WAND2-A versatile wide angle neutron powder/single crystal diffractometer.

Wide Angle Neutron Diffractometer Squared is a high-flux versatile diffractometer with a 2-Dimensional Position Sensitive Detector at the High Flux Isotope Reactor. The instrument has strengths in both powder and single crystal diffraction. It is a unique instrument in the neutron scattering landscape of North America, and its capabilities are at least equal to similar instruments in the world.

The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells.

The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology. Although recent reports correlated high CCR7 levels with more advanced tumor grade and poor prognosis, limited in vivo data are available regarding its specific function in mammary gland neoplasia and the underlying mechanisms involved. To address these questions we generated a bigenic mouse model of breast cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in a considerable delay in tumor onset as well as significantly reduced tumor burden. Importantly, CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. These data characterize the oncogenic properties of CCR7 in mammary epithelial neoplasia and point to a new route for therapeutic intervention to target evasive cancer stem cells.

The Sustainability Cycle and Loop: models for a more unified understanding of sustainability.

In spite of the considerable research on sustainability, reports suggest that we are barely any closer to a more sustainable society. As such, there is an urgent need to improve the effectiveness of human efforts towards sustainability. A clearer and more unified understanding of sustainability among different people and sectors could help to facilitate this. This paper presents the results of an inductive literature investigation, aiming to develop models to explain the nature of sustainability in the Earth system, and how humans can effectively strive for it. The major contributions are two general and complementary models, that may be applied in any context to provide a common basis for understanding sustainability: the Sustainability Cycle (S-Cycle), and the Sustainability Loop (S-Loop). Literature spanning multiple sectors is examined from the perspective of three concepts, emerging as significant in relation to our aim. Systems are shown to provide the context for human action towards sustainability, and the nature of the Earth system and its sub-systems is explored. Activities are outlined as a fundamental target that humans need to sustain, since they produce the entities both needed and desired by society. The basic behaviour of activities operating in the Earth system is outlined. Finally, knowledge is positioned as the driver of human action towards sustainability, and the key components of knowledge involved are examined. The S-Cycle and S-Loop models are developed via a process of induction from the reviewed literature. The S-Cycle describes the operation of activities in a system from the perspective of sustainability. The sustainability of activities in a system depends upon the availability of resources, and the availability of resources depends upon the rate that activities consume and produce them. Humans may intervene in these dynamics via an iterative process of interpretation and action, described in the S-Loop model. The models are briefly applied to a system described in the literature. It is shown that the S-Loop may be used to guide efforts towards sustainability in a particular system of interest, by prescribing the basic activities involved. The S-Cycle may be applied complementary to the S-Loop, to support the interpretation of activity behaviour described in the latter. Given their general nature, the models provide the basis for a more unified understanding of sustainability. It is hoped that their use may go some way towards improving the effectiveness of human action towards sustainability.

Influences on decision for mastectomy in patients eligible for breast conserving surgery.

Increasing emphasis is being placed on low mastectomy rates. Our objective was to investigate factors influencing rates of mastectomy and breast conserving surgery. A group of 171 patients (27%) who could have had breast conserving surgery (BCS) but chose mastectomy was identified as well as all patients who underwent BCS over a 6 year period. A questionnaire asking patient's attitudes to factors which could influence their choice of operation was compiled and sent to this study group. Results showed surgical advice to be the most important factor, with significantly more influence in BCS patients. No significant difference was found in distance to treatment between the groups. Shorter duration radiotherapy would have made 47% of mastectomy patients more likely to accept BCS. BCS rates are a poor measure of quality of patient care. More emphasis should be put on choices offered to patients rather than overall uptake of a specific choice.

Local order in layered NiPS3 and Ni0.7Mg0.3PS3.

The family of two-dimensional magnetic materials M(II)PS(3) where M = Mn, Fe, Ni, Mg, Zn, etc shows a wide range of fascinating magnetic behaviour. It also shows potentially useful chemical properties including intercalation of nonlinear optical molecules and lithium ions. These properties are due to a crystal structure in which the ab planes are well-ordered in the plane but poorly correlated along c. Here, the short-range ordering is modelled in NiPS(3) and Ni(1 - x)Mg(x)PS(3) (x = 0.3). X-ray diffuse scattering from NiPS(3) shows pronounced streaking along c, indicative of stacking faulting in these layered compounds. Electron diffraction from Ni(1 - x)Mg(x)PS(3) (x = 0.3) shows substantial diffuse scattering due to short-range order within the ab plane, and this can be modelled by allowing the metal species to cluster. The possibility of clustering has implications for interpretation of the magnetic behaviour of the family, including the glassiness observed in Fe(1 - x)Mn(x)PS(3).

