Severe Disadvantage Research Articles

A Review on Solid State Hydrogen Storage Material

Hydrogen fuel provided via green method is renewable and environmentally friendly. However, the lack of practical storage methods has restricted its use to such an extent that hydrogen storage is currently a crucial obstacle in the development of a hydrogen economy. For mobile applications hydrogen storage system needs to be lightweight and compact. Current technologies such as compressed gas or liquefied hydrogen have severe disadvantages especially in volumetric terms compared to fossil fuels and the storage of hydrogen in light weight solids could be the solution to further enhances the energy density of hydrogen tanks. This article reveals overview of novel solid hydrogen storage materials, highlighting their main advantages and drawbacks.

Impact of a Rural Regional Myocardial Infarction System of Care in Wyoming.

BackgroundPrimary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients presenting with ST‐segment elevation myocardial infarction; however, to be effective, PCI must be performed in a timely manner. Rural regions are at a severe disadvantage, given the relatively sparse number of PCI hospitals and long transport times.Methods and ResultsWe developed a standardized treatment and transfer protocol for ST‐segment elevation myocardial infarction in the rural state of Wyoming. The study design compared the time‐to‐treatment outcomes during the pre‐ and postintervention periods. Details of the program, changes in reperfusion strategies over time, and outcome improvements in treatment times were reported. From January 1, 2013, to December 31, 2014, 889 patients were treated in 11 PCI‐capable hospitals (4 in Wyoming, 7 in adjoining states). Given the large geographic distance in the state (median of 47 miles between patient and PCI center), 52% of all patients were transfers, and 36% were administered fibrinolysis at the referral facility. Following the intervention, there was a significant shift toward greater use of primary PCI as the dominant reperfusion strategy (from 47% to 60%, P=0.002), and the median total ischemic time from symptom onset to arterial reperfusion was decreased by 92 minutes (P<0.001). There was a similar significant reduction in median time from receiving center door to balloon of 11 minutes less than the baseline time (P<0.01).ConclusionsRural systems of care for ST‐segment elevation myocardial infarction require increased levels of cooperation between emergency medical services agencies and hospitals. This study confirms that total ischemic times can be reduced through a coordinated rural statewide initiative.

Critical role of ethics in clinical management and public health response to the West Africa Ebola epidemic.

The devastation caused by the Ebola virus disease (EVD) outbreak in West Africa has brought to the fore a number of important ethical debates about how best to respond to a health crisis. These debates include issues related to prevention and containment, management of the health care workforce, clinical care, and research design, all of which are situated within the overarching moral problem of severe transnational disadvantage, which has very real and specific impacts upon the ability of citizens of EVD-affected countries to respond to a disease outbreak. Ethical issues related to prevention and containment include the appropriateness and scope of quarantine and isolation within and outside affected countries. The possibility of infection in health care workers impelled consideration of whether there is an obligation to provide health services where personal protection equipment is inadequate, alongside the issue of whether the health care workforce should have special access to experimental treatment and care interventions under development. In clinical care, ethical issues include the standards of care owed to people who comply with quarantine and isolation restrictions. Ethical issues in research include appropriate study design related to experimental vaccines and treatment interventions, and the sharing of data and biospecimens between research groups. The compassionate use of experimental drugs intersects both with research ethics and clinical care. The role of developed countries also came under scrutiny, and we concluded that developed countries have an obligation to contribute to the containment of EVD infection by contributing to the strengthening of local health care systems and infrastructure in an effort to provide fair benefits to communities engaged in research, ensuring that affected countries have ready and affordable access to any therapeutic or preventative interventions developed, and supporting affected countries on their way to recovery from the impact of EVD on their social and economic lives.

Colour vision deficiency and physics teaching

1 in 12 males suffer from some form of colour vision deficiency (CVD) which in the present colour dominated world of education presentation can be a severe disadvantage. Although aware of ‘colourblindness’ most teachers make little or no adjustment for these pupils for whom tasks may be more difficult. This article examines colour vision deficiency and looks at ways in which we can help the many students who have this problem.

