Search results for: Timothy P. Gill
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 140

Search results for: Timothy P. Gill

20 Spatial Ecology of an Endangered Amphibian Litoria Raniformis within Modified Tasmanian Landscapes

Authors: Timothy Garvey, Don Driscoll

Abstract:

Within Tasmania, the growling grass frog (Litoria raniformis) has experienced a rapid contraction in distribution. This decline is primarily attributed to habitat loss through landscape modification and improved land drainage. Reductions in seasonal water-sources have placed increasing importance on permanent water bodies for reproduction and foraging. Tasmanian agricultural and commercial forestry landscapes often feature small artificial ponds, utilized for watering livestock and fighting wildfires. Improved knowledge of how L. raniformis may be exploiting anthropogenic ponds is required for improved conservation management. We implemented telemetric tracking in order to evaluate the spatial ecology of L. raniformis (n = 20) within agricultural and managed forestry sites, with tracking conducted periodically over the breeding season (November/December, January/February, March/April). We investigated (1) potential differences in habitat utilization between agricultural and plantation sites, and (2) the post-breeding dispersal of individual frogs. Frogs were found to remain in close proximity to ponds throughout November/December, with individuals occupying vegetative depauperate water bodies beginning to disperse by January/February. Dispersing individuals traversed exposed plantation understory and agricultural pasture land in order to enter patches of native scrubland. By March/April all individuals captured at minimally vegetated ponds had retreated to adjacent scrub corridors. Animals found in ponds featuring dense riparian vegetation were not recorded to disperse. No difference in behavior was recorded between sexes. Rising temperatures coincided with increased movement by individuals towards native scrub refugia. The patterns of movement reported in this investigation emphasize the significant contribution of manmade water-bodies towards the conservation of L. raniformis within modified landscapes. The use of natural scrubland as cyclical retreats between breeding seasons also highlights the importance of the continued preservation of remnant vegetation corridors. Loss of artificial dams or buffering scrubland in heavily altered landscapes could see the breakdown of the greater L. raniformis meta-population further threatening their regional persistence.

Keywords: habitat loss, modified landscapes, spatial ecology, telemetry

Procedia PDF Downloads 90
19 Insect Cell-Based Models: Asutralian Sheep bBlowfly Lucilia Cuprina Embryo Primary Cell line Establishment and Transfection

Authors: Yunjia Yang, Peng Li, Gordon Xu, Timothy Mahony, Bing Zhang, Neena Mitter, Karishma Mody

Abstract:

Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls, and the parasite has developed resistance to nearly all control chemicals used in the past. It is, therefore, critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi, and insects. However, the environmental instability of dsRNA is a major bottleneck for successful RNAi. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for the controlled release of dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. To investigate the potential of BenPol technology for dsRNA delivery, four different BenPol carriers were tested for their dsRNA loading capabilities, and three of them were found to be capable of affording dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in sheep serum. Based on stability results, dsRNA from potential targeted genes was loaded onto BenPol carriers and tested in larvae feeding assays, three genes resulting in knockdowns. Meanwhile, a primary blowfly embryo cell line (BFEC) derived from L. cuprina embryos was successfully established, aim for an effective insect cell model for testing RNAi efficacy for preliminary assessments and screening. The results of this study establish that the dsRNA is stable when loaded on BenPol particles, unlike naked dsRNA rapidly degraded in sheep serum. The stable nanoparticle delivery system offered by BenPol technology can protect and increase the inherent stability of dsRNA molecules at higher temperatures in a complex biological fluid like serum, providing promise for its future use in enhancing animal protection.

Keywords: lucilia cuprina, primary cell line establishment, RNA interference, insect cell transfection

Procedia PDF Downloads 49
18 Interrelationship between Quadriceps' Activation and Inhibition as a Function of Knee-Joint Angle and Muscle Length: A Torque and Electro and Mechanomyographic Investigation

Authors: Ronald Croce, Timothy Quinn, John Miller

Abstract:

Incomplete activation, or activation failure, of motor units during maximal voluntary contractions is often referred to as muscle inhibition (MI), and is defined as the inability of the central nervous system to maximally drive a muscle during a voluntary contraction. The purpose of the present study was to assess the interrelationship amongst peak torque (PT), muscle inhibition (MI; incomplete activation of motor units), and voluntary muscle activation (VMA) of the quadriceps’ muscle group as a function of knee angle and muscle length during maximal voluntary isometric contractions (MVICs). Nine young adult males (mean + standard deviation: age: 21.58 + 1.30 years; height: 180.07 + 4.99 cm; weight: 89.07 + 7.55 kg) performed MVICs in random order with the knee at 15, 55, and 95° flexion. MI was assessed using the interpolated twitch technique and was estimated by the amount of additional knee extensor PT evoked by the superimposed twitch during MVICs. Voluntary muscle activation was estimated by root mean square amplitude electromyography (EMGrms) and mechanomyography (MMGrms) of agonist (vastus medialis [VM], vastus lateralis [VL], and rectus femoris [RF]) and antagonist (biceps femoris ([BF]) muscles during MVICs. Data were analyzed using separate repeated measures analysis of variance. Results revealed a strong dependency of quadriceps’ PT (p < 0.001), MI (p < 0.001) and MA (p < 0.01) on knee joint position: PT was smallest at the most shortened muscle position (15°) and greatest at mid-position (55°); MI and MA were smallest at the most shortened muscle position (15°) and greatest at the most lengthened position (95°), with the RF showing the greatest change in MA. It is hypothesized that the ability to more fully activate the quadriceps at short compared to longer muscle lengths (96% contracted at 15°; 91% at 55°; 90% at 95°) might partly compensate for the unfavorable force-length mechanics at the more extended position and consequent declines in VMA (decreases in EMGrms and MMGrms muscle amplitude during MVICs) and force production (PT = 111-Nm at 15°, 217-NM at 55°, 199-Nm at 95°). Biceps femoris EMG and MMG data showed no statistical differences (p = 0.11 and 0.12, respectively) at joint angles tested, although there were greater values at the extended position. Increased BF muscle amplitude at this position could be a mechanism by which anterior shear and tibial rotation induced by high quadriceps’ activity are countered. Measuring and understanding the degree to which one sees MI and VMA in the QF muscle has particular clinical relevance because different knee-joint disorders, such ligament injuries or osteoarthritis, increase levels of MI observed and markedly reduced the capability of full VMA.

