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1.
J Chem Phys ; 156(4): 041102, 2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35105059

ABSTRACT

Advancements in x-ray free-electron lasers on producing ultrashort, ultrabright, and coherent x-ray pulses enable single-shot imaging of fragile nanostructures, such as superfluid helium droplets. This imaging technique gives unique access to the sizes and shapes of individual droplets. In the past, such droplet characteristics have only been indirectly inferred by ensemble averaging techniques. Here, we report on the size distributions of both pure and doped droplets collected from single-shot x-ray imaging and produced from the free-jet expansion of helium through a 5 µm diameter nozzle at 20 bars and nozzle temperatures ranging from 4.2 to 9 K. This work extends the measurement of large helium nanodroplets containing 109-1011 atoms, which are shown to follow an exponential size distribution. Additionally, we demonstrate that the size distributions of the doped droplets follow those of the pure droplets at the same stagnation condition but with smaller average sizes.

2.
J Phys Chem A ; 123(28): 5859-5865, 2019 Jul 18.
Article in English | MEDLINE | ID: mdl-31274308

ABSTRACT

Silver clusters were assembled in helium droplets of different sizes ranging from 104 to 1011 atoms. The clusters were heated upon laser irradiation at 355 nm, and evaporation dynamics of He atoms were studied by quadrupole mass spectroscopy using signals from He+, He2+, and He4+ splitter ions. We found that for droplets containing less than 107 atoms the laser irradiation leads to evaporation of He atoms. However, the laser irradiation leads to the breakup of the large droplets into smaller ones.

3.
J Chem Phys ; 148(4): 044302, 2018 Jan 28.
Article in English | MEDLINE | ID: mdl-29390856

ABSTRACT

Electron impact ionization of superfluid helium droplets containing several thousand atoms produces a broad distribution of Hen+ ions that peaks at n = 2 and decreases monotonically toward larger n. In larger droplets (say 105 or more atoms), however, the He4+ signal intensity is anomalously large. We have studied the mechanism for the formation of He4+ ions in large helium droplets by varying the duration of the electron impact excitation pulse. Droplets of different average sizes were generated using the expansion of helium at 20 bars and 9-20 K through a pulsed valve nozzle. The resulting ions were analyzed by time-of-flight mass spectroscopy (TOFMS) and quadrupole mass spectroscopy (QMS). The intensity distributions obtained with the TOFMS technique initially showed much smaller He4+ signals than those obtained using QMS. However, we discovered that the intensity anomaly is associated with the duration of the electron bombardment pulse in the TOFMS instrument. Measurements with different electron bombardment pulse durations enabled us to discern a characteristic time of ∼10 µs for enhanced He4+ production in large droplets under our experimental conditions. A qualitative model is presented in which metastables interact on droplet surfaces, yielding two He2+ cores that share a Rydberg electron while minimizing repulsion between the cores. This is the He4+(4A2) state suggested by Knowles and Murrell.

4.
Methods Enzymol ; 567: 71-95, 2016.
Article in English | MEDLINE | ID: mdl-26794351

ABSTRACT

Multivalent glycoconjugate-protein interactions are central to many important biological processes. Isothermal titration calorimetry (ITC) can potentially reveal the molecular and thermodynamic basis of such interactions. However, calorimetric investigation of multivalency is challenging. Binding of multivalent glycoconjugates to proteins (lectins) often leads to a stoichiometry-dependent precipitation process due to noncovalent cross-linking between the reactants. Precipitation during ITC titration severely affects the quality of the baseline as well as the signals. Hence, the resulting thermodynamic data are not dependable. We have made some modifications to address this problem and successfully studied multivalent glycoconjugate binding to lectins. We have also modified the Hill plot equation to analyze high quality ITC raw data obtained from multivalent binding. As described in this chapter, ITC-driven thermodynamic parameters and Hill plot analysis of ITC raw data can provide valuable information about the molecular mechanism of multivalent lectin-glycoconjugate interactions. The methods described herein revealed (i) the importance of functional valence of multivalent glycoconjugates, (ii) that favorable entropic effects contribute to the enhanced affinities associated with multivalent binding, (iii) that with the progression of lectin binding, the microscopic affinities of the glycan epitopes of a multivalent glycoconjugate decrease (negative cooperativity), (iv) that lectin binding to multivalent glycoconjugates, especially to mucins, involves internal diffusion jumps, (bind and jump) and (v) that scaffolds of glycoconjugates influence their entropy of binding.


