The extreme yet transient nature of glacial erosion.

Ice can sculpt extraordinary landscapes, yet the efficacy of, and controls governing, glacial erosion on geological timescales remain poorly understood and contended, particularly across Polar continental shields. Here, we assimilate geophysical data with modelling of the Eurasian Ice Sheet - the third largest Quaternary ice mass that spanned 49°N to 82°N - to decipher its erosional footprint during the entire last ~100 ka glacial cycle. Our results demonstrate extreme spatial and temporal heterogeneity in subglacial erosion, with rates ranging from 0 to 5 mm a-1 and a net volume equating to ~130,000 km3 of bedrock excavated to depths of ~190 m. A hierarchy of environmental controls ostensibly underpins this complex signature: lithology, topography and climate, though it is basal thermodynamics that ultimately regulates erosion, which can be variously protective, pervasive, or, highly selective. Our analysis highlights the remarkable yet fickle nature of glacial erosion - critically modulated by transient ice-sheet dynamics - with its capacity to impart a profound but piecemeal geological legacy across mid- and high latitudes.

Scalar Signatures of Chaotic Mixing in Porous Media.

Steady laminar flows through porous media spontaneously generate Lagrangian chaos at pore scale, with qualitative implications for a range of transport, reactive, and biological processes. The characterization and understanding of mixing dynamics in these opaque environments is an outstanding challenge. We address this issue by developing a novel technique based upon high-resolution imaging of the scalar signature produced by push-pull flows through porous media samples. Owing to the rapid decorrelation of particle trajectories in chaotic flows, the scalar image measured outside the porous material is representative of in situ mixing dynamics. We present a theoretical framework for estimation of the Lyapunov exponent based on extension of Lagrangian stretching theories to correlated aggregation. This method provides a full characterization of chaotic mixing dynamics in a large class of porous materials.

Nasal obstruction secondary to an inverted midline supernumerary tooth.

We present the case of a 36-year-old man who presented with left-sided nasal obstruction and facial pain. Clinical examination and computed tomography revealed an inverted midline supernumerary tooth buckling and deviating the nasal septum to the left. Full surgical resection of the tooth was achieved through a minimally invasive endoscopic septoplasty with full resolution of symptoms. There is little precedent within the literature to guide our management in this case and therefore we offer a successful surgical treatment strategy.

Cordilleran Ice Sheet mass loss preceded climate reversals near the Pleistocene Termination.

The Cordilleran Ice Sheet (CIS) once covered an area comparable to that of Greenland. Previous geologic evidence and numerical models indicate that the ice sheet covered much of westernmost Canada as late as 12.5 thousand years ago (ka). New data indicate that substantial areas throughout westernmost Canada were ice free prior to 12.5 ka and some as early as 14.0 ka, with implications for climate dynamics and the timing of meltwater discharge to the Pacific and Arctic oceans. Early Bølling-Allerød warmth halved the mass of the CIS in as little as 500 years, causing 2.5 to 3.0 meters of sea-level rise. Dozens of cirque and valley glaciers, along with the southern margin of the CIS, advanced into recently deglaciated regions during the Bølling-Allerød and Younger Dryas.

Outcomes of ventriculoperitoneal shunt insertion in the management of idiopathic intracranial hypertension in children.

PURPOSE: The ventriculoperitoneal (VP) shunt has become the procedure of choice for treatment of idiopathic intracranial hypertension (IIH). We aimed to assess the efficacy of frameless stereotactic placement of VP shunts for the management of medically resistant IIH in children and to assess the role of gender and obesity in the aetiology of the condition. METHODS: This is a retrospective analysis of the case notes of 10 patients treated surgically at the University Hospital of Wales in Cardiff, from May 2006 to September 2012. RESULTS: VP shunts were successful in relieving headache, papilloedema and stabilising vision. No sex predilection was identified, and increased BMI was a feature throughout the population, regardless of age. CONCLUSIONS: Neuronavigated VP shunt insertion is an effective mode of treatment for medically resistant IIH in children. The aetiological picture in children does not seem to be dominated by obesity, as in adults. Literature on childhood IIH is sparse, and larger scale, comparative studies would be of benefit to treating clinicians.

Inner gorges cut by subglacial meltwater during Fennoscandian ice sheet decay.

