Design of a randomised acupuncture trial on functional neck/shoulder stiffness with two placebo controls

Background: Functional neck/shoulder stiffness is one of the most well-known indications for acupuncture treatment in Japan. There is little evidence for the effectiveness of acupuncture treatment for functional neck/shoulder stiffness. Research using two different placebos may allow an efficient method to tease apart the components of real acupuncture from various kinds of ‘non-specific’ effects such as ritual with touch or ritual alone. Herein, we describe a protocol of an ongoing, single-centre, randomised, placebo-controlled trial which aims to assess whether, in functional neck/shoulder stiffness, acupuncture treatment with skin piercing has a specific effect over two types of placebo: skin-touching plus ritual or ritual alone. Methods: Six acupuncturists and 400 patients with functional neck/shoulder stiffness are randomly assigned to four treatment groups: genuine acupuncture penetrating the skin, skin-touch placebo or no-touch placebo needles in a double-blind manner (practitioner-patient blinding) or no-treatment control group. Each acupuncturist applies a needle to each of four acupoints (Bladder10, Small Intestine14, Gallbladder21 and Bladder42) in the neck/shoulder to 50 patients. Before, immediately after and 24 hours after the treatment, patients are asked about the intensity of their neck/shoulder stiffness. After the treatment, practitioners and patients are asked to guess whether the treatment is “penetrating”, “skin-touch” or “no-touch” or to record “cannot identify the treatment”. Discussion In addition to intention-to-treat analysis, we will conduct subgroup analysis based on practitioners’ or patients’ guesses to discuss the efficacy and effectiveness of treatments with skin piercing and various placebo controls. The results of practitioner and patient blinding will be discussed. We believe this study will further distinguish the role of different components of acupuncture. Trial registration Current Controlled Trial ISRCTN7689601

A Detailed Observational Study of Molecular Loops 1 and 2 in the Galactic Center

Fukui et al. (2006) discovered two huge molecular loops in the Galactic center located in (l, b) ~ (355 deg-359 deg, 0 deg-2 deg) in a large velocity range of -180-40 km s^-1. Following the discovery, we present detailed observational properties of the two loops based on NANTEN 12CO(J=1-0) and 13CO(J=1-0) datasets at 10 pc resolution including a complete set of velocity channel distributions and comparisons with HI and dust emissions as well as with the other broad molecular features. We find new features on smaller scales in the loops including helical distributions in the loop tops and vertical spurs. The loops have counterparts of the HI gas indicating that the loops include atomic gas. The IRAS far infrared emission is also associated with the loops and was used to derive an X-factor of 0.7(+/-0.1){\times}10^20 cm^-2 (K km s^-1)^-1 to convert the 12CO intensity into the total molecular hydrogen column density. From the 12CO, 13CO, H I and dust datasets we estimated the total mass of loops 1 and 2 to be ~1.4 {\times} 106 Msun and ~1.9 {\times} 10^6 Msun, respectively, where the H I mass corresponds to ~10-20% of the total mass and the total kinetic energy of the two loops to be ~10^52 ergs. An analysis of the kinematics of the loops yields that the loops are rotating at ~47 km s-1 and expanding at ~141 km s^-1 at a radius of 670 pc from the center. Fukui et al. (2006) presented a model that the loops are created by the magnetic flotation due to the Parker instability with an estimated magnetic field strength of ~150 {\mu}G. We present comparisons with the recent numerical simulations of the magnetized nuclear disk by Machida et al. (2009) and Takahashi et al. (2009) and show that the theoretical results are in good agreements with the observations. The helical distributions also suggest that some magnetic instability plays a role similarly to the solar helical features.Comment: 40 pages, 22 figures, submitted to publication in PAS

Discovery of Molecular Loop 3 in the Galactic Center: Evidence for a Positive-Velocity Magnetically Floated Loop towards L=355∘−359∘L=355^\circ-359^\circ

We have discovered a molecular dome-like feature towards $355^{\circ} \leq l \leq 359^{\circ}$ and $0^{\circ} \leq b \leq 2^{\circ}$. The large velocity dispersions of 50--100 km s$^{-1}$ of this feature are much larger than those in the Galactic disk and indicate that the feature is located in the Galactic center, probably within $\sim1$ kpc of Sgr A$^{*}$. The distribution has a projected length of $\sim600$ pc and height of $\sim300$ pc from the Galactic disk and shows a large-scale monotonic velocity gradient of $\sim130$ km s $^{-1}$ per $\sim600$ pc. The feature is also associated with HI gas having a more continuous spatial and velocity distribution than that of $^{12}$CO. We interpret the feature as a magnetically floated loop similar to loops 1 and 2 and name it "loop 3". Loop 3 is similar to loops 1 and 2 in its height and length but is different from loops 1 and 2 in that the inner part of loop 3 is filled with molecular emission. We have identified two foot points at the both ends of loop 3. HI, $^{12}$CO and $^{13}$CO datasets were used to estimate the total mass and kinetic energy of loop 3 to be \sim3.0 \times 10^{6} \Mo and $\sim1.7 \times 10^{52}$ ergs. The huge size, velocity dispersions and energy are consistent with the magnetic origin the Parker instability as in case of loops 1 and 2 but is difficult to be explained by multiple stellar explosions. We argue that loop 3 is in an earlier evolutionary phase than loops 1 and 2 based on the inner-filled morphology and the relative weakness of the foot points. This discovery indicates that the western part of the nuclear gas disk of $\sim1$ kpc radius is dominated by the three well-developed magnetically floated loops and suggests that the dynamics of the nuclear gas disk is strongly affected by the magnetic instabilities.Comment: 30 pages, 10 figures. High resolution figures are available at http://www.a.phys.nagoya-u.ac.jp/~motosuji/fujishita09_figs

