Location-specific cutaneous electrical stimulation of the footsole modulates corticospinal excitability to the plantarflexors and dorsiflexors during standing

Non-noxious electrical stimulation to distinct locations of the foot sole evokes location-specific cutaneous reflex responses in lower limb muscles. These reflexes occur at latencies that may enable them to be mediated via a transcortical pathway. Corticospinal excitability to the plantarflexors and dorsiflexors was measured in 16 participants using motor evoked potentials (MEPs). Spinal excitability was measured in eight of the original participants using cervicomedullary motor evoked potentials (CMEPs). Measurements were collected with and without preceding cutaneous stimulus to either the heel (HEEL) or metatarsal (MET) locations of the foot sole, and evoked potentials were elicited to coincide with the arrival of the cutaneous volley at either the motor cortex or spinal cord. Plantarflexor MEPs and CMEPs were facilitated with cutaneous stimulation to the HEEL for MEPs (soleus p = 0.04, medial gastrocnemius (MG) p = 0.017) and CMEPs (soleus p = 0.047 and MG p = 0.015), but they were unchanged following MET stimulation for MEPs or CMEPs. Dorsiflexor MEPs were unchanged with cutaneous stimulation at either location, but dorsiflexor CMEPs increased with cutaneous stimulation (p = 0.05). In general, the increase in CMEP amplitudes was larger than the increase in MEP amplitudes, indicating that an increase in spinal excitability likely explains most of the increase in corticospinal excitability. The larger change observed in the CMEP also indicates that excitability from supraspinal sources likely decreased, which could be due to a net change in the excitability of intracortical circuits. This study provides evidence that cutaneous reflexes from foot sole skin are likely influenced by a transcortical pathway

Feedback under the microscope II: heating, gas uplift, and mixing in the nearest cluster core

Using a combination of deep 574ks Chandra data, XMM-Newton high-resolution spectra, and optical Halpha+NII images, we study the nature and spatial distribution of the multiphase plasma in M87. Our results provide direct observational evidence of `radio mode' AGN feedback in action, stripping the central galaxy of its lowest entropy gas and preventing star-formation. This low entropy gas was entrained with and uplifted by the buoyantly rising relativistic plasma, forming long "arms". These arms are likely oriented within 15-30 degrees of our line-of-sight. The mass of the uplifted gas in the arms is comparable to the gas mass in the approximately spherically symmetric 3.8 kpc core, demonstrating that the AGN has a profound effect on its immediate surroundings. The coolest X-ray emitting gas in M87 has a temperature of ~0.5 keV and is spatially coincident with Halpha+NII nebulae, forming a multiphase medium where the cooler gas phases are arranged in magnetized filaments. We place strong upper limits of 0.06 Msun/yr on the amount of plasma cooling radiatively from 0.5 keV and show that a uniform, volume-averaged heating mechanism could not be preventing the cool gas from further cooling. All of the bright Halpha filaments appear in the downstream region of the <3 Myr old shock front, at smaller radii than ~0.6'. We suggest that shocks induce shearing around the filaments, thereby promoting mixing of the cold gas with the ambient hot ICM via instabilities. By bringing hot thermal particles into contact with the cool, line-emitting gas, mixing can supply the power and ionizing particles needed to explain the observed optical spectra. Mixing of the coolest X-ray emitting plasma with the cold optical line emitting filamentary gas promotes efficient conduction between the two phases, allowing non-radiative cooling which could explain the lack of X-ray gas with temperatures under 0.5 keV.Comment: to appear in MNRA

Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters

Extreme AGN Feedback and Cool Core Destruction in the X-ray Luminous Galaxy Cluster MACS J1931.8-2634