Keywords: electromyography, interpolated twitch technique, mechanomyography, muscle activation, muscle inhibition

Procedia PDF Downloads 315
17 Effect of Packaging Material and Water-Based Solutions on Performance of Radio Frequency Identification for Food Packaging Applications

Authors: Amelia Frickey, Timothy (TJ) Sheridan, Angelica Rossi, Bahar Aliakbarian

Abstract:

The growth of large food supply chains demanded improved end-to-end traceability of food products, which has led to companies being increasingly interested in using smart technologies such as Radio Frequency Identification (RFID)-enabled packaging to track items. As technology is being widely used, there are several technological or economic issues that should be overcome to facilitate the adoption of this track-and-trace technology. One of the technological challenges of RFID technology is its sensitivity to different environmental form factors, including packaging materials and the content of the packaging. Although researchers have assessed the performance loss due to the proximity of water and aqueous solutions, there is still the need to further investigate the impacts of food products on the reading range of RFID tags. However, to the best of our knowledge, there are not enough studies to determine the correlation between RFID tag performance and food beverages properties. The goal of this project was to investigate the effect of the solution properties (pH and conductivity) and different packaging materials filled with food-like water-based solutions on the performance of an RFID tag. Three commercially available ultra high-frequency RFID tags were placed on three different bottles and filled with different concentrations of water-based solutions, including sodium chloride, citric acid, sucrose, and ethanol. Transparent glass, Polyethylneterephtalate (PET), and Tetrapak® were used as the packaging materials commonly used in the beverage industries. Tag readability (Theoretical Read Range, TRR) and sensitivity (Power on Tag Forward, PoF) were determined using an anechoic chamber. First, the best place to attach the tag for each packaging material was investigated using empty and water-filled bottles. Then, the bottles were filled with the food-like solutions and tested with the three different tags and the PoF and TRR at the fixed frequency of 915MHz. In parallel, the pH and conductivity of solutions were measured. The best-performing tag was then selected to test the bottles filled with wine, orange, and apple juice. Despite various solutions altering the performance of each tag, the change in tag performance had no correlation with the pH or conductivity of the solution. Additionally, packaging material played a significant role in tag performance. Each tag tested performed optimally under different conditions. This study is the first part of comprehensive research to determine the regression model for the prediction of tag performance behavior based on the packaging material and the content. More investigations, including more tags and food products, are needed to be able to develop a robust regression model. The results of this study can be used by RFID tag manufacturers to design suitable tags for specific products with similar properties.

Keywords: smart food packaging, supply chain management, food waste, radio frequency identification

Procedia PDF Downloads 91
16 A Kunitz-Type Serine Protease Inhibitor from Rock Bream, Oplegnathus fasciatus Involved in Immune Responses

Authors: S. D. N. K. Bathige, G. I. Godahewa, Navaneethaiyer Umasuthan, Jehee Lee

Abstract:

Kunitz-type serine protease inhibitors (KTIs) are identified in various organisms including animals, plants and microbes. These proteins shared single or multiple Kunitz inhibitory domains link together or associated with other types of domains. Characteristic Kunitz type domain composed of around 60 amino acid residues with six conserved cysteine residues to stabilize by three disulfide bridges. KTIs are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis and inflammation. In this study, two Kunitz-type domain containing protein was identified from rock bream database and designated as RbKunitz. The coding sequence of RbKunitz encoded for 507 amino acids with 56.2 kDa theoretical molecular mass and 5.7 isoelectric point (pI). There are several functional domains including MANEC superfamily domain, PKD superfamily domain, and LDLa domain were predicted in addition to the two characteristic Kunitz domain. Moreover, trypsin interaction sites were also identified in Kunitz domain. Homology analysis revealed that RbKunitz shared highest identity (77.6%) with Takifugu rubripes. Completely conserved 28 cysteine residues were recognized, when comparison of RbKunitz with other orthologs from different taxonomical groups. These structural evidences indicate the rigidity of RbKunitz folding structure to achieve the proper function. The phylogenetic tree was constructed using neighbor-joining method and exhibited that the KTIs from fish and non-fish has been evolved in separately. Rock bream was clustered with Takifugu rubripes. The SYBR Green qPCR was performed to quantify the RbKunitz transcripts in different tissues and challenged tissues. The mRNA transcripts of RbKunitz were detected in all tissues (muscle, spleen, head kidney, blood, heart, skin, liver, intestine, kidney and gills) analyzed and highest transcripts level was detected in gill tissues. Temporal transcription profile of RbKunitz in rock bream blood tissues was analyzed upon LPS (lipopolysaccharide), Poly I:C (Polyinosinic:polycytidylic acid) and Edwardsiella tarda challenge to understand the immune responses of this gene. Compare to the unchallenged control RbKunitz exhibited strong up-regulation at 24 h post injection (p.i.) after LPS and E. tarda injection. Comparatively robust expression of RbKunits was observed at 3 h p.i. upon Poly I:C challenge. Taken together all these data indicate that RbKunitz may involve into to immune responses upon pathogenic stress, in order to protect the rock bream.

Keywords: Kunitz-type, rock bream, immune response, serine protease inhibitor

Procedia PDF Downloads 346
15 Fish Catch Composition from Gobind Sagar Reservoir during 2006-2012

Authors: Krishan Lal, Anish Dua

Abstract:

