Observation of coherent elastic neutrino-nucleus scattering.

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ confidence level, using a low-background, 14.6-kilogram CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.

Genetic susceptibility to cutaneous melanoma in southern Switzerland: role of CDKN2A, MC1R and MITF.

BACKGROUND: Nearly 10% of all cases of cutaneous melanoma (CM) occur in patients with a personal or family history of the disease. OBJECTIVES: To obtain information about genetic predisposition to CM in Ticino, the southern region of Switzerland, a zone with moderate-to-high CM incidence. METHODS: We identified germline mutations in highly CM-associated genes (CDKN2A and CDK4) and low/medium-penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first- or second-degree relatives. Healthy blood donors (n = 146) were included as a control group. RESULTS: From July 2010 to July 2012, 57 patients (41 pedigrees) were included. Twenty-six were melanoma-prone families (with at least two cases) and 15 had multiple CMs. Pancreatic cancer was found in six families. The CDKN2A mutation p.V126D was identified in seven patients (four families) with a founder effect, whereas CDKN2A A148T was detected in seven cases (five families) and seven healthy donors (odds ratio 2·76, 95% confidence interval 0·83-9·20). At least one MC1R melanoma-associated polymorphism was detected in 32 patients (78%) and 97 healthy donors (66%), with more than one polymorphism in 12 patients (29%) and 25 healthy donors (17%). The MITF variant p.E318K was identified in four patients from three additional pedigrees (7%) and one healthy control (0·7%). CONCLUSIONS: Inclusion criteria for the Ticino population for genetic assessment should follow the rule of two (two affected individuals in a family or a patient with multiple CMs), as we detected a CDKN2A mutation in almost 10% of our pedigrees (four of 41), MITF p.E318K in 7% (three of 41) and a higher number of MC1R variants than in the control population.

Long-term seafloor monitoring at an open ocean aquaculture site in the western Gulf of Maine, USA: development of an adaptive protocol.

The seafloor at an open ocean finfish aquaculture facility in the western Gulf of Maine, USA was monitored from 1999 to 2008 by sampling sites inside a predicted impact area modeled by oceanographic conditions and fecal and food settling characteristics, and nearby reference sites. Univariate and multivariate analyses of benthic community measures from box core samples indicated minimal or no significant differences between impact and reference areas. These findings resulted in development of an adaptive monitoring protocol involving initial low-cost methods that required more intensive and costly efforts only when negative impacts were initially indicated. The continued growth of marine aquaculture is dependent on further development of farming methods that minimize negative environmental impacts, as well as effective monitoring protocols. Adaptive monitoring protocols, such as the one described herein, coupled with mathematical modeling approaches, have the potential to provide effective protection of the environment while minimize monitoring effort and costs.

Apparatus to characterize gas sensor response under real-world conditions in the lab.

The use of semiconducting metal-oxide (MOX) based gas sensors in demanding applications such as climate and environmental research as well as industrial applications is currently hindered by their poor reproducibility, selectivity, and sensitivity. This is mainly due to the sensing mechanism which relies on the change of conductivity of the metal-oxide layer. To be of use for advanced applications metal-oxide (MOX) gas sensors need to be carefully prepared and characterized in laboratory environments prior to deployment. This paper describes the working principle, design, and use of a new apparatus that can emulate real-world conditions in the laboratory and characterize the MOX gas sensor signal in tailor-made atmospheres. In particular, this includes the control of trace gas concentrations and the control of oxygen and humidity levels which are important for the surface chemistry of metal-oxide based sensors. Furthermore, the sensor temperature can be precisely controlled, which is a key parameter of semiconducting, sensitive layers, and their response to particular gas compositions. The setup also allows to determine the power consumption of each device individually which may be used for performance benchmarking or monitoring changes of the temperature of the gas composition. Both, the working principle and the capabilities of the gas measurement chamber are presented in this paper employing tin dioxide (SnO2) based micro sensors as exemplary devices.

Detection of Trypanosoma evansi infection in wild capybaras from Argentina using smear microscopy and real-time PCR assays.

