The utility of eccentricity index as a measure of right ventricular function in a lung resection cohort

Context: Right ventricular (RV) dysfunction occurs after lung resection and is associated with postoperative morbidity. Noninvasive evaluation of the RV is challenging, particularly in the postoperative period. A reliable measure of RV function would have value in this population. Aims: This study compares eccentricity index (EI) obtained by transthoracic echocardiography (TTE) with cardiovascular magnetic resonance (CMR) determined measures of RV function in a lung resection cohort. CMR is the reference method for noninvasive assessment of RV function. Design and Setting: Prospective observational cohort study at a single tertiary hospital. Materials and Methods: Twenty-eight patients scheduled for elective lung resection underwent contemporaneous TTE and CMR imaging preoperatively, on postoperative day (POD) 2 and at 2-month. Systolic and diastolic EI was measured offline from anonymized and randomized TTE and CMR images. Statistical Analysis: Bland–Altman analysis was performed to determine agreement between EITTE and EICMR. Changes over time and comparison with CMR determined RV ejection fraction (RVEFCMR) was assessed. Results: Bland–Altman analysis showed a negligible mean difference between EITTE and EICMR, but limits of agreement were wide (SD 0.24 and 0.28). There were no significant changes in EITTE and EICMR over time (P > 0.35). We found no association between EITTE with RVEFCMR at all-time points (P > 0.22). Systolic and diastolic EICMR on POD 2 demonstrated moderate association with RVEFCMR (r = −0.54 and r = −0.59, P ≤ 0.01). At 2-month, only diastolic EICMR correlated with RVEFCMR (r = −0.43, P = 0.03). There were no meaningful associations between EITTE and EICMR with TTE-derived RV systolic pressure (P > 0.31). Conclusions: TTE determined EI is not useful as a noninvasive method of assessing RV function following lung resection

Promoter Account Detection in Twitter

Twitter is an online social network and micro-blog that becomes an alternative media for sharing and getting information. In the political area, Twitter provides various features as a media to promote campaign and get a good imaging for political party or contestant. In order to get a good opinion from other users, the contestant can manipulate their success with a massive promotion. This promotion activity could lead to public opinion that is not consistent with the facts. So that, we need to determine whether this is promoter account or not. In this paper, we propose a new framework for promoter account detection. This framework based on twitter content to detect promoter account according to their existence in topic of promotion. This framework employs k-means approach in order to cluster topic of promotion based on twitter\u27s content. From each cluster, we evaluate the existence of promoter account. With very simple approach, the results obtained on experiment show that this framework is effective for promoter account detection

The right ventricular response to lung resection

Lung cancer is the most common cause of cancer death in the UK and although the best opportunity for cure is provided by lung resection, surgery is associated with high rates of cardiorespiratory complications and long-term morbidity. Existing studies indicate right ventricular dysfunction occurs following lung resection and may be implicated in any post-op deterioration. Evaluation of right ventricular function is challenging, with its complex shape, marked load dependence and retrosternal position meaning there is no reliable, non-invasive method of assessment. The majority of previous work examining right ventricular function in the lung resection population has been performed using the volumetric pulmonary artery catheter, the reliability of which has been challenged. The first section of this thesis reviews the right ventricle in terms of anatomy, physiology and assessment, providing context for future investigations (Chapter 1). A review of the literature examining the right ventricular / pulmonary vascular response to lung resection is then presented, along with the rationale for further investigations (Chapter 2). As there is a high frequency of complications in this population, often requiring critical care support, the first investigation (Chapter 3) of this thesis characterises those patients admitted to intensive care following surgery. It also examines the incidence of right ventricular dysfunction in this population. Given the methodological concerns regarding the techniques previously used to assess right ventricular function following lung resection, cardiovascular magnetic resonance imaging was used to sequentially assess the right ventricular response to surgery (Chapter 5). Cardiovascular magnetic resonance is a reference method for assessment of right ventricular function and has not previously been used sequentially in this population. This investigation demonstrates right ventricular function (measured by right ventricular ejection fraction) deteriorates following lung resection with impairment still evident two months following surgery. There were no changes in left ventricular function over the same period. With the difficulties associated with cardiovascular magnetic resonance imaging in this population and its limited use outside of research settings, an alternative method for assessment of right ventricular function would have utility in this population. Trans-thoracic echocardiography is the most commonly used non-invasive method for assessment of right ventricular function with widespread availability and low cost. Chapters 6 and 7 attempt to validate conventional and novel echocardiographic methods for assessment of right ventricular function in this population. The main finding is that established echocardiographic methods; fractional area change, tricuspid annular plane systolic excursion and S' wave velocity at the tricuspid annulus, are not suitable for assessment of right ventricular function in this population. Speckle tracked strain echocardiography is a novel method of assessing right ventricular function that has shown promising results in other patient groups. Chapter 7 demonstrates that right ventricular global strain is not useful, but that right ventricular free-wall strain may have value in this population. Biomarkers of myocardial dysfunction (B-type natriuretic peptide and high sensitivity troponin-t) were measured contemporaneously with the imaging studies (Chapter 8). This investigation demonstrates that both biomarkers increase following lung resection and that their plasma concentration two days following surgery are associated with right ventricular function. There was no association with parameters of left ventricular function suggesting the biomarkers are released in response to changes affecting the right ventricle. On an exploratory basis the association between the peri-operative biomarkers and functional capacity following surgery is also assessed. Finally, potential mechanisms of right ventricular dysfunction following lung resection are explored (Chapter 9). This demonstrates that as pulmonary artery acceleration time (a surrogate measure of right ventricular afterload) increases, right ventricular ejection fraction deteriorates. Using a cardiovascular magnetic resonance surrogate, a deterioration in the matching of right ventricular function with right ventricular afterload (coupling) is also demonstrated. In combination these studies provide a robust answer to the question "what happens to right ventricular function following lung resection?" It provides validated methods for future work in this population and suggests an association between post-operative right ventricular function and right ventricular afterload