Pharmacokinetic properties of tandem d-peptides designed for treatment of Alzheimer's disease

Peptides are more and more considered for the development of drug candidates. However, they frequently exhibit severe disadvantages such as instability and unfavourable pharmacokinetic properties. Many peptides are rapidly cleared from the organism and oral bioavailabilities as well as in vivo half-lives often remain low. In contrast, some peptides consisting solely of d-enantiomeric amino acid residues were shown to combine promising therapeutic properties with high proteolytic stability and enhanced pharmacokinetic parameters. Recently, we have shown that D3 and RD2 have highly advantageous pharmacokinetic properties. Especially D3 has already proven promising properties suitable for treatment of Alzheimer's disease. Here, we analyse the pharmacokinetic profiles of D3D3 and RD2D3, which are head-to-tail tandem d-peptides built of D3 and its derivative RD2. Both D3D3 and RD2D3 show proteolytic stability in mouse plasma and organ homogenates for at least 24h and in murine and human liver microsomes for 4h. Notwithstanding their high affinity to plasma proteins, both peptides are taken up into the brain following i.v. as well as i.p. administration. Although both peptides contain identical d-amino acid residues, they are arranged in a different sequence order and the peptides show differences in pharmacokinetic properties. After i.p. administration RD2D3 exhibits lower plasma clearance and higher bioavailability than D3D3. We therefore concluded that the amino acid sequence of RD2 leads to more favourable pharmacokinetic properties within the tandem peptide, which underlines the importance of particular sequence motifs, even in short peptides, for the design of further therapeutic d-peptides.

Out of society? Retirement affects perceived social exclusion in Germany

Perceived social exclusion (PSE) depends on individual access to resources (e.g. income and social networks) and recognition of a social status. Working provides individuals with both resources and a social status. This situation leaves the non-working population at a severe social disadvantage, which might partly be remedied by retirement. We expected to find differential effects on PSE when individuals retire. For individuals working until retirement the transition might be mostly associated with a loss of resources (leading to an increase in PSE) and for individuals not working before retirement the transition might be more strongly associated with an increase in social status (leading to a decrease in PSE). We used longitudinal data from the German Panel Study of Labor Market and Social Security (PASS) to estimate fixed effects panel regression models for 790 men and women experiencing the transition to retirement (4110 observations). Models were estimated separately for retired persons who worked or did not work prior to retirement. At retirement those working prior to the transition reported lower levels of PSE than those not working. As expected retirement increased PSE for those previously working and for those not previously working retirement decreased PSE in the short term. Both effects remained stable after compensating for resource changes due to retirement. Retirement reduced the differences in PSE between previously working and non-working groups. For those previously working retirement seemed to depict a loss of social acceptance whereas for those previously not working retirement seemed to indicate a reduction of stigmatization. The previous effect of the labor market, however, continued to affect individuals in retirement for a long time.

Multiple paths to inequality. How institutional contexts shape the educational opportunities of second-generation immigrants in Europe

ABSTRACTMost cross-country studies on educational systems aim at identifying the net effects of single institutional aspects on students’ outcomes. In this paper, I argue that educational systems are best conceived as configurations of interconnected elements. The aim of this paper is to provide a systematic assessment of how selected features of the educational system and of the immigration context combine in countries where second-generation immigrants severely underperform their native peers, net of socio-economic differentials. Using PISA data from 2006 and 2009, I compare the relative mathematics achievement of students with and without an immigrant background in 17 Western-European educational systems. The empirical results, based on fuzzy-set Qualitative Comparative Analysis, point to the existence of functional equivalents and institutional complementarities. Equally severe disadvantages can be found in the rigidly tracking systems of German-speaking and Dutch-speaking countries, but also in the highly comprehensive Scandinavian systems, where a delayed entry in the educational system is coupled with a wide distance from the language of instruction. Moreover, even in the absence of tracking, second-generation immigrants critically lag behind their native peers if they are overrepresented in schools with a poor learning environment.