Trypanosoma evansi is a flagellated protozoan that parasitizes a wide variety of mammals, occasionally including humans. In South America, it infects horses, cattle, buffaloes, dogs and wild mammals, causing a disease known as "Mal de Caderas", which results in important economic losses due to a wide range of pathological expressions. Argentina represents the southern limit of its distribution. The capybara (Hydrochoerus hydrochaeris) is a large rodent found in tropical to temperate freshwater wetlands of South America. As capybaras infected with T. evansi present no clinical signs of disease, withstanding high parasitaemia, this species was proposed as a reservoir host. In this study we investigated the prevalence and parasitaemic intensity of T. evansi in samples obtained from 60 free-ranging capybaras of Esteros del Iberá (Corrientes province, northeastern Argentina) using smear microscopy and real-time PCR assays. All the cases of capybaras infected with T. evansi were found during one of the years studied, with no evidence of seasonality. The overall infection prevalence was 10%, but between years it ranged from 0% to 17% (in 2011). This is the first confirmation of T. evansi infection in Argentina by molecular biology techniques. Our results showed no differences between the methods used to detect the presence of T. evansi in capybaras, which indicates that simple methods like microscopy can generate important data on the ecoepidemiology of this parasite. Both techniques used in this study represent a viable tool for ecoepidemiological studies, and can be used to produce good estimates of prevalence and parasitaemic level of the infection, which inform for the implementation of strategies for the control of the disease.

Interaction of bone-dental implant with new ultra low modulus alloy using a numerical approach.

Although mechanical stress is known as being a significant factor in bone remodeling, most implants are still made using materials that have a higher elastic stiffness than that of bones. Load transfer between the implant and the surrounding bones is much detrimental, and osteoporosis is often a consequence of such mechanical mismatch. The concept of mechanical biocompatibility has now been considered for more than a decade. However, it is limited by the choice of materials, mainly Ti-based alloys whose elastic properties are still too far from cortical bone. We have suggested using a bulk material in relation with the development of a new beta titanium-based alloy. Titanium is a much suitable biocompatible metal, and beta-titanium alloys such as metastable TiNb exhibit a very low apparent elastic modulus related to the presence of an orthorhombic martensite. The purpose of the present work has been to investigate the interaction that occurs between the dental implants and the cortical bone. 3D finite element models have been adopted to analyze the behavior of the bone-implant system depending on the elastic properties of the implant, different types of implant geometry, friction force, and loading condition. The geometry of the bone has been adopted from a mandibular incisor and the surrounding bone. Occlusal static forces have been applied to the implants, and their effects on the bone-metal implant interface region have been assessed and compared with a cortical bone/bone implant configuration. This work has shown that the low modulus implant induces a stress distribution closer to the actual physiological phenomenon, together with a better stress jump along the bone implant interface, regardless of the implant design.

Mechanical properties of low modulus beta titanium alloys designed from the electronic approach.

Titanium alloys dedicated to biomedical applications may display both clinical and mechanical biocompatibility. Based on nontoxic elements such as Ti, Zr, Nb, Ta, they should combine high mechanical resistance with a low elastic modulus close to the bone elasticity (E=20 GPa) to significantly improve bone remodelling and osseointegration processes. These elastic properties can be reached using both lowering of the intrinsic modulus by specific chemical alloying and superelasticity effects associated with a stress-induced phase transformation from the BCC metastable beta phase to the orthorhombic alpha(″) martensite. It is shown that the stability of the beta phase can be triggered using a chemical formulation strategy based on the electronic design method initially developed by Morinaga. This method is based on the calculation of two electronic parameters respectively called the bond order (B(o)) and the d orbital level (M(d)) for each alloy. By this method, two titanium alloys with various tantalum contents, Ti-29Nb-11Ta-5Zr and Ti-29Nb-6Ta-5Zr (wt%) were prepared. In this paper, the effect of the tantalum content on the elastic modulus/yield strength balance has been investigated and discussed regarding the deformation modes. The martensitic transformation beta-->alpha(″) has been observed on Ti-29Nb-6Ta-5Zr in contrast to Ti-29Nb-11Ta-5Zr highlighting the chemical influence of the Ta element on the initial beta phase stability. A formulation strategy is discussed regarding the as-mentioned electronic parameters. Respective influence of cold rolling and flash thermal treatments (in the isothermal omega phase precipitation domain) on the tensile properties has been investigated.