The century-long debate over the origins of inner gorges that were repeatedly covered by Quaternary glaciers hinges upon whether the gorges are fluvial forms eroded by subaerial rivers, or subglacial forms cut beneath ice. Here we apply cosmogenic nuclide exposure dating to seven inner gorges along ~500 km of the former Fennoscandian ice sheet margin in combination with a new deglaciation map. We show that the timing of exposure matches the advent of ice-free conditions, strongly suggesting that gorges were cut by channelized subglacial meltwater while simultaneously being shielded from cosmic rays by overlying ice. Given the exceptional hydraulic efficiency required for meltwater channels to erode bedrock and evacuate debris, we deduce that inner gorges are the product of ice sheets undergoing intense surface melting. The lack of postglacial river erosion in our seven gorges implicates subglacial meltwater as a key driver of valley deepening on the Baltic Shield over multiple glacial cycles.

Heart adaptations to long-term aerobic training in paraplegic subjects: an echocardiographic study.

STUDY DESIGN: Case-control. OBJECTIVES: To execute an echocardiographic comparison between trained and untrained spinal cord injury (SCI) subjects, and to evaluate whether long-term heart adjustments to endurance training are comparable to those observed in able-bodied (ABL) subjects. SETTING: Italy. METHODS: We enrolled: (1) 17 male SCI patients (lesion level T1-L3, 34±8 years, body mass index (BMI) 23.0±2.8 kg m(-2)), 10 of whom were aerobically trained for >5 years (SCI(T)); (2) 18 age-, sex- and BMI-matched ABL subjects (35±6 years, BMI 23.6±2.8 kg m(-2)), 10 of whom were aerobically trained for >5 years (ABL(T)). Training frequency and volume were recorded by a dedicated questionnaire. All subjects underwent a trans-thoracic echocardiography; SCI subjects also performed an exhaustive incremental exercise test. Comparisons were made between ABL and SCI groups, between trained and untrained subjects within each group (analysis of variance). RESULTS: Effects of SCI-Compared with ABL subjects, SCI patients showed lower end-diastolic volume (76±21 vs. 113±23 ml, P<0.05) and ejection fraction (61±7% vs. 65±5%, P<0.05). Effects of training-Compared with untrained status, the intra-ventricular septum thickness (SCI, +18%; ABL, +4%), the posterior wall thickness (SCI, +17%; ABL, +2%) and the total normalized heart mass (SCI, +48%; ABL, +5%) were higher in both SCI(T) and in ABL(T). VO2peak was higher in the SCI(T) subgroup compared with the SCI(U) group. CONCLUSIONS: Heart seems to positively adapt to long-term endurance training in SCI patients. Regular exercise may therefore increase heart size, septum and posterior wall thickness, which likely contributes to improved VO2peak. These morphological and functional changes may reduce cardiovascular risk in SCI individuals.

A profile of US-Mexico border mobility among a stratified random sample of Hispanics living in the El Paso-Juarez area.

Examination of border-specific characteristics such as trans-border mobility and transborder health service illuminates the heterogeneity of border Hispanics and may provide greater insight toward understanding differential health behaviors and status among these populations. In this study, we create a descriptive profile of the concept of trans-border mobility by exploring the relationship between mobility status and a series of demographic, economic and socio-cultural characteristics among mobile and non-mobile Hispanics living in the El Paso-Juarez border region. Using a two-stage stratified random sampling design, bilingual interviewers collected survey data from border residents (n = 1,002). Findings show that significant economic, cultural, and behavioral differences exist between mobile and non-mobile respondents. While non-mobile respondents were found to have higher social economic status than their mobile counterparts, mobility across the border was found to offer less acculturated and poorer Hispanics access to alternative sources of health care and other services.

Distension of painful structures in the treatment for chronic pelvic pain in women.

BACKGROUND: There is a lack of established treatment for Chronic pelvic pain (CPP), defined as acyclic pain of at least six months duration. We decided to study the pain-alleviating effects of stretching on defined structures in women with CPP, and the treatment's impact on quality of life variables. DESIGN OF STUDY: An open, randomized study. SETTING: Primary Health Care Centre, Kolbäck, Sweden. METHODS: Fifty women, median age 33 years (range 19-54), complaining of CPP for a median duration of 25.5 months (range 6-264) were randomly assigned to either a treatment or a control group. A short questionnaire containing 17 questions was administered before randomization and two to three weeks after a second treatment of distension of pelvic structures. Visual analog scales were used for questions concerning intensity of pain and quality of life. Five-point scales were used for questions dealing with duration and frequency of pain. RESULTS: Intensity, frequency and duration of pelvic pain, painful intercourse, lower back pain, sleep disturbance, sleep quality, mental fatigue, depression, mood and anger improved significantly more in the treatment group than in the control group. Treatment proved more effective than counseling as reflected by self-rating scales: pain intensity (OR 18.37, 95% CI 3.39-99.64) and pain during intercourse (OR 8.59, 95% CI 1.57-46.68). CONCLUSION: In this open, randomized study, distension of painful pelvic structures in women with CPP resulted in significant relief of pain and improvement in quality of life measures.