Subject(s)
Calorimetry/methods , Entropy , Protein Binding , Thermodynamics
5.
Struct Dyn ; 2(5): 051102, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26798821

ABSTRACT

Lensless x-ray microscopy requires the recovery of the phase of the radiation scattered from a specimen. Here, we demonstrate a de novo phase retrieval technique by encapsulating an object in a superfluid helium nanodroplet, which provides both a physical support and an approximate scattering phase for the iterative image reconstruction. The technique is robust, fast-converging, and yields the complex density of the immersed object. Images of xenon clusters embedded in superfluid helium droplets reveal transient configurations of quantum vortices in this fragile system.

6.
Plant Dis ; 98(7): 995, 2014 Jul.
Article in English | MEDLINE | ID: mdl-30708885

ABSTRACT

Epidemiological investigations in representative chickpea (Cicer arietinum L.) fields in southern Italy (Larino, Campobasso, 41°50'45″ N, 14°55'28″ E) identified severe withering (25 to 51%) of plants during flowering. Diseased plants showed a reduced total root biomass associated with less vigorous and chlorotic foliage. Browning and necrosis of subcortical and xylematic tissues of the crown and main roots were observed in affected plants. Symptomatic root and stem portions from 50 plants were sampled, surface disinfected with a sodium hypochlorite water solution (2% v/v for 2 min), rinsed with sterile distilled water, and placed in petri dishes containing potato dextrose agar with streptomycin sulfate (200 mg/l) and incubated at 25°C for 10 days. The most frequent fungal colony isolated showed macro- and microscopic characters specific of the genus Fusarium (3), with falcate and three-septate macroconidia (24.0 to 43.8 µm long) and microconidia (6.8 to 10.4 µm long) with zero or one septa. The ribosomal DNA of the fungal isolate processed by PCR using the ITS1F/ITS4 primers (2) produced an amplicon of 545 bp (ENA, Accession No. HG423346). A BLAST search with the amplified sequence in the database of the International Mycological Association ( www.mycobank.org ) revealed 99% identity with F. oxysporum sequences. Additional molecular analysis using the specific primers Foc0-12/Foc0-12rf for F. oxysporum f.sp. ciceris (Foc) produced an amplicon only in the chickpea virulent strain Foc-7952, race 0 (1) used as control; furthermore, PCR amplification for the Pisatin Demetylase gene by using the specific primers PDAF2a and PDAR3a (4) yielded the expected amplicon only for the new isolate, whereas no amplification was obtained with the control strain Foc-7952. Pathogenicity assays were carried out to complete Koch's postulates. To this aim, horticultural peat was infested with a conidial suspension (1 × 104 conidia/g of soil) from the new fungal pathogen, dispensed in plastic pots, and sown with surface sterilized seeds of chickpea (cv. Real, ISEA, Italy). Uncontaminated peat was used as control. For both treatments, 3 replicates of 10 seeds were used and experiments repeated twice. The plastic pots were kept in a growth chamber (28°C; 70% RH; 15/9 h light/dark) where the first disease symptoms on plants appeared 20 days after sowing. At the end of the experiments, all plants inoculated with the new isolate showed a high disease severity (98%), whereas non-inoculated plants remained healthy. The seedlings from infested soil demonstrated the same symptoms previously observed in the field, and after re-isolation, the causal agent demonstrated the same morphological features of the isolate used for inoculation. Pathogenicity tests were performed on pea, faba bean, melon, and tomato by using three cultivars for each crop. The results demonstrated high virulence of the new isolate of F. oxysporum f.sp. pisi (Fop) on both chickpea and pea with seed germination reduction, rot on main and secondary roots and cotyledonary leaves, and root biomass reduction and foliage chlorosis. No symptoms were observed on other inoculated vegetal species. Collectively, data of our investigation allow us to affirm that this is the first report of Fop as a new pathogen of chickpea. This result has great economic importance since it enables specific monitoring and management plans for this new disease caused by Fop on chickpea, a key crop for human and animal nutrition. References: (1) M. M. Jiménez-Gasco and R. M. Jiménez-Díaz, Phytopathology 93:201, 2003. (2) I. Larena et al. J. Biotechnol. 75:187, 1999. (3) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell Publishing, Ames, IA, 2006. (4) N. A. Milani et al. Fungal Genet. Biol. 933:942, 2012.

