Implications of predatory specialization for cranial form and function in canids.

Abstract The shape of the cranium varies widely among members of the order Carnivora, but the factors that drive the evolution of differences in shape remain unclear. Selection for increased bite force, bite speed or skull strength may all affect cranial morphology. We investigated the relationship between cranial form and function in the trophically diverse dog family, Canidae, using linear morphometrics and finite element (FE) analyses that simulated the internal and external forces that act on the skull during the act of prey capture and killing. In contrast to previous FE-based studies, we compared models using a newly developed method that removes the effects of size and highlights the relationship between shape and performance. Cranial shape varies among canids based on diet, and different selective forces presumably drove evolution of these phenotypes. The long, narrow jaws of small prey specialists appear to reflect selection for fast jaw closure at the expense of bite force. Generalists have intermediate jaw dimensions and produce moderate bite forces, but their crania are comparable in strength to those of small prey specialists. Canids that take large prey have short, broad jaws, produce the largest bite forces and possess very strong crania. Our FE simulations suggest that the remarkable strength of skulls of large prey specialists reflect the additional ability to resist extrinsic loads that may be encountered while struggling with large prey items

Biomechanical Consequences of Rapid Evolution in the Polar Bear Lineage

The polar bear is the only living ursid with a fully carnivorous diet. Despite a number of well-documented craniodental adaptations for a diet of seal flesh and blubber, molecular and paleontological data indicate that this morphologically distinct species evolved less than a million years ago from the omnivorous brown bear. To better understand the evolution of this dietary specialization, we used phylogenetic tests to estimate the rate of morphological specialization in polar bears. We then used finite element analysis (FEA) to compare the limits of feeding performance in the polar bear skull to that of the phylogenetically and geographically close brown bear. Results indicate that extremely rapid evolution of semi-aquatic adaptations and dietary specialization in the polar bear lineage produced a cranial morphology that is weaker than that of brown bears and less suited to processing tough omnivorous or herbivorous diets. Our results suggest that continuation of current climate trends could affect polar bears by not only eliminating their primary food source, but also through competition with northward advancing, generalized brown populations for resources that they are ill-equipped to utilize

Watermelon configurations with wall interaction: exact and asymptotic results

We perform an exact and asymptotic analysis of the model of $n$ vicious walkers interacting with a wall via contact potentials, a model introduced by Brak, Essam and Owczarek. More specifically, we study the partition function of watermelon configurations which start on the wall, but may end at arbitrary height, and their mean number of contacts with the wall. We improve and extend the earlier (partially non-rigorous) results by Brak, Essam and Owczarek, providing new exact results, and more precise and more general asymptotic results, in particular full asymptotic expansions for the partition function and the mean number of contacts. Furthermore, we relate this circle of problems to earlier results in the combinatorial and statistical literature.Comment: AmS-TeX, 41 page

Examining constipation assessment and management of patients with advanced cancer receiving specialist palliative care: A multi-site retrospective case note review of clinical practice

Constipation is a common symptom for patients receiving palliative care. Whilst international clinical guidelines are available on the clinical management of constipation for people with advanced cancer receiving specialist palliative care (SPC), the extent to which the guidelines are implemented in practice is unclear. This study aimed to examine clinical practices for the assessment and management of constipation for patients with advanced cancer within inpatient SPC settings. A multi-site retrospective case-note review was conducted, consisting of 150 patient case-notes from three inpatient SPC units across the United Kingdom between August 2016 and May 2017. The variables selected for review were determined by the recommendations within the clinical guidelines. Descriptive statistics, cross tabulation, chi square, and bivariate correlations were used to examine clinical practices compared to policy guidelines for the assessment and management of constipation. Reporting was structured by the STROBE checklist for observational research (Additional File 2). A comprehensive assessment, including a full history and performing a physical exam, was recorded for 109 patients (73%), however, no standardised documentation was utilised. Assessment was nurse led, with variable involvement across sites of other members of the multidisciplinary team (MDT). Education on prevention was documented in 30 (20%) case-notes, and 53% recorded evidence of non-pharmacological intervention. Age, gender, and reason for admission did not impact on the likelihood of receiving a comprehensive assessment, education, or non-pharmacological intervention, however, significant differences were evident between sites. Pharmacological management was well developed and aligned to the guidelines however, 33% of patient case-notes recorded no information on the titration of laxatives. Twelve percent of patients experienced partial or complete bowel obstruction, and management strategies were variable. Constipation management is driven by a pharmacological approach, with little evidence of the implementation of preventative and non-pharmacological strategies. The nurse plays a key coordinating role in assessment; however, involvement and roles of the wider MDT varies. Accurate recording of care is essential when examining clinical practice and identifying areas for improvement. Further education is needed to equip HCPs with the knowledge and skills to ensure consistency in assessment and implementation of appropriate non-pharmacological/ preventative strategies

