Polymer mimics of biomacromolecular antifreezes

Antifreeze proteins from polar fish species are remarkable biomacromolecules which prevent the growth of ice crystals. Ice crystal growth is a major problem in cell/tissue cryopreservation for transplantation, transfusion and basic biomedical research, as well as technological applications such as icing of aircraft wings. This review will introduce the rapidly emerging field of synthetic macromolecular (polymer) mimics of antifreeze proteins. Particular focus is placed on designing polymers which have no structural similarities to antifreeze proteins but reproduce the same macroscopic properties, potentially by different molecular-level mechanisms. The application of these polymers to the cryopreservation of donor cells is also introduced

The Berkeley Contact Lens Extended Wear Study. Part I : Study design and conduct.

ObjectiveThe primary aim of the Berkeley Contact Lens Extended Wear Study (CLEWS) was to test the hypotheses that extended wear of rigid gas-permeable (RGP) contact lenses with greater oxygen permeability (Dk) reduces the incidence of contact lens-associated keratopathy (CLAK) and increases the survival rate in RGP extended wear (EW). In this article we describe the clinical trial design in detail, present the results of subject recruitment and retention, and provide the baseline demographic and ocular characteristics of the CLEWS subjects, whose data will be analyzed to address the study aims in a companion article.DesignA randomized, concurrently controlled clinical trial.InterventionSubjects were fitted with day wear (DW) high-Dk RGP lenses and then adapted to EW. Subjects who adapted to EW were then randomly assigned to either high- or medium-Dk RGP lenses for 12 months of 6-nights/week EW.Main outcome measuresSlit-lamp assessment and grading of 17 possible keratopathies, measurement of refractive error and corneal curvature, and symptoms. Follow-up data were collected every 3 months.ResultsFrom 545 subjects entering the DW adaptation phase, 201 adapted to EW and were randomly assigned to medium- or high-Dk lenses for 12 months of EW. The baseline characteristics of the two study groups were similar and did not differ from the 344 DW subjects who failed to adapt to EW. The distributions of oxygen transmissibility for the two study groups were disjoint, indicating that each group received distinctly different levels of hypoxia.ConclusionsWe show that CLEWS was appropriately designed to address the study hypotheses, was conducted with regard for the safety of the subjects, and adhered to rigorous protocols designed to control for bias and ensure the integrity of study data. We establish the internal validity of between-group statistical comparisons and characterize our study population to permit informed evaluation of the applicability of our results to the contact lens-wearing population in general

The Berkeley Contact Lens Extended Wear Study. Part II : Clinical results.

ObjectiveTo describe the principal clinical outcomes associated with 12 months use of rigid gas-permeable (RGP) extended wear contact lenses and address two primary study questions: (1) does extended wear (EW) of high oxygen transmissibility (Dk/t) RGP lenses reduce the incidence of ocular complications, and (2) does the wearing of high-Dk/t lenses reduce the rate of failure to maintain 6-night RGPEW over 12 months?DesignA randomized, concurrently controlled clinical trial.InterventionSubjects who adapted to EW with high Dk (oxygen permeability) RGP lenses were randomized to either high Dk or medium-Dk RGP lenses for 12 months of 6-night EW.Main outcome measuresContact lens-associated keratopathies (CLAK), changes in refractive error and corneal curvature, and survival in EW.ResultsTwo hundred one subjects were randomized to medium or high-Dk lenses for 12 months of EW. Sixty-two percent of the subjects in each group completed 12 months of EW; however, the probability of failure was significantly greater for the medium-Dk group. Although the risk of complications was similar for the two groups, the number of CLAK events that led to termination were 16 versus 5 for the medium-Dk and high-Dk groups, respectively. This suggests that the type of adverse response or the inability to reverse an adverse event was different for the group being exposed to the lower oxygen dose.ConclusionsThe level of oxygen available to the cornea has a significant impact on maintaining successful RGP extended contact lens wear, but not on the initial onset of CLAK. The number of clinical events leading to termination was substantially higher for the medium Dk group, which suggests that corneal hypoxia is an important factor in the development of CLAK. Although overnight contact lens wear should be recommended with caution and carefully monitored for early detection of ocular complications, it appears that high-Dk RGP lenses can be a safe and effective treatment for correction of refractive error for most individuals who can adapt to EW

Targeting quiescent leukemic stem cells using second generation autophagy inhibitors

In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically approved autophagy inhibitor, does not consistently inhibit autophagy in cancer patients, so more potent autophagy inhibitors are needed. We generated a murine model of CML in which autophagic flux can be measured in bone marrow-located LSCs. In parallel, we use cell division tracing, phenotyping of primary CML cells, and a robust xenotransplantation model of human CML, to investigate the effect of Lys05, a highly potent lysosomotropic agent, and PIK-III, a selective inhibitor of VPS34, on the survival and function of LSCs. We demonstrate that long-term haematopoietic stem cells (LT-HSCs: Lin−Sca-1+c-kit+CD48−CD150+) isolated from leukemic mice have higher basal autophagy levels compared with non-leukemic LT-HSCs and more mature leukemic cells. Additionally, we present that while HCQ is ineffective, Lys05-mediated autophagy inhibition reduces LSCs quiescence and drives myeloid cell expansion. Furthermore, Lys05 and PIK-III reduced the number of primary CML LSCs and target xenografted LSCs when used in combination with TKI treatment, providing a strong rationale for clinical use of second generation autophagy inhibitors as a novel treatment for CML patients with LSC persistence

