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.

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.

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.

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.

Role of the PAS1 gene of Pichia pastoris in peroxisome biogenesis.

Several groups have reported the cloning and sequencing of genes involved in the biogenesis of yeast peroxisomes. Yeast strains bearing mutations in these genes are unable to grow on carbon sources whose metabolism requires peroxisomes, and these strains lack morphologically normal peroxisomes. We report the cloning of Pichia pastoris PAS1, the homologue (based on a high level of protein sequence similarity) of the Saccharomyces cerevisiae PAS1. We also describe the creation and characterization of P. pastoris pas1 strains. Electron microscopy on the P. pastoris pas1 cells revealed that they lack morphologically normal peroxisomes, and instead contain membrane-bound structures that appear to be small, mutant peroxisomes, or "peroxisome ghosts." These "ghosts" proliferated in response to induction on peroxisome-requiring carbon sources (oleic acid and methanol), and they were distributed to daughter cells. Biochemical analysis of cell lysates revealed that peroxisomal proteins are induced normally in pas1 cells. Peroxisome ghosts from pas1 cells were purified on sucrose gradients, and biochemical analysis showed that these ghosts, while lacking several peroxisomal proteins, did import varying amounts of several other peroxisomal proteins. The existence of detectable peroxisome ghosts in P. pastoris pas1 cells, and their ability to import some proteins, stands in contrast with the results reported by Erdmann et al. (1991) for the S. cerevisiae pas1 mutant, in which they were unable to detect peroxisome-like structures. We discuss the role of PAS1 in peroxisome biogenesis in light of the new information regarding peroxisome ghosts in pas1 cells.

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.

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.

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.

Prognostic value of dobutamine-atropine stress echocardiography early after acute myocardial infarction. Echo Dobutamine International Cooperative (EDIC) Study.

OBJECTIVES: The aim of this multicenter, multinational, prospective, observational study was to assess the relative value of myocardial viability and induced ischemia early after uncomplicated myocardial infarction. BACKGROUND: Dobutamine-atropine stress echocardiography allows evaluation of rest function (at baseline), myocardial viability (at low dose) and residual ischemia (peak dose, up to 40 micrograms with atropine up to 1 mg) in one test. METHODS: Dobutamine-atropine stress echocardiography was performed 12 +/- 5 days (mean +/- SD) after a first uncomplicated acute myocardial infarction in 778 patients (677 men; mean age 58 +/- 10 years) with technically satisfactory rest echocardiographic study results. Patients were followed-up for 9 +/- 7 months. RESULTS: Dobutamine-atropine stress echocardiographic findings were positive for myocardial ischemia in 436 of patients (56%) and negative in 342 (44%). During follow-up, there were 14 cardiac-related deaths (1.8% of the total cohort), 24 (2.9%) nonfatal myocardial infarctions and 63 (8%) hospital readmissions for unstable angina. One hundred seventy-four patients (22%) underwent coronary revascularization (bypass surgery or coronary angioplasty). Spontaneous events occurred in 61 of 436 patients with positive and 40 of 342 patients with negative findings on dobutamine-atropine stress echocardiography (14% vs. 12%, p = 0.3). When only spontaneously occurring events were considered, the most important predictor was myocardial viability (chi-square 9.7). Using the Cox proportional hazards model, only the presence of myocardial viability (hazard ratio [HR] 2.0, p < 0.002) and age (HR 1.03, p < 0.001) were predictive of spontaneously occurring events. When only hard cardiac events were considered, age was the strongest predictor (chi-square 3.6, p = 0.056), followed by wall motion score index (WMSI) at peak dose (chi-square 3.3, p = 0.06) and remote ischemia (chi-square 2.25, p = 0.1). When cardiac death was considered, WMSI at peak dose was the best predictor (HR 9.2, p < 0.0001). CONCLUSIONS: During dobutamine stress, echocardiographic recognition of myocardial viability is more prognostically important than echocardiographic recognition of myocardial ischemia for predicting unstable angina, whereas WMSI at peak stress was the best predictor of cardiac-related death. Different events can be recognized with different efficiency by various stress echocardiographic variables.

Does stress echocardiography predict the site of future myocardial infarction? A large-scale multicenter study. EPIC (Echo Persantine International Cooperative) and EDIC (Echo Dobutamine International Cooperative) study groups.