Temperature and Density in the Foot Points of the Molecular Loops in the Galactic Center; Analysis of Multi-J Transitions of 12CO(J=1-0, 3-2, 4-3, 7-6), 13CO(J=1-0) and C18O(J=1-0)

Fukui et al. (2006) discovered two molecular loops in the Galactic center and argued that the foot points of the molecular loops, two bright spots at both loops ends, represent the gas accumulated by the falling motion along the loops, subsequent to magnetic flotation by the Parker instability. We have carried out sensitive CO observations of the foot points toward l=356 deg at a few pc resolution in the six rotational transitions of CO; 12CO(J=1-0, 3-2, 4-3, 7-6), 13CO(J=1-0) and C18O(J=1-0). The high resolution image of 12CO (J=3-2) has revealed the detailed distribution of the high excitation gas including U shapes, the outer boundary of which shows sharp intensity jumps accompanying strong velocity gradients. An analysis of the multi-J CO transitions shows that the temperature is in a range from 30-100 K and density is around 10^3-10^4 cm^-3, confirming that the foot points have high temperature and density although there is no prominent radiative heating source such as high mass stars in or around the loops. We argue that the high temperature is likely due to the shock heating under C-shock condition caused by the magnetic flotation. We made a comparison of the gas distribution with theoretical numerical simulations and note that the U shape is consistent with numerical simulations. We also find that the region of highest temperature of ~100 K or higher inside the U shape corresponds to the spur having an upward flow, additionally heated up either by magnetic reconnection or bouncing in the interaction with the narrow neck at the bottom of the U shape. We note these new findings further reinforce the magnetic floatation interpretation.Comment: 40 pages, 23 figures, accepted by PASJ on Vol.62 No.

Sub-millimeter Observations of Giant Molecular Clouds in the Large Magellanic Cloud: Temperature and Density as Determined from J=3-2 and J=1-0 transitions of CO

We have carried out sub-mm 12CO(J=3-2) observations of 6 giant molecular clouds (GMCs) in the Large Magellanic Cloud (LMC) with the ASTE 10m sub-mm telescope at a spatial resolution of 5 pc and very high sensitivity. We have identified 32 molecular clumps in the GMCs and revealed significant details of the warm and dense molecular gas with n(H2) $\sim$ 10$^{3-5}$ cm$^{-3}$ and Tkin $\sim$ 60 K. These data are combined with 12CO(J=1-0) and 13CO(J=1-0) results and compared with LVG calculations. We found that the ratio of 12CO(J=3-2) to 12CO(J=1-0) emission is sensitive to and is well correlated with the local Halpha flux. We interpret that differences of clump propeties represent an evolutionary sequence of GMCs in terms of density increase leading to star formation.Type I and II GMCs (starless GMCs and GMCs with HII regions only, respectively) are at the young phase of star formation where density does not yet become high enough to show active star formation and Type III GMCs (GMCs with HII regions and young star clusters) represents the later phase where the average density is increased and the GMCs are forming massive stars. The high kinetic temperature correlated with \Halpha flux suggests that FUV heating is dominant in the molecular gas of the LMC.Comment: 74 pages, including 41 figures, accepted for publication in ApJ

PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes

PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (T-ex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the T-ex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the T-ex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such T-ex clonotypes, mainly from TDLNs

Analgesia Is Enhanced by Providing Information regarding Good Outcomes Associated with an Odor: Placebo Effects in Aromatherapy?

No previous report has described whether information regarding an odor used in aromatherapy has placebo effects. We investigated whether placebo analgesia was engendered by verbal information regarding the analgesic effects of an odor. Twelve of 24 subjects were provided with the information that a lavender odor would reduce pain (informed), whereas the other 12 subjects were not (not-informed). Concurrent with respiration recording, the subjects were administered a lavender-odor or no-odor treatment during application of painful stimulation to the forefinger. The subjects reported their experience of pain and its unpleasantness on a visual analogue scale after the painful stimulation. The lavender-odor treatment significantly alleviated pain and unpleasantness compared with the no-odor treatment in the informed (P<0.01) and not-informed groups (P<0.05). The no-odor treatment in the informed group significantly alleviated pain and unpleasantness compared with both the no-odor and lavender-odor treatments in the not-informed group (P<0.05). Rapid and shallow breathing induced by the painful stimulation became slow and deep during the lavender-odor and no-odor treatments in both groups. Information regarding a lavender odor, the lavender odor itself, and slower breathing contributed to reduced perceptions of pain and unpleasantness during painful stimulation, suggesting that placebo effects significantly contribute to analgesia in aromatherapy