The utility of trans thoracic echocardiograhic measures of right ventricular systolic function in a lung resection cohort

Right ventricular (RV) dysfunction occurs following lung resection and is associated with post-operative complications and long-term functional morbidity. Accurate peri-operative assessment of RV function would have utility in this population. The difficulties of transthoracic echocardiographic (TTE) assessment of RV function may be compounded following lung resection surgery, and no parameters have been validated in this patient group. This study compares conventional TTE methods for assessing RV systolic function to a reference method in a lung resection population. Right ventricular index of myocardial performance (RIMP), fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE) and S′ wave velocity at the tricuspid annulus (S′), along with speckle tracked global and free wall longitudinal strain (RV-GPLS and RV-FWPLS respectively) are compared with RV ejection fraction obtained by cardiovascular magnetic resonance (RVEFCMR). Twenty-seven patients undergoing lung resection underwent contemporaneous CMR and TTE imaging; pre-operatively, on post-operative day two and at 2 months. Ability of each of the parameters to predict RV dysfunction (RVEFCMR <45%) was assessed using the area under the receiver operating characteristic curve (AUROCC). RIMP, FAC and S′ demonstrated no predictive value for poor RV function (AUROCC <0.61, P > 0.05). TAPSE performed marginally better with an AUROCC of 0.65 (P = 0.04). RV-GPLS and RV-FWPLS demonstrated good predictive ability with AUROCC’s of 0.74 and 0.76 respectively (P < 0.01 for both). This study demonstrates that the conventional TTE parameters of RV systolic function are inadequate following lung resection. Longitudinal strain performs better and offers some ability to determine poor RV function in this challenging population

Diffuse retro-reflective imaging for improved mosquito tracking around human baited bednets

Robust imaging techniques for tracking insects have been essential tools in numerous laboratory and field studies on pests, beneficial insects and model systems. Recent innovations in optical imaging systems and associated signal processing have enabled detailed characterisation of nocturnal mosquito behaviour around bednets and improvements in bednet design, a global essential for protecting populations against malaria. Nonetheless, there remain challenges around ease of use for large scale in situ recordings and extracting data reliably in the critical areas of the bednet where the optical signal is attenuated. Here we introduce a retro-reflective screen at the back of the measurement volume, which can simultaneously provide diffuse illumination, and remove optical alignment issues whilst requiring only one-sided access to the measurement space. The illumination becomes significantly more uniform, although, noise removal algorithms are needed to reduce the effects of shot noise particularly across low intensity bednet regions. By systematically introducing mosquitoes in front and behind the bednet in lab experiments we are able to demonstrate robust tracking in these challenging areas. Overall, the retro-reflective imaging setup delivers mosquito segmentation rates in excess of 90% compared to less than 70% with back-lit systems

Entomological indices of malaria transmission in Chikhwawa district, Southern Malawi

Abstract Background Although malaria is highly prevalent throughout Malawi, little is known of its transmission dynamics. This paper describes the seasonal activity of the different vectors, human biting indices, sporozoite rates and the entomological inoculation rate in a low-lying rural area in southern Malawi. Methods Vectors were sampled over 52 weeks from January 2002 to January 2003, by pyrethrum knockdown catch in two villages in Chikhwawa district, in the Lower Shire Valley. Results In total, 7,717 anophelines were collected of which 55.1% were Anopheles gambiae sensu lato and 44.9% were Anopheles funestus. Three members of the An. gambiae complex were identified by PCR: Anopheles arabiensis (75%) was abundant throughout the year, An. gambiae s.s. (25%) was most common during the wet season and Anopheles quadriannulatus occurred at a very low frequency (n=16). An. funestus was found in all samples but was most common during the dry season. Anopheles gambiae s.s. and An. funestus were highly anthropophilic with human blood indices of 99.2% and 96.3%, respectively. Anopheles arabiensis had fed predominantly on humans (85.0%) and less commonly on cattle (10.9%; 1.2% of blood meals were of mixed origin). Plasmodium falciparum (192/3,984) and Plasmodium malariae (1/3,984) sporozoites were detected by PCR in An. arabiensis (3.2%) and An. funestus (4.5%), and in a significantly higher proportion of An. gambiae s.s. (10.6%)(pP. falciparum sporozoite rate was 4.8%, resulting in estimated inoculation rates of 183 infective bites/ person per annum, or an average rate of ~15 infective bites/person/month. Conclusions The results demonstrate the importance of An. gambiae s.s., An. arabiensis and An. funestus in driving the high levels of malaria transmission in the south of Malawi. Sustained and high coverage or roll out of current approaches to malaria control (primarily insecticide-treated bed nets and indoor residual house spraying) in the area are likely to reduce the observed high malaria transmission rate and consequently the incidence of human infections, unless impeded by increasing resistance of vectors to insecticides.</p

