9 research outputs found
A comparative study of the potential for human retinal pigment epithelium utilising an embryonic chick model of the phenomenon
No full textThe retinal pigment epithelial (RPE) cells of several species, including: chicken, rat, mouse and newt, have been observed to undergo a phenomenon known as transdifferentiation. This involves the re-specification of the RPE phenotype towards a neuroretinal, or lens phenotype, in response to various cues, including basic fibroblast growth factor (bFGF). Transdifferentiation has yet to be described in human RPE cells, however, this investigation has demonstrated that human cells, including primary fetal, and human embryonic stem cell-derived (HESC), RPE, may retain the capacity to undergo some level of bFGF-mediated transdifferentiation. It appears that the process is likely comparable to that observed in the embryonic chick model of the phenomenon, given that human transdifferentiation appears to be restricted to the earliest stages of RPE development (approximately 6 weeks). Additionally, the features of transdifferentiated RPE observed in the earliest available human tissue are shown to resemble that of a similar stage in chick development (HH27), which is shown to display limited transdifferentiation for the first time, in contrast with previous studies which report the loss of potential for transdifferentiation at this stage. It remains unclear as to why RPE cells lose the capacity for transdifferentiation with development, however, it appears to be linked to, but not exclusively a result of, a loss in the expression of Pax6 across the RPE monolayer, given both capacity for transdifferentiation, and Pax6 expression, are both variable in different regions of the same monolayer, in the chick model of transdifferentiation. Known RPE augmentation signaling pathways, including bone morphogenic protein (BMP) and Sonic hedgehog (Shh) were analysed for their potential involvement in the restriction of transdifferentiation, however, neither appeared to be directly involved. Further studies in the embryonic chick model of the phenomenon will be necessary to unlock this potential in human RPE cells
Setting Fair Prices – Fundamental Principle Of Sustainable Marketing
No full textIn commercial area, the price has a major importance, being frequently considered among the main criteria used in buying decision process. Price fairness derives from equity theory and it is focused on assuring in a transaction a reasonable report between the customer’s sacrifice and the value offered by the seller. In three marketing experiments we have evaluated customers’ fairness perceptions of differential prices, this tactic being frequently used by sellers. One important finding was that the motive for setting differential prices is important in fairness evaluation. Price differences based on social motives are perceived fairer than those motivated by company’s interest. The differential prices on customer category are perceived fairer than zone prices. In all three marketing experiments it was demonstrated that price fairness has a significant influence on value perception and on buying intentions. Fair prices setting is one of the principles sustainable marketing is based on, reflecting a long term orientation for a company. By following this decisional direction, the commercial firm increases the value offered to its customers and it becomes more socially responsible.sustainable development, sustainable marketing, fair price, price fairness, differential prices, distributive fairness, procedural fairness
Settlement of Bad Credit with Guarantee of Unregistered Land Rights (Case Study Number 52/Pdt.G/2021/PN Mjk)
No full textThis study aims to find out how to settle bad loans with collateral for land rights that are not registered (study of decision number 52/Pdt.G/2021/PN.Mjk), as well as explain the legal consequences of bad credit agreements with guaranteed land rights that are not registered ( Study of Decision Number 52/Pdt.G/2021/PN Mjk) and how to solve it. The approach method used by the author in this study is normative, according to the results of research on the relationship between borrowing and repayment of debt, the possibility of unexpected events by the debtor cannot be ignored. When a borrower faces difficulties in paying off credit, financial institutions, such as banks, take steps to deal with it with the aim of giving the borrower an opportunity to fulfill his obligations. These actions may involve restructuring payment schedules, adjusting terms, and rearranging. Humans fulfill their life needs by interacting with other humans. Interactions that are often carried out are by making agreements. Many types of agreements are made, including: sale - purchase agreements, lease agreements, accounts payable agreements. In the current era, the Indonesian economy is progressing and the needs of each individual are increasing. Therefore, many individuals, if they cannot make ends meet using their own money, will carry out debts. Good for individuals, savings and loan cooperatives, loans to banks, and others
The Impact of Immigration on the Labour Market Outcomes of Native-born Canadians
No full textAlthough immigration has become a major growth factor for Canadian labour force, there is little economic research on the effect of immigration on native-born Canadians' labour market performance. This paper examines the relationship between changes in the share of immigrants by sub-labour markets (categorized by skill types and geographic areas) and changes in native wage growth by a two-stage regression analysis, using 1991, 1996 and 2001 Canadian Census microdata. After accounting for biases due to native mobility, endogenous location of immigrants and labour demand shifts, the estimated effects of immigration are consistently insignificant or significantly positive. The results are robust over various specifications of sub-labour markets at city, provincial and national levels, suggesting no evidence for a negative impact on native wage growth rate from the large immigrant influx during the 1990s.immigration, labour supply, labour mobility, wage
