A rational approach to cancer therapy

A report on the 20th Annual Lorne Cancer Conference, Lorne, Australia, 14-16 February 2008

Realistic Rashba and Dressehaus spin-orbit coupling for neutral atoms

We describe a new class of atom-laser coupling schemes which lead to spin-orbit coupled Hamiltonians for ultra-cold neutral atoms. By properly setting the optical phases, a pair of degenerate pseudospin states emerge as the lowest energy states in the spectrum, and are thus immune to collisionally induced decay. These schemes use $N$ cyclically coupled ground or metastable internal states. We specialize to two situations: a three level case giving fixed Rashba coupling, and a four-level case that adds a controllable Dresselhaus contribution. We describe an implementation of the four level scheme for \Rb87 and analyze the sensitivity of our approach to realistic experimental limitations and imperfections. Lastly, we argue that no laser coupling scheme can give pure Rashba or Dresselhaus coupling: akin to condensed matter systems, higher order terms spoil the symmetry of these couplings. However, for sufficiently intense laser fields the continuous rotational symmetry approximately holds, making the Rashba Hamiltonian applicable for cold atoms.Comment: 5 pages, 4 figures, accepted as a PRA Brief Repor

Using additive manufacturing with blow moulding to facilitate accurate consumer testing

A South African entrepreneur needed a fast and accurate route to consumer testing for a design of phlegm collection bottle for long-distance runners. Vaal University of Technology was presented with an initial product concept which had to be developed into a fully functional prototype required for field trials. The idea was converted into a practical product proposal and modelled using a 3D computer aided design (CAD) system. The CAD data were used for laser sintering of polyamide to produce an initial prototype for appearance and ergonomic evaluation. For product testing in the field, a short run of fully functional prototypes in thin-walled low density poly-ethylene (LDPE) was required. This required a further design iteration and the production of tooling for the blow moulding process. A novel hybrid modular approach to tool manufacture was followed, where the outer frame of the tools were machined in aluminium and the tool inserts were laser sintered in AlumideTM. Blow moulding trials were undertaken in LDPE which revealed a number of positive and negative issues. The rough surface of the tool inserts produced a desirable textured surface in the resultant blow-moulded bottles but also prevented a clean “shut-off” between the two halves of the tool. This allowed air to escape from the cavity along the split plane, creating unwanted holes in the bottles. In addition, the low thermal conductivity of AlumideTM resulted in an unwanted overheating of the tools. Strategies were identified to overcome these issues and these are explained in the paper

Preparing care home staff to manage challenging behaviours among residents living with dementia: A mixed-methods evaluation

We evaluated an intervention designed to manage challenging behaviours of people with dementia. Framework analysis of interviews (n = 21) showed the intervention modified practice and perceptions. The intervention (n = 58; power calculation proposed n = 160 for medium effect) had no significant effect on attitudes to dementia for time (p = .42) or care home (p = .15). The Maslach burnout scores did not change significantly for person-centredness for time (p = .83) or care home (p = .29). Hope scores showed a significant effect post-intervention (p = .004), but this was not maintained. No significant main effect was found for care home (p = .36). Experiential learning enabled staff to experience benefits of person-centred care firsthand

When Is “Type I” Ovarian Cancer Not “Type I”? Indications of an Out-Dated Dichotomy

The dualistic classification of epithelial ovarian cancer (EOC) into “type I” and “type II” is widely applied in the research setting; it is used as a convenient way of conceptualizing different mechanisms of tumorigenesis. However, this classification conflicts with recent molecular insights of the etiology of EOC. Molecular and cell of origin studies indicate that while type II tumors could be classed together, type I tumors are not homogenous, even within the histological types, and can have poor clinical outcomes. Type II high grade serous carcinoma and type I low grade serous carcinomas best fit the description of the dualistic model, with different precursors, and distinct molecular profiles. However, endometriosis-associated cancers should be considered a separate group, without assuming an indolent course or type I genetic profiles. Furthermore, the very clear differences between mucinous ovarian carcinomas and other type I tumors, including an uncertain origin, and heterogeneous mutational spectrum and clinical behavior, indicate a non-type I classification for this entity. The impression that only type II carcinomas are aggressive, have poor prognosis, and carry TP53 mutations is an unhelpful misinterpretation of the dualistic classification. In this review, we revisit the history of EOC classification, and discuss the misunderstanding of the dualistic model by comparing the clinical and molecular heterogeneity of EOC types. We also emphasize that all EOC research, both basic and clinical, should consider the subtypes as different diseases beyond the type I/type II model, and base novel therapies on the molecular characteristics of each tumor

Effect of abdominal binding on respiratory mechanics during exercise in athletes with cervical spinal cord injury

