• Compaction analysis and optimisation of convex-faced pharmaceutical tablets using numerical techniques

      Baroutaji, Ahmad; Lenihan, Sandra; Bryan, Keith (Elsevier, 2019-12-31)
      Capping failure, edge chipping, and non-uniform mechanical properties of convexfaced pharmaceutical tablets are common problems in pharma industry. In this paper, Finite Element Modelling (FEM) and Design of Experiment (DoE) techniques are adopted to find the optimal shape of convex-faced (CF) pharmaceutical tablet which has more uniform mechanical properties and less capping and chipping tendency. The effects of the geometrical parameters and friction on the compaction responses of convex-faced pharmaceutical tablets were first identified and analysed. The finite element model of the tabletting process was generated using the implicit code (ABAQUS) and validated against experimental measurements. Response Surface Methodology (RSM) was employed to establish the relationship between the design variables, represented by the geometrical parameters and the friction coefficient, and compaction responses of interest including residual die pressure, the variation of relative density within the tablet, and the relative shear stress of the edge of the tablet. A statistical-based optimisation approach is then employed to undertake shape optimisation of CF tablets. The obtained results demonstrated how the geometrical parameters of CF tablet and the friction coefficient have significant effects on the compaction behaviour and quality of the pharmaceutical tablet.
    • Long-term follow-up of intratympanic methylprednisolone versus gentamicin in patients with unilateral Menière’s disease

      Harcourt, Jonny P.; Lambert, Aileen; Wong, Phui Yee; Patel, Mitesh; Agarwal, Kiran; Golding, John F.; Bronstein, Adolfo M. (Lippincott Williams & Wilkins, 2019-12-31)
      Objectives: To determine whether long term (>48 months) symptomatic vertigo control is sustained in patients with Menière’s disease from a previous comparative trial of intratympanic methylprednisolone versus gentamicin, and if the two treatments remain nonsignificantly different at longterm follow-up. Study Design: Mail survey recording vertigo frequency in the previous one and six months, further intratympanic treatment received, and validated symptom questionnaires. Setting: Outpatient hospital clinic setting. Patients: Adult patients with definite unilateral refractory Menie`re’s disease, who previously received in tratympanic treatment in a comparative trial. Intervention: A survey of trial participants who received intratympanic gentamicin (40 mg/mL) or methylprednisolone (62.5 mg/mL). Outcome measures: Primary: number of vertigo attacks in the 6 months prior to receiving this survey compared with the 6 months before the first trial injection. Secondary: : Number of vertigo attacks over the previous 1 month; validated symptom questionnaire scores of tinnitus, dizziness, vertigo, aural fullness, and functional disability. Results: Average follow-up was 70.8 months (standard deviation 17.0) from the first treatment injection. Vertigo attacks in the 6 months prior to receiving the current survey reduced by 95% compared to baseline in both drug groups (intention-to-treat analysis, both p<0.001). No significant difference between drugs was found for the primary and secondary outcomes. Eight participants (methylprednisolone ¼ 5 and gentamicin ¼ 3) required further injections for relapse after completing the original trial. Conclusion: Intratympanic methylprednisolone treatment provides effective long-lasting relief of vertigo, without the known inner-ear toxicity associated with gentamicin. There are no significant differences between the two treatments at long term follow-up.
    • Cariprazine: pharmacology and clinical management of psychiatric disorders

      Antoun Reyad, Ayman; Mishriky, Raafat (Healio, 2019-12-31)
      Cariprazine is a new atypical antipsychotic for schizophrenia and bipolar disorders 2 management. In this article, the role of cariprazine, a partial D2 and D3 receptors 3 agonist with a higher D3 affinity, in the management of psychiatric conditions is 4 illustrated. Cariprazine caused significant improvements in psychiatric scales such 5 as Positive and Negative Syndrome scale (PANSS), clinical global impressions 6 (CGI) and young mania rating scales (YMRS) and was associated with side effects 7 such as akathisia, restlessness and insomnia. These findings will guide psychiatrists 8 and pharmacists in their clinical role for supporting psychiatric patients care.
    • Characterizing the Cell Surface Properties of Hydrocarbon-Degrading Bacterial Strains, a Case Study

