20 research outputs found
Novel mutations in the toll like receptor genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection
Toll like receptors play a central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in TLR1, TLR2 and TLR4 genes may change the PAMP reorganization ability which causes altered responsiveness to the bacterial pathogens. A case control study, performed to assess the association between TLR gene mutations and susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP), revealed novel mutations (TLR1 - Ser150Gly and Val220Met; TLR2 - Phe670Leu) that hindered either PAMP recognition or further downstream TLR pathway activation. A cytokine expression experiments (IL-4, IL-8, IL-10, IL-12 and IFN-γ) in the challenged mutant and wild type moDCs (mocyte derived dendritic cells) confirmed the negative impact of these mutations and altered TLR downstream activation. Further In silico analysis of the TLR1 and TLR4 ectodomains (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR motifs. The most critical positions that may alter the pathogen recognition ability of TLR were: the 9th amino acid position in LRR motif (TLR1, LRR10) and 4th residue downstream to LRR domain (exta LRR region of TLR4). The study describes novel mutations in the TLRs and presents their association with the MAP infection
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Direct observation of the local microenvironment in inhomogeneous CO 2 reduction gas diffusion electrodes via versatile pOH imaging
We demonstrate pOH imaging with confocal microscopy to probe the microenvironment of an operating CO 2 reduction gas diffusion electrode. We find that the micrometer-scale morphology plays an important role in defining the CO 2 reduction performance.
We report how the micrometer-scale morphology of a carbon dioxide reduction (CO 2 R) gas diffusion electrode (GDE) affects the mass transport properties and with it, the local CO 2 R performance. We developed a technique to probe the microenvironment in a CO 2 R GDE via local pOH imaging with time- and three-dimensional spatial, micrometer-scale resolution. The local activity of hydroxide anions (OH − ), represented by the pOH value, around a GDE in contact with an aqueous electrolyte is a crucial parameter that governs the catalytic activity and CO 2 R selectivity. Here, we use fluorescence confocal laser scanning microscopy (CLSM) to create maps of the local pOH around a copper GDE by combining two ratiometric fluorescent dyes, one of which is demonstrated as a pOH sensor for the first time in this work. We observe that the local pOH decreases when current is applied due to the creation of OH − as a byproduct of CO 2 R. Interestingly, the pOH is lower inside microtrenches compared to the electrode surface and decreases further as trenches become more narrow due to enhanced trapping of OH − . We support our experimental results with multiphysics simulations that correlate exceptionally well with measurements. These simulations additionally suggest that the decreased pOH inside microcavities in the surface of a CO 2 R GDE leads to locally enhanced selectivity towards multicarbon (C 2+ ) products. This study suggests that narrow microstructures on the length scale of 5 μm in a GDE surface serve as local CO 2 R hotspots, and thus highlights the importance of a GDE's micromorphology on the CO 2 R performance
An Outline of the Existing Literature on Monetary Economics in India
As per the researchers on monetary economics, a detailed account of the changing role of money from Walrasian and Non-Walrasian settings to the more recent theories on the dynamics of the relationships between money, inflation and growth with reference to their historical evolution are available in Friedman et al. ed. (1998) and such type of theoretical work did not happen in India. There is a tendency among the Indian researchers to apply the theories developed abroad to up to date empirical data in econometrics models and then, with the help of econometric techniques and compare the results. For example Dash and Goal (2001) applied the theory of Foster (1992) and Chona (1976) applied the theory of Ahrensdorf and Thasan (1960). This paper dealt with such applications, their lacunae and attempts to resolve the issues unaddressed till 2005.monetary policy, money, interest rate, Keynes, monetarist, neo Keynesian, Quantity Theory, LM curve, Nachane, Brahmananda, Tobin, post Keynesian, endogenous, money supply, financial markets, bank, credit, loan
The development of a relationship marketing framework that captures the delivery of value in entrepreneurial SMEs
There are a number of environmental pressures facing SMEs and the high failure rates
amongst young SMEs highlights the need for research to develop a framework that will
permit SMEs to achieve growth with a minimal risk of failure. This research will show
that both relationship marketing and entrepreneurship have significantly contributed to
allowing entrepreneurial SMEs to pursue a low risk strategy of growth through pursuing
a customer retention, development and targeted acquisition strategy. To understand the
nature of entrepreneurial SMEs and the factors influencing growth.
The author cites literature that argues entrepreneurship is not an 'absolute' and thus
believes that less entrepreneurial firms have the potential to learn from their more
successful counterparts. Whilst this does offer some specific management suggestions,
the author also recognises that the task is not an easy one, for the SME has not only to
create an internal culture that is capable of embracing relationship marketing but one that
also enables it to act in an entrepreneurial fashion. Despite these challenges the author
will capitalise on the research findings to develop a framework for successfully adopting
relationship marketing and entrepreneurial behaviour, to assist SMEs to overcome the
hurdle of high failure rate amongst SMEs.
