Solar particle event storm shelter requirements for missions beyond low Earth orbit.

Protecting spacecraft crews from energetic space radiations that pose both chronic and acute health risks is a critical issue for future missions beyond low Earth orbit (LEO). Chronic health risks are possible from both galactic cosmic ray and solar energetic particle event (SPE) exposures. However, SPE exposures also can pose significant short term risks including, if dose levels are high enough, acute radiation syndrome effects that can be mission- or life-threatening. In order to address the reduction of short term risks to spaceflight crews from SPEs, we have developed recommendations to NASA for a design-standard SPE to be used as the basis for evaluating the adequacy of proposed radiation shelters for cislunar missions beyond LEO. Four SPE protection requirements for habitats are proposed: (1) a blood-forming-organ limit of 250 mGy-equivalent for the design SPE; (2) a design reference SPE environment equivalent to the sum of the proton spectra during the October 1989 event series; (3) any necessary assembly of the protection system must be completed within 30 min of event onset; and (4) space protection systems must be designed to ensure that astronaut radiation exposures follow the ALARA (As Low As Reasonably Achievable) principle.

Comparison of direct in-house cerebrospinal fluid cytology with commercial pathology results in dogs.

OBJECTIVES: To investigate the correspondence between in-house direct cytological assessment of cerebrospinal fluid and results from a commercial veterinary pathology laboratory. METHODS: Prospective inclusion of samples from dogs that were presented for investigation of suspected neurological disease and had cerebrospinal fluid samples submitted to a commercial pathology laboratory for analysis. A board-certified veterinary pathologist assessed all cerebrospinal fluid samples, and a line smear was assessed in-house by two observers. Nucleated cell count, red blood cell count and differential cell counts were recorded and compared. RESULTS: In-clinic and commercial pathology nucleated cell counts and red blood cell counts were strongly correlated. In-house line smear results were compared with the gold standard of a defined dichotomous rating of 'increased nucleated cell count' provided by the external pathology service. Sensitivity was 93% and specificity 80% for samples with at least two cells per linear field. CLINICAL APPLICATION: Although not a replacement for the assessment of cerebrospinal fluid samples by specialist veterinary pathologists, this method can provide rapid and clinically meaningful information before externally processed sample results are available.

Primary immune-mediated thrombocytopenia and immune-mediated neutropenia suspected in a 21-week-old Maine Coon cat.

CASE REPORT: A 21-week-old Maine Coon cat presented with an acute-onset coagulopathy. Severe concurrent thrombocytopenia and neutropenia were identified on peripheral blood smears and bone marrow cytology supported a peripheral consumptive process. Other than mild superficial haemorrhage, the cat was clinically well and screening for retroviral diseases, abdominal ultrasound examination, thoracic radiography, haematology and biochemistry panels did not identify an underlying disease. There was no historical pharmaceutical or toxicological trigger noted and the cat was from an area without endemic Ehrlichia spp. There was a rapid resolution of both cytopenias following treatment with immunosuppressive doses of prednisolone, though a mild relapse occurred during gradual prednisolone withdrawal and was responsive to a dose increase. CONCLUSIONS: This report describes this combination of diseases for the first time in a cat and presents a younger patient than previously described with feline primary immune-mediated haematological disease.

Thrombosis in ovarian cancer: a case control study.

BACKGROUND: Thrombotic events are common in cancer patients and have been associated with an adverse prognosis in large registry-based studies. METHODS: A retrospective cohort of 417 patients with ovarian cancer treated at a tertiary cancer centre between 2006 and 2009 was studied to identify the incidence and risk factors for thrombotic events and the prognostic impact of thrombosis. Patient outcomes were evaluated against a matched control group without thrombosis. RESULTS: Ninety-nine thrombotic events occurred in 90 patients (21.6%) from 8 months before diagnosis to 56 months following diagnosis, peaking in the 4 months following diagnosis. Patients with thrombosis were older (mean 65 vs 61 years, P=0.007), had a worse performance status (PS ≥2: 29.9% vs 9.5%, P<0.0001) and had a more advanced FIGO stage (FIGO III/IV 75.6% vs 56.9%, P<0.0001) than patients without thrombosis. Shorter overall survival was seen in patients with pulmonary embolism and pelvic/lower limb deep vein thrombosis than without thrombosis (P=0.001). When the control group was matched for stage and PS, no survival difference was seen (P=0.91). CONCLUSION: Ovarian cancer patients with thrombotic events had a shorter survival. However, when matched for prognostic factors (PS and FIGO stage), thrombosis did not impact upon prognosis.

Diagnostic accuracy of small intestine ultrasonography using an oral contrast agent in Crohn's disease: comparative study from the UK.

