Demonstration and imaging of cryogenic magneto-thermoelectric cooling in a van der Waals semimetal.

Attaining viable thermoelectric cooling at cryogenic temperatures is of considerable fundamental and technological interest for electronics and quantum materials applications. In-device temperature control can provide more efficient and precise thermal environment management compared with conventional global cooling. The application of a current and perpendicular magnetic field gives rise to cooling by generating electron-hole pairs on one side of the sample and to heating due to their recombination on the opposite side, which is known as the Ettingshausen effect. Here we develop nanoscale cryogenic imaging of the magneto-thermoelectric effect and demonstrate absolute cooling and an Ettingshausen effect in exfoliated WTe2 Weyl semimetal flakes at liquid He temperatures. In contrast to bulk materials, the cooling is non-monotonic with respect to the magnetic field and device size. Our model of magneto-thermoelectricity in mesoscopic semimetal devices shows that the cooling efficiency and the induced temperature profiles are governed by the interplay between sample geometry, electron-hole recombination length, magnetic field, and flake and substrate heat conductivities. The observations open the way for the direct integration of microscopic thermoelectric cooling and for temperature landscape engineering in van der Waals devices.

Direct observation of vortices in an electron fluid.

Vortices are the hallmarks of hydrodynamic flow. Strongly interacting electrons in ultrapure conductors can display signatures of hydrodynamic behaviour, including negative non-local resistance1-4, higher-than-ballistic conduction5-7, Poiseuille flow in narrow channels8-10 and violation of the Wiedemann-Franz law11. Here we provide a visualization of whirlpools in an electron fluid. By using a nanoscale scanning superconducting quantum interference device on a tip12, we image the current distribution in a circular chamber connected through a small aperture to a current-carrying strip in the high-purity type II Weyl semimetal WTe2. In this geometry, the Gurzhi momentum diffusion length and the size of the aperture determine the vortex stability phase diagram. We find that vortices are present for only small apertures, whereas the flow is laminar (non-vortical) for larger apertures. Near the vortical-to-laminar transition, we observe the single vortex in the chamber splitting into two vortices; this behaviour is expected only in the hydrodynamic regime and is not anticipated for ballistic transport. These findings suggest a new mechanism of hydrodynamic flow in thin pure crystals such that the spatial diffusion of electron momenta is enabled by small-angle scattering at the surfaces instead of the routinely invoked electron-electron scattering, which becomes extremely weak at low temperatures. This surface-induced para-hydrodynamics, which mimics many aspects of conventional hydrodynamics including vortices, opens new possibilities for exploring and using electron fluidics in high-mobility electron systems.

Long-range nontopological edge currents in charge-neutral graphene.

Van der Waals heterostructures display numerous unique electronic properties. Nonlocal measurements, wherein a voltage is measured at contacts placed far away from the expected classical flow of charge carriers, have been widely used in the search for novel transport mechanisms, including dissipationless spin and valley transport1-9, topological charge-neutral currents10-12, hydrodynamic flows13 and helical edge modes14-16. Monolayer1-5,10,15-19, bilayer9,11,14,20 and few-layer21 graphene, transition-metal dichalcogenides6,7 and moiré superlattices8,10,12 have been found to display pronounced nonlocal effects. However, the origin of these effects is hotly debated3,11,17,22-24. Graphene, in particular, exhibits giant nonlocality at charge neutrality1,15-19, a striking behaviour that has attracted competing explanations. Using a superconducting quantum interference device on a tip (SQUID-on-tip) for nanoscale thermal and scanning gate imaging25, here we demonstrate that the commonly occurring charge accumulation at graphene edges23,26-31 leads to giant nonlocality, producing narrow conductive channels that support long-range currents. Unexpectedly, although the edge conductance has little effect on the current flow in zero magnetic field, it leads to field-induced decoupling between edge and bulk transport at moderate fields. The resulting giant nonlocality at charge neutrality and away from it produces exotic flow patterns that are sensitive to edge disorder, in which charges can flow against the global electric field. The observed one-dimensional edge transport is generic and nontopological and is expected to support nonlocal transport in many electronic systems, offering insight into the numerous controversies and linking them to long-range guided electronic states at system edges.