Gobind Sagar Reservoir has been created in Himachal Pradesh, India (31° 25´ N and 76 ° 25´E) by damming River Sutlej at village Bhakra in 1963. The average water spread area of this reservoir is 10,000 hectares. Fishermen have organized themselves in the form of co-operative societies. 26 fisheries co-operative societies were working in Gobind Sagar Reservoir up till 2012. June and July months were observed as closed season, no fishing was done during this period. Proper record maintaining of fish catch was done at different levels by the state fisheries department. Different measures like minimum harvestable size, mesh size regulation and prohibition of illegal fishing etc. were taken for fish conservation. Fishermen were actively involved in the management. Gill nets were used for catching fishes from this reservoir. State fisheries department is realizing 15% royalty of the sold fish. Data used in this paper is about the fish catch during 2006-2012 and were obtained from the state fisheries department, Himachal Pradesh. Catla catla, Labeo rohita, Cirrhinus mrigala, Sperata seenghala, Cyprinus carpio, Tor putitora, Hypophthalmichthys molitrix, Labeo calbasu, Labeo dero and Ctenopharyngodon idella etc., were the fish species exploited for commercial purposes. Total number of individuals of all species caught was 3141236 weighing 5637108.9 kg during 2006-2012. H. molitrix was introduced accidently in this reservoir and was making a good share of fish catch in this reservoir. The annual catch of this species was varying between 161279.6 kg, caught in 2011 and 788030.8 kg caught in 2009. Total numbers of individuals of C. idella caught were 8966 weighing 64320.2 kg. The catch of Cyprinus carpio was varying between 144826.1 kg caught in 2006 and 214480.1 kg caught in 2010. Total catch of Tor putitora was 180263.2 kg during 2006-2012. Total catch of L. dero, S. seenghala and Catla catla remained 100637.4 kg, 75297.8 kg and 561802.9 kg, respectively, during 2006-2012. Maximum fish catch was observed during the months of August (after observing Closed Season). Maximum catch of exotic carps was from Bhakra area of the reservoir which has fewer fluctuations in water levels. The reservoir has been divided into eight beats for administrative purpose, to avoid conflicts between operating fisheries co-operative societies for area of operation. Fish catch was more by co-operative societies operating in the area of reservoir having fewer fluctuations in water level and catch was less by co-operative societies operating in the area of more fluctuations in water level. Species-wise fish catch by different co-operative societies from their allotted area was studied. This reservoir is one of most scientifically managed reservoirs.

Keywords: co-operative societies, fish catch, fish species, reservoir

Procedia PDF Downloads 171
14 Mobulid Ray Fishery Characteristics and Trends in East Java to Inform Management Decisions

Authors: Muhammad G. Salim, Betty J.L. Laglbauer, Sila K. Sari, Irianes C. Gozali, Fahmi, Didik Rudianto, Selvia Oktaviyani, Isabel Ender

Abstract:

Muncar, East Java, is one of the largest artisanal fisheries in Indonesia. Sharks and rays are caught as both target and bycatch, for local meat consumption and with some derived products exported. Of the seven mobulid ray species occurring in Indonesia, five have been recorded as retained bycatch at Muncar fishing port: the spinetail devil ray (Mobula mobular), the bentfin devil ray (Mobula thurstoni), the sicklefin devil ray (Mobula tarapacana), the oceanic manta ray (Mobula birostris) and the reef manta ray (Mobula alfredi). Both manta ray species are listed as Vulnerable by the International Union for the Conservation of Nature and are protected in Indonesia despite still being captured as bycatch, while all the three devil ray species mentioned here are listed as Endangered and do not currently benefit from any protection in Indonesian waters. Mobulid landings in East Java are caused primarily by small-scale drift gillnets but they also occasionally occur on longlines and in purse-seines operating off the coast of East Java and occasionally in fishing grounds located as far as the Makassar and Sumba Straits. Landing trends from 2015-2019 (non-continuous surveys) revealed that the highest abundance of mobulid rays at Muncar fishing port occurs during the upwelling season from June-October. During El-Nino or above-average temperature years, this may extend until November (such as in 2015 and 2019). The strong seasonal upwelling along the East Java coast is linked to higher zooplankton abundance (inferred from chlorophyll-a sea-surface concentrations), on which mobulids forage, along with teleost fishes constituting the primary target of gillnet fisheries in the Bali Strait. Mobulid ray landings in Muncar were dominated by Mobula mobular, followed by M. thurstoni, M. tarapacana, M. birostris and M. alfredi, however, the catch varied across years and seasons. A majority of immature individuals were recorded in M. mobular and M. thurstoni, and slight decreases in landings, despite no known changes in fishing effort, were observed across the upwelling seasons of 2015-2018 for M. mobular. While all mobulids are listed on Appendix II of the Convention on International Trade in Endangered Species, which regulates international trade in gill plates sought after in the Chinese Medicine Trade, local and national-level management measures are required to sustain mobulid populations. The findings presented here provide important baseline data, from which potential management approaches can be identified.

Keywords: devil ray, mobulid, manta ray, Indonesia

Procedia PDF Downloads 146
13 Testing Nitrogen and Iron Based Compounds as an Environmentally Safer Alternative to Control Broadleaf Weeds in Turf

Authors: Simran Gill, Samuel Bartels

Abstract:

Turfgrass is an important component of urban and rural lawns and landscapes. However, broadleaf weeds such as dandelions (Taraxacum officinale) and white clovers (Trifolium repens) pose major challenges to the health and aesthetics of turfgrass fields. Chemical weed control methods, such as 2,4-D weedicides, have been widely deployed; however, their safety and environmental impacts are often debated. Alternative, environmentally friendly control methods have been considered, but experimental tests for their effectiveness have been limited. This study investigates the use and effectiveness of nitrogen and iron compounds as nutrient management methods of weed control. In a two-phase experiment, the first conducted on a blend of cool season turfgrasses in plastic containers, the blend included Perennial ryegrass (Lolium perenne), Kentucky bluegrass (Poa pratensis) and Creeping red fescue (Festuca rubra) grown under controlled conditions in the greenhouse, involved the application of different combinations of nitrogen (urea and ammonium sulphate) and iron (chelated iron and iron sulphate) compounds and their combinations (urea × chelated iron, urea × iron sulphate, ammonium sulphate × chelated iron, ammonium sulphate × iron sulphate) contrasted with chemical 2, 4-D weedicide and a control (no application) treatment. There were three replicates of each of the treatments, resulting in a total of 30 treatment combinations. The parameters assessed during weekly data collection included a visual quality rating of weeds (nominal scale of 0-9), number of leaves, longest leaf span, number of weeds, chlorophyll fluorescence of grass, the visual quality rating of grass (0-9), and the weight of dried grass clippings. The results drawn from the experiment conducted over the period of 12 weeks, with three applications each at an interval of every 4 weeks, stated that the combination of ammonium sulphate and iron sulphate appeared to be most effective in halting the growth and establishment of dandelions and clovers while it also improved turf health. The second phase of the experiment, which involved the ammonium sulphate × iron sulphate, weedicide, and control treatments, was conducted outdoors on already established perennial turf with weeds under natural field conditions. After 12 weeks of observation, the results were comparable among the treatments in terms of weed control, but the ammonium sulphate × iron sulphate treatment fared much better in terms of the improved visual quality of the turf and other quality ratings. Preliminary results from these experiments thus suggest that nutrient management based on nitrogen and iron compounds could be a useful environmentally friendly alternative for controlling broadleaf weeds and improving the health and quality of turfgrass.