The Mir-193 Family Antagonizes Stem Cell Pathways and Is a Potent Tumor Suppressor in Childhood and Adult Acute Myeloid Leukemia

MicroRNAs (miRNAs) are essential for maintenance and differentiation of normal hematopoietic cells and their dysregulation is strongly implicated in leukemias. In order to identify tumor suppressor miRNAs in the context of hematological malignancies, we performed two complementary miRNA expression screenings in normal hematopoiesis as well as in childhood and adult acute myeloid leukemias (AML). We reasoned that tumor suppressor miRNAs are upregulated in mature myeloid cells, as compared to normal hematopoietic stem and progenitor cells (HSPCs), and downregulated in AML.Based on this screening strategy, we identified the miR-193 family members as potent suppressors of HSPC activity and AML growth. During normal hematopoiesis mmu-miR-193a-3p is exclusively expressed in mature myeloid cells and absent in normal HSPCs. Accordingly, in a cohort of 165 pediatric AML patients hsa-miR-193b-3p was broadly repressed throughout the cytogenetically characterized subgroups. In addition, in a cohort of 43 adult AML patients, its homolog hsa-miR-193a-3p was significantly upregulated in APL cases (p=0.0025, n=7) compared to bone marrow from healthy donors (n=5).To assess the impact of the miR-193 family members on AML maintenance and development, we lentivirally expressed miR-193a/b in the MLL-rearranged cell lines ML2 and THP1, which induced monocytic differentiation in concert with calcitriol treatment, measured by CD11b/CD14 expression (p=0.024). Consistently, enforced miR-193-expression led to a significant growth disadvantage in ML2 and THP1 cells (p=<0.001 and p=0.02, respectively) as well as to reduced colony formation (p=0.008) in methylcellulose-based colony-forming unit (CFU) assays. Noteworthy, these effects were not restricted to MLL-rearranged AML cell lines only, but were also evident in six other AML cell lines representing the most common AML subgroups, such as t(8;21) and t(15;17). Beyond the growth-suppressive and differentiation-inductive effect of miR-193 in human AML cell lines, overexpression of miR-193a caused a significant decrease of proliferation in murine bone marrow cells immortalized in vitro by retroviral expression of Hoxa9 or Hoxa9 and Meis1 (p=0.019 and p=0.008, respectively).Based on these findings in AML, we further investigated the impact of the miR-193 family on normal hematopoiesis. We retrovirally expressed miR-193a in 32D cells treated with granulocyte-colony stimulating factor (G-CSF), which resulted in a strong induction of myeloid differentiation already after day 2 (p=0.006) as assessed by CD11b/Gr-1 surface marker expression. We lentivirally transduced mouse lineage negative (Lin-) HSPCs and transplanted them into irradiated isogenic recipients. Bleedings performed on weeks 4, 8 and 11, as well as the examination of the bone marrow on week 11, showed a severe competitive disadvantage of miR-193-transduced cells (week 11: 2% GFP+ miR-193- vs. 25% GFP+ miR-NSC-transduced cells). These results were further refined using highly purified ESLAM (CD45+ EPCR+ CD48− CD150+) HSCs which failed to reconstitute hematopoiesis when overexpressing miR-193a, indicated by the absence of miR-193a/GFP+ cells at week 8 post transplantation. These observations might be explained by a potent G1 cell cycle arrest in HSPCs when overexpressing miR-193a/b (4-fold decrease in the S phase population) and induction of apoptosis.Our results in normal and malignant hematopoiesis suggested that the miR-193 family acts globally through targeting relevant stem cell pathways. To validate this hypothesis we quantified the knockdown of ten predicted miR-193 target genes. qRT-PCR analysis confirmed the down regulation of KIT, KRAS, SOS2 (key components of the MAPK signaling pathway) and CCND1, a CDK regulator of G1/S phase transition. We propose a dual regulatory platform where firstly, miR-193 targets CCND1 and controls the cell cycle kinetics of stem cells. Secondly, miR-193 interferes with the KIT proto-oncogene and the RAS pathway thereby inhibiting crucial pro-proliferation and anti-apoptotic signaling cascades.Taken together, we identified the miR-193 family as a pan-tumor suppressor in childhood and adult AML. Its anti-leukemic effect is mediated by targeting the stem cell KIT/SOS2/RAS/RAF axis. DisclosuresNo relevant conflicts of interest to declare.