Bone properties surrounding hydroxyapatite-coated custom osseous integrated dental implants.

Calcium phosphate (hydroxyapatite or HA) coatings have been applied to Custom Osseous Integrated Implants (COIIs) to improve the quality of the bone-implant integration, yet little is known concerning the biomechanical properties of bone surrounding the HA-coated implants in humans over the long term. The purpose of this study was to characterize the mechanical and histomorphometric properties of the bone along the implant interface. Specimens were prepared from three similar mandibular implants that were functional in three female patients for about 11 years. Histomorphometric analyses showed bone-implant contact averaging 75% for all specimens. Area coverage of residual HA-coating ranged from 52 to 70%. When compared with previous studies, these results show a relatively high percentage of residual HA after a decade in vivo. Nanoindentation showed similar average values of hardness and modulus (p = 0.53 and p = 0.56, respectively) comparing bone adjacent to residual HA-coating and regions where the coating was absent. The elastic modulus was significantly lower for bone near the bone-implant interface (<200 µm) as compared with bone distant (>1000 µm) from the interface (p = 0.05), thereby reflecting different properties of the bone near these interfaces. Backscattered electron imaging showed darker gray levels which indicated decreased mineral content in bone adjacent to the implant, consistent with the nanoindentation results.

Human postmortem device retrieval and analysis--orthopaedic, cardiovascular, and dental systems.

On the basis of decades of analyzing implant devices, tissues, and clinical records from revision surgical explants (called device failure), studies now include postmortem donors and in situ conditions (called success). A key issue has been information exchange from an interdisciplinary team where basic physical and biological studies complement details of the clinical conditions for each device. Overall, the summary information has shown that most revisions were based on factors associated with the patient health, disease, and compliance, with few outcomes directly correlated with technology and device-specific factors. However, because of the large numbers of devices implanted annually (millions), any sampling that reveals adverse circumstances could result in a high level of importance and the need for additional studies of this type. Experience from prior retrieval and analysis demonstrates significant value where peer reviewed results from investigations have altered the discipline and have improved the quality and longevity of health care associated with implanted devices. This report summarizes completed and ongoing studies of cardiovascular, dental, and orthopaedic systems. Endovascular stents from autopsies showed damage including fretting and corrosion from overlapping and intersecting conditions, plus some corrosion and element transfers to tissues from individual stents. Studies are proposed to increase numbers to evaluate clinical significance. Dental implants from postmortem donors that functioned more than 10 years provided evaluations of cobalt alloy devices and calcium phosphate bone graft substitutes originally investigated in the 1970s. Tissue integration and stability correlated with data from prior laboratory in vitro and in vivo investigations. Studies of articulation and fixation from orthopaedic total joint arthroplasties showed some limitations related to surface changes of YTZ zirconia, specific damage due to implantation procedures, which led to modified instrumentation and techniques, and several examples of conditions leading to longer-term device-to-bone fixation. These types of multidisciplinary studies are continuing.

Synthesis and Mechanical Wear Studies of Ultra Smooth Nanostructured Diamond (USND) Coatings Deposited by Microwave Plasma Chemical Vapor Deposition with He/H(2)/CH(4)/N(2) Mixtures.