Supra-maximal effort and reaction and movement times in a non-compatible response time task.

AIM: The primary purpose of this study was to examine the effect of attempting to exercise supra-maximally on reaction time and movement time in a non-compatible response time task. METHODS: Subjects (n=9) undertook a 4-choice non-compatible response time test at rest, while cycling at 70 rpm with a resistance of 35 W (low intensity exercise), cycling at 70% of their maximum power output (MPO), cycling at 100% MPO and attempting to cycle at 70 rpm, with a resistance that was 28 W greater than the resistance required to elicit MPO (supra-maximal effort). RESULTS: Reaction time, movement time, intra-individual variations in reaction time and movement time at each exercise intensity were compared by a series of repeated measures analyses of variance. A significant effect of exercise was shown for movement time, F(4,32)=6.05, p<0.001, eta2=0.44, Power=0.97 and intra-individual variation in reaction time, F(4,32)=4.98, p<0.005, eta2=0.38, Power=0.93. For movement time, Tukey post-hoc tests showed that performance at rest was significantly slower than that during exercise at 70%, 100% MPO and supra-maximal effort. Performance at low intensity exercise was significantly slower than that at MPO. For intra-individual variations in reaction time, Tukey tests found that variations under supra-maximal effort and MPO were significantly greater than those at low intensity and 70% MPO. CONCLUSIONS: It was concluded that exercise facilitates speed of movement when the limbs used for the motor task are not the ones that are being exercised. Reaction time during maximal and supra-maximal exercise demonstrates large intra-individual variations.

Quantification of groundwater contamination in an urban area using integral pumping tests.

In this paper, the integral groundwater investigation method is used for the quantification of PCE and TCE mass flow rates at an industrialized urban area in Linz, Austria. In this approach, pumping wells positioned along control planes perpendicular to the groundwater flow direction are operated for a time period on the order of days and sampled for contaminants. The concentration time series of the contaminants measured during operation of the pumping wells are then used to determine contaminant mass flow rates, mean concentrations and the plume shapes and positions at the control planes. The three control planes used in Linz were positioned downstream of a number of potential source zones, which are distributed over the field site. By use of the integral investigation method, it was possible to identify active contaminant sources, quantify the individual source strength in terms of mass flow rates at the control planes and estimate the contaminant plume position relative to the control planes. The source zones emitting the highest PCE and TCE mass flow rates could be determined, representing the areas where additional investigation and remediation activities will be needed. Additionally, large parts of the area investigated could be excluded from further investigation and remediation activities.

Flow cytometric analysis of macaque whole blood for antigen-specific intracellular cytokine production by T lymphocytes.

We report here the standardized conditions for stimulation of macaque whole blood samples with various protein or peptide antigens, and production of significant intracellular levels of interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in CD4+ as well as CD8+ T lymphocytes. We observed significantly higher levels of TNF-alpha compared with IFN-gamma in both CD4+ and CD8+ T lymphocytes from all the macaque whole blood samples stimulated with staphylococcal enterotoxin B (SEB) as an antigen. Similarly, when whole blood samples from rhesus macaques immunized with an HIV envelope peptide cocktail vaccine were stimulated with either the peptide cocktail or recombinant gp160, we observed production of significant levels of TNF-alpha by both CD4+ and CD8+ T lymphocytes. These results strongly support the utility of the whole blood cytokine flow cytometry methodology for determining antigen-specific immune responses of macaques in vaccine studies.

Vascular anomalies and tracheoesophageal compression: a single institution's 25-year experience.