The more the better? Optimal degree of supply-chain cooperation between competitors

We consider the outsourcing strategy problem of two competing original equipment manufacturers (OEMs) whose products are each made up of two components. The OEMs have different specializations, and therefore the component that each firm can produce in-house is different. Each firm must decide whether to outsource the other component to the competing OEM or to a third-party supplier. Prior research has demonstrated that competitors can be better off cooperating as supply-chain partners; therefore, one might expect that, as long as the OEMs are not at a severe cost disadvantage, they should maximize their cooperation as supply-chain partners, especially when competition between products is strong. Interestingly, this study finds that more cooperation between competitors may actually be harmful. Under certain conditions, while one of the OEMs should outsource to the competing firm, the other should outsource to a third-party supplier, even when the third-party supplier is more expensive and the competition is intense.

Critical Localisms and Global Education in Jeju’s Local Streets

Globalization and global competitiveness have become principal concerns in Jeju Island, a former agrarian periphery whose leadership aspires to become a prime international destination. Despite trophy accolades in the form of UNESCO designations and the New Seven Wonders selection, Jeju’s development remains uneven and contradictory. Jeju Island also still lacks an active citizen participation in framing and debating globalization issues. A lack of consensus, democratic process, and resident participation has deepened divisions existing in island society and further puts native locals at a severe disadvantage. Where policymakers have failed, however, grassroots efforts are taking up the task of globalizing Jeju residents. Using the two examples of JICEA’s “Wondosim Yetgil Tamheom”(“Exploring Jeju City’s Old Town Streets”) walks and Global Inner Peace’s September 2015 UN Peace Day event, I discuss the ways these locally-based and locally-founded NGOs are utilizing local experience to provide more nuanced critiques of globalization discourse or to reframe it. I argue that a form of critical localism is necessary to foster more global perspectives.

Facultative control of matrix production optimizes competitive fitness in Pseudomonas aeruginosa PA14 biofilm models.

As biofilms grow, resident cells inevitably face the challenge of resource limitation. In the opportunistic pathogen Pseudomonas aeruginosa PA14, electron acceptor availability affects matrix production and, as a result, biofilm morphogenesis. The secreted matrix polysaccharide Pel is required for pellicle formation and for colony wrinkling, two activities that promote access to O2. We examined the exploitability and evolvability of Pel production at the air-liquid interface (during pellicle formation) and on solid surfaces (during colony formation). Although Pel contributes to the developmental response to electron acceptor limitation in both biofilm formation regimes, we found variation in the exploitability of its production and necessity for competitive fitness between the two systems. The wild type showed a competitive advantage against a non-Pel-producing mutant in pellicles but no advantage in colonies. Adaptation to the pellicle environment selected for mutants with a competitive advantage against the wild type in pellicles but also caused a severe disadvantage in colonies, even in wrinkled colony centers. Evolution in the colony center produced divergent phenotypes, while adaptation to the colony edge produced mutants with clear competitive advantages against the wild type in this O2-replete niche. In general, the structurally heterogeneous colony environment promoted more diversification than the more homogeneous pellicle. These results suggest that the role of Pel in community structure formation in response to electron acceptor limitation is unique to specific biofilm models and that the facultative control of Pel production is required for PA14 to maintain optimum benefit in different types of communities.

Decellularized human placenta chorion matrix as a favorable source of small-diameter vascular grafts

Biomaterials based on decellularized tissues are increasingly attracting attention as functional alternatives to other natural or synthetic materials. However, a source of non-cadaver human allograft material would be favorable. Here we establish a decellularization method of vascular tissue from cryopreserved human placenta chorionic plate starting with an initial freeze–thaw step followed by a series of chemical treatments applied with a custom-made perfusion system. This novel pulsatile perfusion set-up enabled us to successfully decellularize the vascular tissue with lower concentrations of chemicals and shorter exposure times compared to a non-perfusion process. The decellularization procedure described here lead to the preservation of the native extracellular matrix architecture and the removal of cells. Quantitative analysis revealed no significant changes in collagen content and a retained glycosaminoglycan content of approximately 29%. In strain-to-failure tests, the decellularized grafts showed similar mechanical behavior compared to native controls. In addition, the mechanical values for ultimate tensile strength and stiffness were in an acceptable range for in vivo applications. Furthermore, biocompatibility of the decellularized tissue and its recellularizationability to serve as an adequate substratum for upcoming recellularization strategies using primary human umbilical vein endothelial cells (HUVECs) was demonstrated. HUVECs cultured on the decellularized placenta vessel matrix performed endothelialization and maintained phenotypical characteristics and cell specific expression patterns. Overall, the decellularized human placenta vessels can be a versatile tool for experimental studies on vascularization and as potent graft material for future in vivo applications. Statement of significanceIn the US alone more than 1million vascular grafts are needed in clinical practice every year. Despite severe disadvantages, such as donor site morbidity, autologous grafting from the patient’s own arteries or veins is regarded as the gold standard for vascular tissue repair. Besides, strategies based on synthetic or natural materials have shown limited success. Tissue engineering approaches based on decellularized tissues are regarded as a promising alternative to clinically used treatments to overcome the observed limitations. However, a source for supply of non-cadaver human allograft material would be favorable. Here, we established a decellularization method of vascular tissue from the human placenta chorionic plate, a suitable human tissue source of consistent quality. The decellularized human placenta vessels can be a potent graft material for future in vivo applications and furthermore might be a versatile tool for experimental studies on vascularization.

