hodgkin's lymphoma in Sweden: high incidence of post transplant lymphoproliferative disorder.

Allogeneic transplantation after reduced intensity conditioning (allo-RIC) is a treatment option for patients with Hodgkin's lymphoma (HL) relapsing after autologous transplantation. In all, 23 adult patients with HL underwent allo-RIC in Sweden between 2000 and 2007. The median number of previous treatment lines was five and 20 patients (87%) were previously autografted. TRM at 100 days and at 1 year was 13 and 22% respectively. Acute GVHD grades II-IV developed in 7 out of 23 patients (30%) and chronic GVHD in 10 out of 20 patients at risk (50%). The OS and EFS at three years was 59 and 27%, respectively. Four patients (17%) developed post transplant lymphoproliferative disease (PTLD) after a median time of 55 days (range 38-95); two of these patients later died. The study confirmed that allo-RIC is feasible, but associated with a substantial relapse rate: only 20% of the patients were still alive 7 years after the transplant. A finding of high incidence of PTLD needs to be confirmed in a larger trial that includes patients with non-HL and CLL.

MR imaging of brain volumes: evaluation of a fully automatic software.

BACKGROUND AND PURPOSE: Automatic assessment of brain volumes is needed in research and clinical practice. Manual tracing is still the criterion standard but is time-consuming. It is important to validate the automatic tools to avoid the problems of clinical studies drawing conclusions on the basis of brain volumes estimated with methodologic errors. The objective of this study was to evaluate a new commercially available fully automatic software for MR imaging of brain volume assessment. Automatic and expert manual brain volumes were compared. MATERIALS AND METHODS: MR imaging (3T, axial T2 and FLAIR) was performed in 41 healthy elderly volunteers (mean age, 70 ± 6 years) and 20 patients with hydrocephalus (mean age, 73 ± 7 years). The software Q(Brain) was used to manually and automatically measure the following brain volumes: ICV, BTV, VV, and WMHV. The manual method has been previously validated and was used as the reference. Agreement between the manual and automatic methods was evaluated by using linear regression and Bland-Altman plots. RESULTS: There were significant differences between the automatic and manual methods regarding all volumes. The mean differences were ICV = 49 ± 93 mL (mean ± 2SD, n = 61), BTV = 11 ± 70 mL, VV = -6 ± 10 mL, and WMHV = 2.4 ± 9 mL. The automatic calculations of brain volumes took approximately 2 minutes per investigation. CONCLUSIONS: The automatic tool is promising and provides rapid assessment of brain volumes. However, the software needs improvement before it is incorporated into research or daily use. Manual segmentation remains the reference method.

Health education improves both arthritis-related illness and self-rated health: an intervention study among older people in rural Bangladesh.

OBJECTIVES: To examine changes in self-reported arthritis-related illness and self-rated health as a result of a health education intervention, and the association between self-reported arthritis-related illness and self-rated health. STUDY DESIGN: A quasi-experimental study was conducted in eight randomly selected villages in rural Bangladesh (intervention = 4; control = 4). METHODS: The intervention consisted of home-based physical activities, health advice and aspects of healthcare management over 15 months followed by a 3-month latent period. Data were collected before the intervention and after the latent period. Analyses included 839 participants (≥60 years of age) who participated in both surveys. Participants in the intervention area were further categorized into two groups who self-reported compliance or non-compliance with recommended health advice. Self-rated health was assessed using a single global question. Self-reported arthritis-related illness was indicated by the presence of arthritis, back and joint pain, biting sensation, swelling and inflammation in the joints. RESULTS: Hierarchical logistic regression analyses revealed that positive effects on episodes of arthritis-related illness [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.3-2.8] and self-rated health (OR 1.4, 95% CI 1.0-1.9) were more likely among the compliant group compared with the control group. Furthermore, positive self-rated health was more likely among participants reporting a positive change in their arthritis-related illness (OR 2.2, 95% CI 1.5-3.2). The results also showed that literate and non-poor participants were more likely to report positive health, and participants with advancing age were less likely to report positive health. CONCLUSION: Community-based health education is effective in reducing the burden of arthritis-related illness and in enhancing general health in old age.