Comparison of early outcomes of arthroscopic labral repair or debridement A STUDY USING THE UK NON-ARTHROPLASTY HIP REGISTRY DATASET
No full text\ua9 2022 Author(s) et al. Aims This study uses prospective registry data to compare early patient outcomes following arthroscopic repair or debridement of the acetabular labrum. Methods Data on adult patients who underwent arthroscopic labral debridement or repair between 1 January 2012 and 31 July 2019 were extracted from the UK Non-Arthroplasty Hip Registry. Patients who underwent microfracture, osteophyte excision, or a concurrent extra-articular procedure were excluded. The EuroQol five-dimension (EQ-5D) and International Hip Outcome Tool 12 (iHOT-12) questionnaires were collected preoperatively and at six and 12 months post-operatively. Due to concerns over differential questionnaire non-response between the two groups, a combination of random sampling, propensity score matching, and pooled multivariable linear regression models were employed to compare iHOT-12 improvement. Results A total of 2,025 labral debridements (55%) and 1,659 labral repairs (45%) were identified. Both groups saw significant (p < 0.001) EQ-5D and iHOT-12 gain compared to preoperative scores at 12 months (iHOT-12 improvement: labral repair = +28.7 (95% confidence interval (CI) 26.4 to 30.9), labral debridement = +24.7 (95% CI 22.5 to 27.0)), however there was no significant difference between procedures after multivariable modelling. Overall, 66% of cases achieved the minimum clinically important difference (MCID) and 48% achieved substantial clinical benefit at 12 months. Conclusion Both labral procedures were successful in significantly improving early functional outcome following hip arthroscopy, regardless of age or sex. Labral repair was associated with superior outcomes in univariable analysis, however there was no significant superiority demonstrated in the multivariable model
Hip arthroscopy for femoroacetabular impingement is associated with significant improvement in early patient reported outcomes: analysis of 4963 cases from the UK non-arthroplasty registry (NAHR) dataset
No full text\ua9 2022, The Author(s). Purpose: Results from recent randomised controlled trials demonstrate the superiority of surgery over physiotherapy in patients with femoroacetabular impingement (FAI) of the hip in early follow-up. However, there is paucity of evidence regarding which factors influence outcomes of FAI surgery, particularly notable is the lack of information on the effect of impingement subtype (cam or pincer or mixed) on patient reported outcomes measures (PROMs). This study aims to evaluate the early outcomes of hip arthroscopy for FAI, and their determinants. Methods: This is a retrospective analysis of prospectively collected data from the UK Non-Arthroplasty Hip Registry (NAHR) of patients undergoing arthroscopic intervention for FAI between 2012 and 2019. The null hypothesis was that there is no difference in PROMs, based on morphological subtype of FAI treated or patient characteristics, at each follow-up timepoint. The outcome measures used for the study were the iHOT-12 score and the EQ5D Index and VAS 6- and 12-month follow-up. Results: A cohort of 4963 patients who underwent arthroscopic treatment of FAI were identified on the NAHR database. For all FAI pathology groups, there was significant improvement from pre-operative PROMs when compared to those at 6 and 12 months. Overall, two-thirds of patients achieved the minimum clinically important difference (MCID), and almost half achieved substantial clinical benefit (SCB) for iHOT-12 by 12 months. Pre-operatively, and at 12-month follow-up, iHOT-12 scores were significantly poorer in the pincer group compared to the cam and mixed pathology groups (p < 0.01). Multivariable analysis revealed PROMS improvement in the setting of a higher-grade cartilage lesion. Conclusion: This registry study demonstrates that hip arthroscopy is an effective surgical treatment for patients with symptomatic FAI and results in a statistically significant improvement in PROMs which are maintained through 12 months follow-up. Level of evidence: III
Microbubbling and microencapsulation by co-axial electrohydrodynamic atomization
No full textMicrobubbles coated with polymers or surfactants have been used in medical imaging
for several years as ultrasound contrast agent particles and are now being investigated
by researchers as drug and gene delivery vehicles and blood substitutes. Current
methods available for the preparation of microbubbles are insufficient as they result in
microbubbles with a wide size distribution and as such filtration is necessary before
their use. With a view to fill the above demand, a detailed investigation has been carried
out in this research to learn the viability of co-axial electrohydrodynamic atomization
(CEHDA) technique to prepare microbubbles. The research also focuses on the effects
of the process parameters such as flow rates, applied voltage and material parameters
such as electrical conductivity, surface tension and viscosity with the objective of
preparing polymer or surfactant coated stabilized microbubbles with diameters < 8 μm
and with a narrow size distribution. A model glycerol-air system was used so that the
CEHDA technique was modified to generate suspensions of microbubbles to a diameter
< 8 μm with a narrow size distribution and then to characterise the CEHDA
microbubbling process in terms of size and stability with varying process parameters
and material parameters. Construction of a parametric plot between the air flow rate and
the liquid flow rate was extremely useful in identifying the flow rate regime of air and
liquid or suspension or solution for the continuous microbubbling of the system used.