Influence of expiratory flow-limitation during exercise on systemic oxygen delivery in humans.

To determine the effects of exercise with expiratory flow-limitation (EFL) on systemic O(2) delivery, seven normal subjects performed incremental exercise with and without EFL at approximately 0.8 l s(-1) (imposed by a Starling resistor in the expiratory line) to determine maximal power output under control (W'(max,c)) and EFL (W'(max,e)) conditions. W'(max,e) was 62.5% of W'(max,c), and EFL exercise caused a significant fall in the ventilatory threshold. In a third test, after exercising at W'(max,e) without EFL for 4 min, EFL was imposed; exercise continued for 4 more minutes or until exhaustion. O(2) consumption (V'(O)(2)) was measured breath-by-breath for the last 90 s of control, and for the first 90 s of EFL exercise. Assuming that the arterio-mixed venous O(2) content remained constant immediately after EFL imposition, we used V'(O)(2) as a measure of cardiac output (Q'(c)). Q'(c) was also calculated by the pulse contour method with blood pressure measured continuously by a photo-plethysmographic device. Both sets of data showed a decrease of Q'(c) due to a decrease in stroke volume by 10% (p < 0.001 for V'(O)(2)) with EFL and remained decreased for the full 90 s. Concurrently, arterial O(2) saturation decreased by 5%, abdominal, pleural and alveolar pressures increased, and duty cycle decreased by 43%. We conclude that this combination of events led to a decrease in venous return secondary to high expiratory pressures, and a decreased duty cycle which decreased O(2) delivery to working muscles by approximately 15%.

The prognostic value of myocardial viability recognized by low dose dipyridamole echocardiography in patients with chronic ischaemic left ventricular dysfunction.

AIMS: The aim of this study was to assess the prognostic value of myocardial viability recognized as a contractile response to vasodilator stimulation in patients with left ventricular dysfunction in a large scale, prospective, multicentre, observational study. METHODS AND RESULTS: Three hundred and seven patients (mean age 60 +/- 10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction and severe left ventricular dysfunction (ejection fraction <35%; mean ejection fraction: 28 +/- 7%) were enrolled in the study. Each patient underwent low dose dipyridamole echo (0.28 mg x kg(-1) in 4 min). Myocardial viability was identified as an improvement of >0.20 in the wall motion score index. By selection, all patients were followed up for a median of 36 months. One-hundred and twenty-four were revascularized either by coronary artery bypass grafting (n=83) or coronary angioplasty (n=41). The only end-point analysed was cardiac death. In the revascularized group, cardiac death occurred in one of the 41 patients with and in 16 of the 83 patients without a viable myocardium (2.4% vs 19.3%, P<0.01). Outcome, as estimated by Kaplan-Meier survival, was better for patients with, compared to patients without, a viable myocardium, who underwent coronary revascularization (97.6 vs 77.4%, P=0.01). Using a Cox proportional hazards model, the presence of myocardial viability was shown to exert a protective effect on survival (chi-square 4.6, hazard ratio 0.1, 95% CI 0.01-0.8, P<0.03). The survival rate in medically treated patients was lower than in revascularized patients irrespective of the presence of a viable myocardium (79.7% vs 86.2, P=ns). CONCLUSION: In severe left ventricular ischaemic dysfunction, myocardial viability, as assessed by low dose dipyridamole echo, is associated with improved survival in revascularized patients.

High-throughput expression of fusion proteins.

The expression of putative ORFs as fusion proteins can accelerate research greatly. The availability of an epitope tag allows the use of Western blotting as an efficient means to identify useful recombinant plasmids, which can then be used to study protein function. In addition, the epitope tag can be extremely useful in downstream applications such as protein purification, immunolocalization, and immunoprecipitation experiments. The preceding protocols should be applicable to a variety of expression vectors, and should be useful in the identification of functional plasmids. The protocols require no exotic equipment and can be adapted for use in high-throughput transfection assays, protein purification protocols, and immunolocalization studies.

The transcriptional response of yeast to saline stress.

