scholarly journals Activation and inactivation of single calcium channels in snail neurons.

1984 ◽  
Vol 83 (5) ◽  
pp. 751-769 ◽  
Author(s):  
A M Brown ◽  
H D Lux ◽  
D L Wilson

Activation and inactivation properties of Ca currents were investigated by studying the behavior of single Ca channels in snail neurons. The methods described in the previous paper were used. In addition, a zero-phase digital filter has been incorporated to improve the analysis of latencies to first opening, or waiting times. It was found that a decrease in the probability of single channel opening occurred with time. This was especially marked at 29 degrees C and paralleled the inactivation observed in macroscopic currents. The fact that a single channel was observed means that there is a significant amount of reopening from the "inactivated" state. Small depolarizations at 18 degrees C showed little inactivation. From these measurements, histograms of single channel open, closed, and waiting times were analyzed to estimate the rate constants of a three-state model of activation. Two serious discrepancies with the model were found. First, waiting time distributions at -20 mV were slower than those predicted by parameters obtained from an analysis of the single channel closed times. Second, it was shown that the time and the magnitude of the peak of the waiting time histogram were inconsistent with a three-state model. It is concluded that a minimum of four states are involved in activation. Some four-state models may be eliminated from further consideration. However, a comprehensive model of Ca channel kinetics must await further measurements.

2019 ◽  
Vol 151 (11) ◽  
pp. 1265-1271 ◽  
Author(s):  
Michael A. Geeves ◽  
Sherwin S. Lehrer ◽  
William Lehman

In a recent JGP article, Heeley et al. (2019. J. Gen. Physiol. https://doi.org/10.1085/jgp.201812198) reopened the debate about two- versus three-state models of thin filament regulation. The authors review their work, which measures the rate constant of Pi release from myosin.ADP.Pi activated by actin or thin filaments under a variety of conditions. They conclude that their data can be described by a two-state model and raise doubts about the generally accepted three-state model as originally formulated by McKillop and Geeves (1993. Biophys. J. https://doi.org/10.1016/S0006-3495(93)81110-X). However, in the following article, we follow Plato’s dictum that “twice and thrice over, as they say, good it is to repeat and review what is good.” We have therefore reviewed the evidence for the three- and two-state models and present our view that the evidence is overwhelmingly in favor of three structural states of the thin filament, which regulate access of myosin to its binding sites on actin and, hence, muscle contractility.


2013 ◽  
Vol 141 (4) ◽  
pp. 467-478 ◽  
Author(s):  
Prasad Purohit ◽  
Anthony Auerbach

Agonist molecules at the two neuromuscular acetylcholine (ACh) receptor (AChR) transmitter-binding sites increase the probability of channel opening. In one hypothesis for AChR activation (“priming”), the capping of loop C at each binding site transfers energy independently to the distant gate over a discrete structural pathway. We used single-channel analyses to examine the experimental support for this proposal with regard to brief unliganded openings, the effects of loop-C modifications, the effects of mutations to residues either on or off the putative pathway, and state models for describing currents at low [ACh]. The results show that (a) diliganded and brief unliganded openings are generated by the same essential, global transition; (b) the radical manipulation of loop C does not prevent channel opening but impairs agonist binding; (c) both on- and off-pathway mutations alter gating by changing the relative stability of the open-channel conformation by local interactions rather than by perturbing a specific site–gate communication link; and (d) it is possible to estimate directly the rate constants for agonist dissociation from and association to both the low and high affinity forms of the AChR-binding site by using a cyclic kinetic model. We conclude that the mechanism of energy transfer between the binding sites and the gate remains an open question.


2018 ◽  
Author(s):  
Akim Manaor Hara Pardede

In modern times currently demanded everything must be quick and precise. This is because the more the increase of population in the world today that keeps growing. The queue is a aktifiitas where customers wait to obtain a service. In the system queue sometimes experiencing aproblem, the problem arises because the number of queued on the serve. A long queue occurs because of the large number of transactions at the teller either transfers, cash with drawals, mortgage payments, retirement funds are taking and receive cash retention. Queueing models discussed in this research is a queue where customers come in groups. The number of customers in each group is a random variable, and the time between the arrival of the exponential distribution is. On the research of Exponential method is used to calculate the time of service with a single channel to be able to observe how the performance of the system. Based on research results, gained sufficient servers to serve is as much as 3 servers, if only 1 server will result in average waiting times are too long resulting in the customer will get tired of waiting for a while if you're using 4 the server will result inan average waiting time of very little until the server is idle.