Vocation, Belongingness, and Balance: A Qualitative Study of Veterinary Student Well-Being

An elevated risk for suicide among veterinarians has stimulated research into the mental health of the veterinary profession, and more recently attention has turned to the veterinary student population. This qualitative study sought to explore UK veterinary students' perceptions and experiences of university life, and to consider how these may affect well-being. Semi-structured interviews were conducted with 18 students from a single UK school who were purposively selected to include perspectives from male, female, graduate-entry, standard-entry (straight from high school), and widening participation students across all 5 years of the program. Three main themes were identified: a deep-rooted vocation, navigating belongingness, and finding balance. Participants described a long-standing goal of becoming a veterinarian, with a determination reflected by often circuitous routes to veterinary school and little or no consideration of alternatives. Although some had been motivated by a love of animals, others were intrinsically interested in the scientific and problem-solving challenges of veterinary medicine. Most expressed strong feelings of empathy with animal owners. The issue of belongingness was central to participants' experiences, with accounts reflecting their efforts to negotiate a sense of belongingness both in student and professional communities. Participants also frequently expressed a degree of acceptance of poor balance between work and relaxation, with indications of a belief that this imbalance could be rectified later. This study helps highlight future avenues for research and supports initiatives aiming to nurture a sense of collegiality among veterinary students as they progress through training and into the profession

Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation

Removal processes for tributyltin during municipal wastewater treatment

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Springer.The fate and behaviour of tributyltin (TBT) at two wastewater treatment works was examined. Both sites had two inlet streams, and each utilised high rate biological filters (biofilters) on one the streams, before treatment of the combined flows on trickling filters, with one having additional tertiary processes, installed to remove ammonia and solids. The study was designed to determine if these processes enhanced the removal of TBT. Degradation of TBT was observed in one of the biofilters, possibly as a result of temperature and hydraulic loading. At the treatment works with tertiary processes, the mass flux showed the overall removal of TBT was 68 %, predominantly due to removal with solids in the primary settlement processes. However, overall removal of 95 % was observed in the conventional trickling filter works with 94 % of this due to biodegradation in the trickling filter. The two works both removed TBT, but at different treatment stages and by different processes. Differences in the form (solubility) of TBT in the influent may have attributed to this, although further understanding of factors controlling degradation would allow for a more complete assessment of the potential of biological processes to remove hazardous compounds from wastewaters.United Utilities PL

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

<b>Background</b><p></p> To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.<p></p> <b>Methods</b><p></p> An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.<p></p> <b>Results</b><p></p> The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.<p></p> <b>Conclusions</b><p></p> It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability

Poverty and maternal mortality in Nigeria: towards a more viable ethics of modern medical practice

Poverty is often identified as a major barrier to human development. It is also a powerful brake on accelerated progress toward the Millennium Development Goals. Poverty is also a major cause of maternal mortality, as it prevents many women from getting proper and adequate medical attention due to their inability to afford good antenatal care. This Paper thus examines poverty as a threat to human existence, particularly women's health. It highlights the causes of maternal deaths in Nigeria by questioning the practice of medicine in this country, which falls short of the ethical principle of showing care

Computers from plants we never made. Speculations

We discuss possible designs and prototypes of computing systems that could be based on morphological development of roots, interaction of roots, and analog electrical computation with plants, and plant-derived electronic components. In morphological plant processors data are represented by initial configuration of roots and configurations of sources of attractants and repellents; results of computation are represented by topology of the roots' network. Computation is implemented by the roots following gradients of attractants and repellents, as well as interacting with each other. Problems solvable by plant roots, in principle, include shortest-path, minimum spanning tree, Voronoi diagram, $\alpha$-shapes, convex subdivision of concave polygons. Electrical properties of plants can be modified by loading the plants with functional nanoparticles or coating parts of plants of conductive polymers. Thus, we are in position to make living variable resistors, capacitors, operational amplifiers, multipliers, potentiometers and fixed-function generators. The electrically modified plants can implement summation, integration with respect to time, inversion, multiplication, exponentiation, logarithm, division. Mathematical and engineering problems to be solved can be represented in plant root networks of resistive or reaction elements. Developments in plant-based computing architectures will trigger emergence of a unique community of biologists, electronic engineering and computer scientists working together to produce living electronic devices which future green computers will be made of.Comment: The chapter will be published in "Inspired by Nature. Computing inspired by physics, chemistry and biology. Essays presented to Julian Miller on the occasion of his 60th birthday", Editors: Susan Stepney and Andrew Adamatzky (Springer, 2017