Ultra smooth nanostructured diamond (USND) coatings were deposited by microwave plasma chemical vapor deposition (MPCVD) technique using He/H(2)/CH(4)/N(2) gas mixture. The RMS surface roughness as low as 4 nm (2 micron square area) and grain size of 5-6 nm diamond coatings were achieved on medical grade titanium alloy. Previously it was demonstrated that the C(2) species in the plasma is responsible for the production of nanocrystalline diamond coatings in the Ar/H(2)/CH(4) gas mixture. In this work we have found that CN species is responsible for the production of USND coatings in He/H(2)/CH(4)/N(2) plasma. It was found that diamond coatings deposited with higher CN species concentration (normalized by Balmer H(α) line) in the plasma produced smoother and highly nanostructured diamond coatings. The correlation between CN/H(α) ratios with the coating roughness and grain size were also confirmed with different set of gas flows/plasma parameters. It is suggested that the presence of CN species could be responsible for producing nanocrystallinity in the growth of USND coatings using He/H(2)/CH(4)/N(2) gas mixture. The RMS roughness of 4 nm and grain size of 5-6 nm were calculated from the deposited diamond coatings using the gas mixture which produced the highest CN/H(α) species in the plasma. Wear tests were performed on the OrthoPOD(®), a six station pin-on-disk apparatus with ultra-high molecular weight polyethylene (UHMWPE) pins articulating on USND disks and CoCrMo alloy disk. Wear of the UHMWPE was found to be lower for the polyethylene on USND than that of polyethylene on CoCrMo alloy.

ONYX-411, a conditionally replicative oncolytic adenovirus, induces cell death in anaplastic thyroid carcinoma cell lines and suppresses the growth of xenograft tumors in nude mice.

Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer variant, accounting for 1-2% of all cases, but 33% of deaths, and exhibiting an average life expectancy of 5 months. ATC is largely unresponsive to radioactive iodine, chemotherapy, external beam radiation or surgery, underscoring the need for new and effective therapies. We evaluated the therapeutic potential of an oncolytic adenovirus, ONYX-411, that replicates selectively in and kills cells with dysfunction of the retinoblastoma (RB) pathway. In the present study, we report that ONYX-411 is able to induce cell death in eight human anaplastic carcinoma cell lines in vitro. The cytopathic effect of the virus is specific to cells with RB dysfunction, which appears to be frequent in ATC. We confirmed the expression of the coxsackie adenovirus receptor, CAR, in all ATC cell lines, demonstrating the potentially universal application of this oncolytic viral therapy to ATC. In addition, the growth of xenograft tumors induced in athymic mice with the ARO and DRO cell lines was significantly reduced by ONYX-411 treatment. These results indicate that ONYX-411 can be a potential therapeutic agent for the treatment of ATC, rendering this class of conditionally replicating adenoviruses an attractive candidate for clinical trials.

Reboxetine and cytochrome P450--comparison with paroxetine treatment in humans.

OBJECTIVES: The noradrenaline-selective antidepressant reboxetine in vitro is a weak inhibitor of both cytochrome P450 (CYP) 2D6 and CYP3A4. Thus, in this study the pharmacokinetics of reboxetine in relation to pharmacogenetics and the effects of reboxetine compared to paroxetine treatment on the CYP2D6 and CYP3A4 phenotype were analyzed in healthy control subjects. METHODS: Healthy male volunteers were treated with either 6 mg reboxetine (n = 26) or 30 mg paroxetine (n = 25). On Days 10/11 of treatment, serum concentrations of the antidepressants were measured and pharmacokinetic parameters calculated. Volunteers were phenotyped at the end of treatment and after at least 3 weeks washout (true phenotype) using 30 mg dextromethorphan (DM) hydrobromide given orally and measuring DM and metabolites in serum 2 h after intake. CYP2D6 and CYP2C19 genotypes were determined in parallel. RESULTS AND CONCLUSION: Reboxetine serum concentrations showed no correlation with the CYP2D6 genotype and the CYP2D6 phenotype, whereas paroxetine concentrations showed some dependence on CYP2D6. In contrast to in vitro investigations, indicating a major role of CYP3A4 in reboxetine metabolism, reboxetine concentrations in serum showed no correlation with the respective DM metabolic ratios. There was also no correlation between paroxetine concentrations and the CYP3A4 phenotype data. The CYP2C19 genotype (only heterozygosity) had no influence on reboxetine and paroxetine pharmacokinetics. There were only minor changes in the DM metabolite pattern on treatment with reboxetine and no evidence of enzyme inhibition was obtained. In contrast and as expected, paroxetine strongly inhibited CYP2D6. Thus, reboxetine treatment has no effect on the CYP2D6 genotype and no clinically relevant drug interactions involving CYP2D6 are anticipated.