AIM: To evaluate the usefulness of small intestine contrast-enhanced ultrasonography (SICUS) using an oral contrast agent in routine clinical practice by assessing the level of agreement with the established techniques, small bowel follow-through (SBFT) and computed tomography (CT), and diagnostic accuracy compared with the final diagnosis in the detection of small bowel Crohn's disease (CD) and luminal complications in a regional centre. MATERIALS AND METHODS: All symptomatic known or suspected cases of CD who underwent SICUS were retrospectively reviewed. The level of agreement between SICUS and SBFT, CT, histological findings, and C-reactive protein (CRP) level was assessed using kappa (κ) coefficient. Sensitivity was demonstrated using the final diagnosis as the reference standard defined by the outcome of clinical assessment, follow-up, and results of investigations other than SICUS. RESULTS: One hundred and forty-three patients underwent SICUS of these 79 (55%) were female. Eighty-six (60%) were known to have CD and 57 (40%) had symptoms suggestive of intestinal disease with no previous diagnosis. Forty-six (55%) of the known CD patients had had at least one previous surgical resection. The sensitivity of SICUS in detecting active small bowel CD in known CD and undiagnosed cases was 93%. The kappa coefficient was 0.88 and 0.91 with SBFT and CT, respectively. SICUS detected nine patients who had one or more small bowel strictures and six patients with a fistula all detected by SBFT or CT. CONCLUSION: SICUS is not only comparable to SBFT and CT but avoids radiation exposure and should be more widely adopted in the UK as a primary diagnostic procedure and to monitor disease complications in patients with CD.

Nasal cryptococcosis in two dogs in New Zealand.

CASE HISTORY: Two young, large-breed female dogs were presented with an acute onset of sneezing and nasal discharge. One patient had concurrent epistaxis and facial deformity. CLINICAL FINDINGS: Decreased airflow was noted through the left nostril in Case 1, while Case 2 showed facial deformity. Nasal radiographs from Case 1 showed a soft tissue opacity in the left nasal cavity and frontal sinus. Rhinoscopy revealed roughened, erythematous nasal turbinates in both patients, and a mass in the left caudal nasal cavity of Case 1. Cryptococcus spp. were demonstrated histopathologically on a nasal biopsy. Tissue culture and serum antigen titres were positive for Cryptococcus spp. DIAGNOSIS: Chronic rhinitis secondary to Cryptococcus gattii infection in Case 1, and Cryptococcus neoformans infection in Case 2. CLINICAL RELEVANCE: These are the first reported cases of Cryptococcus spp. rhinitis in dogs in New Zealand.

Drug-like inhibitors of protein-protein interactions: a structural examination of effective protein mimicry.

Protein-protein interactions represent targets for drug discovery that are highly relevant in a biological sense, but have proven difficult in a practical sense. Nevertheless, there have been recent successes in discovering drug-like small molecule inhibitors of protein-protein systems. To build on this progress, it is worth analyzing successful cases to understand at a molecular level the strategies by which these compounds effectively interfere with protein-protein pairing. A commonly observed situation is one wherein the small molecule acts as a direct mimic of one of the protein partners. This review focuses exclusively on cases where this strategy is employed, and examines the structural characteristics of the binding sites and the conformational attributes of the small molecule ligands. Common traits shared among these successful examples are identified, and formulated into potentially useful guidance for drug discovery efforts within this target class.

Rheology of concentrated carbon nanotube suspensions.

The rheological properties of non-Brownian carbon nanotube suspensions are measured over a range of nanotube volume fractions spanning the transition from semidilute to concentrated. The polymer-stabilized nanotubes are "sticky" and form a quiescent elastic network with a well-defined shear modulus and yield stress that both depend strongly on nanotube volume fraction with different but related critical exponents. We compare controlled-strain-rate and controlled-stress measurements of yielding in shear flow, and we study the effect of slow periodic stress reversal on yielding and the arrest of flow. Our measurements support a universal scaling of both the linear viscoelastic and steady-shear viscometric response. The former allows us to extract the elastic shear modulus of semidilute nanotube networks for values that are near or below the resolution limit of the rheometers used, while the latter provides a similar extrapolation of the yield stress. A simple scaling argument is used to model the dependence of yield stress and elastic modulus on concentration.

Nonequilibrium phase diagram of sticky nanotube suspensions.

We report a universal phase diagram describing the evolution from solidlike networks to flowing nematics for "sticky" nanotube suspensions under an applied shear stress. Although the nanotubes are strongly non-Brownian, we find features characteristic of first-order phase transitions, including a discontinuity in the nematic order parameter at the isotropic-(para)nematic phase boundary. Using simple physical arguments, we account for the shape of the coexistence curves, as well as the dependence of the order parameter on concentration and stress.