The research has focused on the business services industry, since this sector is
experiencing the highest growth. In the main this sector covered printing, marketing
services and computer services, and so would be offering clients both a pure service and a
product / service mix. Additionally this sector because of its service nature would have a
high contact with its customer base. A sampling frame was developed that resulted in
identifying 102 SMEs in West Yorkshire (UK) that met the criteria for selection. An
initial quantitative survey was administered that provided statistical evidence that
entrepreneurial SMEs had a greater relationship marketing orientation. The results from
the survey were further investigated through in-depth semi structured interviews to reveal
a richer picture of the phenomenon
A randomised controlled trial to assess the clinical effectiveness and safety of the endometrial scratch procedure prior to first-time IVF, with or without ICSI
\ua9 The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.STUDY QUESTION: What is the clinical-effectiveness and safety of the endometrial scratch (ES) procedure compared to no ES, prior to usual first time in vitro fertilisation (IVF) treatment? SUMMARY ANSWER: ES was safe but did not improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF cycle, with or without intracytoplasmic sperm injection (ICSI). WHAT IS KNOWN ALREADY: ES is an \u27add-on\u27 treatment that is available to women undergoing a first cycle of IVF, with or without ICSI, despite a lack of evidence to support its use. STUDY DESIGN, SIZE, DURATION: This pragmatic, superiority, open-label, multi-centre, parallel-group randomised controlled trial involving 1048 women assessed the clinical effectiveness and safety of the ES procedure prior to first time IVF, with or without ICSI, between July 2016 and October 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants aged 18-37 years undergoing their first cycle of IVF, with or without ICSI, were recruited from 16 UK fertility clinics and randomised (1:1) by a web-based system with restricted access rights that concealed allocation. Stratified block randomisation was used to allocate participants to TAU or ES in the mid-luteal phase followed by usual IVF with or without ICSI treatment. The primary outcome was live birth after completing 24 weeks gestation within 10.5 months of egg collection. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 1048 women randomised to TAU (n = 525) and ES (n = 523) were available for intention to treat analysis. In the ES group, 453 (86.6%) received the ES procedure. IVF, with or without ICSI, was received in 494 (94.1%) and 497 (95.0%) of ES and TAU participants respectively. Live birth rate was 37.1% (195/525) in the TAU and 38.6% (202/523) in the ES: an unadjusted absolute difference of 1.5% (95% CI -4.4% to 7.4%, P = 0.621). There were no statistical differences in secondary outcomes. Adverse events were comparable across groups. LIMITATIONS, REASONS FOR CAUTION: A sham ES procedure was not undertaken in the control group, however, we do not believe this would have influenced the results as objective fertility outcomes were used. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest trial that is adequately powered to assess the impact of ES on women undergoing their first cycle of IVF. ES was safe, but did not significantly improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF or ICSI cycle. We recommend that ES is not undertaken in this population. STUDY FUNDING/COMPETING INTEREST(S): Funded by the National Institute of Health Research. Stephen Walters is an National Institute for Health Research (NIHR) Senior Investigator (2018 to present) and was a member of the following during the project: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Clinical Trials and Evaluation Committee (2011-2017), NIHR HTA Commissioning Strategy Group (2012 to 2017); NIHR Programme Grants for Applied Research Committee (2020 to present); NIHR Pre doctoral Fellowship Committee (2019 to present). Dr. Martins da Silva reports grants from AstraZeneca, during the conduct of the study; and is Associate editor of Human Reproduction and Editorial Board member of Reproduction and Fertility. Dr. Bhide reports grants from Bart\u27s Charity and grants and non-financial support from Pharmasure Pharmaceuticals outside the submitted work. TRIAL REGISTRATION NUMBER: ISRCTN number: ISRCTN23800982. TRIAL REGISTRATION DATE: 31 May 2016. DATE OF FIRST PATIENT’S ENROLMENT: 04 July 2016
Elective freezing of embryos versus fresh embryo transfer in IVF: a multicentre randomized controlled trial in the UK (E-Freeze)
STUDY QUESTION: Does a policy of elective freezing of embryos, followed by frozen embryo transfer result in a higher healthy baby rate, after first embryo transfer, when compared with the current policy of transferring fresh embryos? SUMMARY ANSWER: This study, although limited by sample size, provides no evidence to support the adoption of a routine policy of elective freeze in preference to fresh embryo transfer in order to improve IVF effectiveness in obtaining a healthy baby. WHAT IS KNOWN ALREADY: The policy of freezing all embryos followed by frozen embryo transfer is associated with a higher live birth rate for high responders but a similar/lower live birth after first embryo transfer and cumulative live birth rate for normal responders. Frozen embryo transfer is associated with a lower risk of ovarian hyperstimulation syndrome (OHSS), preterm delivery and low birthweight babies but a higher risk of large babies and pre-eclampsia. There is also uncertainty about long-term outcomes, hence shifting to a policy of elective freezing for all remains controversial given the delay in treatment and extra costs involved in freezing all embryos. STUDY DESIGN, SIZE, DURATION: A pragmatic two-arm parallel randomized controlled trial (E-Freeze) was conducted across 18 clinics in the UK from 2016 to 2019. A total of 619 couples were randomized (309 to elective freeze/310 to fresh). The primary outcome was a healthy baby after first embryo transfer (term, singleton live birth with appropriate weight for gestation); secondary outcomes included OHSS, live birth, clinical pregnancy, pregnancy complications and cost-effectiveness. