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This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Grammatical morphology often links small acoustic forms to abstract semantic domains. Deaf and hard-of-hearing (DHH) children have reduced access to the acoustic signal and frequently have delayed acquisition of grammatical morphology (e.g., Tomblin, Harrison, Ambrose, Walker, Oleson & Moeller, 2015). This study investigated the naturalistic use of aspectual morphology in DHH children to determine if they organize this semantic domain as normal hearing (NH) children have been found to do. Thirty DHH children (M = 6;8) and 29 NH children (M = 5;11) acquiring English participated in a free-play session and their tokens of perfective (simple past) and imperfective (-ing) morphology were coded for the lexical aspect of the predicate they marked. Both groups showed established prototype effects, favoring perfective + telic and imperfective + atelic pairings over perfective + atelic and perfective + atelic ones. Thus, despite reduced access to the acoustic signal, this DHH group was unimpaired for aspectual organization.
Although many researchers appeal to performance limitations to account for children’s non-adult-like use of language, few studies have explicitly linked specific cognitive abilities to specific dimensions of language. This study investigated a well-studied underextension in children’s language involving linguistic aspect and tested participants in an aspectual comprehension task as well as a series of assessments evaluating neurocognitive and linguistic skills. Adults (N = 32) and 5-year-old children (N = 32) participated. The results for the children replicated the classic pattern of underextension, with children showing an uneven pattern of success even though all items were equally grammatical. In addition, children’s skill with items that involved overriding lexical information in favor of morphological information was predicted by their performance on an inhibitory control task while children’s skill with items that involved integrating contextual world knowledge was predicted by their performance on a receptive vocabulary task. These results demonstrate how specific dimensions of linguistic processing are supported differentially and sensibly by specific dimensions of cognition.
The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining.
Speech is commonly claimed to relate to mirror neurons because of the alluring surface analogy of mirror neurons to the Motor Theory of speech perception, which posits that perception and production draw upon common motor-articulatory representations. We argue that the analogy fails and highlight examples of systems-level developmental approaches that have been more fruitful in revealing perception–production associations.
Italy's invasion of Abyssinia in October 1935 prompted a major European crisis. This article applies the main theories of foreign policy analysis to the British Government's handling of this crisis. It argues that bureaucratic politics existed, but had little impact on outcomes. Domestic politics had more influence, but did not provide detailed instructions on how to act. The perceptions of key actors, informed by reasoned judgement, determined this. Fears of the threat posed by rival states coalesced with concerns about Britain's own military weakness, leading decision-makers to emphasise the need to act in tandem with France. British policy was therefore motivated by the tension between the public's desire to see action against Italy and the Government's wish to minimise any breach with her allies. These findings highlight the weaknesses of the bureaucratic politics model and show how domestic politics can affect foreign policy outcomes. They also demonstrate the interaction between rational analysis defined in terms of reasoned judgement, and actors' perceptions. It is thus argued that benefits are to be gleaned from combining these theories.
Ensembles of indium phosphide nanowires were grown on amorphous quartz substrates and their optical properties were examined at various cryogenic temperatures. Complex dynamics result from the large areal densities, random orientation, combination of both zincblende and wurtzite phases, and the geometries of the nanowires. Those complex dynamics are discussed in relation to their effect on the temperature dependence of photoluminescence and Raman spectroscopy. Five peaks are found to exist in the photoluminescence spectra at low temperatures which are attributed to radiative recombinations associated with quantum confined zinc blende, quantum confined excitons in zinc blende, quantum confined wurtzite, excitons in bulk zinc blende and impurity states. An energy transfer mechanism between two types of radiative recombinations among the five is proposed to explain intensity variations and the temperature dependence of the PL peaks is discussed. The Raman spectra is observed to have peaks created by a combination of zinc blende and wurtzite vibrational modes which is explained by folding the phonon dispersion.
Biological markers or ‘biomarkers’ of organ damage and dysfunction occupy a central position in the armamentarium of the clinician that is used for the screening, diagnosis and management of disease. Our knowledge of the pathophysiological basis of individual diseases continues to increase inexorably and the discoveries emanating from the Human Genome Project are set to enhance this knowledge immeasurably. Understanding the aetiopathogenesis of changes that take place in individual tissues, organs or compartments of the body can help in the search for markers that reflect these changes. Some of these changes may be directly related to the pathological abnormality while others might be a secondary consequence of the abnormality.
Basic research into the pathophysiology of a disease provides the foundation of knowledge that can lead to the discovery of valuable biomarkers. This foundation can also act as the starting point for the discovery of pharmaceutical interventions. Increasingly, with a more systematic approach to biomarker development and drug discovery, we are seeing the measurement of the biomarker playing a greater role in monitoring the efficacy and/or side effects of the therapeutic intervention. From a clinical standpoint, this can have a major benefit in assessing compliance with therapy, which is acknowledged to be one of the key determinants of efficacy, especially when there is no other ready means to judge the patient's response.
The discovery of a new biomarker is complemented by the development and validation of appropriate analytical technology.
This publication takes a critical, evidence-based look at the efficacy of diagnostic tests which are increasingly being used to evaluate organ damage and dysfunction. The use of biomarkers is growing, with a steady stream of products being brought out by the pharmaceutical industry. Some of these assist in diagnosis, others provide a means of monitoring the state of progression of disease and the effectiveness of therapeutic options. However, in many cases the evidence which supports the use of these methods as opposed to traditional biochemical tests has not yet been demonstrated, and it is intended that this volume will help clarify the strengths and weaknesses of using these biomarkers across a wide range of applications and in the various organs of the body. This approach will provide pathologists, clinical biochemists and medical laboratory scientists with an invaluable overview of the diverse applications of biomarkers in medicine.