OBJECTIVES: We sought to assess whether the site of future myocardial infarction can be predicted on the basis of induced dyssynergy ("area at risk") recognized by stress echocardiography. BACKGROUND: The severity and extent of stress-induced dyssynergy are strong predictors of subsequent major cardiac events. However, high grade stenotic lesions are not strictly associated with the site of future coronary occlusions. METHODS: From the stress echocardiography multicenter trials data bank, we selected 70 patients (56 men; mean age +/- SD 58 +/- 11 years) meeting the following inclusion criteria: 1) dipyridamole (n = 53) or dobutamine (n = 17) stress echocardiography; 2) a spontaneously occurring infarction, with no intercurrent revascularization procedure between the initial study and the infarction; and 3) a follow-up rest echocardiogram obtained 41 +/- 90 days after the infarction. RESULTS: A complete ischemia-infarction mismatch (infarct-related dysfunction in a patient with negative stress test results) occurred in 29 patients (41%). A partial mismatch (ischemic dysfunction in a territory different from the infarct area) occurred in nine patients (13%). A match (ischemia-related and infarction-related dyssynergy involving the same region) occurred in 32 patients (46%). The average time interval between the stress examination and the occurrence of infarction or reinfarction was 144 +/- 160 days in patients with a match and 439 +/- 622 days in patients with a mismatch (p < 0.05). CONCLUSIONS: Induced ischemia (imaged as transient dyssynergy by pharmacologic stress echocardiography) inconsistently identifies the site of future infarction. The majority of spontaneous coronary occlusions leading to infarction are unheralded by induced ischemia. However, most infarctions occurring within 1 year of stress testing are in the area identified as ischemic during testing.

The atropine factor in pharmacologic stress echocardiography. Echo Persantine (EPIC) and Echo Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests--dipyridamole and dobutamine--with state of the art protocols in a large multicenter prospective study. BACKGROUND: In the continuing quest for ideal diagnostic accuracy, pharmacologic stress echocardiography has quickly moved over the years from low to high dose regimens and is currently performed with atropine coadministration. METHODS: Dobutamine (up to 40 microgram/kg body weight per min) plus atropine (up to 1 mg over 4 h) and dipyridamole (up to 0.84 mg/kg per min over 10 h) plus atropine (up to 1 mg over 4 h) stress echocardiography was performed on different days, in random order and within 1 week in 360 patients with chest pain syndrome. Thirteen different echocardiographic laboratories, all fulfilling quality control criteria for stress echocardiographic reading, contributed to the study. RESULTS: No major complications occurred during either test. The test was interrupted before achievement of predetermined end points for limiting side effects in 37 dobutamine-atropine and 7 dipyridamole-atropine stress echocardiographic studies (feasibility 90% vs. 98%, p < 0.01). Diagnostic accuracy was assessed in a subset of 110 patients with no obvious rest dyssynergy (akinesia or dyskinesia) who underwent coronary angiography independently of test results and within 1 week of testing. Significant coronary artery disease (> or = 50% diameter reduction in at least one major coronary vessel by quantitative coronary angiography) was found in 92 patients. Sensitivity for detection of coronary artery disease was 84% (77 of 92) for dobutamine-atropine and 82% (75 of 92) for dipyridamole-atropine stress echocardiography (p = NS), with a specificity of 89% (16 of 18) for dobutamine-atropine and 94% (17 of 18) for dipyridamole-atropine stress echocardiography (p = NS). A significant correlation was present between peak wall motion score index during dipyridamole-atropine and dobutamine-atropine stress echocardiography (r = 0.83, p < 0.0001). CONCLUSIONS: Dobutamine-atropine and dipyridamole-atropine stress echocardiography are safe and feasible, although submaximal studies are more frequent with dobutamine. The two stresses have comparable accuracy in the detection of angiographically assessed coronary artery disease, although dobutamine is marginally more sensitive and dipyridamole marginally more specific. Stratification of the ischemic response in the space domain is also comparable with the two stresses.

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.

Labeling of peroxisomes with green fluorescent protein in living P. pastoris cells.

We exploited the light-activated fluorescent properties of the green fluorescent protein (GFP) of the jellyfish Aequorea victoria for studies on the peroxisomal sorting of polypeptides. GFP and GFP-SKL (containing a C-terminal, tripeptide peroxisomal targeting signal, SKL) were expressed from a methanol-inducible, alcohol oxidase (AOX1) promoter in the methylotrophic yeast Pichia pastoris. GFP was cytosolic, whereas the GFP-SKL fusion protein was targeted to peroxisomes, as demonstrated by biochemical fractionation of organelles on Nycodenz gradients. Neither GFP nor GFP-SKL affected the viability of yeast cells but both were fluorescent on excitation with 395-nm UV light. The subcellular locations of GFP and GFP-SKL in living yeast cells were monitored by fluorescence microscopy and their fluorescence was coupled to photo-oxidation of diaminobenzidine (DAB), resulting in the deposition of electron-dense oxidized DAB at intracellular locations of GFP derivatives. This photooxidation procedure permitted facile ultrastructural localization of GFP in cells by electron microscopy, and provided further evidence that GFP produced in P. pastoris is cytosolic, whereas GFP-SKL is peroxisomal. The GFP-SKL fusion protein is therefore a versatile reporter for the peroxisomal compartment, with many applications for studies involving peroxisomal import and biogenesis.