Measuring progress towards the MDG for maternal health: including a measure of the health system's capacity to treat obstetric complications.

OBJECTIVE: This paper argues for an additional indicator for measuring progress of the Millennium Development Goal for maternal health-the availability of emergency obstetric care. METHODS: MDG monitoring will be based on two indicators: the maternal mortality ratio and the proportion of births attended by skilled personnel. Strengths and weaknesses of a third indicator are discussed RESULTS: The availability of EmOC measures the capacity of the health system to respond to direct obstetric complications. Benefits to using this additional indicator are its usefulness in determining an adequate distribution of services and showing management at all levels what life-saving interventions are not being provided, and stimulate thought as to why. It can reflect programmatic changes over a relatively short period of time and data requirements are not onerous. CONCLUSION: A measure of strength of the health system is important since many interventions depend on the health system for their implementation.

Global patterns in availability of emergency obstetric care.

OBJECTIVE: This paper examines the availability of basic and comprehensive emergency obstetric care (EmOC), interventions used to treat direct obstetric complications. Determining what interventions are provided in health facilities is the first priority in analyzing a country's capabilities to treat obstetric emergencies. There are eight key interventions, six constitute basic EmOC and all eight comprehensive EmOC. METHODS AND RESULTS: Based on data from 24 needs assessments, the following global patterns emerge: comprehensive EmOC facilities are usually available to meet the recommended minimum number for the size of the population, basic EmOC facilities are consistently not available in sufficient numbers, both in countries with high and moderate levels of maternal mortality, and the majority of facilities offering maternity services provide only some interventions indicating an unrealized potential. CONCLUSION: Upgrading maternities, health centers and hospitals to at least basic EmOC status would be a major contributing step towards maternal mortality reduction in resource-poor countries.

The availability of life-saving obstetric services in developing countries: an in-depth look at the signal functions for emergency obstetric care.

OBJECTIVE: This paper examines the frequency with which a set of life-saving interventions or signal functions was performed to treat major obstetric complications. METHODS AND RESULTS: The basic signal functions include parenteral antibiotics, anticonvulsants and oxytocics, and the procedures of manual removal of the placenta, removal of retained uterine products, and assisted vaginal delivery. Comprehensive functions include the six basic functions, cesarean delivery, and blood transfusions. Data from 1906 health facilities in 13 countries indicate that the most likely functions to be reported are oxytocics and antibiotics. The basic function least likely to be reported is assisted vaginal delivery. Many of the facilities surveyed did not have the infrastructure to perform operations or provide blood transfusions. CONCLUSIONS: These data can help governments allocate their budgets appropriately, help policy makers and planners identify systemic bottlenecks and prioritize solutions. Monitoring the performance of the functions informs us of the capacity of the health system to provide key interventions when obstetric emergencies occur.

Rheo-optical studies of carbon nanotube suspensions.

We use a polarization-modulation technique to investigate the optical anisotropy of multi- and single-wall carbon nanotubes suspended in a variety of solvents under simple shear flow. Measurements of birefringence and dichroism are performed as a function of shear rate, tube concentration, and solvent viscosity. At fixed volume fraction, the anisotropy increases with increasing shear stress due to enhanced flow alignment. At fixed shear stress, the anisotropy increases with volume fraction due to rotational excluded-volume interactions. By considering the rotational diffusivity as a function of nanotube length, diameter, concentration, and solvent viscosity, we demonstrate a leading-order scaling relation for the optical anisotropy in terms of rotary Peclet number Pe. At low Pe, our results are in qualitative agreement with the theoretical predictions of Doi and Edwards. At high Pe, our data suggest that the degree of nanotube alignment scales as Pe16.

Anisotropy of sheared carbon-nanotube suspensions.

We measure the anisotropy of sheared carbon-nanotube suspensions for a broad range of concentration, aspect ratio, and strain rate using a variety of methods. Our measurements highlight the importance of excluded-volume interactions in the semidilute regime, with scaling in terms of a dimensionless shear rate. Our results also suggest that such interactions might be exploited to fractionate carbon nanotubes by length in simple shear flow.

The evidence for emergency obstetric care.

