Pioneering disadvantage : consumer reactions to marketing mix strategies / M. Sadiq Sohail and Mohamad Farid Mahmood

Prior research has focused on the early entrant advantage, although a growing body of knowledgde suggests suggests that late movers have been outselling pioneers. In this research, the authors examine the issue of a pay phone service provider in Malaysia. In 1990, the company launches its product and creates an industry, but by the turn of the century, it has a meager 17 per cent of the market share. The Paper examines the specific issue of how a market pioneer has been eclipsed. It is hypothesized that the main cause of the declining sales is the in appropriate marketing mix strategies. The major findings based on a survey include consumers' acceptance level of the product, price, place, promotion, people, process and physical evidence strategies of the company

Re-Evaluation of the Action Potential Upstroke Velocity as a Measure of the Na+ Current in Cardiac Myocytes at Physiological Conditions

Background: The SCN5A encoded sodium current (INa) generates the action potential (AP) upstroke and is a major determinant of AP characteristics and AP propagation in cardiac myocytes. Unfortunately, in cardiac myocytes, investigation of kinetic properties of INa with near-physiological ion concentrations and temperature is technically challenging due to the large amplitude and rapidly activating nature of INa, which may seriously hamper the quality of voltage control over the membrane. We hypothesized that the alternating voltage clamp-current clamp (VC/CC) technique might provide an alternative to traditional voltage clamp (VC) technique for the determination of INa properties under physiological conditions. Principal Findings: We studied INa under close-to-physiological conditions by VC technique in SCN5A cDNA-transfected HEK cells or by alternating VC/CC technique in both SCN5A cDNA-transfected HEK cells and rabbit left ventricular myocytes. In these experiments, peak INa during a depolarizing VC step or maximal upstroke velocity, dV/dtmax, during VC/CC served as an indicator of available INa. In HEK cells, biophysical properties of INa, including current density, voltage dependent (in)activation, development of inactivation, and recovery from inactivation, were highly similar in VC and VC/CC experiments. As an application of the VC/CC technique we studied INa in left ventricular myocytes isolated from control or failing rabbit hearts

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Sodium current inhibition by nanosecond pulsed electric field (nsPEF)--fact or artifact?

In two recent publications in Bioelectromagnetics it has been demonstrated that the voltage-gated sodium current (I(Na)) is inhibited in response to a nanosecond pulsed electric field (nsPEF). At the same time, there was an increase in a non-inactivating "leak" current (I(leak)), which was attributed to the formation of nanoelectropores or larger pores in the plasma membrane. We demonstrate that the increase in I(leak), in combination with a residual series resistance, leads to an error in the holding potential in the patch clamp experiments and an unanticipated inactivation of the sodium channels. We conclude that the observed inhibition of I(Na) may be largely, if not fully, artifactua

Pacemaker activity of the human sinoatrial node: Role of the hyperpolarization-activated current, I-f

The mechanism of primary, spontaneous cardiac pacemaker activity of the sinoatrial node (SAN) has extensively been studied in several animal species, but is virtually unexplored in man. Understanding the mechanisms of human SAN pacemaker activity is important for developing new therapeutic approaches for controlling the heart rate in the sick sinus syndrome and in diseased myocardium. Here we review the functional role of the hyperpolarization-activated 'funny' current, I-f, in human SAN pacemaker activity. Despite the many animal studies performed over the years, the contribution of I-f to pacemaker activity is still controversial and not fully established. However, recent clinical data on mutations in the I-f encoding HCN4 gene, which is thought to be the most abundant isoform of the HCN gene family in SAN, suggest a functional role of I-f in human pacemaker activity. These clinical findings are supported by recent experimental data from single isolated human SAN cells that provide direct evidence that I-f contributes to human SAN pacemaker activity. Therefore, controlling heart rate in clinical practice via I-f blockers offers a valuable approach to lowering heart rate and provides an attractive alternative to conventional treatment for a wide range of patients with confirmed stable angina, while upregulation or artificial expression of I-f may relieve disease-causing bradycardias. (C) 2008 Elsevier Ireland Ltd. All rights reserve