West CR, Goosey-Tolfrey VL, Campbell IG, Romer LM. Effect of abdominal binding on respiratory mechanics during exercise in athletes with cervical spinal cord injury. J Appl Physiol 117: 36–45, 2014. First published May 22, 2014; doi:10.1152/japplphysiol.00218.2014.—We asked whether elastic binding of the abdomen influences respiratory mechanics during wheelchair propulsion in athletes with cervical spinal cord injury (SCI). Eight Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) performed submaximal and maximal incremental exercise tests on a treadmill, both with and without abdominal binding. Measurements included pulmonary function, pressure-derived indices of respiratory mechanics, operating lung volumes, tidal flow-volume data, gas exchange, blood lactate, and symptoms. Residual volume and functional residual capacity were reduced with binding (77 18 and 81 11% of unbound, P 0.05), vital capacity was increased (114 9%, P 0.05), whereas total lung capacity was relatively well preserved (99 5%). During exercise, binding introduced a passive increase in transdiaphragmatic pressure, due primarily to an increase in gastric pressure. Active pressures during inspiration were similar across conditions. A sudden, sustained rise in operating lung volumes was evident in the unbound condition, and these volumes were shifted downward with binding. Expiratory flow limitation did not occur in any subject and there was substantial reserve to increase flow and volume in both conditions. V ˙ O2 was elevated with binding during the final stages of exercise (8 –12%, P 0.05), whereas blood lactate concentration was reduced (16 –19%, P 0.05). V ˙ O2/heart rate slopes were less steep with binding (62 35 vs. 47 24 ml/beat, P 0.05). Ventilation, symptoms, and work rates were similar across conditions. The results suggest that abdominal binding shifts tidal breathing to lower lung volumes without influencing flow limitation, symptoms, or exercise tolerance. Changes in respiratory mechanics with binding may benefit O2 transport capacity by an improvement in central circulatory function.This article has been made available through the Brunel Open Access Publishing Fund

Alice in recidivism land: The Queens logic and child protection workers\u27 assessment of sexual dangerousness

This article is based on a case that highlights the dearth of cogent and pertinent risk assessment information in the reports and testimonies of many involved in assessing risks to children in real life problematic circumstances. In the case, the decision to exclude an intrafamilial sexual offender from the family home was made in large measure on the basis that the offender\u27s wife accepted the offender\u27s "denial of guilt" to accusations previously made against him. Keeping families apart should not be entertained without reliable and valid evidence pointing to that decision. However, as will be seen, the evidence often relied upon by child protection workers, albeit in good faith, is neither. The assessment processes described in the case point directly to what appears to be a wider lack of knowledge specific to assessment of recidivism, to misrepresentation of risk assessment information, and to overarching epistemological issues that appear to be widely ignored and/or misunderstood within the overall field of risk assessment and threat management. The purpose of this article is to describe how the information used to decide upon exclusion in the case cannot be considered probative and to iterate the methodological processes that must be considered in such cases if miscarriages of justice are to be avoided

Sulfide saturation in evolving porphyry systems: El Abra porphyry Cu deposit, northern Chile, and the Grasberg-Ertsberg porphyry-skarn Cu-Au district, Papua, Indonesia

Sulfide saturation during the magmatic evolution of porphyry systems is emerging as an important control on chalcophile element fertility. Platinum group elements (PGE) have extreme sulfide melt-silicate melt partition coefficients that make them sensitive indicators of the timing of sulfide saturation in an evolving magmatic system. We report PGE and Re concentrations of intrusions from the Grasberg-Ertsberg porphyry-skarn Cu-Au district, Papua, Indonesia. Unaltered to weakly altered samples contain up to 0.023 ppb Rh, 5.5 ppb Pt, 11.6 ppb Pd and 162 ppb Re. The most altered and/or mineralized samples typically contain greater concentrations; up to 0.065 ppb Rh, 17.6 ppb Pt, 95 ppb Pd and 218 ppb Re. The results suggest that sulfide saturation did not occur during magmatic evolution of the intrusions, and so Cu, Au, and PGE were concentrated by fractional crystallization and partitioned into the mineralizing fluid. These findings contrast with the intrusions of the El Abra-Pajonal suite and porphyry Cu deposit, Chile, where a rapid drop in Pt and Pd abundance indicates that sulfide saturation started before ore-fluid saturation. However, at El Abra, a porphyry Cu deposit was still able to form because the amount of sulfide melt that formed was small, stripping the magma of most of its Au and PGE but little Cu. Sulfide saturation therefore has a governing control over both the availability of the chalcophile elements to partition into the hydrothermal ore-fluid phase and the type of porphyry mineralization that can form, i.e. Cu, Cu-Au, or Cu-Au-(Pd)

Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease

There is mounting evidence for a role of the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in inflammatory disease, including arthritis. In the present study, we examined the effectiveness of treatment of collagen-induced arthritis (CIA) with a neutralizing mAb to GM-CSF. DBA/1 mice were immunized for the development of CIA and treated at different times, and with different doses, with neutralizing mAb to GM-CSF or isotype control mAb. Anti-GM-CSF mAb treatment prior to the onset of arthritis, at the time of antigen challenge, was effective at ameliorating the ensuing disease. Modulation of arthritis was seen predominantly as a reduction in overall disease severity, both in terms of the number of limbs affected per mouse and the clinical score of affected limbs. Importantly, anti-GM-CSF mAb treatment ameliorated existing disease, seen both as a reduction in the number of initially affected limbs progressing and lower numbers of additional limbs becoming affected. By histology, both inflammation and cartilage destruction were reduced in anti-GM-CSF-treated mice, and the levels of tumor necrosis factor-a and IL-1? were also reduced in joint tissue washouts of these mice. Neither humoral nor cellular immunity to type II collagen, however, was affected by anti-GM-CSF mAb treatment. These results suggest that the major effect of GM-CSF in CIA is on mediating the effector phase of the inflammatory reaction to type II collagen. The results also highlight the essential role of GM-CSF in the ongoing development of inflammation and arthritis in CIA, with possible therapeutic implications for rheumatoid arthritis