      Pouran, Hamid (Springer, 2019-03-29)
      This chapter describes some of the most common methods used to characterize the cell surface properties of the bacterial cells. As a case study, the focus of this chapter is on Sphingomonas spp., Sph2, which is a Gram negative and hydrophilic bacterial strain. The species used in this research was isolated from groundwater at a phenol-contaminated site. This hydrocarbon-degrading strain that can participate in bioremediation of polluted environments belongs to Sphingomonadaceae family. This group of bacteria is unique among Gram-negative cells because of having glycosphingolipids (GSL) instead of the lipopolysaccharide (LPS) layer in their cell wall. To characterize this strain, its surface properties were examined using potentiometric titration, modelling surface protonation sites using ProtoFit, zeta potential measurements, and attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. There is no published detailed study about cell wall characteristics of Sph2 yet, and this research reports such information for the first time. In addition, to investigate effects of the solution ionic strength on Sph2 adhesion behavior on metal oxides, its biofilm formation on hematite, as the model mineral, was evaluated in three different ionic strengths; ≈200 mM, 100 mM, and 20 mM. The ATR-FTIR analysis showed that despite the unique cell wall chemistry of Sph2 among the Gram-negative strains, its surface functional groups are similar to other bacterial species. Hydroxyl, carboxyl, phosphoryl, and amide groups were detected in Sph2 infrared spectra. The potentiometric titration results showed that Sph2 PZC is approximately 4.3. Optimizing the titration data based on ProtoFit non-electrostatic model (NEM) provided compatible results to the infrared spectroscopy analysis and four pKa values were identified; 3.9 ± 0.3, 5.9 ± 0.2, 8.9 ± 0.0, and 10.2 ± 0.1, which could be assigned to carboxyl, phosphate, amine, and hydroxyl groups, respectively. Zeta potential measurements demonstrated that changing the ionic strength from ≈200 mM to ≈20 mM shifts the zeta potential by ≈−20 mV. Direct observation showed that this alteration in the ionic strength coincides with a tenfold increase in the number of Sph2 attached cells to the hematite surface. This could be attributed to both electrostatic interactions between the cell and surface, and conformational changes of Sph2 surface biopolymers. In addition to reporting Sph2 cell wall characterization results for the first time, this study highlights importance of ionic strength in the cell adhesion to the mineral surfaces, which directly influence biofilm formation, bioremediation, and bacterial transport in aqueous systems.
    • Engineered Nanomaterials in the Environment, their Potential Fate and Behaviour and Emerging Techniques to Measure Them

      Pouran, Hamid (Springer, 2019-03-29)
      “There is plenty of room at the bottom” – this was title of Richard Feynman’s famous talk to the American Physical Society more than half a century ago. The Nobel Laureate, in his historic lecture, discussed the possibility of the direct manipulation of materials on the atomic and molecular level to unleash novel functions. Now, after decades of research, nanoscience faces a historic moment: moving from fundamental research towards a publically available technology, a turning point towards commercialization.
    • Bacterial Cell-Mineral Interface, Its Impacts on Biofilm Formation and Bioremediation

      Pouran, Hamid (Springer, 2019-03-29)
      This chapter aims to provide a better understanding of the bacterial cell attachment and biofilm formation on the mineral surfaces, which would result in improving our knowledge about: the interfacial forces governing the bacterial cell attachment, predicting trends of the biofilm formation and consequently biodegradation rates, and the contaminant’s fate in the diverse geological media (Pouran HM. Studying molecular and nanoscale interactions at metal oxide surfaces and their effects on bacterial adhesion, 2009). In both aqueous and terrestrial environments, bacterial cells tend to be attached to a surface and form biofilm. If they are associated to, e.g., a mineral surface, bacterial cells would remain in a more stable microenvironment instead of being removed by the water shear stress. Even the bacterial planktonic phase can be considered as a mechanism for translocation from one surface to the other rather than a prime lifestyle (Watnick and Kolter 2000; Young 2006). The biofilm formation, which completely covers the surface, initially begins by the adhesion of a small quantity of cells (Vadillo-rodri et al. 2006; Pouran et al. 2017). Among the different indigenous microbial species in the contaminated environments, some are capable of degrading pollutants and participating in the environmental remediation process. The bioremediation process of the contaminated soils and waters is often considered a promising low risk management tool. Even when the contamination poses an imminent threat and other approaches are essential, bioremediation often is a viable secondary strategy for the site maintenance (Haws et al. 2006; Pouran et al. 2017). Natural environments are dynamic and complex systems; therefore, characterization and identifying the underlying processes governing the contaminant’s fate are not easy. Examples of the natural environments heterogeneity are the diverse physicochemical properties of the soils and aquifers matrices (Stumm and Morgan 1996). As the soils and sediments are the prime surfaces for the bacterial cell attachment in most natural environments, elucidation of the surface properties of these constituents and their role in initiating cell adhesion and biofilm formation are of the key importance in understanding the bioremediation process. In fact, the cell-mineral interface reactions not only influence the biodegradation process but many natural phenomena are affected by them. Understanding role of physicochemical interactions at the bacterial cells and minerals interface in the cell adhesion (as well as biofilm formation, development, and behavior) is essential for planning effective bioremediation techniques. It could potentially help us to predict the contaminants’ fate, and trends of the biodegradation rates in different environments. Consequently, the improved knowledge of the cell-mineral interface enable us to design and apply more sophisticated bioremediation techniques as a viable approach towards tackling the soil and water environmental pollution problems. Figure 1 schematically represents an aquifer and biofilm formation on some of the most abundant minerals in the environment, iron and aluminum oxides. It also indicates some the major effects of cell-mineral interface interactions on different environmental processes (Stumm and Morgan 1996; Zachara and Fredrickson 2004; Cornell and Schwertmann 2003).
    • Species