BACKGROUND: Vascular rings are uncommon anomalies in which preferred strategies for diagnosis and treatment may vary among institutions. In this report, we offer a description of our approach and a review of our 25-year experience. METHODS: A retrospective review was conducted of all pediatric patients with symptomatic tracheoesophageal compression secondary to anomalies of the aortic arch and great vessels diagnosed from 1974 to 2000. RESULTS: Thirty-one patients (38%) of eighty-two patients (mean age, 1.7 years), were identified with double aortic arch, 22 patients (27%) with right arch left ligamentum, and 20 patients (24%) with innominate artery compression. Our diagnostic approach emphasized barium esophagram, along with echocardiography. This regimen was found to be reliable for all cases except those with innominate artery compression for which bronchoscopy was preferred, and except those with pulmonary artery sling for which computed tomography or magnetic resonance imaging, in addition to bronchoscopy, were preferred. Left thoracotomy was the most common operative approach (70 of 82; 85%). Ten patients (12%) had associated heart anomalies, and 6 (7%) patients underwent repair. Complications occurred in 9 (11%) patients and led to death in 3 (4%) patients. CONCLUSIONS: In our practice, barium swallow and echocardiography are sufficient in diagnosing and planning the operative strategy in the majority of cases, with notable exceptions. Definitive intraoperative delineation of arch anatomy minimizes the risk of misdiagnosis or inadequate treatment.

Functional dynamics in the active site of the ribonuclease binase.

Binase, a member of a family of microbial guanyl-specific ribonucleases, catalyzes the endonucleotic cleavage of single-stranded RNA. It shares 82% amino acid identity with the well-studied protein barnase. We used NMR spectroscopy to study the millisecond dynamics of this small enzyme, using several methods including the measurement of residual dipolar couplings in solution. Our data show that the active site of binase is flanked by loops that are flexible at the 300-micros time scale. One of the catalytic residues, His-101, is located on such a flexible loop. In contrast, the other catalytic residue, Glu-72, is located on a beta-sheet, and is static. The residues Phe-55, part of the guanine base recognition site, and Tyr-102, stabilizing the base, are the most dynamic. Our findings suggest that binase possesses an active site that has a well-defined bottom, but which has sides that are flexible to facilitate substrate access/egress, and to deliver one of the catalytic residues. The motion in these loops does not change on complexation with the inhibitor d(CGAG) and compares well with the maximum k(cat) (1,500 s(-1)) of these ribonucleases. This observation indicates that the NMR-measured loop motions reflect the opening necessary for product release, which is apparently rate limiting for the overall turnover.

A longitudinal analysis of the pediatric surgeon workforce.

OBJECTIVE: To describe the trends in the pediatric surgeon workforce during the last 25 years and to provide objective data useful for planning graduate medical education requirements. SUMMARY BACKGROUND DATA: In 1975, the Study on U.S. Surgical Services (SOSSUS) was published, including a model to survey staffing. A pediatric surgeon workforce study was initiated in conjunction with SOSSUS as a population, supply, and need-based study. The study has been updated every 5 years using the same study model, with the goals of determining the number and distribution of pediatric surgeons in the United States, the number needed and where, and the number of training programs and trainee output required to fill estimated staffing needs. This is the only such longitudinal workforce analysis of a surgical specialty. METHODS: Questionnaires were sent to 100 pediatric surgeons representing the 62 standard metropolitan statistical areas (SMSAs) in the United States with a population of 200,000 or more to verify the names and locations of all active pediatric surgeons and to gain information about the 5-year need for new pediatric surgeons by region. A program was developed to predict the number of pediatric surgeons relative to the total population and the 0-to-17-year-old population in the subsequent 30 years using updated data on the present number and ages of pediatric surgeons, age-specific death and retirement rates, projections of U.S. population by age group, and varying numbers of trainees graduated per year. As each 5-year update was done, previous projections were compared with actual numbers of pediatric surgeons found. The trends during the last 25 years were analyzed and compared and additional information regarding the demographics of practice, trends in reimbursement, and volume and scope of surgery was obtained. RESULTS: The birth rate has been stable since 1994. The 0-to-17-year-old population has been increasing at 0.65% per year; a 0.64% annual rate is projected to 2040. At present, 661 pediatric surgeons are distributed in every SMSA of 200,000 or more population, with an average age of 45 and an average age of retirement 65. The actual number of pediatric surgeons in each 5-year survey has consistently validated previous projections. Trainee output has increased markedly in the past 10 years. The rate of growth of the pediatric surgeon workforce at present is 50% greater than the forecasted rate of increase in the pediatric age group, and during the past 25 years the rate of growth of the pediatric surgeon workforce has been double that of the pediatric population growth. Nationally, significant changes in reimbursement, volume of surgery, and demographics of practice have occurred.

