Origin of broad polydispersion in functionalized dendrimers and its effects on cancer cell binding affinity

Nanoparticles with multiple ligands have been proposed for use in nanomedicine. The multiple targeting ligands on each nanoparticle can bind to several locations on a cell surface facilitating both drug targeting and uptake. Experiments show that the distribution of conjugated ligands is unexpectedly broad, and the desorption rate appears to depends exponentially upon the mean number of attached ligands. These two findings are explained with a model in which ligands conjugate to the nanoparticle with a positive cooperativity of $\approx 4kT$, and that nanoparticles bound to a surface by multiple bonds are permanently affixed. This drives new analysis of the data, which confirms that there is only one time constant for desorption, that of a nanoparticle bound to the surface by a single bond.Comment: 4 pages, with 6 figure

The influence of 'significant others' on persistent back pain and work participation: a qualitative exploration of illness perceptions

Background Individual illness perceptions have been highlighted as important influences on clinical outcomes for back pain. However, the illness perceptions of 'significant others' (spouse/partner/close family member) are rarely explored, particularly in relation to persistent back pain and work participation. The aim of this study was to initiate qualitative research in this area in order to further understand these wider influences on outcome. Methods Semi-structured interviews based on the chronic pain version of the Illness Perceptions Questionnaire-Revised were conducted with a convenience sample of UK disability benefit claimants, along with their significant others (n=5 dyads). Data were analysed using template analysis. Results Significant others shared, and perhaps further reinforced, claimants' unhelpful illness beliefs including fear of pain/re-injury associated with certain types of work and activity, and pessimism about the likelihood of return to work. In some cases, significant others appeared more resigned to the permanence and negative inevitable consequences of the claimant's back pain condition on work participation, and were more sceptical about the availability of suitable work and sympathy from employers. In their pursuit of authenticity, claimants were keen to stress their desire to work whilst emphasising how the severity and physical limitations of their condition prevented them from doing so. In this vein, and seemingly based on their perceptions of what makes a 'good' significant other, significant others acted as a 'witness to pain', supporting claimants' self-limiting behaviour and statements of incapacity, often responding with empathy and assistance. The beliefs and responses of significant others may also have been influenced by their own experience of chronic illness, thus participants lives were often intertwined and defined by illness. Conclusions The findings from this exploratory study reveal how others and wider social circumstances might contribute both to the propensity of persistent back pain and to its consequences. This is an area that has received little attention to date, and wider support of these findings may usefully inform the design of future intervention programmes aimed at restoring work participation

The frequency and properties of young tidal dwarf galaxies in nearby gas-rich groups

We present high-resolution Giant Metrewave Radio Telescope (GMRT) HI observations and deep Canada-France-Hawaii Telescope (CFHT) optical imaging of two galaxy groups: NGC 4725/47 and NGC 3166/9. These data are part of a multi-wavelength unbiased survey of the gas-rich dwarf galaxy populations in three nearby interacting galaxy groups. The NGC 4725/47 group hosts two tidal knots and one dIrr. Both tidal knots are located within a prominent HI tidal tail, appear to have sufficient mass (M_gas~10^8 M_sol) to evolve into long-lived tidal dwarf galaxies (TDGs) and are fairly young in age. The NGC 3166/9 group contains a TDG candidate, AGC 208457, at least three dIrrs and four HI knots. Deep CFHT imaging confirms that the optical component of AGC 208457 is bluer -- with a 0.28 mag g-r colour -- and a few Gyr younger than its purported parent galaxies. Combining the results for these groups with those from the NGC 871/6/7 group reported earlier, we find that the HI properties, estimated stellar ages and baryonic content of the gas-rich dwarfs clearly distinguish tidal features from their classical counterparts. We optimistically identify four potentially long-lived tidal objects associated to three separate pairs of interacting galaxies, implying that TDGs are not readily produced during interaction events as suggested by some recent simulations. The tidal objects examined in this survey also appear to have a wider variety of properties than TDGs of similar mass formed in current simulations of interacting galaxies, which could be the result of pre- or post-formation environmental influences.Comment: 18 pages, 14 figures, accepted for publication in MNRA

Coordinated and tailored work rehabilitation: a randomized controlled trial with economic evaluation undertaken with workers on sick leave due to musculoskeletal disorders