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples undergoing their first, second or third cycle of IVF/ICSI treatment, with at least three good quality embryos on Day 3 where the female partner was ≥18 and <42 years of age were eligible. Those using donor gametes, undergoing preimplantation genetic testing or planning to freeze all their embryos were excluded. IVF/ICSI treatment was carried out according to local protocols. Women were followed up for pregnancy outcome after first embryo transfer following randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 619 couples randomized, 307 and 309 couples in the elective freeze and fresh transfer arms, respectively, were included in the primary analysis. There was no evidence of a statistically significant difference in outcomes in the elective freeze group compared to the fresh embryo transfer group: healthy baby rate {20.3% (62/307) versus 24.4% (75/309); risk ratio (RR), 95% CI: 0.84, 0.62 to 1.15}; OHSS (3.6% versus 8.1%; RR, 99% CI: 0.44, 0.15 to 1.30); live birth rate (28.3% versus 34.3%; RR, 99% CI 0.83, 0.65 to 1.06); and miscarriage (14.3% versus 12.9%; RR, 99% CI: 1.09, 0.72 to 1.66). Adherence to allocation was poor in the elective freeze group. The elective freeze approach was more costly and was unlikely to be cost-effective in a UK National Health Service context. LIMITATIONS, REASONS FOR CAUTION: We have only reported on first embryo transfer after randomization; data on the cumulative live birth rate requires further follow-up. Planned target sample size was not obtained and the non-adherence to allocation rate was high among couples in the elective freeze arm owing to patient preference for fresh embryo transfer, but an analysis which took non-adherence into account showed similar results. WIDER IMPLICATIONS OF THE FINDINGS: Results from the E-Freeze trial do not lend support to the policy of electively freezing all for everyone, taking both efficacy, safety and costs considerations into account. This method should only be adopted if there is a definite clinical indication. STUDY FUNDING/COMPETING INTEREST(S): NIHR Health Technology Assessment programme (13/115/82). This research was funded by the National Institute for Health Research (NIHR) (NIHR unique award identifier) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care. J.L.B., C.C., E.J., P.H., J.J.K., L.L. and G.S. report receipt of funding from NIHR, during the conduct of the study. J.L.B., E.J., P.H., K.S. and L.L. report receipt of funding from NIHR, during the conduct of the study and outside the submitted work. A.M. reports grants from NIHR personal fees from Merck Serono, personal fees for lectures from Merck Serono, Ferring and Cooks outside the submitted work; travel/meeting support from Ferring and Pharmasure and participation in a Ferring advisory board. S.B. reports receipt of royalties and licenses from Cambridge University Press, a board membership role for NHS Grampian and other financial or non-financial interests related to his roles as Editor-in-Chief of Human Reproduction Open and Editor and Contributing Author of Reproductive Medicine for the MRCOG, Cambridge University Press. D.B. reports grants from NIHR, during the conduct of the study; grants from European Commission, grants from Diabetes UK, grants from NIHR, grants from ESHRE, grants from MRC, outside the submitted work. Y.C. reports speaker fees from Merck Serono, and advisory board role for Merck Serono and shares in Complete Fertility. P.H. reports membership of the HTA Commissioning Committee. E.J. reports membership of the NHS England and NIHR Partnership Programme, membership of five Data Monitoring Committees (Chair of two), membership of six Trial Steering Committees (Chair of four), membership of the Northern Ireland Clinical Trials Unit Advisory Group and Chair of the board of Oxford Brain Health Clinical Trials Unit. R.M. reports consulting fees from Gedeon Richter, honorarium from Merck, support fees for attendance at educational events and conferences for Merck, Ferring, Bessins and Gedeon Richter, payments for participation on a Merck Safety or Advisory Board, Chair of the British Fertility Society and payments for an advisory role to the Human Fertilisation and Embryology Authority. G.S. reports travel and accommodation fees for attendance at a health economic advisory board from Merck KGaA, Darmstadt, Germany. N.R.-F. reports shares in Nurture Fertility. Other authors' competing interests: none declared. TRIAL REGISTRATION NUMBER: ISRCTN: 61225414. TRIAL REGISTRATION DATE: 29 December 2015. DATE OF FIRST PATIENT'S ENROLMENT: 16 February 2016
Ways out of poverty : diffusing best practices and creating capabilities - perspectives on policies for poverty reduction