7.
J Med Device ; 7(2): 210051-210055, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23904907

ABSTRACT

In this work, we modified the topography of commercial titanium orthopedic screws using electrochemical anodization in a 0.4 wt% hydrofluoric acid solution to produce titanium dioxide nanotube layers. The morphology of the nanotube layers were characterized using scanning electron microscopy. The mechanical properties of the nanotube layers were investigated by screwing and unscrewing an anodized screw into several different types of human bone while the torsional force applied to the screwdriver was measured using a torque screwdriver. The range of torsional force applied to the screwdriver was between 5 and [Formula: see text]. Independent assessment of the mechanical properties of the same surfaces was performed on simple anodized titanium foils using a triboindenter. Results showed that the fabricated nanotube layers can resist mechanical stresses close to those found in clinical situations.

8.
Ultrasonics ; 53(5): 1012-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23453558

ABSTRACT

The acoustic nonlinearity of water is investigated using a variation of the finite amplitude method with harmonic generation. The finite amplitude method provides information on the coefficient of nonlinearity, ß, through the ratio of the amplitude of the fundamental and that of the second harmonic. The pressure of both the fundamental, p1, and that of the second harmonic, p2, are determined experimentally at different transmitter-receiver separation distances, eliminating the need for knowledge of the sound absorption in the medium. It was found that the experimental relationship between the slope of p2(x)/p1(2)(x) and transmitter-receiver separation distance, x, follows a linear relationship only in the near-field, in good agreement with theoretical predictions. A ß of 3.5±0.1 is determined for water at room temperature, in good agreement with previous results from both the isentropic equation of state and finite amplitude method.

9.
Clin Genet ; 83(4): 321-31, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22725725

ABSTRACT

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1-2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex-influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre-symptomatic diagnosis has the greatest clinical utility.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/genetics , Membrane Proteins/genetics , Mutation , Adult , Aged , Aged, 80 and over , Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Arrhythmogenic Right Ventricular Dysplasia/pathology , Electrocardiography/methods , Female , Humans , Male , Middle Aged , Pedigree , Phenotype
10.
J Neurosci ; 32(44): 15533-46, 2012 Oct 31.
Article in English | MEDLINE | ID: mdl-23115190

ABSTRACT

Mutations in the CACNA1A gene are associated with neurological disorders, such as ataxia, hemiplegic migraine, and epilepsy. These mutations affect the pore-forming α(1A)-subunit of Ca(V)2.1 channels and thereby either decrease or increase neuronal Ca(2+) influx. A decreased Ca(V)2.1-mediated Ca(2+) influx has been shown to reduce the regularity of cerebellar Purkinje cell activity and to induce episodic cerebellar ataxia. However, little is known about how ataxia can be caused by CACNA1A mutations that increase the Ca(2+) influx, such as the S218L missense mutation. Here, we demonstrate that the S218L mutation causes a negative shift of voltage dependence of Ca(V)2.1 channels of mouse Purkinje cells and results in lowered thresholds for somatic action potentials and dendritic Ca(2+) spikes and in disrupted firing patterns. The hyperexcitability of Cacna1a(S218L) Purkinje cells was counteracted by application of the activators of Ca(2+)-dependent K(+) channels, 1-EBIO and chlorzoxazone (CHZ). Moreover, 1-EBIO also alleviated the irregularity of Purkinje cell firing both in vitro and in vivo, while CHZ improved the irregularity of Purkinje cell firing in vitro as well as the motor performance of Cacna1a(S218L) mutant mice. The current data suggest that abnormalities in Purkinje cell firing contributes to cerebellar ataxia induced by the S218L mutation and they advocate a general therapeutic approach in that targeting Ca(2+)-dependent K(+) channels may be beneficial for treating ataxia not only in patients suffering from a decreased Ca(2+) influx, but also in those suffering from an increased Ca(2+) influx in their Purkinje cells.