Introduction In Denmark, the magnitude and impact of work disability on the individual worker and society has prompted the development of a new "coordinated and tailored work rehabilitation" (CTWR) approach. The aim of this study was to compare the effects of CTWR with conventional case management (CCM) on return-to-work of workers on sick leave due to musculoskeletal disorders (MSDs). Methods The study was a randomized controlled trial with economic evaluation undertaken with workers on sick leave for 4-12 weeks due to MSDs. CTWR consists of a work disability screening by an interdisciplinary team followed by the collaborative development of a RTW plan. The primary outcome variable was registered cumulative sickness absence hours during 12 months follow-up. Secondary outcomes were work status as well as pain intensity and functional disability, measured at baseline, 3 and 12 months follow-up. The economic evaluation (intervention costs, productivity loss, and health care utilization costs) was based on administrative data derived from national registries. Results For the time intervals 0-6 months, 6-12 months, and the entire follow-up period, the number of sickness absence hours was significantly lower in the CTWR group as compared to the control group. The total costs saved in CTWR participants compared to controls were estimated at US $1,366 per person at 6 months follow-up and US$ 10,666 per person at 12 months follow-up. Conclusions Workers on sick leave for 4-12 weeks due to MSD who underwent "CTWR" by an interdisciplinary team had fewer sickness absence hours than controls. The economic evaluation showed that-in terms of productivity loss-CTWR seems to be cost saving for the society

The creation view of opportunities at the base of the pyramid

This research aims to understand how multinational corporations (MNCs) enter the base of the pyramid (BoP) by adopting the creation view of opportunities. We employ actor–network theory and explore the key actors, the process and the opportunity development that enable MNCs to tackle the relative poverty of the BoP market. Our qualitative exploratory case study illustrates that, at the BoP, MNCs have to involve beneficiary stakeholders such as non-governmental organizations and BoP communities. In this process, they should be open to modifying their business model continuously to build awareness about the product among the poor and ensure affordability, availability and acceptability. At the BoP, opportunities do not exist in the external environment and they should be developed by identifying and addressing the real needs of the poor, enhancing their quality of life and being patient about earning a profit. This research contributes to the entrepreneurship literature by expanding the creation perspective of opportunities and provides implications for the managers of companies targeting the BoP market

Comparison between resistive and collisionless double tearing modes for nearby resonant surfaces

The linear instability and nonlinear dynamics of collisional (resistive) and collisionless (due to electron inertia) double tearing modes (DTMs) are compared with the use of a reduced cylindrical model of a tokamak plasma. We focus on cases where two q = 2 resonant surfaces are located a small distance apart. It is found that regardless of the magnetic reconnection mechanism, resistivity or electron inertia, the fastest growing linear eigenmodes may have high poloidal mode numbers m ~ 10. The spectrum of unstable modes tends to be broader in the collisionless case. In the nonlinear regime, it is shown that in both cases fast growing high-m DTMs lead to an annular collapse involving small magnetic island structures. In addition, collisionless DTMs exhibit multiple reconnection cycles due to reversibility of collisionless reconnection and strong ExB flows. Collisionless reconnection leads to a saturated stable state, while in the collisional case resistive decay keeps the system weakly dynamic by driving it back towards the unstable equilibrium maintained by a source term.Comment: 15 pages, 9 figure

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Cold gas outflows from the Small Magellanic Cloud traced with ASKAP

Feedback from massive stars plays a critical role in the evolution of the Universe by driving powerful outflows from galaxies that enrich the intergalactic medium and regulate star formation. An important source of outflows may be the most numerous galaxies in the Universe: dwarf galaxies. With small gravitational potential wells, these galaxies easily lose their star-forming material in the presence of intense stellar feedback. Here, we show that the nearby dwarf galaxy, the Small Magellanic Cloud (SMC), has atomic hydrogen outflows extending at least 2 kiloparsecs (kpc) from the star-forming bar of the galaxy. The outflows are cold, $T<400~{\rm K}$, and may have formed during a period of active star formation $25 - 60$ million years (Myr) ago. The total mass of atomic gas in the outflow is $\sim 10^7$ solar masses, ${\rm M_{\odot}}$, or $\sim 3$% of the total atomic gas of the galaxy. The inferred mass flux in atomic gas alone, $\dot{M}_{HI}\sim 0.2 - 1.0~{\rm M_{\odot}~yr^{-1}}$, is up to an order of magnitude greater than the star formation rate. We suggest that most of the observed outflow will be stripped from the SMC through its interaction with its companion, the Large Magellanic Cloud (LMC), and the Milky Way, feeding the Magellanic Stream of hydrogen encircling the Milky Way.Comment: Published in Nature Astronomy, 29 October 2018, http://dx.doi.org/10.1038/s41550-018-0608-