Keywords: broadleaf weeds, nitrogen, iron, turfgrass

Procedia PDF Downloads 37
12 A Galectin from Rock Bream Oplegnathus fasciatus: Molecular Characterization and Immunological Properties

Authors: W. S. Thulasitha, N. Umasuthan, G. I. Godahewa, Jehee Lee

Abstract:

In fish, innate immune defense is the first immune response against microbial pathogens which consists of several antimicrobial components. Galectins are one of the carbohydrate binding lectins that have the ability to identify pathogen by recognition of pathogen associated molecular patterns. Galectins play a vital role in the regulation of innate and adaptive immune responses. Rock bream Oplegnathus fasciatus is one of the most important cultured species in Korea and Japan. Considering the losses due to microbial pathogens, present study was carried out to understand the molecular and functional characteristics of a galectin in normal and pathogenic conditions, which could help to establish an understanding about immunological components of rock bream. Complete cDNA of rock bream galectin like protein B (rbGal like B) was identified from the cDNA library, and the in silico analysis was carried out using bioinformatic tools. Genomic structure was derived from the BAC library by sequencing a specific clone and using Spidey. Full length of rbGal like B (contig14775) cDNA containing 517 nucleotides was identified from the cDNA library which comprised of 435 bp in the open reading frame encoding a deduced protein composed of 145 amino acids. The molecular mass of putative protein was predicted as 16.14 kDa with an isoelectric point of 8.55. A characteristic conserved galactose binding domain was located from 12 to 145 amino acids. Genomic structure of rbGal like B consisted of 4 exons and 3 introns. Moreover, pairwise alignment showed that rock bream rbGal like B shares highest similarity (95.9 %) and identity (91 %) with Takifugu rubripes galectin related protein B like and lowest similarity (55.5 %) and identity (32.4 %) with Homo sapiens. Multiple sequence alignment demonstrated that the galectin related protein B was conserved among vertebrates. A phylogenetic analysis revealed that rbGal like B protein clustered together with other fish homologs in fish clade. It showed closer evolutionary link with Takifugu rubripes. Tissue distribution and expression patterns of rbGal like B upon immune challenges were performed using qRT-PCR assays. Among all tested tissues, level of rbGal like B expression was significantly high in gill tissue followed by kidney, intestine, heart and spleen. Upon immune challenges, it showed an up-regulated pattern of expression with Edwardsiella tarda, rock bream irido virus and poly I:C up to 6 h post injection and up to 24 h with LPS. However, In the presence of Streptococcus iniae rbGal like B showed an up and down pattern of expression with the peak at 6 - 12 h. Results from the present study revealed the phylogenetic position and role of rbGal like B in response to microbial infection in rock bream.

Keywords: galectin like protein B, immune response, Oplegnathus fasciatus, molecular characterization

Procedia PDF Downloads 327
11 Transforming Gender Norms through Play: Qualitative Findings from Primary Schools in Rwanda, Ghana, and Mozambique

Authors: Geetanjali Gill

Abstract:

International non-governmental organizations (INGOs) and development assistance donors have been implementing education projects in Sub-Saharan Africa and the global South that respond to gender-based inequities and that attempt to transform socio-cultural norms for greater gender equality in schools and communities. These efforts are in line with the United Nations Sustainable Development Goal number four, quality education, and goal number five, gender equality. Some INGOs and donors have also championed the use of play-based pedagogies for improved and more gender equal education outcomes. The study used the qualitative methods of life history interviews and focus groups to gauge social norm change amongst male and female adolescents, families, and teachers in primary schools that have been using gender-responsive play-based pedagogies in Rwanda, Ghana, and Mozambique. School administrators and project managers from the INGO Right to Play International were consulted in the selection of two primary schools per country (in both rural and urban contexts), as well as the selection of ten male and ten female students in grades four to six in each school, using specific parameters of social norm adherence. The parents (or guardians) and grandparents of four male and four female students in each school who were determined to be ‘outliers’ in their adherence to social norms were also interviewed. Additionally, sex-specific focus groups were held with thirty-six teachers. The study found that gender-responsive play-based pedagogies positively impactedsocio-cultural norms that shape gender relations amongst adolescents, their families, and teachers. Female and male students who spoke about their beliefs about gender equality in the roles and educational and career aspirations of men/boys and women/girls made linkages to the play-based pedagogies and approaches used by their teachers. Also, the parents and grandparents of these students were aware of generational differences in gender norms, and many were accepting of changed gender norms. Teachers who were effectively implementing gender-responsive play-based pedagogies in their classrooms spoke about changes to their own gender norms and how they were able to influence the gender norms of parents and community members. Life history interviews were found to be well-suited for the examination of changes to socio-cultural norms and gender relations. However, an appropriate framing of questions and topics specific to each target group was instrumental for the collection of data on socio-cultural norms and gender. The findings of this study can spur further academic inquiry of linkages between gender norms and education outcomes. The findings are also relevant for the work of INGOs and donors in the global South and for the development of gender-responsive education policies and programs.