Subject(s)
Calcium Channels, N-Type/physiology , Calcium Channels, P-Type/genetics , Calcium Channels, Q-Type/genetics , Cerebellar Ataxia/drug therapy , Cerebellar Ataxia/genetics , Potassium Channels, Calcium-Activated/agonists , Action Potentials/drug effects , Action Potentials/physiology , Animals , Behavior, Animal/physiology , Benzimidazoles/pharmacology , Calcium/physiology , Calcium Channels, N-Type/drug effects , Calcium Channels, N-Type/genetics , Calcium Signaling/drug effects , Cerebellar Ataxia/psychology , Chlorzoxazone/therapeutic use , Extracellular Space/physiology , Female , Homeostasis/physiology , Male , Mice , Muscle Relaxants, Central/pharmacology , Mutation/genetics , Mutation/physiology , Patch-Clamp Techniques , Psychomotor Performance/physiology , Purkinje Cells/physiology
11.
Environ Technol ; 33(10-12): 1289-98, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22856301

ABSTRACT

The effect of aerator module configuration, liquid flow rate and diffuser submergence on oxygen transfer efficiency was examined in a surface aeration system with venturi injectors using the clean water test. Six venturi aerator modules were evaluated and the results indicated that better aeration efficiencies could be achieved by simply changing the way the venturi aerators were connected. Among all the configurations examined (modules a-f), two and three aerators connected in parallel (modules d, e and f) were able to bring more oxygen into water than the others. An increase in liquid flow rate led to an enhancement of the oxygen transfer coefficients, but the improvement was reduced if the liquid flow rate was too high. The oxygen transfer coefficient was found to have a relationship with the depth of diffusing pipes (surface aeration depth) for the surface aeration system and an optimal depth of around 40 cm was obtained from this study.


Subject(s)
Air , Waste Management/methods , Manure , Oxygen , Sewage
12.
Int J Food Microbiol ; 159(1): 17-24, 2012 Sep 17.
Article in English | MEDLINE | ID: mdl-22921968

ABSTRACT

The influence of temperature and relative humidity (RH) on the activity of three biocontrol agents-the yeast Metschnikowia pulcherrima LS16 and two strains of the yeast-like fungus Aureobasidium pullulans LS30 and AU34-2-against infection by A. carbonarius and ochratoxin A (OTA) accumulation in wine grape berries was investigated in lab-scale experiments. The presence of wounds on grape skin dramatically favored infection of berries by A. carbonarius strain A1102, since unwounded berries showed very low levels of infection at all conditions of RH and temperature tested. Artificially wounded berries pre-treated with the biocontrol agents were inoculated with the ochratoxigenic A. carbonarius strain A1102 and were incubated for 5 days at two levels of RH (60% and 100%) and three different temperatures (20, 25 and 30 °C). The three biocontrol agents were able to prevent infections at 60% RH and 20 °C. At 60% RH and 25 °C only strain AU34-2 achieved some protection on day 5, whereas at 30 °C a limited biocontrol efficacy was evident only up to day 2. At 100% RH, LS16, LS30 and AU34-2 showed effective protection of grape berries at 20 °C until the 5th day of incubation. The three biocontrol agents achieved significant protection at higher temperatures only until the 2nd day after the beginning of the experiment: all three strains at 25 °C, and only strain LS16 at 30 °C. After 5 days, the three biocontrol agents were able to significantly reduce the level of OTA in berries at all the conditions tested. This occurred even when protection from infection was not significant, except at 30 °C and 100% of RH for all the three strains, and at 25 °C and 100% of RH for strain LS16. The biocontrol agents displayed a higher rate of colonization on grape berries at 20 and 25 °C than at 30 °C. The higher value of RH (100%) appeared to increase the rate of colonization, in particular at 20 and 25 °C. Taken together, our results emphasize the significant influence of environmental factors on the effectiveness of biocontrol against A. carbonarius as well as on OTA contamination in wine grape berries, and the need for biocontrol agents that can cope with the environmental conditions that are conducive to attack by A. carbonarius.


