Acupuncture randomized trials (ART) in patients with chronic low back pain and osteoarthritis of the knee - Design and protocols

Background: We report on the study design and protocols of two randomized controlled trials (Acupuncture Randomized Trials = ART) that investigate the efficacy of acupuncture in the treatment of chronic low back pain and osteoarthritis of the knee, respectively. Objective: To investigate whether acupuncture is more efficacious than (a) no treatment or (b) minimal acupuncture in the treatment of low back pain and osteoarthritis. Design: Two randomized, controlled, multicenter trials with three treatment arms and a total follow-up time of 52 weeks. Setting: 30 practitioners and outpatient units in Germany specialized in acupuncture treatment. Patients: 300 patients will be included in each study. In the low back pain trial, patients will be included according to clinical diagnosis. In the osteoarthritis pain trial, patients will be included according to the American College of Rheumatology criteria. Interventions: Patients are randomly assigned to receive either (1) semi-standardized acupuncture (150 patients), (2) minimal acupuncture at non-acupuncture points (75 patients), or (3) no treatment for two months followed by semi-standardized acupuncture (75 patients, waiting list control). Acupuncture treatment consists of 12 sessions per patient over a period of 8 weeks. Main Outcome Measure: The main outcome measure is the difference between baseline and the end of the 8-week treatment period in the following parameters: pain intensity as measured by a visual analogue scale (VAS; 0-100 mm) in the low back pain trial and by the Western Ontario and McMaster Universities Osteoarthritis Score (WOMAC) in the osteoarthritis trial. Outlook: The results of these two studies (available in 2004) will provide health care providers and policy makers with the information needed to make scientifically sound assessments of acupuncture therapy

M-theory on eight-manifolds revisited: N=1 supersymmetry and generalized Spin(7) structures

The requirement of ${\cal N}=1$ supersymmetry for M-theory backgrounds of the form of a warped product ${\cal M}\times_{w}X$, where $X$ is an eight-manifold and ${\cal M}$ is three-dimensional Minkowski or AdS space, implies the existence of a nowhere-vanishing Majorana spinor $\xi$ on $X$. $\xi$ lifts to a nowhere-vanishing spinor on the auxiliary nine-manifold $Y:=X\times S^1$, where $S^1$ is a circle of constant radius, implying the reduction of the structure group of $Y$ to $Spin(7)$. In general, however, there is no reduction of the structure group of $X$ itself. This situation can be described in the language of generalized $Spin(7)$ structures, defined in terms of certain spinors of $Spin(TY\oplus T^*Y)$. We express the condition for ${\cal N}=1$ supersymmetry in terms of differential equations for these spinors. In an equivalent formulation, working locally in the vicinity of any point in $X$ in terms of a `preferred' $Spin(7)$ structure, we show that the requirement of ${\cal N}=1$ supersymmetry amounts to solving for the intrinsic torsion and all irreducible flux components, except for the one lying in the $\bf{27}$ of $Spin(7)$, in terms of the warp factor and a one-form $L$ on $X$ (not necessarily nowhere-vanishing) constructed as a $\xi$ bilinear; in addition, $L$ is constrained to satisfy a pair of differential equations. The formalism based on the group $Spin(7)$ is the most suitable language in which to describe supersymmetric compactifications on eight-manifolds of $Spin(7)$ structure, and/or small-flux perturbations around supersymmetric compactifications on manifolds of $Spin(7)$ holonomy.Comment: 24 pages. V2: introduction slightly extended, typos corrected in the text, references added. V3: the role of Spin(7) clarified, erroneous statements thereof corrected. New material on generalized Spin(7) structures in nine dimensions. To appear in JHE

Homeopathic medical practice: Long-term results of a cohort study with 3981 patients

