Chondrodystrophia foetalis in the foetus and the infant

1. Two definite varieties of chondrodystrophia foetalis can be recognised clinically as well as microscopically. 2. It is a general disease, affecting many tissues but mainly those parts of the skeleton developed in cartilage. 3. A definite diagnosis can always.be made with the aid of X-rays. 4. The disease is present before ossification commences in any given bone and results in defective preparation for ossification in cartilage, causing a deficient attraction of true bone-forming cells. 5. It is highly probable that softness i of the skeleton due to disease affecting the cartilage, enables mechanical influences, most likely pressure of the amnion, to cause the deformities of achondroplasia. 6. The knowledge we possess of the metabolic influence of the pituitary and sexual glands points to an abnormal function of either or both of these structures as the most likely agent to cause the disturbance in the cartilage and elsewhere

Pharmaceutical care for elderly patients shared between community pharmacists and general practitioners: A randomised evaluation. RESPECT (Randomised Evaluation of Shared Prescribing for Elderly people in the Community over Time) [ISRCTN16932128]

Background: This trial aims to investigate the effectiveness and cost implications of 'pharmaceutical care' provided by community pharmacists to elderly patients in the community. As the UK government has proposed that by 2004 pharmaceutical care services should extend nationwide, this provides an opportunity to evaluate the effect of pharmaceutical care for the elderly. Design: The trial design is a randomised multiple interrupted time series. We aim to recruit 700 patients from about 20 general practices, each associated with about three community pharmacies, from each of the five Primary Care Trusts in North and East Yorkshire. We shall randomise the five resulting groups of practices, pharmacies and patients to begin pharmaceutical care in five successive phases. All five will act as controls until they receive the intervention in a random sequence. Until they receive training community pharmacists will provide their usual dispensing services and so act as controls. The community pharmacists and general practitioners will receive training in pharmaceutical care for the elderly. Once trained, community pharmacists will meet recruited patients, either in their pharmacies (in a consultation room or dispensary to preserve confidentiality) or at home. They will identify drug-related issues/problems, and design a pharmaceutical care plan in conjunction with both the GP and the patient. They will implement, monitor, and update this plan monthly. The primary outcome measure is the 'Medication Appropriateness Index'. Secondary measures include adverse events, quality of life, and patient knowledge and compliance. We shall also investigate the cost of pharmaceutical care to the NHS, to patients and to society as a whole.published_or_final_versio

Estrogen Receptor Genotypes, Menopausal Status, and the Effects of Tamoxifen on Lipid Levels: Revised and Updated Results

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109960/1/cptclpt2010143.pd

Chapter 10: Deciding Whether to Complement a Systematic Review of Medical Tests with Decision Modeling

Limited by what is reported in the literature, most systematic reviews of medical tests focus on “test accuracy” (or better, test performance), rather than on the impact of testing on patient outcomes. The link between testing, test results and patient outcomes is typically complex: even when testing has high accuracy, there is no guarantee that physicians will act according to test results, that patients will follow their orders, or that the intervention will yield a beneficial endpoint. Therefore, test performance is typically not sufficient for assessing the usefulness of medical tests. Modeling (in the form of decision or economic analysis) is a natural framework for linking test performance data to clinical outcomes. We propose that (some) modeling should be considered to facilitate the interpretation of summary test performance measures by connecting testing and patient outcomes. We discuss a simple algorithm for helping systematic reviewers think through this possibility, and illustrate it by means of an example

Quantum catastrophe of slow light

Catastrophes are at the heart of many fascinating optical phenomena. The rainbow, for example, is a ray catastrophe where light rays become infinitely intense. The wave nature of light resolves the infinities of ray catastrophes while drawing delicate interference patterns such as the supernumerary arcs of the rainbow. Black holes cause wave singularities. Waves oscillate with infinitely small wave lengths at the event horizon where time stands still. The quantum nature of light avoids this higher level of catastrophic behaviour while producing a quantum phenomenon known as Hawking radiation. As this letter describes, light brought to a standstill in laboratory experiments can suffer a similar wave singularity caused by a parabolic profile of the group velocity. In turn, the quantum vacuum is forced to create photon pairs with a characteristic spectrum. The idea may initiate a theory of quantum catastrophes, in addition to classical catastrophe theory, and the proposed experiment may lead to the first direct observation of a phenomenon related to Hawking radiation.Comment: Published as "A laboratory analogue of the event horizon using slow light in an atomic medium

De novo cost-effectiveness model framework for nonalcoholic steatohepatitis—modeling approach and validation