Improvement of pseudoelasticity and ductility of Beta III titanium alloy--application to orthodontic wires.

The pseudoelasticity of metastable Beta III titanium alloy (TMAtrade mark) used for orthodontic applications is obtained by cold wiredrawing. This wire has higher rigidity than cold-drawn NiTi (Nitinoltrade mark, superelastic NiTi SE) and lower recoverable deformation. The low ductility value of Beta III is due to the deformation imposed by wiredrawing. The aim of this research was to improve the behaviour of this alloy by modifying the microstructural parameters to decrease the rigidity and increase the recoverable deformation and ductility of the alloy. The effects of second phase precipitate, grain size, and deformation on the wire mechanical properties were also examined. The isothermal precipitation of alpha (alpha) or omega (omega(isoth)) phases precludes the expression of the pseudoelastic effect. The presence of an omega(isoth) phase considerably increases fracture strength, whereas the alpha phase strongly decreases the ductility and adversely affects the strain recovery (epsilon(r)). To control the grain size, the growth of the recrystallized grains was studied by considering several parameters, which are known to have an influence on grain size, including the cold rolled strain, the temperature, the time of annealing, and the initial grain size. A structure with coarse grains, quenched from a temperature higher than the beta transus (T(beta)), associated with a plastic pre-deformation, contributed to an improved pseudoelastic behaviour, due to the presence of a reversible martensite phase (alpha'') induced by the pre-deformation.

Elastic and viscoelastic properties of the human pubic symphysis joint: effects of lateral impact joint loading.

The human pelvis is susceptible to severe injury in vehicle side impacts owing to its close proximity to the intruding door and unnatural loading through the greater trochanter. Whereas fractures of the pelvic bones are diagnosed with routine radiographs (x-rays) and computerized tomography (CT scans), non-displaced damage to the soft tissues of pubic symphysis joints may go undetected. If present, trauma-induced joint laxity may cause pelvic instability, which has been associated with pelvic pain in non-traumatic cases. In this study, mechanical properties of cadaveric pubic symphysis joints from twelve normal and eight laterally impacted pelves were compared. Axial stiffness and creep responses of these isolated symphyses were measured in tension and compression (perpendicular to the joint). Bending stiffness was determined in four primary directions followed by a tension-to-failure test. Loading rate and direction correlated significantly (p<0.05) with stiffness and tensile strength of the unimpacted joints, more so than donor age or gender. The impacted joints had significantly lower stiffness in tension (p <0.04), compression (p<0.003), and posterior bending (p<0.03), and more creep under a compressive step load (p<0.008) than the unimpacted specimens. Tensile strength was reduced following impact, however, not significantly. We concluded that the symphysis joints from the impacted pelves had greater laxity, which may correlate with post-traumatic pelvic pain in some motor vehicle crash occupants.

Regional trabecular bone matrix degeneration and osteocyte death in femora of glucocorticoid- treated rabbits.

Glucocorticoids at pharmacological concentrations cause osteoporosis and aseptic necrosis, particularly in the proximal femur. Several mechanisms have been proposed, but the primary events are not clear. We studied changes in the bone structure and cellular activity in femora of glucocorticoid-treated rabbits before the occurrence of fracture or collapse. In rabbits treated 28 days with 4 micromol/kg.day of methylprednisolone acetate, changes in the cortical bone were minor. However, metabolic labeling showed that bone formation was virtually absent in the subarticular trabecular bone, and scanning electron microscopy showed resorption of 50-80% of the trabecular surface. Thus, reduction in bone synthesis and increased resorption were involved in bone loss. Vascular changes, which have been hypothesized to mediate glucocorticoid damage, were not seen, but histological changes suggested that trabecular bone was damaged. Matrix integrity was examined using laser scanning confocal microscopy to detect passive tetracycline adsorption. In treated animals, but not controls, tetracycline was adsorbed, in a novel lamellar pattern, in 50--200 microm regions extending deep into trabeculae. This showed that the matrix, which is normally impervious, was exposed at these sites. TUNEL assays showed that matrix damage correlated with cell death in the subarticular trabecular bone of treated animals. The pattern of cell death involving cohorts of osteoblasts and osteocytes comprised up to half of the bone volume in affected regions and is consistent with an apoptotic mechanism. Small numbers of TUNEL-labeled osteoblasts, but no osteocytes, were detected in control bone. We conclude that exposure of bone matrix permeability and that regional cell death consistent with apoptosis is an early event in glucocorticoid-induced bone damage.