Effects of chronic salicylate on GABAergic activity in rat inferior colliculus.

It is well accepted that salicylate ototoxicity results in reversible tinnitus in humans. Salicylate-induced tinnitus may be an example of plasticity of the central auditory system and could potentially serve as a model to further understand mechanisms of tinnitus generation. This study examined levels of glutamic acid decarboxylase (GAD) and the binding characteristics of the GABA(A) receptor in auditory brainstem structures of Long-Evans rats chronically treated with salicylate. Western blotting revealed a significant 63% (P<0.008) elevation of GAD levels in the inferior colliculus (IC) of salicylate-treated subjects. This occurred in subjects demonstrating behavioral evidence of tinnitus. Muscimol saturation analysis was indicative of a salicylate-related increase in receptor affinity. Linear regression of [(3)H]muscimol saturation analysis data revealed a significant (P<0.05) reduction in K(d) values in whole IC (-48%), as well as in the central nucleus of IC (CIC, -58%) and combined external and dorsal cortex of IC (E/DCIC, -46%). The number of GABA(A) binding sites (B(max)) were also significantly (P<0.05) decreased. These changes were observed only in central auditory structures. This suggests that GAD expression and GABA(A) receptor binding characteristics may be altered with chronic exposure to sodium salicylate and these changes may represent aberrant plasticity clinically experienced as tinnitus.

GAD levels and muscimol binding in rat inferior colliculus following acoustic trauma.

Pharmacological studies of the inferior colliculus (IC) suggest that the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) plays an important role in shaping responses to simple and complex acoustic stimuli. Several models of auditory dysfunction, including age-related hearing loss, tinnitus, and peripheral deafferentation, suggest an alteration of normal GABA neurotransmission in central auditory pathways. The present study attempts to further characterize noise-induced changes in GABA markers in the IC. Four groups (unexposed control, 0 h post-exposure, 42 h post-exposure, and 30 days post-exposure) of 3-month-old male Fischer 344 rats were exposed to a high intensity sound (12 kHz, 106 dB) for 10 h. Observed hair cell damage was primarily confined to the basal half of the cochlea. There was a significant decrease in glutamic acid decarboxylase (GAD(65)) immunoreactivity in the IC membrane fraction compared to controls (P<0.05) at 0 h (-41%) and 42 h (-28%) post-exposure, with complete recovery by 30 days post-exposure (P>0.98). Observed decreases in cytosolic levels of GAD(65) were not significant. Quantitative muscimol receptor binding revealed a significant increase (+20%) in IC 30 days after sound exposure (P<0.05). These data suggest that changes in GABA neurotransmission occur in the IC of animals exposed to intense sound. Additional studies are needed to determine whether these changes are a result of protective/compensatory mechanisms or merely peripheral differentiation, as well as whether these changes preserve or diminish central auditory system function.

Age-related changes in GABA(A) receptor subunit composition and function in rat auditory system.

A decline in the ability to discriminate speech from noise due to age-related hearing loss (presbycusis) may reflect impaired auditory information processing within the central nervous system. Presbycusis may result, in part, from functional loss of the inhibitory neurotransmitter GABA. The present study assessed age-related changes of the GABA(A) receptor in the inferior colliculus of young-adult, middle-aged, and aged rats related to: (i) receptor subunit composition and (ii) receptor function. Western blotting was used to measure protein levels of selected GABA(A) receptor subunits in preparations obtained from the inferior colliculus of Fischer 344 and Fischer 344/Brown-Norway F1 hybrid rats. In both strains, the aged group exhibited significant increases in gamma1 subunit protein and a decrease in alpha1 subunit protein. To examine the functional consequence of this putative age-related subunit change, we measured the ability of exogenous GABA to flux/translocate chloride ions into microsac preparations derived from Fischer 344 inferior colliculus. GABA-mediated chloride influx was significantly increased in samples prepared from the inferior colliculus of aged animals. Together with previous studies, these results strongly suggest an age-related change in GABA(A) receptor composition. These changes may reflect a compensatory up-regulation of inhibitory function in the face of significant loss of presynaptic GABA release. These findings provide one example of plastic neurotransmitter receptor changes which can occur during the ageing process.

