36 research outputs found
Genetic control of Aedes aegypti: data-driven modelling to assess the effect of releasing different life stages and the potential for long-term suppression
Background
Control of the world’s most important vector-borne viral disease, dengue, is a high priority. A lack of vaccines or effective vector control methods means that novel solutions to disease control are essential. The release of male insects carrying a dominant lethal (RIDL) is one such approach that could be employed to control Aedes aegypti. To maximise the potential of RIDL control, optimum release strategies for transgenic mosquitoes are needed. The use of field data to parameterise models allowing comparisons of the release of different life-stages is presented together with recommendations for effective long-term suppression of a wild Ae. aegypti population.
Methods
A compartmental, deterministic model was designed and fitted to data from large-scale pupal mark release recapture (MRR) field experiments to determine the dynamics of a pupal release. Pulsed releases of adults, pupae or a combination of the two were simulated. The relative ability of different release methods to suppress a simulated wild population was examined and methods to maintain long-term suppression of a population explored.
Results
The pupal model produced a good fit to field data from pupal MRR experiments. Simulations using this model indicated that adult-only releases outperform pupal-only or combined releases when releases are frequent. When releases were less frequent pupal-only or combined releases were a more effective method of distributing the insects. The rate at which pupae eclose and emerge from release devices had a large influence on the relative efficacy of pupal releases. The combined release approach allows long-term suppression to be maintained with smaller low-frequency releases than adult- or pupal-only release methods.
Conclusions
Maximising the public health benefits of RIDL-based vector control will involve optimising all stages of the control programme. The release strategy can profoundly affect the outcome of a control effort. Adult-only, pupal-only and combined releases all have relative advantages in certain situations. This study successfully integrates field data with mathematical models to provide insight into which release strategies are best suited to different scenarios. Recommendations on effective approaches to achieve long-term suppression of a wild population using combined releases of adults and pupae are provided
Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis
BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms
Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications
Superparamagnetic iron oxide nanoparticles
can providemultiple benefits for biomedical applications
in aqueous environments such asmagnetic separation or
magnetic resonance imaging. To increase the colloidal
stability and allow subsequent reactions, the introduction
of hydrophilic functional groups onto the particles’
surface is essential. During this process, the original
coating is exchanged by preferably covalently bonded
ligands such as trialkoxysilanes. The duration of the
silane exchange reaction, which commonly takes more
than 24 h, is an important drawback for this approach. In
this paper, we present a novel method, which introduces
ultrasonication as an energy source to dramatically
accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove
the generic character, different functional groups were
introduced on the surface including polyethylene glycol
chains, carboxylic acid, amine, and thiol groups. Their
colloidal stability in various aqueous buffer solutions as
well as human plasma and serum was investigated to
allow implementation in biomedical and sensing
applications.status: publishe
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups
Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
Moderating effects of MNCs' size in the relationship between knowledge characteristics and degree of inter-firm technology transfer in international joint ventures
The main objective of this paper is to empirically examine the moderating effect of size of MNCs on the relationships between knowledge characteristics: tacitness, complexity and specificity and two distinct dimensions of degrees of technology transfer: degrees of tacit and explicit knowledge in inter-firm technology transfer within IJVs. Using the moderated multiple regression, the theoretical models and hypotheses in this study were tested based on empirical data gathered from 128 joint venture companies registered with the Registrar of Companies of Malaysia (ROC). The results revealed that size of MNCs has significantly affected the relationships between knowledge characteristics (tacitness, complexity and specificity) and both degrees of tacit and explicit knowledge; where the relationships were found stronger for medium/small MNCs than large MNCs. The study has bridged the literature gaps in such that it offers empirical evidence on the moderating effect of size of MNCs on the relationships between knowledge characteristics and two distinct degrees of technology transfer: degrees of tacit and explicit knowledge using the Malaysian sample
The effects of absorptive capacity and recipient collaborativeness as technology recipient characteristics on degree of inter-firm technology transfer
