2,082 research outputs found
Medicine’s inconvenient truth: The placebo/nocebo effect
Placebo and nocebo effects are often regarded by clinicians as either a quaint reminiscence from the
pre-therapeutic era, or simply as a technique for establishing the efficacy of therapeutic
interventions within the locus of evidence-based practice. However, neither of these explanations
sufficiently account for their complexity or their persistence and impact in clinical medicine. Placebo
and nocebo effects are embedded in the very fabric of therapeutic relationships and are both a
manifestation and outcome of the rituals that characterise clinical practice. They are also a stark
reminder of the many personal and environmental factors, including the attitudes, beliefs and
expectations of both doctor and patient, that shape the outcomes of health professional-patient
interactions. We describe how recent biological and neuropsychiatric data have clarified the
operation of placebo and nocebo effects in clinical practice – demonstrating the ability of the
therapeutic context to modulate endogenous biological processes in a targeted manner. This, in
turn, illustrates the potent philosophical and sociocultural aspects of medical praxis.
Keywords: placebo; nocebo; context effect; medical therapeutics; medical practice; medical ethic
Medicine’s inconvenient truth: The placebo/nocebo effect
Placebo and nocebo effects are often regarded by clinicians as either a quaint reminiscence from the pre-therapeutic era, or simply as a technique for establishing the efficacy of therapeutic interventions within the locus of evidence-based practice. However, neither of these explanations sufficiently account for their complexity or their persistence and impact in clinical medicine. Placebo and nocebo effects are embedded in the very fabric of therapeutic relationships and are both a manifestation and outcome of the rituals that characterise clinical practice. They are also a stark reminder of the many personal and environmental factors, including the attitudes, beliefs and expectations of both doctor and patient, that shape the outcomes of health professional-patient interactions. We describe how recent biological and neuropsychiatric data have clarified the operation of placebo and nocebo effects in clinical practice – demonstrating the ability of the therapeutic context to modulate endogenous biological processes in a targeted manner. This, in turn, illustrates the potent philosophical and sociocultural aspects of medical praxis. Keywords: placebo; nocebo; context effect; medical therapeutics; medical practice; medical ethic
Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies.
Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event
The Pure Virtual Braid Group Is Quadratic
If an augmented algebra K over Q is filtered by powers of its augmentation
ideal I, the associated graded algebra grK need not in general be quadratic:
although it is generated in degree 1, its relations may not be generated by
homogeneous relations of degree 2. In this paper we give a sufficient criterion
(called the PVH Criterion) for grK to be quadratic. When K is the group algebra
of a group G, quadraticity is known to be equivalent to the existence of a (not
necessarily homomorphic) universal finite type invariant for G. Thus the PVH
Criterion also implies the existence of such a universal finite type invariant
for the group G. We apply the PVH Criterion to the group algebra of the pure
virtual braid group (also known as the quasi-triangular group), and show that
the corresponding associated graded algebra is quadratic, and hence that these
groups have a (not necessarily homomorphic) universal finite type invariant.Comment: 53 pages, 15 figures. Some clarifications added and inaccuracies
corrected, reflecting suggestions made by the referee of the published
version of the pape
Impact of Tail Loss on the Behaviour and Locomotor Performance of Two Sympatric Lampropholis Skink Species
Caudal autotomy is an anti-predator behaviour that is used by many lizard species. Although there is an immediate survival benefit, the subsequent absence of the tail may inhibit locomotor performance, alter activity and habitat use, and increase the individuals' susceptibility to future predation attempts. We used laboratory experiments to examine the impact of tail autotomy on locomotor performance, activity and basking site selection in two lizard species, the delicate skink (Lampropholis delicata) and garden skink (L. guichenoti), that occur sympatrically throughout southeastern Australia and are exposed to an identical suite of potential predators. Post-autotomy tail movement did not differ between the two Lampropholis species, although a positive relationship between the shed tail length and distance moved, but not the duration of movement, was observed. Tail autotomy resulted in a substantial decrease in sprint speed in both species (28–39%), although this impact was limited to the optimal performance temperature (30°C). Although L. delicata was more active than L. guichenoti, tail autotomy resulted in decreased activity in both species. Sheltered basking sites were preferred over open sites by both Lampropholis species, although this preference was stronger in L. delicata. Caudal autotomy did not alter the basking site preferences of either species. Thus, both Lampropholis species had similar behavioural responses to autotomy. Our study also indicates that the impact of tail loss on locomotor performance may be temperature-dependent and highlights that future studies should be conducted over a broad thermal range
Anarchy in the UK: Detailed genetic analysis of worker reproduction in a naturally occurring British anarchistic honeybee, Apis mellifera, colony using DNA microsatellites
Anarchistic behaviour is a very rare phenotype of honeybee colonies. In an anarchistic colony,
many workers’ sons are reared in the presence of the queen. Anarchy has previously
been described in only two Australian colonies. Here we report on a first detailed genetic
analysis of a British anarchistic colony. Male pupae were present in great abundance above
the queen excluder, which was clearly indicative of extensive worker reproduction and is the