Redesigned and chemically-modified hammerhead ribozymes with improved activity and serum stability

BACKGROUND: Hammerhead ribozymes are RNA-based molecules which bind and cleave other RNAs specifically. As such they have potential as laboratory reagents, diagnostics and therapeutics. Despite having been extensively studied for 15 years or so, their wide application is hampered by their instability in biological media, and by the poor translation of cleavage studies on short substrates to long RNA molecules. This work describes a systematic study aimed at addressing these two issues. RESULTS: A series of hammerhead ribozyme derivatives, varying in their hybridising arm length and size of helix II, were tested in vitro for cleavage of RNA derived from the carbamoyl phosphate synthetase II gene of Plasmodium falciparum. Against a 550-nt transcript the most efficient (t(1/2 )= 26 seconds) was a miniribozyme with helix II reduced to a single G-C base pair and with twelve nucleotides in each hybridising arm. Miniribozymes of this general design were targeted to three further sites, and they demonstrated exceptional cleavage activity. A series of chemically modified derivatives was prepared and examined for cleavage activity and stability in human serum. One derivative showed a 10(3)-fold increase in serum stability and a doubling in cleavage efficiency compared to the unmodified miniribozyme. A second was almost 10(4)-fold more stable and only 7-fold less active than the unmodified parent. CONCLUSION: Hammerhead ribozyme derivatives in which helix II is reduced to a single G-C base pair cleave long RNA substrates very efficiently in vitro. Using commonly available phosphoramidites and reagents, two patterns of nucleotide substitution in this derivative were identified which conferred both good cleavage activity against long RNA targets and good stability in human serum

Combined target site (kdr) mutations play a primary role in highly pyrethroid resistant phenotypes of Aedes aegypti from Saudi Arabia

Background Pyrethroid resistance is a threat to effective vector control of Aedes aegypti, the vector of dengue, Zika and other arboviruses, but there are many major knowledge gaps on the mechanisms of resistance. In Jeddah and Makkah, the principal dengue-endemic areas of Saudi Arabia, pyrethroids are used widely for Ae. aegypti control but information about resistance remains sparse, and the underlying genetic basis is unknown. Findings from an ongoing study in this internationally significant area, are reported here. Methods Aedes aegypti collected from each city were raised to adults and assayed for resistance to permethrin, deltamethrin (with and without the synergist piperonyl butoxide, PBO), fenitrothion, and bendiocarb. Two fragments of the voltage-gated sodium channel (Vgsc), encompassing four previously identified mutation sites, were sequenced and subsequently genotyped to determine associations with resistance. Expression of five candidate genes (CYP9J10, CYP9J28, CYP9J32, CYP9M6, ABCB4) previously associated with pyrethroid resistance was compared between assay survivors and controls. Results Jeddah and Makkah populations exhibited resistance to multiple insecticides and a similarly high prevalence of resistance to deltamethrin compared to a resistant Cayman strain, with a significant influence of age and exposure duration on survival. PBO pre-exposure increased pyrethroid mortality significantly in the Jeddah, but not the Makkah strain. Three potentially interacting Vgsc mutations were detected: V1016G and S989P were in perfect linkage disequilibrium in each strain and strongly predicted survival, especially in the Makkah strain, but were in negative linkage disequilibrium with 1534C, though some females with the Vgsc triple mutation were detected. The candidate gene CYP9J28 was significantly over-expressed in Jeddah compared to two susceptible reference strains, but none of the candidate genes was consistently up-regulated to a significant level in the Makkah strain. Conclusions Despite their proximity, Makkah and Jeddah exhibit significant differences in pyrethroid resistance phenotypes, with some evidence to suggest a different balance of mechanisms, for example with more impact associated with CYP450s in the Jeddah strain, and the dual kdr mutations 989P and 1016G in the more resistant Makkah strain. The results overall demonstrate a major role for paired target site mutations in pyrethroid resistance and highlight their utility for diagnostic monitoring