      Kaburu, Stefano S. K (Springer, 2019-02-08)
    • Sex differences in scent-marking in captive red-ruffed lemurs

      Janda, Ellese D.; Perry, Kate L.; Hankinson, Emma; Walker, David; Vaglio, Stefano (Wiley, 2019-01-21)
      Primate chemical communication remains underappreciated, as primates are considered to rely on other sensory modalities. However, various lines of evidence suggest that olfaction plays an important role in primate societies, including the conspicuous scent-marking behavior of many strepsirrhines and callitrichines. Although lemurs typically show scent-marking, little is known about this behavior in red-ruffed lemurs (Varecia variegata rubra). We combined behavioral observations and semiochemistry analyses to improve our understanding of scent-marking in two captive troops housed at Dudley and Twycross zoos(UK). We collected olfactory behavioral observations by focusing on two family troops (N=7) for 132hr. We investigated the volatile compounds of ano-genital scent-marks using solid-phase microextraction and gas chromatography-mass spectrometry and compared volatile chemical profiles with features of the signaller. Males scent-marked most frequently and predominantly in specific meaningful areas of the enclosure, while within females the occurrence of scent-marking was related to their age. We found behavioral sexual dimorphism, with male predominantly depositing secretions via neck and mandible glands and females via ano-genital glands. We identified a total of 32 volatile components of ano-genital gland secretion, including compounds that have already been found in other mammals as sex pheromones and cues to fitness, in ano-genital scent-marks spontaneously left on filter paper by adult females. Our findings suggest that red-ruffed lemurs might use scent-marking to convey information about sex and female age, with male neck marking behavior playing defensive territorial functions and ano-genital marking related to socio-sexual communication.
    • Endemic, endangered, and evolutionarily significant: Cryptic lineages in Seychelles’ frogs (Anura: Sooglossidae)

      Labisko, Jim; Griffiths, Richard A.; Chong-Seng, Lindsay; Bunbury, Nancy; Maddock, Simon T; Bradfield, Kay S.; Taylor, Michelle L. (Oxford University Press, 2019-01-12)
      Cryptic diversity corresponding with island of origin has been previously reported in the endemic, geographically restricted sooglossid frogs of the Seychelles archipelago. The evolutionary pattern behind this has not been fully explored, and given current amphibian declines and the increased extinction risk faced by island species, we sought to identify evolutionarily significant units (ESUs) to address conservation concerns for these highly threatened anurans. We obtained genetic data for two mitochondrial (mtDNA) and four nuclear (nuDNA) genes from all known populations of sooglossid frog (on the islands of Mahé, Praslin and Silhouette) for phylogenetic analyses and to construct nuDNA haplotype networks. Bayesian and maximum likelihood analyses of mtDNA support the monophyly and molecular differentiation of populations in all species that occur on multiple islands. Haplotype networks using statistical parsimony revealed multiple high-frequency haplotypes shared between islands and taxa, in addition to numerous geographically distinct (island-specific) haplotypes for each species. We consider each island-specific population of sooglossid frog as an ESU and advise conservation managers to do likewise. Furthermore, our results identify each island lineage as a candidate species, evidence for which is supported by analyses of mtDNA based on Bayesian Poisson tree processes, and independent analyses of mtDNA and nuDNA using the multispecies coalescent. Our findings add to the growing understanding of the biogeography and hidden diversity within this globally important region.
    • Developments of policies related to smart cities: a critical review