Subject(s)
Aspergillus/growth & development , Biological Control Agents , Vitis/microbiology , Yeasts/pathogenicity , Aspergillus/metabolism , Environment , Food Microbiology , Fruit , Humidity , Ochratoxins/metabolism , Saccharomyces cerevisiae , Temperature , Wine/microbiology
13.
Cell ; 149(5): 1112-24, 2012 May 25.
Article in English | MEDLINE | ID: mdl-22632974

ABSTRACT

Activity-dependent gene expression triggered by Ca(2+) entry into neurons is critical for learning and memory, but whether specific sources of Ca(2+) act distinctly or merely supply Ca(2+) to a common pool remains uncertain. Here, we report that both signaling modes coexist and pertain to Ca(V)1 and Ca(V)2 channels, respectively, coupling membrane depolarization to CREB phosphorylation and gene expression. Ca(V)1 channels are advantaged in their voltage-dependent gating and use nanodomain Ca(2+) to drive local CaMKII aggregation and trigger communication with the nucleus. In contrast, Ca(V)2 channels must elevate [Ca(2+)](i) microns away and promote CaMKII aggregation at Ca(V)1 channels. Consequently, Ca(V)2 channels are ~10-fold less effective in signaling to the nucleus than are Ca(V)1 channels for the same bulk [Ca(2+)](i) increase. Furthermore, Ca(V)2-mediated Ca(2+) rises are preferentially curbed by uptake into the endoplasmic reticulum and mitochondria. This source-biased buffering limits the spatial spread of Ca(2+), further attenuating Ca(V)2-mediated gene expression.


Subject(s)
CREB-Binding Protein/metabolism , Calcium Channels, L-Type/metabolism , Calcium Channels, N-Type/metabolism , Calcium Signaling , Hippocampus/metabolism , Animals , Calcium/metabolism , Cell Nucleus/metabolism , Gene Expression , Hippocampus/cytology , Mitochondria/metabolism , Rats , Rats, Sprague-Dawley
14.
Neurosci Res ; 70(1): 2-8, 2011 May.
Article in English | MEDLINE | ID: mdl-21352861

ABSTRACT

In excitable cells, membrane depolarization and activation of voltage-gated Ca²+ (Ca(V)) channels trigger numerous cellular responses, including muscle contraction, secretion, and gene expression. Yet, while the mechanisms underlying excitation-contraction and excitation-secretion coupling have been extensively characterized, how neuronal activity is coupled to gene expression has remained more elusive. In this article, we will discuss recent progress toward understanding the relationship between patterns of channel activity driven by membrane depolarization and activation of the nuclear transcription factor CREB. We show that signaling strength is steeply dependent on membrane depolarization and is more sensitive to the open probability of Ca(V) channels than the Ca²+ entry itself. Furthermore, our data indicate that by decoding Ca(V) channel activity, CaMKII (a Ca²+/calmodulin-dependent protein kinase) links membrane excitation to activation of CREB in the nucleus. Together, these results revealed some interesting and unexpected similarities between excitation-transcription coupling and other forms of excitation-response coupling.


Subject(s)
Action Potentials/physiology , Calcium Channels/physiology , Ganglia, Sympathetic/physiology , Neurons/physiology , Animals , Calcium Channels/genetics , Calcium Signaling/physiology , Ganglia, Sympathetic/cytology , Humans
15.
Crit Care ; 15(1): R60, 2011.
Article in English | MEDLINE | ID: mdl-21320330

ABSTRACT

INTRODUCTION: This small observational study was motivated by our belief that scaling the tidal volume in mechanically ventilated patients to the size of the injured lung is safer and more 'physiologic' than scaling it to predicted body weight, i.e. its size before it was injured. We defined Total Lung Capacity (TLC) as the thoracic gas volume at an airway pressure of 40 cm H2O and tested if TLC could be inferred from the volume of gas that enters the lungs during a brief 'recruitment' maneuver. METHODS: Lung volume at relaxed end expiration (Vrel) as well as inspiratory capacity (IC), defined as the volume of gas that enters the lung during a 5 second inflation to 40 cm H2O, were measured in 14 patients with respiratory failure. TLC was defined as the sum of IC and Vrel. The dependence of IC and Vrel on body mass index (BMI), respiratory system elastance and plateau airway pressure was assessed. RESULTS: TLC was reduced to 59 ± 23% of that predicted. Vrel/TLC, which averaged 0.45 ± 0.11, was no different than the 0.47 ± 0.04 predicted during health in the supine posture. The greater than expected variability in observed Vrel/TLC was largely accounted for by BMI. Vrel and IC were correlated (r = 0.76). Taking BMI into account strengthened the correlation (r = 0.92). CONCLUSIONS: We conclude that body mass is a powerful determinant of lung volume and plateau airway pressure. Effective lung size can be easily estimated from a recruitment maneuver derived inspiratory capacity measurement and body mass index.