A paramedic study comparing the use of the Airtraq, Airway Scope and Macintosh laryngoscopes in simulated prehospital airway scenarios.

In a randomised, cross-over study, we compared the use of the Airtraq , Airway Scope and Macintosh laryngoscopes by paramedics for tracheal intubation in three simulated prehospital scenarios. Fifty-four paramedics were invited to take part. When evaluated in a difficult airway manikin, median IQR [range] time to intubation with the Airtraq (21 (16-37 [6-80] s) and Airway Scope (16 (5-75 [12-23] s) was shorter than that with the Macintosh laryngoscope (39 (25-54 [7-120] s; p < 0.0001). The success rate within 30 s was greater with the Airtraq (61%) and Airway Scope (93%) than with the Macintosh laryngoscope (22%; p < 0.0001). When used for a standard intubation and in the sitting position, we found minimal differences among the three laryngoscopes. We conclude that the Airway Scope and Airtraq have significant advantages over the Macintosh laryngoscope and that of the two, the Airway Scope is the more effective device to use in the prehospital environment.

"Covering our backs": ambulance crews' attitudes towards clinical documentation when emergency (999) patients are not conveyed to hospital.

BACKGROUND: Up to 30% of people who call for an emergency ambulance are, for various reasons, not conveyed to hospital. Across the UK, the majority of ambulance services have policies and procedures requiring ambulance crews to complete clinical documentation for these patients, as they do for patients who travel to hospital. However, studies have suggested that documentation does not get completed for a large proportion of non-conveyed patients. METHODS: A qualitative study in one large ambulance service trust used focus groups to explore crew members' attitudes towards clinical documentation and non-conveyed patients. RESULTS: Considerable ambiguity was found: crews were aware of the need to "cover their backs" by completing clinical records, but at the same time expressed doubts about the value of this documentation. There appeared to be two main circumstances in which records were not completed. Firstly, there were the cases where crews may have been unable to obtain necessary information from patients who were intoxicated or otherwise uncooperative. Secondly, there were cases where the crews may not have recognised their encounter with a patient as having a clinical dimension, such as older people who had fallen but were apparently uninjured. These circumstances were combined with a lack of monitoring by managers of whether forms were being completed, and a disinclination on the part of some crew members to do what they regarded as unnecessary work. CONCLUSION: The low rates of completion of clinical records for non-conveyed patients appeared to result from crew members not believing they were important in every circumstance, combined with a lack of management focus. Low rates of completion may lead in turn to clinical risk and a risk of litigation if things go wrong.

Tuberculosis screening in migrants in selected European countries shows wide disparities.

Well-established tuberculosis screening units in Western Europe were selectively sampled. Three screening units in Norway, two in the UK, one in the Netherlands and one in Switzerland were evaluated. The aim of this study was to describe a range of service models used at a number of individual tuberculosis units for the screening of new entrants into Europe. Semi-structured interviews were conducted with clinicians, nurses and administrators from a selected sample of European tuberculosis screening units. An outline of key themes to be addressed was forwarded to units ahead of scheduled interviews. Themes included the history of the unit, structure, processes and outputs involved in screening new entrants for tuberculosis. Considerable variation in screening services exists in the approaches studied. Units are sited in transit camps or as units within hospital facilities. Staff capacity and administration varies from one clinic per week with few dedicated staff to fully dedicated units. Only one site recorded symptoms; tuberculin testing was universal in children, but varied in adults; chest radiograph screening was universal except at one site where a positive tuberculin skin test or symptoms were required in those <35 yrs of age before ordering a radiograph. Few output data are routinely and systematically collected, which hinders comparison and determination of effectiveness and efficiency. Service models for screening new immigrants for tuberculosis appear to vary in Western Europe. The systematic collection of data would make international comparisons between units easier and help draw conclusions that might usefully inform service development.

Less IS less: a randomised controlled trial comparing cautious and rapid nalbuphine dosing regimens.