Action potential transfer at the Purkinje - Ventricular junction: Role of transitional cells

At the Purkinje (P) - ventricular (V) junction a zone of "transitional (T)" cells is found. In the present study we investigated the role of these T cells in P-to-V conduction. Using the "model clamp" technique, an experimentally recorded rabbit P cell was coupled to a phase-2 Luo and Rudy (LR) model cell, which in turn was coupled to a strand of phase-2 LR model cells. In our experiments, the single LR model represents the T cell, while the strand of LR models represents subendocardial V cells. This approach enabled us to change selectively coupling conductance (Gc) between cells, presence of T cell, and relative size of cells. We demonstrated that: 1) a decrease of Gc between P-T and T-V increases the delay of V activation, 2) the delay of V activation is importantly due to conduction between T and V cells, 3) there is a critical Gc for successful conduction at the P-V junction, 4) the critical value of Gc for conduction at the P-V junction is lower in presence (11.0±0.7 nS) than in absence (13.7±0.8 nS) of the T cell, and 5) enlargement of the T zone size hampers successful P-to-V conduction

Beta-Adrenergic Modulation of Heart Rate:Contribution of the Slow Delayed Rectifier K+ Current (IKs)

To assess the role of the slow delayed rectifier potassium current (IKs) in the β-adrenergic modulation of heart rate, we experimentally determined the effect of β adrenergic stimulation on IKs and used the thus obtained data in computer simulations of SA nodal pacemaker activity, employing the mathematical model of a primary rabbit SA node pacemaker cell by Kurata and coworkers. Incorporation of our experimental findings into the SA nodal cell model resulted in a 12 ms decrease in cycle length. This decrease in cycle length is similar to the 13 ms decrease observed upon incorporation of our experimental data on the effect of β-adrenergic stimulation on the hyperpolarization-activated funny current' (If), also known as 'pacemaker current'. We conclude that IKs is an important contributor to the β-adrenergic modulation of heart rat

Effects of heart failure on brain-type Na+ channels in rabbit ventricular myocytes: Reply

La conférence annuelle de la British Sociological Association (BSA) aura lieu du 7 au 9 avril 2010 à Glasgow Caledonian University. Le thème de la conférence est inégalités et justice sociale (Inequalities & Social Justice). L'appel à contribution est ouvert

Effects of heart failure on brain-type Na+ channels in rabbit ventricular myocytes: Reply

AIMS: Brain-type alpha-subunit isoforms of the Na(+) channel are present in various cardiac tissue types and may control pacemaker activity and excitation-contraction coupling. Heart failure (HF) alters pacemaker activity and excitation-contraction coupling. Here, we studied whether HF alters brain-type Na(+) channel properties. METHODS AND RESULTS: HF was induced in rabbits by volume/pressure overload. Na(+) currents of ventricular myocytes were recorded in the cell-attached mode of the patch-clamp technique using macropatches. Macropatch recordings were conducted from the middle portions of myocytes or from intercalated disc regions between cell pairs. Both areas exhibited a fast activating and inactivating current, 8.5 times larger in intercalated disc regions. Tetrodotoxin (TTX) (50 nM) did not block currents in the intercalated disc regions, but did block in the middle portions, indicating that the latter currents were TTX-sensitive brain-type Na(+) currents. Macropatch recordings from these regions were used to study the effects of HF on brain-type Na(+) current. Neither current density nor gating properties (activation, inactivation, recovery from inactivation, slow inactivation) differed between CTR and HF. CONCLUSION: The density and gating properties of brain-type Na(+) current are not altered in our HF model. In the volume/pressure-overload rabbit model of HF, the role of brain-type Na(+) current in HF-induced changes in excitation-contraction coupling is limite