Subject(s)
Body Mass Index , Lung Injury/pathology , Lung/pathology , Respiration, Artificial/methods , Adult , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Organ Size , Total Lung Capacity
16.
Health Hum Rights ; 12(1): 47-59, 2010 Jun 15.
Article in English | MEDLINE | ID: mdl-20930253

ABSTRACT

Health is increasingly seen as relevant to foreign policy; nevertheless, it remains subordinate to other interests. In particular, the interests of security and economics are often presented as more critical than health. This is due to a failure to sufficiently recognize the legal obligations that states have undertaken to ensure the human right to health. This article argues that health should be an imperative of foreign policy, equally valid, and prioritized in resource allocation. We suggest application of the human rights approach with attention to the legal duty of cooperation and the necessity of ensuring broad participation. We suggest that the human rights approach to health can contribute to achieving this result and is compatible with, and beneficial to, other foreign policy concerns. Finally, we conclude that the human rights approach to health requires that health be an imperative in foreign policymaking processes.


Subject(s)
International Cooperation/legislation & jurisprudence , Patient Rights/legislation & jurisprudence , Public Policy/legislation & jurisprudence , Health Policy/legislation & jurisprudence , Health Policy/trends , Health Status Disparities , Human Rights/legislation & jurisprudence , Humans , Politics , Resource Allocation , Social Justice
17.
Ann Neurol ; 67(1): 85-98, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20186955

ABSTRACT

OBJECTIVE: The CACNA1A gene encodes the pore-forming subunit of neuronal Ca(V)2.1 Ca2+ channels. In patients, the S218L CACNA1A mutation causes a dramatic hemiplegic migraine syndrome that is associated with ataxia, seizures, and severe, sometimes fatal, brain edema often triggered by only a mild head trauma. METHODS: We introduced the S218L mutation into the mouse Cacna1a gene and studied the mechanisms for the S218L syndrome by analyzing the phenotypic, molecular, and electrophysiological consequences. RESULTS: Cacna1a(S218L) mice faithfully mimic the associated clinical features of the human S218L syndrome. S218L neurons exhibit a gene dosage-dependent negative shift in voltage dependence of Ca(V)2.1 channel activation, resulting in enhanced neurotransmitter release at the neuromuscular junction. Cacna1a(S218L) mice also display an exquisite sensitivity to cortical spreading depression (CSD), with a vastly reduced triggering threshold, an increased propagation velocity, and frequently multiple CSD events after a single stimulus. In contrast, mice bearing the R192Q CACNA1A mutation, which in humans causes a milder form of hemiplegic migraine, typically exhibit only a single CSD event after one triggering stimulus. INTERPRETATION: The particularly low CSD threshold and the strong tendency to respond with multiple CSD events make the S218L cortex highly vulnerable to weak stimuli and may provide a mechanistic basis for the dramatic phenotype seen in S218L mice and patients. Thus, the S218L mouse model may prove a valuable tool to further elucidate mechanisms underlying migraine, seizures, ataxia, and trauma-triggered cerebral edema.


Subject(s)
Calcium Channels, P-Type/genetics , Calcium Channels, P-Type/metabolism , Calcium Channels, Q-Type/genetics , Calcium Channels, Q-Type/metabolism , Cortical Spreading Depression/genetics , Cortical Spreading Depression/physiology , Migraine Disorders/genetics , Migraine Disorders/physiopathology , Animals , Brain/physiopathology , Calcium Channels, N-Type , Disease Models, Animal , Female , Genetic Predisposition to Disease , Male , Membrane Potentials/physiology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mutation, Missense , Neuromuscular Junction/physiopathology , Neurons/physiology , Neurotransmitter Agents/metabolism , Syndrome
18.
Health Hum Rights ; 12(1): [14], 2010.
Article in English | LILACS, BDS | ID: biblio-833495

ABSTRACT

Health is increasingly seen as relevant to foreign policy; nevertheless, it remains subordinate to other interests. In particular, the interests of security and economics are often presented as more critical than health. This is due to a failure to sufficiently recognize the legal obligations that states have undertaken to ensure the human right to health. This article argues that health should be an imperative of foreign policy, equally valid, and prioritized in resource allocation. We suggest application of the human rights approach with attention to the legal duty of cooperation and the necessity of ensuring broad participation. We suggest that the human rights approach to health can contribute to achieving this result and is compatible with, and beneficial to, other foreign policy concerns. Finally, we conclude that the human rights approach to health requires that health be an imperative in foreign policymaking processes.