Keywords: education, gender equality, ghana, international development, life histories, mozambique, rwanda, socio-cultural norms, sub-saharan africa, qualitative research

Procedia PDF Downloads 157
10 Prevalent Features of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017

Authors: Lei Zhou, Dan Li, Ruiqi Ren, Chao Li, Yali Wang, Daxin Ni, Zijian Feng, Timothy M. Uyeki, Qun Li

Abstract:

Since the first human infections with avian influenza A(H7N9) virus were identified in early 2013, 1533 cases of laboratory-confirmed A(H7N9) virus infections were reported and confirmed as of September 13, 2017. The fifth epidemic was defined as starting from September 1, 2016, and the number of A(H7N9) cases has surged since the end of December in 2016. On February 18, 2017, the A(H7N9) cases who were infected with highly pathogenic avian influenza (HPAI) virus was reported from Southern China. The HPAI A(H7N9) cases were identified and then an investigation and analyses were conducted to assess whether disease severity in humans has changed with HPAI A(H7N9) compared with low pathogenic avian influenza (LPAI) A(H7N9) virus infection. Methods: All confirmed cases with A(H7N9) virus infections reported throughout mainland China from September 1, 2016, to September 13, 2017, were included. Cases' information was extracted from field investigation reports and the notifiable infectious surveillance system to describe the demographic, clinical, and epidemiologic characteristics. Descriptive statistics were used to compare HPAI A(H7N9) cases with all LPAI A(H7N9) cases reported during the fifth epidemic. Results: A total of 27 cases of HPAI A(H7N9) virus were identified infection from five provinces, including Guangxi (44%), Guangdong (33%), Hunan (15%), Hebei (4%) and Shangxi (4%). The median age of cases of HPAI A(H7N9) virus infection was 60 years (range, 15 to 80) and most of them were male (59%) and lived in rural areas (78%). All 27 cases had live poultry related exposures within 10 days before their illness onset. In comparison with LPAI A(H7N9) case-patients, HPAI A(H7N9) case-patients were significantly more likely to live in rural areas (78% vs. 51%; p = 0.006), have exposure to the sick or dead poultry (56% vs. 19%; p = 0.000), and be hospitalized earlier (median 3 vs. 4 days; p = 0.007). No significant differences were observed in median age, sex, prevalence of underlying chronic medical conditions, median time from illness onset to first medical service seeking, starting antiviral treatment, and diagnosis. Although the median time from illness onset to death (9 vs. 13 days) was shorter and the overall case-fatality proportion (48% vs. 38%) was higher for HPAI A(H7N9) case-patients than for LPAI A(H7N9) case-patients, these differences were not statistically significant. Conclusions: Our findings indicate that HPAI A(H7N9) virus infection was associated with exposure to sick and dead poultry in rural areas when visited live poultry market or in the backyard. In the fifth epidemic in mainland China, HPAI A (H7N9) case-patients were hospitalized earlier than LPAI A(H7N9) case-patients. Although the difference was not statistically significant, the mortality of HPAI A (H7N9) case-patients was obviously higher than that of LPAI A(H7N9) case-patients, indicating a potential severity change of HPAI A(H7N9) virus infection.

Keywords: Avian influenza A (H7N9) virus, highly pathogenic avian influenza (HPAI), case-patients, poultry

Procedia PDF Downloads 142
9 Antifungal Activity of Processed Sulfur Solution as Potential Eco-Friendly Disinfectant against Saprolegnia parasitica and Its Safety in Freshwater-Farmed Fish

Authors: Hye-Hyun Lee, Hyo-Kon Chun, Kyung-Hee Kim Kim, Mi-Hee Kim, Saet-Byul Chu, Sang-Jong Lee, Seung-Hyeop Lee, Seung-Won Yi

Abstract:

Some chemicals such as malachite green, methylene blue, and copper sulfate had been used frequently as disinfectants controlling fungal infection in aquaculture. However, their carcinogenicity, mutagenicity and teratogenicity were reported in mammals. After their accumulation in food fish and its consumers was confirmed, concerns about public health has resulted in enhanced monitoring and increased demand for eco-friendly treatments. Therefore, this study aimed to evaluate safety to fish and efficacy of sulfur solution processed by effective microorganisms (EM-PSS) against Saprolegnia parasitica, for use of a potential aquatic fungicidal disinfectant. The natural sulfur purchased from Kawah Ijen volcano, East Java, Indonesia was processed by the liquid mixture consisting of following twelve effective microorganisms (Rapha-el®; Lbiotech, Jeonnam, Korea), Lactobacillus parafarraginis, L. paracasei, L. harbinensis, L. buchneri, L. perolens, L. rhamnosus, L. vaccinostercus, Acetobacter lovaniensis, A. peroxydans, Pichia fermentans, Candida ethanolica, Saccharomycopsis schoenii isolated from fermentation process of oriental medicinal herbs including green tea, privet, and puer tea. The material was applied to in vitro antifungal activity test for Saprolegnia parasitica using agar dilution method. In addition, an acute toxicity test was performed on carp (Cyprinus carpio), eel (Anguilla japonica), and mud fish (Misgurnus mizolepis) for 96 hours. After three species of fish (n=15) were accustomed to experimental water environment for three days, the EM-PSS was added to each tank as final concentrations to be 0 to 500 ppm. The fish were taken into necropsy, and the histological sections of the gill, liver, and spleen were counter-stained with hematoxylin and eosin (H-E). And hence, no observed effect concentration (NOEC) of the solution was used for taking a medicinal bath for mudfish infected by Saprolegnia parasitica in practice. The result of in vitro antifungal activity test showed the growth inhibition of the fungus at 100 ppm, which and the lower concentrations occurred no fatal case in any fish species tested until the end of the examination. The 125 ppm of the solution, however, resulted in 13.3 %, 13.3 %, and 6.3 % of mortality in carp, eel, and mudfish, respectively. But both 250 and 500 ppm of the solution leaded lethality to all population of each fish species within 24 hours. Besides, H-E staining also showed no specific evidence for toxicity in fish at lesser than 100 ppm of EM-PSS. On the other hand, as a result of field application of the solution, no growth of fungal mycelium was found in fish bodies from gross observation 5 days post treatment. In conclusion, 100ppm of EM-PSS resulted in inhibition and treatment of Saprolegnia parasitica infection. In addition, the use of EM-PSS lower than 100 ppm is safe for fish. Therefore, EM-PSS could be used as aquatic fungicide, and also may be possible to be a potential eco-friendly disinfectant in aquaculture.