Reproducibility of wall motion score and its correlation with left ventricular ejection fraction in patients with acute myocardial infarction.

The inter- and intraobserver variability, as well as the relation to left ventricular (LV) function indexes, of LV wall motion score calculated using the 16- and 11-segment models of LV segmentation were assessed in 105 patients with acute myocardial infarction who were examined at 36 +/- 7 hours from onset of symptoms. In these patients, the use of the 16-segment model of LV segmentation portends to a significantly higher inter- and intraobserver reproducibility of segmental wall motion score than the use of the 11-segment model. In addition, wall motion score assessed with the more detailed 16-segment model of LV segmentation showed a significantly higher correlation with LV ejection fraction than the wall motion score assessed using the 11-segment model.

Spontaneous retroperitoneal hemorrhage: unusual presentation of renal cancer.

Spontaneous retroperitoneal hemorrhage as the presenting sign of renal cancer is rare. A case of spontaneous retroperitoneal hemorrhage from a renal carcinoma is described and management possibilities presented. While it is true that renal angiomyolipomas are the main cause of spontaneous retroperitoneal renal bleeding, the possibility of renal cancer should be entertained more often in the differential diagnosis.

Transitional cell carcinoma occurring in ureterocele.

A case of transitional cell cancer developing in a ureterocele stump several years after a heminephroureterectomy is described. The role of ultrasonography in establishing the diagnosis is emphasized. This case illustrates the potentially dangerous effect of leaving a defunctionalized ureteral stump and ureterocele. Recommendation is made for removal of the ureteral stump and ureterocele at the time of heminephroureterectomy to prevent the aforementioned complication.

Ureteral stump calculi.

We report 2 cases of ureteral stump calculi presenting years after nephrectomy. Stones in the ureteral stump are extremely uncommon, and their occurrence has led us to review the possible mechanisms underlying their etiology.

Percutaneous management of postoperative lymphocele.

A case report of a pelvic lymphocele developing after lymphadenectomy for staging of prostatic carcinoma is described. This collection was successfully managed by percutaneous catheter drainage. The incidence, pathophysiology, clinical symptomatology, differential diagnosis, and treatment options of pelvic lymphocele are reviewed. We believe that percutaneous catheter drainage is currently the optimal treatment modality.

Bilateral testicular germ cell malignancy.

The other testicle was involved in 6 of 235 patients (2.69 per cent) with a history of testicular germ cell tumor. It occurred more often following seminoma (4 of 113, 3.5 per cent cases). The mean age at occurrence of the first tumor (twenty-five years) was earlier than expected, and the mean interval between tumors was 8.8 years. Accurate clinical staging of second tumors is impeded by alteration in the routes of metastatic dissemination, and treatment options are limited by previous therapy for the first tumor.

Opioid delta-receptor involvement in supraspinal and spinal antinociception in mice.

The possibility that the opioid delta-receptor mediates antinociception in tests where heat is the noxious stimulus was investigated using highly selective mu- and delta-agonist and -antagonists. Antinociceptive dose-response curves were constructed for mu ([D-Ala2,NMePhe4,Gly-ol]enkephalin, DAGO; morphine) and delta ([D-Pen2,D-Pen5]enkephalin, DPDPE)-agonists in the absence, and in the presence of the mu non-surmountable antagonist, beta-funaltrexamine (beta-FNA) or the delta-antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, where Aib is alpha-amino-isobutyric acid). Agonists and ICI 174,864 were given alone in the same intracerebroventricular (i.c.v.) or intrathecal (i.th.) injection to mice 20 min prior to testing in the warm-water (55 degrees C) tail-withdrawal test (+10 min for i.th. DPDPE); beta-FNA was given as a single i.c.v. or i.th. pretreatment dose (20 and 0.01 nM, respectively) 4 h prior to testing. I.c.v. pretreatment with beta-FNA resulted in a rightward displacement of the DAGO and morphine antinociceptive dose-response lines, but failed to displace the i.c.v. DPDPE curve. Similarly, i.th. pretreatment with beta-FNA displaced the i.th. morphine dose-response curve to the right without affecting the i.th. DPDPE antinociceptive dose-response line. ICI 174,864 (1 and 3 micrograms) produced a dose-related antagonism of i.c.v. or i.th. DPDPE, but did not alter the antinociceptive effects of DAGO or morphine given by the same routes. Co-administration of ICI 174,864 (3 micrograms) with i.c.v. morphine in beta-FNA pretreated (but not control) mice resulted in a further rightward displacement of the morphine dose-response line.(ABSTRACT TRUNCATED AT 250 WORDS)