Subject(s)
Human Rights , International Acts , Health Care Rationing , Health Priorities
19.
CJEM ; 11(6): 523-8, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19922711

ABSTRACT

OBJECTIVE: Emergency physicians (EPs) rarely find out what happens to patients after the patients leave their care, a process we call "outcome feedback." Some suggest this hinders the practice of emergency medicine (EM); however, evidence is lacking. We sought to evaluate EPs' perception of the current and potential role of outcome feedback in EM. METHODS: We surveyed practising French- and English speaking EPs from emergency departments within 100 km of Ottawa, Ont., in the provinces of Ontario and Quebec. The main outcomes included the prevalence, role and effect of outcome feedback. RESULTS: Of the 297 physicians surveyed, 231 (77.8%) respond ed. The sample contained good representation of language groups, practice settings, sexes and age groups. All participants indicated that knowing outcomes is "essential" (62.6%) or "beneficial" (37.4%) to gaining experience in EM. Participants reported currently receiving passive outcome feedback in 10.0% of all cases, and seeking out (active) outcome feedback in 7.5% of all cases. The great majority of participants (97.3%) stated that they would like to receive more outcome feedback and believed that this would improve diagnostic accuracy (97.3%), clinical efficiency (85.5%), treatment outcomes (95.6%) and job satisfaction (95.1%). When asked to indicate "any possible negative effects that might arise from increased outcome feedback," 62.1% indicated none.However, 17.9% hypothesized negative emotional effects and 11.5% suggested increased time requirements. CONCLUSION: The overwhelming majority of EPs receive very little outcome feedback. Most would like more outcome feedback and believe it would improve the practice of EM.


Subject(s)
Emergency Medicine/standards , Feedback , Outcome Assessment, Health Care , Physicians/psychology , Adult , Chi-Square Distribution , Clinical Competence , Female , Humans , Job Satisfaction , Male , Ontario , Practice Patterns, Physicians'/standards , Quebec , Statistics, Nonparametric , Surveys and Questionnaires
20.
CJEM ; 11(6): 545-52, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19922715

ABSTRACT

OBJECTIVE: The organization of emergency medical care limits the ability of emergency physicians to know the outcomes of most of their patients after the patients leave the emergency department. This lack of outcome feedback may hinder the practice of emergency medicine (EM) by preventing "calibration" of the decision tools of practitioners. We sought to determine what is currently known about outcome feedback in EM, including its incidence, impact and modifiers. DATA SOURCE: We searched the following databases: PreMEDLINE, MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, DARE, Health Technology Assessment Database and AMED. We performed manual searches on abstract databases, reference lists, various health information and research websites, and nonindexed journals. STUDY SELECTION: Selection entailed a 2-step screening pro cess to exclude articles not pertaining to outcome feedback in EM. DATA EXTRACTION: Our search yielded 1128 bibliographic records, from which screening identified 7 relevant reports: 5 surveys, 1 system level evaluation and 1 intervention trial. DATA SYNTHESIS: All studies were found to have "inadequate" or "unable to assess" reporting and study quality. Systems for outcome feedback to EM residents have been increasingly available since 1984, though they are perceived to be inadequate. Commonly used mechanisms for outcome feedback include automatic routing of discharge summaries, case conferences for admitted patients and telephone calls to patients or families for discharged patients. With respect to attending emergency physicians, no conclusions or clinical recommendations can be made given the level of available evidence. CONCLUSION: The potential importance of outcome feedback remains, at this time, underevaluated. We propose a research framework, and hypothesize that increasing outcome feedback would increase emergency physician diagnostic accuracy, therapeutic outcomes, clinical efficiency and job satisfaction. Future research in this area should include surveys and focus groups, as well as simulated or real-world intervention trials.


Subject(s)
Clinical Competence , Emergency Medicine/standards , Feedback , Outcome Assessment, Health Care , Physicians/psychology , Humans
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