Multiple causes of the Younger Dryas cold period

The Younger Dryas cooling event disrupted the overall warming trend in the North Atlantic region during the last deglaciation. Climate change during the Younger Dryas was abrupt and thus provides insights into the sensitivity of the climate system to perturbations. The sudden Younger Dryas cooling has traditionally been attributed to a shutdown of the Atlantic Meridional Overturning Circulation by meltwater discharges. However, alternative explanations such as strong negative radiative forcing14 and a shift in atmospheric circulation have also been offered. Here we investigate the importance of these different forcings in coupled climate model experiments constrained by data assimilation. We find that the Younger Dryas climate signal as registered in proxy evidence is best simulated using a combination of processes: a weakened Atlantic Meridional Overturning Circulation, moderate negative radiative forcing and an altered atmospheric circulation. We conclude that none of the individual mechanisms alone provide a plausible explanation for the Younger Dryas cold period. We suggest that the triggers for abrupt climate changes such as the Younger Dryas are more complex than suggested so far, and that studies on the response of the climate system to perturbations should account for this complexity.

Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls

In multiple sclerosis (MS), fatigue is a common and often disabling symptom. It has multiple causes with central motor fatigue playing an important role.

How do indirect measures of evaluation work? Evaluating the inference of prejudice in the Implicit Association Test

There has been significant interest in indirect measures of attitudes like the Implicit Association Test (IAT), presumably because of the possibility of uncovering implicit prejudices. The authors derived a set of qualitative predictions for people's performance in the IAT on the basis of random walk models. These were supported in 3 experiments comparing clearly positive or negative categories to nonwords. They also provided evidence that participants shift their response criterion when doing the IAT. Because of these criterion shifts, a response pattern in the IAT can have multiple causes. Thus, it is not possible to infer a single cause (such as prejudice) from IAT results. A surprising additional result was that nonwords were treated as though they were evaluated more negatively than obviously negative items like insects, suggesting that low familiarity items may generate the pattern of data previously interpreted as evidence for implicit prejudice.

Internal displacement and the Kampala Convention: an opportunity for development actors

According to the African Union (AU), Africa is "a continent disproportionately affected by internal displacement". The African region, with almost 10 million people internally displaced in 22 countries by armed conflict and other forms of violence, hosts more than one third of the 26.4 million internally displaced persons (IDPs) worldwide at the end of 2011. Sudan, the Democratic Republic of the Congo and Somalia rank globally among the states with the five biggest displacement situations. Even in African countries with smaller figures, very large percentages of people may be in displacement in regions primarily affected by violence. Such violence has multiple causes, including the long-lasting consequences of colonial heritage, outside intervention, crises of identity in multi-ethnic countries and conflicts over resources. Today, political exclusion and inequality between ethnic, regional or religious groups are particularly important drivers of violence.

Multiple small "imaging" branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia?

Most screening programs for familial pancreatic cancer are currently based on endoscopic ultrasonography and/or magnetic resonance imaging (MRI). Cystic lesions, especially those suspicious for small intraductal pancreatic mucinous neoplasms (IPMNs) of the branch ducts, can be visualized in up to 40 % of individuals at risk, but their pathological importance in the setting of FPC is yet not well established. Individuals at risk from a prospective screening program for familial pancreatic cancer with small "imaging" IPMNs of the branch-duct type (BD-IPMN) who underwent pancreatic resection were analysed regarding clinico-pathological data and the locations of pancreatic lesions. Five of 125 individuals at risk who underwent screening had multiple small (size 2-10 mm) unicystic lesions and/or multicystic single lesions in the pancreatic body and tail suspicious for BD-IPMNs upon MRI imaging and decided to undergo surgical resection after interdisciplinary counselling, although none fulfilled the consensus criteria for IPMN resection. Histological examination revealed BD-IPMNs with low or moderate dysplasia of the gastric type in combination with multifocal PanIN2 and PanIN3 lesions in 4 individuals. The remaining patient had only tiny ductectasias in the pancreatic tail with multifocal PanIN 2 lesions in the entire gland and one PanIN3 lesion in the pancreatic head. Intriguingly, the location of the most dysplastic histological lesions (PanIN3) did not correspond to the preoperatively detected lesions and were not visible in preoperative imaging. In the setting of FPC, the presence of multiple small "imaging" BD-IPMNs may indicate the presence of high-grade PanIN lesions elsewhere in the pancreas.