Author(s):  
A. K. Warps ◽  
◽  
M. P. M. de Neree tot Babberich ◽  
E. Dekker ◽  
M. W. J. M. Wouters ◽  
...  

Abstract Purpose Interhospital referral is a consequence of centralization of complex oncological care but might negatively impact waiting time, a quality indicator in the Netherlands. This study aims to evaluate characteristics and waiting times of patients with primary colorectal cancer who are referred between hospitals. Methods Data were extracted from the Dutch ColoRectal Audit (2015-2019). Waiting time between first tumor-positive biopsy until first treatment was compared between subgroups stratified for referral status, disease stage, and type of hospital. Results In total, 46,561 patients were included. Patients treated for colon or rectal cancer in secondary care hospitals were referred in 12.2% and 14.7%, respectively. In tertiary care hospitals, corresponding referral rates were 43.8% and 66.4%. Referred patients in tertiary care hospitals were younger, but had a more advanced disease stage, and underwent more often multivisceral resection and simultaneous metastasectomy than non-referred patients in secondary care hospitals (p<0.001). Referred patients were more often treated within national quality standards for waiting time compared to non-referred patients (p<0.001). For referred patients, longer waiting times prior to MDT were observed compared to non-referred patients within each hospital type, although most time was spent post-MDT. Conclusion A large proportion of colorectal cancer patients that are treated in tertiary care hospitals are referred from another hospital but mostly treated within standards for waiting time. These patients are younger but often have a more advanced disease. This suggests that these patients are willing to travel more but also reflects successful centralization of complex oncological patients in the Netherlands.


Sensors ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 2845
Author(s):  
Fahd Alhaidari ◽  
Abdullah Almuhaideb ◽  
Shikah Alsunaidi ◽  
Nehad Ibrahim ◽  
Nida Aslam ◽  
...  

With population growth and aging, the emergence of new diseases and immunodeficiency, the demand for emergency departments (EDs) increases, making overcrowding in these departments a global problem. Due to the disease severity and transmission rate of COVID-19, it is necessary to provide an accurate and automated triage system to classify and isolate the suspected cases. Different triage methods for COVID-19 patients have been proposed as disease symptoms vary by country. Still, several problems with triage systems remain unresolved, most notably overcrowding in EDs, lengthy waiting times and difficulty adjusting static triage systems when the nature and symptoms of a disease changes. In this paper, we conduct a comprehensive review of general ED triage systems as well as COVID-19 triage systems. We identified important parameters that we recommend considering when designing an e-Triage (electronic triage) system for EDs, namely waiting time, simplicity, reliability, validity, scalability, and adaptability. Moreover, the study proposes a scoring-based e-Triage system for COVID-19 along with several recommended solutions to enhance the overall outcome of e-Triage systems during the outbreak. The recommended solutions aim to reduce overcrowding and overheads in EDs by remotely assessing patients’ conditions and identifying their severity levels.


2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
Z Hayat ◽  
E Kinene ◽  
S Molloy

Abstract Introduction Reduction of waiting times is key to delivering high quality, efficient health care. Delays experienced by patients requiring radiographs in orthopaedic outpatient clinics are well recognised. Method To establish current patient and staff satisfaction, questionnaires were circulated over a two-week period. Waiting time data was retrospectively collected including appointment time, arrival time and the time at which radiographs were taken. Results 84% (n = 16) of radiographers believed patients would be dissatisfied. However, of the 296 patients questioned, 56% (n = 165) were satisfied. Most patients (89%) felt the waiting time should be under 30 minutes. Only 36% were seen in this time frame. There was moderate negative correlation (R=-0.5); higher waiting times led to increased dissatisfaction. Mean waiting time was 00:37 and the maximum 02:48. Key contributing factors included volume of patients, staff shortages (73.7%), equipment shortages (57.9%) and incorrectly filled request forms. Eight (42.1%) had felt unwell from work related stress. Conclusions A concerted effort is needed to improve staff and patient opinion. There is scope for change post COVID. Additional training and exploring ways to avoid overburdening the department would benefit. Numerous patients were open to different days or alternative sites. Funding requirements make updating equipment, expanding the department and recruiting more staff challenging.