OBJECTIVE: This study aimed to determine which of two paramedic administered nalbuphine dosing regimens combined the greater analgesic effect with the minimum of adverse events. METHODS: Patients suffering from chest pain or trauma were randomised to receive either a rapid dosing regimen (10 mg over 30 seconds, repeated once after three minutes if pain score remained above three) or a cautious regimen (5 mg over two minutes, repeated at three minute intervals if pain score remained above three to a maximum dose of 20 mg). Data were collected on analgesic effectiveness, changes in vital signs, and patient reported side effects. RESULTS: The pain score fell by a mean of 4.29 and 3.49 in the rapid and cautious regimen groups respectively (difference = 0.79, 95% CI 0.09 to 1.5, p = 0.028). However, over half the patients in both groups continued to suffer significant pain on arrival at hospital. There were no significant changes in vital signs after nalbuphine, but there was a greater incidence of patient reported drowsiness in rapid regimen patients (42% compared with 21%, 95% CI = 6.96 to 34.12%, p = 0.003). CONCLUSION: A rapid dosing regimen of nalbuphine using 10 mg increments is more effective than and equally as safe as a cautious regimen using 5 mg increments. Further research is required to determine if a maximum dose exceeding 20 mg would result in fewer patients continuing to suffer significant pain before arrival at hospital.

Improving surveillance for injuries associated with potential motor vehicle safety defects.

OBJECTIVE: To improve surveillance for deaths and injuries associated with potential motor vehicle safety defects. DESIGN: Vehicles in fatal crashes can be studied for indications of potential defects using an "early warning" surveillance statistic previously suggested for screening reports of adverse drug reactions. This statistic is illustrated with time series data for fatal, tire related and fire related crashes. Geographic analyses are used to augment the tire related statistics. RESULTS: A statistical criterion based on the Poisson distribution that tests the likelihood of an expected number of events, given the number of events that actually occurred, is a promising method that can be readily adapted for use in injury surveillance. CONCLUSIONS: Use of the demonstrated techniques could have helped to avert a well known injury surveillance failure. This method is adaptable to aid in the direction of engineering and statistical reviews to prevent deaths and injuries associated with potential motor vehicle safety defects using available databases.

The porcine hemodialysis access model.

PURPOSE: To create a porcine hemodialysis access model that reliably reproduces intimal hyperplasia (IH) of the outflow vein similar to that which causes access failure in human patients undergoing dialysis treatments. MATERIALS AND METHODS: Surgical technique for creation of side-to-side iliac-artery-to-ipsilateral-iliac-vein (IAV) native fistulas and IAV conduits was optimized in three standard-bred pigs. Persistent patency of fistulas and conduits was demonstrated in two additional pigs allowed to survive for 1 week. IAV fistulas and contralateral 2-cm polytetrafluoroethylene IAV conduits were created in five additional pigs. Venous outflow from these fistulas and conduits was evaluated with venography and intravascular ultrasound (IVUS) immediately after creation (day 0) and at 2-week intervals for as long as 64 days. Animals were killed at 30 days (n = 1), 42 days (n = 2), or 64 days (n = 2), and the arteries, veins, and conduits were evaluated histologically. RESULTS: IAV native fistulas remained patent until the animals' death and conduits remained patent for at least 14 days in four of five pigs; both the fistula and conduit likely occluded before 16-day follow-up in the fifth pig. At 42-64 days, venography demonstrated maximum fistula outflow vein diameter stenoses of 53%-76% and maximum conduit outflow vein stenoses of 44%-84%, and IVUS demonstrated maximum area stenoses of 64%-86% and 43%-82%, respectively. Three of five conduits occluded, one before 16-day follow-up, one between 14 and 28 days, and the other after 42 days. Histologic sections demonstrated IH predominantly affecting the veins at the anastomoses and central (cephalad) to the anastomoses in all pigs. CONCLUSION: This porcine model reproduces IH in the fistula or conduit outflow vein with measurable stenosis. Such a model might allow relevant preclinical evaluation of interventional devices and techniques intended to reduce the effects of IH in human patients undergoing dialysis treatments.

Hexosamines regulate leptin production in human subcutaneous adipocytes.