Education on health risks of smoking in Magadan, Russia.

PURPOSE: The purpose of this project was to educate young Russians on the health risks of smoking. METHOD: The American Cancer Society, Alaska Division, sponsored a project to deliver its teaching modules on the health risks of tobacco use to first- through third-graders in Magadan, Russia. Starting with a $4,400 (U.S.) contribution designated for this purpose, a young teacher, Irina Alishova, was contacted in Magadan in 1993. She translated the modules of the American Cancer Society oriented to the first- to the third-grade level. Irina also made contact with the Magadan school system, specifically the principal of Middle School Number 29, Alla Vakulyuk. Principal Vakulyuk encouraged the project and worked with the other schools in the Magadan school system. RESULTS: Throughout the 1993-94 school year, nearly all of the first- and second-grade classes and a portion of the third-grade classes received and participated in the 50-minute teaching module. An American representative for the American Cancer Society observed one of the classes and noted thoughtful and enthusiastic participation by the schoolchildren.

Efficacy of partial wrap fundoplication for gastroesophageal reflux after repair of esophageal atresia.

Gastroesophageal reflux (GER) often develops in children who have undergone prior repair of esophageal atresia/tracheoesophageal fistula (EA/TEF). Fundoplication is necessary in many of these children. The complete wrap (Nissen) fundoplication is often used in this setting. However, poor results have been noted, with a mean failure rate of 30% reported in four recent studies. A partial wrap fundoplication for GER associated with EA/TEF is theoretically attractive, because the poor esophageal motility and diminished acid clearance (already physiologically present) is exacerbated by a complete wrap fundoplication. The authors reviewed their extensive experience with partial wrap (Thal) fundoplication in EA/TEF to determine if the failure rate was better than that reported for the Nissen fundoplication. In the past 18 years, the authors performed 1,467 fundoplication procedures. During the same period, 143 children underwent repair of EA/TEF. Fifty-nine children underwent fundoplication after a previous EA/TEF repair. Most of the fundoplications (58 of 59, 98%) were Thal procedures. Defining failure strictly as a need for reoperation, the failure rate in our series was 15% (9 of 59 children). Compared with the failure rate in the 1,408 non-EA/TEF patients (61 of 1408, 4.3%), results were significantly worse for the EA/TEF group (P > .001). The failure rate of Thal fundoplication performed for GER in the EA/TEF population is substantially higher than the non-EA/TEF patients. The same factors responsible for the development of reflux in these children (poor acid clearance, altered motility, esophageal shortening) may contribute to the higher failure rate. Although partial wrap fundoplication frequently failed (15%), the results were still substantially better than those reported for Nissen fundoplication in these children (30% failure rate).

Update on the analysis of the need for pediatric surgeons in the United States.

UNLABELLED: Accurate estimations of pediatric surgical manpower needs are necessary if this specialty is to avoid the consequences of under- or oversupply, and reasonable decisions must be made relative to the number of training programs needed. METHODS: Fifteen, 10, and 5 years ago, pediatric surgeons (PSs) in 62 standard metropolitan statistical areas (SMSAs) having a population of at least 200,000 were asked to estimate the number of PSs needed in their localities. A computer program analogous to the SOSSUS program was designed to project the number of PSs that would result from various numbers of trainee graduates per year. The program has been updated for comparison. Known input data included the present number and age of PSs, age range of trainees, current US population projections to the year 2025, and the average retirement age. RESULTS: These PSs estimated that 88 additional PSs are needed in the next 10 years. Currently, 26 programs in the United States graduate an average of 24 trainees per year, and six programs in Canada graduate six trainees per year. The previous projection indicated that 20 trainees per year would result in 525 PSs in 1993, and the actual number is 559; so the figures indicate that 27 or 28 PSs are entering practice each year. The apparent increase in numbers is related to entry of Canadian trainees primarily, and a few others, into practice. The current computer projection indicates that 20 graduate trainees per year would result in an absolute increase of 0.55% per year, and 25 per year would result in an increase of 1.43% per year, to 2020, while the increases in the US population would be 1.02% per year for all ages and 0.52% for 0 to 15 year olds. If all programs currently being considered for approval are certified, as many as 36 trainees per year--or 7 times the rate of the 0-15-year population increase--will result. CONCLUSION: Although an average of 20 graduates per year entering practice would keep pace with the pediatric population, 25 to 27 graduates per year--or 3.5 to 4 times the rate of the 0- to 15-year population increase--can be accommodated now into the current system of delivery of pediatric surgical care on the basis of estimated need. Many more graduates than this would create an excess of surgeons before long.