PURPOSE: We searched for evidence for the effectiveness of emergency obstetric care (EmOC) interventions in reducing maternal mortality primarily in developing countries. METHODS: We reviewed population-based studies with maternal mortality as the outcome variable and ranked them according to the system for ranking the quality of evidence and strength of recommendations developed by the US Preventive Services Task Force. A systematic search of published literature was conducted for this review, including searches of Medline, PubMed, Cochrane Database of Systematic Reviews, the Cochrane Pregnancy and Childbirth Database and the Cochrane Controlled Trials Register. RESULTS: The strength of the evidence is high in several studies with a design that places them in the second and third tier in the quality of evidence ranking system. No studies were found that are experimental in design that would give them a top ranking, due to the measurement challenges associated with maternal mortality, although many of the specific individual clinical interventions that comprise EmOC have been evaluated through experimental design. There is strong evidence based on studies, using quasi-experimental, observational and ecological designs, to support the contention that EmOC must be a critical component of any program to reduce maternal mortality.

Program note: applying the UN process indicators for emergency obstetric care to the United States.

The United Nations Process Indicators for emergency obstetric care (EmOC) have been used extensively in countries with high maternal mortality ratios (MMR) to assess the availability, utilization and quality of EmOC services. To compare the situation in high MMR countries to that of a low MMR country, data from the United States were used to determine EmOC service availability, utilization and quality. As was expected, the United States was found to have an adequate amount of good-quality EmOC services that are used by the majority of women with life-threatening obstetric complications.

Cluster shape anisotropy in irreversibly aggregating particulate systems.

The results for cluster shape anisotropy over a broad range (10)(-3)-10(-1)) of monomer volume fractions, fv values, are presented for both two- (2d) and three-dimensional (3d) simulations of diffusion-limited (DLCA), ballistic-limited (BLCA), and reaction-limited (RLCA) cluster-cluster aggregation classes. We find that all three aggregation classes have different dilute-limit shape anisotropies, with the diffusion-limited model having the largest value of anisotropy and the reaction-limited model having the smallest. The simulation result for the cluster shape anisotropy for each of the three aggregation classes is slightly less than the corresponding prediction of the hierarchial model. In addition, we find excellent agreement between the 2d DLCA simulation results and experimental measurements of shape anisotropy. At late times, shape anisotropy decreases from the dilute-limit value.

Structural crossover in dense irreversibly aggregating particulate systems.

Cluster-cluster aggregation has been simulated by off-lattice Monte Carlo methods for diffusion-limited (DLCA), ballistic-limited, and reaction-limited cluster aggregation classes. We find that as the system evolves and becomes dense, the largest cluster develops a hybrid structure with mass fractal dimension D(f) approximately 2.6 over large length scales, while at smaller length scales, the early time dilute-limit fractal structure is frozen in. The largest cluster is thus an aggregate of smaller aggregates with a different fractal dimension, and we call it a "superaggregate." The crossover length separating the two morphologies, which we call the critical radius of gyration, can be calculated based on a simple theory that assumes a monodisperse cluster size distribution. This agrees well with simulation results for DLCA. However, for other classes we find that the increasing polydispersity in cluster size pushes the simulated crossover length radius of gyration to values systematically larger than the predicted value.

A phase I study of AMD473 and docetaxel given once every 3 weeks in patients with advanced refractory cancer: a National Cancer Institute of Canada-Clinical Trials Group trial, IND 131.

BACKGROUND: AMD473 (previously ZD0473) is a new-generation platinum compound with activity against a wide range of human tumour cell lines and xenografts, including carboplatin- and cisplatin-resistant lines. To assess its potential combined with a taxane, a phase I study of AMD473 and docetaxel in advanced cancer was initiated by the National Cancer Institute of Canada-Clinical Trials Group. PATIENTS AND METHODS: Patients with advanced cancer, measurable disease, performance status Eastern Cooperative Oncology Group 0-2, no major organ dysfunction, and one or no previous taxane regimen received escalating doses of AMD473 and docetaxel every 3 weeks, with a starting dose of AMD473 80 mg/m(2) and docetaxel 60 mg/m(2). RESULTS: Thirty-three patients enrolled on four dose levels were evaluable for toxicity and 25 patients were evaluable for response. The maximum tolerated dose was dose level 4 (AMD473 120 mg/m(2) and docetaxel 75 mg/m(2)), with grade 4 neutropenia in both minimally and heavily pretreated patients causing dose-limiting toxicity. As well at dose level 4, one patient had grade 3 vomiting despite premedication. Dose level three was expanded for both groups of patients and was defined as the recommended phase II dose at AMD473 100 mg/m(2) and docetaxel 75 mg/m(2). Non-hematologic toxicities included fatigue, diarrhoea and other mild toxicities. There was one partial response in a patient with prostate cancer and stable disease in 15 patients. No apparent pharmacokinetic interaction was noted. CONCLUSION: AMD473 and docetaxel can be combined with a recommended phase II dose level of 100 mg/m(2) and 75 mg/m(2), respectively, given intravenously every 3 weeks. The combination has activity and should be explored in responsive tumour types.