We report on a deep, multiwavelength study of the galaxy cluster MACS J1931.8-2634 using Chandra X-ray, Subaru optical, and VLA 1.4 GHz radio data. This cluster (z=0.352) harbors one of the most X-ray luminous cool cores yet discovered, with an equivalent mass cooling rate within the central 50 kpc is approximately 700 solar masses/yr. Unique features observed in the central core of MACSJ1931.8-2634 hint to a wealth of past activity that has greatly disrupted the original cool core. We observe a spiral of relatively cool, dense, X-ray emitting gas connected to the cool core, as well as highly elongated intracluster light (ICL) surrounding the cD galaxy. Extended radio emission is observed surrounding the central AGN, elongated in the east-west direction, spatially coincident with X-ray cavities. The power input required to inflate these `bubbles' is estimated from both the X-ray and radio emission to reside between 4 and 14e45 erg/s, putting it among the most powerful jets ever observed. This combination of a powerful AGN outburst and bulk motion of the cool core have resulted in two X-ray bright ridges to form to the north and south of the central AGN at a distance of approximately 25 kpc. The northern ridge has spectral characteristics typical of cool cores and is consistent with being a remnant of the cool core after it was disrupted by the AGN and bulk motions. It is also the site of H-alpha filaments and young stars. The X-ray spectroscopic cooling rate associated with this ridge is approximately 165 solar masses/yr, which agrees with the estimate of the star formation rate from broad-band optical imaging (170 solar masses/yr). MACS J1931.8-2634 appears to harbor one of most profoundly disrupted low entropy cores observed in a cluster, and offers new insights into the survivability of cool cores in the context of hierarchical structure formation.Comment: 19 pages, 15 figures, 5 tables. Accepted by MNRAS for publication September 30 201

Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

BACKGROUND: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classifi- cation of cases as H pylori negative when they were infected in the past. AIMS: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection.To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. METHODS: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer. RESULTS: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to noncardia cancers (OR 3.0; 95% CI 2.3–3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4–10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7–1.4). CONCLUSIONS: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated

Transport of Cosmic Rays in Chaotic Magnetic Fields

The transport of charged particles in disorganised magnetic fields is an important issue which concerns the propagation of cosmic rays of all energies in a variety of astrophysical environments, such as the interplanetary, interstellar and even extra-galactic media, as well as the efficiency of Fermi acceleration processes. We have performed detailed numerical experiments using Monte-Carlo simulations of particle propagation in stochastic magnetic fields in order to measure the parallel and transverse spatial diffusion coefficients and the pitch angle scattering time as a function of rigidity and strength of the turbulent magnetic component. We confirm the extrapolation to high turbulence levels of the scaling predicted by the quasi-linear approximation for the scattering frequency and parallel diffusion coefficient at low rigidity. We show that the widely used Bohm diffusion coefficient does not provide a satisfactory approximation to diffusion even in the extreme case where the mean field vanishes. We find that diffusion also takes place for particles with Larmor radii larger than the coherence length of the turbulence. We argue that transverse diffusion is much more effective than predicted by the quasi-linear approximation, and appears compatible with chaotic magnetic diffusion of the field lines. We provide numerical estimates of the Kolmogorov length and magnetic line diffusion coefficient as a function of the level of turbulence. Finally we comment on applications of our results to astrophysical turbulence and the acceleration of high energy cosmic rays in supernovae remnants, in super-bubbles, and in jets and hot spots of powerful radio-galaxies.Comment: To be published in Physical Review D, 20 pages 9 figure

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics:Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

Attitudes and Practices Among Internists Concerning Genetic Testing

Many questions remain concerning whether, when, and how physicians order genetic tests, and what factors are involved in their decisions. We surveyed 220 internists from two academic medical centers about their utilization of genetic testing. Rates of genetic utilizations varied widely by disease. Respondents were most likely to have ordered tests for Factor V Leiden (16.8 %), followed by Breast/Ovarian Cancer (15.0 %). In the past 6 months, 65 % had counseled patients on genetic issues, 44 % had ordered genetic tests, 38.5 % had referred patients to a genetic counselor or geneticist, and 27.5 % had received ads from commercial labs for genetic testing. Only 4.5 % had tried to hide or disguise genetic information, and <2 % have had patients report genetic discrimination. Only 53.4 % knew of a geneticist/genetic counselor to whom to refer patients. Most rated their knowledge as very/somewhat poor concerning genetics (73.7 %) and guidelines for genetic testing (87.1 %). Most felt needs for more training on when to order tests (79 %), and how to counsel patients (82 %), interpret results (77.3 %), and maintain privacy (80.6 %). Physicians were more likely to have ordered a genetic test if patients inquired about genetic testing (p  < .001), and if physicians had a geneticist/genetic counselor to whom to refer patients (p  < .002), had referred patients to a geneticist/genetic counselor in the past 6 months, had more comfort counseling patients about testing (p  < .019), counseled patients about genetics, larger practices (p  < .032), fewer African‐American patients (p  < .027), and patients who had reported genetic discrimination (p  < .044). In a multiple logistic regression, ordering a genetic test was associated with patients inquiring about testing, having referred patients to a geneticist/genetic counselor and knowing how to order tests. These data suggest that physicians recognize their knowledge deficits, and are interested in training. These findings have important implications for future medical practice, research, and education