BACKGROUND: On the range of diagnoses, course of treatment, and long-term outcome in patients who chose to receive homeopathic medical treatment very little is known. We investigated homeopathic practice in an industrialized country under everyday conditions. METHODS: In a prospective, multicentre cohort study with 103 primary care practices with additional specialisation in homeopathy in Germany and Switzerland, data from all patients (age >1 year) consulting the physician for the first time were observed. The main outcome measures were: Patient and physician assessments (numeric rating scales from 0 to 10) and quality of life at baseline, and after 3, 12, and 24 months. RESULTS: A total of 3,981 patients were studied including 2,851 adults (29% men, mean age 42.5 ± 13.1 years; 71% women, 39.9 ± 12.4 years) and 1,130 children (52% boys, 6.5 ± 3.9 years; 48% girls, 7.0 ± 4.3 years). Ninety-seven percent of all diagnoses were chronic with an average duration of 8.8 ± 8 years. The most frequent diagnoses were allergic rhinitis in men, headache in women, and atopic dermatitis in children. Disease severity decreased significantly (p < 0.001) between baseline and 24 months (adults from 6.2 ± 1.7 to 3.0 ± 2.2; children from 6.1 ± 1.8 to 2.2 ± 1.9). Physicians' assessments yielded similar results. For adults and young children, major improvements were observed for quality of life, whereas no changes were seen in adolescents. Younger age and more severe disease at baseline were factors predictive of better therapeutic success. CONCLUSION: Disease severity and quality of life demonstrated marked and sustained improvements following homeopathic treatment period. Our findings indicate that homeopathic medical therapy may play a beneficial role in the long-term care of patients with chronic diseases

Homeopathic treatment of patients with chronic sinusitis: A prospective observational study with 8 years follow-up

<p>Abstract</p> <p>Background</p> <p>An evaluation of homeopathic treatment and the outcomes in patients suffering from sinusitis for ≥12 weeks in a usual care situation.</p> <p>Methods</p> <p>Subgroup analysis including all patients with chronic sinusitis (ICD-9: 473.9; ≥12 weeks duration) of a large prospective multicentre observational study population. Consecutive patients presenting for homeopathic treatment were followed-up for 2 years, and complaint severity, health-related quality of life (QoL), and medication use were regularly recorded. We also present here patient-reported health status 8 years post initial treatment.</p> <p>Results</p> <p>The study included 134 adults (mean age 39.8 ± 10.4 years, 76.1% women), treated by 62 physicians. Patients had suffered from chronic sinusitis for 10.7 ± 9.8 years. Almost all patients (97.0%) had previously been treated with conventional medicine. For sinusitis, effect size (effect divided by standard deviation at baseline) of complaint severity was 1.58 (95% CI 1.77; 1.40), 2.15 (2.38; 1.92), and 2.43 (2.68; 2.18) at 3, 12, and 24 months respectively. QoL improved accordingly, with SF-36 changes in physical component score 0.27 (0.15; 0.39), 0.35 (0.19; 0.52), 0.44 (0.23; 0.65) and mental component score 0.66 (0.49; 0.84), 0.71 (0.50; 0.92), 0.65 (0.39; 0.92), 0.74 (0.49; 1.00) at these points. The effects were still present after 8 years with SF-36 physical component score 0.38 (0.10; 0.65) and mental component score 0.74 (0.49; 1.00).</p> <p>Conclusion</p> <p>This observational study showed relevant improvements that persisted for 8 years in patients seeking homeopathic treatment because of sinusitis. The extent to which the observed effects are due to the life-style regulation and placebo or context effects associated with the treatment needs clarification in future explanatory studies.</p

Optical Gravitational Lensing Experiment. OGLE-1999-BUL-19: The First Multi-Peak Parallax Event