Modulation of mechanical properties in multiple-component tissue adhesives.

In vitro, ex vivo, and in vivo studies were performed to investigate the effect of mixing upon the mechanical properties of a two-component tissue adhesive. The hypothesis investigated was that a more complete mixing of the two components would yield an increase in the mechanical performance of the adhesive. This in turn would be demonstrated by improved outcomes in models of clinical sealant application. In vitro stereological analysis of tissue adhesive mixed and delivered by several different applicators demonstrated variation in the amount of mixing provided by each type of delivery system. Ex vivo tensile adhesive strength showed that there was a correlation between the amount of mixing and bonding strength; that is, more thorough mixing demonstrated higher adhesive strength. No significant difference was seen, however, between the different applicator types and impact on in vivo dermal incisional closure strength. There was a correlation, though, in amount of mixing and in vivo hemostasis. In a rabbit spleen incision model, a more thoroughly mixed sealant corresponded with a decrease in time to obtain complete hemostasis, as well as less sealant used. The effects of mixing on tissue-adhesive mechanical performance were influenced somewhat by the amount of mixing provided by the applicator. This effect, however, was dependent upon the sealant formulation and the type of in vivo application.

Acetabular fracture patterns: associations with motor vehicle crash information.

BACKGROUND: Motor vehicle crashes are the most common cause of acetabular fractures, which have been associated with significant morbidity and mortality. METHODS: To date, medical and collision information has been collected on 83 acetabular fracture patients treated at the University of Alabama at Birmingham's Level I trauma center. The fractures were grouped according to the Judet-Letournel classification scheme and investigated for correlation with age, sex, vehicle type, impact direction, and seat-belt use. RESULTS: The database included 41 women and 42 men with a combined average age of 32.8 years. Femoral shaft axis loading fractures correlated significantly with male sex, trucks, and frontal impacts. Greater trochanter loading fractures occurred statistically more frequently in side impacts. Women received a significant higher percentage of off-axis loading fractures, which were associated more in angled frontal impacts. CONCLUSION: Acetabular fracture type strongly correlated with impact direction, supporting the fracture mechanisms proposed by Judet and Letournel.

Strut fracture mechanisms of the Björk-Shiley convexo-concave heart valve.

Investigations of convexo-concave (C/C) valve outlet strut fractures (OSFs) were initially confounded by knowledge that the strut was subject to bending forces in arresting the opening disc. Pulse duplicator studies subsequently showed that closing loads were all born by the inlet strut, along with an understandable focus on the nature of the welds, where most fractures occurred. As observations of explanted valves accumulated, certain features pointed to unusual closing loads that might be contributory factors, but these hypothetical forces could not be verified. Epidemiological extrapolations and case-matched control studies have shown that certain valve and patient characteristics were each associated independently with increased OSF risk, leading to clinically valuable risk stratification, but little additional understanding of why OSFs continued to occur. Detection of the causative, highly transient (< 0.5 ms), outlet-strut-tip impacts due to closing disc over-rotation that have almost ten times the force of disc opening, and the capability of inducing leg-base bending stresses beyond the strut wire's fatigue endurance limit had to await the development of computer-controlled pulse duplicators and strut-leg strain gaging. Exercised young animals easily achieved such strut loading, but most human patients would probably have more difficulty. The actual OSF mechanism is a long-term, valve-patient interaction that requires the concurrence of susceptible valve geometry and sufficient ventricular contractility potential to develop the isovolumic, high dP/dt needed for forceful disc over-rotation. Critical strut tip loading must then occur often enough to fatigue fracture both strut legs within the patient's lifetime with the valve.