Defining Molecular Basis for Longevity Traits in Natural Yeast Isolates.

Background:The budding yeast has served as a useful model organism in aging studies, leading to the identification of genetic determinants of longevity, many of which are conserved in higher eukaryotes. However, factors that promote longevity in a laboratory setting often have severe fitness disadvantages in the wild.Aims and Methods:To obtain an unbiased view on longevity regulation, we analyzed how a replicative lifespan is shaped by transcriptional, translational, metabolic, and morphological factors across 22 wild-type Saccharomyces cerevisiae isolates.Results:We observed significant differences in lifespan across these strains and found that their longevity is strongly associated with up-regulation of oxidative phosphorylation and respiration and down-regulation of amino- acid and nitrogen compound biosynthesis.Conclusions:As calorie restriction and TOR signaling also extend the lifespan by adjusting many of the identified pathways, the data suggest that the natural plasticity of yeast lifespan is shaped by the processes that not only do not impose cost on fitness, but also are amenable to dietary intervention.

Psychiatric disorders in child and adolescent offspring of patients with schizophrenia and bipolar disorder: A controlled study

BackgroundEarly clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively. MethodsSZ and BP parents with offspring aged 7–17years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations. ResultsWe found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP-offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP-offspring, and BP-offspring presented a higher prevalence of depression than CC-offspring. ConclusionsThe higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP.

MtgA Deletion-Triggered Cell Enlargement of Escherichia coli for Enhanced Intracellular Polyester Accumulation

Bacterial polyester polyhydroxyalkanoates (PHAs) have been produced in engineered Escherichia coli, which turned into an efficient and versatile platform by applying metabolic and enzyme engineering approaches. The present study aimed at drawing out the latent potential of this organism using genome-wide mutagenesis. To meet this goal, a transposon-based mutagenesis was carried out on E. coli, which was transformed to produce poly(lactate-co-3-hydroxybutyrate) from glucose. A high-throughput screening of polymer-accumulating cells on Nile red-containing plates isolated one mutant that produced 1.8-fold higher quantity of polymer without severe disadvantages in the cell growth and monomer composition of the polymer. The transposon was inserted into the locus within the gene encoding MtgA that takes part, as a non-lethal component, in the formation of the peptidoglycan backbone. Accordingly, the mtgA-deleted strain E. coli JW3175, which was a derivate of superior PHA-producing strain BW25113, was examined for polymer production, and exhibited an enhanced accumulation of the polymer (7.0 g/l) compared to the control (5.2 g/l). Interestingly, an enlargement in cell width associated with polymer accumulation was observed in this strain, resulting in a 1.6-fold greater polymer accumulation per cell compared to the control. This result suggests that the increase in volumetric capacity for accumulating intracellular material contributed to the enhanced polymer production. The mtgA deletion should be combined with conventional engineering approaches, and thus, is a promising strategy for improved production of intracellularly accumulated biopolymers.