hallmark of anarchy. Seventeen microsatellite loci were used to analyse these male pupae,
allowing us to address whether all the males were indeed workers’ sons, and how many
worker patrilines and individual workers produced them. In the sample, 95 of 96 of the
males were definitely workers’ sons. Given that
≈
1% of workers’ sons were genetically
indistinguishable from queen’s sons, this suggests that workers do not move any
queen-laid eggs between the part of the colony where the queen is present to the area above
the queen excluder which the queen cannot enter. The colony had 16 patrilines, with an
effective number of patrilines of 9.85. The 75 males that could be assigned with certainty to
a patriline came from 7 patrilines, with an effective number of 4.21. They were the offspring of at least 19 workers. This is in contrast to the two previously studied Australian naturally occurring anarchist colonies, in which most of the workers’ sons were offspring of one patriline. The high number of patrilines producing males leads to a low mean relatedness between laying workers and males of the colony. We discuss the importance of studying such colonies in the understanding of worker policing and its evolution
Random attractors for degenerate stochastic partial differential equations
We prove the existence of random attractors for a large class of degenerate
stochastic partial differential equations (SPDE) perturbed by joint additive
Wiener noise and real, linear multiplicative Brownian noise, assuming only the
standard assumptions of the variational approach to SPDE with compact
embeddings in the associated Gelfand triple. This allows spatially much rougher
noise than in known results. The approach is based on a construction of
strictly stationary solutions to related strongly monotone SPDE. Applications
include stochastic generalized porous media equations, stochastic generalized
degenerate p-Laplace equations and stochastic reaction diffusion equations. For
perturbed, degenerate p-Laplace equations we prove that the deterministic,
infinite dimensional attractor collapses to a single random point if enough
noise is added.Comment: 34 pages; The final publication is available at
http://link.springer.com/article/10.1007%2Fs10884-013-9294-
Evolution of opinions on social networks in the presence of competing committed groups
Public opinion is often affected by the presence of committed groups of
individuals dedicated to competing points of view. Using a model of pairwise
social influence, we study how the presence of such groups within social
networks affects the outcome and the speed of evolution of the overall opinion
on the network. Earlier work indicated that a single committed group within a
dense social network can cause the entire network to quickly adopt the group's
opinion (in times scaling logarithmically with the network size), so long as
the committed group constitutes more than about 10% of the population (with the
findings being qualitatively similar for sparse networks as well). Here we
study the more general case of opinion evolution when two groups committed to
distinct, competing opinions and , and constituting fractions and
of the total population respectively, are present in the network. We show
for stylized social networks (including Erd\H{o}s-R\'enyi random graphs and
Barab\'asi-Albert scale-free networks) that the phase diagram of this system in
parameter space consists of two regions, one where two stable
steady-states coexist, and the remaining where only a single stable
steady-state exists. These two regions are separated by two fold-bifurcation
(spinodal) lines which meet tangentially and terminate at a cusp (critical
point). We provide further insights to the phase diagram and to the nature of
the underlying phase transitions by investigating the model on infinite
(mean-field limit), finite complete graphs and finite sparse networks. For the
latter case, we also derive the scaling exponent associated with the
exponential growth of switching times as a function of the distance from the
critical point.Comment: 23 pages: 15 pages + 7 figures (main text), 8 pages + 1 figure + 1
table (supplementary info
A Large Scale Double Beta and Dark Matter Experiment: GENIUS
The recent results from the HEIDELBERG-MOSCOW experiment have demonstrated
the large potential of double beta decay to search for new physics beyond the
Standard Model. To increase by a major step the present sensitivity for double
beta decay and dark matter search much bigger source strengths and much lower
backgrounds are needed than used in experiments under operation at present or
under construction. We present here a study of a project proposed recently,
which would operate one ton of 'naked' enriched GErmanium-detectors in liquid
NItrogen as shielding in an Underground Setup (GENIUS). It improves the
sensitivity to neutrino masses to 0.01 eV. A ten ton version would probe
neutrino masses even down to 10^-3 eV. The first version would allow to test
the atmospheric neutrino problem, the second at least part of the solar
neutrino problem. Both versions would allow in addition significant
contributions to testing several classes of GUT models. These are especially
tests of R-parity breaking supersymmetry models, leptoquark masses and
mechanism and right-handed W-boson masses comparable to LHC. The second issue
of the experiment is the search for dark matter in the universe. The entire
MSSM parameter space for prediction of neutralinos as dark matter particles
could be covered already in a first step of the full experiment - with the same
purity requirements but using only 100 kg of 76Ge or even of natural Ge -
making the experiment competitive to LHC in the search for supersymmetry.
The layout of the proposed experiment is discussed and the shielding and
purity requirements are studied using GEANT Monte Carlo simulations. As a
demonstration of the feasibility of the experiment first results of operating a
'naked' Ge detector in liquid nitrogen are presented.Comment: 22 pages, 12 figures, see also
http://pluto.mpi-hd.mpg.de/~betalit/genius.htm
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