Fundamentally, poverty reduction is about bringing growth processes to poor areas. Because poor areas can benefit from technical and organizational innovations made elsewhere in the world, it is possible today to create productive jobs faster and in greater quantity than ever before. The puzzle is what helps spread such"best practices."Saving, investment, education, resources, and new technology are all needed-and fairly easy to obtain. What is hard to obtain are the institutions that allow these factors of production to be combined and translated into productive job creation. Firms are the key vehicles that spread best practices and productive jobs to areas where poor people live. Because we can never be sure which firm will be successful, it is necessary that new firms can enter markets, that substandard firms are allowed to fail, and that good firms face few barriers to growth. This is the definition of competition, and competition is what selects good firms and thus drives the spread of best practice and productive jobs. Governments need to provide the framework in which capable firms can emerge. Yet, the right mix of state activity and how it best interacts with firms are not fully understood. Some selection mechanism, which allows for policy experiments and selects successful ones, is valuable for national, provincial, and local governments. Thus competition among jurisdictions and firms is an integral part of dynamic social systems that hold promise for creating wealth and ending poverty.Labor Policies,Public Health Promotion,Economic Theory&Research,Health Monitoring&Evaluation,Environmental Economics&Policies,Achieving Shared Growth,Health Monitoring&Evaluation,Environmental Economics&Policies,Governance Indicators,Economic Theory&Research
Stock market development and long-run growth
The authors empirically evaluate the relationship between stock market development and long-term growth. The data suggest that stock market development is positively associated with economic growth. Moreover, instrumental variables procedures indicate a strong connection between the predetermined component in the long run. While cross-country regressions imply a strong link between stock market development and economic growth, the results should be viewed as suggestive partial correlations that stimulate additional research rather than as conclusive findings. Careful case studies might help identify causal relationships and further research could bedone on the time-series property of such relationships.Economic Theory&Research,Financial Intermediation,Health Economics&Finance,Environmental Economics&Policies,Labor Policies,Economic Theory&Research,Financial Intermediation,Achieving Shared Growth,Governance Indicators,Health Economics&Finance
Rehabilitation service models for people with physical and/or mental disability living in low- and middle-income countries: A systematic review
Objective: To compare models of rehabilitation services for people with mental and/or physical disability in order to determine optimal models for therapy and interventions in low- to middle-income countries.
Data sources: CINAHL, EMBASE, MEDLINE, CENTRAL, PsycINFO, Business Source Premier, HINARI, CEBHA and PubMed.
Study selection: Systematic reviews, randomized control trials and observational studies comparing >2 models of rehabilitation care in any language.
Date extraction: Standardized forms were used. Methodological quality was assessed using AMSTAR and quality of evidence was assessed using GRADE.
Data synthesis: Twenty-four systematic reviews which included 578 studies and 202,307 participants were selected. In addition, four primary studies were included to complement the gaps in the systematic reviews. The studies were all done at various countries. Moderate- to high-quality evidence supports the following models of rehabilitation services: psychological intervention in primary care settings for people with major depression, admission into an inpatient, multidisciplinary, specialized rehabilitation unit for those with recent onset of a severe disabling condition; outpatient rehabilitation with multidisciplinary care in the community, hospital or home is recommended for less severe conditions; However, a model of rehabilitation service that includes early discharge is not recommended for elderly patients with severe stroke, chronic obstructive pulmonary disease, hip fracture and total joints.
Conclusion: Models of rehabilitation care in inpatient, multidisciplinary and specialized rehabilitation units are recommended for the treatment of severe conditions with recent onset, as they reduce mortality and the need for institutionalized care, especially among elderly patients, stroke patients, or those with chronic back pain. Results are expected to be generalizable for brain/spinal cord injury and complex fractures
Micromachined glass apertures for artificial lipid bilayer formation in a microfluidic system
The use of spark assisted chemical engraving (SACE) to produce glass apertures that are suitable for the formation of artificial bilayer lipid membranes is described. Prior to use, the glass apertures were rendered hydrophobic by a silanization process and were then incorporated into a simple microfluidic device. Successful bilayer lipid membrane (BLM) formation and the subsequent acquisition of single-channel recordings are demonstrated. Due to the simplicity and rapidity of the SACE process, these glass apertures could be easily integrated into an all-glass microfluidic system for BLM formation