1973 ◽  
Vol 5 (01) ◽  
pp. 153-169 ◽  
Author(s):  
J. H. A. De Smit

Pollaczek's theory for the many server queue is generalized and extended. Pollaczek (1961) found the distribution of the actual waiting times in the model G/G/s as a solution of a set of integral equations. We give a somewhat more general set of integral equations from which the joint distribution of the actual waiting time and some other random variables may be found. With this joint distribution we can obtain distributions of a number of characteristic quantities, such as the virtual waiting time, the queue length, the number of busy servers, the busy period and the busy cycle. For a wide class of many server queues the formal expressions may lead to explicit results.


2002 ◽  
Vol 18 (3) ◽  
pp. 611-618
Author(s):  
Markus Torkki ◽  
Miika Linna ◽  
Seppo Seitsalo ◽  
Pekka Paavolainen

Objectives: Potential problems concerning waiting list management are often monitored using mean waiting times based on empirical samples. However, the appropriateness of mean waiting time as an indicator of access can be questioned if a waiting list is not managed well, e.g., if the queue discipline is violated. This study was performed to find out about the queue discipline in waiting lists for elective surgery to reveal potential discrepancies in waiting list management. Methods: There were 1,774 waiting list patients for hallux valgus or varicose vein surgery or sterilization. The waiting time distributions of patients receiving surgery and of patients still waiting for an operation are presented in column charts. The charts are compared with two model charts. One model chart presents a high queue discipline (first in—first out) and another a poor queue discipline (random) queue. Results: There were significant differences in waiting list management across hospitals and patient categories. Examples of a poor queue discipline were found in queues for hallux valgus and varicose vein operations. Conclusions: A routine waiting list reporting should be used to guarantee the quality of waiting list management and to pinpoint potential problems in access. It is important to monitor not only the number of patients in the waiting list but also the queue discipline and the balance between demand and supply of surgical services. The purpose for this type of reporting is to ensure that the priority setting made at health policy level also works in practise.


2000 ◽  
Vol 40 (supplement) ◽  
pp. S139
Author(s):  
K-I. Sano ◽  
K. Maeda ◽  
Y. Maeda

2009 ◽  
Vol 16 (3) ◽  
pp. 148-154 ◽  
Author(s):  
CA Graham ◽  
WO Kwok ◽  
YL Tsang ◽  
TH Rainer

Objective To explore why patients in Hong Kong seek medical advice from the emergency department (ED) and to identify the methods by which patients would prefer to be updated on the likely waiting time for medical consultation in the ED. Methods The study recruited 249 semi-urgent and non-urgent patients in the ED of Prince of Wales Hospital from 26th September 2005 to 30th September 2005 inclusive. A convenience sample of subjects aged ≥15 years old in triage categories 4 or 5 were verbally consented and interviewed by research nurses using a standardized questionnaire. Results From 1715 potential patients, 249 were recruited ad hoc (mean age 44 years [SD18]; 123 females). About 63% indicated that an acceptable ED waiting time was less than or equal to two hours, and 88% felt that having individual number cards and using a number allocation screen in the ED waiting area would be useful. Perceived reasons for attending the ED rather than other health care providers such as primary health care or the general outpatient clinic (GOPC) included: a desire for more detailed investigations (56%); a perception that more professional medical advice was given in the ED (35%); patients were under the continuing care of the hospital (19%); and patients were referred to the ED by other health care professionals (11%). Notably, 26% of participants had considered attending the GOPC prior to attending the ED. Patients educated to tertiary level expected a shorter waiting time than those educated to lesser degrees (p=0.026, Kruskal-Wallis test). Suggestions were made on how to provide a more pleasant ED environment for the wait for consultations, which included the provision of a television screen with sound in the waiting area (43%), more comfortable chairs (37%) and health care promotion programs (32%). Conclusion Patients chose ED services because they believed they would receive more detailed investigations and more professional medical advice than available alternatives. Clear notification of the likely waiting times and enhancement of comfort before consultation are considered desirable by patients. Enhanced public education about the role of the ED and making alternatives to ED care more accessible may be useful in reducing inappropriate ED attendances in Hong Kong.


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