Deletion of exon 8 from the EXT1 gene causes multiple osteochondromas (MO) in a family with three affected members.

Multiple osteochondromas (also called hereditary multiple exostoses) is an autosomal dominant disorder characterized by multiple cartilaginous tumors, which are caused by mutations in the genes for exostosin-1 (EXT1) and exostosin-2 (EXT2). The goal of this study was to elucidate the genetic alterations in a family with three affected members. Isolation of RNA from the patients' blood followed by reverse transcription and PCR amplification of selected fragments showed that the three patients lack a specific region of 90 bp from their EXT1 mRNA. This region corresponds to the sequence of exon 8 from the EXT1 gene. No splice site mutation was found around exon 8. However, long-range PCR amplification of the region from intron 7 to intron 8 indicated that the three patients contain a deletion of 4318 bp, which includes exon 8 and part of the flanking introns. There is evidence that the deletion was caused by non-homologous end joining because the breakpoints are not located within a repetitive element, but contain multiple copies of the deletion hotspot sequence TGRRKM. Exon 8 encodes part of the active site of the EXT1 enzyme, including the DXD signature of all UDP-sugar glycosyltransferases. It is conceivable that the mutant protein exerts a dominant negative effect on the activity of the EXT glycosyltransferase since it might interact with normal copies of the enzyme to form an inactive hetero-oligomeric complex. We suggest that sequencing of RNA might be superior to exome sequencing to detect short deletions of a single exon.

Trunk sway in mildly disabled multiple sclerosis patients with and without balance impairment

Multiple sclerosis (MS) causes a broad range of neurological symptoms. Most common is poor balance control. However, knowledge of deficient balance control in mildly affected MS patients who are complaining of balance impairment but have normal clinical balance tests (CBT) is limited. This knowledge might provide insights into the normal and pathophysiological mechanisms underlying stance and gait. We analysed differences in trunk sway between mildly disabled MS patients with and without subjective balance impairment (SBI), all with normal CBT. The sway was measured for a battery of stance and gait balance tests (static and dynamic posturography) and compared to that of age- and sex-matched healthy subjects. Eight of 21 patients (38%) with an Expanded Disability Status Scale of 1.0-3.0 complained of SBI during daily activities. For standing on both legs with eyes closed on a normal and on a foam surface, patients in the no SBI group showed significant differences in the range of trunk roll (lateral) sway angle and velocity, compared to normal persons. Patients in the SBI group had significantly greater lateral sway than the no SBI group, and sway was also greater than normal in the pitch (anterior-posterior) direction. Sway for one-legged stance on foam was also greater in the SBI group compared to the no SBI and normal groups. We found a specific laterally directed impairment of balance in all patients, consistent with a deficit in proprioceptive processing, which was greater in the SBI group than in the no SBI group. This finding most likely explains the subjective symptoms of imbalance in patients with MS with normal CBT.

The role of thrombelastography in multiple trauma

Hemorrhage and traumatic coagulopathyis are major causes of early death in multiply injured patients. Thrombelastography (TEG) seems to be a fast and accurate coagulation test in trauma care. We suggest that multiply injured trauma patients would benefit the most from an early assessment of coagulation by TEG, mainly RapidTEG, to detect an acute traumatic coagulopathy and especially primary fibrinolysis, which is related with high mortality. This review gives an overview on TEG and its clinical applications.