The hexosamine biosynthetic pathway has recently been proposed as a mechanism through which cells "sense" nutrient flux to regulate leptin release. This study was undertaken to examine the regulation of leptin production by hexosamines in human adipocytes. Adipose tissue UDP-N-acetylglucosamine, an end product of hexosamine biosynthesis, was elevated 3.2-fold, and ob messenger ribonucleic acid was elevated 2-fold in the sc adipose tissue of 17 obese [body mass index (BMI), 41.3+/-12.0 kg/m2; age, 31+/-5 yr] subjects compared to 14 lean (BMI, 23.4+/-1.6 kg/m2; age, 33+/-11 yr) subjects. Serum leptin was increased 2.7-fold in the obese subjects. A significant positive relationship was found between adipose tissue UDP-N-acetylglucosamine and BMI (Spearman correlation = 0.576; P = 0.0007) and between UDP-N-acetylglucosamine and serum leptin (Spearman correlation = 0.4650; P = 0.0145). Treatment of isolated sc adipocytes with 1 mmol/L glucosamine, an intermediate product in UDP-N-acetylglucosamine biosynthesis, increased leptin release 21.4+/-17.6% (mean +/- SD) over control (P = 0.0365) and 74.5+/-82.8% over control (P = 0.0271) in adipocytes from lean (BMI, 23.2+/-1.6 kg/m2; n = 6) and obese (BMI, 55.4+/-13.0 kg/m2,; n = 9) subjects, respectively, by 48 h of culture. Inhibition of UDP-N-acetylglucosamine biosynthesis with 6-diazo-5-oxo-norleucine reduced glucose-stimulated leptin release from cultured adipocytes 21.8+/-32.4% (P = 0.0395; n = 12) and ob gene expression 19.9+/-18.9% (P = 0.0208; n = 8) by 48 h of treatment. These findings suggest that hexosamine biosynthesis regulates leptin production in human adipose tissue.

HIV seroprevalence by anonymous testing in patients with Mycobacterium tuberculosis and in tuberculosis contacts.

Having witnessed a large increase in Mycobacterium tuberculosis notifications in south London, we wanted to ascertain the prevalence of HIV and tuberculosis co-infection in our patients. All patients with tuberculosis and their contacts were anonymously tested for HIV in blood and saliva, respectively. 11.4% of patients (from various demographic groups) with tuberculosis who attend chest clinics in south London are HIV positive. In addition, 5% of individuals seen in the tuberculosis contact screening clinics and 4% new entrants are HIV positive. All patients with Mycobacterium tuberculosis, irrespective of background, should be urged to have an HIV test.

Evaluation of the role of intercellular adhesion molecule 1 in a rodent model of chronic venous hypertension.

PURPOSE: To evaluate the role of intercellular adhesion molecule 1 (ICAM-1) in cutaneous leukocyte trapping in venous disease, we used our rodent model of venous hypertension (VH). MATERIALS AND METHODS: VH was created in adult rats by ligation of the inferior vena cava, bilateral common iliac veins, and bilateral common femoral veins. In the Phase I experimental (exptl) group, anti-ICAM-1 monoclonal antibody (1A29) was given intravenously prior to venous ligations. Acute venous pressures were measured in the exptl and control (ctrl) (ligation only) groups. Bilateral forelimb and hindlimb skin specimens were harvested for myeloperoxidase (MPO) assay. In Phase II, VH was created in a chronic group; in a sham-operated group, ties were placed around the same vessels without ligations. Two weeks later, venous pressures were measured and radiolabeled ((125)I and (131)I) monoclonal antibody (mAb) to ICAM-1 was injected and allowed to circulate for 5 min before the level of radiolabeled antibody within forelimb and hindlimb specimens was measured. RESULTS: In the acute study with 1A29, hindlimb pressures were significantly elevated in both the ctrl (n = 4) and exptl (n = 4) hindlimbs (15.4 +/- 0.239 and 13.8 +/- 1.89 mm Hg, respectively) compared with ctrl and exptl forelimbs (1.38 +/- 0.554 and 1.50 +/- 0.612 mm Hg, respectively). However, MPO activity was significantly elevated in the hindlimbs of the ctrl group compared with the hindlimbs of the exptl animals (19.8 +/- 1.54 U vs 6.71 +/- 2.46 U). In the chronic VH rats (n = 5) given radiolabeled anti-ICAM-1 mAb, the hindlimb pressures (10.1 +/- 4.52 mm Hg) were significantly elevated (P < 0.05) compared with forelimb pressures (1 +/- 0.447 mm Hg) and compared with the forelimb and hindlimb pressures in the sham-operated animals (n = 4) (1.63 +/- 0.813 and 4.25 +/- 2.13 mm Hg, respectively). However, there was not a significant difference in the quantity of ICAM-1-hindlimb versus forelimb or chronic VH versus sham. CONCLUSIONS: Anti-ICAM-1 mAb decreased MPO activity in hypertensive hindlimb skin, supporting the instrumental role of ICAM-1 in cutaneous leukocyte trapping. However, the constituent endothelial ICAM-1 is not elevated by VH.