Problem statement: As an efficient means to increase global competitiveness, technological capabilities and potential for local innovation, organizations in the developing countries are working hard to collaborate, learn and internalize their foreign partner’s technological knowledge by forming strategic alliances or International Joint Ventures (IJVs). Technology recipient characteristics, as one of the important actors/facilitators of inter-firm technology transfer, have increasingly become crucial factors in determining the success or failure of inter-firm technology transfer within IJVs. Since the current issue on inter-firm Technology Transfer (TT) in the developing countries is centered on the efficiency and effectiveness of the transfer process by the Multinationals (MNCs) therefore the success is often associated with or measured by degree of technology transferred to local partners. Based on the underlying knowledge-based view and organizational learning perspective, this study aims to empirically examine the effects of two critical elements of technology recipient characteristics: Absorptive Capacity (ACAP) and Recipient Collaborativeness (RCOL) on degree of technology transfer: Degree of tacit and explicit knowledge in IJVs. Approach: Using the quantitative analytical approach, the theoretical model and hypotheses in this study were tested based on empirical data gathered from 128 joint venture companies registered with the Registrar of Companies Of Malaysia (ROC). Data obtained from the survey questionnaires were analyzed using the correlation coefficients and multiple linear regression analyses. Results: The results revealed that recipient collaborativeness as the critical element of technology recipient characteristics has strong significant effects on both degrees of tacit and explicit knowledge. Although absorptive capacity has been strongly emphasized of its significance effect, however, the results are not statistically significant. Conclusion/Recommendations: The study had bridged the literature gaps in such that it provides empirical evidence on the effects of two generic technology recipient attributes: absorptive capacity and recipient collaborativeness on degree of inter-firm technology transfer: degree of tacit and explicit knowledge
Moderating effects of MNCs' size in the relationship between degree of inter-firm technology transfer and local firms' performance
The inter-firm technology transfers (TT) through international joint ventures (IJVs), among others, have significantly contributed to a higher degree of local innovation performance/capabilities, technological capabilities, competitive advantage, organizational learning effectiveness, productivity, technological development of local industry, and the economic growth of the host country. Since the focus of inter-firm TT in developing countries has shifted to degree of technology transfer, organizations in developing countries are attempting to assess not only the significant role of technology transfer in strengthening their corporate and human resource performance but also the influence of other critical variables such as MNCs’ size (MNCSIZE), age of JVs, country of origin, and MNC’s type of industries that could significantly moderate the relationship. Based on the underlying knowledge-based view (KBV) and organizational learning (OL) perspectives, the main objective of this paper is to empirically examine the moderating effect of size of MNCs (large vs. medium/small MNCs) in the relationships between degree of inter-firm technology transfer and two dimensions of local firms’ performance: corporate and human resource performances. Using the moderated multiple regression (MMR) analysis, the theoretical models and hypotheses in this study were tested based on empirical data gathered from 128 joint venture companies registered with the Registrar of Companies of Malaysia (ROC). The results revealed that size of MNCs has significantly affected the relationships between degrees of technology transfer and local firms’ human resource performance; where the relationship was found stronger for large MNCs as compared to medium/small MNCs. However, size of MNCs did not significantly moderate the relationship between degree of technology transfer and local firms’ corporate performance. The study has bridged the literature gaps in such that it offers empirical evidence and new insights on the significant moderating effects of size of MNCs in the relationships between degree of inter-firm technology transfer and local firms’ performance technology using the Malaysian sample
Evolution and development of technology transfer models and the influence of knowledge-based view and organizational learning on technology transfer
The main objective of this paper is to review the evolution and development of technology transfer models before and after the 1990s. These technology transfer models will be reviewed in terms of focus of each model, strengths and limitations of the models, and to highlight the significance influence of knowledge-based view and organizational learning perspectives, which have strong theoretical foundation, on the current technology transfer models. The early technology transfer models were developed to govern the implementation of technology transfer activities and their application to market place; where emphasis was given on the promotion, adoption and diffusion of new innovations and technologies to potential users as well as on technology transfer processes. Nonetheless, with the emergence of knowledge-based economies, the technology transfer models have been gradually developed by management researchers to explain the dynamic role of knowledge underlying technology as the organizations’ strategic asset and organizational learning through inter-firm technology transfer