Adaptation to changes in extracellular salinity is a critical event for cell survival. Genome-wide DNA chip analysis has been used to analyze the transcriptional response of yeast cells to saline stress. About 7% of the genes encoded in the yeast genome are induced more than 5-fold after a mild and brief saline shock (0.4 m NaCl, 10 min). Interestingly, most responsive genes showed a very transient expression pattern, as mRNA levels dramatically declined after 20 min in the presence of stress. A quite similar set of genes increased expression in cells subjected to higher saline concentrations (0.8 m NaCl), although in this case the response was delayed. Therefore, our data show that cells respond to saline stress by inducing the expression of a very large number of genes and suggest that stress adaptation requires regulation of many cellular aspects. The transcriptional induction of most genes that are strongly responsive to salt stress was highly or fully dependent on the presence of the stress-activated mitogen-activated protein kinase Hog1, indicating that the Hog1-mediated signaling pathway plays a key role in global gene regulation under saline stress conditions.

Sampling a terahertz dipole transition with subcycle time resolution.

We present a time-resolved technique to measure optical excitation processes with a time resolution shorter than the oscillation period of the exciting light. Our terahertz (THz) experiments fully resolve the polarization dynamics of electrons in semiconductor heterostructures when they are excited by a THz pulse. The time resolution of the polarization enables us to deduce the population dynamics of the excited state, which includes the dynamics of a virtual population in the case of off-resonant excitation.

Genome-scale cloning and expression of individual open reading frames using topoisomerase I-mediated ligation.

The in vitro cloning of DNA molecules traditionally uses PCR amplification or site-specific restriction endonucleases to generate linear DNA inserts with defined termini and requires DNA ligase to covalently join those inserts to vectors with the corresponding ends. We have used the properties of Vaccinia DNA topoisomerase I to develop a ligase-free technology for the covalent joining of DNA fragments to suitable plasmid vectors. This system is much more efficient than cloning methods that require ligase because the rapid DNA rejoining activity of Vaccinia topoisomerase I allows ligation in only 5 min at room temperature, whereas the enzyme's high substrate specificity ensures a low rate of vector-alone transformants. We have used this topoisomerase I-mediated cloning technology to develop a process for accelerated cloning and expression of individual ORFs. Its suitability for genome-scale molecular cloning and expression is demonstrated in this report.

The early diagnosis of dementia: triggers, early signs and luxating events.

BACKGROUND: In order to make it possible and feasible that GPs diagnose dementia at an earlier phase than usual, it is important to know what elements in the available information on the patient and the family may trigger the diagnostic hypothesis of dementia. METHOD: By qualitative research, the stories of family members of dementia patients, according to DSM-III-R criteria, were analysed. RESULTS AND CONCLUSIONS: This work produced the following hypotheses: disturbances in functioning at work and ADL-IADL disturbances, the seeking of the carer's support and emotional problems-in addition to the more classical memory problems-are early signs and may be essential triggers for the GP to consider the possibility of an emerging dementia. Change of medication, narcosis, loss of the carer and hospital admission are luxating moments for the sudden appearance of symptoms and disturbances caused by dementia. Further research should be carried out to develop instruments for the early detection of dementia that step across neuropsychological tests and are feasible for daily use in a primary care setting.

Prognostic value of myocardial viability in medically treated patients with global left ventricular dysfunction early after an acute uncomplicated myocardial infarction: a dobutamine stress echocardiographic study.

BACKGROUND: Residual viable myocardium identified by dobutamine stress after myocardial infarction may act as an unstable substrate for further events such as subsequent angina and reinfarction. However, in patients with severe global left ventricular dysfunction, viability might be protective rather than detrimental. The aim of this study was to assess the impact on survival of echocardiographically detected viability in medically treated patients with global left ventricular dysfunction evaluated after acute uncomplicated myocardial infarction. METHODS AND RESULTS: The data bank of the large-scale, prospective, multicenter, observational Echo Dobutamine International Cooperative (EDIC) study was interrogated to select 314 medically treated patients (271 men; age, 58+/-9 years) who underwent low-dose (1.6). Patients were followed up for 9+/-7 months. Low-dose dobutamine stress echocardiography identified myocardial viability in 130 patients (52%). Dobutamine-atropine stress echocardiography was positive for ischemia in 148 patients (47%) and negative in 166 patients (53%). During the follow-up, there were 12 cardiac deaths (3.8% of the total population). With the use of Cox proportional hazards model, delta low-dose WMSI (the variation between rest WMSI and low-dose WMSI) was shown to exert a protective effect by reducing cardiac death by 0.8 for each decrease in WMSI at low-dose dobutamine (coefficient, -0.2; hazard ratio, 0.8; P<0.03); WMSI at peak stress was the best predictor of cardiac death in this set of patients (hazard ratio, 14.9; P<0.0018). CONCLUSIONS: In medically treated patients with severe global left ventricular dysfunction early after acute uncomplicated myocardial infarction, the presence of myocardial viability identified as inotropic reserve after low-dose dobutamine is associated with a higher probability of survival. The higher the number of segments showing improvement of function, the better the impact is of myocardial viability on survival. The presence of inducible ischemia in this set of patients is the best predictor of cardiac death.