An absent right and persistent left superior vena cava in an infant requiring extracorporeal membrane oxygenation therapy.

A persistent left superior vena cava (PLSVC) is the most common anomaly of the major veins. However, an absent right superior vena cava and PLSVC is much less common; fewer than 100 cases have been reported in the world literature in patients with situs solitus. This rare variation was encountered in a newborn requiring extracorporeal membrane oxygenation (ECMO) for meconium aspiration and interfered with venous cannulation. The anomaly was not suspected before an unusual cannula position was observed on the chest radiograph, and it was confirmed by bedside venography. Adequate venous cannulation was obtained through the anomalous vessel using a flexible catheter, allowing for an uneventful ECMO course. The epidemiology and embryology of this incidental anomaly are reviewed, and the methods used to circumvent the difficulties it presented in this case are described.

Abbreviated esophageal pH monitoring as an indication for fundoplication in children.

Intraesophageal pH recordings from 40 patients with abnormal studies who underwent fundoplication during a 1-year period were evaluated. Scores were recalculated for the first 12, 16, and 20 hours, respectively. Five of the recordings were for less than 24 hours, but were grossly abnormal and mathematically could not have normalized at 24 hours. The percentage of studies which were normal at 12, 16, and 20 hours were 20%, 15%, and 0%, respectively. One fifth of the patients would have been denied a fundoplication based on 12-hour results. In addition, 75 consecutive pH recordings were evaluated prospectively. Total scores were determined for the first 12, 16, and 20 hours with accuracies of 85%, 93%, and 92%, respectively. The sensitivity of 12-hour monitoring was only 78%. All abbreviated studies had a low rate of false positives; however, any false positives may be significant when used to determine the need for an operation. Abbreviated studies were associated with high false-negative rates (up to 52% for the 12-hour studies) for the calculated mean duration of sleep reflux, a parameter that has been found to be useful in identifying patients with respiratory symptoms secondary to gastroesophageal reflux. The use of abbreviated pH monitoring is discouraged.

Relief of subglottic stenosis by anterior cricoid resection: an operation for the difficult case.

Anterior cricoid resection is an effective procedure to relieve subglottic stenosis. This is well documented in adults, although reports of the procedure in growing airways are limited. Over an 11-year period, seven pediatric patients underwent anterior cricoid resection for recalcitrant subglottic stenosis. In four patients, the stricture was secondary to prolonged intubation, one developed subglottic stenosis following a high placement of tracheostomy for epiglottitis and another had congenital subglottic stenosis. One child had subglottic stenosis combined with laryngotracheoesophageal cleft and more distally located tracheoesophageal fistula. All patients had failed to respond to previous treatment: dilatations (3 to 20), steroid injection (3 patients), and Evan's tracheoplasty (2 patients). All patients had an excellent result from anterior cricoid resection. The median age of children undergoing anterior cricoid resection was 3 years. There was no mortality. Tracheostomy decannulation was accomplished within 12 weeks following operation in all patients. It was necessary to remove a tracheal granuloma in one patient. Anterior cricoid wedge resection leaving the posterior portion of the cricoid in place is done to avoid recurrent nerve injury. It is a relatively simple and effective procedure. There has been minimal morbidity and no mortality. Follow-up from 1 to 11 years shows no recurrence of stenosis. There has been normal laryngeal and airway growth.