With further investigations into the CEHDA microbubbling technique, it was possible
to develop strategies, first, to prepare suspensions of stabilized phospholipids-coated
microbubbles with a mean diameter of ~ 5 μm and a polydispersivity index of 9%, and
second, polymeric microspheres with a mean diameter of 400 nm and a polydispersivity
index of 8% using a biocompatible polymer
Mislocalisation of BEST1 in iPSC-derived retinal pigment epithelial cells from a family with autosomal dominant vitreoretinochoroidopathy (ADVIRC)
No full textAutosomal dominant vitreoretinochoroidopathy (ADVIRC) is a rare, early-onset retinal dystrophy characterised by distinct bands of circumferential pigmentary degeneration in the peripheral retina and developmental eye defects. ADVIRC is caused by mutations in the Bestrophin1 (BEST1) gene, which encodes a transmembrane protein thought to function as an ion channel in the basolateral membrane of retinal pigment epithelial (RPE) cells. Previous studies suggest that the distinct ADVIRC phenotype results from alternative splicing of BEST1 pre-mRNA. Here, we have used induced pluripotent stem cell (iPSC) technology to investigate the effects of an ADVIRC associated BEST1 mutation (c.704T > C, p.V235A) in patient-derived iPSC-RPE. We found no evidence of alternate splicing of the BEST1 transcript in ADVIRC iPSC-RPE, however in patient-derived iPSC-RPE, BEST1 was expressed at the basolateral membrane and the apical membrane. During human eye development we show that BEST1 is expressed more abundantly in peripheral RPE compared to central RPE and is also expressed in cells of the developing retina. These results suggest that higher levels of mislocalised BEST1 expression in the periphery, from an early developmental stage, could provide a mechanism that leads to the distinct clinical phenotype observed in ADVIRC patients
Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell Transplantation in the Retinal Dystrophic Rat
No full textTransformation of somatic cells with a set of embryonic transcription factors produces cells with the pluripotent properties of embryonic stem cells (ESCs). These induced pluripotent stem (iPS) cells have the potential to differentiate into any cell type, making them a potential source from which to produce cells as a therapeutic platform for the treatment of a wide range of diseases. In many forms of human retinal disease, including age-related macular degeneration (AMD), the underlying pathogenesis resides within the support cells of the retina, the retinal pigment epithelium (RPE). As a monolayer of cells critical to photoreceptor function and survival, the RPE is an ideally accessible target for cellular therapy. Here we report the differentiation of human iPS cells into RPE. We found that differentiated iPS-RPE cells were morphologically similar to, and expressed numerous markers of developing and mature RPE cells. iPS-RPE are capable of phagocytosing photoreceptor material, in vitro and in vivo following transplantation into the Royal College of Surgeons (RCS) dystrophic rat. Our results demonstrate that iPS cells can be differentiated into functional iPS-RPE and that transplantation of these cells can facilitate the short-term maintenance of photoreceptors through phagocytosis of photoreceptor outer segments. Longterm visual function is maintained in this model of retinal disease even though the xenografted cells are eventually lost, suggesting a secondary protective host cellular response. These findings have identified an alternative source of replacement tissue for use in human retinal cellular therapies, and provide a new in vitro cellular model system in which to study RPE diseases affecting human patients