Two AAA family peroxins, PpPex1p and PpPex6p, interact with each other in an ATP-dependent manner and are associated with different subcellular membranous structures distinct from peroxisomes.

Two peroxins of the AAA family, PpPex1p and PpPex6p, are required for peroxisome biogenesis in the yeast Pichia pastoris. Cells from the corresponding deletion strains (Pp delta pex1 and Pp delta pex6) contain only small vesicular remnants of peroxisomes, the bulk of peroxisomal matrix proteins is mislocalized to the cytosol, and these cells cannot grow in peroxisome-requiring media (J. A. Heyman, E. Monosov, and S. Subramani, J. Cell Biol. 127:1259-1273, 1994; A. P. Spong and S. Subramani, J. Cell Biol. 123:535-548, 1993). We demonstrate that PpPex1p and PpPex6p interact in an ATP-dependent manner. Genetically, the interaction was observed in a suppressor screen with a strain harboring a temperature-sensitive allele of PpPEX1 and in the yeast two-hybrid system. Biochemially, these proteins were coimmunoprecipitated with antibodies raised against either of the proteins, but only in the presence of ATP. The protein complex formed under these conditions was 320 to 400 kDa in size, consistent with the formation of a heterodimeric PpPex1p-PpPex6p complex. Subcellular fractionation revealed PpPex1p and PpPex6p to be predominantly associated with membranous subcellular structures distinct from peroxisomes. Based on their behavior in subcellular fractionation experiments including flotation gradients and on the fact that these structures are also present in a Pp delta pex3 strain in which no morphologically detectable peroxisomal remnants have been observed, we propose that these structures are small vesicles. The identification of vesicle-associated peroxins is novel and implies a role for these vesicles in peroxisome biogenesis. We discuss the possible role of the ATP-dependent interaction between PpPex1p and PpPex6p in regulating peroxisome biogenesis events.

The elusive link between coronary lesion morphology and dobutamine stress echocardiography results. The EDIC (Echo Dobutamine International Cooperative) Study Group.

BACKGROUND: Coronary lesion angiographic morphology of the complex type is associated to enhanced susceptibility to ischemia during vasodilator adenosinergic stress testing and attributed to the reduced vasodilatory capacity of the damaged endothelium. Whether coronary lesion morphology can also influence the results of adrenergic pharmacologic stress test remains unknown. The aim of our study was to assess the relationship between coronary plaque morphology and dobutamine-atropine stress echocardiography (DASE) results. METHODS AND RESULTS: We analyzed DASE (up to 40 mcg/kg/min plus atropine) and coronary angiography data of 42 patients with single vessel disease and no totally occluded vessel at angiography. 7 patients had angina, 35 had previous infarction. A diagnostic DASE was performed in all patients within 1-10 (mean 4.7 +/- 3.4) days before coronary angiography. An angiographic lesion was considered complex when irregular borders and/or intraluminal lucencies, suggestive of ulcer and/or thrombus were present. According to the angiographic lesion morphology (Ambrose classification), 2 groups were identified: Group I, with simple lesion; Group II with complex lesion. The two groups were similar for number of patients (n = 21), age (I = 55 +/- 11 vs II = 53 +/- 7 years, p = ns), coronary stenosis severity expressed as % diameter reduction (I = 77 +/- 14 vs II = 78 +/- 15%, p = ns), presence of previous infarction (I = 17 vs II = 18 pts, p = ns). No difference was found in the prevalence of positivity between the two groups (I = 72 vs II = 62%, p = ns). The two groups achieved a similar peak dobutamine dose (I = 32 +/- 9 vs II = 33 +/- 9 mcg/kg/min, p = ns) and peak Wall Motion Score Index (I = 1.5 +/- 0.26 vs II = 1.45 +/- 0.28, p = ns). CONCLUSIONS: In patients with non occlusive single vessel disease, coronary morphology of complex type is not associated with greater vulnerability to dobutamine induced ischemia.