      Keshvardoost, Sina; Renukappa, Suresh; Suresh, Subashini (IEEE, 2019-01-10)
      In recent years, the idea of smart sustainable cities has come to the fore. Furthermore, it is quickly gaining momentum, and worldwide attention as a promising response to the challenge of urban sustainability. This pertains especially to ecologically and technologically advanced nations. This paper provides a comprehensive overview of smart (and) sustainable cities in terms of their underlying foundations, assumptions, state– of–the art research development, policies, and future planning practices. As to the design strategy, the paper reviews existing sustainable city models and smart city approaches. Their strengths and weaknesses are examined by focusing on the degree to which cities to the objectives and whether the latter incorporate these goals. To distinguish the related challenges, these models and adopt methodologies are assessed and contrasted against each other in line with the notion of sustainability. The gaps in the exploration inside the field of smart sustainable cities are recognized as in accordance with the research being proposed. Subsequently, a coordinated approach is proposed in view of an applied theoretical perspective to align the existing problems and solutions identified for future practices in the area of smart, sustainable urban planning and smart cities policy development. With regard to knowledge contribution, the paper demonstrates Policy developments related to smart cities in general and particular problems within the policy development, as well as considering the commitment to the application of the policy. Also, diverse country’s approach on policies for smart cities and their policy related to Governance It also reveals that numerous research opportunities are available and can be realized within the realm of smart sustainable cities.
    • Athena SWAN in Higher Education Sector - a Built Environment Perspective

      Suresh, Subashini; Abdul-Aziz, Abdul-Rashid; Renukappa, Suresh (University of Wolverhampton, 2018-12-19)
      Higher education tends to recognise gender equality in terms of representation, progression and success for students and staff. Athena SWAN is a Charter which addresses gender equality. This paper is based on critical review of literature and secondary data analysis. A thorough literature review explores the best practices adopted by Universities in UK who were awarded Gold, Silver and Bronze. In doing so, 39 Universities were identified from the CHOBE members (Council of Heads of the Built Environment Heads of Department of Construction, Property and Surveying) in the year 2017 who have built environment students and staff. The results revealed that none of the Universities had gold award of Athena SWAN whereas 26 Universities had bronze awards. From the secondary data analysis of three years data from Equality in higher education, statistical reports on student and staff shows areas of concern for built environment where the female percent of student and staff are in the lower end of the spectrum. Therefore, initiatives and lessons learnt from other successful awarded Universities will be discussed in this paper so that awareness and adoption of the best practices by the built environment sector is encouraged.
    • Are young adults encouraged to join the construction industry?

      Stride, Mark; Chung, Sammy; Subashini, Suresh (University of Wolverhampton, 2018-12-19)
      The construction industry is currently suffering from a lack of skilled workers, from builders and plumbers, to quantity surveyors and architects. Reasons for this include the recession and that the retiring workforce is not being replaced by younger generations. This is having a huge impact on the country’s ability to keep up with the demand for houses that need building; consequently meaning there is a shortage in homes in the country also. The research question addressed in the paper is: What can be done to encourage young adults (14-16 years old) to join the construction industry? The research question is answered through a critical literature review and analysis of questionnaire responses. The results show that there is little education on the construction industry to encourage young adults, and that it is perceived to be a dirty and low status industry to work in. On this basis, it is recommended that the Government and professional bodies need to do more to educate children in schools on what the construction industry truly is, and what opportunities it has for a good career. An initiative that was introduced in 2017 was the apprenticeship levy, which persuades companies to employ apprentices and up skill current employees subsequently encouraging school children to move directly into the construction industry. By schools, universities, colleges and businesses supporting each other it allows longevity and sustainability of the construction industry to be strengthened.
    • The adoption of big data concepts for sustainable practices implementation in the construction industry