Keywords: antifungal activity, effective microorganism, toxicity, saprolegnia, processed sulfur solution

Procedia PDF Downloads 230
8 Effective Affordable Housing Finance in Developing Economies: An Integration of Demand and Supply Solutions

Authors: Timothy Akinwande, Eddie Hui, Karien Dekker

Abstract:

Housing the urban poor remains a persistent challenge, despite evident research attention over many years. It is, therefore, pertinent to investigate affordable housing provision challenges with novel approaches. For innovative solutions to affordable housing constraints, it is apposite to thoroughly examine housing solutions vis a vis the key elements of the housing supply value chain (HSVC), which are housing finance, housing construction and land acquisition. A pragmatic analysis will examine affordable housing solutions from demand and supply perspectives to arrive at consolidated solutions from bilateral viewpoints. This study thoroughly examined informal housing finance strategies of the urban poor and diligently investigated expert opinion on affordable housing finance solutions. The research questions were: (1) What mutual grounds exist between informal housing finance solutions of the urban poor and housing expert solutions to affordable housing finance constraints in developing economies? (2) What are effective approaches to affordable housing finance in developing economies from an integrated demand - supply perspective? Semi-structured interviews were conducted in the 5 largest slums of Lagos, Nigeria, with 40 informal settlers for demand-oriented solutions, while focus group discussion and in-depth interviews were conducted with 12 housing experts in Nigeria for supply-oriented solutions. Following a rigorous thematic, content and descriptive analyses of data using NVivo and Excel, findings ascertained mutual solutions from both demand and supply standpoints that can be consolidated into more effective affordable housing finance solutions in Nigeria. Deliberate finance models that recognise and include the finance realities of the urban poor was found to be the most significant supply-side housing finance solution, representing 25.4% of total expert responses. Findings also show that 100% of sampled urban poor engage in vocations where they earn little irregular income or zero income, limiting their housing finance capacities and creditworthiness. Survey revealed that the urban poor are involved in community savings and employ microfinance institutions within the informal settlements to tackle their housing finance predicaments. These are informal finance models of the urban poor, revealing common grounds between demand and supply solutions for affordable housing financing. Effective, affordable housing approach will be to modify, institutionalise and incorporate the informal finance strategies of the urban poor into deliberate government policies. This consolidation of solutions from demand and supply perspectives can eliminate the persistent misalliance between affordable housing demand and affordable housing supply. This study provides insights into mutual housing solutions from demand and supply perspectives, and findings are informative for effective, affordable housing provision approaches in developing countries. This study is novel in consolidating affordable housing solutions from demand and supply viewpoints, especially in relation to housing finance as a key component of HSVC. The framework for effective, affordable housing finance in developing economies from a consolidated viewpoint generated in this study is significant for the achievement of sustainable development goals, especially goal 11 for sustainable, resilient and inclusive cities. Findings are vital for future housing studies.

Keywords: affordable housing, affordable housing finance, developing economies, effective affordable housing, housing policy, urban poor, sustainable development goal, sustainable affordable housing

Procedia PDF Downloads 42
7 A Second Chance to Live and Move: Lumbosacral Spinal Cord Ischemia-Infarction after Cardiac Arrest and the Artery of Adamkiewicz

Authors: Anna Demian, Levi Howard, L. Ng, Leslie Simon, Mark Dragon, A. Desai, Timothy Devlantes, W. David Freeman

Abstract:

Introduction: Out-of-hospital cardiac arrest (OHCA) can carry a high mortality. For survivors, the most common complication is hypoxic-ischemic brain injury (HIBI). Rarely, lumbosacral spinal cord and/or other spinal cord artery ischemia can occur due to anatomic variation and variable mean arterial pressure after the return of spontaneous circulation. We present a case of an OHCA survivor who later woke up with bilateral leg weakness with preserved sensation (ASIA grade B, L2 level). Methods: We describe a clinical, radiographic, and laboratory presentation, as well as a National Library of Medicine (NLM) search engine methodology, characterizing incidence/prevalence of this entity is discussed. A 70-year-old male, a longtime smoker, and alcohol user, suddenly collapsed at a bar surrounded by friends. He had complained of chest pain before collapsing. 911 was called. EMS arrived, and the patient was in pulseless electrical activity (PEA), cardiopulmonary resuscitation (CPR) was initiated, and the patient was intubated, and a LUCAS device was applied for continuous, high-quality CPR in the field by EMS. In the ED, central lines were placed, and thrombolysis was administered for a suspected Pulmonary Embolism (PE). It was a prolonged code that lasted 90 minutes. The code continued with the eventual return of spontaneous circulation. The patient was placed on an epinephrine and norepinephrine drip to maintain blood pressure. ECHO was performed and showed a “D-shaped” ventricle worrisome for PE as well as an ejection fraction around 30%. A CT with PE protocol was performed and confirmed bilateral PE. Results: The patient woke up 24 hours later, following commands, and was extubated. He was found paraplegic below L2 with preserved sensation, with hypotonia and areflexia consistent with “spinal shock” or anterior spinal cord syndrome. MRI thoracic and lumbar spine showed a conus medullaris level spinal cord infarction. The patient was given IV steroids upon initial discovery of cord infarct. NLM search using “cardiac arrest” and “spinal cord infarction” revealed 57 results, with only 8 review articles. Risk factors include age, atherosclerotic disease, and intraaortic balloon pump placement. AoA (Artery of Adamkiewicz) anatomic variation along with existing atherosclerotic factors and low perfusion were also known risk factors. Conclusion: Acute paraplegia from anterior spinal cord infarction of the AoA territory after cardiac arrest is rare. Larger prospective, multicenter trials are needed to examine potential interventions of hypothermia, lumbar drains, which are sometimes used in aortic surgery to reduce ischemia and/or other neuroprotectants.

Keywords: cardiac arrest, spinal cord infarction, artery of Adamkiewicz, paraplegia

Procedia PDF Downloads 169
6 The Increasing Trend in Research Among Orthopedic Residency Applicants is Significant to Matching: A Retrospective Analysis

Authors: Nickolas A. Stewart, Donald C. Hefelfinger, Garrett V. Brittain, Timothy C. Frommeyer, Adrienne Stolfi

Abstract:

Orthopedic surgery is currently considered one of the most competitive specialties that medical students can apply to for residency training. As evidenced by increasing United States Medical Licensing Examination (USMLE) scores, overall grades, and publication, presentation, and abstract numbers, this specialty is getting increasingly competitive. The recent change of USMLE Step 1 scores to pass/fail has resulted in additional challenges for medical students planning to apply for orthopedic residency. Until now, these scores have been a tool used by residency programs to screen applicants as an initial factor to determine the strength of their application. With USMLE STEP 1 converting to a pass/fail grading criterion, the question remains as to what will take its place on the ERAS application. The primary objective of this study is to determine the trends in the number of research projects, abstracts, presentations, and publications among orthopedic residency applicants. Secondly, this study seeks to determine if there is a relationship between the number of research projects, abstracts, presentations, and publications, and match rates. The researchers utilized the National Resident Matching Program's Charting Outcomes in the Match between 2007 and 2022 to identify mean publications and research project numbers by allopathic and osteopathic US orthopedic surgery senior applicants. A paired t test was performed between the mean number of publications and research projects by matched and unmatched applicants. Additionally, simple linear regressions within matched and unmatched applicants were used to determine the association between year and number of abstracts, presentations, and publications, and a number of research projects. For determining whether the increase in the number of abstracts, presentations, and publications, and a number of research projects is significantly different between matched and unmatched applicants, an analysis of covariance is used with an interaction term added to the model, which represents the test for the difference between the slopes of each group. The data shows that from 2007 to 2022, the average number of research publications increased from 3 to 16.5 for matched orthopedic surgery applicants. The paired t-test had a significant p-value of 0.006 for the number of research publications between matched and unmatched applicants. In conclusion, the average number of publications for orthopedic surgery applicants has significantly increased for matched and unmatched applicants from 2007 to 2022. Moreover, this increase has accelerated in recent years, as evidenced by an increase of only 1.5 publications from 2007 to 2001 versus 5.0 publications from 2018 to 2022. The number of abstracts, presentations, and publications is a significant factor regarding an applicant's likelihood to successfully match into an orthopedic residency program. With USMLE Step 1 being converted to pass/fail, the researchers expect students and program directors will place increased importance on additional factors that can help them stand out. This study demonstrates that research will be a primary component in stratifying future orthopedic surgery applicants. In addition, this suggests the average number of research publications will continue to accelerate. Further study is required to determine whether this growth is sustainable.

Keywords: publications, orthopedic surgery, research, residency applications

Procedia PDF Downloads 109
5 Strengthening Facility-Based Systems to Improve Access to In-Patient Care for Sick Newborns in Brong Ahafo Region, Ghana

Authors: Paulina Clara Appiah, Kofi Issah, Timothy Letsa, Kennedy Nartey, Amanua Chinbuah, Adoma Dwomo-Fokuo, Jacqeline G. Asibey

Abstract:

Background: The Every Newborn Action Plan provides evidence–based interventions to end preventable deaths in high burden countries. Brong Ahafo Region is one of ten regions in Ghana with less than half of its district hospitals having sick newborn units. Facility-based neonatal care is not prioritized and under-funded, and there is also inadequate knowledge and competence to manage the sick. The aim of this intervention was to make available in–patient care for sick newborns in all 19 district hospitals through the strengthening of facility-based systems. Methods: With the development and dissemination of the National Newborn Strategy and Action Plan 2014-2018, the country was able to attract PATH which provided the region with basic resuscitation equipment, supported hospital providers’ capacity building in Helping Babies Breathe, Essential Care of Every Baby, Infection Prevention and Management and held a symposia on managing the sick newborn. Newborn advocacy was promoted through newborn champions at the facility and community levels. Hospital management was then able to mobilize resources from communities, corporate organizations and from internally generated funds; created or expanded sick newborn care units and provided essential medicines and equipment. Kangaroo Mother Care was initiated in 6 hospitals. Pediatric specialist outreach services initiated comprised telephone consultations, teaching ward rounds and participating in perinatal death audits meetings. Newborn data capture and management was improved through the provision and training on the use of standard registers provided from the national level. Results: From February 2015 to November 2017, hospitals with sick newborn units increased from 7 to 19 (37%-100%). 180 pieces each of newborn ventilation bags and masks size 0, 1 and penguin suction bulbs were distributed to the hospitals, in addition to 20 newborn mannequin sets and 90 small clinical reminder posters. 802 providers (96.9%) were trained in resuscitation, of which 96% were successfully followed up in 6 weeks, 91% in 6 months and 80% in 12 months post-training. 53 clinicians (65%) were trained and mentored to manage sick newborns. 56 specialist teaching ward rounds were conducted. Data completeness improved from 92.6% - 99.9%. Availability of essential medicines improved from 11% to 100%. Number of hospital cots increased from 116 to 248 (214%). Cot occupancy rate increased from 57.4% to 92.5%. Hospitals with phototherapy equipment increased from 0 to 12 (63%). Hospitals with incubators increased from 1 to 12 (5%-63%). Newborn deaths among admissions reduced from 6.3% to 5.4%. Conclusion: Access to in-patient care increased significantly. Newborn advocacy successfully mobilized resources required for strengthening facility –based systems.

Keywords: facility-based systems, Ghana, in-patient care, newborn advocacy

Procedia PDF Downloads 201
4 An Architecture of Ingenuity and Empowerment

Authors: Timothy Gray

Abstract:

This paper will present work and discuss lessons learned during a semester-long travel study based in Southeast Asia, which was run in the Spring Semester of 2019 and again in the summer of 2023. The first travel group consisted of fifteen students, and the second group consisted of twelve students ranging from second-year to graduate level, student participants majoring in either architecture or planning. Students worked in interdisciplinary teams, each team beginning their travel study, living together in a separate small town for over a month in (relatively) remote conditions in rural Thailand. Students became intimately familiar with these towns, forged strong personal relationships, and built reservoirs of knowledge one conversation at a time. Rather than impose external ideas and solutions, students were asked to learn from and be open to lessons from the people and the place. The following design statement was used as a point of departure for their investigations: It is our shared premise that architecture exists in small villages and towns of Southeast Asia in the ingenuity of the people, that architecture exists in a shared language of making, modifying, and reusing. It is a modest but vibrant architecture, an architecture that is alive and evolving, an architecture that is small in scale, accessible, and one that emerges from the people. It is an architecture that can exist in a modified bicycle, a woven bamboo bridge, or a self-built community. Students were challenged to engage in existing conditions as design professionals, both empowering and lending coherence to the energies that already existed in the place. As one of the student teams noted in their design narrative: “During our field study, we had the unique opportunity to tour a number of informal settlements and meet and talk to residents through interpreters. We found that many of the residents work in nearby factories for dollars a day. Others find employment in self-generated informal economies such as hand carving and textiles. Despite extreme poverty, we found these places to be vibrant and full of life as people navigate these challenging conditions to live lives with purpose and dignity.” Students worked together with local community members and colleagues to develop a series of varied proposals that emerged from their interrogations of place and partnered with community members and professional colleagues in the development of these proposals. Project partners included faculty and student colleagues Yangon University, the mayor's Office, Planning Department Officials and religious leaders in Sawankhalok, Thailand, and community leaders in Natonchan, Thailand, to name a few. This paper will present a series of student community-based design projects that emerged from these conditions. The paper will also discuss this model of travel study as a way of building an architecture which uses social and cultural issues as a catalyst for design. The paper will discuss lessons relative to sustainable development that the Western students learned through their travels in Southeast Asia.