Clinical utility of vinblastine therapeutic drug monitoring for the treatment of infantile myofibroma patients:A case series

Infantile myofibroma is a rare, benign tumour of infancy typically managed surgically. In a minority of cases, more aggressive disease is seen and chemotherapy with vinblastine and methotrexate may be used, although evidence for this is limited. Chemotherapy dosing in infants is challenging, and vinblastine disposition in infants is unknown. We describe the use of vinblastine therapeutic drug monitoring in four cases of infantile myofibroma. Marked inter- and intrapatient variability was observed, highlighting the poorly understood pharmacokinetics of vinblastine in children, the challenges inherent in treating neonates, and the role of adaptive dosing in optimising drug exposure in challenging situations.</p

Search for Light Gluinos via the Spontaneous Appearance of pi+pi- Pairs with an 800 GeV/c Proton Beam at Fermilab

We searched for the appearance of pi+pi- pairs with invariant mass greater than 648 MeV in a neutral beam. Such an observation could signify the decay of a long-lived light neutral particle. We find no evidence for this decay. Our null result severely constrains the existence of an R0 hadron, which is the lightest bound state of a gluon and a light gluino, and thereby also the possibility of a light gluino. Depending on the photino mass, we exclude the R0 in the mass and lifetime ranges of 1.2 -- 4.6 GeV and 2E-10 -- 7E-4 seconds, respectively. (To Appear in Phys. Rev. Lett.)Comment: Documentstyle aps,epsfig,prl (revtex), 6 pages, 7 figure

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase

There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 µg/mL—greater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals

First Observation of the decay KL -> pi0 e e gamma

We report on the first observation of the decay KL -> pi0 ee gamma by the KTeV E799 experiment at Fermilab. Based upon a sample of 48 events with an estimated background of 3.6 +/- 1.1 events, we measure the KL -> pi0 ee gamma branching ratio to be (2.34 +/- 0.35 +/- 0.13)x10^{-8}. Our data agree with recent O(p^6) calculations in chiral perturbation theory that include contributions from vector meson exchange through the parameter a_V. A fit was made to the KL -> pi0 ee gamma data for a_V with the result -0.67 +/- 0.21 +/- 0.12, which is consistent with previous results from KTeV.Comment: Submitted to Physical Review Letters, 5 pages, 5 figure

Search for the Decay K_L -> pi^0 nu nubar using pi^0 -> e^+ e^- gamma

We report on a search for the decay K_L -> pi^0 nu nubar, carried out as a part of E799-II, a rare K_L decay experiment at Fermilab. Within the Standard Model, the K_L -> pi^0 nu nubar decay is dominated by direct CP violating processes, and thus an observation of the decay implies confirmation of direct CP violation. Due to theoretically clean calculations, a measurement of B(K_L -> pi^0 nu nubar) is one of the best ways to determine the CKM parameter eta. No events were observed, and we set an upper limit B(K_L -> pi^0 nu nubar) < 5.9 times 10^-7 at the 90% confidence level.Comment: 5 pages, 4 figure