Practicability of nitrogen multiple-breath washout measurements in a pediatric cystic fibrosis outpatient setting

BACKGROUND: Although lung clearance index (LCI) is a sensitive indicator of mild cystic fibrosis (CF) lung disease, it is rarely measured due to lengthy protocols and the commercial unavailability of multiple-breath washout (MBW) setups and tracer gases. We used a newly validated, commercially available nitrogen (N(2) ) MBW setup to assess success rate, duration, and variability of LCI within a 20 min timeframe, during clinical routine. We also evaluated the relationship between LCI and other clinical markers of CF lung disease. METHODS: One hundred thirty six children (83 with CF) between 4 and 16 years were studied in a pediatric CF outpatient setting. One hundred eighteen out of 136 children were naïve to MBW. Within 20 min, each child was trained, N(2) MBW was performed, and LCI was analyzed. We assessed intra- and between-test reproducibility in a subgroup of children. RESULTS: At least one LCI was feasible in 123 (90%) children, with a mean (range) of 3.3 (1.2-6.4) min per test. Two or more measurements were feasible in 56 (41%) children. Comparing LCI in CF versus controls, LCI mean (SD) was 12.0 (3.9) versus 6.1 (0.9), and the intra- and inter-test coefficient of repeatability was 1.00 versus 0.81 and 0.96 versus 0.62, respectively. LCI was correlated with spirometry, blood gases, and Pseudomonas aeruginosa infection. CONCLUSIONS: Using available N(2) MBW equipment, LCI measurements are practical and fast in children. LCI is correlated with markers of CF lung disease. Longer timeframes would be required for triplicate N(2) MBW tests in inexperienced children. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Development and simultaneous application of multiple care protocols in critical care: a multicenter feasibility study

OBJECTIVE: To test the feasibility of and interactions among three software-driven critical care protocols. DESIGN: Prospective cohort study. SETTING: Intensive care units in six European and American university hospitals. PATIENTS: 174 cardiac surgery and 41 septic patients. INTERVENTIONS: Application of software-driven protocols for cardiovascular management, sedation, and weaning during the first 7 days of intensive care. MEASUREMENTS AND RESULTS: All protocols were used simultaneously in 85% of the cardiac surgery and 44% of the septic patients, and any one of the protocols was used for 73 and 44% of study duration, respectively. Protocol use was discontinued in 12% of patients by the treating clinician and in 6% for technical/administrative reasons. The number of protocol steps per unit of time was similar in the two diagnostic groups (n.s. for all protocols). Initial hemodynamic stability (a protocol target) was achieved in 26+/-18 min (mean+/-SD) in cardiac surgery and in 24+/-18 min in septic patients. Sedation targets were reached in 2.4+/-0.2h in cardiac surgery and in 3.6 +/-0.2h in septic patients. Weaning protocol was started in 164 (94%; 154 extubated) cardiac surgery and in 25 (60%; 9 extubated) septic patients. The median (interquartile range) time from starting weaning to extubation (a protocol target) was 89 min (range 44-154 min) for the cardiac surgery patients and 96 min (range 56-205 min) for the septic patients. CONCLUSIONS: Multiple software-driven treatment protocols can be simultaneously applied with high acceptance and rapid achievement of primary treatment goals. Time to reach these primary goals may provide a performance indicator.

Monitoring Programmes, Multiple Stress Analysis and Decision Support for River Basin Management

The identification of plausible causes for water body status deterioration will be much easier if it can build on available, reliable, extensive and comprehensive biogeochemical monitoring data (preferably aggregated in a database). A plausible identification of such causes is a prerequisite for well-informed decisions on which mitigation or remediation measures to take. In this chapter, first a rationale for an extended monitoring programme is provided; it is then compared to the one required by the Water Framework Directive (WFD). This proposal includes a list of relevant parameters that are needed for an integrated, a priori status assessment. Secondly, a few sophisticated statistical tools are described that subsequently allow for the estiation of the magnitude of impairment as well as the likely relative importance of different stressors in a multiple stressed environment. The advantages and restrictions of these rather complicated analytical methods are discussed. Finally, the use of Decision Support Systems (DSS) is advocated with regard to the specific WFD implementation requirements.

MRTAB: Stata module to compute one- and two-way tables/graphs of multiple responses

mrtab tabulates multiple responses which are held as a set of indicator variables or as a set of polytomous response variables.