      Reyes, Paola; Suresh, Subashini; Renukappa, Suresh (IEEE, 2018-12-17)
      The global construction business is on a point of a paradigm shift. The exponential growth of digital technologies, the increasing impacts of climate change, impending Brexit and looming social and environmental pressures are driving change to the construction industry. Increasingly policies press for the adoption of sustainability and construction organisations are realising that small sustainable impacts are no longer enough. Therefore, measurement is one of the keys to the implementation of sustainable construction strategies. Advances in data gathering, computing power and connectivity mean that construction organisations have more information and data than ever before. Collecting, analysing and understanding those large volumes of available data, known as Big Data, about how an organisation operates sustainably leads to knowledge that can improve decision making, refine goals and focus efforts. However, when it comes to sustainability the great thing about big data is that it is unlocking the ability of businesses to understand and act on what is typically their biggest sustainable (i.e. economic, social and environmental) impacts - the ones outside their control. Measuring and understanding how doing business really does affect the natural world will open new opportunities for bringing sustainability inside an organisation: creating change, cutting costs and boosting long-term profitability in a resource-constrained world. Still, there are issues and challenges around gathering sustainability-related data, as well as in analysing and interpreting of data points. Therefore, the aim of this research is to explore the barriers to adopting big data related to sustainable strategies. The relationship between Policy Making, Big Data and sustainability is still in early stages, but already several applications can be mention to the environment, health and construction, such as biodiversity loss monitoring, pollution zones Identification, endangered species location, smart energy management, cost reduction or investment assessment. In the same way, barriers and opportunities were identified, for instance: the lack of financial resources and business case, skills and training, unequal opportunity and security and disclosure issues among the barriers, and partnership, emerging and accessible technology, personalization of the environment among the opportunities. Finally, the biggest challenge presented by the implementation of Big Data is concept standardization, since there are many areas in which one way or another is making use of this technology without being recognized as such. In the same way, the greatest asset that represents the use of Big Data for sustainability is the identification of the future causes and consequences of climate change and its subsequent prevention or mitigation in time.
    • Bionic cartilage acellular matrix microspheres as scaffold for engineering cartilage

      Liu, Jun; Yu, Cheng; Lu, Gonggong; Tang, James Zhenggui; Wang, Yonghui; Zhang, Boqing; Sun, Yong; Lin, Hai; Wang, Qiguang; Liang, Jie; Fan, Yujiang; Zhang, Xingdong (Royal Society of Chemistry, 2018-12-12)
      Extracellular matrix (ECM) scaffolds made from decellularized natural cartilage have been successfully used in cartilage lesion repair, but allogeneic cartilage donors are always in shortage and xenogeneic cartilage tissues may have the risk of unknown disease transfer. In this study, we constructed artificial bionic cartilage microspheres by encapsulating MSCs in collagen microspheres and cultured in a chondrogenic-inducing medium. Then, acellular matrix microsphere (BCAMM) scaffolds were fabricated from the cultured microspheres at three different developmental stages. A novel technique was introduced to fabricate BCAMM scaffolds, which enabled the production and utilization of the scaffolds in a short time. Due to the differences in surface morphologies and biological compositions, the three BCAMM scaffolds showed different chondrogenic effects. The 10-day BCAMM (10-BCAMM) scaffold showed the best overall results, successfully inducing MSC chondrogenesis without any additional fetal bovine serum or induction components (TGF-β or dexamethasone). In comparison, the 5-day BCAMM (5-BCAMM) scaffold showed potential osteogenic effects. The advantages of micron-sized BCAMMs are outlined, specifically in the easier decellularization process without grinding, homogeneous cell seeding and infiltration, chondrogenic induction and better fitting to the irregular lesion shape.
    • Cardiomyocyte calcineurin is required for the onset and progression of cardiac hypertrophy and fibrosis in adult mice.