Background: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with hepatic morbidity and mortality and extra-hepatic comorbidities. Published NASH cost-effectiveness models (CEMs) are heterogeneous and consistently omit comorbid conditions that frequently co-exist alongside NASH. We aimed to develop a de novo CEM framework that incorporates extra-hepatic disease states and outcomes alongside hepatic components to enable future estimation of the cost-effectiveness of NASH interventions. Methods: Patient-level simulation and cohort-level Markov models were implemented in the same framework. Model inputs included fibrosis progression; late-stage liver disease outcomes; comorbidity outcomes for cardiovascular disease, type 2 diabetes, and obesity; mortality; health-related quality of life; and direct medical costs. The prototype analysis assessed the cost-effectiveness of obeticholic acid versus standard of care from a US payer perspective over a lifetime horizon with costs and effects discounted at 3% per annum. However, the CEM was designed for easy adaptation to other countries, time horizons, and other considerations. Efficacy and adverse event parameters were obtained from the 18-month interim analysis of the REGENERATE trial. Outputs include total and incremental costs, total life years, and quality-adjusted life years. Results: In this model, total costs, total life years, and quality-adjusted life years were all higher with obeticholic acid compared with standard of care. Cross-validation of this model with the 2016 and 2020 Institute for Clinical and Economic Review models revealed marked differences, mainly driven by mortality inputs, transition probability estimates, and incorporation of the effect of treatment and comorbidities. Conclusion: This is the first CEM in NASH to incorporate the clinical consequences of several comorbidities. The flexible yet standardized framework permits estimation of the cost-effectiveness of NASH interventions in a variety of settings. The model currently includes several assumptions and will be further developed as more relevant data become available

Dual Vortex Theory of Strongly Interacting Electrons: Non-Fermi Liquid to the (Hard) Core

As discovered in the quantum Hall effect, a very effective way for strongly-repulsive electrons to minimize their potential energy is to aquire non-zero relative angular momentum. We pursue this mechanism for interacting two-dimensional electrons in zero magnetic field, by employing a representation of the electrons as composite bosons interacting with a Chern-Simons gauge field. This enables us to construct a dual description in which the fundamental constituents are vortices in the auxiliary boson fields. The resulting formalism embraces a cornucopia of possible phases. Remarkably, superconductivity is a generic feature, while the Fermi liquid is not -- prompting us to conjecture that such a state may not be possible when the interactions are sufficiently strong. Many aspects of our earlier discussions of the nodal liquid and spin-charge separation find surprising incarnations in this new framework.Comment: Modified dicussion of the hard-core model, correcting several mistake

Time resolution of the plastic scintillator strips with matrix photomultiplier readout for J-PET tomograph

Recent tests of a single module of the Jagiellonian Positron Emission Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips have proven its applicability for the detection of annihilation quanta (0.511 MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved resolution is almost by a factor of two better with respect to the current TOF-PET detectors and it can still be improved since, as it is shown in this article, the intrinsic limit of time resolution for the determination of time of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much lower. As the major point of the article, a method allowing to record timestamps of several photons, at two ends of the scintillator strip, by means of matrix of silicon photomultipliers (SiPM) is introduced. As a result of simulations, conducted with the number of SiPM varying from 4 to 42, it is shown that the improvement of timing resolution saturates with the growing number of photomultipliers, and that the 2 x 5 configuration at two ends allowing to read twenty timestamps, constitutes an optimal solution. The conducted simulations accounted for the emission time distribution, photon transport and absorption inside the scintillator, as well as quantum efficiency and transit time spread of photosensors, and were checked based on the experimental results. Application of the 2 x 5 matrix of SiPM allows for achieving the coincidence resolving time in positron emission tomography of $\approx$ 0.170 ns for 15 cm axial field-of-view (AFOV) and $\approx$ 0.365 ns for 100 cm AFOV. The results open perspectives for construction of a cost-effective TOF-PET scanner with significantly better TOF resolution and larger AFOV with respect to the current TOF-PET modalities.Comment: To be published in Phys. Med. Biol. (26 pages, 17 figures

Ductile-Phase Toughening of Brazed Joints

A heat treatment is presented that uses ductile-phase toughening to mitigate the effect of brittle intermetallics in a Ni-based braze alloy. The fracture resistance has been enhanced by creating a microstructure containing elongated ductile γ-(Ni) domains that align, preferentially, across the joint. The development of this beneficial microstructure is based on an understanding of the transient dissolution, isothermal solidification, and coarsening phenomena. Due to slow kinetics, the elimination of intermetallics by diffusion is avoided in favor of ductile domain formation through solidification control. The toughening has been attributed to a combination of bridging and process zone dissipation, enabled by the ductile phase

"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base