Keywords: travel study, CAPasia, architecture of empowerment, modular housing

Procedia PDF Downloads 24
3 Implementing Urban Rainwater Harvesting Systems: Between Policy and Practice

Authors: Natàlia Garcia Soler, Timothy Moss

Abstract:

Despite the multiple benefits of sustainable urban drainage, as demonstrated in numerous case studies across the world, urban rainwater harvesting techniques are generally restricted to isolated model projects. The leap from niche to mainstream has, in most cities, proved an elusive goal. Why policies promoting rainwater harvesting are limited in their widespread implementation has seldom been subjected to systematic analysis. Much of the literature on the policy, planning and institutional contexts of these techniques focus either on their potential benefits or on project design, but very rarely on a critical-constructive analysis of past experiences of implementation. Moreover, the vast majority of these contributions are restricted to single-case studies. There is a dearth of knowledge with respect to, firstly, policy implementation processes and, secondly, multi-case analysis. Insights from both, the authors argue, are essential to inform more effective rainwater harvesting in cities in the future. This paper presents preliminary findings from a research project on rainwater harvesting in cities from a social science perspective that is funded by the Swedish Research Foundation (Formas). This project – UrbanRain – is examining the challenges and opportunities of mainstreaming rainwater harvesting in three European cities. The paper addresses two research questions: firstly, what lessons can be learned on suitable policy incentives and planning instruments for rainwater harvesting from a meta-analysis of the relevant international literature and, secondly, how far these lessons are reflected in a study of past and ongoing rainwater harvesting projects in a European forerunner city. This two-tier approach frames the structure of the paper. We present, first, the results of the literature analysis on policy and planning issues of urban rainwater harvesting. Here, we analyze quantitatively and qualitatively the literature of the past 15 years on this topic in terms of thematic focus, issues addressed and key findings and draw conclusions on research gaps, highlighting the need for more studies on implementation factors, actor interests, institutional adaptation and multi-level governance. In a second step we focus in on the experiences of rainwater harvesting in Berlin and present the results of a mapping exercise on a wide variety of projects implemented there over the last 30 years. Here, we develop a typology to characterize the rainwater harvesting projects in terms of policy issues (what problems and goals are targeted), project design (which kind of solutions are envisaged), project implementation (how and when they were implemented), location (whether they are in new or existing urban developments) and actors (which stakeholders are involved and how), paying particular attention to the shifting institutional framework in Berlin. Mapping and categorizing these projects is based on a combination of document analysis and expert interviews. The paper concludes by synthesizing the findings, identifying how far the goals, governance structures and instruments applied in the Berlin projects studied reflect the findings emerging from the meta-analysis of the international literature on policy and planning issues of rainwater harvesting and what implications these findings have for mainstreaming such techniques in future practice.

Keywords: institutional framework, planning, policy, project implementation, urban rainwater management

Procedia PDF Downloads 263
2 Implications of Agricultural Subsidies Since Green Revolution: A Case Study of Indian Punjab

Authors: Kriti Jain, Sucha Singh Gill

Abstract:

Subsidies have been a major part of agricultural policies around the world, and more extensively since the green revolution in developing countries, for the sake of attaining higher agricultural productivity and achieving food security. But entrenched subsidies lead to distorted incentives and promote inefficiencies in the agricultural sector, threatening the viability of these very subsidies and sustainability of the agricultural production systems, posing a threat to the livelihood of farmers and laborers dependent on it. This paper analyzes the economic and ecological sustainability implications of prolonged input and output subsidies in agriculture by studying the case of Indian Punjab, an agriculturally developed state responsible for ensuring food security in the country when it was facing a major food crisis. The paper focuses specifically on the environmentally unsustainable cropping pattern changes as a result of Minimum Support Price (MSP) and assured procurement and on the resource use efficiency and cost implications of power subsidy for irrigation in Punjab. The study is based on an analysis of both secondary and primary data sources. Using secondary data, a time series analysis was done to capture the changes in Punjab’s cropping pattern, water table depth, fertilizer consumption, and electrification of agriculture. This has been done to examine the role of price and output support adopted to encourage the adoption of green revolution technology in changing the cropping structure of the state, resulting in increased input use intensities (especially groundwater and fertilizers), which harms the ecological balance and decreases factor productivity. Evaluation of electrification of Punjab agriculture helped evaluate the trend in electricity productivity of agriculture and how free power imposed further pressure on the extant agricultural ecosystem. Using data collected from a primary survey of 320 farmers in Punjab, the extent of wasteful application of groundwater irrigation, water productivity of output, electricity usage, and cost of irrigation driven electricity subsidy to the exchequer were estimated for the dominant cropping pattern amongst farmers. The main findings of the study revealed how because of a subsidy has driven agricultural framework, Punjab has lost area under agro climatically suitable and staple crops and moved towards a paddy-wheat cropping system, that is gnawing away the state’s natural resources like water table has been declining at a significant rate of 25 cms per year since 1975-76, and excessive and imbalanced fertilizer usage has led to declining soil fertility in the state. With electricity-driven tubewells as the major source of irrigation within a regime of free electricity and water-intensive crop cultivation, there is both wasteful application of irrigation water and electricity in the cultivation of paddy crops, burning an unproductive hole in the exchequer’s pocket. There is limited access to both agricultural extension services and water-conserving technology, along with policy imbalance, keeping farmers in an intensive and unsustainable production system. Punjab agriculture is witnessing diminishing returns to factor, which under the business-as-usual scenario, will soon enter the phase of negative returns to factor.

Keywords: cropping pattern, electrification, subsidy, sustainability

Procedia PDF Downloads 157
1 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

Procedia PDF Downloads 157