      Martínez-Martínez, Sara; Lozano-Vidal, Noelia; López-Maderuelo, María Dolores; Jiménez-Borreguero, Luis Jesús; Armesilla, Ángel Luis; Redondo, Juan Miguel (Wiley, 2018-12-07)
      Previous studies have demonstrated that activation of calcineurin induces pathological cardiac hypertrophy. In these studies, loss-of-function was mostly achieved by systemic administration of the calcineurin inhibitor cyclosporin A. The lack of conditional knockout models for calcineurin function has impeded progress toward defining the role of this protein during the onset and the development of cardiac hypertrophy in adults. Here, we exploited a mouse model of cardiac hypertrophy based on the infusion of a hypertensive dose of angiotensin II (AngII) to model the role of calcineurin in cardiac hypertrophy in adulthood. AngII-induced cardiac hypertrophy in adult mice was reduced by treatment with cyclosporin A, without affecting the associated increase in blood pressure, and also by induction of calcineurin deletion in adult mouse cardiomyocytes, indicating that cardiomyocyte calcineurin is required for AngII-induced cardiac hypertrophy. Surprisingly, cardiac-specific delection of calcineurin, but not treatment of mice with cyclosporin A, significantly reduced AngII-induced cardiac fibrosis and apoptosis. Analysis of pro-fibrotic genes revealed that AngII-induced expression of Tgfβ-family members and Lox was not inhibited by cyclosporin A but was markedly reduced by cardiac-specific calcineurin deletion. These results show that AngII induces a direct, calcineurin-dependent pro-hypertrophic effect in cardiomyocytes, as well as a systemic hypertensive effect that is independent of calcineurin activity. This article is protected by copyright. All rights reserved.
    • The taxonomic history of the enigmatic Papuan snake genus Toxicocalamus (Elapidae: Hydrophiinae), with the description of a new species from the Managalas Plateau of Oro Province, Papua New Guinea, and a revised dichotomous key

      O'Shea, Mark; Allison, Allen; Kaiser, Hinrich (Societas Europaea Herpetologica, 2018-11-15)
      We trace the taxonomic history of Toxicocalamus, a poorly known genus of primarily vermivorous snakes found only in New Guinea and associated island archipelagos. With only a relatively limited number of specimens to examine, and the distribution of those specimens across many natural history collections, it has been a difficult task to assemble a complete taxonomic assessment of this group. As a consequence, research on these snakes has undergone a series of fits and starts, and we here present the first comprehensive chronology of the genus, beginning with its original description by George Albert Boulenger in 1896. We also describe a new species from the northern versant of the Owen Stanley Range, Oro Province, Papua New Guinea, and we present a series of comparisons that include heretofore underused characteristics, including those of unusual scale patterns, skull details, and tail tip morphology. Defined by the smallest holotype in the genus, the new species is easily differentiated from all other Toxicocalamus by a combination of the following eidonomic characters: fused prefrontal-internasal scute; single preocular, separate, not fused with prefrontal; minute circular, counter-sunk naris in the centre of a large, undivided, nasal scute; paired postoculars; single anterior temporal and paired posterior temporals; six supralabials, with 3rd and 4th supralabial contacting the orbit; dorsal scales in 15-15-15 rows; 235 ventral scales, 35 paired subcaudal scales; paired cloacal scales preceded by paired precloacal scales; and a short, laterally slightly compressed, ‘Ultrocalamus-type’ tail, terminating in a short conical scale. Differences from congeners in skull morphology include a reduced anterior extent of the parasphenoid, termination of the palatine tooth row at the anterior level of the parasphenoid, extent and shape of the premaxilla, shape and size of the prootics, extent and shape of the exoccipitals and occipital condyles, and features of the atlas-axis complex. This is the fifteenth species in the genus Toxicocalamus.
    • The crucial role of leucine concentration on spray dried mannitol-leucine as a single carrier to enhance the aerosolization performance of Albuterol sulfate

      Molina, Carlos; Kaialy, Waseem; Nokhodchi, Ali (Elsevier, 2018-11-09)
      Generally, DPI formulations show low fine particle fraction (FPF) due to poor detachment of drug particles from carrier during inhalation. l-Leucine, with varying concentrations (ranging from 0 to 10% w/w), were introduced into a 60%w/v mannitol solution where the solutions were then spray dried to achieve a new processed carrier. The spray dried samples were blended with Albuterol sulfate to determine the efficacy of their aerosolization performance. Analyzing each formulation was completed via the implementation of numerous analytical techniques such as particle size distribution analysis via laser diffraction, differential scanning calorimetry (DSC), scanning electron microscope (SEM), powder X-Ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, and an in vitro deposition study. It was shown the concentration of leucine in spray dried is really crucial to achieve the highest FPF possible. The highest FPF was obtained for the samples containing 10% w/w leucine which was 52.96 ± 5.21%. It was interesting to note that the presence of leucine produced different polymorphic forms for mannitol. Moreover, through this study, the authors were able to conclude that mannitol can serve as an alternative carrier in DPI formulations containing Albuterol sulfate tailored for lactose intolerant patients.
    • Atmin modulates Pkhd1 expression and may mediate autosomal recessive polycystic kidney disease (ARPKD) through altered non-canonical Wnt/planar cell polarity (PCP) signalling