We describe a highly unusual microlensing event, OGLE-1999-BUL-19, which exhibits multiple peaks in its light curve. The Einstein radius crossing time for this event is approximately one year, which is unusually long. We show that the motion of the Earth induces these multiple peaks in the light curve, since the relative transverse velocity of the lens projected into the observer plane is very small (v = 12.5 km/s). This is the lowest velocity so far published and we believe that this is the first multiple-peak parallax event ever observed. We also believe that this event may be exhibiting slight binary-source signatures in addition to these parallax-induced multiple peaks. With spectroscopic observations it is possible to test this `parallax plus binary-source' hypothesis and (if this hypothesis turns out to be correct) to simultaneously fit both models and obtain a measurement of the lens mass. Furthermore, spectroscopic observations could also supply information regarding the lens properties, possibly providing another avenue for determining the lens mass. We found that most of the I-band blending is probably caused by light from the lens or a binary companion to the source. However, in the V-band, there appears to be a second blended source 0.35" away from the lensed source. HST observations will be very useful for understanding the nature of the blends. We also suggest that a radial velocity survey of all parallax events will be very useful for further constraining the lensing kinematics and understanding the origins of these events and the excess of long events toward the bulge.Comment: 36 pages, 7 figures. Accepted for publication in MNRA

N=4 Supergravity Lagrangian for Type IIB Orientifold on T^6/Z_2 in Presence of Fluxes and D3-Branes

We derive the Lagrangian and the transformation laws of N=4 gauged supergravity coupled to matter multiplets whose sigma-model of the scalars is SU(1,1)/U(1)x SO(6,6+n)/SO(6)xSO(6+n) and which corresponds to the effective Lagrangian of the Type IIB string compactified on the T^6/Z_2 orientifold with fluxes turned on and in presence of n D3-branes. The gauge group is T^12 x G where G is the gauge group on the brane and T^12 is the gauge group on the bulk corresponding to the gauged translations of the R-R scalars coming from the R-R four--form. The N=4 bulk sector of this theory can be obtained as a truncation of the Scherk-Schwarz spontaneously broken N=8 supergravity. Consequently the full bulk spectrum satisfies quadratic and quartic mass sum rules, identical to those encountered in Scherk-Schwarz reduction gauging a flat group. This theory gives rise to a no scale supergravity extended with partial super-Higgs mechanism.Comment: 49 pages, LaTex, 2 figures. Misprints corrected, more comments adde

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

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High sensitivity (1)H-NMR spectroscopy of homeopathic remedies made in water

BACKGROUND: The efficacy of homeopathy is controversial. Homeopathic remedies are made via iterated shaking and dilution, in ethanol or in water, from a starting substance. Remedies of potency 12 C or higher are ultra-dilute (UD), i.e. contain zero molecules of the starting material. Various hypotheses have been advanced to explain how a UD remedy might be different from unprepared solvent. One such hypothesis posits that a remedy contains stable clusters, i.e. localized regions where one or more hydrogen bonds remain fixed on a long time scale. High sensitivity proton nuclear magnetic resonance spectroscopy has not previously been used to look for evidence of differences between UD remedies and controls. METHODS: Homeopathic remedies made in water were studied via high sensitivity proton nuclear magnetic resonance spectroscopy. A total of 57 remedy samples representing six starting materials and spanning a variety of potencies from 6 C to 10 M were tested along with 46 controls. RESULTS: By presaturating on the water peak, signals could be reliably detected that represented H-containing species at concentrations as low as 5 μM. There were 35 positions where a discrete signal was seen in one or more of the 103 spectra, which should theoretically have been absent from the spectrum of pure water. Of these 35, fifteen were identified as machine-generated artifacts, eight were identified as trace levels of organic contaminants, and twelve were unexplained. Of the unexplained signals, six were seen in just one spectrum each. None of the artifacts or unexplained signals occurred more frequently in remedies than in controls, using a p < .05 cutoff. Some commercially prepared samples were found to contain traces of one or more of these small organic molecules: ethanol, acetate, formate, methanol, and acetone. CONCLUSION: No discrete signals suggesting a difference between remedies and controls were seen, via high sensitivity (1)H-NMR spectroscopy. The results failed to support a hypothesis that remedies made in water contain long-lived non-dynamic alterations of the H-bonding pattern of the solvent