Correcting for non-response bias in contingent valuation surveys concerning environmental non-market goods: an empirical investigation using an online panel

Data collection for economic valuation by using Internet surveys and pre-recruited Internet panels can be associated with severe disadvantages. Problems concerning sample coverage and sample representativeness can be expected. Representation errors may occur since people can choose whether to be part of an Internet panel and subsequently whether they wish to participate in the survey, thereby introducing two elements of potential self-selection. These elements may be correlated with preferences, thus making the respondents a non-random and non-representative sample, ultimately biasing results. This paper analyses a sample used for an Internet contingent valuation method survey eliciting preferences for improvements in water quality of a river. We find that some variables that affect the survey participation decision also affect willingness-to-pay, consequently biasing our welfare estimates. We show how adjusting willingness-to-pay for this bias can be accomplished by using a grouped data model incorporating a correlation parameter to account for selection.

Do Women Suffer from Network Closure? The Moderating Effect of Social Capital on Gender Inequality in a Project-Based Labor Market, 1929 to 2010

That social capital matters is an established fact in the social sciences. Less clear, however, is how different forms of social capital affect gender disadvantages in career advancement. Focusing on a project-based type of labor market, namely the U.S. film industry, this study argues that women suffer a “closure penalty” and face severe career disadvantages when collaborating in cohesive teams. At the same time, gender disadvantages are reduced for women who build social capital in open networks with higher degrees of diversity and information flow. Using large-scale longitudinal data on career profiles of about one million performances by 97,657 film actors in 369,099 film productions between the years 1929 and 2010, I analyze career survival models and interaction effects between gender and different measures of social capital and information openness. Findings reveal that female actors have a higher risk of career failure than do their male colleagues when affiliated in cohesive networks, but women have better survival chances when embedded in open, diverse structures. This study contributes to the understanding of how and what type of social capital can be either a beneficial resource for otherwise disadvantaged groups or a constraining mechanism that intensifies gender differences in career advancement.

Gray Becomes Black and White: Exploring Options for U.S. Businesses in Wake of the Kirtsaeng Decision

In Kirtsaeng v. John Wiley &amp; Sons, Inc., 133 S. Ct. 1351 (2013), the Supreme Court held that gray market goods are protected by the first sale doctrine of the Copyright Act of 1976 ("Copyright Act"). U.S. manufacturers are typically at a severe disadvantage when competing with gray marketers who offer essentially the same or comparable goods at lower prices. Accordingly, businesses should explore new avenues to limit the economic power of gray market goods by using: (1) licenses for copyrighted works; (2) contract provisions restricting distribution; (3) remedies under trademark law, such as Lever rule protection under section 42 of the Lanham Act or by curtailing the importation of certain foreign-manufactured merchandise through section 526 of the Tariff Act; and (4) consumer protection laws in applicable states such as California, Connecticut, and New York.

Diameter-dependent release of a cisplatin pro-drug from small and large functionalized carbon nanotubes.

The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes' inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(IV) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(IV)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(IV)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(IV)@CNT exposure demonstrate that they can promote drug accumulation inside cells in comparison with treatment with the free complex. To conclude, our study shows that CNTs are promising nanocarriers to improve the accumulation of a chemotherapeutic drug and its slow release inside tumor cells, by tuning the CNT diameter, without inducing a high inflammatory response.

Can a luxury hotel compete without a spa facility?—Opinions from senior managers of London's luxury hotels

The development of the wellness facility within the luxury hotel sector around the world has been evident, with many professionals believing that spas are an expected element within luxury hotels. This paper has been written to provide further consideration for hoteliers who are looking to open a luxury hotel within the city of London, to add to the body of knowledge on spas and to stimulate further research in the field. The literature revealed a lack of realistic insight by hotel professionals. Statistics are quite broad and look more at other markets than directly at hotels in the city of London. By interviewing five senior managers of London's best known luxury hotels, the importance the spa plays to the hotel, its overall purpose of being in operation, personal managerial opinions on the facility and the overall economic benefit for the hotel are explored. The findings uncover some of the current positive and negative issues in the London luxury hotel spa sector. There turned out to be ambiguity among the interviewees about the definition of a hotel spa and the amenities it should offer. It was concluded that a luxury hotel will be at a severe disadvantage if it has no wellness facilities. What those facilities must consist of, however, is not clearly defined. Further research is needed to look from the consumer's point of view when defining the value of a hotel spa. It would benefit both the hotels and their guests to have more understanding of what actually is expected from the spa experience.