      Richards, Taylor; Modarage, Kavindiya; Dean, Charlotte; McCarthy-Boxer, Aidan; Hilton, Helen; Esapa, Chris; Wilson, Patricia; Goggolidou, Paraskevi (Elsevier, 2018-11-07)
      Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a genetic disorder with an incidence of ~1:20,000 that manifests in a wide range of renal and liver disease severity in human patients and can lead to perinatal mortality. ARPKD is caused by mutations in PKHD1, which encodes the large membrane protein, Fibrocystin, required for normal branching morphogenesis of the ureteric bud during embryonic renal development. The variation in ARPKD phenotype suggests that in addition to PKHD1 mutations, other genes may play a role, acting as modifiers of disease severity. One such pathway involves non-canonical Wnt/Planar Cell Polarity (PCP) signalling that has been associated with other cystic kidney diseases, but has not been investigated in ARPKD. Analysis of the AtminGpg6 mouse showed kidney, liver and lung abnormalities, suggesting it as a novel mouse tool for the study of ARPKD. Further, modulation of Atmin affected Pkhd1 mRNA levels, altered non-canonical Wnt/PCP signalling and impacted cellular proliferation and adhesion, although Atmin does not bind directly to the C-terminus of Fibrocystin. Differences in ATMIN and VANGL2 expression were observed between normal human paediatric kidneys and age-matched ARPKD kidneys. Significant increases in ATMIN, WNT5A, VANGL2 and SCRIBBLE were seen in human ARPKD versus normal kidneys; no substantial differences were seen in DAAM2 or NPHP2. A striking increase in E-cadherin was also detected in ARPKD kidneys. This work indicates a novel role for non-canonical Wnt/PCP signalling in ARPKD and suggests ATMIN as a modulator of PKHD1.
    • Gender, microcredit, and poverty alleviation in a developing country: the case of women entrepreneurs in Pakistan

      Hussain, Javed; Mahmood, Samia; Scott, Jonathan (Wiley, 2018-11-06)
      The paper explores the impact of financial exclusion on financial and human poverty amongst women in Pakistan. The findings suggest that persistent financial exclusion, gender discrimination, and conservative religious values adversely impact women’s empowerment. There is an inverse correlation between the size of microcredit and women’s financial poverty, which is not the case for human poverty. Larger families experienced higher rates of poverty reduction than smaller families. The study offers evidence, and supports theories on the impact of microcredit upon poverty alleviation. These findings inform policy makers, women entrepreneurs, and microfinance institutions.
    • Metamaterial Superlenses Operating at Visible Wavelength for Imaging Applications

      Haxha, Shyqyri; AbdelMalek, Fathi; Ouerghi, Faouzi; Charlton, Martin; Aggoun, Amar; Fang, Xu (Nature Research, 2018-10-31)
      In this paper, a novel design for a metamaterial lens (superlens) based on a Photonic Crystal (PC) operating at visible wavelengths is reported. The proposed superlens consist of a gallium phosphide (GaP) dielectric slab waveguide with a hexagonal array of silver rods embedded within the GaP dielectric. In-house 2DFDTD numerical method is used to design and optimize the proposed superlens. Several superlenses are designed and integrated within a same dielectric platform, promoting the proof-of-concept (POC) of possible construction of an array of superlenses (or sub-lenses to create an M-Lens) for light field imaging applications. It is shown that the concavity of the superlens and positioning of each sub-lens within the array strongly affects the performances of the image in terms of resolution. Defects and various geometrical shapes are introduced to construct and optimize the proposed superlenses and increase the quality of the image resolution. It is shown that the orientation of the active region (ellipse) along x and y axis has tremendous influence on the quality of image resolution. In order to investigate the performance characteristics of the superlenses, transmitted power is calculated using 2D FDTD for image projections at various distances (in x and y plane). It is also shown, how the proposed superlens structures could be fabricated using standard micro fabrication techniques such as electron beam lithography, inductively coupled Reactive ion etching, and glancing angle evaporation methods. To the best of our knowledge, these are the first reported POC of superlenses, integrated in a monolithic platform suitable for high imaging resolution that can be used for light field imaging applications at visible wavelength. The proposed superlenses (integrated in a single platform M-Lens) will have tremendous impact on imaging applications.