The beta1-integrin cytosolic domain optimizes phospholipase A2-mediated arachidonic acid release required for NIH-3T3 cell spreading.

Inhibition of PLA2 activity and rescue by addition of exogenous AA was used to demonstrate that AA production is essential for integrin-mediated NIH-3T3 murine cell spreading. Both AA release and cell spreading after attachment to a FN substrate were inhibited by the PLA2 inhibitor mepacrine. AA release was essential for signaling spreading since the inhibition of spreading induced by mepacrine was overcome by exogenous AA. Cells ectopically expressing full-length chicken beta1-integrins both released AA and spread fully on a substrate of anti-chicken beta1-integrin monoclonal antibody, and inhibition of PLA2 by mepacrine suppressed both spreading and AA release. Exogenous AA also reversed this mepacrine-induced inhibition of spreading. The role of the beta1-integrin cytosolic domain in AA release was examined by comparing responses of cells expressing full-length chicken beta1-integrins versus cells expressing a deletion mutant chicken beta1-integrin with a truncated cytosolic domain. Cells expressing a truncated chicken beta1-integrin released significantly less AA and failed to spread on the anti-chicken beta1-integrin antibody substrate. Furthermore, clustering full-length receptors with soluble antibody stimulated greater AA release than clustering of receptors having truncated cytosolic domains. These data suggest the beta1-integrin cytosolic domain is required for optimal PLA2 activation to produce AA necessary for cell spreading.

Seating positions and children's risk of dying in motor vehicle crashes.

OBJECTIVES: To determine the effects of seating position, combined with restraint use and airbag status, on children's risk of dying in crashes. METHODS: Using 1988-95 data from the United States Fatality Analysis Reporting System, risk of death was compared among front and rear seated passengers aged 12 and younger who were involved in fatal crashes for different categories of restraint use and in vehicles with and without passenger airbags. RESULTS: Restrained children in rear seats had the lowest risk of dying in fatal crashes. Among children seated in the rear, risk of death was reduced 35% in vehicles without any airbags, 31% in vehicles equipped only with driver airbags, and 46% in vehicles with passenger airbags. Both restrained and unrestrained children aged 0-12 were at lower risk of dying in rear seats. Rear seats also afforded additional protection to children aged 5-12 restrained only with lap belts compared with lap/shoulder belted children in front seats. Children were about 10-20% less likely to die in rear center than in rear outboard positions. CONCLUSIONS: Parents and others who transport children should be strongly encouraged to place infants and children in rear seats whether or not vehicles have airbags. Existing laws requiring restraint use by children should be strengthened and actively enforced.

Prisoners' knowledge and attitude toward prophylactic treatment and therapy.

Identifying factors that hinder an inmate's compliance with Pneumocystis carinii pneumonia (PCP) prophylaxis therapy can be critical in preventing or decreasing the occurrence of PCP in this population. Anticipated factors include lack of knowledge about PCP and its proposed treatment, fear of the adverse effects of prophylaxis therapy, and lack of trust in the correctional facility medical team. Structured interviews were administered to HIV-positive male inmates chosen randomly (n = 104) at a medium- to maximum-security medical correctional facility located in the western portion of the United States. A basic "HIV 101 and Early Intervention" program encompassed the presentation of HIV facts and knowledge as well as safer sex practices. The results revealed that 95% of the respondents were knowledgeable about PCP and the side effects of their medications, and 56% of the respondents were afraid of the medications' side effects. Significant differences based on age were recorded for several specific knowledge questions, including the preventable nature of PCP.